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ENDOKR�N S�STEM

9/7/2010

ENDOKR�N (HORMONAL) S�STEM

Geli�mi� ve karma��k yap�l� hayvanlarda bir�ok v�cut k�sm�n�n i�leyi�i iki b�y�k sistem taraf�ndan d�zenlenir. Birincisi sinir sistemi di�eri ise endokrin sistemdir. Sinir sistemi ve duyu organlar�, de�i�en �evreye birka� milisaniye i�erisinde tepki g�stermek suretiyle canl�n�n uyumunu sa�lamas�na kar��n, endokrin bezler arac�l��yla g�sterilen tepkiler �ok daha yava� olu�ur. Bu s�re, dakikalar, saatler ve hatta haftalar alabilir. Fakat hormonlarla olu�an tepkiler, sinirsel tepkilerden �ok daha uzun s�re etkili olur. Bazen bu iki sistemin s�n�rlar�n�n belirli olmad�� durumlar vard�r. �rne�in sinirle ta��nan maddelerin oldu�u ve bunlar�n hormonlardan pek farkl� olmad�� bilinmektedir ( sempatik sinirlerin noradrenalini, b�brek �st� bezinin adrenalini gibi ). Keza hipotalmus gibi hem sinirsel hem de hormonal etki yapan sistemler de vard�r. Endokrin bez sistemlerin salg�lar�na "Hormon" denir. Hormonlar ya diff�zyonlar ya da kan ile belirli organlara veya dokulara ta��narak oradaki i�levleri d�zenlerler. T�m metabolik i�levler, �ok tipik olarak b�y�me, �reme ve edokrinal d�zenlemenin etkisi alt�ndad�r. Glikozun, sodyumun, potasyumun, kalsiyumun, fosfat�n ve suyun hem kanda hem h�cre aras� s�v�da belirli deri�imler de tutulmas�nda bu hormonlar�n �ok b�y�k �nemi vard�r. Hormonal d�zenleme ve denetim, b�ceklerde, kabuklularda, halkal� solucanlarda, yumu�ak�alarda, di�er baz� omurgas�zlarda ve omurgal�larda do�al olarak ta insanda saptanm��t�r.

ENDOKRIN BEZLER
Endokrin bezler, suda ya da ya�da eriyen salg�lar�n� do�rudan do�ruya kana ( lenfe ve serebrospinal s�v�ya) verirler. Ayr�ca bir salg� kanallar� yoktur. Pankreas hem endokrin hem de eksokrin bezdir. Enzimlerini, pankreas kanal�yla ba��rsa��n onikiparmak b�lgesine ak�t�r ve meydana getirdi�i hormonlar� da kan yoluyla di�er v�cut k�s�mlar�na g�nderiri. Ayr�ca yumurtal�k ve testis de hem endokrin hem eksokrin �zellik g�sterir.
Hormon terimi ilk defa 1905 y�l�nda �ngiliz fizyolo�u E.H. Starling denen ara�t�rmac� taraf�ndan, pankreas�n onikiparma�a d�kt�� salg�n�n sekretin ile denetimi �zerinde �al��t��nda, kullan�lm��t�r. Starling, hormonu v�cudun belirli k�s�mlar�ndaki h�crelerden �retilen herhangi bir maddenin, kan yoluyla uzaklara ta��narak orada i�levlerin iyi y�r�mesini sa�layan maddeler olarak tan�mlam��t�r.
�zole edilen hormonlar�n, protein ( dolay�s�yla aminoasit ), ya� asidi ya da stereoyitlerden olu�tu�u g�sterilmi�tir. Normal v�cut i�levleri i�in t�m hormonlar�n optimal miktarda bulunmalar� gereklidir. Herhangi birinin az veya fazla salg�lanmas�nda patolojik baz� anormallikler ortaya ��kar…
Binlerce y�l �nce insanlar�n ve hayvanlar�n k�s�rla�t�r�lmas�yla endokrinoloji �zerinde ilk uygulamal� g�zlemeler yap�lm��t�r. Nitekim 1849 y�l�nda Berholda, bir ku�tan di�er ku�a testis nakli yapmak suretiyle, bu bezlerin kanda ta��nan baz� maddeler salg�lad��n� ve bu salg�lar�n da ikincil e�ey �zelliklerini ortaya ��kard��n� buldu. �ngiliz fizik�isi ADDISON, 1855"de bug�n kendi ad�yla an�lan hastal��n semptomlar�n� g�zledi ve bu hastal��n b�brek �st� bezi adrenalinin kabuk k�sm�n�n bozulmas�yla ortaya ��kt��n� buldu. �lk endokrinolojik terapi 1889"da Frans�z fizyologu BROWN-SEQUARD taraf�ndan, testis �z�t�n�n kendine enjekte edilmesiyle yap�ld�. Bu ara�t�r�c� al�n�n testis hormonlar�yla insanlar�n tekrar gen�liklerine veya en az�ndan eski e�eysel etkinliklerine d�nebilece�ini savunuyordu. �lk defa izole edilmi� ve kimyasal yap�s� ayd�nlat�lm�� hormon epinefrindir.Bu deney 1902 y�l�nda yap�lm��t�r.
Hormonal etki g�sterebilen kimyasal maddeler �ok �e�itlidir. Bunlar amino asitler ya da onlar�n t�revleri, p�rinler, protein ve steroitler olabilir.
Pek az hormon �e�idi v�cuttaki t�m h�crelerin metabolizmas�na etki eder. Her h�cre bu hormonlar�n varl��na tepki g�sterdi�i gibi, yoklu�una da bir�ok olumsuz metabolik de�i�iklik meydana getirmek suretiyle tepki g�sterir. Bununla birlikte �o�u hormon, kanla, v�cudun her taraf�na kar��n, ancak belirli h�crel

ENDOKR�N BEZLER VE HORMONAL D�ZENLEME

9/7/2010

ENDOKR�N BEZLER VE HORMONAL D�ZENLEME
Endokrin sistem endokrin bez ad� verilen i� salg� bezlerinden olu�mu�tur. Bu bezlerin salg�s�na(�retti�i s�v�ya) hormon denir. �retilen hormonlar direkt kana verilir ve kon yoluyla �al��mas�n� d�zenleyece�i organa yani hedef organa ula��r. Baz� hormonlar i�in hedef organ t�m v�cut olurken baz�lar� i�in de belirli organlar hedef organ olur. �rne�in; hipofizden salg�lanan STH(b�y�me hormonu) ve tiroit bezinden salg�lanan tiroksin hormonu i�in hedef organ t�m v�cuttur fakat yine hipofiz bezinin bir salg�s� olan ACTH(adrenokortikotropin) hormonu i�in sadece b�brek �st� bezler,ince ba��rsaktan salg�lanan sekretin hormonu i�in pankreas gastrin hormonu i�in de mide bezleri hedef organlard�r. Hedef organlarda hormonlar� tan�yacak ve alg�layacak �zel alma�lar vard�r. Hormonlar�n as�l g�revi organlar�n �al��mas�n� d�zenleyerek v�cut i�i dengeyi(HOMEOSTAS�S) sa�lamakt�r. Hormonal sisteme bitkilerde ve hayvanlarda rastlanm��t�r. Hormonlar �ok etkili maddeler olup v�cuttaki normal oranlar�n�n �ok az de�i�mesi bile dengeyi bozar. Baz� hormonlar laboratuar ortam�nda yapay(sentetik) olarak �retilebilir. �ns�lin hormonu buna en iyi �rnektir.
A-B�TK�SEL HORMONLAR
Bitkilerdeki hormon sistemi hayvanlardan farkl� olarak bez yerine belirli b�lgelerde �zelle�mi� h�creler taraf�ndan i�lemektedir. Hayvanlarda oldu�u gibi h�crelerde �retilen hormonlar hedef organa ta��n�r. Bu hormonlar bitkilerin b�y�mesini,geli�mesini,farkl�la�mas�n� sa�larken yaralar�nda iyile�mesinde etkilidir. Bitkisel hormonlar� ikiye ay�rmak m�mk�nd�r.
1-B�TK� B�Y�MES�N� TE�V�K EDENLER:
a-OKS�N: Bitkilerde ke�fedilen ilk hormondur. �lk defa darwin taraf�ndan bulunmu� fakat kimyasal yap�s� went taraf�ndan ��z�lm��t�r. Yapay �retilen oksin hormonu tarlalarda yabani otlar�n yok edilmesinde kullan�l�r. Kimyasal ismi indol asetik asittir(IAA). En fazla g�vde ve k�k u�lar�nda salg�lan�r. Oksin hormonunu bitkiler �zerinde bir �ok etkisi bulunmaktad�r. Bunlar:
*Meristematik b�y�me
*H�cre b�l�nmesini h�zland�rma
*Ksilem demet geli�imi
*�i�ek geli�imi
*Meyva geli�imi
*K�klerin a�a�� filizlerin yukar� b�y�mesini sa�lama
*Bitkinin ��a y�nelmesini sa�lama
*D�llenmi� �i�e�in d�k�lmesini engelleme
*Fazla salg�lanmas�nda b�y�meyi durdurma
*Az salg�lanmas�nda yapraklar�n d�k�lmesi
b-S�TOK�N�N: k�klerde �retilen sitokinin ksilem(odun-cans�z) borular� sayesinde ta��n�rlar. �lk defa gen� bitkilerin embriyo ve tohumunda bulunmu�tur. Etkileri �unlar�d�r:
*B�y�me ve tohum olu�turma
*Tomurcuk geli�tirme
*H�cre b�l�nmesini sa�lama
*Yapraklar�n erken d�k�lmesini engelleme
*Yapraklar�n ye�il kalmas�n� sa�lama
*�imlenmeyi geciktirme
c-G�BERELL�N:1920"li y�llarda bu hormon pirin�lerde giberalla fujikurol adl� mantar�n sebep oldu�u hastal�k incelenirken bulunmu�tur. Bu hormon ad� alt�nda incelenen 58 tane hormon benzeri yap� bulunmu�tur. Etkileri �unlard�r:
*G�vde uzamas�n� sa�lama
*H�cre b�l�nmesi ve floem h�crelerinin farkl�la�mas�n� sa�lama
*Tohumu �imlendirme
*�i�eklenmeyi sa�lama
*�ekirdeksiz meyva olu�turma
2-B�TK� B�Y�MES�N� ENGELLEYENLER:
a-ABS�S�K AS�T(ABA): Olgun yaprak h�crelerinde
�retilir. �evreden gelen etkilere tepki olu�turdu�u i�in stres hormonu ad� da verilir. Etkileri �unlard�r:
*Uzun s�ren susuzluk zaman� stomalar� kapat�r ve terlemeyi azalt�r.
*H�cre b�l�nmesini durdurur.
*Tohumun �imlenmesini engeller.
*Tomurcuk k�n� olu�turarak bitkiyi kurumaktan korur.
b-ET�LEN:Kimyasal yap� bak�m�ndan en basit bitkisel hormondur. Di�er hormonlar s�v� oldu�u halde etilen gaz fazdad�r. Bu y�zden sadece �retildi�i bitkiyi de�il di�er bitkileri de etkiler. Etkileri �unlard�r:
*Oksin hormonu miktar� artt�� zaman daha fazla �retilmesini engeller. B�y�meyi durdurur.
*Meyva olgunla�mas�n� sa�lar.
*Meyvada bulunan ni�asta ve asitlerin �ekere d�n��mesini sa�lar.
*H�cre duvar�ndaki pektin maddesini y�karak meyvan�n yumu�amas�na sebep olur.

�NSANDA ENDOKR�N BEZLER VE HORMONLAR
�nsanlarda endokrin sistemi olu�turan belli ba�l� endokrin bez

MANAGEMENT OF DIABETES MELLITUS IN RAMADAN FASTING MONTH

9/7/2010

Management of Diabetes Mellitus in Ramadan Fasting Month

PHYLOSOPHY OF FASTING
During Ramadan, Muslims must fast from dawn to sunset.
Food and fluids may be consumed freely during the night, but forbidden during day time, including oral and parenteral medication.
This will involve a sudden and major change in the daily meals.

This include meal timing, total calories, food type and consistency.
Prior to the month of Ramadan, people usually take 3 major meals (breakfast, lunch, dinner/supper)
This will change to only two meal named Iftar and Sahur. Iftar will be around 6:00 pm and Sahur will be around 3:00 am.
Things Happened During Ramadan
Eating habits change in many ways, not only do mealtimes change, but patterns of meals, the short of food eaten and caloric intake all change in a stereotyped way.
Increased in post prandial physical activity during the nighttimes associated with Tarawih.
Psychological changes due to the general spiritual atmosphere during Ramadan, which create a feeling of inner well-being
Physiological State of Healthy Individuals During Ramadan (Kuwait study) (1)
Body weight decrease transiently during the first half of Ramadan, but recovered by the end.
Respiratory and cardiovascular parameters during exercise were perturbed.
Plasma osmolarity and protein concentration were increased during Ramadan, maybe an indication of dehydration.

Physiological State of Healthy Individuals During Ramadan (2)
Increases in acid and pepsin secretion were noted with no changes in plasma gastrin, mucogastrin, or the duodeno-gastric reflex. (Moroccan study)
Decrease in fasting plasma glucose and insulin. Increase in plasma proteins. Lipid parameters were not altered.(Tunisian study)
Impact of Fasting in Diabetics During Ramadan
Blood glucose levels  triggered homeostatic mechanism to prevent hypoglycemia. But in diabetics, this mechanism can be disrupted, and also perturbed by medication.
Risk of hypoglycemia during daytime and hyperglycemia following Iftar are 6 % and 3 % respectively.
Changes in timing medication are important.
Impact of Fasting in Diabetics During Ramadan
If a proper medication regimen is followed, stable and uncomplicated patients on OHA should be able to fast without problems.
Patients taking single dose insulin or combination therapy may be able to fast but needs to be evaluated on an individual basis.
Impact of Fasting in Diabetics During Ramadan
In the fasting state, individual depends totally on endogenous substrates for energy.
Fasting subject is considered in a state of catabolism since his source of energy are all decreasing.
The liver supplies glucose by glycogenolysis.

Impact of Fasting in Diabetics During Ramadan
Glucose oxidation in liver and muscles is spared as soon as increased quantities of FFA becomes available.
A balance is reached at a plasma glucose level sufficient to ensure adequate brain function and at insulin and glucagon levels sufficient to prevent excessive depletion of previously stored nutrients.

Observational study
N=60 (30 males and 30 females)
Well controlled type 2 diabetics treated with OHA (PPG 200 mg%)
Mean body weight 0,75 Kg
Mean Post Prandial Glucose 9,32 mg%
No correlation from both parameters.

Observational study
Well controlled diabetics with out severe complication
N=55; 49 on diet and 6 on diet +OHA
No Changes in BW, BG and lipid profile
There is no negative effects of fasting during Ramadan, as long as they followed the instructions.

Observational study
N=22; controlled diabetic
Diet and medication were maintain
Blood glucose levels from 8 to 11 am at the first and last week of fasting month, but not from 11 am to 6 pm.
Hypoglycemia should be anticipated when good controlled diabetics are going to fast.

Observational study
N=41 type 2 diabetics (9 on diet, 12 on single OHA, and 20 on combined OHA)
Number of symptomatic hypoglycemic periods, which were not biochemically verified, increased in eight of pat

HEPARIN-INDUCED THROMBOCTOPENIA

9/7/2010

Heparin-Induced Thrombocytopenia

Recent Advances in Management
Heparin-induced Thrombocytopenia
Heparin-induced thrombocytopenia (HIT), an antibody-mediated syndrome, is associated with significant morbidity and mortality
considered a rarity in the past
unrecognized by many clinicians
diagnoses can be difficult to confirm
until recently there was no therapeutic options other than discontinuation of heparin
Epidemiology
thrombocytopenia is one of the most common laboratory abnormalities found among hospitalized patients
serologically proven HIT occurs in 1.5% to 3% of patients with heparin exposure

Epidemiology
the chance of significant exposure to heparin exceeds 50% in hospitalized patients
acute coronary syndrome (UA / MI)
pulmonary embolism
deep venous thrombosis and prophylaxis
stroke / atrial fibrillation
heparinized pulmonary wedge catheters
heparin flush
Bleeding and Clotting
present with mucocutaneous bleeding, ranging from petechiae and ecchymoses to life-threatening gastrointestinal and intracranial hemorrhage
paradoxically, the most feared consequence in these patients with a low platelet count is not bleeding but clotting
Thrombosis
thrombosis is mostly venous not arterial
may result in

bilateral deep venous thrombosis of the legs
pulmonary embolism
venous gangrene of fingers, toes, penis, or nipples
myocardial infarction, stroke
mesenteric arterial thrombosis
limb ischemia and amputation
Thrombosis

thromboembolic complications
occurs in at least 30% to 40% of HIT cases
mortality estimated at 30%
increased length of hospital stay
Differential Diagnosis of Acquired Thrombocytopenia
Drugs
heparin
procainamide
diuretics (furosemide)
H2 blockers (cimetidine)
thrombolytic therapy
GP IIb/IIIa antagonists
Devices
membrane oxygenator
intra-aortic balloon pump
Pseudothrombocytopenia
platelet clumping
hemodilution

Associated disorders
hypersplenism
infections/sepsis
hypotension and subsequent disseminated intravascular coagulation
Other causes
chronic idiopathic thrombocytopenia purpura with exacerbation
antiphospholipid antibody syndrome
Mechanisms of Thrombocytopenia
Increased Platelet Destruction
Non-immune
Immune
Decreased Platelet Production
Increased Platelet Destruction
Non-immune
Septicemia / Inflammation
Disseminated intravascular coagulation
Thrombotic thrombocytopenic purpura

Increased Platelet Destruction
Immune
Autoimmune: idiopathic or secondary immune thrombocytopenia
Alloimmune: post-transfusion purpura
Drug-induced: heparin, gold, quinine, quinidine, sulfa antibiotics, rifampin, vancomycin, nonsteroidal antiinflammatory, and others
Heparin Induced Thrombocytopenia

HIT(heparin-induced thrombocytopenia)
HAT(heparin-associated thrombocytopenia)
White- clot syndromefirst noted in the surgical literature
HIT Syndrome
Type I
associated with an early (within 4 days) and usually mild decrease in platelet count (rarely 100 x 109/L)
typically recovers within 3 days despite continued use of heparin
nonimmunologic mechanisms (mild direct platelet activation by heparin)
not associated with any major clinical sequelae
occurs primarily with high dose iv heparin
HIT Syndrome
Type II
substantial fall in platelet count ( 50%)
count in the 50,000 - 80,000 /mm range
typical onset of 4-14 days
occurs with any dose by any route
induced by immunologic mechanisms
rarely causes bleeding (think of alternative Dx)
potential for development of life-threatening thromboembolic complications
Risks for HIT
Type I
intravenous high-dose heparin
Type II
varies with dose of heparin
unfractionated heparin LMWH
bovine porcine
surgical medical patients
HIT
An immunoglobulin-mediated adverse drug reaction characterized by:
platelet activation
thrombocytopenia
thrombotic complications
Pathogenesis of Drug-induced thrombocytopenia
Certain drugs (quinine, quinidine, sulfa antibiotics) link non-covalently to platelet membrane glycoproteins
very rarely, IgG antibodies are produced that recognize these drug-glycoprotein comple

ENDOKR�N S�STEM ORGANLAR

9/7/2010

ENDOKR�N S�STEM ORGANLAR
Endokrin organlar asl�nda salg�lama sistemlerinde ve organ i�indeki �zel h�cresel organizasyonlar�yla farkl�l�klar sergileyen salg� epitelinden olu�maktad�rlar. H�creler �zel d�zenlemelerle kordonlar veya h�cre kitleleri olu�turacak �ekilde biraraya gelirken, bunlar�n aras�nda retik�ler liflerce zengin �ok az bir ba� dokusu yer al�r. Bu bezlerin en belirgin yap�sal �zelli�i h�crelerin zengin kapiller a� �evresinde lokalize olmalar�d�r. B�ylece salg�lad�klar� hormonlar� direk kapiler l�mene ileterek kan yoluyla h�zla hadef doku h�cresine (target organ) ula�mas�n� sa�larlar. Bu �zelliklerinden dolay� endokrin bez (i� salg� bezi) terimiyle tan�mlan�rlar
Endokrin bezler ba��ms�z spesifik organlar �eklinde organize olduklar� gibi ba�ka fonksiyonlar� olan organlar�n i�erisinde h�cre gruplar ya da sadece bir ka� h�cre �eklinde serpi�tirilmi� organizasyonlarla veya ge�ici organlar �eklinde kar��m�za ��kabilir.
Ba�l�ca endokrin organlar
Hipofiz (pituitary)
Epifiz (corpus pinealis)
Tiroid (Glandula thyreoideae)
Paratiroid (Glandulae paral�yreoideae
B�brek�st� bezi (Glandulla suprarenaIes)
Paraganglionlard�r.
Bunlar�n d��nda h�cre gruplar� ya da tek tek h�creler �eklinde organlar i�erisinde serpi�tirilmi� yap�lar
pankreas (Langerhans adac�klar�)
Testis (Leydig h�creleri)
Ovarium (Korpus luteum, Granulosa h�creleri)
Plasenta
Mide
Ba��rsaklar
B�brek gibi organlarda g�r�l�r.
�� salg� bezleri salg�lar�yla hedef h�crede dolay�s�yla organlarda, morfolojik, histokimyasal, dolay�siyle fonksiyonel de�i�iklikler meydana getirerek bu organlar�n �al��malar�n� d�zenlerler. Hormonlar organizmada protein, karbohidrat ve ya�lar�n metabolizmalar�n� d�zenleyerek ya�amsal olaylar� y�nlendirmenin yan�s�ra, ki�ilik, seks�el �zelliklerin belirmesi ve genel g�r�n�� zerinde de etkili olurlar. �� salg� organlar�, salg�lad�klar� hormonlar yoluyla birbirlerini de etkileyebilirler Ayr�ca hormonal d�zenlemenin denetimini yapan otonom sinir sistemine ilave olarak hormonal yolla da denetlerler. Organizmada ger�ekle�tirilen metabolik olaylar�n d�zenlenmesinde sinirsel ve endokrin sistemlerin uyumlu bir �ekilde �al��mas� bir N�roendokrin sistemi yani N�roendokrin hipotalamo-hipofizer sistemi (NHS) ortaya koymu�tur.
Ya�amsal denge: �mpuls Sinirsistem
> N�roendokrin Sistem
Hormon Endokrin sistem
________________________________________
H�POF�Z (Pituitary gland)
Hipofiz sfenoid kemi�in sella turcica"s�na yerle�mi�, hipofiz sap� ve infundibulum vas�tas�yla diencefalona ba�l� olan olduk�a geni� etki alan�na sahip �nemli bir endokrin organd�r.
Organ embriyoljik olarak iki farkl� kaynaktan geli�en farkl� morfolojiye sahip iki loptan olu�ur. Embriyonal kaynaklardan birisi membrana bukkofaringean�n hemen �n�nde embriyonal a��z bo�lu�u (stomedium) tavan�n�n bir divertik�l �eklinde diensefalona do�ru y�kselmesiyle ou�an Rathke kesesidir. Kafa kemiklerinin olu�umundan �nce bu b�lgeye ula�an divertik�l kemiklerin geli�imiyle a��z bo�lu�uyla il�kisini kaybeder ve Rathke kesesini olu�turur. Rathke kesesi �n duvar� prolifere olarak hipofizin �n lobunu (lobus anterior) olu�tururken arka duvar daha az geli�erek ara lobu (pars intermedia) olu�turur.
Hipofizin geli�imine kaynakl�k eden di�er b�lge diencephalonda 3 �nc� ventrik�l�n taban�ndan Rathke kesesine do�ru uzanan divertk�ld�r. Bu nerv�z taslak Rathke kesesini birmiktar sararak hipofizin arka lobunu (lobus posterior) olu�turur. Arka lobu arabeyine ba�layan hypophys sap� ve infundibulum, k�relmez, hayat boyunca kal�r. Hipofiz boyutlar� cinsiyete ve ya�a ba�l� olarak olduk�a de�i�iklik g�stermesine ra�men yakla��k 0.5-0.6gr a��rl��a sahiptir. Ya�l�l�kta k��len hipofizin gebelik d�neminde a��rl�� bir miktar artar.
Hipofiz mikroskopik yap�, k�ken ve fonksiyonlar� bak�m�ndan birbirinden tamamiyle farkl� olan iki k�s�mdan olu�ur. Bunlar
Adenohipofiz (Pars glandularis)
N�rohipofiz (Pars nervosa), olarak adland�r�l�r.
Aden�hipofiz;
�n lop lob (lobus anterior-pars distalis)
Ara lob (Pars intermedia)
Pars t�beralis"ten olu�ur.
N�rohipofiz
Arka lob (lobus posterior),
Hipofiz sap�
�nfundibulum"dan ibarettir.
Hipofiz t�m�yle olduk�a kal�n fibroz bir kaps�l (stratum fibrosum) ile sar�l�d�r. Kaps�l ile sella tursican�n periosteumu aras�nda venlerden zengin bir ba�dokusu (stratum vasculare) yer a

D�ABETES MELL�TUS PREVALANS

9/7/2010

Diyabetes Mellitus Prevalans

�lkemizde ~ 5.000.000
ABD"de 15.000.000
~ 100.000 (SDBY) (%7)
Avrupa 22.500.000
~ 100-120.000 (SDBY) (%0.5)
SDBY (son d�nem b�brek yetmezli�i)

Diyabetes Mellitus (Hiperglisemi)
Afferent arteriyoler vazodilatasyon
Atriyal natri�retik peptid (ANP)
Prostaglandinler
Nitrik oksid (NO)
�nsulin like growth fakt�r (IGF-1)
Ca+ kanallar�n�n fonksiyon bozuklu�u
K+ kanallar�n�n aktivitesinde art��
�nsulin eksikli�i
Efferent arteriyoler vazokonstriksiyon
Anjiyotensin II (AII)
Endotelin-1
�nsulin eksikli�i

Glukoz metabolizma yolunun enzimatik aktivasyonu

�ntrasel�ler sorbitol olu�umu
( Aldoz red�ktaz enzimi)
Protein kinaz-C (PKC) aktivasyonu

Protein Kinaz-C Aktivasyonu
Bazal membran kal�nla�mas�
Vask�ler okl�zyon
Vask�ler permeabilite art��
Anjiyogeneziste art��
H�zlanm�� ateroskleroz

Diyabetik glomeruloskleroz

Humoral dengesizlik
- �ntrarenal hormonlar ve sitokinlerin art��
(TGF-β,Anjiyotensin II, Endotelin-1, prostaglandin, tromboksan, nitrik oksid, IGF-1, PDGF
Oksidatif stres
Diyabetik glomeruloskleroz klinik evreleri
Erken d�nem
�leri d�nem
Nefrotik sendrom ve son d�nem b�brek yetmezli�i
Diyabetik glomeruloskleroz( erken d�nem )
Mikroalbumin�ri
GFR normal veya hafif artm��
B�brek boyutlar� normal
Geri d�n��ml� olabilir
Diyabetik glomeruloskleroz( ileri d�nem )
Protein�ri (dipstick, salisilsulfonik asit)
GFR progresif azalma (y�lda 5-10 ml/dk)
B�brek boyutlar� normal
Hipertansiyon (%80 Na-s�v� retansiyonu %20 vazokonstrikt�rler)
�dem
Diyabetik glomeruloskleroz( nefrotik sendrom ve SDBY)
A��r� protein�ri ve Nefrotik sendrom
GFR da h�zl� azalma (2-3 y�l i�inde terminal d�nem b�brek yetmezli�i)
Hipertansiyon (kontrol� g�� ve �ok fakt�rl�)
Belirgin ekstrarenal D.Mellitus organ komplikasyonlar� (�zellikle kardiyovask�ler)
Ateromat�z RAS insidans�nda artma
N�rojenik mesane insidans�nda artma
Diyabetik glomerulosklerozun di�er glomer�ler patolojilerden farkl� �zellikleri
Mikroskopik patolojik idrar bulgusu yoktur

Son d�nem b�brek yetmezli�i durumlar�nda b�brek boyutu k��lmez
Son d�nem b�brek yetmezli�i durumlar�nda protein�rinin �iddetinde azalma olmaz
Diyabetik glomeruloskleroz histopatoloji
--Mezan�ial geni�leme
Glomer�ler bazal membran kal�nla�mas�
Glomer�ler skleroz

Diff�z interkapiller glomeruloskleroz
Nod�ler glomeruloskleroz

Diyabetik glomeruloskleroz tedavi yakla��m�

Kan �ekeri mutlak reg�le olmal�
Risk fakt�rleri ortadan kald�r�lmal�
Hiperfiltrasyon �nlenmeli
�ntrarenal ve intraglomer�ler bas�n� d��r�lmeli
Sistemik kan bas�nc� d��k (120/70 mmHg) tutulmal�d�r.

Diyabetik glomeruloskleroz tedavi (erken d�nem)

- Protein k�s�tlamas� (1 gr/kg/g�n)
- Hipertansiyon varsa ilk se�enek ila�
ACE-i veya AT1 resept�r blokerleri
- Risk fakt�rlerini ta��yan hastalarda Organ koruyucu dozda ACE-i veya
AT1 Resept�r blokerleri

Diyabetik glomeruloskleroztedavi (ileri d�nem)

- Protein k�s�tlamas� (0.7 gr/kg/g�n)
- Antihipertansif tedavi
. Sodyum k�s�tlamas�
. D��k doz di�retik(furosemid)
. ACE-i, AT1 resept�r blokeri (GFR ve serum K+ d�zeyi izlenerek)
( renal arter stenozu !!)
. -bloker, KKB, -bloker
Diyabetik glomeruloskleroztedavi (nefrotik sendrom+SDBY )
- Protein k�s�tlamas� (0.5-0.7 gr/kg/g�n) - Konservatif nefrotik sendrom tedavisi
- Antihipertansif tedavi
. Se�ici KKB
. Se�ici -bloker . Santral etkili antihipertansifler . -bloker
. ACE-i ve AT1 resept�r blokerleri ?
- Diyaliz, b�brek transplantasyonu !!
Diyabetik hastalarda renal replasman tedavisi
Hemodiyaliz (veya hemodiyafiltrasyon)
Periton diyalizi (SAPD)
B�brek ± pankreas veya adac�k h�cre transplantasyonu
Diyabetik hastalarda hemodiyaliz
Erken diyaliz
Ba�lang��ta insulin gereksinimi azal�rken, sonra anoreksinin d�zelmesi ile artar
Hiperglisemi s

D�ABET�N DER� BULGULARI VE D�YABET�K AYAK

9/7/2010

D�ABET�N DER� BULGULARI VE D�YABET�K AYAK

D�ABETES MELL�TUS
�ns�lin salg�s�n�n eksikli�i
�ns�lin rezistans�
Hiperglisemi
Karbonhidrat, ya� ve protein metabolizmas� bozukluklar�
Akut ve kronik komplikasyonlar� ile y�ksek morbidite ve mortalite
D�ABET�N YEN� SINIFLAMASI (ADA)
Tip 1 DM
Otoimm�n
�diopatik
Tip 2 DM
Nonobez
Obez
Subgrublar : Sendrom X
MODY
LADA (Tip 1.5)
Maln�trisyonla �l�.

Gestasyonel DM
Bozulmu� Glukoz Tolerans� (IGT) ve Bozulmu� A�l�k Glukozu (IFG)

Diabetes Mellitus v�cudun t�m sistemleri+deri
DM"lilerin ortalama %30"unda deri lezyonlar�+
Patognomonik deri bulgusu yok
Birden fazla deri belirtisi

Patogenezinde serbest deri �ekerinin rol�
Normal ki�ilerde deri �ekeri %60 mg. DM"lilerde%150-200 mg.
�ns�lin derinin de�i�ik komponentlerini �zellikle dermal fibroblastlar� etkiler.
�ns�linin rol�:*Epidermal h�crelere
glukozun giri�i
*Deride glukoz utilizasyonu
*Glukozun intrasell�ler
da��l�m�n�n reg�lasyonu

DM"lilerin derisinde h�creleraras� kollagen eksik
Glukoz d�zeyinin art��Enzimatik olarak glikozillenmi� kollagenin �apraz ba�lanmas� ve fibril olu�umunun inhibisyonu
Diabetteki mikroanjiyopati, n�ropati, ateroskleroz ve immun de�i�ikliklerDeri komplikasyonlar�
Diabetteki deri bulgular� ile HbA1c d�zeyi aras�nda bir ili�ki yok
Diabetes Mellitusta Deri Belirtileri
I.Akut metabolik d�zensizlikleri yans�tanlar
II.Kronik dejeneratif komplikasyonlar� yans�tanlar
III.Metabolik d�zensizlik ve dejeneratif komplikasyonlar�n bulunmad�� hastalarda s�k g�r�lenler
I. Akut Metabolik D�zensizlikleri Yans�tanlar
Lokalize veya jeneralize pruritus
Stafilokok ve kandida enfeksiyonlar�
Alt ekstremitelerde steatotik g�r�n�m
Ksantomlar
Lokalize veya Jeneralize Pruritus
Pruritusun s�k nedenlerinden biriDiabet
Diabetin �iddeti ile pruritus aras�nda ili�ki yoktur.
Sa�l� derinin lokalize persistan pruritusuDiabetin bir bulgusu
Antipruritik tedavi
Diabetli kad�nlardaki anogenital ka��nt� Kandida enfeksiyonuna ba�l� olabilir
Stafilokok Enfeksiyonlar�
Staphylococcus aureusa ba�l� deri enfeksiyonlar� DM"lilerde s�k g�r�l�r. Bunun sebebi bilinmemektedir ve derideki y�ksek glukoz seviyesine ba�l� olarak da a��klanamam��t�r.
�nsulin ve antibiyotik tedavisi ile daha �nceden �ok yayg�n olan fronk�l ve karbonk�ller art�k kolayca tedavi edilebilmektedir.

Kandida Enfeksiyonlar�
Diabetiklerde a��z, t�rnak k�vr�mlar�, genital ve intertrigin�z b�lgelerde yayg�n
�drar, genel v�cut s�v�lar� ve terdeki y�ksek glukoz seviyesi, ketoasidozis durumunda PMNL"in fagositoz yeteneklerinin bozulmas�; diabetik hastalar� kandidiyazise kar�� hassasla�t�r�r, kandidalar�n h�zl� �o�almas�na neden olabilir.
Kandida vulvovajiniti ve balaniti diabetiklerde s�k

Non-Klostridyal Gazl� Gangren
Gangren�z bir odak yan�ndaki yumu�ak dokularda geli�en bir komplikasyondur
Gangren,�lser+DM"lilerin %17"sinde
Patojenler; E.coli, Klebsiella, Pseudomanas, Bacteroides
Tedaviye iyi cevap
Pseudomanas Enfeksiyonlar�
Malign eksternal otitte�nvaziv pseudomonas enfeksiyonu geli�ir
*Sel�litis
*Osteitisten
*Kranyal sinir hasar�
*Menenjite sebep olur
% 53 oran�nda mortalite +

Tinea Pedis Ve Onikomikoz
Ayak parmak aralar�ndaki infeksiyonlar �nflamasyon ve fiss�rasyon Diabetik ayakl� bir hastada bakteriyel infeksiyonlara giri� kap�s�
�nflamasyonlu b�lgenin artm�� oksijen ihtiyac�Mikrosirk�lasyondaki yetersizlik Gangrene gidi�
N�rovask�ler komplikasyonlar� +DM"liler tinea pedis infeksiyonlar� agresif tedavisi gerekir.

Ayak t�rnaklar�n�n dermatofit infeksiyonlar� (onikomikoz)  Ya�l� DM"lilerde s�k
Diabetiklerde immun yan�ttaki bozukluklar nedeniyle mantar infeksiyonlar�n�n insidans�nda art��
T�rnak distrofisi ciddi t�rnak bak�m�
4-6 ay boyunca haftada bir kez 400

OVERVIEW OF NITROGEN METABOLISM

9/7/2010

Overview of nitrogen metabolism

H�PERT�RO�D� VEA T�ROTOKS�KOZ NED�R

9/7/2010

Hipertiroidi veya tirotoksikoz nedir?
Hipertiroidi, tiroit glandinin fazla �alismasina bagli olarak tiroit hormonlarinin fazla miktarda salgilanmasi sonucu ortaya �ikan klinik tabloya verilen isimdir.
Tirotoksikoz, degisik nedenlerle �rnegin fazla miktarda tiroit tableti alinmasi yada tiroiditlerde oldugu gibi tiroit depolarindan kana ani olarak tiroit hormonlarinin bosalmasi sonucu kanda tiroit hormonlarinin y�kselmesine verilen isimdir. Iki durumda da klinik olarak ayni tablo ortaya �ikar

Hipertiroidi ve tirotoksikozun sebepleri nelerdir?
Hipertiroidiyi meydan getiren degisik nedenler mevcuttur. Bunlari kabaca 4 sinifa ayirabiliriz.
1. Tiroidin asiri uyarilmasi:
Tiroidin asiri uyarilmasi degisik nedenlerle olur. Bunlar:
a. Basedow-Graves hastaligi
b. Asiri HCG
c. Hipofiz t�m�rleri
d. Asiri iyot alinimi.
2. Tiroit nod�llerine bagli gelisen hipertiroidi sebepleri
a. Toksik otonom fonksiyonel tiroit nod�l�
b. Toksik multinod�ler guatr
3. Tiroit zedelenmesine bagli gelisen hipertiroidiler
a. Subakut tiroidit
b. Postpartum tiroiditi
c. Agrisiz veya sessiz tiroidit
d. Radyasyona bagli gelisen tiroidit
e. Akut supuratif tiroidit
4. Degisik nedenlere bagli gelisen hipertiroidiler
a. T-3 veya T4 hormonlarinin asiri alinmasi
b. Struma ovari

a. Basedow-Graves hastaligi nedir? Sebebi nedir?
�lkemizde en sik rastlanan hipertiroidi nedenlerinden biridir. Hipertiroidi belirtileri, bazen guatr, g�z ve deri belirtileri ile kendini g�sterir. Otoimmun bir hastaliktir. Bu hastalikta kanda otoantikorlar bulunur. Antikorlar, yabanci maddelere, vir�slere veya bakterilere karsi olusan proteinlerdir. Otoantikorlar ise v�cudun kendi dokularina veya kimyasina karsi olusmus antikorlardir. Basedow-Graves hastaliginda TSH resept�rlerine karsi antikorlar olusur. Bu antikorlara Tiroit Resept�r Antikorlari (TRAb) denir. Bunlar TSH resept�rleri ile birlestigi zaman TSHdan daha fazla miktarda tiroit hormon yapimini artirir.
Bu antikorlar v�cutta nasil olusur?
Genetik burada �nemli rol oynar. Dolayisiyla, bir ailede birden fazla fertlerde ve �zellikle kadinlarda g�r�l�r. Kendisinde Graves hastaligi tespit edilen bir kadin diger aile fertlerine de bunu bildirerek onlarin da bu hastaliktan haberdar olmalarini saglamalidir. Hashimoto hastaligi da ailevi bir hastalik oldugundan bu iki hastaliga ayni aile fertlerinde rastlanilabilmektedir.
Otoantikorlarin olusmasinda ikinci mekanizma, baskilayici T lenfosit h�crelerinin yetersiz olusudur. Bu durumda B lenfosit h�crelerinde antikor yapimi baslar. T h�crelerindeki baskilayici etkinin kalkmasi b�y�k psisik travmalardan (kaza, �l�m, ayrilik veya islerin iyi gitmemesi) sonra meydana gelir. Diger yandan bazi arastiricilar, stresin hipertiroidiye neden olmadigini mevcut olan hafif hipertiroidiyi siddetlendirdigini ileri s�rmektedirler. Bazilarina g�re ise birtakim vir�slerin etkisi ile TSH resept�rleri degismekte ve yabanci cisim (antijen) olarak algilanarak buna karsi antikor �retilmektedir. Sonu� olarak, hipertiroidide antikor yapimini uyaran sistemin hen�z tam olarak anlasilmis oldugunu s�yleyemeyiz. �zellikle hastalarim arasinda psisik travmalardan sonra hipertiroidi gelismesine �ok sik rastladigimi s�yleyebilirim. �SS sinavina giren bir hastamda b�y�k �mitle bekledigi sonucun d�s�nd�g� gibi �ikmamasi �zerine birka� g�n i�erisinde siddetli ekzoftalmi, �arpinti ve zayiflama baslamisti.
Hashimoto hastaliginda g�r�len otoantikorlarin en azindan %50si Basedow-Graves hastaliginda da bulunur. Basedow-Graves hastaligi diger otoimmun hastaliklardan olan vitiligo ve olgunlasmamis gri sa� ile birlikte de g�r�lebilir. Agir otoimmun hastaliklardan olan myasthenia gravis, romatoid artrit, sistemik lupus ertiromatosus ve diyabet ile �ok daha az siklikla birlikte bulunur.

b. Human chorionic gonadotropin (HCG)
Hiperitroidinin nadir rastlanan nedenlerinden biri de hamilelik sirasinda salgilanan ve HCG denilen hormonun asiri salgilanmasidir. Bu hormonun bir molek�l� TSHya benzemekte ve hamilelik sirasinda tiroit glandini uy

HYPOTHALAMIC-PITUITAR AXIS

9/7/2010

ypothalamic-Pituitary Axis

Anterior Pituitary(Adenohypophysis)
Secretion of Anterior Pituitary Hormones
Determined by
hypothalamic hormones
peripheral feedback
intrapituitary cytokines

Hypothalamic-Pituitary-Target OrganConcept of Feedback
Secretion of Anterior Pituitary Hormones
Points to note
CNS inputs
Pulsatile secretion
Negative feedback
Diurnal/monthly rhythms
Stress
Drugs

Intrapituitary cytokines
Intrapituitary control by cytokines is an important control mechanism for pituitary hormone secretion
Several of these cytokines signal through a common receptor subunit (GP 130) linked to the Janus kinase signal transduction activation transcription cascade (JAK-STAT)
ACTH and GH are induced by cytokines in this group including IL6 and leukaemia inhibitory factor
Hypothalamic Hormones
Hormone Function
GnRH (10aa)Releases LH & FSH

TRH (3aa)Releases TSH & PRL

GHRH (44aa)Releases GH

CRH (41aa)Releases ACTH

GHIH (14aa)Inhibits GH &TRH
(Somatostatin)

Dopamine Inhibits Prolactin (Catecholamine)
Anterior Pituitary Hormones
Glycoproteins
Follicle Stimulating Hormone (FSH)
Luteinising Hormone (LH)
Thyroid Stimulating Hormone (TSH)

Single Chain Polypetides
Growth Hormone (GH)
Adrenocorticotrophic hHoemone (ACTH)
Prolactin
Anterior Pituitary Hormones: Glycoproteins
FSH, LH and TSH (HCG)
Each is composed of two subunits; α and β
The α -subunit is common to all.
The β -subunit is unique to each hormone and confers both biological and immunological specificity
About 30% carbohydrate
Anterior Pituitary Hormones: Polypeptides
Prolactin:
High mw forms present: Macroprolactin
Homology with HGH, HPL
ACTH
39AA but 24 N terminal AA for biological activity
Large family of precursors and related peptides
GH
Multiple molecular weight variants present in plasma
Homology with HPL (85%) + Prolactin (16%)
Gonadotrophin Isoforms
Heterogeneity due to variation in carbohydrate chains
Isoform pattern different in pituitary, serum and urine
Isoform profile varies in normal menstrual cycle
Isoform profile varies in disease (e.g.. PCO)
Not known if isoforms have different in vivo and in vitro biological activity

Assessment of hypothalamic-pituitary-end organ axis
1.Baseline hormone levels
- pituitary
- end organ
2.Dynamic function tests
Hypothalamic-Pituitary-Adrenal Axis
Hypothalamic-Pituitary-Thyroid Axis
Hypothalamic-Pituitary-Gonadal Axis
Growth Hormone-IGF-1 Axis
Prolactin
Posterior Pituitary(Neurohypophysis)

Posterior Pituitary Hormones
ADHOxytocin
Aminoacids9aa9aa
MW10841007
½ Life5-10 mins5-10mins
NeurophypohyealNeurophysin IINeurophysin I
binding protein
Plasma BindingNone None

Anti-diuretic Hormone
Produced in supraoptic and paraventricular nuclei
Released by posterior pituitary
Osmoreceptors: Plasma osmolality
Baroreceptors: Blood pressure/volume
Acts on renal collecting ducts to increase water reabsorption from urine

Anti-diuretic Hormone
Thirst
Maximum ADH drive
Maximum urine concentration (minimum renal water loss)

If then ECF osmolality continues to rise, water intake increased by CNS thirst centre
Stimuli to ADH release
Anti-diuretic Hormone
Other Stimuli
Neural eg sight of food
Nausea & vomiting
Hypoglycaemia
Angiotensin 11
Stress, Heat, pain
Drugs

Anti-diuretic Hormone
Other possible functions with supraphysiological levels
Arterial contraction
Improves memory
Glycogenolysis and lipolysis
Stimulates ACTH

Oxytocin
Regulation
Suckling
Pregnancy and Parturition
Functions
Uterine contraction during parturition
Promotes milk ejection during lactation
Disorders
None known
Hypopituitarism.
Causes of Hypopituitarism
Commoner Causes
Pituitary Tumour
Parasellar and suprasellar tumours
Pituitary and parapituitary Radiation
Pituitary Apoplexy
Causes of Hypopituitarism
Less Common Causes
Infiltrative disease
Granuloma
Haemochromatosis
Sarcoidosis
Infection
TB
Mycoses
Miscellaneous
Empty se

TERAP�A DE REEMPLAZO HORMONAL MENOPAUS�A

9/7/2010

Terapia de Reemplazo Hormonal: Menopausia

Definición
Climaterio: Transición entre la fase reproductiva y la no reproductiva de la vida.
Menopausia: Comienza un año después del último periodo menstrual.
Evento fisiológico, puede ser determinado geneticamente.
Los síntomas menopáusicos se presentan en el 70% y generalmente se resuelven con el tiempo.

Incidencia

Mortalidad por enfermedad cardiovascular por 1000 pacientes/añoRenfro and Paisley Survey
Síntomas
Disminución de la función ovárica

Psicológicos

Factores socioculturales
Signos y síntomas
Amenorrea o menstruación irregular
Síntomas vasomotores
Atrofia genitourinaria
Osteoporosis
Insomnio
Sistema cardiovascular
Esquelético
Presentación
Evolución natural
Cambios inducidos en las lipoproteinas por la menopausia.(Observación transversal)
Efectos cardiovasculares de los estrógenos y posibles efectos cardioprotectores
Lípidos
Perfil favorable (25-50% de reducción de riesgo)
Antioxidante directo??
Mecanismo de la coagulación
Disminuye el fibrinógeno
Disminuye el factor inhibidor del plasminógeno
Relajación directa de los vasos sanguineos
Favorece la angiogénesis
Diagnóstico:
Cese de la menstruación con o sin síntomas de inestabilidad vasomotora
Elevación de FSH y LH (seguimiento por un año)
FSH 100 mUI/ml
LH 75 mUI/ml
The Nurses Health Study: CHD Risk and Postmenopausal Estrogen + Progestin Use
59,337 mujeres, edad 30-55, seguimiento por 16 años.
RR para eventos coronarios del 0.60 en el grupo de estrógenos y el grupo estrógenos + progestin del 0.39.
Dosis de estrógenos de 0.3 y 0.625 mg fueron los de mayor beneficio.
Mujeres de 60-71 años de edad tuvieron los mismos beneficios al igual que las mujeres jóvenes.

Postmenopausal Estrogen/Progestin Interventions Trial (PEPI)
875 Mujeres sanas postmenopáusicas, 45-64 años de edad.
Grupo de intervención paralelo:
Placebo
EEC 0.625 mg/d
EEC 0.625 mg/d + AMP 10 mg/d x 12 d/mo
EEC 0.625 mg/d + AMP 2.5 mg/d
EEC 0.625 mg/d + AMP 200 mg/d x 12 d/mo
Puntos finales:
HDL-C
Presión arterial sistólica
Fibrinógeno
Insulina
Resultados PEPI
Lipoproteinas:
HDL-C: Incremento en todos los Tx activos (Mejor con EEC y EEC +AMP)
LDL-C: Disminución por igual en todos los grupos de tratamiento.
Triglicéridos: Incremento por igual en todos los grupos.
Presión sistólica: Incremento similar en todos los grupos.
Insulina: No diferencias en ayunas o 2 horas en todos los grupos de tratamiento.
Fibrinógeno: No diferencia en los grupos TX
Cambios en la concentración de Lipoproteina (a) 2 meses después de TRH
Groupo A(N=29) Groupo B(N=87) Groupo C(N=65) Groupo D(N=23)
Basal36.4  43.34 36.7  30.9 36.5  35.2 31.2  33.8
2 Months36.4  37.93 28.5  24.4 28.1  30.7 24.6  30.4
Change, % -14.7 -22.2 -25.7
PNS .0001 .0001 .001
A = Placebo
B = Premarin 0.625 mg + Provera 2.5 mg
C = Premarin 0.625 + Provera 5 mg
D = Premarin 0.625 mg

Efecto de varios tratamientos de reemplazo hormonal sobre lipoproteinas en 12 meses
LipoproteinasN=140N=97N=109N=134N=71(mg/dL)EECEEC+AMP5EEC+AMP10 ES+Nor Control
23  1425  1825  1825  18 24  27Lp(a)(-37%)(-28%)(-30%)(-30%)
LDL-C128  114 130  112 128  113126  104131 129
HDL-C67  8068  7666  7563  6468  69
Trig132  145 116  122132  118134  90140  139
Efecto de los estrógenos en los lípidos
WHI: Women´s Health Initiative
Women´s Health Initiative (WHI) Clinical Trial
WHI TRH
16,608 mujeres randomizadas
Mujeres con útero intacto
EEC 0.625 mg/día+ AMP 2.5 mg/día o Placebo
Mujeres sin útero
EEC 0.625 mg/día o Placebo
Puntos finales primarios: Enf. Cardiovascular (IAM)
Secundarios: F

HORMONLAR

9/7/2010

HORMONAL D�ZENLEME

Geli�mi� ve karma��k yap�l� hayvanlarda bir �ok v�cut k�sm�n�n i�leyi�i iki b�y�k sistem taraf�ndan d�zenlenir. Birincisi sinirsel, ikincisi ise hormonal d�zenlemedir. Sinir sistemi ve duyu organlar�, de�i�en �evreye birka� milisaniye i�erisinde tepki g�stermek suretiyle hayvan�n uyumunu sa�lamas�na kar��n, endokrin bezler arac�l��yla g�sterilen tepkiler �ok daha yava� olur. Bu s�re dakikalar, saatler ve hatta haftalarla �l��lebilir. Fakat hormonlarla olu�an tepkiler, sinirsel tepkilerden �ok daha uzun s�re etkili olur. Bazen bu iki sistemin s�n�rlar�n�n belirli olmad�� durumlar vard�r. �rne�in sinirlerle ta��nan maddelerin oldu�u ve bunlar�n hormonlardan pek farkl� olmad�� bilinmektedir (simpatik sinirlerin noradrenalini, b�brek �st� bezinin adrenelini gibi). Keza hipotalamus gibi hem sinirsel hem de hormonal etki yapan sistemlerde vard�r. Endokrin bez sistemlerinin salg�lar�na hormon denir. Hormonlar ya diff�zyonla ya da kan ile belirli organlara veye dokulara ta��narak oradaki i�levleri d�zenlerler. T�m metabolik i�levler, b�y�me ve �reme gibi �ok tipik olaylar endokrinal d�zenlemenin etkisi alt�ndad�r. Glikozun, sodyumun, potasyumun, kalsiyumun, fosfat�n ve suyun hem kanda hem h�cre aras� suda belirli deri�imlerde tutulmas�nda da hormonlar�n �ok b�y�k �nemi vard�r. Hormonal d�zenleme ve denetim bitkilerde, b�ceklerde, kabuklularda, halkal� solucanlarda, yumu�ak�alarda, di�er baz� omurgas�zlarda ve omurgal�larda saptanm��t�r.
Bitkilerde denetim ve d�zenleme i�i sadece hormonal sistemle ger�ekle�tirilir. Hormonlar�n hem bitkilere hem de hayvanlarda salg�lanmalar� optimal (en uygun) d�zeyde olmal�d�r. Fazla ya da az salg�lanmalar� her zaman bir anamoliye neden olur.
Geri Besleme Sistemi (Feed-Back Mekanizmas�)
�nsanlarda di�er endokrin bezlerin �al��mas�n� d�zenledi�i i�in temel bez olarak adland�r�lan hipofizin hormon salg�lamas�n� durdurmas� veya azaltmas� di�er bezlerin kontrol� alt�ndad�r. ��yle ki; hipofiz salg�lad�� tiroid uyar�c� hormon ile tiroit bezinin salg� yapmas�n� sa�lar. Tiroit bezinin salg�lad�� tiroksin hormonunun deri�iminin kandaki miktar� belirli bir seviyeye ula�t��nda bu hipofizin tiroit uyar�c� hormon salg�s�n� azaltmas� yada kesmesi y�n�nde bir uyart� olu�turur. Hipofiz bezinin di�er bezlerle bu etkile�imine geri besleme sistemi denir.
�nsanda salg�lanan hormonlar�n isimlerini salg�land�klar� yerleri ve etkilerini bir tablo arac�l�� ile vermeye �al��al�m.
HORMONSALGILANDI�I YERF�ZYOLOJ�K ETK�LER�
TiroksinTiroit beziBazal metabolizmay� art�r�r
TriiyodotironinTiroit beziBazal metabolizmay� art�r�r.
ParathormonParatiroit beziKalsiyum ve fosfor metabolizmas�n� d�zenler
KalsitoninTiroit"in C h�crelerindenKalsiyum ve fosforu d�zenler (parathormonun antigonisti)
�ns�linPankreas�n beta h�creleriKasta ve di�er h�crelerde glikoz kullan�m�n� art�r�r, kan �ekerini azalt�r, glikojen depolanmas�n� ve glikoz metabolizmas�n� art�r�r.
GlukagonPankreas�n alfa h�creleriKaraci�er glikojenini kan glikozuna �eviren mekanizmay� uyar�r.
SekretinOnikiparmak mukozas�Pankreas s�v�s�n�n salg�lanmas�n� uyar�r.
KolessistokininOnikiparmak mukozas�Safra kesesinden safran�n b�rak�lmas�n� uyar�r.
Epinefrin (Adrenelin)Adrenel medullaSimpatik sistemi destekler, karaci�er ve kas glikojeninin y�k�m�n� uyar�r.
Norepinefrin (Noradrenalin)Adrenel medullaKan damarlar�n� daralt�r.
KortizolAdrenel korteksProteinlerin karbonhidratlara d�n��m�n� uyar�r
AldosteronAdrenel korteksSodyum ve potasyum metabolizmas�n� d�zenler.
DehidroepiandrosteronAdrenel korteksAndrojen, erkek e�eysel �zelliklerinin geli�imini uyar�r.
Somatotropin (B�y�me hormonu�n hipofizKemik ve genel v�cut b�y�mesini denetler, ya� protein ve karbonhidrat metabolizmas�na etki eder.
Tirotropin (Tiroit uyar�r�c� hormon = TUH = TSH)�n hipofizTiroidin b�y�mesini ve tiroit hormonlar�n�n salg�lanmas�n� uyar�r.
Adrenokortikotropin (ACTH)�n hipofizAdrenel korteksin b�y�mesini ve kortikal hormonun salg�lanmas�n� uyar�r.
Luteinize

FACTORS INFLUENCING HORMONE ASSA RESULT INTERPRETATION

9/7/2010

Factors influencing hormone assay result interpretation

Accuracy
are we measuring the correct amount of analyte
Precision
how variable are the results of the analysis of a sample
within a batch
between batches
Specificity
do other substances interfere in the measurement
Sensitivity
can we measure low levels of the analyte
Linearity
is the correct result obtained when we dilute the sample

Ref range
Serum T4 =175 nmol/L[50 - 150]
Serum TSH = 0.01 mU/L[0.5 - 5.5]

?Thyrotoxic

Serum cortisol = 750 nmol/L[250 - 650]

?Cushings Syndrome

Good immunoassay
Coefficient of variation = 10%

T4 result of 175 nmol/L
95% confidence limits = 140 - 210 nmol/l

Cortisol result of 750 nmol/L
95% confidence limits = 600 - 700 nmol/l
Female age 27
Increasing hirsutism
? Late onset congenital adrenal hyperplasia

Ref range
Serum cortisol (9am)1730 nmol/L[250 -650]
17 hydroxyprogesterone260 nmol/L[up to 30]
Testosterone12 nmol/L[1.0 - 2.4]
Androstenedione 32 nmol/L[4 - 12]
Female age 27
Cholesterol

ProgesteroneAndrogens
[Testosterone]
17 OH progesterone[Androstenedione]
21 hydroxylase
11 deoxycortisol

CORTISOL
Interference in the assay
Antibodies not 100% specific
e.g. Cortisol
Many other steroids have similar structure
Patients with CAH  precursor steroids build up  cross react in cortisol assay  give high result when true result is low
HCG in some LH assays
Other steroids in assay for testosterone in females
T4 in T3 assay
Hydrocortisone / prednisolone in cortisol assay
Patient CB, female, age 32
Hypothyroid
Ref range
Serum T4= 214 nmol/L[50 - 150]
TSH= 15 mU/L[0.5 - 5.5]
T3= 2.0 nmol/L[1.0 - 2.4]
Free T4= 16 pmol/L[8 - 22]
TBG= 38 mg/L[15 - 30]
Male patient, age 52
Arrythmia
?Hyperthyroid
Thyroid function testsRef range
Total T4= 230 nmol/L[50 - 150]
TSH= 0.2 mU/L[0.5 - 5.5]
Total T3= 1.0 nmol/L[1.0 - 2.4]
Free T4= 36 pmol/L[8 - 22]
TBG= 20 mg/L[15 - 30]

METABOLIC MUSCLE DISEASE

9/7/2010

METABOLIC MUSCLE DISEASE

INHERITED DISORDERS OF METABOLIC PATHWAYS CAUSING MUSCLE DISEASE.
MUSCLE TISSUE IS MONOFUNCTIONAL
MUSCLE IS AN ATP GENERATING FACTORY
METABOLIC MUSCLE DISEASE EITHER CAUSES:-
ATP DEPLETION
STRUCTURAL DAMAGE

ADRENAL DISEASE

9/7/2010

Adrenal Disease

Clinical manifestations result from:-
Overproduction or deficiency of: -
Glucocorticoids
Mineralocorticoids
Androgens
Hyper-secretion may present differently depending on the disease mechanism.
Hypo-secretion may only be apparent at times of stress.
Adrenal Disease
Causes of dysfunction: -
Hyper-secretion:-
Primary adrenal pathology:-
Adenoma
Hyperplasia
Carcinoma
Enzyme defects
Secondary: -
Increased/autonomous ACTH production
Pathology of the Renin/angiotensin system
Receptor defects
Enzyme defects.
Adrenal Disease
Hypo-function:-
Primary adrenal dysfunction: -
Autoimmune
Infiltration
Infection
Enzyme deficiencies
Secondary: -
Pituitary disease
Iatrogenic
Adrenal Disease
General Concept for Investigations: -
Establish Hyper - or Hypo-function: -
Use screening tests:-
Short synacthen, dexamethasone suppression
Differentiate the cause of the dysfunction: -
Use secondary tests:-
ACTH measurement , long synacthen, high dose dexamethasone.
Investigation of Adrenal Disease
Requires knowledge of: -
Biological rhythms
Concept of feedback controls
Limitations of analytical techniques.
Glucocorticoid Excess
Cushing"s syndrome:-
Features of glucocorticoid excess.
Low ACTH.
High ACTH: ectopic or exogenous.
Cushing"s disease: -
Glucocorticoid excess
High ACTH: -
Pituitary origin as described by Cushing.
Pseudo-Cushing"s disease: -
Alcohol = functional 11-OH steroid dehydrogenase deficiency?
Cushings Syndrome
Epidemiology:
Prevalence 1/100.000
Age:
Cushing"s disease 25-45 years old.
Ectopic ACTH 40-65 years.
Sex:
Pituitary = female preponderance
Ectopic = male preponderance
Cushing"s SyndromeClinical Features
Skin
Thin Skin
Hirsutes
Acne
Striae
Bruising
Cardio-vascular
Hypertension
Psychiatric
Depression
Musculoskeletal
Moonface
Buffalo hump
Truncal obesity
Thin Limbs
Proximal weakness
Metabolic
Hyperglycaemia
Osteoporosis
Hypo-kalaemia
Cushing"s SyndromeLaboratory Findings: Non-Endocrine
Haematology:
Polycythaemia, leucocytosis, low eosinophil count
Biochemistry:
Glucose intolerance
insulin resistance due to glucocorticoid
Electrolyte disturbances
Hypokalaemia & hypernatraemia (mineralocortiocoid)
Screening for Cushing"s Syndrome
Low dose dexamethasone suppression test.Ann Clin Biochem 1997;34:222-229.
Procedure: -
1mg dexamethasone 23.00-24.00h
Serum cortisol 09.00h following day.
Cortisol should = 50 nmol/L
Interpretation: -
Cortisol should = 50 nmol/L (method dependant?)
2% False negatives
Requirement to measure dexamethasone ( 5.6 nmol/L)?
Screening for Cushings Syndrome
Low dose dexamethasone suppression test.
Drug effects = false positive:-
Oestrogen & tamoxifen due to effect on Cortisol Binding Globulin.
Nasal decongestants and oral contraceptives
Obesity = no effect
Weight reduction = false positives in 25%
Alcohol = false positives
Depressive illness = 30 - 50% false positives
Screening for Cushings Syndrome
Alternative protocol: -
0.5 mg dexamethasone 6 hourly for 48 hours
Serum cortisol 09.00h day 3 or 24 hour Urinary free cortisol.
Specificity = 97-100% v 87.5% for overnight procedure.
Screening for Cushings Syndrome
Urinary Free Cortisol: -
24 hour collection to give an integrated result.
Reference values vary with assay:-
Males 300 nmol/24 hours
Females 210
Elevated in 95% of Cushing"s and in stressed subjects (False +ve)
Assays are cumbersome, often involving extractions.
Use as part of screening process for in-patients.
Screening for Cushings Syndrome
Diurnal variation: -
Serum Cortisol at Midnight and 09.00h.
Avoid stress.
Normal:-
08.00h - 10.00h130-690 nmol/L
22.00h - 24.00h 260 nmol/Lor 50% of 09.00h valueCheck local reference values
Cushings:-
Loss of diurnal variation.
Differential Diagnosis of Cushing"s Syndrome
Primary Adrenal disease? Non-ACTH dependant.
ACTH measurement = low.
High dose dexamethasone suppression test.
Metyrapone testing (historical ?).
Measurement of androgens (DHEAS).
Secondary Disease? ACTH dependant.
ACTH measurement = high or inappropria

T�RO�D BEZ� HASTALIKLARINDA TANI VE TEDAV�

9/7/2010

T�RO�D BEZ� HASTALIKLARINDA TANI VE TEDAV�

Tiroid bezi i�inde 2 endokrin organ vard�r:

Tiroid hormonlar� ve kalsitonin salg�layan k�s�m (tiroid organ�)

Paratiroid hormon salg�layan k�s�m (paratiroid organ�)
Hipotalamik Pituitar Bez �li�kisi
Histoloji
Tiroid follik�ler yap� diyagramlar�. A: Normal fizyolojik durum. B: �stirahat durumu. C: Y�ksek aktivite.
Tiroid Hormon Sentezi
1. Kandan iyot al�nmas�
2. �yodun oksidasyonu ve tiroglobulin iyodinasyonu
3. Tiroglob�lin i�inde iyodotirozin molek�llerinin ba�lanmas� (T3 ve T4 olu�umu)
4. Tiroglob�lin proteolizisi
5. �yodotirozinlerin deiyodinasyonu
6. T3 ve T4"�n intratiroidal deiyodinasyonu
Tiroid Hormonu Etkileri
Fetal beyin ve iskelet mat�rasyonu
Artm�� bazal metabolizma h�z�
Kalp �zerine inotropik ve kronotropik etkiler
Katekolaminlere artm�� hassasiyet
Gut motilitesini uyar�r
Artm�� kemik turnover
Artm�� serum glukoz, azalm�� serum kolesterol

Guatrojenezis
�yot eksikli�i hipotiroidizme yol a�ar

Artm�� TSH tiroid hipertrofisine sebep olur (diff�z nontoksik guatr)

Follik�ller b�y�r, otonomi ve fonksiyonel kapasite kazan�r (multinodular guatr)

Follik�ller azalan TSH"ya ra�men b�y�meye ve fonksiyonel kapasite kazanmaya devam eder (toksik multinod�ler guatr)
Guatr
Troid bezinin b�y�mesidir.

Diff�z, nod�ler (soliter, multinod�ler)

Toksik, non-toksik

Endemik, sporadik, ailesel
TE�H�S
Hikaye
Ya�
Cinsiyet
Ba�lang�� ve b�y�me h�z�
Radyasyon
Aile hikayesi
Ge�irilmi� tiroid cerrahisi
A�r�, ses k�s�kl��, dispne, �ks�r�k, yutma g��l��
Hemoptizi, hematemez
Fizik Muayene

Benign tiroid nod�lleri

Mobil

D�zg�n s�n�rl�

Yumu�ak veya lastik k�vam�ndad�r. Ancak, kalsifiye olmu� ve i�erisi yo�un bir �ekilde s�v�yla dolmu� nod�ller sert k�vamdad�r.

Fizik Muayene
Malign tiroid nod�lleri

Fikse

�rreg�ler

Daha �nce bulunmayan bir nod�l varl��

S�presyon tedavisine ra�men nod�lde b�y�menin devam� ve h�zl� b�y�me

4 cm.den b�y�k kistik nod�ller

Fizik Muayene
A�r� ve duyarl�l�k

Subakut granulomat�z, radyasyon, invaziv fibr�z, akut s�p�ratif tiroidit

Kist veya dejeneratif bir nod�l i�ine kanama

H�zl� seyreden anaplastik karsinom gibi malignansiler

Fizik Muayene
Vokal kord paralizisi

Tiroid kanseri

B�y�k benign nod�ller

�ntratorasik guatr

Riedel tiroiditi
Laboratuvar
TSH ve tiroid hormon d�zeyleri

�tiroidi
Tiroid nod�l� olan hastalar�n �o�u
Tiroid kanserleri

Hipertiroidi
Soliter toksik nod�l
Toksik multinod�ler guatr
Graves zemininde geli�mi� nod�l

Hipotiroidi
Hashimoto tiroiditi (Kronik lenfositik tiroidit) zemininde geli�en nod�l veya lenfoma
Laboratuvar
Antikor �al��malar�: Otoimm�n hastal�klarda
Serum antitiroglobulin
Serum antimikrozomal antikor

Kalsitonin: Med�ller karsinom tan�s�nda ve takibinde

Sedimantasyon: Tiroiditler gibi enflamatuvar olaylarda

G�r�nt�leme Y�ntemleri
Radyoizotop y�ntemler: Tc 99 perteknetat, radyoiyodin (I-123) ve Talyum 201 en s�k kullan�l�r. I-131 ise metastatik tiroid kanserinin taranmas� ve radyoaktif iyot tedavisi ile s�n�rl�d�r.

Mediastinal nod
Substernal guatr
Ektopik tiroid dokusu
Giri�imsel tiroid anomalilerinin ara�t�r�lmas�
Boyunda tiroid karsinom metastazlar�n�n g�sterilmesi
Uzun kemikler ve akci�erlerdeki fonksiyoner metastazlar�n g�sterilmesi
S�cak ve so�uk nod�llerin g�sterilmesi

TESTOSTERONE REPLACEMENT FOR MEN AND WOMEN

9/7/2010

Testosterone Replacement for Men and Women

Presenting from the Premises of Port Power

The human ovary produces more testosterone than oestrogen- weight for weight
The postmenopausal ovary continues to produce testosterone after the cessation of follicular activity cuts off the supply of oestrogen
As the ovary fails, it continues to produce testosterone and perhaps in increased amounts…for a variable number of years.This is the so called… "continuation of ovarian function postmenopausally".i.e. progressive androgenisation!
With the introduction of HRT (oestrogen only or ERT), testosterone status falls to zero.This is due to two factors
It follows therefore, that any woman taking oestrogen or producing excess oestrogens is relatively or absolutely testosterone deficiente.g.the oral contraceptivemulticystic ovaryoestrogen replacement
Oestrogen and progesterone are the mainstay of ERT.Testosterone may still be viewed as the,"Cinderella of the hormonal ball"…but she got to marry Prince Charming!
Symptoms
Testosterone replacement is generally regarded as indicated for loss of libido
(by a predominantly male profession)

….. and while this may be true, other symptoms are of greater importance.
Indications for testosterone replacement
Symptoms
Vulval discomfort
? Voiding dysfunction
Painful benign breast disease
? Prevention of breast cancer
Osteoporosis
Symptoms relieved
Variable mood state-tearful or aggressive
Loss of energy and stamina
Impaired concentration and memory
General skin and scalp hair dryness
Loss of sexual arousability
Painful breasts
Vulval skin dryness/ discomfort/ itching
Voiding disorder ?
Restored/ increased muscle strength
Odds and ends

may improve tachycardias
seems to suppress petit mal
(despite warnings on the P.I.)
some headaches improve
neck and back pain
improves athletic competition
improved sleep quality
increases insulin sensitivity
lichen sclerosis
Objective aims ofAndrogen Replacement Therapy (ART)
improved quality of life
increase bone density (5-12% p.a.)
suppression benign breast disease
reduction of the incidence of breast cancer
maintain the cardioprotective effect of ERT
improved muscle strength (skeletal and myocardial)
Side Effects ♀
evening restlessness
excess libido
nightmares
possible relationship disruption
facial greasiness and acne
male type scalp hair loss
facial hair

T�RO�D VE PARAT�RO�D BEZ� HASTALIKLARI

9/7/2010

T�RO�D VE PARAT�RO�D BEZ� HASTALIKLARI

T�RO�D BEZ� HASTALIKLARI
SINIFLANDIRMA
A-Fonksiyonel hastal�klar
1-Hipertiroidiler
-Diff�z hipertiroidi
-Nod�ler hipertiroidi
2-Hipotiroidiler
-Spontan:tiroidit ve t�m�rler
-Cerrahi, s�presyon ve radyoterapiB-Organik hastal�klar
1-Tiroiditler
-Akut tiroiditler: Bakteriyel
-Subakut tiroiditler
Gran�lomat�z (De Quervain) tiroidit
Lenfositik (sessiz) tiroidit
-Kronik tiroiditler
Hashimato hastal�� (kronik lenfositik tiroidit, struma lenfomatoza)
Riedel strumas� (fibr�z yada invaziv tiroidit)
2-T�m�r grubu hastal�klar
-Diff�z tiroid b�y�mesi
-Benign b�y�meler
Adenomat�z guatr
Follik�ler adenom
Hiperfonksiyon g�ren adenom
3-Malign b�y�meler
Papiller tiroid Ca.
Follik�ler tiroid Ca.
Med�ller tiroid Ca.
�ndiferansiye tiroid Ca.
Di�er: Epidermoid karsinom, Lenfoma, Sarkom, Metastatik karsinomlar
F�ZYOLOJ�
Tiroid hormonu protein yap�s�ndad�r. Tirozin amino asidi 3-4 adet iyot molek�l� ile birle�ince tiroid hormonlar� olu�ur. Tiroid hormonlar� follik�ller i�inde tiroglob�ne ba�l� olarak depolan�r. Follik�lden de�i�ik kontrol mekanizmalar�n�n etkisi alt�nda T3 ve T4 olarak salg�lan�r.T3"�n aktivitesi y�ksek fakat k�sa �m�rl�d�r, T4 ise aktivitesi d��k, uzun etkilidir ve periferde T3"e d�n��erek aktivitesini artt�rabilir.
Tiroid hormon salg�s� ba�l�ca TSH ile kontrol edilir. TSH ise TRH ile kontrol edilir.
T�RO�D BEZ�N�N DE�ERLEND�R�LMES�
Hastada kitle bulgusuna ba�l� olarak ses k�s�kl��, yutma g��l��, �zellikle substernal guatrda solunum yollar�nda t�kanma g�r�l�r. Tiroid bezi trakeaya fikse oldu�undan yutkunma ile hareket eder. Hasta yutkunurken hareket eden hareket eden bezin b�y�kl�� incelenir. Sonra boyun ekstansiyona getirilip tiroid bezi �n ve arkadan muayene edilir. Loblar�n b�y�kl�k ve geni�li�i santimetre olarak �l��l�r. Ayr�ca palpasyonla tiroid y�z�n�n d�z, irreg�ler, lob�ll�, nod�ler olup olmad�� ve k�vam� belirtilir. A�r� olup olmad�� sorulur. Servikal LAP maligniteyi g�sterebilir. Substernal kitleler trakeada deviasyona neden olabilir.
LABORATUAR �ALI�MALARI
1-Bazal metabolizma ve a�il refleksi
2-Serum hormon d�zeylerinin �l��lmesi (T3, T4, serbest T3 ve T4 seviyesi, TSH)
3-Serum tiroglob�n seviyesi
4-Tiroid otoimm�nite testleri (antitiroglob�n, antimikrozomal antikorlar ve LATS)
5-Radyoaktif iyot tutulumu
6-Tiroid stim�lasyon testi: TSH ile yap�l�r
7-Proteine ba�l� iyot �l��m�
8-Serum kolestrolu: hipertiroidide azal�r,hipotiroidide artar
9-Sintigrafi: Normal tutulum
:So�uk tutulum; tiroid hipofonksiyonu
:S�cak tutulum; tiroid hiperfonksiyonu
10-Ultrasonografi: Solid nod�l;
sintigrafi ile so�uk oldu�u saptan�rsa malignite lehine
sintigrafi ile s�cak oldu�u saptan�rsa hipertiroidi lehine
: Kistik nod�l
11-Biopsi: �zellikle so�uk nod�llerde endikedir.
-��AB; %90"�n �zerinde do�ru sonu� verir.
-Silverman i�nesi ile doku biopsisi; g�n�m�zde fazla kullan�lm�yor.
-A��k biopsi

H�PERT�RO�D�
Tiroid hormon d�zeyinin kanda artmas� sonucu bazal metabolizma ve sempatik sistem uyar�m�na ba�l� semptomlarla giden hastal�k halidir. Nedenleri;
- Graves Basedov Hastal��: Hipertiroidinin en s�k nedenidir. Otoimm�n bir hastal�kt�r. �� komponenti vard�r:
a-Toksik diff�z guatr
b-�nfiltratif oftalmopati
c-�nfiltratif dermopati; pretibial �dem
20-40 ya�lar� aras�nda kad�nlarda s�kt�r. Tiroid dokusunda TSH resept�r�ne kar�� antikor vard�r (LATS ). Ailesel �zellik g�sterir. Di�er otoimm�n hastal�klarla birlikte g�r�lebilir (pernisiy�z anemi, myastenia gravis gibi).
- Plummer Hastal�� (Toksik nod�ler guatr); Genellikle 40-65 ya� aras�nda uzun s�reli noduler guatrl� olanlarda g�r�l�r.
- Jod-Basedov Hastal��; Multinoduler guatrl� olan ki�ilerde fazla iyot al�m�ndan sonra ortaya ��kar.
-Tirotoksikozis fastidia; A��r� eksojen tiroid al�m�na ba�l�d�r.
- Struma ovari ve mol hidatiform
- Tiroid

HORMONLAR

9/7/2010

MONLAR

�nsan v�cudunda hormon denen kimyasal ileticilere dayal� �zel bir bilgi ta��ma sistemi vard�r. Bu organik kimyasal maddeler kanals�z i� salg� bezlerinde yap�l�r ve do�rudan kan dola��m�na verilir. �o�u durumda bu hormonlar kan dola��m�yla hedef organlara ula��r ve orada biyokimyasal tepkimeleri ba�lat�r ya da durdurur.
En �nemli i� salg� bezleri hipofiz, tiroit, paratiroitler, pankreas, b�brek�st� bezleri ile yumurtal�klar ve erbezleridir. A�a��da bu salg� bezlerinin �retti�i hormonlar incelenecektir. Mide, inceba��rsaklar ve b�brekler de hormon �retir. Ayr�ca epifiz bezi ve timus bezinin de hormon salg�lad�� d��n�l�r.
Gebe kalan memeli hayvanlar�n etenelerinin de salg� i�levi vard�r. Etene hem yumurtal�k ve hipofiz hormonlar�n� yapabilir, hem de kendine �zg� hormon salg�lar.
Canl�lar�n pek �o�u hormon �retir. �rne�in b�ceklerin ya�amlar�n�n de�i�ik evrelerinde b�y�melerini durduran ya da h�zland�ran hormon salg�lar� vard�r. Bu hormonlar�n dengede tutulmas�yla b�cek normal bir geli�me g�sterir. B�ceklerin deri de�i�tirmelerini ve ba�kala�malar�n� etkileyen ektizom �nemli bir b�cek hormonudur.
Bitkiler de hormon �retir. En iyi bilinen bitki hormonu, k�k ve g�vde b�y�mesini uyaran indoliasetik asittir.

Hipofiz Bezi �b�r Salg� Bezlerini Denetler
Beynin alt�nda yer alan hipofiz bezinin �n lob (adenohipofiz) ve arka lob (n�rohipofiz) adl� iki b�l�m� vard�r. Baz� hayvanlarda bulunan orta lob da �n lobla birlikte de�erlendirilir.
Hipofiz bezi v�cuttaki �b�r i� salg� bezlerinin bir�o�unun i�leyi�ini etkiler. Hipofiz hormonlar�n�n b�y�k b�l�m� �n lobda yap�ld��ndan �n hipofiz v�cudun "ana" salg� bezi olarak an�l�r. �n hipofiz hormonlar� kimyasal a��dan polipeptit ya da karma��k protein yap�s�ndad�r. Bu gruptaki hormonlar b�y�me hormonu (GH), prolaktin hormonu, adrenokortikotrop hormon (ACTH), lipotropik hormon (LPH), tiroid uyar�c� hormon (TSH), folik�l uyar�c� hormon (FSH), ara h�cre uyar�c� hormon (ICSH) ve melanosit uyar�c� hormondur (MSH). Hipofiz arka lobu ise hormon �retmez; beynin hipotalamus b�l�m�nden �retilen iki hormonu depolar. Her ikisi de polipeptit yap�s�nda olan bu hormonlar vazopressin ve oksitosindir.
Hemen hemen b�t�n �n hipofiz hormonlar� belirli dokular �zerinde etki g�sterir. Yaln�z b�y�me hormonu v�cudun b�t�n�n� etkiler; ayr�ca �b�r hormonlar� destekler. Prolaktin meme dokusunun geli�imini ve s�t yap�m�n� denetler. ACTH b�brek �st� bezlerinin steroid hormonlar� salg�lamas�n� sa�lar. TSH tiroit bezinin tiroksin salg�s�n� uyar�r. FSH ile ICSH gonatlar�n, yani yumurtal�k ve erbezlerinin e�ey hormonlar� salg�lamalar�n� sa�lar. MSH derideki renk de�i�ikli�ini belirleyen melanositleri uyar�r. LPH de ya� dokular�ndaki lipiti harekete ge�irir.
Hipofiz bezinin ya�am�n ilk y�llar�nda tam gerekti�i kadar b�y�me hormonu salg�lamas� gerekir. E�er bu d�nemde gerekenden az b�y�me hormonu salg�lan�rsa �ocukta c�celik, a��r� hormon salg�lan�rsa da devlik geli�ir. Ama bu hastal�k maymunlardan elde edilen b�y�me hormonu ya da insan b�y�me hormonu (HGH) verilerek tedavi edilir. Yeti�kinlikte a��r� b�y�me hormonu �retimi akromegali hastal��na yol a�ar ve �ene, el ve ayaklar b�y�r. Bu durumda hipofiz bezinin ameliyatla al�nmas� gerekir.
Hipofiz bezinin arka lobundan salg�lanan vazopressin hormonu damarlar� etkileyerek tansiyonu y�kseltir. V�cudun su tutmas�na yard�mc� oldu�undan bazen antidi�retik hormon olarak da adland�r�l�r. Bu hormon b�breklerin a��r� idrar �retmesini engeller. Vazopressin yoklu�unda insanlarda �ekersiz diyabet hastal�� g�r�l�r ve hasta g�nde 30 litreye kadar idrar yapar. Oksitosin d�lyata��n�n kaslar�n� kasarak do�umu ba�lat�r; annenin memelerinden s�t salg�lamas�na yol a�ar ve do�um sonras� kanamay� denetler.

Tiroit Bezi V�cut Enerjisini D�zenler
Tiroit bezi boyunda, soluk borusunun her iki yan�nda yer al�r. �ki lobu ortadan birle�tiren dokuyla tiroit bezi "H" harfine benzer. Yeti�kinlerde tiroit bezinin a��rl�� ortalama 30 gr"d�r. TSH"nin s�rekli etkisi alt�nda �al��an tiroit bezi, g�dalarl

SEROTONIN MECHANISMS IN THE PATHOPHSIOLOG OF SCHIZOPHRENIA

9/7/2010

Serotonin Mechanisms in the Pathophysiology of Schizophrenia

SLIDE 1
Schizophrenia Pathophysiology and Pharmacologic
Profile of Antipsychotic Drugs (APDs)
Historically in psychiatry, clinicians found effective treatments
for schizophrenia and then took the drugs into the laboratory
to explain how they worked. Before the 1990s, antipsychotic
drug (APD) development focused exclusively on agents with
substantial activity at dopamine-D2-receptor sites. Although
blockade of D2 receptors results in decreased positive symptoms,
such as hallucinations and delusions, D2 antagonists are
associated with discomforting neurological side effects that
are often present at their clinically effective doses. In addition,
these agents have limited efficacy for important symptom
dimensions in schizophrenia, particularly negative and
cognitive symptoms.
The development of the "atypical" antipsychotic clozapine
renewed interest in the role of serotonin (5-HT) in schizophrenia.
Clozapine is associated with reduced liability for
extrapyramidal symptoms (EPS) and is effective in 30% to
50% of treatment-resistant patients.1 Clozapine is characterized
by weak activity at D2 receptors and potent activity at
serotonin 5-HT2A, 5-HT2C, and 5-HT3; histaminic; a-adrenergic;
D1 and D4; and cholinergic receptors.2
The field is abandoning single neurotransmitter models and
an exclusive focus on dopamine-D2 receptors and is moving
toward more integrative models that encompass multiple
neurotransmitter systems, including serotonergic, glutamatergic,
dopaminergic, and cholinergic systems. This slide kit
focuses on the role of serotonin in schizophrenia and its
interactions with other centrally active neurotransmitters.
2
SLIDE 2
Receptor Binding Profiles of Conventional
and Atypical APDs
For conventional APDs, clinical characteristics were recognized
well in advance of understanding the pharmacologic
profile of the drugs. In contrast, in vitro profiles have been
established for the atypical APDs in an effort to understand
the role of particular neurotransmitters and their receptors in
the effectiveness and tolerability of these compounds.
Haloperidol is a potent D2-receptor antagonist, with moderate
affinity for the a1-adrenergic receptor.3 The atypical APDs are
characterized by balanced D2/5-HT2-receptor antagonism
plus moderate affinities at a number of other receptor sites.
Antagonism at the 5-HT2-receptor site is believed to contribute
to the improved tolerance with atypical APDs in terms of
classic D2 side effects, such as EPS. However, the multiple
receptor activity of many atypical agents produces a number
of other potential side effects, including weight gain, sexual
dysfunction, hypotension, and sedation as well as contributing
to efficacy.3 The characteristics of D2 binding, loose versus
tight, appear to influence the drugs" atypicality.3a
3
SLIDE 3
Impact of Schizophrenia Symptoms
on Functional Outcomes
The characteristic symptoms of schizophrenia have been
conceptualized as falling into 3 broad categories: positive,
negative (or deficit), and cognitive (or disorganized).4 Positive
symptoms include delusions and hallucinations. Cognitive
symptoms include disorganized speech, thoughts, and behavior,
and poor attention. Negative symptoms include restricted
range and intensity of emotional expression (flattened affect),
reduced thought and speech productivity (alogia), anhedonia,
and decreased initiation of goal-directed behavior (avolition).4
Negative symptoms recently have been divided further into
the following three components: (1) deficit or primary enduring
negative symptoms that may not respond to treatment;
(2) primary nonenduring negative symptoms; and (3) secondary
negative symptoms.5 Primary negative symptoms are
thought to be intrinsic to schizophrenia, and little is known
about their neurobiology or effective treatment. Secondary
negative symptoms appear as a consequence of other factors,
including positive symptoms, neuroleptic-induced
Parkin

ANK�LOZAN SPOND�L�TTE GONADAL VE ADRENAL C�NS�YET STERO�DLER�

9/7/2010

ANK�LOZAN SPOND�L�TTE GONADAL VE ADRENAL C�NS�YET STERO�DLER�

Baz� raporlar, gonadal hormonlar�n ankilozan spondilitin (AS) etyolojisiyle ba�lant�l� olabilece�ini g�stermektedir, fakat AS"nin etyolojisindeki genetik ve imm�nolojik unsurlara ili�kin bulgular, halihaz�rda daha ge�erlidir. Fakat, endokrin fakt�rlerin bu hastal��n genetik ve imm�n mekanizmalar�yla etkile�me ihtimali halen mevcuttur. HLA - B27 y�n�nden pozitif olan �ah�slarda, AS ve di�er spondiloartropatilere kar�� olan yatk�nl��n artmas�, iyi bir �ekilde belgelenmi�tir. Tan�mlanmam�� gen lokuslar�n�n AS"nin patogenezinde rol� olmas� ihtimali vard�r. AS ile h�cre y�zeyindeki s�n�f - 1 MHC molek�l� olan HLA - B27 aras�ndaki ba�lant�n�n alt�n� �izen baz� hipotezler mevcuttur, fakat bu mekanizmalar bu g�zden ge�irme �al��mas�n�n konusunun d��ndad�r. Klebsiyella enterokolitika, klamidya trakomatis ve bunlardan biraz daha hipotetik olan Yersiniya, Kampilobakter, Klostiridyum, Salmonella ve �igella gibi mikroorganizmalar da, AS"nin patogenezinde rol oynayabilir.

Enflamatuvar Hastal�klardaki �arp�k Cinsiyet Oran� :

Baz� hastal�klar�n �arp�k bir cinsiyet oran� vard�r. E�er bu �arp�k da��l�m ba�kaca bir unsurla a��klanamazsa, cinsiyet steroidleri bir a��klama olarak d��n�lebilir. SLE, imm�n trombopeni, Sj�gren hastal��, romatoid artrit, skleroderma, multiple skleroz, birincil primer siroz, tiroidit ve Graves hastal�� gibi otoimm�n veya romatik hastal�klar�n �o�u, kad�nlarda a��rl�kl� olarak daha fazla g�r�l�r. Da��l�mdaki bu �arp�kl��n, en az�ndan k�smen imm�n cevab�n �strojenlerce art�r�lmas�n�n veya imm�n bask�lanman�n ve androjenlerin bir neticesi olabilece�i d��n�lmektedir. Cinsiyet hormonlar�n�n kronik enflamatuvar hastal�klar� uyarabilece�i hipotezine kar�� bir ba�ka g�r��, kad�nlarda �strojen kullan�m�n�n bu t�r hastal�klar�n g�r�lme s�kl��nda art��a yol a�mad�� g�zlemine dayanmaktad�r. Enflamatuvar hastal�klarda cinsiyet hormonlar�nca meydana gelen bu imm�n mod�lasyon tek ba��na a��klanamaz, ��nk� �lseratif kolit, Crohn hastal�� ve sarkoidoz gibi �arp�k bir cinsiyet da��l�m� sergilemeyen di�er enflamatuvar rahats�zl�klar da mevcuttur. Aksine AS, poliarteritis nodoza ve Wegener gran�lomatozu gibi baz� enflamatuvar hastal�klar da, erkek bask�nl�� g�stermektedir. AS"nin tan�s� i�in daha az �zg�n �l��tlere sahip erken �al��malar, yak�n ge�mi�li �o�u �al��mada daha d��k ��kan ve en fazla 3:1 civar�nda oldu�u tahmin edilen oranlara ra�men, y�ksek erkek / kad�n oran� g�stermi�lerdir. Sporadik vakalardaki erkek bask�nl��, ailesel vakalardan biraz daha fazlad�r. AS"li hastalar�n birinci dereceden erkek ve kad�n akrabalar�ndaki g�r�lme s�kl�� kabaca ayn� olmas�na ra�men, sporadik vakalardaki erkek bask�nl�� ailesel vakalardan biraz daha fazlad�r. AS"nin cinsiyet da��l�m�na ba�l� tan�ml� fig�rlerin temin edilmesi, halihaz�rda zor bir i�tir. �ncelikle, AS"ye ili�kin isabetli prevalans verisi konusunda eksiklikler vard�r. Bu eksiklikler, k�smen hastal��n farkl� �l��t setlerinin bir neticesidir. 16 ya� alt�ndaki hastalarda, AS"nin tan�s�nda mihenk ta�lar�ndan biri olan sakroiliyak eklemlerdeki anormal radyolojik bulgular�n de�erlendirilmesi g��t�r. 16 ya� �ncesinde hastal��a yakalanan AS"li hastalardaki cinsiyet oran�n�n 2.6 : 1 oldu�u rapor edilmektedir. Ereklerdeki bu risk art��, pubertedeki testosteron patlamas�na ba�lanm��t�r. Hastal�k, kendisini hemen daima 45 ya� �ncesinde belli eder. AS, 45 ya� sonras�nda nadiren g�r�l�r ve daha ileriki ya�larda g�r�len daha denk cinsiyet da��l�m�, hormon profillerinde ya�lanmayla birlikte cinsiyet farkl�l�klar�n�n azalmas�yla izah edilmektedir. Kad�nlar menapoz sonras�nda �ok az �strojen salg�lar, fakat testosteron buna g�re % 10 - 25"lik daha hafif bir d�� g�sterir. Di�er baz� unsurlar�n da, cinsiyet oranlar�n�n isabetli bir �ekilde tahmin edilmesini etkileyebilece�i de ak�lda tutulmal�d�r. Kal�tsal y�nden yerel farkl�l�klar vard�r ve �evresel tetikleyiciler de, d�nyan�n farkl� b�lgelerinde �e�itlilik g�sterir.

�LER� SEV�EDE FARKLILA�MI� T�RO�D KANSERL� HASTALARDA RADYOAKT�F �OT TEDAV�S� �NCES�NDE REKOMB�NANT �NSAN T�ROTROP�N HORMONUNUN KULLANIMI

9/7/2010

�leri Seviyede Farkl�la�m�� Tiroid Kanserli Hastalarda Radyoaktif �yot Tedavisi �ncesinde Rekombinant �nsan Tirotropin Hormonunun Kullan�m�

�zet :

Farkl�la�m�� tiroid kanserli (DTC) hastalarda iyot - 131"li radyoablatif tedavinin kullan�m�, iyotun tiroid dokusu taraf�ndan etkin �ekilde tutulmas� i�in yeterli seviyede TSH serum yo�unlu�unu gerekmektedir. Serum TSH seviyesini art�rmada standart bir y�ntem olan tiroid hormon bask�lama tedavisinin (THST) geri �ekilmesinin bir se�enek olmad��, ileri derecede ve / veya tekrarlayan (5"i papiller ve 6"s� folik�ler) DTC"li 11 hastada, ablatif radyoaktif iyot tedavisiyle (RIT) birlikte rekombinant insan TSH (rhTSH) hormonunun kullan�m�n� izah ettik. Bu hastalarda rhTSH kullan�m endikasyonlar� aras�nda, �ok zay�f fiziki �artlara ba�l� olarak tiroid hormonlar�n�n geri �ekilmesini kar��layamama veya THST"nin geri �ekilmesinin akabinde yeterli seviyede serum TSH yo�unlu�unun sa�lanamamas� gibi durumlar vard�r. On hastaya tiroidektomi ameliyat� yap�ld� ve bu hastalar�n �o�u (11 hastadan 9"u), THST"nin �ekilmesini m�teakiben ablatif RIT tedavisi ald�lar. Taban tiroglob�lin seviyeleri, hasta pop�lasyonunun heterojenitesini yans�t�r �ekilde 25 ile yakla��k 30,000 ng / mL. aras�nda de�i�mektedir. (5 hastay� i�eren) yedi vakada, iyot - 131 tedavisinden sonraki ortalama 4,3 ay sonra (2 - 10 ay aras�nda) de�erlendirilen tedavi sonras� tiroglob�lin seviyeleri, tedavi �ncesindeki seviyelere g�re en az % 30 oran�nda azalm��t�. Yap�lan takiplerde �� hasta, klinik y�nden belirgin iyile�me ve v�cut taramas�nda, tedavi �ncesindeki taramalara nazaran t�m�r kitlesinde sabit kalma veya k��lme durumunu sergiledi. �� hasta, tedaviye ba�lan�lmas�ndan sonraki iki ay i�erisinde ve takip de�erleri yap�lmadan �nce, hastal��n ilerlemesi dolay�s�yla �ld�ler. Elde edilen neticeler rhTSH"nin, ba�ka �ekilde bu tedaviyi alamayan tekrar eden ileri seviye DTC"li hastalarda, etkin TSH uyar�m�n�n akabinde ablatif RIT"e imkan sa�lamak i�in THST"nin geri �ekilmesine bir alternatif vaadetti�ini �ng�rmektedir. Bu yeni ajan�n klinik potansiyelini art�ran tedavi endikasyonu, bu ilac�n iyot - 131 ile birlikte tan� amac�yla etkin bir �ekilde kullan�labilece�ini g�stermi�tir.

Farkl�la�m�� tiroid kanserinin (DTC), tam veya b�t�ne yak�n tiroidektomi ameliyat� ve radyoiyot ablasyonu ve akabinde, tiroid hormonlar�n�n endojen TSH ile bask�lanmas�n�n ard�ndan, m�kemmel bir prognozu oldu�u iyi bilinmektedir. Fakat, tahminen hastalar�n y�zde 5 ile y�zde 20"sinde yerel veya b�lgesel n�kzler ve % 10 - 15"inde de, ablatif radyoaktif iyot tedavisi (RIT) gerektiren uzak metastazlar mevcuttur. Radyoaktif iyodun tan� maksad�yla kullan�lmas�na benzer �ekilde, tiroid dokusundaki iyot al�m�ndaki art��la birlikte (x 30 mU / L), endojen TSH seviyelerinin y�kselmesi i�in iyot - 131 tedavisi tatbik edilen DTC"li hastalara, birka� hafta tiroid hormonu verilmemesi gerekmi�tir. Fakat, neticede ortaya ��kan hipotiroidizm, s�kl�kla zay�f bir �ekilde kar��lan�r ve baz� vakalarda, k�t� durumdaki hastalarda �l�mc�l bile olabilir. Ek olarak, hastalar yeterli iyot - 131 al�m� i�in gereken endojen TSH seviyelerine sahip olamayabilirler. Baz� vakalarda, bu durum beyindeki metastazlara neticesinde ortaya ��kan pit�iter yetmezli�e (ikincil hipotiroidizm) ba�l� olabilir.

Tiroid hormonlar�n�n kesilmesine bir alternatif olarak serum TSH seviyelerini art�rmak i�in rekombinant insan TSH hormonunun kullan�lmas�n�n, DTC"li hastalar�n takibinde etkin bir ara� oldu�u g�sterilmi�tir. Yak�n ge�mi�teki �al��malar, rhTSH"nin tiroid dokusundan sal�nan serum tiroglob�lininin sal�nmas�n� uyard��n� ve sintigrafi i�in iyot - 131 al�m�n� art�rd��n� g�stermi�tir. Tan� taramas� maksad�yla radyoaktif iyot verilmeden �nce rhTSH ile tedavi edilen 400"den fazla hastan�n hi�birinde, bug�ne dek herhangi bir ciddi yan etki rapor edilmemi�tir. DTC"li hastalar�n takip sintigrafileriyle ilgili olarak �ok yak�n ge�mi�te ger�ekle�tirilen rhTSH"nin Faz - III denemesinden elde edilen neticele

OBEZ�TE

9/7/2010

G�R��
�i�manl�k (obezite); sa�l�� bozacak d�zeyde v�cutta ya� miktar�n�n artmas�d�r. Di�er bir tan�mla v�cut a��rl��n�n ya�,cinsiyet ve boy uzunlu�una g�re %20 ve �zerinden fazla olmas�d�r. Ancak bu tan�ma g�re birey �i�man m� yoksa kas kitlesi mi fazla tan�mlanamamaktad�r. V�cuttaki ya� miktar�na ve da��l�m�na ba�l� olarak hastal�klar�n mobidite ve mortalitesi de�i�kenlik g�stermekte, ya�am kalitesi ve s�resi olumsuz y�nde etkilenmektedir. Kalp hastal�klar�, hipertansiyon, kanser (meme,prostat, kolon, endometrium), Tip2diyabetosteoartrit, safra kesesi hastal�klar�, uyku apnesi solunum yetmezli�i g�r�lme s�kl�� artmaktad�r.(8) �lkel insanlardan g�n�m�ze, modern insana uzanan bir yolda hareketin biyolojik olarak �ok farkl� bir boyuta geldi�ini g�rmekteyiz. (6)
Tekerle�in icad� ile insano�lu kendine verilmi� �zel kuvvet ve g�c� makineler yard�m�yla kullanmaya ba�lam��t�r. G�nl�k ya�ant�m�za makinelerin girmesi ile; ba�ta y�r�me, ko�ma , olmak �zere t�rmanma, inme, s��rama, ��melme, e�ilme gibi temel ve do�al hareketler insan ya�am�nda azalmaktad�r. Evlerde i� kolayla�t�ran aletlerin �o�almas�, ula��m kolayl�klar� televizyon, bilgisayar kullan�m�n�n yayg�nla�mas�, aktivitenin ve enerji harcamas�n�n azalmas�na yol a�m��t�r. G�nl�k ya�amdaki bu de�i�ikliklere paralel olarak, birey beslenme al��kanl��n� de�i�tirmedi�i ve bedensel aktivitesini artmad�� i�in al�nan enerjinin kullan�lan enerjiden fazla olmas� sonucu �i�manl�k ortaya ��kmaktad�r. (9)
�i�manl�k 20. y�zy�l�n estetik kavram�na uymamaktad�r; gen�ler i�in bir �z�nt� kayna��d�r. �i�man �ocuklarda puberte belirtileri daha erken ��kmaktad�r. Bu erken geli�me, gen�lik �a��nda ruhsal sorunlara yol a�maktad�r. Yeti�kinlerde ise �i�manl�k sa�l�� olumsuz y�nde etkilemekte ve erken �l�mlere sebep olmas� nedeni ile istenmemektedir. �zellikle kalp damar hastal�klar�nda �i�man ki�iler normal a��rl�ktakilere g�re daha fazla risk alt�ndad�r.
G�n�m�zde �i�manl�k konusu t�m d�nyada oldu�u gibi T�rkiye"de de g�ncelli�ini devam ettirmektedir. Bug�n milyonlarca insan �i�manl�klar�ndan kurtulmak i�in kilolar�yla sava� vermektedirler. Geli�mi� �lkelerde insanlar zay�flama haplar�na milyarlarca dolar harcamaktad�rlar. Bunlar probleme sadece k�sa �m�rl� ��z�mler sa�lamakta ve v�cut a��rl��nda b�y�k dalgalanmalara neden olmaktad�r.
Yap�lan �e�itli ara�t�rmalar, �i�manl��n tedavisinde egzersizin, ya� kaybedilirken ya�s�z dokunun korunmas�na yard�m etti�ini g�steren sonu�lar bulunmu�tur. Total v�cut kitlesi ve ya� kitlesi genellikle dayan�kl�l�k sporlar�yla (uzun s�reli orta �iddette yap�lan sporlar; 10 km h�zl� y�r�y��) d��r�l�r ya�s�z kitle ayn� kal�r yada hafif�e artar.
Optimal v�cut bile�imi de�i�ikli�i kalori k�s�tlamas� ile beraber egzersiz yap�ld�� zaman meydana gelmektedir. Diyet ve egzersiz kombinasyonu bir taraftan ya� kitlesini azalt�rken di�er taraftan ya�s�z v�cut kitlesinin muhafaza edilmesine yard�mc� olmaktad�r. Bir�ok ara�t�rmac�lar�n bulgular� bu iddialar� destekler niteliktedir. (9)
1- OBEZ�TEN�N TANIMI
�i�manl�k, v�cutta a��r� ya� depolanmas� sonucu ortaya ��kan bir beslenme sorunudur.Ya� ilerledik�e s�kl�� artmaktad�r.�i�manl�k, sadece bir g�r�n�� kusuruna, bedensel faaliyet yeteneklerinde k�s�tlamaya yol a�makla kalmaz, kesin olarak �mr� k�saltan bir fakt�rd�r.
V�cut ya� miktar�, v�cudun en de�i�ken k�sm�d�r ve ayr� cins, boy ve a��rl�ktaki bireyler aras�nda de�i�ir.Yap�sal olarak �i�manl�ktan s�z edilirken �i�manl�k, v�cudun di�er k�s�mlar�na g�re ya� kitlesindeki art��t�r. Genellikle kad�nlarda v�cut ya� miktar� erkeklerden fazlad�r.Kad�nlarda toplam v�cut a��rl��n�n %26,9"u, erkeklerde ise %14,7"si ya�d�r.A�a��daki Tablo-1"de referans erkek ve kad�nda v�cut ya� da��l�m� verilmi�tir.
Tablo 1. Referans Erkek ve Kad�nda V�cut Ya� Da��l�m� ( kg )
Ya� Da��l�m�

SHORT BOWEL SNDROME

9/7/2010

Short Bowel Syndrome

1- Inadequate length of intestine
2- Diarrhoea
3- Steatorrhoea
4- Weight loss
5- Nutritional deficiency
6- Rapid intestinal transit
7- Hypergastrinaemia

- The mean length of the adult small intestine in life has been estimated at 450 cm but it is 200 cm longer when measured at autopsy
- Precise measurement is impossible because of constant variations in tone and contractility, which can be modified by drugs and by stretching
- Repeated measurements at laparotomy on the same patient invariably produce a different answer each time, so any claim to precision is entirely illusory
- As a general rule 50 % of the small intestine can be resected without causing severe or persistent malabsorption
- Lifelong dependence on medical support is inevitable for any patient with less than 100 cm of small intestine
- This phase begins as soon as the postoperative ileus has recovered and lasts for about 4 weeks.
- Its characteristic feature is profuse watery diarrhoea with the passage of 5 to 10 L of fluid daily per rectum or through the stoma.
- Severe fluid and electrolyte depletion is liable to occur and unless the loss is replaced as it takes place, a life-threatening situation can rapidly develop.
- These problems, which basically arise as a consequence of acute loss of much of the intestinal surface area and rapid intestinal transit.
- The problem is compounded by gastric hypersecretion secondary to the hypergastrinaemia which commonly occurs.
- Acute peptic ulceration (stress ulcer) is liable to develop and routine prophylaxis with proton pump blocker or H2 receptor antagonists and antacids is a sensible precaution.- Fluid losses gradually diminish and, provided there has been adequate replacement of water and electrolytes by parenteral nutrition, the patient will survive to enter the adaptive phase.

HORMONE REPLACEMENT THERAPY

9/7/2010

HORMONE REPLACEMENT THERAPY

INDICATIONS
MENOPAUSE
CLIMECTERIC
OSTEOPOROSIS
CARDIOVASCULAR
PRE MATURE MENOPAUSE

MENOPAUSAL SYMPTOMS
PHYSICAL
PSYCHOLOGICAL
PSYCHOLOGICAL SYMPTOMS
DEPRESSION
IRRITABILITY
TIREDNESS / POOR SLEEP
ANXIETY
LOSS OF LIBIDO
WEEPINESS
FORGETFULNESS &
LOSS OF CONCENTRATION
PHYSICAL SYMPTOMS
IRREGULAR PERIODS
HOT FLUSHES
NIGHT SWEATS
PALPITATIONS
SEXUAL CHANGES
SKIN & HAIR
JOINT PAINS
URINARY SYMPTOMS
WEIGHT GAIN
HEADACHE
LONG TERM MENOPAUSAL EFFECTS
HORMONES/DRUGS INHRT
NATURAL ESTROGENS

PROGESTOGENS

TIBOLONE

RALOXIFENE(SELECTIVE ESTROGEN RECEPTOR MODULATORS)
ROUTS OF T/M
ORAL

TRANSDERMAL

IMPLANTS

VAGINAL CREAMS & PESSARIES
STRATEGIES OF T/M
T/M OF PRE-MENOPAUSAL WOMEN
RISKS OF UNOPPOSED ESTROGENS
ENDOMETRIAL HYPER PLASIA

ADENOCARCINOMA

INCREASED RISK OF Ca BREAST

2-4FOLD INCREASED RISK OF
DEVELOPING THROMBOLIC DISEASE
RISKS OF PROGESTOGENS
DEPRESSION
WEIGHT GAIN
BLOATING
ADVERSE AFFECT ON SERUM
LIPIDS
CONTRAINDICATIONSOF HRT
PREVIOUSTHROMBOEMBOLIC DISEASE
IMPAIRED LFT/ LIVER DISEASE
Ca BREAST
Ca ENDOMETRIUM
FIBROIDS &ENDOMETRIOSIS(relative) HYPERTENTION,DIABETES,CARDIO-VASCULAR DISEASE ARE NOT C/I

HORMONE REPLACEMENT THERAP REVIEW OF OPTIONS

9/7/2010

Hormone Replacement Therapy - Review of Options

Why Hormone Replacement Therapy?
With a marked increase in longevity, women now spend 1/3 rd of their lives in the post-menopausal period. It is estimated that 1/3 rd of total female population are in menopause. Therefore they would have to cope with the post menopausal syndrome and face the consequences .HRT relieves the well known symptoms of post menopausal syndrome .Again women are now asking for a quality life after menopause. So HRT is a hot topic in this era as it is no more for symptomatic management for PMS, but for the total management from prophylactic to curative .
Since estrogen deficiency is a major cause of the long-term complications of the menopause, estrogen replacement is the rational treatment to address the cause of the problems after menopause .But as there are limitations of estrogen therapy as HRT, some other drugs are also used besides estrogen
DRUGS USED IN HRT
Oral: -
Conjugated equine estrogen (CEE): 0.625 mg (Estrone Sulphate + equilin sulphate +17 d dihydro equilin)
Estradiol valerate (1, 2, 4 mg).
Estrial succinate (1, 2 mg).
Transdermal (estradiol): -
Patches: 25 micro gm, 50 micro gm / 24 hour twice weekly.
Gel : 75 micro gm / 24 hours daily.
Sub cutaneous implant (estradiol): -
25 / 50 / 100 mg. 6 monthly.
Vaginal: cream.
DRUGS USED IN HRT
Oral route -.
Norgestrol: 150 mg /day.
Micronised progesterone: 200 mg /day.
Dydrogesterone: 20 mg / day.
Medroxy progesterone acetate: 10mg/day.
Norethisterone acetate : 0.7 - 2.5 mg/ day.
Hormone releasing intra uterine system -.
Levonorgestrel: 20 mcg / day.
Progestasert: 65mcg / day.
Vaginal - natural progesterone gel / pessary.
Transdermal - sequential / continuous patch.
DRUGS USED IN HRT
Synthetic steroid, tissue specific HRT
2 hydroxy metabolites are estrogenic
D 4 isomer binds to progesterone & androgen receptors
Addition of progesterone not required
DRUGS USED IN HRT
Estrogen alone: in post hysterectomy cases
E + P
Cyclic sequential: E on day 1-25; P on day 14 -25 (for climacteric patients with intact uterus )
Continuous sequential: E daily; P for 12 days at 16 days interval (for post menopausal patients with intact uterus)
Continuous combined: E + P taken daily
Progesterone alone: cyclic / continuous
Estrogen + Progesterone + Androgen
Benefits of HRT
Vasomotor symptoms:
Hot flushes & night sweats resulting from hyperactivity of mid brain-hypothalamic-pituitary axis & characteristic of climacteric are relieved by HRT
Sleep disturbances:
Early morning awakening and inability to get back to sleep is a frequent complaint in postmenopausal women. Estrogen receptors are present in Reticular Activation System, preoptic area, and hypothalamus. Estrogen replacement improves sleep by acting at these sites.
Benefits of HRT
Mood & psychological changes:
Estrogen replacement appears to have a direct mental tonic effect on the cognitive functions even in the absence of vasomotor symptoms .It over comes anxiety, over sensitivity, tearfulness, irritability, aggression. However if progesterone is also given, it may reduce the beneficial effects of estrogen on libido & mood.
Benefits of HRT
Atrophy of genital tract
leading to vaginal dryness & postmenopausal bleeding from atrophic vaginitis / atrophic endometrium respond to estrogen therapy.
Dyspareunea
due to vaginal dryness is not a problem in menopause, but it is a problem during climacteric.
Loss of libido
also responds to estrogen replacement. Some also get benefit from testosterone.
Benefits of HRT
Urinary symptoms:
Incontinence -Urethral abnormality, Detrussor instability, Overflow Incontinence
Frequency, Urgency, Dysuria
Difficulty in voiding
Estrogen may produce considerable improvement in these symptoms by increasing
Epithelial thickness, vascularity, closing pressure of urethra
Adrenergic receptor in bladder urethral muscle
Collagen content of connective tissue
Benefits of HRT
Bone & skeleton:
Post menopausal women, due to increase

ROMATOID ARTRIT VE ANKILOZAN SPONDILIT"DE ADRENAL VE GONADAL SEKS STEROIDLERININ SERUM D�ZEYLERININ KARSILASTIRILMASI VE HASTALIK PARAMETRELERI ILE ILISKISININ ARASTIRILMASI

9/7/2010

ROMATOID ARTRIT VE ANKILOZAN SPONDILIT"DE ADRENAL VE GONADAL SEKS STEROIDLERININ SERUM D�ZEYLERININ KARSILASTIRILMASI VE HASTALIK PARAMETRELERI ILE ILISKISININ ARASTIRILMASI

I�INDEKILER
�ns�z......................................................................................................................ii
Simgeler ve Kisaltmalar.........................................................................................iii
I�indekiler...............................................................................................................iv
I. GIRIS..........................................................................................................1
II. GENEL BILGILER....................................................................................3
1. Romatoid Artrit.......................................................................................3
2. Ankilozan Spondilit................................................................................13
3. Seks Hormonlarinin Immun Sistem �zerine Etkileri.............................24
4. Romatoid Artrit Fizyolojisinde Seks Hormonlari...................................25
5.Ankilozan Spondilit ve Seks Hormonlari................................................31
III. MATERYAL ve METOD..........................................................................36
IV. BULGULAR..............................................................................................38
V. TARTISMA ve SONU�............................................................................45
�ZET......................................................................................................................53
SUMMARY............................................................................................................54
KAYNAKLAR.......................................................................................................55
v
GIRIS
Kronik artritlerde hastaligin etiyopatogenez ve immun mod�lasyonunda seks
hormonlarinin rol� ilgi �ekmektedir. Klinik ve deneysel �alismalar, seks
hormonlarinin immun cevabi mod�le ettigi ve otoimmun hastaliklarin olusmasinda
etkili olabilecegini g�stermistir (1).
N�roendokrin immun mekanizmalarin romatoid artrit (RA) gibi otoimmun
romatolojik hastaliklarin progresyon ve patogenezinde, genetik fakt�rlerle birlikte
etkili oldugu ortaya konulmustur (2). RA hedef ajanlarin epitoplari (�r, virusler) ve
insan l�kosit antijen (HLA) epitoplari arasinda iliski, stres cevap sisteminin durumu
(Hipotalamus-pituiter-adrenal aks), �strojenlerin immun cevabi arttirmasi ve
androjenlerin ve progesteronun dogal suppes�r etkilerinin g�sterildigi gonodal
hormonlari i�eren birtakim predispozan fakt�rlerin kombinasyonu sonucunda
meydana gelir (3). Seks hormonlari, direk olarak otoimmun hastaliklara neden
olmasa da immunolojik ve enflamatuvar cevaplari ve dolayisiyla hastalik tablosunu
etkileyebilirler.
Yapilan �alismalarda, RA"li hastalarda d�s�k serum dehidroepiandrosterone
sulfat (DHEAS) ve erkek RA"li hastalarda d�s�k testosteron konsantrasyonlari gibi
degismis �strojen-androjen orani ve anormal seks hormon metabolizmasi
tanimlanmistir (4). RA"li erkeklerde, hastalik alevlenmeleri sirasinda relatif androjen
eksikligine rastlanabilir (5). RA"li kadin hastalarda ise d�s�k serum DHEAS
seviyeleri tespit edilmistir. RA g�r�lme sikliginin menapozla birlikte en �st seviyeye
y�kselmesi, �strojen ve progesteron eksikliginin hastalikta bir rol oynadigina isaret
etmektedir ve elde edilen �ogu veriler, �strojenlerin h�cresel immuniteyi
baskiladigini g�stermektedir (5).
Buna karsin ankilozan spondilit (AS) gibi seronegatif spondiloartropatili
hastalarda testosteron d�zeylerinin patolojik olarak y�ksek oldugu ve hastalarin antiandrojenik
tedaviden fayda g�rebilecegi bildirilmistir (6, 7). Daha �nce yapilan bir
�alismada AS"li erkek hastalarda luteinize edici hormonun (LH) y�ksek seviyeleri ve
tersine d�nen �strojen /testosteron oranlari g�r�ld�g� ayrica gebelik �ncesinde
mevc

GESTATIONAL DIABETES MELLITUS

9/7/2010

Gestational Diabetes Mellitus
Helping Your Client Make Healthy Lifestyle Choices

Introduction
Following appropriate screening guidelines, understanding causation and associated conditions, and effectively managing the client with GDM can improve both short term and long term health conditions associated with GDM
Definitions
Gestational Diabetes (GDM)
Insulin Resistance (IR)
Glycemic Index (GI)
Syndrome X
Body Mass Index (BMI)

Gestational Diabetes (GDM)
A carbohydrate intolerance of varying degrees and severity with onset or first recognition during pregnancy with a probable resolution after the end of pregnancy. Diabetes, glucose intolerance or insulin resistance may have existed before the pregnancy. GDM is not the same as Type 1 or Type 2 Diabetes
Insulin Resistance (IR)
Insulin resistance is the resistance of the skeletal muscles and adipose to the affects of insulin. The pancreas produces more insulin, and over time cells become more and more resistant to the actions of insulin. As blood sugars and insulin increase, eventually the pancreas fails to produce enough insulin and diabetes occurs.
Glycemic Index (GI)
The glycemic index ranks foods on how they affect our blood sugar levels. This index measures how quickly an individuals blood sugar increases in the two or three hours after eating.
http://www.mendosa.com/gi.htm

Factors That Affect the GI
The GI of a food is influenced by the characteristics of the food or meal.
Processing, preparation, storage, physical form, and ripeness of foods affect the GI.
The GI varies within the same individual and between individuals.

Value of the GI
Each client can determine how she reacts to certain foods by monitoring food intake and postprandial blood glucose levels
The primary goal of GDM management is to achieve and maintain euglycemia throughout pregnancy to improve the outcomes for both mother and fetus

Syndrome X
The loss of responsiveness of the body to insulin is associated with a "clustering" of cardiovascular risk factors that includes abdominal obesity, hypertension, dyslipidemia, glucose intolerance and hyperinsulinemia.
This association is referred to as the insulin resistance syndrome, which is also known as Syndrome X.
Body Mass Index (BMI)
A commonly used measure to differentiate underweight, normal weight, overweight and obesity. Obtained by dividing the weight of the subject (in kilos) by the square of his (her) height in meters.
A BMI of approximately 25 kg/m2 corresponds to about 10 percent over ideal body weight.
http://www.americanheart.org/Heart_and_Stroke_A_Z_Guide/body.html
Body Mass Index Definitions
Body Mass Index and Recommended Weigh Gain
How These Conditions Are Related
Women with a history of GDM are metabolically vulnerable with insufficient ß-cell reserve, and many are insulin resistant. Approximately 50 % of women who are diagnosed with gestational diabetes during pregnancy will develop it in future pregnancies, and are at a much greater risk of developing type 2 diabetes in later life. The insulin resistance is the factor that exists in the woman with GDM. The aim of the lifestyle changes to be discussed here are to decrease insulin resistance.
Pregnancy Pathophysiology
Insulin resistance occurs because the hormonal changes associated with pregnancy partially block the effects of insulin.
Insulin resistance causes glucose to be shunted from the mother to the fetus to facilitate fetal growth and development.
Pregnancy Pathophysiology
During the third trimester of pregnancy, insulin resistance increases by 50%.
Maternal pancreatic beta cells increase insulin secretion almost threefold to compensate for increased insulin resistance.
Pregnancy Pathophysiology
The subsequent increase in insulin secretion causes the maternal glucose levels to increase 80% of the blood levels of non-pregnant women
If the mother"s pancreas is unable to produce sufficient insulin to overcome insulin resistance, maternal glucose levels increase and GDM occurs
Pregnan

OT�ST�K BOZUKLUK VE �E��TLER�

9/7/2010

OT�ST�K BOZUKLUK VE �E��TLER�

TANIM : Otistik spektrum bozuklu�u, ileri d�zeyde ve karma��k bir geli�imsel yetersizlik �e�ididir. Otistik spektrum bozuklu�u, do�u�tan varolabildi�i gibi, �� ya�a kadar olan d�nemler de ba�layabilir. Otistik spektrum bozuklu�unun, n�rolojik sorunlardan kaynaklanan bir yetersizlik oldu�u san�lmaktad�r. Ancak, hen�z bu konuda net bilimsel g�stergelerle ula��labilmi� de�ildir.
Otistik spektrum bozuklu�unun, ilk ortaya ��kt�� y�llarda, baz� anne-baba �zellikleriyle ve �ocuk yeti�tirme bi�imleriyle ili�kili olabilece�i y�n�nde g�r��ler �ne s�r�lm��t�r. �rne�in, "so�uk" diye nitelendirilen annelerin �ocuklar�nda otistik �zelliklerin daha s�k g�r�ld�� y�n�nde savlar olmu�tur. Ancak, yap�lan ara�t�rmalar, otistik spektrum bozuklu�unun anne-babalar�n ki�ilik �zellikleriyle ya da �ocuk yeti�tirme bi�imleriyle ili�kili olmad��n� g�stermi�tir. Ayr�ca, otistik spektrum bozuklu�u ile ailesel �zellikler (�rne�in, etnik k�ken ya da ailenin sosyoekonomik d�zeyi) aras�nda da herhangi bir ili�ki bulunamam��t�r.
Otistik spektrum bozuklu�una, baz� ailelerde daha s�k rastlanmaktad�r. Bu nedenle, otistik spektrum bozuklu�unun genetik olabilece�i d��n�lmekteydi. Ge�ti�imiz aylarda, yedinci insan kromozomunun t�m�n�n gen diziliminin tamamland�� a��kland�. Yap�lan a��klamalarda, ba�ta otizm olmak �zere �e�itli geli�im bozukluklar�ndan sorumlu �ok say�da gen bulundu�u belirtildi. Bu a��klamalar�, her an yeni a��klamalar ve bilimsel geli�meler izleyebilir.
�statistiksel bulgular, otistik spektrum bozuklu�unun yakla��k her 500 �ocuktan birinde g�r�ld�� y�n�ndedir. Otistik spektrum bozuklu�unun erkeklerde g�r�lme s�kl��, k�zlardan d�rt kat fazlad�r; ancak, k�zlarda genellikle daha ileri d�zeyde seyretti�i g�zlenmektedir.

SINIFLAMA
�e�itli bilimsel kaynaklar otistik spektrum bozuklu�unu �e�itli �ekillerde s�n�fland�rmaktad�r. Ruhsal Bozukluklara �li�kin Tan� ve �statistik El Kitab� IV, psikoloji alan�ndaki sorunlara ili�kin referans al�nan en g�venilir kaynaklardan biridir. DSM IV otistik spektrum bozuklu�unu be� alt gruba ay�rmaktad�r: Otizm, Asperger sendromu, �ocukluk disintegratif bozuklu�u, Rettsendromu ve atipik otizm (PDD-NOS). Bu alt gruplar�n her biri a�a��da k�saca a��klanmaktad�r.
Otizm: Otizm, otistik spektrum bozuklu�u kategorisindeki en temel alt gruptur. Otizmin �� ya�tan �nce ba�lad�� kabul edilmektedir. Otizm; (a) sosyal etkile�imde �nemli yetersizliklerle, (b) ileti�im ve oyunda �nemli yetersizliklerle, (c) �e�itli tak�nt�larla kendini g�sterir. bu �zelliklerin her birinin ayr�nt�lar� a�a��da yer alan Belirtiler alt b�l�m�nde a��klanmaktad�r.
Asperger Sendromu: Asperger sendromunda da, sosyal etkile�imde yetersizlik ve �e�itli tak�nt�lar g�r�l�r. Ancak, otizmden farkl� olarak, dil ve zihin geli�iminde geriliklere rastlanmaz. Asperger sendromu tan�s� alm�� bireylerin s�zel i�levleri, �rne�in, s�zc�k da�arc�klar� ve dilbilgisi geli�imleri, genelde iyidir. Ancak, g�rsel-alg�sal ve g�rsel-devinsel i�levlerde yetersizdirler. Ayr�ca, �o�unda denge ve devinsel e�g�d�m sorunlar� g�zlenir.
�ocukluk Disintegratif Bozuklu�u: �ocukluk disintegratif bozuklu�u, �ok seyrek rastlanan bir otistik spektrum bozuklu�u kategorisidir. Bu tan�y� alan �ocuklar, ya�amlar�n�n en az ilk iki y�l�nda normal geli�im g�sterirler. Bozuklu�un ba�lamas�yla, daha �nce kazan�lm�� olan beceriler h�zla yitirilir ve otizm i�in belirtilen �zellikler kendini g�sterir. �o�u �ocu�un zihinsel becerileri, ileri derecede zihin �z�rl� d�zeyine kadar geriler. �ocukluk disintegratif bozuklu�u tan�s� alan �ocuklar, birka� y�l i�inde, otizm tan�s� alan �ocuklarla benzer �zellikleri payla��r hale gelir.
Rett Sendromu: Rett sendromu, en az be� ay normal geli�im g�steren �ocuklarda g�r�l�r ve yaln�zca k�zlarda ortaya ��kan genetik bir otistik spektrum bozuklu�udur. Sendromun ba�lamas�yla birlikte, ba� b�y�mesi yava�lar, el becerileri (�rne�in; tutma, a�ma vb.) yitirilir, tak�nt�l� el hareketleri ba�lar. Zamanla t�m devinsel beceriler geriler

PRACTICAL APPROACH TO THERAP

9/7/2010

Practical Approach to Therapy

This program and all of its components are the exclusive property of and are copyrighted by Medical Age Publishing, Division of Snyder Healthcare Communications Worldwide, Stamford, Connecticut. The contents of this program, including design and written information, may not be altered in any way. This program may not be disseminated, reproduced, copied, or published other than with the prior express written consent from Medical Age Publishing, Division of Snyder Healthcare Communications Worldwide.
TYPE 2 DIABETESManagement Goals
Eliminate symptoms and improve well-being
Prevent and retard microvascular complications
optimize glycemic control
target blood pressure levels
Reduce macrovascular events
optimize glycemic control
target blood pressure levels
target lipid levels
TYPE 2 DIABETESMetabolic Targets
ParameterTarget Value
Fasting blood glucose80-120 mg/dL
HbA1coptimal 6%goal 7%action level 8%
Total cholesterol 200 mg/dLLDL-C optimal 100 mg/dL initiate treatment 130 mg/dLHDL-C 45 mg/dL
Triglycerides 200 mg/dL
UKPDSDeterioration in Median HbA1c Values Over Time
IntensiveIntensive ConventionalPolicyConventionalPolicyPolicy (Metformin)Policy
10-year 7.0%7.9%7.4%8.0% follow-up
0-5 years6.6%7.4%6.7%7.5%
5-10 years7.5%8.4%7.9%8.5%
10-15 years8.1%8.7%8.3%8.8%
Antihyperglycemic Agents for Type 2 Diabetes:The Six Classes
ClassAvailable Agents
a-Glucosidase inhibitorAcarbose, miglitol
ThiazolidinedioneTroglitazone
BiguanideMetformin
MeglitinideRepaglinide
SulfonylureaAcetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, tolazamide, tolbutamide
InsulinMany
Antihyperglycemic Agents:Major Sites of Action
Antihyperglycemic Agents:Mechanisms of Action
DelayAugmentEnhanceCarbohydrateInsulin SupplyInsulin Action Absorption
SulfonylureasBiguanidesa-Glucosidaseinhibitors
MeglitinidesThiazolidinediones
Insulins
The a-Glucosidase Inhibitors:Basic Characteristics of Acarbose and Miglitol
Mechanism of actionDelays carbohydrate absorption
Depends uponPostprandial hyperglycemia
PowerDecreases HbA1c 0.5% to 1%
Dosing Three times daily
Side effectsFlatulence
Main riskLiver enzyme elevation (rare)
MONOTHERAPYThe a-Glucosidase Inhibitors:Effect on Postprandial Glucose
MONOTHERAPYAcarbose: Effect on HbA1c
The Thiazolidinediones:Basic Characteristics of Troglitazone
Mechanism of actionEnhances muscle and adiposetissue response to insulin
Depends upon Presence of insulin and resistanceto its action
PowerDecreases HbA1c 0.5% to 1.3%
DosingOnce daily
Side effectsEdema, weight gain, anemia
Main riskLiver failure
MONOTHERAPYTroglitazone After Diet:Effect on HbA1c
MONOTHERAPYTroglitazone After Sulfonylurea:Effect on HbA1c
The Biguanides:Basic Characteristics of Metformin
Mechanism of actionDecreases hepatic glucoseproduction
Depends upon Presence of insulin
PowerDecreases HbA1c 1% to 2%
DosingOne to three times daily
Side effectsDiarrhea, nausea
Main riskLactic acidosis
Metformin:Mechanism of Action
Molecular basis is not well understood
Enhances hepatic response to insulin
In some cases, especially at high doses, promotes weight loss (~2-3 kg)
Weight loss may improve muscle response to insulin
MONOTHERAPYMetformin: Effect on Glucose and Insulin
MONOTHERAPYMetformin:Effect on HbA1c
MONOTHERAPYDose-Response to Metformin:Effect on HbA1c
Placebo500 mg1000 mg1500 mg2000 mg2500 mgTime(n=79)(n=73)(n=73)(n=76)(n=73)(n=77)
BaselineHbA1c (%)9.9 ± 1.910.1 ± 1.710.0 ± 2.09.7 ± 1.510.1 ± 2.110.0 ± 1.8

Week 7+1.1+0.4* - 0.01† - 0.3*-0.05† - 0.1†
Week 11+1.2+0.2† - 0.1† - 0.6† - 0.9† - 0.5†
End point+1.2+0.3*+0.01† - 0.5† - 0.8† - 0.4†

ASMPTOMATIC HPERCALCEMIA PRIMAR HPERPARATHROIDISM

9/7/2010

Asymptomatic Hypercalcemia Primary Hyperparathyroidism

Causes of Hypercalcemia
Primary hyperparathyroidism
Humoral hypercalcemia of malignancy
Familial hypocalciuric hypercalcemia
Drug-induced hypercalcemia
Primary Hyperparathyroidism
accounts for 70% of cases of asymptomatic hypercalcemia in ambulatory patients
incidence: 1 case / 800 persons / year
most common in the 5th-6th decades
3 x more common in women than in man
Primary Hyperparathyroidism
asymptomatic in 50% of cases
mainly a biochemical diagnosis
serum calcium generally mildly elevated 12.0 mg/dl (normal range 8.5-10.5)
PTH level is elevated in 90% of cases
mild hyperchloremia and metabolic acidosis is common
Primary Hyperparathyroidismcauses
Solitary benign parathyroid adenoma
Diffuse hyperplasia of all parathyroid glands
Multiple parathyroid adenoma
Parathyroid carcinoma
Primary Hyperparathyroidismcauses
Solitary benign parathyroid adenoma
accounts for 80-85% of cases
surgical removal produces long-term remission
recurrence rate is 0.6% at 8-10 years
Primary Hyperparathyroidismcauses
Hyperplasia of all parathyroid glands
accounts for 15% of cases
may occur sporadically or as part of multiple endocrine neoplasm syndrome
Type I (Werner Syndrome)pituitary, parathyroid, pancrease
Type II (Sipple Syndrome)medullary thyroid cancer, pheochromocytoma, hyperparathyroidism
Primary Hyperparathyroidismcauses
Multiple parathyroid adenoma
found in only 1% - 2% of cases
sporadic or familial
Parathyroid carcinoma
very rare, 0.5% of cases
average serum calcium is 14 mg/dl
marked elevation in intact PTH
aggressive surgical resection
Surgery for Primary Hyperparathyroidism
Serum calcium level 1 mg above upper limits of normal
Urinary calcium excretion 400 mg/day
Overt clinical manifestation
classic neuromuscular disease
nephrocalcinosis
nephrolithiasis
osteitis fibrosa cystica
Surgery for Primary Hyperparathyroidism
Cortical bone density in the distal radius 2 standard deviation (Z score -2 SD)
Reduced creatinine clearance in theabsence of other cause
age 50 years
Humoral Hypercalcemiaof malignancy
accounts for 50% of cases of hypercalcemia in hospitalized patients
most common malignant diseases:lung, breast, myeloma, lymphoma, renal cell carcinoma
Humoral Hypercalcemiaof malignancy
Mechanism of hypercacemia
tumor secretion of : PTH-related peptide, lymphotoxins, interlukin-1, 1,25 vit D
hypercalcemia precedes the diagnosis of malignancy in 20%
majority of malignant disease is already advanced

Familial Hypocalciuric Hypercalcemia
A benign autosomal dominant condition caused by decreased renal clearance of calcium
a very low fractional excretion of calcium ( 0.01), normal or mildly  PTH levels, mild  serum magnesium
no treatment required
Drug-induced Hypercalcemia
estrogen
tamoxifen (antiestrogen)
lithium
theophyllin
thiazide diuretics
vitamin A
vitamin D

ENDOKR�N BEZLER VE HORMONAL D�ZENLEME

9/7/2010

SEROTONIN MECHANISMS IN THE PATHOPHSIOLOG OF SCHIZOPHRENIA

9/7/2010

Serotonin Mechanisms in the Pathophysiology of Schizophrenia

Schizophrenia Pathophysiology and Pharmacologic Profile of Antipsychotic Drugs (APDs)
Receptor Binding Profiles of Conventional and Atypical APDs
Impact of Schizophrenia Symptoms on Functional Outcomes
Serotonergic Pathways and Innervation
Dopaminergic Pathways and Innervation
Evidence of Serotonin Involvement in Schizophrenia Pathophysiology
Postmortem Studies in Schizophrenics
Increase in 5-HT transmission and 5-HT-transporter density in subcortical regions, but no change or decrease in cortical regions
Decrease or no change in 5-HT2-receptor density in prefrontal cortex
Cerebrospinal Fluid (CSF) Studies of 5-HT Metabolites
Inconsistent results between studies
Agonist-Challenge Studies
Administration of m-chlorophenylpiperazine (mCPP) a partial 5-HT agonist:
- Exacerbates symptoms in unmedicated schizophrenics
- Has no effect in healthy volunteers
Serotonin-Dopamine Interactions
Serotonin-Dopamine Interactions: Electrophysiologic and Neurochemical Studies
Midbrain
5-HT inhibits the firing of dopaminergic neurons
Acute administration of 5-HT2 antagonists increases the firing rate of VTA and SN neurons
Chronic administration of typical and atypical APDs attenuates the number of spontaneously active neurons
Serotonin-Dopamine Interactions: Electrophysiologic and Neurochemical Studies
Prefrontal Cortex
5-HT2 antagonists increase dopamine release
Serotonin-Dopamine Interactions: Behavioral Studies
Amphetamine-Induced and Spontaneous Locomotor Activity
Serotonin depletion via pCPA, a tryptophan-free diet, or lesions by 5,6-dihydroxytryptamine administration enhances amphetamine-induced hyperlocomotion
Serotonin depletion or lesions of midbrain raphe increase spontaneous locomotor activity
Catalepsy
Inhibition of serotonin induced by electrolytic lesions of the raphe, administration of pCPA or 5-HT antagonists decreases neuroleptic-induced catalepsy
Serotonergic enhancement via the addition of 5-HT agonists, precursors, and uptake inhibitors increases neuroleptic-induced catalepsy
NMDA-Antagonist Model of SchizophreniaKetamine Effects in Healthy Human Subjects
Serotonin-Glutamate-Dopamine Interactions
NMDA Antagonist-Induced Behaviors
NMDA Antagonist-Stimulated Hyperlocomotion
MK-801 and PCP induce a behavioral syndrome that includes hyperlocomotion, head-weaving, body-rolling, ataxia, reduced rearing, and stereotypes
Conventional and atypical APDs reduce MK-801-stimulated hyperlocomotion
- Clozapine is more potent at decreasing locomotor behavior than stereotypic movements
NMDA Antagonist-Induced Disruptions in Prepulse Inhibition (PPI)
PPI is used as a model of attentional processes, and disruptions in PPI
- Have been observed in schizophrenic patients,
- Can be induced by NMDA antagonists, such as PCP, ketamine, and MK-801, and
- Are prevented by atypical APDs, including clozapine, risperidone, quetiapine, and olanzapine

TARGETING INSULIN RESISTANCE A STRATEG FOR IMPROVING GLCEMIC CONTROL IN TYPE 2 DIABETES

9/7/2010

Targeting Insulin Resistance: A Strategy for Improving Glycemic Control in Type 2 Diabetes

Diabetes Mellitus in the US: Health Impact of the Disease

Diabetes Mellitus in the US: Disproportionate Impact on Annual Healthcare Costs

ADA Targets for Glycemic Control and Recommended Action Levels
Biochemical Index

Diabetes Care: Percentage of Type 2 Diabetes Patients Receiving Basic Services With Non-HMO Coverage
Complicationsof Diabetes Mellitus

Heart Disease and Stroke in Diabetes Patients
Evidence of CHD in 7.5%-20% of diabetes patients 45 years old in the US
- 55% of deaths in diabetes patients are caused bycardiovascular disease
5-year average cost of surviving acute MI: $51,000
Stroke occurs 2X- 4X more often in diabetes patients

Kidney Disease in Diabetes Patients
27,851 new cases of ESRD in diabetes patients in 1995
40% of all new cases in the US
Nearly 99,000 diabetes patients required dialysis or kidney transplantation that year
Annual cost of ESRD:
$45,000 in diabetic patients ages 45-64
Relationship Between Hyperglycemia and Nephropathy
Diabetic nephropathy: persistent proteinuria (total excretion 500 mg/day), resulting in ESRD
25% to 50% of diabetes cases
mortality from all causes in ESRD patients 20X to 40X higher than in those without renal dysfunction
Preceded by microalbuminuria (protein excretion 30-300 mg/day)
20X higher risk of nephropathy than in normoalbuminuric patients
Relationship Between Hyperglycemia and Neuropathy
Slowly progressive disease preferentially affecting the long axons
30% to 40% of all diabetics are symptomatic
60% have neuropathy (symptomatic or asymptomatic)
Peripheral symptoms:
numbness/tingling in the feet, cramps, sensitivity/ insensitivity to touch, loss of balance/coordination
Autonomic symptoms:
urinary incontinence, loss of sexual response, gastric stasis, orthostatic hypotension
Exact etiology unknown
Foot Ulcers and Amputations in Diabetes Patients
50% of lower limb amputations in the US
67,000/yr (1993 -1995)
Foot ulcers occur in 15% of diabetes patients over a lifetime
Cost of diabetes-related amputation: $27,000
Retinopathy and Blindness in Diabetes Patients
It is estimated that retinopathy affects 80%-97% of patients with diabetes of ³15 years" duration
Diabetes is the leading cause of new cases of blindness in adults*
Diabetic retinopathy accounts for the majority of these cases
Minimum cost of blindness for working-age adult is estimated at $12,769 per year
The Diabetes Control and Complications Trial (DCCT)
Multicenter, randomized study of type 1 diabetes patients
To assess effect of intensive glycemic control vs conventional therapy on:
development and progression of retinopathy and other long-term complications
Results of this trial led to similar studies of type 2 diabetes patients
DCCT: Risk of Sustained Retinopathy Progression by HbA1c Level and Yearsof Follow-up
Overall Results of the DCCT Trial
Intensive control of blood glucose reduced risk of diabetic complications
retinopathy onset ¯76% in patients with no retinopathy at baseline (P£0.002)
retinopathy progression ¯54% in patients with mild retinopathy at baseline (P£0.002)
nephropathy ¯54% (P 0.04)
neuropathy ¯60% (P£0.002)
There was, however, a 2- to 3-fold greater incidence of severe hypoglycemia
Intensive Glycemic Control in Type 2 Diabetes Patients
Prospective, randomized study of 110 Japanese patients
55 patients without retinopathy or microalbuminuria (primary prevention cohort)
55 patients with mild retinopathy and microalbuminuria (secondary prevention cohort)
Randomization to intensive or conventional insulin therapy
Evaluation at months 3, 6, and every 6 months over 6-year period for onset and progression of retinopathy, nephropathy, and neuropathy

ELEKTR�KLE TAHR�K I

9/7/2010

Amplidinin Uygulamalar�

*Do�ru ak�m generat�r�n�n gerilim kontrol�,
*Ak�m kontrol�,
*Ak�m s�n�rland�rma kontrol�,
*Devir say�s� ayar�,
*Durum kontrol�,
*Alternat�r geriliminin kontrol�dur.

Ak�m s�n�rland�rma kontrol�

Do�ru ak�m generat�r�n� a��r� y�k ve k�sa devrelere kar�� korumak i�in �o�u zaman ak�m s�n�rland�rma kullan�l�r. �ekil 1"de amplidinle kontrol edilen bir d.a. generat�r�n�n ak�m s�n�rland�rma ba�lant�s� g�sterilmi�tir. Amplidinin boyuna alan�na her biri ayr� birer ak�m kayna��ndan beslenen iki kontrol sarg�s� eklenmi�tir. Birinci f1 kontrol sarg�s� bir ayar direnci �zerinden direkt olarak bir d�� referans ak�m kayna��na ba�l�d�r. �kinci f2 kontrol sarg�s� ise ikinci bir d.a. kayna��na ak�m� s�n�rland�r�lacak generat�r�n end�vi devresine seri olarak sokulan bir R2 direnci �zerinden ba�l�d�r. Ba�lang��ta amplidin her iki kontrol sarg�s� taraf�ndan birlikte ikaz edilir. Her iki alan sarg�s�ndan ayn� y�nde ge�en ak�mlar amplidinin boyuna alan�n� meydana getirirler. Generat�r�n end�vi gerilimi, end�vi ak�m� ve d�� devreye verilen g�� f1 alan kontrol sarg�s� ile uygun bir de�ere ayarlanabilir. Y�k direnci veya referans giri�inden dolay� generat�r end�vi ak�m� artarak a��r� bir de�er al�rsa R2 direncinde artan gerilim d��m�nden dolay� f2 alan kontrol sarg�s�ndan ge�en ak�m y�n� ile birlikte MMK"n�n y�n� de de�i�ir. B�ylece generat�r y�k�ndeki bir art�� amplidinin giri�ine etkimek suretiyle end�vi EMK"n�n d��mesine neden olur. B�ylece y�k ak�m� s�n�rland�r�lm�� olur.

�ekil 1. Amplidinle kontrol edilen bir d.a. generat�r�nde ak�m s�n�rland�rma ba�lant�s�.

Devir Say�s� Ayar�

Daha geni� bir alan i�inde s�hhatli ve seri ayar istenen tahrik ve kontrol sistemlerinde g�� amplifikat�r� olarak serbest uyart�ml� normal bir d.a. generat�r� yerine y�ksek kazanc� olan amplidin generat�r kullan�l�r. Ward-Leonard tahrik sisteminde kontrol edilen g�� k��k oldu�u zaman (40-50 kW"a kadar) ayar generat�r� yerine amplidin generat�r kulla

DENESEL D�YABET�KLERDE SELENUMUN D�� EK�M YARASININ �Y�LE�MES� �ZER�NE ETK�S�N�N �NCELENMES�

9/7/2010

Deneysel Diyabetiklerde Selenyumun Di� �ekim Yaras�n�n �yile�mesi �zerine Etkisinin �ncelenmesi

Antioksidan �zelli�e sahip ve canl�lar i�in �nemli bir eser element olan selenyum (Se) ile diyabetin sebep oldu�u baz� patolojilerin tedavisinde ba�ar�l� sonu�lar elde edilmi�tir. Bu �al��man�n amac�, di� �ekim yaras�n�n iyile�mesinde diyabete ba�l� meydana gelebilecek bozukluklar� ve selenyumun olas� pozitif etkilerini ara�t�rmakt�r.

�al��maya 36 adet Wistar cinsi s��an dahil edilerek kontrol grubu, selenyum verilen kontrol grubu, diyabetik grup ve selenyum verilen diyabetik grup olmak �zere 4 gruba ayr�lm��t�r. Deneysel diyabet, tek doz intraperitonal (i.p.) streptozotosin (STZ) (50 mg/kg) enjeksiyonuyla olu�turulmu�tur. Alt sol 1. ve 2. molarlar�n �ekimini takiben Diyabet + selenyum ve kontrol + selenyum gruplar�na 5 µmol/kg/g�n olacak �ekilde tek doz i.p. sodyum selenit uygulan�rken, diyabet ve kontrol gruplar�na ayn� ko�ullarda distile su (i.p.) uygulanm��t�r. 3. 7. 14.ve 21. g�nlerde her bir gruptan iki�er adet s��an sakrifiye edilerek �ekim yap�lan mandibular segment ��kart�larak mikroskobik inceleme yap�lm��t�r.

Ara�t�rma sonucunda, diyabet grubunda �ekim yaras�n�n iyile�mesinde bozukluk olu�tu�u ve bu durumun selenyum verilerek d�zeltilebildi�i g�r�lm��t�r.
Anahtar S�zc�kler: Diabetes mellitus, Di� �ekimi, Yara iyile�mesi, Selenyum.

SUMMARY

The Investigation Of Effect Of Selenium On The Tooth Extraction Wound Healing In Experimental Diabetics
In the treatment of diabetes induced pathologies, beneficial results have been obtained with selenium (Se), which is an antioxidant and essential trace element for organisms. The aim of this study is to investigate the possible effect of selenium on the tooth extraction wound healing of experimental diabetics.

Thirty-six Wistar rats were included in this study and control, selenium given control, diabetic and selenium given diabetic groups were formed. Experimental diabetes was induced by single dose i.p. (50 mg/kg) injection of streptozotocin (STZ). Following the extraction of mandibular 1. and 2. molars, at 3., 7., 14. and 21. days two animals from each group were sacrificed and the mandibular segments were processed for microscobic examination. Diabetic + selenium and Control + selenium groups received i.p. one daily dose of 5 µmol/kg/day sodium selenate for 4 weeks while diabetic and control groups received distilled water. Mandibulae of all animals were excised and processed for densitometric, diffractometric and histopathological investigation.
We conclude that, the impaired wound healing in diabetics can be improved by selenium administration.
Key Words: Diabetes mellitus, Tooth extraction, Wound healing, Selenium.

2. AMA� VE KAPSAM

2.1. Di� �ekim Yaras�n�n �yile�mesi
Di� �ekiminden hemen sonra alveole kan dolar, eritrositler k�me yaparak ��ker. Fibrin a�lar� olu�urken, periodontal membrandaki damarlar b�z��r. �ekimden sonraki ilk saatler �ok �nemlidir. Alveole kan dolmas� engellenirse yara iyile�mesi gecikir ve k�smen de iyile�me olmayabilir (Shafer- Hine-Levy, 1966).
1. g�n: 24 saat sonra damar yataklar�nda de�i�imler ba�lar. Damar geni�lemelerini l�kosit diapedesisi izler. Alveol� dolduran fibrin iyile�menin temelidir.
2. g�n: Periodontal membrandan ��kan fibroblastlar yara �evresinden i�erilere yay�lmaya ba�larlar. Y�zey epiteli proliferasyona ba�lar. Di�i sarm�� olan alveol kemi�inde osteoklastik bir aktivasyon belirlenir. Bu arada �o�alan birka� tane endotel h�cresi g�r�lebilir.
5. g�n: Yara taban�nda fibroblastlardan ve damar endotellerinden yap�l� bir doku g�r�l�r. Periodontal membran art�klar� hala mevcuttur fakat, yeni yap�lacak kemikle ilgili hi�bir belirti g�r�lmez. Yara y�zeyinde kal�n bir l�kosit tabakas� ve kenarlarda y�zey epiteli proliferasyonu vard�r.
7. g�n: Fibrin a�� i�indeki fibroblastlar �o�alm��t�r. Yeni kapillerlerin say�s� artm��t�r. Periodontal membran art�klar�nda dejenerasyonlar vard�r. Alveol kemi�inde olduk�a belirgin a

INSULIN THERAP IN TPE 2 DIABETES

9/7/2010

Insulin Therapy in Type 2 Diabetes

Table of Contents
Page Slide
6 1. Issues in the Management of Type 2 Diabetes
6 2. Prevalence of Type 2 Diabetes Mellitus
6 3. Incidence of Type 2 Diabetes Mellitus
7 4. Risk Factors for Type 2 Diabetes
7 5. Trend in Prevalence of Obesity: NHANES Data
8 6. Link Between Obesity and Type 2 Diabetes: Nurses" Health Study
8 7. Link Between Obesity and Type 2 Diabetes: Nurses" Health Study (cont"d)
9 8. ADA Treatment Guidelines
9 9. Medical Nutrition Therapy for Type 2 Diabetes
10 10. Pharmacologic Therapy for Type 2 Diabetes
11 11. Treatment Algorithm
12 12. Considerations in Pharmacologic Treatment of Type 2 Diabetes
13 13. Tight Glycemic Control: Reducing the Risk of Complications
14 14. Improvement in HbA1c in the VA CSDM
14 15. VA CSDM: Results at Endpoint
15 16. The Kumamoto Trial: Effects of Conventional vs. Intensive Insulin
Therapy
15 17. UKPDS: Effect of Intensive Therapy on Glycemia
16 18. UKPDS 10-Year Cohort Data: Reductions With Intensive vs.
Conventional Therapy
16 19. Summary of Key Findings
17 20. Pharmacokinetics of Current Insulin Preparations
18 21. Clinical Efficacy of Insulin Lispro
19 22. Strategies for Insulin Therapy in Elderly Patients
20 23. Combination Therapy: Oral Agents Plus Insulin
21 24. Meta-Analysis of Sulfonylurea/Insulin Combination Therapy
4
Insulin Therapy in Type 2 Diabetes
Table of Contents
(continued)
Page Slide
21 25. Comparison of Insulin Regimens Among Oral Treatment Failures
22 26. Total Direct Costs of Type 2 Diabetes
22 27. Total Indirect Costs of Type 2 Diabetes
23 28. Ideal Basal Insulin
23 29. Pharmacokinetics of Current Insulin Preparations Compared With
Insulin Glargine
24 30. Structure of Insulin Glargine: A New Long-Acting Insulin Analogue
24 31. Characteristics of Insulin Glargine
25 32. Blood Glucose Profile of Insulin Glargine in Normal Volunteers
25 33. Exogenous Insulin Concentration of Insulin Glargine in Normal
Volunteers
26 34. Efficacy of Insulin Glargine in Type 1 and Type 2 Diabetes
26 35. Safety of Insulin Glargine in Type 1 and Type 2 Diabetes
27 36. Other Long-Acting Insulin Analogues
27 37. Need for Novel Delivery Systems of Insulin
28 38. Insulin Pump
28 39. Insulin Pump
29 40. Insulin Pen
29 41. Insulin Pen
30 42. Inhaled Insulin Formulations
30 43. Continuous Glucose Sensors
31 44. Conclusions
31 45. Conclusions (cont"d)
5
Type 2 diabetes accounts for 90% to 95% of all diagnosed cases of
diabetes; the proportion is even higher among patients older than
45 years. In population surveys, therefore, diabetes in adults is typically
considered to be type 2; the results of these surveys are interpreted
as reflecting trends in the prevalence and incidence of type 2 diabetes
of persons aged 25 years or older.1,2
The Centers for Disease Control and Prevention (CDC) conducted
The National Health Interview Survey (NHIS) from 1980 through
1994 to obtain estimates of the prevalence and incidence of diabetes in
the United States. In 1994, there were approximately 7.7 million cases
of diagnosed diabetes in the United States, an increase of 2.2 million
since 1980. From 1980 to 1994, both the prevalence (number of existing
cases) and incidence (number of new cases) of diagnosed diabetes
increased significantly (P 0.01). The prevalence increased from 25.4
to 29.8 per 1000 population, or 17%, and the incidence increased
from 2.5 to 3.7 per 1000, or 48%.2 These increases have been most
dramatic during the 1990s, when the number of newly diagnosed cases has
averaged 727,000 per year.
The prevalence of diagnosed diabetes also increased significantly
(P 0.01) with age and race during this period. This increase was
observed in three age groups examined: 44 years or younger, 45 to
64 years, and 65 years or older. The age-adjusted prevalence increased
33% among blacks (P=0.05) and 11% among whites (P 0.01).
1. Kenney SJ, Aubert RE, Geiss LS. Prevalence and incidence of non-insulin-dependent
diabetes. In: Diabetes in America, 2nd ed. Bethesda, Md: Nati

ROMATO�D ARTR�TTE C�NS�YET HORMONU ADJUVAN TEDAV�S�

9/7/2010

Romatoid Artritte Cinsiyet Hormonu Adjuvan Tedavisi

Romatoid artrit, normal insanlarda komplikasyona yol a�mayan muhtemel bir patojen antijene kar�� hastan�n a��r� imm�n ve enflamatuvar cevap vermesinden kaynaklanabilen �o�ul unsurlu otoimm�n bir romatik hastal�� ifade etmektedir. Anormal cevab�n, baz� �nc�l unsurlardan kaynakland��na inan�lmaktad�r. Bu unsurlar aras�nda, antijenlerin epitoplar�yla doku uyumluluk epitoplar� aras�ndaki ili�kiler, stres cevap sisteminin (hipotalamik - pit�iter - adrenokortikal eksen) durumu ve �strojenlerin en az�ndan h�m�ral imm�nite �zerinde uyar�c� ve androjenlerle progesteronlar�n da tabii imm�n bask�lay�c�lar olarak d��n�ld�� cinsiyet hormon durumu vard�r. Cinsiyet hormonlar�n�n fizyolojik etkilerine ili�kin bilgilerde, milattan �nce ikinci y�zy�ldan bu yana olduk�a fazla bir art�� olmu�tur. Cinsiyet hormonlar�, ilk kez eski �in"de s�blimasyon tekni�iyle idrardan elde edilmi�tir. �strojenler ve androjenler, safla�t�r�ld�ktan sonra hipogonadizm ve dismenore gibi baz� durumlarda kullan�lm��lard�r. Bundan iki milenyum sonra bile, �strojenler halen oral kontraseptiflerde veya menapoz sonras� d�nemde kemik kayb�n� ve osteoporozu engellemek maksad�yla, farmakolojik veya fizyolojik m�stahzarlar olarak yayg�n bir �ekilde kullan�lmaya devam etmektedir. Ge�en elli sene boyunca, romatoid artritte �strojenlerin ve androjenlerin kulan�lmas� g�ndeme gelmi� ve bunun molek�ler taban�yla klinik neticeleri, bu makalede sunulmu�tur.

Arka Plan :

Romatoid artritli hastalarda, glukokortikoid tedavisi �ncesinde cinsiyet hormon yo�unluklar� de�erlendirilmi� ve bu de�erlerin, �zellikle menapoz �ncesi d�nemdeki kad�nlarda ve erkeklerde de�i�ti�i bulunmu�tur. Romatoid artritli kad�n ve erkek hastalar�n v�cut s�v�lar�nda, d��k imm�n bask�lay�c� androjen seviyelerinin muhtemel bir patojenik rol� oldu�unu destekler mahiyette, �zellikle d��k gonadal ve adrenal androjen (DHT, DHEA ve DHEAS) seviyeleri ve androjen / �strojen oran�nda azalma oldu�u tesbit edilmi�tir. Cinsiyet hormon �retim yollar�, kolesterol ve progestinin testosteron gibi androjenlere ve en sonunda �strojenlere (17 - beta �stradiol) s�ral� olarak indirgenmesini i�erir. Bu yol her iki cinste de mevcuttur ve dola��mdaki cinsiyet hormon yo�unluklar�, androjenlerin ve �strojenlerin g�receli olarak �evrilmesinin bir yans�mas�d�r. Kad�na kar�� erkek dengesini sa�layan, androjenlerle �strojenler aras�ndaki orand�r. Cinsiyet hormonlar�, �retildikleri dokular �zerinde yerel parakrin etkiler g�sterebilirler veya dola��ma girerler. Mens d�ng�s�n�, gebeli�i, do�um sonras� periyodu, menapozu, stresi, enflamatuvar sitokinleri, kortikosteroidleri, oral kontraseptifleri ve steroid hormonlar�n�n yerine konmas�n� i�eren baz� fizyolojik, patolojik ve terap�tik durumlar, cinsiyet hormonlar�n�n dengesini veya bunlar�n �evresel d�n��m�n� de�i�tirebilir. Yak�n ge�mi�te, hormonlar� ve �zellikle de cinsiyet steroidlerini taklit eden kimyasal maddeleri inceleyen yeni bir endokrinoloji sahas� olan endokrin k�r�lma konusu, olduk�a yo�un ilgi oda�� olmu�tur. "�strojenik Zenobiyotikler" de denilen ve �strojenleri taklit eden kimyasal maddeler, bu ara�t�rman�n as�l odak noktas� olmu�tur. Androjenlere olan maruziyet, �strojenlere olan maruziyet neticesinde g�r�lenlere benzer de�i�ikliklere, androjenlerin etkinli�ini bloke ederek yol a�abilir. Plastik, pestisitler, bitkiler ve zirai �r�nler gibi g�receli olarak s�k ve a��rl�kl� olarak kar��la��lan kaynaklarda, �evresel �strojenler bulunmaktad�r ve bunlar, imm�n cevab�n �n�ne ge�ebilirler. Androjenlerin ve �strojenlerin seviyelerini ve i�levlerini etkileyen genetik polimorfizm, karma��k hormonal - imm�n sistem etkile�imleri aras�nda dengesizli�e yol a�abilir ve romatoid artritin etyolojisine katk�da bulunabilir. �strojen sentaz lokusu olan CPY19, C19 androjenlerinin C18 �strojenlerine d�n��m�n� katalizleyen sitokrom - p450"dir. Romatoid artritte, 50 ya� �zeri hastal�k g�r�len birbirine akraba ailelerde bu lokusla bir ba�lant

REDISCOVERING INSULIN FOR TPE 2 DIABETES

9/7/2010

Rediscovering Insulin for Type 2 Diabetes

Insulin Therapy for Type 2 Diabetes
Type 2 Diabetes . . . A Progressive Disease
Barriers to Insulin Therapy
Mimicking Nature With Insulin Therapy
Insulin Tactics
Practical Guidelines
TYPE 2 DIABETES . . . A PROGRESSIVE DISEASEHbA1c in the UKPDS

TYPE 2 DIABETES . . . A PROGRESSIVE DISEASE Messages From the UKPDS
Sulfonylureas, metformin, and insulin all reduce microvascular complications by improving glycemic control
There is no evidence that sulfonylureas or insulin increase cardiovascular risk
Early  almost from the outset  combination therapy is needed to control glucose
Earlier introduction of insulin therapy can be expected in the progressive management of Type 2 Diabetes
TYPE 2 DIABETES . . . A PROGRESSIVE DISEASE Natural History of Type 2 Diabetes
TYPE 2 DIABETES . . . A PROGRESSIVE DISEASE
Over time,most patients will needinsulinto control glucose
Barriers to Insulin TherapyCommon Concerns
Insulin therapy might cause
Worsening Insulin Resistance
More Cardiovascular Risk
Weight Gain
Hypoglycemia
BARRIERS TO INSULIN THERAPYInsulin Sensitivity in Glucose Clamp StudiesImproved by Insulin Treatment
BARRIERS TO INSULIN THERAPYLipids and Blood PressureImproved or Unchanged by Insulin Treatment
BARRIERS TO INSULIN THERAPYCardiovascular RiskMortality After MI Reduced by Insulin Therapy in the DIGAMI Study
BARRIERS TO INSULIN THERAPYWeight Gain in the UKPDS
BARRIERS TO INSULIN THERAPYWeight Gain Is Minimized by Metformin
BARRIERS TO INSULIN THERAPYHypoglycemia in the UKPDS
BARRIERS TO INSULIN THERAPYReassurance About Common Concerns
Insulin Therapy in Type 2 DM
Improves Insulin Sensitivity by Reducing Glucotoxicity
Probably Reduces Cardiovascular Risk
Causes Modest Weight Gain
Rarely Causes Severe Hypoglycemia

Mimicking Nature
The Basal/Bolus Insulin Concept
MIMICKING NATURE WITH INSULIN THERAPYInsulin and Glucose PatternsNormal and Type 2 Diabetes
MIMICKING NATURE WITH INSULIN THERAPY Insulin and Glucose PatternsBasal vs Mealtime Hyperglycemia in Early Type 2 Diabetes
MIMICKING NATURE WITH INSULIN THERAPY
Over time,
most patients will need
both basal and mealtime insulin
to control glucose
MIMICKING NATURE WITH INSULIN THERAPYThe Basal/Bolus Insulin Concept
Basal Insulin
Suppresses glucose production between meals and overnight
Nearly constant levels
50% of daily needs
Bolus Insulin (Mealtime or Prandial)
Limits hyperglycemia after meals
Immediate rise and sharp peak at 1 hour
10% to 20% of total daily insulin requirement at each meal
Ideally, for insulin replacement therapy, each component should come from a different insulin with a specific profile
BARRIERS TO INSULIN THERAPYPractical Limitations of Conventional Tactics

Complexity of Starting Insulin Therapy
Need to Mix and Inject Insulins
Limitations of Insulin Preparations
INSULIN TACTICS Comparison of Human Insulins and Analogues
Insulin Onset ofDuration ofPreparations Action Peak Action
Lispro/Aspart5-15 minutes1-2 hours4-6 hours
Human Regular30-60 minutes2-4 hours6-10 hours
Human NPH/Lente1-2 hours4-8 hours10-20 hours
HumanUltralente2-4 hoursUnpredictable16-20 hours
Glargine1-2 hoursFlat~24 hours
INSULIN TACTICS Twice-daily Split-mixed Regimens
INSULIN TACTICS Multiple Daily Injections (MDI)NPH + Regular
INSULIN TACTICS Multiple Daily Injections (MDI)Ultralente + Regular
INSULIN TACTICSLimitations of Human Regular Insulin
Slow onset of action
Requires inconvenient administration: 20 to 40 minutes prior to meal
Risk of hypoglycemia if meal is further delayed
Mismatch with postprandial hyperglycemic peak
Long duration of activity
Up to 12 hours" duration
Increased at higher dosages
Potential for late postprandial hypoglycemia
INSULIN TACTICSShort-acting Analogues: Lispro and AspartClinical Features
Convenient administration immediately prior to meals
Faster onset of action
Limit postprandial hyperglycemic peaks
Shorter duration of activity
Redu

RATIONALE FOR IMPROVED GLCEMIC CONTROL

9/7/2010

Rationale for Improved Glycemic Control

This program and all of its components are the exclusive property of and are copyrighted by Medical Age Publishing, Division of Snyder Healthcare Communications Worldwide, Stamford, Connecticut. The contents of this program, including design and written information, may not be altered in any way. This program may not be disseminated, reproduced, copied, or published other than with the prior express written consent from Medical Age Publishing, Division of Snyder Healthcare Communications Worldwide.
DCCTIntensive Insulin Treatment in Type 1 Diabetes
DCCTMicrovascular Risk Reduction With Intensive Treatment
DCCTRelationship of HbA1c to Risk of Microvascular Complications
WESDRProgression to Proliferative Retinopathy
UKPDSOverall Study Design
UKPDSMetformin, Acarbose, and Hypertension Substudies
Metformin
1704 overweight subjects
conventional treatment policy or intensive treatment policy (sulfonylurea, insulin, or metformin)
537 subjects (overweight and nonoverweight) with sulfonylurea failure
metformin + sulfonylurea versus sulfonylurea alone
Acarbose
1946 subjects in main randomization study
acarbose added to prior treatment versus placebo
Blood-pressure control
1148 hypertensive subjects
tight control with atenolol or captopril versus less-tight control with other agents
UKPDSBlood Glucose Control Study:Aims
To determine whether improved glycemic control will prevent clinical complications
To determine whether treatment with a sulfonylurea, insulin, or metformin has specific advantages or disadvantages
UKPDSMain Randomization
UKPDSEffect of Treatment on HbA1c
UKPDSRisk Reduction of Microvascular Complications
UKPDSIntensive Treatment Policy and Risk Reduction
UKPDSMyocardial Infarction Risk Reduction by Intensive Treatment
UKPDSMetformin Substudy Design
UKPDS METFORMIN SUBSTUDYIntensive Treatments and HbA1c
UKPDS METFORMIN SUBSTUDYIntensive Treatments and Weight Change
UKPDS METFORMIN SUBSTUDYRisk Reduction of Microvascular Complications
UKPDS METFORMIN SUBSTUDYDiabetes-Related Deaths
UKPDSDifferences Among Intensive Treatment Groups:Conclusions
Sulfonylurea, insulins, and metformin can all reduce risk of complications
No increased risk with any single therapy
Combination therapy with agents with different actions will be needed earlier
More patients will need insulin over time
UKPDSMetformin + Sulfonylurea Substudy
Increased relative risks in metformin + sulfonylurea group
Diabetes-related deaths increased (95%)
Total mortality increased (60%)
Contentious issues
Not placebo-controlled
Short duration (4 years)
Small numbers
Overlap of treatments between groups
Not substantiated by epidemiologic analysis

SERUM ANDROJEN ANABOL�K HORMONLARI VE ROMATO�D ARTR�T R�SK�

9/7/2010

SERUM ANDROJEN ANABOL�K HORMONLARI VE ROMATO�D ARTR�T R�SK�

Ama� : �o�unlukla dolayl� bulgulara dayan�larak, androjen anabolik hormonlar�n�n d��k serum konsantrasyonlar�n�n romatoid artritin etyolojisinde rol oynayabilece�i �ne s�r�lm��t�r.

Y�ntemler : 1973 - 1977 y�llar� aras�nda yap�lan incelemede, herhangi bir artrit rahats�zl�� olmayan 19,072 Finli �ah�s �zerinde, vaka kontrol �al��mas� yap�lm��t�r. 1989 y�l� itibariyle, daha sonra romatoid artrit geli�en 116 vakadan, hastal�k �ncesindeki testosteron ve DHEAS seviyeleri i�in serum �rnekleri toplanm��t�r. Herbir vaka i�in ya�, cinsiyet ve ya�an�lan b�lge y�nlerinden e�lenilk olan �� adet kontrol temin edilmi�tir.

Sonu�lar : Ortalama testosteron seviyeleri, 84 kad�n hastada ve kontrolerde 1.4 nmol / litreydi ve DHEAS seviyeleri de, hastalarda 5.2, kontrollerde 5.5 mikromol / litreydi. 32 erkek hastadaki ortalama testosteron seviyesi 26.1 nmol / litre ve kontrollerde 26.4 nmol / litreydi. Bu gruptaki DHEAS seviyeleri, s�ras�yla hastalarda 11.2 ve kontrolerde de 10.1 mikromol / litreydi. Alt gruplar�n�n ve hormon da��l�mlar�n�n analizi, herhangi bir farkl�l�k g�stermedi.

Var�lan Netice : Elde edilen bulgular, d��k testosteron ve DHEAS seviyelerinin romatoid artritin etyolojisinde bir rol oynayabilece�i g�r��yle ayn� �izgide de�ildir. Romatoid artrit, �zellikle �retkenlik �a��ndaki kad�nlarda, cinsiyet hormonlar�n�n etyolojide yeralabilece�ine i�aret edecek �ekilde erkeklerden daha y�ksektir. Hormonlar�n rol�ne ili�kin daha ileri bulgular, hastal��ngebelik esnas�nda hafiflemesinin g�zlenmesinden gelmektedir. Gebeli�in uzun d�nemli koruyucu etkisi kadar, kontraseptif haplarla ve menapoz sonras� �strojen tedavisiyle sa�lanan korumaya ili�kin bilgiler tart��mal�d�r. Yukar�daki sebeplerden dolay�, kontrollerle k�yasland��nda, romatoid artritli hastalar�n cinisyet hormon durumlar�ndaki farkl�l�klar� g�zetmek etmek mant�kl�yd�. Biyolojik y�nden etkin cinsiyet hormonlar�, �stradiol ve testosterondur. DHEA ve DHEAS, adrenal bezlerin ana salg� �r�nleridir, fakat bunlar�n i�levleri halen tam olarak bilinmemektedir. DHEA, kad�nlarda zay�f bir androjen gibi davran�rken, erkeklerde �strojene benzer etkileri vard�r. �strojen de�erleri y�n�nden, romatoid artritli hastalarla kontroller aras�nda belirgin bir farkl�l�k g�zlenmemi�tir. Romatoid artritli erkek hastalarda, testosterondaki d��k konsantrasyonun DHEAS seviyesi i�in de ge�erli oldu�u konusunda g�r�� birli�i mevcuttur. Kad�nlardaki bulgular tart��mal�d�r. Bunun sebepleri, k�smen kontrollerin se�imine ba�l� olabilir. Romatoid artritteki androjen anabolik hormonlar�n i�lev bozukluklar�n�n veya eksikli�inin hastal��n sebeplerinden bir mi oldu�u, yoksa sadece hastal��a ikincil olarak m� ortaya ��kt�� sorusu hen�z ��z�lmemi�tir. Farkl�l��n en az�ndan k�smen hastal��n etkinli�iyle izah edilebilece�ine ili�kin bulgular vard�r. Di�er yandan, HLA ile romatoid artrite olan zafiyet ve d��k testosteron seviyeleri aras�nda baz� ba�lant�lar rapor edilmi�tir. Bu konudaki �nc�l bir rapora g�re, menapoz �ncesi d�nemdeki kad�nlardaki d��k DHEAs konsantrasyonlar�n�n, romatoid artritin klinik olarak ortaya ��kmas�ndan �nce g�r�lmektedir. 1973 - 1977 aras�nda, Sosyal Sigortalar Kurumunun Gezici Sa�l�k �nitesi, Finlandiya"n�n d�rt b�lgesindeki 12 belediyelikte �o�ul fazl� sa�l�k taramas� ger�ekle�tirdi. D�rt co�rafik b�lgenin her birinde, o b�lgenin b�t�n sakinleri veya k�rsal kesim ve �ehirlerde oturanlar ve fabrika �al��anlar�, bu sa�l�k taramas�na kat�lmalar� i�in davet edildiler. 20 ya� ve �zerindeki (davet edilenlerin % 83"�) toplam 19,518 ki�i, bu organizasyonda yerald�. Kat�l�mc�lar�n ya� ortalamas� 45"ti (20 - 98 ya� aral��). Risk alt�ndakiler (19,072 ki�i), Sosyal Sigortalar Kurumu"nun kay�tlar�na veya anketlere g�re daha �nceden herhangi bir artrit hastal�� veya di�er bir romatik hastal�k hikayesi mevcut olmayan �ah�slard�. �ncelene b�t�n �ah�slar�n morbidite ve mortalitesi, s�rekli takip edildi. Daha sonradan kronik artrit

THE CONTROL OF THROID FUNCTION

9/7/2010

The Control of Thyroid Function

Thyroid Status
A working definition - usually in terms of
serum fT4 & fT3; TSH

An approximate biochemical definition
The number of functional receptors, occupied by T3,
on thyroid response elements of genes.

Which response element
Which gene
Which receptor
What is functionality
Which tissue

Where is physiological control exerted?

1 Hypothalamic-Pituitary-Thyroid Axis

2 Metabolic Control - deiodination

3 At the site of initiation of action - nucleus

4 Other sites?

�OCUKLARDA GH YETMEZL�� TANISI

9/7/2010

�OCUKLARDA GH YETMEZL�� TANISI

GROWTH HORMON
Adenohipofizdeki en �ok �retilen hormon
21 kD 191 aa 2 dis�lfit ba��
%70-75"i 22 k-Da form
%15-20"i 20 k-Da
Plazmada GHBP ba�l� ta��n�r. GHBP, GHR nin proteolitik y�k�m�yla olu�ur
PRL e ve hCS ye benzer
Depolan�r ve sirkadien sal�n�r
G�n i�inde seviyesi 2 ng/ml
Yemek ve egzersizden 3 saat sonra pikler olur
Uykudan 90 dakika sonra sal�n�m h�zlan�r
Derin uykuda maximum sal�n�m

DER� VE YUMU�AK DOKU �NFEKS�YONLARI VE AMP�S�D

9/7/2010

DER� VE YUMU�AK DOKU �NFEKS�YONLARI VE AMP�S�D

a)Deri Ve Yumu�ak Doku �nfeksiyonlar�n�n Tan�m�:

�MPET�GO : �mpetigo �ok rastlanan y�zeysel bir cilt enfeksiyonudur. Y�zde, bacaklarda ve kollarda ka��nt�l�, y�zeyi sar� veya gri kabuklu k�rm�z� yaralar �eklinde kendini g�sterir. Stafilokok, streptokok veya her iki t�r bakteri bu rahats�zl�� yapabilir. D�zg�n cilttede g�r�lebilir. Ama bu bakteriler genelde yara bere izi, �izik, b�cek �s�r�� olan yerlere h�cum etmeyi severler. Ayr�ca dermatit gibi ba�ka bir cilt hastal��yla da yan yana g�r�lebilir.
Enfeksiyon �nce bir k�zar�kl�k �eklinde ba�lar, sivilce olu�ur, patlar ve 1-2 g�n s�z�nt� yapar. Bunun sonucunda yap��kan bir kabuk tutar. Yara geni�leme e�ilimindedir ve bula��c�d�r. Ak�nt�daki bakteriler fiziksel temas ve ka��ma ile bedenin di�er k�s�mlar�na da da��l�r ve yaralar olu�ur, ayr�ca ba�ka ki�ilere de bula��r.
�mpetigo, en �ok temizlikten uzak, fakir �evrelerde ya�ayan �ocuklarda g�r�l�r. Yeti�kinlerde ba�ka bir cilt sorununun komplikasyonu olarak ortaya ��kar. �mpetigo te�hisi yaradan bir doku al�p labaratuvarda incelenerek konulabilir.
S�n�rl� ve k��k enfeksiyonlarda lokal ila�lar etkilidir. Daha yayg�n enfeksiyonlar i�in oral antibiyotik (ampisilin - sulbaktam yada eritromisin gibi) verilebilir. Antibakteriyel sabun veya temizleyici ile g�nde birka� defa y�kamakla kabuklar yumu�ay�p kolayca ��kart�labilir. Enfeksiyonu yaymamak i�in havlular, giyim e�yalar�, tra� malzemeleri payla��lmamal� ve hastal�k ge�ene kadar deri temas�ndan sak�nmal�d�r.

ABSE: Abse, dermis veya subkutiste, yani derinin derin k�s�mlar�nda i�inde cerahat bulunan bir kitledir. Genellikle eritemli bir �i�lik olarak g�r�l�r. Palpasyonda ba�lang��ta hen�z yumu�amam�� bir kitle saptan�r. Zamanla yumu�ar, deri y�zeyine a��l�r ve cerahat bo�alt�r. Deri alt� doku veya organlarda geli�en s�p�ratif olaylar, deriye yay�l�p deride abse olu�turabilir.
T�m abseli hastalarda mikrobiyolojik incelemeler vazge�ilmezdir. Akut abseler, kesinlikle bakteriyolojik olarak incelenmelidir. Yaln�zca stafilokoksik bir enfeksiyonu kan�tlamak a��s�ndan de�il, tedavide kullan�lacak olan antibiyoti�i se�mek a��s�ndan da bu incelemeler gerekir. Kronik abselerde bazen cerahat kullan�larak yap�lan t�m mikrobiyolojik incelemeler, tekrarlayan titiz u�ra�lara kar��n sonu� vermeyebilir. B�yle durumlarda abse duvar�ndan al�nan doku par�alar�ndaki histopatolojik bulgular enfeksiyonun etkenine �zg� olabilir.

FRONK�L ve KARBONK�L: Fronk�l halk aras�nda ��ban olarak bilinir. K�l follik�l�n�n stafilokoksik bir absesidir. Ortas�nda k�l ostiumuna uyan bir yerde beyaz veya gri bir t�ka� g�steren f�nd�k veya ceviz irili�inde akut inflamasyon g�sterir. Zamanla t�kac� at�l�r ve i�indeki cerahat bo�al�r. �nflamasyon �iddetli ise skar b�rakabilir. Gerek lokal gerekse sistemik nedenler ile �ok say�da fronk�l geli�mesine veya s�k s�k n�ksetmesine fronk�loz denir. Birbirine kom�u k�l follik�llerinin s�p�ratif enfeksiyonu olan karbonk�l daha b�y�k bir akut inflamasyon pla��nda birden fazla a��zdan cerahat bo�alt�r. Fronk�l her b�lgede bulunabilirken, karbonk�l daha �ok boyun arkas�nda olu�ur. Etken s�kl�kla stafilacoccus aureustur.
Y�z ortas�nda yerle�en genellikle ate� veya �evresinde yayg�n sell�lit olan olgularda antistafilakokkal antibiyotikle tedavi edilmelidir. Ate�, ��me, titreme, halsizlik veya ba�a�r�s� gibi sistemik semptomlar varsa antibiyotikler parenteral olarak uygulanmal�d�r.

SELL�L�T: Sell�lit, genellikle streptokoklara ba�l� olarak geli�en, deri ve deri alt� dokusunun diff�z enfeksiyonudur. Akut inflamasyon bulgular� g�sterir. Nadiren �zerinde hemarojik b�ller geli�ebilir. Bazen sell�lit pla��ndan proksimale do�ru eritemli bir �erit yani lenfanjit uzanabilir. Bakteriler i�in bir giri� noktas�na gereksinim vard�r. Bu giri� noktas� burunda k�l �ekme veya ayak parmak aras�ndaki mantak enfeksiyonu (tinea pedis) sonucu olu�abilir. Bu nedenle, sell�lit s�kl�kla y�z, ayak ve bacakta yerle�ir.
Sell�lit tedavisinde temel ila� si

HPERTHROIDISM

9/7/2010

Hyperthyroidism

Diagnosis
If the history and findings on physical examination suggest that the patient may have thyrotoxicosis, the diagnosis can be readily confirmed by the combined finding of:

An abnormally high concentration of serum thyroid hormones.
Because of negative feedback inhibition on the pituitary, a subnormal serum TSH level, not previously measurable as such.
Serum free T4 concentration is increased in approximately 95% of ambulatory hyperthyroid patients.

The laboratory tests useful in the diagnosis of hyperthyroidism are summarized as follows:
Measurement of the FT4 level is the simplest and most widely available test. Normal FT4 Level is 4.5-10.9 ug/dl (58-140 nmol/L)
A suppressed TSH level is as sensitive as FT4 and more specific than FT4. Normal TSH is 0.5-5.0 uU/ml
The serum T3 level is sometimes elevated when the T4 is not.
When the goal is to exclude hyperthyroidism as the diagnosis, the sensitive TSH assay is best: a normal value, combined with a normal FTI, is adequate to rule out this diagnosis.
An FT4 level is often useful when the patient is taking a medication that alters TBG levels.
RAIU is not usually needed to confirm the diagnosis of hyperthyroidism and therefore is often omitted from the workup.

Treatment
Three principal therapies are available for hyperthyroidism:

Antithyroid drugs
Subtotal thyroidectomy
Radioactive iodine.

Antithyroid Drugs
Antithyroid drugs are reversible, effective in most patients, and generally safe
Two principle drugs: Methimazole and Propylthiouracil
They principally block oxidation of iodine and its incorporation into tyrosine residues
Methimazole also increases the number and activity of suppressor T cells and diminishes the activity of helper T cells. As a result, the drug inhibits production of antimicrosomal and anti-TSH receptor antibodies.
Propranolol can be used to control symptoms like palpitations, tremors and excessive sweating. It is also used before surgery and during thyroid storm
Favorable prognostic signs for permanent remission include a short history, mild disease, and a small goiter (best factor)
Dosage
Propylthiouracil, in an initial dosage of 100 mg every eight hours, or methimazole, in an initial dosage of 10 mg every 8 to 12 hours, will render almost all patients euthyroid in one to six months
To simplify treatment and encourage compliance, a single daily dose of methimazole, 20 to 40 mg, can be tried in any but the most florid cases
Methimazole is probably preferable to propylthiouracil for most patients because it can be administered once a day, produces fewer adverse reactions, and is less expensive. Propylthiouracil is preferable during pregnancy and perhaps for treating thyroid storm

Side Effects
The complications of antithyroid drugs are allergic ones and include:
Minor or major skin reactions
Arthralgias
Hepatitis
Agranulocytosis, a potentially serious but rare occurrence. Agranulocytosis occurs most often in patients older than 40 years who are given more than 30 mg of methimazole a day.
 All of the complications tend to resolve spontaneously if drugs are withdrawn promptly.
Side Effects - Hypothyroidism
Hypothyroidism may develop after antithyroid drugs. Symptoms vary but certain ones are :
Arthralgias
Paresthesias
Muscle cramps
Enlarging goiter
Side Effects - Hypothyroidism
Symptoms of hypothyroidism are particularly common in recently hyperthyroid patients who have been rapidly rendered hypothyroid. To avoid hypothyroidism when the patient has entered the euthyroid range or when the level of TSH, previously suppressed by the toxic state, begins to rise, either 0.1 mg of thyroxine daily can be added or the dosage of antithyroid drug can be reduced.

Subtotal Thyroidectomy
Although much less often used now, subtotal thyroidectomy is a venerable approach to hyperthyroidism. For reasons that remain obscure, extensive but incomplete removal induces remission in most patients with Graves disease
Rapid prepar

FEOKROMAS�TOMA

9/7/2010

FEOKROMAS�TOMA

Tan�m
Feokromasitoma, katekolamin ve baz� olgularda di�er peptid hormonlar� sentezleyen kromaffin h�crelerden geli�en bir t�m�rd�r.
Extra-adrenal kromaffin h�crelerden k�ken alan tipi ekstra-adrenal feokromasitoma veya paraganglioma olarak adland�r�lmaktad�r.
Nadir rastlanan genellikle hipertansif krizlerle kendini g�steren % 80-90 oran�nda benign k�rabl bir hastal�kt�r.
Semptomlar katekolaminlerin etkilerine ba�l� ortaya ��kmaktad�r.
Sporadik, familial veya multipl endokrin neoplazilerin bir par�as� olabilir.

Tarih�e
Feokromasitoma ilk olarak 1886 y�l�nda Frankl taraf�ndan tan�mlanm��t�r.
Alfa blokerlerin kullan�ma girmesinden �nce genelde hastalar ameliyat s�ras�nda hipertansiyon ve ameliyat sonras�nda hipotansiyon nedeni ile kaybedilmekteydiler.
Alfa blokerlerin kullan�ma girmesiyle ba�ar�l� bir �ekilde tedavi edilebilmi�lerdir.
�nsidans
Genel populasyonda oran 100.000 de 1-2.
Otopsilerde onbinde 5 ile binde 1 oran�ndad�r.
Hipertansiyon olan hastalar�n % 0.1 inde idrarda katekolamin tayini sonucu feokromasitoma saptanmaktad�r.
Malignite insidans� % 5 ila % 46 aras�ndad�r.
Extra-adrenal feokromasitomalarda malignite potansiyeli daha fazlad�r.

Etiyoloji
Etiyolojisi tam olarak a��kl��a kavu�turulamam��t�r. Bu t�m�r n�ral krestten k�ken alan kromaffin h�crelerden geli�mekte, bu durum diferansiyasyonun her a�amas�nda meydana gelebilmektedir.
Genetik �al��malarda ras onkogeninin t�m�r olu�umunda etkili olmad�� anla��lm��t�r.

Lokalizasyon ve morfoloji
Feokromasitomalar�n geli�ti�i kromaffin h�creler fetal hayatta t�m v�cutta yayg�nd�r.
T�m�r eri�kinlerde % 80 �nilateral adrenal (�o�u sa�da)
% 10 bilateral adrenal
% 10 extra-adrenal yerle�imlidir.
�aplar� genelde 10 cm den k��kt�r, a��rl�klar� genelde 100 gr alt�ndad�r. 3 kg a kadar t�m�rler bildirilmi�tir.
T�m�rlerin �o�u gri renkte yumu�ak k�vaml� solit yap�dad�r. B�y�k t�m�rlerde kistik komponentler olabilir. Mikroskopik olarak b�y�k polihedral, pleomorfizm g�steren kromaffin h�creler g�r�l�r.
Extra-adrenal feokromasitoma
�ocuklarda % 35, eri�kinlerde % 10 oran�nda extra-adrenal yerle�imlidir.
Adrenal d��nda:
Abdomende
Paraaortik b�lgede bifurkasyondaki Zuckerkandl organ�nda
Mesanede
B�brekte
Karaci�er hilusunda bulunur...
Extra-adrenal yerle�imli feokromasitomalar genelde 5 cm �ap�n alt�nda ve 20-40 g aras�ndad�r. �o�unlukla (%20) multisentrik ve malign potansiyeli olan t�m�rlerdir.
Malign Feokromasitoma
Adrenaldeki feokromasitomalar�n % 10 u, adrenal d�� olanlar�n % 30 u maligndir.
Malign feokromasitomalar olduk�a yava� b�y�yen, ciddi hipertansiyon ve di�er semptomlara neden olan bir t�m�rd�r.
En s�k akci�ere, kemik ve yumu�ak dokulara metastaz yapar.
Malign feokromasitomal� hastalar�n 5 y�ll�k ya�am s�resi % 44 t�r.
Histopatolojik olarak benign-malign ay�r�mlar� zordur. Temel kriter uzak organ metastazlar�d�r.

Familyal feokromasitoma ve multipl endokrin neoplaziler
Familyal feokromasitoma % 5 oran�nda g�r�len otozomal dominant bir hastal�kt�r.
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INSULIN THERAPY IN TPE 2 DIABETES

9/7/2010

Insulin Therapy in Type 2 Diabetes

Table of Contents
Page Slide
2 SLIDE 1. Attaining Glycemic Goals for Type 2 Diabetes Using
Monotherapy
2 SLIDE 2. Attaining Glycemic Goals Using Monotherapy in Obese Patients
With Type 2 Diabetes
3 SLIDE 3. Diabetes Management in Primary Care
4 SLIDE 4. Intrasubject Variability: NPH Insulin
4 SLIDE 5. Intrasubject Variability: Ultralente Insulin
5 SLIDE 6. Intrasubject Variability: Insulin Glargine
5 SLIDE 7. Insulin Glargine vs NPH Insulin: Glycemic Control and
Hypoglycemia
6 SLIDE 8. Pharmacodynamics/Pharmacokinetics of Insulin Aspart vs
Regular Insulin
6 SLIDE 9. Pharmacodynamics/Pharmacokinetics of NN304 vs
NPH Insulin
7 SLIDE 10. New Concepts in Insulin Delivery: Changes in Plasma Glucose
With Inhaled Human Insulin
7 SLIDE 11. Effects of Pioglitazone, Rosiglitazone, and Troglitazone on Liver
Function
7 SLIDE 12. Efficacy and Safety of Triple Therapy: Troglitazone + Metformin +
Sulfonylurea
8 SLIDE 13. Improved Glycemic Control With Rosiglitazone in Patients With
Type 2 Diabetes
9 SLIDE 14. Effects of Pioglitazone on Glycemia in Patients With Type 2
Diabetes
10 SLIDE 15. Management of Gestational Diabetes Mellitus
11 SLIDE 16. Type 2 Diabetes in the Pediatric Population: First Nation Data
11 SLIDE 17. Clinical Trends in Practice Outcomes of Diabetes Care
12 SLIDE 18. Economic Trends in Type 2 Diabetes Care
2
Insulin Therapy in Type 2 Diabetes: UPDATE
In the subgroup of patients described in Slide 1 who were obese,
metformin was a fourth monotherapy option.1 In this subgroup,
23%, 45%, 44%, and 34% attained a HbA1c level 7% after 3 years
of monotherapy with diet, a sulfonylurea, metformin, or insulin,
respectively. After 9 years, those proportions were substantially lower:
11%, 21%, 13%, and 24%, respectively.
1. Turner RC, Cull CA, Frighi V, et al. Glycemic control with diet, sulfonylurea, metformin,
or insulin in patients with type 2 diabetes mellitus: progressive requirement for
multiple therapies. JAMA. 1999;281:2005-2012.
SLIDE 2
Data from more than 4000 patients with type 2 diabetes who participated
in the UK Prospective Diabetes Study (UKPDS) were analyzed
to determine factors that might predict the need for multiple
therapies.1 The patients were checked every 3 months over 9 years of
treatment with diet alone, a sulfonylurea, metformin (in obese
patients), or insulin. Fasting plasma glucose (FPG) concentrations and
HbA1c levels were determined at each clinic visit.
The data from the UKPDS were analyzed with respect to the proportion
of patients who achieved and maintained their target glycemic
levels during monotherapy with diet alone, a sulfonylurea, or insulin.1
The analysis included the total patient population, ie, normal-weight
and overweight patients. At 3 years, 25%, 50%, and 47% of patients
had achieved a HbA1c level 7% after monotherapy with diet, a sulfonylurea,
or insulin, respectively. The proportion of patients who
maintained target glycemic levels declined markedly during the 9 years
of follow-up. After 9 years, only 8%, 24%, and 42% of the patients
treated with diet, a sulfonylurea, or insulin, respectively, had maintained a
HbA1c level 7%.
A univariate logistic regression analysis found that for patients with a HbA1c
level 7% at 3 years, a young age at diagnosis, and increased body mass index
or waist circumference, baseline values for HbA1c, FPG, and plasma triglycerides
were significantly associated (P ≤0.02) with the likelihood of requiring
multiple therapies to maintain glycemic control. The only variable that did not
correlate significantly with an increased probability was a positive result for
islet cell and glutamic acid decarboxylase antibodies. With the exception of an
elevated baseline HbA1c value and a positive result for antibodies, all other factors
analyzed also correlated significantly (P ≤0.002) with the likelihood for
multiple therapies in patients who had an FPG level 140 mg/dL at 3 years.
1. Turner RC, Cull CA, Frighi V, et al.

KRON�K B�BREK YETMEZL��NDEK� ENDOKR�N ANORMALL�KLER

9/7/2010

Kronik B�brek Yetmezli�indeki Endokrin Anormallikler

A.B.D"de, son d�nem b�brek yetmezli�i (SDBY) olan 300,000"den fazla hasta vard�r. D�zenlenen kesitsel bir Milli Sa�l�k Ve Beslenme Tetkik Anketi"nde, serum kreatinin seviyelerinde art�� tesbit edilmesinde oldu�u gibi, 6,2 milyon Amerikal�"n�n anormal b�brek i�levine sahip oldu�u (serum kreatinini 1,5 mg / dl) tahmin edilmektedir. Bu grubun i�indekilerin �o�u, son d�nem b�brek yetmezli�ine ilerlemeyecek olmas�na ra�men, bu pop�lasyon genel n�fus i�inde y�ll�k yakla��k % 6 - 7"lik bir SDBY potansiyelini de b�nyesinde bar�nd�rmaktad�r. Bir grup olarak, diyaliz tedavisi alan SDBY hastalar�n�n ortalama ya�am s�relerinde ve hayat standartlar�nda, genel n�fus i�inde bu hastalara ya� ve cinsiyet y�n�nden uyan kontrollere nazaran belirgin bir d�� mevcuttur. A.B.D"de, SDBY"li hastalar genel t�bbi bak�m alan n�fusun % 0,5"lik bir k�sm�n� te�kil etmeelrine ra�men, toplam y�ll�k tedavi gider maliyetinin % 5"lik k�sm�na sahiptirler. A.B.D"de, diyaliz hastalar� aras�ndaki �l�m oran�, y�ll�k 100 hastada yakla��k 20 ki�i gibi hala y�ksek bir orana sahiptir. Olgunla�mam�� ve h�zlanm�� aterosklerotik koroner hastal�klar, sol ventrik�l hipertrofisi ve kalp yetmezli�i, kalbe ili�kin olaylar� bu kesimdeki en s�k �l�m sebebi haline getirmektedir. Orta derecede yetmezli�in mevcut oldu�u kronik b�brek yetmezli�inde, endokrin anormallikler erken d�nemde s�k olarak g�r�lmektedir, yaln�z bu bozukluklar, b�brek yetmezli�i ilerledik�e daha da belirginle�ir. Bu anromalliklerin patofizyolojik mekanizmalar� aras�nda, b�breklere y�nelik endokrin ve egzokrin hormon �retiminde azalma, hormonlar�n b�breklerden ve di�er yollardan metabolik olarak temizlenmesinde azalma, kronik b�brek yetmezli�inde homeostatik sinyal mekanizmas�nda ya�anan de�i�iklikler, hormon ba�lanmas�nda ve dokular�n bu hormonlara verdikleri cevaplarda g�r�len de�i�iklikler vard�r. B�brek yetmezli�inde pek �ok endokrin anormallikler g�zlenmesine ra�men, bunlardan g�receli olarak az bir k�sm� klinik y�nden bir problem te�kil eder. Yerin k�s�tl� olmas� dolay�s�yla, bu makale endokrin rahats�zl�klar�n nefroloji uzmalar�n�n kar��s�na �nemli sorunlar olarak ��kt�� ve hastan�n morbidite, mortalite ve hayat kalitesi gibi durumlar�n� �nemli derecede etkiledi�i, s�k g�r�len �� durumu ele almaktad�r : (1) Fosfor, kalsiyum, D vitamini ve paratiroid hormon aras�ndaki dengede meydana gelen de�i�iklikler, (2) eritroprotein eksikli�i ve (3) �remide g�r�len cinsel i�lev bozuklu�u.

Fosfor, Kalsiyum, D Vitamini ve Paratiorid Hormon :

Kalsiyum ve fosfor dengesinde, D vitamini metabolizmas�nda ve paratiroid hormon d�zenlenmesinde meydana gelen rahats�zl�klar, b�brek yetmezlikli hastalarda s�k olarak g�r�lmektedir. Bu rahats�zl�klarda, her zaman renal osteodistrofi gibi iskelete ili�kin etkiler �zerine vurgu yap�lm��t�r. SDBY"li hastalar, d�zensiz mineral metabolizmas�na d��k ve y�ksek d�n��m h�zl� kemik hastal�klar� olarak, karma��k ve �e�itlilik g�steren bir klinik cevap verirler. A.B.D"de diyaliz hastalar� �zerinde yap�lan toplumsal tabanl� �al��malar, iskelete ili�kin olarak meydana gelen bu fenotipik de�i�ikliklerden kaynaklanan k�r�k g�r�lme riskinde, birka� misli art�� oldu�una i�aret etmektedir. Ge�ti�imiz y�llarda, genel yakla��mda metastatik kalsifikasyonlar�n b�rakt�� iskelet d�� sekellerin, �zellikle de damarsal kalsifikasyonlar�n �nemini kavramayla neticelenen bir de�i�iklik ya�anm��t�r. 1998"de Block ve arkada�lar�, hemodiyaliz hastalar�nda fosforun 5,5 - 6,5 mg / dl"nin veya kalsiyum x fosforun 55 - 65 mg2 / dl2"nin �zerine ��kt�� zaman, bu durumun hastalardaki mortalite oranlar�ndaki �izgisel bir art��la bir arada oldu�unu ilk kez g�steren ve Birle�ik Devletler B�brek Veri Sistemi"nden elde edilen verileri yay�nlad�lar. �o�ul de�i�kenli bir takip analizinde, koroner arter hastal��ndan �l�m oran�, artan serum fosforuyla yak�ndan ili�kiliydi. Dolay�s�yla, kronik b�brek yetmezli�indeki d�zensiz mineral metabolizmas�na ili�kin herhangi b

INSULIN THERAP IN TPE 2 DIABETES CURRENT AND FUTURE DIRECTIONS

9/7/2010

Insulin Therapy in Type 2 Diabetes:Current and Future Directions

Issues in the Management ofType 2 Diabetes
Type 2: Deterioration of beta cells over time
Increasing prevalence with increasing risk factors, eg, obesity
Hyperglycemia affects morbidity, mortality, and resources
Tight glycemic control with insulin may reduce costly complications
30% to 40% of patients ultimately require insulin
Regimen-related limitations with current insulin formulations and delivery systems
Newer semisynthetic insulins and delivery systems may improve compliance and achieve better glycemic control with less hypoglycemia
Prevalence of Type 2 Diabetes Mellitus
Incidence of Type 2 Diabetes Mellitus
Risk Factors for Type 2 Diabetes
Nonmodifiable
Genetic factors
Age
Ethnicity
Modifiable
Weight
Physical activity
Trend in Prevalence of Obesity*: NHANES Data
Link Between Obesity and Type 2 Diabetes:Nurses" Health Study
Link Between Obesity and Type 2 Diabetes:Nurses" Health Study (cont"d)
ADA Treatment Guidelines
Medical Nutrition Therapy for Type 2 Diabetes
Diet
Improved food choices
Spacing meals
Individualized carbohydrate content
Moderate calorie restriction
Exercise
Pharmacologic Therapy for Type 2 Diabetes
Sulfonylureas (glyburide, glipizide, glimepiride)
Biguanides (metformin)
Alpha-glucosidase inhibitors (acarbose, miglitol, voglibose)
Benzoic acid analogues (repaglinide)
Thiazolidinediones (troglitazone, rosiglitazone, pioglitazone)
Insulin (human insulin, insulin analogues)
Treatment Algorithm
Considerations in Pharmacologic Treatment of Type 2 Diabetes
Efficacy (HbA1c lowering capacity)
Mechanisms of action of drugs
Impact on weight gain
Complications/tolerability
Frequency of hypoglycemia
Compliance/complexity of regimen
Cost
Tight Glycemic Control:Reducing the Risk of Complications
Epidemiologic evidence in type 2 diabetes to link microvascular disease and hyperglycemia — first suggested in DCCT
Type 2 diabetes studies: Veterans Affairs Cooperative Study on Type 2 Diabetes (VA CSDM), United Kingdom Prospective Diabetes Study (UKPDS), and Kumamoto trial
Intensive blood glucose control with insulin, sulfonylurea, or metformin reduced risk of micro- and macrovascular complications
Glycemic threshold to prevent onset and progression of microvascular complications: HbA1c 6.5%, FBG 110 mg/dL, 2-hr postprandial glucose 180 mg/dL
Improvement in HbA1c in the VA CSDM
VA CSDM: Results at Endpoint
The Kumamoto Trial: Effects of Conventional vs. Intensive Insulin Therapy
UKPDS: Effect of Intensive Therapy on Glycemia
UKPDS 10-Year Cohort Data: Reductions With Intensive vs. Conventional Therapy
Summary of Key Findings
VA CSDM:
Glycemic control achievable with intensive insulin treatment: control maintained 2 years
Intensive treatment not associated with severe hypoglycemia, weight gain, hypertension, or dyslipidemia
Kumamoto trial:
Intensive insulin treatment reduced microvascular complications
Established glycemic threshold to prevent onset and progression of complications
UKPDS:
Diet therapy alone inadequate in two thirds of patients
Pharmacologic therapy plus nutrition/exercise necessary
Weigh benefit:risk ratio
No threshold for HbA1c reduction in reducing complications
Insulin does not increase macrovascular disease
Pharmacokinetics of Current Insulin Preparations
Effective
OnsetPeakDuration

Insulin lispro 15 min1 hr3 hr
Regular0.5-1 hr2-3 hr3-6 hr
NPH/Lente2-4 hr6-12 hr10-16 hr
Ultralente4-8 hrVaries18-20 hr
Clinical Efficacy of Insulin Lispro
Worldwide clinical trials of insulin lispro in 10,000 patients with type 1 or type 2 diabetes
1-year parallel group comparisons or 6-month crossovers (3 months on each insulin) studies
Dosage regimen: insulin lispro 10 min before and soluble human insulin 30 to 45 minutes before meals, with NPH or ultralente insulin as the basal insulin supplement
Strategies for Insulin Therapy in Elderly Patients
Insulin therapy often considered a last resort in the elderly
Therapeutic go

HORMONAL D�ZENLEME

9/7/2010

HORMONAL D�ZENLEME

Sistemli canl�larda organ ve dokular�n fizyolojik aktivite b�t�nl�� ile sitemler aras�nda i�birli�ini sa�layan d�zenleyici maddelere hormon denir. Ancak her d�zenleyici madde hormon de�ildir.Mesela; Kandaki CO2 konsantrasyonu; beyinde solunum merkezini uyar�r. Ancak CO2 bir hormon de�ildir.
Hormonlar sistemli canl�larda �zellikle organ ve dokular aras� i�birli�ini sa�layan mesaj ta��y�c�lard�r. Bitkilerde dokular aras�nda haberle�me hormonlarla yap�lmaktad�r. Hayvanlarda ise dokular ve organlar aras� haberle�me ba�l�ca iki sistem ile yap�l�r. Bunlardan birisi sinir sistemidir. Di�er is hormonla sistemdir. Hayvanlarda canl�l�k olaylar�n�n kontrol, devaml�l�� ve fizyolojik b�t�nl�� sinir ve hormonal sistemin birlikte �al��mas�yla sa�lanmaktad�r.
Hormonlar organizmalarda belirli bezlerden salg�lan�r. Bu bezlere endokrin bezler denir. Ancak hayvanlarda sinir h�crelerinin u� k�sm�ndan da hormonal aktiviteye sahip dopamin, histamin, asetil colin gibi maddeler salg�lamaktad�r. Dolay�s�yla hormonlar sadece endokrin bezlerden salg�lanmaz. Bitkilerde hormonlar belirli b�lgedeki h�crelerden salg�lan�r. Salg�lana hormonlar de�i�ik doku ve organlara ta��narak gitti�i b�lgede etkili olur. Gerek endokrin bezlerden, gerekse sinir h�crelerinin u� k�sm�yla, bitkilerin �zel h�crelerinden salg�lanan hormonlar, salg�land�� dokuda de�il hedef dokularda; g�rev yapar. Hormonlar hedef dokularda b�y�meyi farkl�la�may�, yaralar�n tamirini, h�cre zar�ndan madde al��veri�ini, organizmadaki s�v�lar�n pH"�n� ve osmotik bas�nc�n� d�zenleyen do�al organik maddelerdir.

B�TK�SEL HORMONLAR

Bitkisel hormonlar h�cre metabolizmas� �zerinde son derece etkindir (az miktarda dahi olsa). Bitkisel hormonlar hayvansal hormonlarda oldu�u gibi sentezlendikleri b�lgeden az veya �ok uzak b�lgeden az veya �ok uzak b�lgede etkili olurlar.
Bitki hormonlar�; �ncelikler aktif b�y�me g�steren dokularda, k�k ve g�vde u�lar�nda bulunan b�y�me noktalar�ndaki meristematik dokularda meydana gelir.
Bitkisel hormonlar�n bitkilere ait farkl� b�lgelerde meydana getirdikleri etkileri a�a��daki gibi s�ralayabiliriz.
1)Bitkinin b�y�me b�lgesinde boyuna uzamay� sa�lar.
2)Yeni k�klerin, �zellikle yan k�klerin olu�umunu sa�lar.
3)�i�ek k�s�mlar�ndan �i�ek ve meyve olu�umunu h�zland�r�r.
4)Kambiyumda h�cre b�l�nmesini h�zland�r�r.
5)Yan tomurcuklar�n geli�imini durdurur.
6)Absisyon tabakalar�n�n olu�umuna engel olur.(Absisyon tabakas�: Yapraklar�n d�k�lmesi esnas�nda yaprak sap�nda olu�an mantar dokusu=
Bitkisel hormonlar do�al organik maddelerdir. Bu maddelerden bilinenleri oksinler, giberellinler, sitkininler, absisik asit ve etilen say�labilir.
a)Oksinler: Bitkilerde en etkin b�y�me ger�ekle�tiren hormondur. Ancak oksinler bu etkiyi di�er hormonlarla beraber ger�ekle�tirirler. Oksinler meristematik h�crelerde b�l�nme, h�cre ve doku farkl�la�mas� gibi olaylarda etkin rol oynamaktad�r. Oksinler bitkide �zet olarak yaprak d�k�m�, �i�ek a�ma ve meyve verme gibi herkes taraf�ndan g�r�lebilecek faaliyetleri d�zenler. Mesela yapraklarda d�k�lme olay�na bitkide oksin hormonunun azalmas� neden olmaktad�r. Etilen de oksinle birlikte yaprak d�k�m�nde etkilidir.
b)Giberellinler: Bu hormonlar baz� bitkilerde g�vde uzamas�n�n ve meyve b�y�mesinin h�zland�r�r. Giberellinlerin en �nemli �zelli�i tohum �imlenmelerini uyarmalar�d�r.

c)Sitokininler: T�t�n bitkisinden izole edilmi� bir hormondur. �zellikle sitokininler ile giberellinler daha �ok erken geli�me d�neminde etkide bulunarak b�y�meyi sa�lar. Oksinler ise geli�me evresinden sonra etkili olurlar. Tomurcuk geli�mesi tohum �imlenmesi yapraklar�n ge� ya�lanmas� gibi olaylarda sitokininler etkilidir.
d)Absisik Asit: Tomurcuklarda uyuklama veya geli�meyi durdurucu bir etkiye sahiprtir.
e)Etilen: Bu hormon sadece �retildi�i yerde etkili olmaktad�r. Bu madde yaprak d�k�m� ve meyve olgunla�mas�nda etkilidir.

ENDOKR�N BEZLER
�NSANDA ENDOKR�N BEZLER VE HORMONLAR

A) H�POF�Z BEZ�

Yakla��k 1,25 santim �arp�nda, cevize benzer k��c�k bir salg� bezidir ve kafatas�n�n alt k�sm�nda beynin alt�na yerle�mi� bulunmaktad�r. �n ve arka olmak �zere iki k�sma ayr�lm��t�r ve her k�s�mda kan ak�m�na ayr� cins hormonlar ifraz eden ayr� tip h�creler bulunmaktad�r.
Hipofiz salg� bezi v�cuttaki b�t�n bezlerin fonksiyonunu kontrol etti�i i�in "Ba�l�ca Bez" denilebilir

a) Hipofizden Salg�lanan Hormonlar

ENDOKR�NOLOJ� VE KBB

9/7/2010

ENDOKR�NOLOJ� VE KBB

Giri�
Ba� ve boyun b�lgesinin muayenesinde elde edilen bulgular de�erlendirilirken endokrinolojik ve metabolik hastal�klar mutlaka d��n�lmelidir. Endokrin sistemi ilgilendiren yak�nmas� olan pek �ok hasta otolarengolo�a ba�- boyun b�lgesi sorunlar� ile m�racat edebilir. Muayenede elde edilen bulgular hastan�n endokrinolo�a y�nlendirilmesinde anahtar rol oynar. Do�ru tan� ve tedavide hastan�n hekime ilk m�racat� s�ras�ndaki yakla��m �ok �nemlidir. Otolarengolog muayenesinde, kafatas�, kafa derisi, sa�lar, g�zler, y�z, cilt, al�n, ka�lar, burun, dudaklar, �ene, di� etleri, di�ler, dil, a��z bo�lu�u, orofarenks ve boyunu tam bir de�erlendirmeye tabi tutmal�, elde etti�i bulgular� not etmelidir. Muayene bulgular� ve tetkik sonu�lar� kombine edildi�inde sistemik bir problemi i�aret ediyorsa, endokrin sistem ve hastal�klar� akla getirilmelidir.
Endokrin Sistem
Endokrin sistemi olu�turan organlar; hipofiz, tiroid bezi, paratiroid bezler, pankreas, b�brek �st� bezleri, gonadlard�r(over ve testisler). Endokrin sistemi olu�turan organlar�n �e�itli patolojilerinden kaynaklanan hipo ve hiperfonksiyonlar� kendilerini lokal ve sistemik bulgularla g�sterirler.
Hipofiz
Embriyoloji ve Anatomi
Hipofiz bezi sfenoid kemikteki sella tursikan�n i�inde yeral�r. Arteriyel beslenmesi internal karotid arterden ayr�lan hipofizeal arterler iledir. Ven�z drenaj� kavern�z sin�s sisteminedir.
Hipofiz embriyolojik olarak 2 farkl� orijine sahiptir. Posterior hipofiz(n�rohipofiz) 3. ventrik�l taban�ndan geli�ir ve santral sinir sisteminin direk uzant�s�d�r. N�rohipofiz oksitosin ve ADH(Antidi�retik hormon) sal�n�m�ndan sorumludur. �n hipofiz (adenohipofiz) ratke po�undan geli�ir. Eskiden asidofil, bazofil, kromofob h�crelerden olu�tu�u d��n�lmekteyken, g�n�m�zde ayr� hormonlar�n sal�n�m�ndan sorumlu 5 h�cre tipinden (kortikotrop, tirotrop, somatotrop, laktotrop, gonadotrop) olu�tu�u ileri s�r�lmektedir. ACTH, TSH, LH, FSH, prolaktin, GH sal�n�m� adenohipofiz taraf�ndan yap�lmaktad�r.
Fizyoloji
ACTH
ACTH(adrenokortikotropik hormon)�n adenohipofizden sal�n�m� pulsatildir. Serumdaki en y�ksek seviyesi sabah 6.00 ile 8.00 aras�ndad�r(sirkadian ritm). ACTH adrenal bezlerde steroidogenezizi , ya� h�crelerinde lipolizi, kasa aminoasid ve glikoz al�m�n�, pankreastaki beta h�crelerinde ins�lin sal�n�m�n�, hipofizin somatotrop h�crelerinden GH(growth hormon) sal�n�m�n� uyar�r.
ACTH�n sal�n�m�, hipotalamustan sal�nan CRH(kortikotrop releasing hormon) ve dola��mdaki adrenal kortizollerin kontrol� alt�ndad�r. ACTH�n fazla sal�n�m� Cushing sendromuna yol a�arken, yetersiz sal�n�m� Addison hastal��na benzer semptomlara yol a�ar. Ya�la beraber glukokortikoidlerin ACTH �zerindeki etkisi(negatif feedback) azalabilir.
TSH
TSH adenohipofizdeki tirotrop h�creler taraf�ndan yap�l�r. Tirotropin resept�rleri tiroid h�crelerin ve di�er h�crelerin(adiposit gb.) plazma membranlar�nda lokalizedir. TSH sal�n�m� TRH taraf�ndan stim�le edilir. Sal�n�m�n inhibisyonunda somatostatin ve GH rol oynar. Tiroid hormonlar�n�n (T3, T4) TSH sal�n�m� �zerinde negatif feddback etkisi vard�r. �ntrasell�ler T3�n %75i T4ten kaynaklan�r.
GH
GH adenohipofizin %35-45ini olu�turan somatotropik h�creler taraf�ndan sal�n�r. Hormonun sal�n�m� pulsatildir. Uykuda en y�ksek seviyeye ula��r. GH kartilaj ve kemik geli�imini stim�le eder. Nitrojen ve protein metabolizmas�, ya�, karbonhidrat metabolizmas�, yumu�ak doku geli�imi �zerine etkilidir.
GH sekresyonu hipotalamik peptidler taraf�ndan d�zenlenir. Sekresyon GH RH taraf�ndan stim�le, somatostatin taraf�ndan inhibe edilir. Egzersiz, stres, n�rolojik stim�lanlar, santral alfa adrenerjik agonistler sekresyonu art�r�r. Alfa adrenerjik blok�rler, beta adrenerjik agonistler sekresyonu azalt�r. Hormonun fazla sal�n�m� gigantizme ve akromegaliye neden olur. Hormon eksikli�i izole veya di�er hipofiz hormonlar�n�n eksikli�iyle beraber olabilir.
Prolaktin
Prolaktin sal�n�m� diurnal paterndedir. Hipofizin %10 ile %25ini olu�turan laktotro

DAVRANI�IN B�YOLOJ�K TEMEL�

9/7/2010

DAVRANISIN BIYOLOJIK TEMELI:

Sinir sisteminin temel birimi norondur.Caplari mm in 1/10-1/100 arasinda degisir. Dantiritler sinir hucresinin alici organlaridir. Aksonlar siniri ileten kisimlaridir.

Noronlar uce ayrilir:
1-Duyusal noronlar
2-Motor noronlar
3-Inter noronlar

Duyusal noronlar: Cevreden gelen uyarimlari merkezi sinir sistemine iletirler.
Motor noronlar:Beyinden yada omurilikten gelen kampusleri organlara, kaslara ve salgi bezlerine tasirlar.
Inter noronlar:Duyusal noronlardan gelen impulslari alir motor norona iletirler.

*Sinirlerimizde binlerce noron vardir.
*Bir noronun digeriyle iliskisine sinops denir.

Sinir sistemi ikiye ayrilir

1-Merkezi sinir sistemi
2-Perifer sinir sistemi

Merkezi sinir sistemi:Beyin ve omurilikteki tum noronlari ve vucudun buyuk bir kismindaki noronlari kapsar.

*Tum sinirler omurilikte biraraya gelir.Orada bir sinir demeti olusturur ve bunlar kemiklerle korunur.

*Beyin:

-Merkezi Cekirdek
-Medulla
-Beyincik
-Talamus
-Hipotalamus
-Retikuler sistem
-Limbik sistem
-Beyin yarikureleri

Medulla:Omuriligin beyne girdigi yerde, girdikten sonra, biraz buyudugu kisim.Gorevi:Solunum, yutkunum, kalp atimi, sindirim gibi faaliyetleri denetler ve vucudun dik durmasina yardimci olur.Medulla da omurilikten beyne, beyinden omuriligi giden sinirler carpraz haldedir.

Beyincik:(serebellum) Islevi:Vucudun dengesini ve istemli hareketlerin koordinasyonunu saglamak.Baligin yuzmesi, kusun ucmasi gibi.Hasarinda otomatik hareket yapilamaz. Yurume gibi...

Talamus:Beyin yari kurelerinin icinde, beyin sapinin yukarisinda yumurta bicimli yapidir.Omurilikten beyne, beyinden omurilige giden sinirlerin gectigi yerdir.Uykunun uyanikligin denetlenmesinde rol oynar.

Hipotalamus:Talamusun altindaki kucuk yapidir,Homeostasis i saglar. (vucut isisi, kalp atisi, kan basinci gibi organizmanin faaliyetlerini duzene koyma mekanizmasina homeostasis denir)Ayni zamanda duygu ve heyecanlarlada ilgilidir.Cesitli bolgelerinin uyarilmasi haz ve aci verir.
Hipotalamusun altinda hipofiz denilen bir salgi bezi vardir.Hipotalamus hipofiz bezinide etkileyerek korku ve strese karsi hormonal tepkileri denetler.

Retikuler sistem:Bir ag tabakasidir.Bir norol yapidir.Beyin sapindan cikip, talamusa kadar genisleyen merkezi cekirdek yapilari uzerinde bir ag tabakadir.Islevi: Genel uyarilmislik ve farkindalik halini denetlemede onemli rol oynar.Bu sistem bazi uyarimlarin beyin korteksine gecmesine izin verir, bazilarina vermez.

Limbik sistem:Beyin merkezi cekirdegini cevreleyen beyin yari kurelerinin en icindeki bir kac yapidan olusan yapinin tamamina denir.Evrimsel goruse gore merkezi cekirdekten daha sonra gelismistir ve yalnizca memelilerde bulunur.Gorevi:Temel ihtiyaclari karsilayan hareketler ve duygu ve heyecanlarla ilgilidir.Hipotalamusla yakin bir bagi vardir.Hipotalamus ve beyin sapi tarafindan yonetilen ic gudusel davranislarin bazilari uzerinde denetim yapar.Memelilerde bazi icgudusel davranislari engeller ve organizmanin cevresine daha esnek ve uyumlu olmasini saglar.
Bellek duzeninde onemli bir etkisi vardir.Limbik sistemin bir bolumunun adi hipokampusdur.Hipokampus bellek uzerinde etkilidir.Bu bolgenin hasarinda bilgiler bellekte saklanamaz fakat eski bilgiler hatirlanir.

Beyin yarikureleri:Beynin korteks denen bir dis kabugu vardir.Bu kabuk gri renktedir. Cunku miyelinsiz liflerden olusmustur,Ic kismi ise beyazdir.Burasida miyelinli liflerden olusmustur.Beyin kabugunun altindaki kisim ise serebrum adini alir.

Sol yarikure:Konusma, okuma-yazma ve aritmatik yetileri denetler.Mantiksal analitik bir calisma tarzi vardir.Ayrintida odaklasir ve tekil ozellikler algilar.

Sag yarikure:Muzik ve guzel sanatlara iliskin yeteneklerde, imgelem ve dus kurmada, karmasik geometrik oruntulerin algilanmasinda ozel bir rolu vardir.

*Sag yarikure sol yarikureden daha cok duygu-heyecan gosterir.

*Butun ust duzey zihinsel faaliyetler beyin korteksinde olusur.Yukari dogru cikildikca beynin kivrimlari artar.Yani korteksin beyin dokusunun toplam miktarina orani artar.
Beyinde gorme, isitme, dokunma gibi faaliyetlerle ilgili cesitli alanlar vardir.Vucudun motor hareketleriyle ilgili alanlar vardir.
Birde baglanti alanlari vardir.Bunlar daha karmasik faaliyetlerle ilgilidir. Konusma, dusunme, bellek gibi....

Motor alan:Frontal lobda merkezi yarigin ustundeki motor alan, vucudun istemli hareketlerini kontrol

INSULIN THERAP IN TPE 2 DIABETES CURRENT AND FUTURE DIRECTIONS

9/7/2010

Insulin Therapy in Type 2 Diabetes: Current and Future Directions

Issues in the Management ofType 2 Diabetes
Type 2: Deterioration of beta cells over time
Increasing prevalence with increasing risk factors, eg, obesity
Hyperglycemia affects morbidity, mortality, and resources
Tight glycemic control with insulin may reduce costly complications
30% to 40% of patients ultimately require insulin
Regimen-related limitations with current insulin formulations and delivery systems
Newer semisynthetic insulins and delivery systems may improve compliance and achieve better glycemic control with less hypoglycemia
Prevalence of Type 2 Diabetes Mellitus
Incidence of Type 2 Diabetes Mellitus
Risk Factors for Type 2 Diabetes
Nonmodifiable
Genetic factors
Age
Ethnicity
Modifiable
Weight
Physical activity
Trend in Prevalence of Obesity*: NHANES Data
Link Between Obesity and Type 2 Diabetes:Nurses" Health Study
Link Between Obesity and Type 2 Diabetes:Nurses" Health Study (cont"d)
ADA Treatment Guidelines
Medical Nutrition Therapy for Type 2 Diabetes
Diet
Improved food choices
Spacing meals
Individualized carbohydrate content
Moderate calorie restriction
Exercise
Pharmacologic Therapy for Type 2 Diabetes
Sulfonylureas (glyburide, glipizide, glimepiride)
Biguanides (metformin)
Alpha-glucosidase inhibitors (acarbose, miglitol, voglibose)
Benzoic acid analogues (repaglinide)
Thiazolidinediones (troglitazone, rosiglitazone, pioglitazone)
Insulin (human insulin, insulin analogues)
Treatment Algorithm
Considerations in Pharmacologic Treatment of Type 2 Diabetes
Efficacy (HbA1c lowering capacity)
Mechanisms of action of drugs
Impact on weight gain
Complications/tolerability
Frequency of hypoglycemia
Compliance/complexity of regimen
Cost
Tight Glycemic Control:Reducing the Risk of Complications
Epidemiologic evidence in type 2 diabetes to link microvascular disease and hyperglycemia — first suggested in DCCT
Type 2 diabetes studies: Veterans Affairs Cooperative Study on Type 2 Diabetes (VA CSDM), United Kingdom Prospective Diabetes Study (UKPDS), and Kumamoto trial
Intensive blood glucose control with insulin, sulfonylurea, or metformin reduced risk of micro- and macrovascular complications
Glycemic threshold to prevent onset and progression of microvascular complications: HbA1c 6.5%, FBG 110 mg/dL, 2-hr postprandial glucose 180 mg/dL
Improvement in HbA1c in the VA CSDM
VA CSDM: Results at Endpoint
The Kumamoto Trial: Effects of Conventional vs. Intensive Insulin Therapy
UKPDS: Effect of Intensive Therapy on Glycemia
UKPDS 10-Year Cohort Data: Reductions With Intensive vs. Conventional Therapy
Summary of Key Findings
VA CSDM:
Glycemic control achievable with intensive insulin treatment: control maintained 2 years
Intensive treatment not associated with severe hypoglycemia, weight gain, hypertension, or dyslipidemia
Kumamoto trial:
Intensive insulin treatment reduced microvascular complications
Established glycemic threshold to prevent onset and progression of complications
UKPDS:
Diet therapy alone inadequate in two thirds of patients
Pharmacologic therapy plus nutrition/exercise necessary
Weigh benefit:risk ratio
No threshold for HbA1c reduction in reducing complications
Insulin does not increase macrovascular disease
Pharmacokinetics of Current Insulin Preparations
Effective
OnsetPeakDuration

Insulin lispro 15 min1 hr3 hr
Regular0.5-1 hr2-3 hr3-6 hr
NPH/Lente2-4 hr6-12 hr10-16 hr
Ultralente4-8 hrVaries18-20 hr
Clinical Efficacy of Insulin Lispro
Worldwide clinical trials of insulin lispro in 10,000 patients with type 1 or type 2 diabetes
1-year parallel group comparisons or 6-month crossovers (3 months on each insulin) studies
Dosage regimen: insulin lispro 10 min before and soluble human insulin 30 to 45 minutes before meals, with NPH or ultralente insulin as the basal insulin supplement

�K� TARAFLI TALAM�K LEZONLAR

9/7/2010

�ki Tarafl� Talamik Lezyonlar

Talamus, insanlarda beynin stratejik �ekirdeklerinden biridir. Talamik fonksiyonlara ve talamik lezyonlar�n klinik sonu�lar�na ili�kin olarak, giderek artan miktarda bilgi mevcuttur. Tek tarafl� talamik lezyonlar, genellikle tek yanl� ge�ici veya kal�c� davran��sal, duyusal veya ok�ler motor bozukluklara yola�ar. �ki tarafl� lezyonlar, tek tarafl� olanlara nazaran daha ciddi davran��sal bozukluklara sebep olur. �o�u rapor, bir veya iki talamo - subtalamik arterin t�kanmas�na ba�l� olarak, paramedyan arter b�lgesinde iki yanl� meydana gelen enfarktlar hakk�ndad�r. Buna ra�men, �e�itli talamik arter b�lgelerinin iki yanl� e�zamanl� lezyonlar�n�n klinik getirilerine ili�kin bir bilgi mevcut de�ildir. E�zamanl� iki tarafl� talamik enfarktlar� olan 16 ard��k hastan�n manyetik rezonans g�r�nt�leme �al��malar�yla teyit edilen klinik ve davran��sal �zellikleri ve bunun etyolojisi �zerinde �al��t�k.

Malzemeler ve Y�ntemler :

�al��ma alt grubu, Ocak - 1992 ile Haziran - 1998 tarihleri aras�nda merkezimize ard��k olarak m�racaat eden ve ilk kez iskemik inme olan 2750 ki�ilik bir grubu i�eren inmeli hastalardan m�te�ekkildi. Kay�tlar�m�zdaki klinik, radyolojik ve n�ropsikolojik de�erlendirmeler, b�t�n inmeli hastalar i�in rutindi. Hastalar�n bu �al��mada yeralma �l��t�, �unlara g�re belirlendi : �lk kez talamik inme ge�irmi� olanlar, MRda iki tarafl� e�zamanl� lezyonlar� olanlar ve inmeden itibaren 48 saat i�inde m�racaat edenler. E�zamanl� yeni enfarktlar, genellikle enfarkttan sonraki bir hafta i�inde BT ve 1.5 Teslal�k g�ce sahip MR ile g�r�nt�lendi. MRla yap�lan �al��malar T1, T2 ve proton a��rl�kl� olarak ger�ekle�tirildi. Gadolinyum enjeksiyonu sonras�nda, T1 a��rl�kl� ve 5er milimetrelik kesitlere sahip sagittal ve transvers kontrast g�r�nt�ler al�nd�. Akut enfarktlar, (T1 a��rl�kl� g�r�nt�lerde d��k yo�unluklu ve T2 a��rl�kl� g�r�nt�lerde de y�ksek yo�unluklu sinyaller �reten) ve geni�lemi� Vir�ov - Robin perivask�ler bo�lu�undan daha b�y�k iskemik lezyonlar �eklinde tan�mland� ve bunlar, gadolinyumla geni�leme g�stermekteydi. Arka serebral, baziler ve vertebral arterlerin 64 dilimlik, 0.8 - 1 milimetre hassasiyetli 3 boyutlu MR anjiyografisi de, b�t�n hastalara tatbik edildi. Vertebral arterlerin kafa d��ndaki k�s�mlar� �zerinde, Doppler do�rulamal� MR anjiyografiyle opasite de�i�ikleri y�n�nden �al��ld�. B�t�n hastalar �zerinde tam kan, biyokimya, T�T, transkraniyal Doppler, karotid ve vertebral arterlerin duplike sonografisi, EKG �l��mleri temeline dayal� standart bir protokolle �al��t�k. 5 hastaya trans�sofajiyal ekho ve 3 hastaya da Seldinger tekni�inin kullan�ld�� konvansiyonel anjiyografi uyguland�. Talamik iskemik lezyonlar i�in �u risk fakt�rleri kaydedildi : Ya�, cinsiyet, DM, sigara, hiperkolesterolemi ve (ge�irilmi� MI, sol ventrik�l anevrizmas�, hipokinezi, akinezi, kornik valv�ler olmayan atriyal fibrilasyon, MS, kalp kapak�� protezi gibi) kalp hastal�klar�. Bogouslavski ve arkada�lar�na g�re, talamik �ekirde�i besleyen d�rt b�y�k damar b�lgesi �u �ekildedir : 1-) Kutupsal arter, 2-) Paramedyan (talamo - subtalamik) arter, 3-) Talamogenik�lat arter ve 4-) Arka koroidal arter b�lgeleri. �u durumlar�, talamik enfarkt�n muhtemel sebepleri olarak d��nd�k : 1-) B�y�k arter hastal��na ba�l� arterden artere embolizm, MR anjiyografisinde g�sterildi�i �zere damar bo�lu�u �ap�n�n en az % 70inin t�kal� oldu�u hastalarda, di�er ba�ka etyolojilerin mevcut olmad�� durumlarda �ng�r�lm��t�r. 2-) K��k arter hastal��, uzun bir m�ddetten bu yana hipertansiyonu veya DMsi olan hastalarda, kalbe veya damarlara ait potansiyel emboli kaynaklar�n�n bulunmamas� durumunda �ng�r�lm��t�r. 3-) Atriyal fibrilasyonu, sol ventrik�lde diskinetik k�s�mlar�, kalp i�i t�m�r veya tromb�s�, mitral stenozu ve di�er daha nadir kaynaklar� da i�eren kalbe ait potansiyel emboli kaynaklar� (PCSE). 4-) Geni� arter hastal��n�n ve PCSEnin bir arada bulundu�u durumlarda, kar��k etyoloji d��n�lm��t�r. 5-) Di�er tan�

ADRENO-CORTICAL STEROIDS

9/7/2010

Adreno-Cortical Steroids

Protein Binding of Steroids in the Circulation
Cortisol: -
10% free (will rise if CBG swamped)
75% Cortisol Binding Globulin (CBG: limited capacity)
15% Albumin (large capacity "sponge")
DHEA, DHEA-SO4, Androstenedione: -
Weakly bound to albumin
Aldosterone
30-40% free
loosely bound to CBG

HORMONE MEASUREMENT

9/7/2010

Hormone measurement

The Problem
very small amounts of hormone in a very complex mixture
Pre-immunoassay
complex and insensitive methods (chemical methods, whole animal or tissue bioassay)
insensitive
imprecise
inaccurate
Immunoassay
first described in 1960
very rapid expansion since early 1970s
advantages (simplicity, speed, precision, accuracy, sensitivity)
Where is immunoassay used
Medical laboratory
hormones, drugs, tumour markers, specific proteins, viral antigens, etc,etc
Point of Care Testing
Drugs, cardiac markers, anticoagulants etc
Over the Counter
Pregnancy tests, fertility tests etc

Agriculture, veterinary, pharmaceuticals, research etc

Limited reagent immunoassay
Limited reagent immunoassay standard curve
2-site immunometric assay
2-site immunometric assay standard curve
Basic requirements for immunoassay
Standards
Specific antibodies
Labelled antigen or antibody
Separation system
Quality control
Types of label
Radioactive (125I, 3H, 32P etc)
Fluorescence (Direct, time-resolved)
Enzyme (colorimetry, fluorimetry, enhanced chemiluminescence)
Luminescence (bioluminescence, phosphorescence)
Microparticle
Streptavidin/avidin-biotin
Amplification

Ideal immunoassay label
Advantages of 2-site immunometric assays
Increased sensitivity
Increased precision
Better specificity
Greater assay range
Shorter assay times
Disadvantages of 2 site immumetric assays
Need for large quantities of pure antibody (monoclonal antibodies usually employed)
2 antibody binding sites required (limit range of analysis)
High dose "hook" effect
Need for multiple washing steps
Non specific interference due to heterophyllic antibodies
Advantages of isotopic labels
Simple coupling reactions
Label properties do not alter on coupling
No background signal
Efficient/convenient detection systems
No additional cost to detect signal
Very useful for research assays
Non isotopic labels - advantages
No radioactivity
safety aspects
disposal
Extended life of label
Speed of detection
Ease of automation
Theoretical increase in sensitivity
Possibility of homogeneous assays
Simple/safe label preparation
Non isotopic labels - disadvantages
Safety aspects of labels/substrates
Serum/buffer effects
Extra manipulations in detection
Inefficient detection in some cases
No recounting possible in some systems
Limitation of separation system
"Dedicated" instruments
Commercial pressures
Specialised Immunoassays
Free hormone assays
Homogeneous (non separation ) immunoassays

Measurement of free hormones
? Free hormones closely reflect the true (active) hormonal state in the body
In theory, these are an optimal test of hormonal function
Measurement presents a challenge
very low concentrations
avoiding disturbing equilibrium between bound and free hormone during measurement
sera from some patients (non-thyroidal illness) contain interfering substances that can invalidate measurements
Measurement of free hormones
Reference methods
Initial separation by equilibrium dialysis or ultrafiltration and measurement of analyte in the separated fraction by immunoassay
Only minimal dilution of sample possible
Expensive, time consuming, unsuitable for high volume work
Commercial methods now available
Methods of free hormone estimation
Index methods (calculation)
2 step immunoassay
Analogue immunoassay
Labelled antibody assays
Index Method
Correct total hormone concentration for abnormal binding protein concentration
Measure total hormone (free and bound)
Measure binding protein (i.e. TBG, SHBG)
Apply formulae to estimate free hormone
Simple, rapid, inexpensive
Variable performance
Not accurate at very high or low binding protein concentrations
2 Step Immunoassay
Extract free hormone from serum by adding solid phase antibody
Wash
Add label which binds to remaining unoccupied antibody binding sites
Analogue Immunoassay
Label = analogues which bind to antibody but not to binding proteins (disputed)
Mix sample, antibody and analogue label
binding of label to antibody is inversely proporti

INTRODUCTION TO CLINICAL ENDOCRINOLOG

9/7/2010

Introduction to Clinical Endocrinology

Learning Objectives
Know common endocrine diseases
Understand relationship between pathological processes of autoimmunity, neoplasia, hyperplasia and atrophy and failure of feedback regulation and those diseases
Understand how biochemical testing (and imaging) are used to diagnose endocrine disease
Endocrine Glands
Hypothalamus
CRF, GRF, GHIH, Dopamine,TRH, GnRH
Pituitary
ACTH, GH, Prolactin, TSH, FSH, LH
ADH, Oxytocin
Thyroid
T4, T3, Calcitonin
Parathyroid
Parathyroid Hormone
Adrenal
Cortisol, Aldosterone, Androgens
Catecholamines
Pancreas
Insulin, Glucagon, Somatostatin
Gonads
Oestrogen/Testosterone
GIT tract
Gastrin, Neurotensin, Secretin, GIP, GLP
Kidney
Renin, Erythropoietin, 1,25-dihydroxyvitamin D Placenta
HCG, HPL
Endocrine Disease
Endocrine Gland Malfunction
Enlarging
Becoming overactive
Becoming underactive
Undersecretion
Hormone resistance
Investigations
Diagnostic:
Biochemical tests
Imaging
Autoantibodies
Systemic effects of endocrine disease
Local effects of endocrine disease i.e. pressure effects (eg radiology)
Monitoring
Continuing Disease/recurrence
Hormone replacement therapy
Laboratory Endocrine Tests
Single Hormones (limited value)
Hormone Pairs
Serial Measurements
Dynamic Function Tests:
Stimulation Tests when hypofunction is suspected and confirmed by a failure of hormones to be stimulated
Suppression tests when hyperfunction is suspected and confirmed by failure of hormones to suppress
Factors influencing interpretation of Laboratory Endocrine Tests
Age
Gender
Biological Rhythms
Pulsatile secretion
Stress
Fasting
Posture
Co-morbidity

Drugs
Binding Proteins
Sample tubes
Differences in immunoasay
Assay interferences
Hormone Pairs
.
Case: Concept of appropriateness
60 yr old House-wife with recurrent renal calculi.

Calcium 3.16 mmol/(2.00 - 2.60)
Albumin 40 g/L (36-42)
Phosphate 0.70 mmol/L(0.8 -1.4)
Creatinine 70 mol/L (60 -120)
Alkaline Phosp 111 IU/L (30-130)
Parathormone 4.3 pmol/L (0.5 -5.5)

Primary Hyperparathyroidism
Dynamic Function Tests Where and Who ?
"Pituitary Function testing should be performed in an investigation unit with appropriate facilities for sample collection, handling, analysis and interpretation of results. All centres should have access to an accredited hormone assay service which participates in a National Quality Control Scheme"

[Pituitary Tumours. Recommendations for Service Provision and Guidelines for Management of patients. Royal College of Physicians of London. 1997]

Hormone Replacement therapy
Establish a diagnosis - Lifelong
Free NHS Prescriptions
Minimal effective dose
Replacement of missing target organ hormone (exception hypoparathyroidism)
Timing of dose: to mimic health
Hormone Replacement therapy:Monitoring
Patient well-being
Measure Hormone
Measure other biochemical end-point (eg HbA1c)
Clinical end-point (BP)
Compliance
Avoid under-replacement
Avoid over-replacement

LEFT VENTRICULAR HYPERTROPH

9/7/2010

Left Ventricular Hypertrophy

An increase in the size of myocardial fibers in the main cardiac pumping chamber, usually takes months to years to develop
LVH, from any cause, are at increased risk for major cardiovascular complications including
congestive heart failure
cardiac arrhythmias

Causes of LVH
Hypertrophy is usually the response to chronic
pressure overload
systemic hypertension
aortic stenosis
volume overload
aortic or mitral valve regurgitation
dilated cardiomyopathy

Other Causes of LVH
Ventricular septal defects cause both right and left ventricular volume overload
Hypertrophic cardiomyopathy occurs in the absence of any apparent hemodynamic pressure or volume overload
The athletic heart is often associated with ECG voltage criteria for LVH with increase in wall thickness and left ventricular and diastolic volume

Evaluation of LVH
Electrocardiogram
a useful but imperfect tool for detecting LVH
advantage: relatively inexpensive and widely available
disadvantage: moderate sensitivity or specificity depending upon which of the many proposed sets of criteria are applied [2,3].
Echocardiography
the procedure of choice for diagnosing LVH
permit quantitation of LV mass and give important information about the etiology of LVH (such as aortic or mitral valve disease, or hypertrophic cardiomyopathy)

GENERAL ELECTROCARDIOGRAPHIC FINDINGS
Left ventricular hypertrophy can produce five major ECG changes: 1. increased QRS voltage2. increased QRS duration3. left axis deviation4. repolarization (ST-T) changes5. left atrial abnormality

GENERAL ELECTROCARDIOGRAPHIC FINDINGS1. Increased QRS voltage
An increase in left ventricular mass augments the amplitude of voltage generated with an increase in the
amplitude of positive forces (R waves) recorded over the left chest leads and
negative forces (S waves) recorded over the right chest leads
amplitude of R waves in those limb leads that record the projection of these positive forces (typically I and aVL with a horizontal or leftward QRS axis)

GENERAL ELECTROCARDIOGRAPHIC FINDINGS2. Increased QRS duration
An increase in LV mass is often associated with widening of the QRS duration
may be subtle
may be associated with incomplete, or eventually complete, left bundle branch block (LBBB)
LVH can lead to LBBB by other mechanisms such as calcification or fibrosis of the proximal ventricular conduction system which lies close to the valve ring in calcific aortic stenosis
On the other hand, most patients with LBBB have underlying LVH
GENERAL ELECTROCARDIOGRAPHIC FINDINGS3. Left axis deviation
LVH is usually associated with

a horizontal or frankly leftward (  -30°) QRS axis in the frontal plane leads, or
vertical QRS axis (or even rightward axis), especially in young adults or patients with biventricular hypertrophy.

GENERAL ELECTROCARDIOGRAPHIC FINDINGS4. Repolarization abnormalities
Severe LVH, especially due to a pressure load, is often associated with
LV strain with ST depression and T wave inversions in leads with tall R waves
may be due to primary alteration in repolarization of hypertrophied muscle or to relative subendocardial ischemia
present in 15% of hypertensive patients with LVH, more common in those with coronary heart disease (29% versus 11 %)
LVH with a volume load state (due to mitral or aortic regurgitation) is sometimes associated with prominent positive T waves in the lateral chest leads
GENERAL ELECTROCARDIOGRAPHIC FINDINGS5. Left atrial abnormality
Most patients with LVH develop abnormalities in left atrial depolarization due to conduction delay or actual atrial enlargement
The two major markers of left atrial abnormal are increased duration of P waves ( or =120 ms) in the limb leads and/or biphasic P waves with a prominent negative component ( or =40 ms in duration and/or or = 1 mV in depth) in V1.
The presence of a left atrial abnormality may be particularly helpful in the setting of a left bundle branch block.

ELEKTR�K �EBEKELER�NDE REAKT�F G�� KOMPANZASYONU

9/7/2010

ELEKTR�K �EBEKELER�NDE
REAKT�F G�� KOMPANZASYONU

D�nyam�z�n son y�llarda kar�� kar��ya kald�� enerji krizi, ara�t�rmac�lar� bir yandan yeni enerji kaynaklar�na y�neltirken di�er yandan daha verimli sistemlerin tasar�mlanmas� ve kurulmu� olan enerji kaynaklar�n�n en verimli �ekilde kullan�lmas� y�n�nde �al��malar�n yo�unla�mas�na neden olmu�tur.
Bilindi�i gibi sanayile�menin ana girdilerinden ba�ta geleni elektrik enerjisidir. Elektrik enerjisinin kullan�ma;
*Kaliteli
*S�rekli
*Yeterli
*Ucuz
olarak sunulmas� esast�r. Oysa �lkemizde �zellikle 1973 y�l�nda ba� g�steren petrol krizi nedeniyle bu 4 �zelli�in sa�lanmas�nda g��l�klerle kar��la��lm��t�r. Petrol krizi yan�nda �lkemize has baz� hususlarda eklenince �nce enerji yetmezli�i bununla beraberde g�� yetmezli�i ba� g�stermi�tir. Bu yetmezliklerin olumsuz etkilerini gidermek �zere;
*�leri saat rejimi (Halen s�rmektedir.)
*Frekans ve gerilim d��r�lmesi (1974"ten sonra uygulanmam��t�r.)
*Kesinti ve k�s�nt� (Halen s�rmektedir.)
y�ntemlerine ba�vurulmu�tur. Bu arada TEK tesislerine ��nt kondansat�rler yerle�tirilmi�tir. Bu tedbir, reaktif enerjinin t�ketildi�i yerde �retilmesi gerekti�inden ancak yerel baz� sa�layabilmi�tir.
Elektrik enerjisinin, asr�m�z�n en yayg�n kaynaklar�ndan biri olarak �retildi�i, santralden en k��k al�c�ya kadar da��t�m�nda en az kay�pla ta��man�n yollar� ve hesaplar� yap�lmaktad�r.
D�nyam�zda elektrik enerjisine ihtiyac�n her ge�en g�n biraz daha artmas�, enerji �retiminin biraz daha pahal�la�mas�, ta��nan enerjinin de kaliteli, ucuz ve hakiki i� g�ren aktif enerji olmas�n� daha zorunlu k�lmaktad�r.
G�� sistemlerinde i�letmeyi kolayla�t�rmak, verimlili�i artt�rmak ve enerji tutumlulu�unu sa�laman�n en etkin �nlemlerinden birini Reaktif G�� Kompanzasyonu olu�turmaktad�r.

AL�AK GER�L�MDE KOMPANZASYON

Elektrik �ebekelerinde abone g�c� artt�k�a reaktif y�klerde �ok h�zl� bir �ekilde artmaya devam etmektedir. Bunun neticesi olarak ta g�� katsay�s� ( Cos ) 0.50 - 0.80 aras�nda muhtelif de�erlerde seyretmeye ba�lam��t�r.
Trafo merkezlerinde, hatlarda ve generat�rlerde g��lerin artmas�; aktif g�� kadar ve belki de daha �nemli miktarda reaktif g��lerinde artmas�na sebep olmu�tur.
A��r� y�klenmeler ve gerilim d��melerinin �nlenmesi i�in, reaktif y�klerin kompanze edilmesi zorunlu hale gelmi�tir.
�ehir �ebekelerindeki �rnekler g�stermi�tir ki ��k�� da��t�m fiderlerinde genelde ortalama Cos = 0.80"den k��kt�r. Baz� hallerde 0.70"in alt�na d��t�� g�r�lmektedir.
Sanayi aboneleri bulunmayan beldelerde reaktif t�ketimin artmas�na sebep; �zellikle ticari ve sosyal b�lgeleri besleyen da��t�m hatlar� ve trafo merkezleri �zerindeki irili - ufakl� motor ve Neon ��klar�n�n artmas�d�r.
Sosyal hayat�n geli�mesi ile ba�layan refah; Buzdolab�, �ama��r makinas�, klima vs. gibi �s�tma, havaland�rma ve so�utma cihazlar�n�n kullan�m�n� artt�rm�� ve bu durum g�n�m�zde reaktif enerji t�ketimini artt�rm��t�r.
Kompanzasyonda genel kaide olarak en ger�ek�i yol; reaktif ak�mlar kendilerini t�keten cihazlara en yak�n noktada �retilmelidirler. Bu durumda abonelerden ba�layarak da��t�m hatlar�ndan itibaren �retim kayna��na kadar s�z konusu cihazlar i�in gerekli reaktif enerji sistemden ta��nmayacak ve bu sebeple;
*�ebekedeki g�� kay�plar� �nemli oranda azalacak,
*�retim ve da��t�m sisteminin kapasitesi artacak,
*Gerilim d��m�n�n ta��nan g�c� s�n�rlad�� da��t�m hatlar�nda enerji ta��ma kapasitesi b�y�k oranda artm�� olacakt�r.
G�n�m�zde �nemli �l��de artan aktif ve reaktif

HYPERSENSITIVIT REACTIONS AND TISSUE INJUR

9/7/2010

Hypersensitivity Reactions and Tissue injury

Hypersensitivity is a misnomer
These diseases result from normal immune responses
Not Excessive or "Hyper" responses
Classification based on Immunologic Mechanisms
Type I - Hypersensitivity
Anaphylactic Type
Also called immediate hypersensitivity
Examples include hay fever and asthma
Mediated by antigen binding with antibody previously bound to mast cells or basophils
Type I - Hypersensitivity
Two Phase Reaction
Initial response is rapid - 5-30 min after exposure to antigen
Vasodilatation, edema, smooth muscle spasm
Late phase response - 2-8 hrs later
Occurs in 50% of patients
Infiltration by mono"s, eo"s, baso"s and PMN"s
Type I - HypersensitivityMast Cells and Basophils
Mast cells in tissues; Basophils circulate
Both contain granules with Inflammatory Mediators
Activated by crosslinking to IgE Fc receptors
Type I - Hypersensitivity
CD4+ T-cells are induced and produce cytokines which:
Stimulate IgE production by B - cells
Act as growth factors for mast cells
Recruit eosinophils
IgE binds and the cells are Primed
"Lock and Load"
Type I - Hypersensitivity Primary Mediators
Preformed and stored in granules
Histamine
Chemotactic factors for eo"s and PMN"s
Proteases
Type I - Hypersensitivity Secondary Mediators
Lipid Mediators
Platelet Activating Factor
Arachidonic Acid
Leukotrienes and Prostaglandin
Cytokines
TNF-alpha
Interleukins 1, 4, 5, 6
Type I - Hypersensitivity
Is the result of release of "a variety of chemotactic, vasoactive and spasmogenic compounds" (Table 5-3 Kumar p 89)
Type I - Hypersensitivity Clinical Manifestations
Systemic Disorder
Local Reaction
Type I - Hypersensitivity Systemic Anaphylaxis
Penicillin or Anti-sera administration
Itching, hives, skin erythema - minutes
Then respiratory difficulty
smooth muscle spasm - pulmonary vasoconstriction and bronchiolar spasm
Hypersecretion of mucus and laryngeal edema
Shock and Death can occur within minutes
Type I - Hypersensitivity Local Reactions
Skin or Mucosal Surfaces
Urticaria (Hives)
Skin and food allergies
Hay fever
Atopy - familial predisposition to allergy
Type I - HypersensitivityWhat good is it?
Fights Worm infection
EEEEWWWWWW!!!!
Type II - Antibody Dependent
Antibodies formed against normal or altered cell membrane components
Type II - Antibody Dependent
The antigens are intrinsic to the cells that are damaged
This is unlike Type III Hypersensitivity Reaction (Immune complex type)
Mediated by Antigen-Antibody complexes
Type II - Antibody Dependent Complement Mediated
Binding of antibody to cell surface antigen
Fixation of complement
Cell Lysis

Type II - Antibody Dependent Complement Mediated
Transfusion Reaction
Ab"s from host coat incompatible RBC"s
Rh Reaction
Rh-negative mother produces ab"s against an Rh+ baby
Autoimmune Reaction
Develop Ab"s against own blood elements
Autoimmune hemolytic anemia, etc
Type II - Antibody Dependent Cell Mediated
Target cell coated with IgG
Destroying cells have receptors for Fc
Lysis of the target cell requires contact
But not fixation of complement
Effector cells include:
PMN"s, EO"s, Macrophages and NK cells
Type II - Antibody Dependent Cell Mediated
This reaction is useful against targets too large to be phagocytised
Attacks on Neoplastic Cells and possibly a more minor role in the fight against parasites such as worms, flukes, helminths, etc.
Major Reaction against parasites is the Type I
Antibody Dependent Cell Mediated Reaction
Type II - Antibody Dependent Cellular Dysfunction
Antibodies against cell surface receptors impair or stimulate cell function without causing cell injury or inflammation
Myasthenia Gravis
Graves Disease
Goodpasture"s Disease
Anti-Receptor Antibody
Type III - Immune Complex Mediated
Antigen - Antibody Complexes initiate acute inflammation
Complement activation and accumulation of PMN"s
Endogenous Antigens - DNA
Exogenous Antigens - Bacteria, Viruses etc.
Immune Complexes form in circulation or
Antigens are "planted" and IC"s fo

AKUT HEPAT�TLER

9/7/2010

Hepatit Vir�sleri
A Hepatiti (HAV)
B hepatiti (HBV)
C hepatiti (HCV)
D hepatiti (HDV)
E hepatiti (HEV)
Sitomegalovir�s (CMV)
Epstein-Barr vir�s (EBV)
Herpes vir�s (HSV)
AVH-A
�ocuklardaki akut hepatitlerin �o�undan sorumludur
1973 y�l�nda ilk kez tan�mlanm�� ve 1979"da h�cre k�lt�r� yap�labilmi�tir 60 C s�cakl�kta 1 saat ya��yabilir, ancak 100 C"de �l�r
AVH-A
Seroloji:
Viremi d�nemi olduk�a k�sad�r. Hastal�k ba�lad��nda �o�unlukla vir�s kanda saptanamaz
Hastal�k ba�lad��nda olgular�n %50"sinde d��k�da saptanabilir, ilk haftada ise %25"inde saptanabilir.
Anti HAV IgM birka� hafta i�inde pik de�erine ula��r. D��k titrede 4-5 ay kalabilir. Baz� hastalarda ise hastal�k d�zeldikten sonra da 1-3 y�l boyunca pozitif kalabilir.
Anti HAV IgG hayat boyu pozitif kal�r.
AVH-A
�nsanda kronik ta��y�c�l�k yoktur.
HAV enf. ge�irme prevalans� ya� ilerledik�e ve sosyoekonomik d�zey d��t�k�e artar.

AVH-A
Patogenez:
Temasdan 1-2 hafta sonra kona��n kc"inde vir�se rastlan�r. 3-4 hafta i�inde ise kc"deki konsantrasyonu pik de�ere var�r.
HAV replikasyonu �ncelikle hepatositin sitoplazmas�nda olur.
Daha sonra sin�soidlerle kana, safra kanalc�klar� yolu ile safraya at�l�r. Vir�s�n d��k� ile at�m� en �ok prodromal d�nemde, biyokimyasal olarak hepatit tan�s� konulmadan �nce olur.
Viremik yay�l�m sonucu ekstrahepatik organlarda da saptanabilir (dalak, t�kr�k bezleri, pankreas, bb"ler)
AVH-A
Klinik:
�ocuklar�n %90"�nda sar�l�k g�r�lmez
D��k bir ate�, G�S bulgular�, sar�l�k
Koyu idrar, a��k renkte d��k�, nadiren hemat�ri
Aminotransferazlar y�kselir, hiperbilir�binemi
HAV enf"unun tetikledi�i otoimm�n hepatitler bildirilmi�tir.
F�lminan hepatit s�t �ocuklar�na g�re adolesanlarda daha s�kt�r. (% 0.1-0.5)

TPE 2 DIABETES MANAGEMENT GOALS

9/7/2010

Type 2 Diabetes Management Goals

Prevent and retard microvascular complications
Early detection and monitoring
Optimal glycemic control
Normal blood pressure
Reduce macrovascular complications
LDL-Cholesterol 100 mg/dL (Statins)
BP 130/85 mm Hg (ACE inhibitors)
Weight loss ~5% to 10% body weight
ASA
No Smoking
Realistic exercise

Implementing Diabetes Treatment GoalsStrategies
Earlier diagnosis and treatment
Acting on results of SMBG and HbA1c
Matching pharmacology and physiology
Combination therapy
Multiple oral agents (Type 2)
Oral agents + insulin or insulin analogues (Type 2)
Insulin or insulin analogues (Type 1)
UKPDSType 2 Diabetes . . . A Progressive DiseaseEffect of Treatment on HbA1c
UKPDS: THE BOTTOM LINEMain Messages for Management of Type 2 Diabetes
Sulfonylureas, insulin, and metformin are effective in reducing risk of complications by improving glycemic control
No evidence of increased risk of complications for any single therapy
Combination therapy required almost from the outset to achieve near-normoglycemia
Much earlier use of insulin Rx in most patients as expected therapy in the progressive management of Type 2 diabetes
How Much Combination Therapy in Type 2 Diabetes?
Pharmacologic Management of Type 2 Diabetes Current and Potential Agents
Insulin Secretagogues
Sulfonylureas
Glimepiride
Glipizide
Glyburide
Benzoic acid
Repaglinide
D-Phenylalanine
Nateglinide
GLP-1
Delayed Glucose Absorption
a-Glucosidase Inhibitors
Acarbose
Miglitol
Voglibose
Insulin Sensitizers
Metformin
Glitazones
Troglitazone
Rosiglitazone
Pioglitazone
Others
G-1216570
MCC-555
PNU-182716
. . . and INSULIN
ADA "Consensus" on Type 2 Diabetes Therapy
Combination Therapy in Type 2 DiabetesDecision Considerations
HbA1c efficacy
Reductions from baseline
Reaching target
Synergy of mechanisms of action
Side effects and toxicity profile
Frequency and severity of hypoglycemia
Effect on weight gain
Avoiding polypharmacy and complex regimens
Compliance and convenience
Cost
Combination Therapy in Type 2 DiabetesEstimated Improvement
Type 2 DiabetesTreat to Target
HbA1c 7%
FBG 80-120 mg/dL (4.4 to 6.7 mmol/L)
Postprandial BG 180 mg/dL (10 mmol/L)
Practical Management of Type 2 Diabetes Mellitus
Evolving criteria
If FBG 140 mg/dL (126 mg/dL?)
HbA1c 8% (7%?)
Add second oral agent and titrate to maximum dose
If no improvement:
Try a different sensitizer
Or try triple therapy?
Or Continue oral agent(s)and add insulin Rx at PM or HS
MONOTHERAPYPlacebo-Subtracted Dose-Response to Oral Agents Effect on HbA1c
MONOTHERAPYRosiglitazone: Effects on HbA1c
MONOTHERAPYPioglitazone: Effects on HbA1c
Monotherapy in Type 2 Diabetes MellitusSecondary Failure
Secondary failure rate 5% to 10% a year(UKPDS 7% a year)
Decreasing b-cell function
Obesity
Non-adherence to treatment
Lack of exercise
Intercurrent illness
COMBINATION THERAPYEstimated Improvements in Glycemic Control
COMBINATION THERAPYSulfonylurea + MetforminEffect on HbA1c
Change in Mean HbA1c (%)
COMBINATION THERAPYSulfonylurea + TroglitazoneEffect on HbA1c
Change in Mean HbA1c (%)
COMBINATION THERAPYSulfonylurea + PioglitazoneEffect on HbA1c and FBG
COMBINATION THERAPYMetformin + GlitazoneEffect on HbA1c
COMBINATION THERAPYMetformin + AcarboseEffect on HbA1c
Mean Change in HbA1c (%)

HEPARIN INDUCED THROMBOCTOPENIA AND THE USE OF ARGATROBAN

9/7/2010

Heparin Induced Thrombocytopenia and the use of Argatroban

Heparin
Quinine, Quinidine, and Sulfa
Risk of thrombotic complication
Platelet activation
Thrombocytopenia
Heparin Induced Thrombocytopenia
Type I
Non-immunological
Likely direct heparin stimulation
Primarily a "high" dose occurrence
Platelet count rarely 100,000
"Mild" platelet activation
NO associated sequelae
Treatment:
Simple cessation of Heparin
Heparin Induced Thrombocytopenia
Type II
Immunological in origin
Occurs at all dose ranges
Subcutaneous
Heparin flushes
Thrombotic
ALL types of Heparin
Porcine Beef
Medical Surgical
LMW unfractionated
100% cross reaction

Heparin Induced Thrombocytopenia
Physiology
Platelet Factor 4
IgG
Heparin
Thrombin
Multimolecular Complex
PF4-Heparin-polysaccaride-protein
Negates Heparin effect
Binds to platelet Fc receptors
Results in increased Thrombin formation
Heparin Induced Thrombocytopenia
Coagulatory Effect
Increased Thrombin generation
Increased Thrombin-antithrombin activity
Immunoinjury by the HIT molecule
Generates Tissue Factor
Initiates the extrinsic pathway
Increased D-Dimers
DIC
Hypofibrinogenemia

Heparin Induced Thrombocytopenia
Frequency
3% surgical patients
1 % Major thrombotic episode
33% risk of ALL HIT patients
Lesser with LMW heparin
Cath lab studies
90-100% cross reactivity in HIT II patients
Heparin Induced Thrombocytopenia
Management
Ancrod
"Snake Venom"
Danaparoid
Heparan Sulfate, dermatan sulfate, and Chondroitin sulfate
Hirudin/Refludin
Leech saliva extract
Refludin is recombinant product
Argatroban
Synthetic

Heparin Induced Thrombocytopenia
Management
Ancrod
Not an antithrombin agent
Defibrinogenic and renders afibrinogenemic
Thrombin production secondarily enhanced
Slow onset (must give for 24 hrs)
Implicated in limb gangrene
Warfarin strictly contraindicated

Heparin Induced Thrombocytopenia
Direct Thrombin Inhibitors
Refludin
Recombinant Leech anticoagulant
Powerful thrombin inhibition
Half life of 1.3 hours
Monitored by ECT
Eliminated by renal function
Heparin Induced Thrombocytopenia
Direct Thrombin Inhibitors
Argatroban
Synthetic antithrombin
Half life of 30-51 minutes
No risk of heparin antibody cross reactivity
Eliminated by hepatic function
Monitored by ACT

Heparin Induced Thrombocytopenia
Lepirudin is currently the only FDA approved therapy

The card used to measure ECT is an investigational device
Case Study
54 year old white male
Diagnoses
Congestive Heart Failure
4+ mitral regurgitation
Acute myocardial infarction
Cardiogenic shock
Ventricular Tachycardia (refractory)
Case Study
Diagnoses
Multi-system organ failure
Pneumonia
Tuberculosis
Alcohol abuse
Leukocytosis
Anemia
Tobacco abuse
Case Study
Diagnoses
Thrombocytopenia
Positive Heparin antibody
DIC
Thrombogenesis
Foot
Hand
Abdominal petechiae

Case Study
Wednesday
Arrives @ SVI
Heparin
IABP in place
1:1
Dopamine
BP 95/65
Primacor
PA 68/32
Case Study
Wednesday afternoon
Cr: 3.2- BUN:73
Scheduled for surgery Friday AM
Recathed
4+MR
"remaining" coronaries OK
20 % EF

Case Study
Friday
Platelets: 38,000
pTT 150
pT: 72.9
D-Dimers:18,000
+ HAT
Refludin
Sent for ECT equipment
Rescheduled for Monday AM

Case Study
Monday (early AM)
Rash
Anaphylaxis
Refludin sensitivity
Resuscitation
Argatroban
The call for help
Rescheduled for Wednesday

Case Study
Tuesday
Denver @1030
Denmark @ 1:15 PM
Germany @ 5:30 PM

The Call
Local cardiologist Dr. Al Peters
The Call
Wednesday Morning
Lab
Hct: 29%
pT: 29.7
pTT: 70.3
Platelets: 219,000
BUN: 37 Cr: 2.1
ACT: 159
D-Dimers: 1500

MULTIPLE ENDOCRINE NEOPLASIA

9/7/2010

Multiple Endocrine Neoplasia

Multiple Endocrine Neoplasia
MEN 1MEN 2AMEN 2B

ParathyroidMedullary thyroid Medullary thyroid
cancer cancer

Pancreatic Phaeochromocytoma Phaeochromocytoma

PituitaryParathyroid Mucosal Neuromas

CarcinoidLichen amyloidosis Habitus and eye abnormalities
LipomaHirschsprung"s Disease
Multiple Endocrine Neoplasia
Gastroenteropancreatic tumours
Gastrinoma: Zollinger -Ellison syndrome
Resistant peptic ulceration
Diarrhoea + Steatorrhoea

Increased Gastric Acid output with inappropriate hypergastrinaemia

Removal of tumour: but often small and multiple
Gastrectomy: Historical
Proton Antagonists: Treatment of choice

Gastric Acid Secretion
Hypochlorhydric Hypergastrinaemia
(Appropriate hypergastrinaemia)
Pernicious anaemia
Atrophic gastritis
Postgastrectomy
Postvagotomy
Medication: H2 receptor antagonists
Proton inhibitors
Antacids
Hyperchlorhydric Hypergastrinaemia
(Inappropriate hypergastrinaemia)
Gastrinoma: Zollinger-Ellison syndrome
Antral G Hyperplasia
Chronic renal failure
Pyloric/parapyloric obstruction
Hyperchlorhydric hypergastrinaemia
Gastrinoma Antral G Cell
Hyperplasia
Gastrin response
to Secretin Exaggerated Normal

Gastrin response
to calcium Exaggerated Normal

Gastric acid response
To Pentagastrin No increase Normal
VIPOMA
Secretion of VIP and PPM

WDHA: Watery Diarrhoea, Hypokalaemia, Alkalosis
Acidosis may be presenting feature due to gut loss of HCO3-

Surgery
Octreotide: Symptomatic relief.

Carcinoid Tumours
Foregut, Midgut and Hindgut
Foregut assoc with MEN I

Local effects: haempotysis, bowel obstruction.
Hormonal effects: Flushing, diarrhoea, bronchospasm. (Pulmonary stenosis)
Pellagra: Relative deficiency of Nicotinamde

Chromogranin A, GAWK
Increased Urinary 5HIAA
Carcinoid Tumours
Surgery
Chemotherapy
Octreotide: Symptomatic relief

Multiple Endocrine Neoplasia
Neoplasia: May be fatal

Autosommal Dominant: Family screening

Molecular Genetics

Clinical Diagnosis: Two or more specific endocrine tumours in an individual
Molecular Genetic Screening: MEN 1
Mutation of gene encoding Menin on chromosome 11q13 in 70-80%

Tumour suppressor gene

Diagnosis of MEN 1 cannot be excluded if no gene mutation is detected.

Variable Genotype-Phenotype correlation
Molecular Genetic Screening: MEN 1
Biochemical screening depends on index case

TumourAgeBiochemical Tests/yr Imaging/3yr
Parathyroid 8yrsCa, PTHNone
Ant Pituitary5yrsPRL, IGF-1MRI
Insulinoma5yrsFasting glucose
Gastrinoma20yrsGastrin studies
Enteropancreatic20yrsChromogranin A Octreotide scan Gut hormones
Carcinoid20yrsNoneCT Scan
Molecular Genetic Screening: MEN 2
RET mutations
REarrangement through Transfection

Located on chromosome 10q11.2

Proto-oncogene

Mutation leads to continuous activation of Receptor Tyrosine Kinase Activity

Strong Genotype-Phenotype correlation

HYPERTHROID HEART DISEASE

9/7/2010

Hyperthyroid Heart Disease

Alterations in Cardiac Parameters
 resting heart rate
 myocardial contractility
 left ventricular muscle mass
predisposition to atrial arrhythmias
Molecular and Cellular Mechanisms
Action of thyroid hormones on the heart

direct effect on the transcription of specific and nonspecific cardiac genes
non-genomic action on plasma membranes, mitochondria, and the sarcoplasmic reticulum
Cardiac Manifestations
Classical symptoms
heat intolerance, irritability, nervousness, emotional the ability, muscle weakness,menstrual abnormalities, weight loss
Cardiovascular symptoms
tachycardia (90%), palpitation (85%), dyspnea on exertion and fatigue (50%), angina pectoris is uncommon
Physical findings
bounding peripheral pulses, wide pulse pressure, active precordium, systolic ejection murmur (50%), Means-Lerman scratch (rubbing of the hyperdynamic pericardium against the pleura, mimicking pericarditis),an increased incidence of mitral valve prolapse
Prevalence of Symptoms and Signs

tachycardia90
palpitations85
exercise intolerance65
bounding pulses75
wide pulse pressure75
hyperactive precordium75

Rhythm Disturbances
Atrial fibrillation
the most common complication of hyperthyroidism
occurs in approximate 15% of patients
more common among men and with advancing age (25 to 40% in individuals over the age of 60)
subclinical hyperthyroidism (low-TSH) is associated with 3x increase and the risk of developing AF
atrial flutter, paroxysmal SVT, and VT are uncommon
Heart Failure
the hyperthyroid heart may be performing at its maximal capacity, with little cardiac reserve - even at resting conditions
"high-output heart failure" usually occurs in young individuals with severe and long-standing hyperthyroidism and respond well to treatment with diuretics
"hyperthyroid cardiomyopathy" may be due to the detrimental effect of sustained tachycardia on the heart; the systolic dysfunction is often but not always reversible once a euthyroid state is reestablished
Hypertension
systolic hypertension is found in 1/3 of patients, this is partly due to the inability of the vascular system to accommodate the increase in stroke volume
diastolic hypertension is rare in hyperthyroidism due to the fall in SVR
establishment ofa a euthyroid state leads to complete reversal of these changes
Diagnosis of Suspected Hyperthyroidism
serum TSH concentration permits the detection of subclinical and occult hyperthyroidism
measurement of free T4 is helpful
T3 should also be measured to detect patients with T3- toxicosis
Causes of Hyperthyroidism
Graves" disease
Hyperfunctioning adenoma
Toxic or nodular goiter
Subacute thyroiditis
Chronic thyroiditis with transient thyrotoxicosis
Thyrotoxicosis facticia
Ectopic thyroid hormone production
Stroma ovarri
Metastatic follicular carcinoma
Excess production of TSH Trophoblastic tumor
Abnormal Thyroid Hormone Levels
nonthyroidal systemic illnesses may cause
low T3 state in up to 50% of hospitalized patients, or
low T3/T4 state with normal TSH levels in severely ill pts
chronic amiodarone therapy
50% of patients have elevated T4 levels (at an average of 44% of baseline) with normal T3 and TSH
2-24% of treated patients may develop clinical hyperthyroidism with decrease TSH level

HORMONE REPLACEMENT THERAPY (HRT)

9/7/2010

HORMONE REPLACEMENT THERAPY (HRT)

Evidence-based Guidelines
Introduction
HRT does not suit everyone.
Each woman needs to be aware of the benefits and potential risks of HRT (pros and cons) so that she can make an informed decision.
Our duty as clinicians is to ensure that women are provided with consistent and up-to-date information

HRT and Menopausal Symptoms
VASOMOTOR HOT FLUSHES includes night sweats
Grade A
HRT is an effective treatment for hot flushes

Tibolone is effective for alleviating the severity and reducing the frequency of hot flushes

VASOMOTOR HOT FLUSHES (includes night sweats)
Grade B
Unopposed estrogen may be effective for reducing the waking episodes that are associated with sleep disruption.
There is no evidence that HRT is effective for vasomotor symptoms such as headaches and dizziness.

Vaginal atrophy
Grade A
Low dose topical estrogen is an effective treatment
E3 (estriol) therapy is also effective but requires either the addition of progestogen or close monitoring of the endometrium
Tibolone has been shown to be effective for vaginal atrophy

PSYCHOLOGICAL SYMPTOMS
These include depression, mood changes, anxiety, irritability, loss of libido, lack of energy and memory loss.

PSYCHOLOGICAL SYMPTOMS
Grade A
Estrogen is not an effective treatment in elderly women with established Alzheimers disease
The addition of low doses of androgens to HRT provides relief in women with either a premature or surgical menopause who suffer from low libido ( for 2 years).

PSYCHOLOGICAL SYMPTOMS
Grade A
Tibolone is effective in providing relief from low libido in postmenopausal women
Estrogen replacement therapy is not an effective treatment for loss of libido in postmenopausal women.

PSYCHOLOGICAL SYMPTOMS
There is insufficient or inconsistent evidence that HRT

Improves measures of cognition

2-Prevents or delays the onset of Alzheimers disease

3-Elevates mood or relieves depression

RISK OF BREAST CANCER

Continuous combined HRT was associated with an increased breast cancer risk if used for four years or more
However this increased risk dissipates quickly once use is discontinued.

RISK OF BREAST CANCER

Inspite of an increased risk of breast cancer diagnosis, the mortality from breast cancer is unchanged

RISK OF ENDOMETRIAL CANCER
Grade A
Unopposed estrogen therapy should not be used in women with a uterus because of an increased risk of endometrial cancer.

Women who have had a hysterectomy may take unopposed estrogen therapy
RISK OF ENDOMETRIAL CANCER
A
Combined continuous regimens offer better protection of the endometrium than sequential regimens.

RISK OF OVARIAN CANCER
Grade A
There is no conclusive evidence that combined regimens HRT either increases or decreases the risk of developing ovarian cancer.

RISK OF OVARIAN CANCER
Researchers from the National Cancer Institute (NCI) have found that women in a large study more than 44000 women who used estrogen replacement therapy after menopause were at increased risk for ovarian cancer.

HRT and Osteoporosis
Grade A
HRT and Bisphosphonates has positive effects on bone density in postmenopausal women whether or not they have osteoporosis

HRT and Osteoporosis
Grade B
Maintaining HRT use decreases the risk of vertebral and non-vertebral fractures in women after surgical menopause ,early postmenopausal women and in women with established osteoporosis

HRT and Osteoporosis
Grade B
Selective Estrogen Receptor Modulators (SERMs) may be useful in the prevention of vertebr

GESTATIONAL DIABETES (GDM)

9/7/2010

Gestational Diabetes (GDM)

Prevalence
Diabetes affects 2-4% of pregnancies overall in the U.S.
90% of cases are Gestational Diabetes
10% with pre-existing DM (65% type 2)
Higher in African-American, Hispanic, Native-American and Asian women
Etiology
During pregnancy, the placenta is secreting diabetogenic hormones, which increase insulin production
growth hormone
corticotropin releasing hormone
human placental lactogen
progesterone
Etiology (continued)
GDM occurs when the woman"s pancreas can not function sufficiently to overcome her relative insulin resistance and increased fuel consumption
GDM defined by ACOG as "carbohydrate intolerance first recognized during pregnancy"
Risk Factors for GDM
family history
pre-pregnancy weight of 110% of ideal body weight
age 25 years old
previous history of large baby (9 lbs.)
Risk Factors (cont"d)
history of abnormal glucose tolerance
ethnic group with higher incidence of Diabetes Mellitus Type 2
previous unexplained perinatal loss or malformed child
mother was large at birth
GDM associated with increased incidence of:
Preeclampsia
Hydramnios
Fetal macrosomia
Birth trauma
Operative deliveries
Later development of DM in mother
Increased incidence (cont"d):
Neonatal metabolic complications
Hyperbilirubinemia
Hypocalcemia
Polycythemia
Perinatal mortality
Hypoglycemia
Increased incidence (cont"d)due to poor control:
Congenital malformations (4 fold)
caudal regression
spina bifida
anencephalus
heart anomalies
rectal atresia
renal agenesis
situs inversus
Screening
Selective
suggested by ADA
USPSTF ("C" recommendation)
Universal
done at 24-28 weeks in all women
may do earlier if suspicious
Screening Test
50 gram oral glucose load
serum glucose 1 hour later
abnormal result is 140 mg/dL
sensitivity improves if patient is fasting
if result is abnormal, the diagnostic test is a 3-hour Glucose Tolerance Test (GTT)
Other testing
do diagnostic GTT if:
any random plasma glucose 200 mg/dL
any fasting plasma glucose 126 mg/dL
fasting 86 mg/dL had specificity 76% and sensitivity of 81% for detecting GDM
fasting 90 mg/dL and HbA1C above normal able to detect macrosomia
Diagnostic Test - 3 hour GTT
Management
Metabolic control
Diet
Medication
Fetal evaluation
Delivery considerations
Post-partum
Metabolic control
"level of glycemia to reduce fetal and neonatal complications in GDM has not been established"
frequent visits
frequent accu-checks
fasting
pre-prandial
post-prandial
Metabolic control (cont"d)
Diet
caloric intake based on BMI and weight gain
2,200 to 2,400 kcal
composition
protein 12-20%
carbohydrate 50-60%
fat 20-30%
Diet (cont"d)
Diet (cont"d)
Timing
breakfast 25% of calories
lunch 30%
supper 30%
15% as HS snack
Medication
Insulin
multiple injections
long and short acting
insulin pump
Oral
not used
recent study using glyburide
NEJM Oct. 19, 2000
Fetal Evaluation
Screening for neural tube defects
AFP at 16-20 weeks
Ultrasound at 18-20 weeks
Echo at 20-22 weeks
Third trimester
maternal monitoring of fetal activity
biophysical testing (NST, BPP, CST)
Other reasons to increase fetal evaluation
keto-acidosis
pyelonephritis
pre-eclampsia
poor adherence
Delivery considerations
Must weigh maternal and fetal risks
With excellent glycemic control and normal fetal surveillance, can await spontaneous labor
If antepartum testing is non-reassuring and lungs are mature - deliver patient
Delivery (cont"d)
With high risk patients, goal is to reach pulmonary maturity
vascular disease
poor control
adherence problems
previous still birth

SERUM ANDROJEN ANABOL�K HORMONLARI VE ROMATO�D ARTR�T R�SK�

9/7/2010

H�PERT�RO�D� VEYA T�ROTOKS�KOZ NED�R?

9/7/2010

veribaz.com - Endokrinoloji / Metabolizma Hastal�klar - T�rkiye'nin veri bankas�

ENDOKR�N S�STEM

ENDOKR�N BEZLER VE HORMONAL D�ZENLEME

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HEPARIN-INDUCED THROMBOCTOPENIA

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TARGETING INSULIN RESISTANCE A STRATEG FOR IMPROVING GLCEMIC CONTROL IN TYPE 2 DIABETES

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INSULIN THERAP IN TPE 2 DIABETES

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REDISCOVERING INSULIN FOR TPE 2 DIABETES

RATIONALE FOR IMPROVED GLCEMIC CONTROL

SERUM ANDROJEN ANABOL�K HORMONLARI VE ROMATO�D ARTR�T R�SK�

THE CONTROL OF THROID FUNCTION

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ADRENO-CORTICAL STEROIDS

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INTRODUCTION TO CLINICAL ENDOCRINOLOG

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HEPARIN INDUCED THROMBOCTOPENIA AND THE USE OF ARGATROBAN

MULTIPLE ENDOCRINE NEOPLASIA

HYPERTHROID HEART DISEASE

HORMONE REPLACEMENT THERAPY (HRT)

GESTATIONAL DIABETES (GDM)

SERUM ANDROJEN ANABOL�K HORMONLARI VE ROMATO�D ARTR�T R�SK�

H�PERT�RO�D� VEYA T�ROTOKS�KOZ NED�R?

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