Quality of Life of Short-Statured Children Born Small for Gestational Age or Idiopathic Growth Hormone Deficiency Within 1 Year of Growth Hormone Treatment

Aside from clinical endpoints like height gain, health-related quality of life has also become an important outcome indicator in the medical field. However, the data on short stature and health-related quality of life is inconsistent. Therefore, we examined changes in health-related quality of life in German children with idiopathic growth hormone deficiency or children born small for gestational age before and after 12 months of human growth hormone treatment. Children with idiopathic short stature without treatment served as a comparison group. At baseline, health-related quality of life data of 154 patients with idiopathic growth hormone deficiency (n = 65), born small for gestational age (n = 58), and idiopathic short stature (n = 31) and one parent each was collected. Of these, 130 completed health-related quality of life assessments after 1-year of human growth hormone treatment. Outcome measures included the Quality of Life in Short Stature Youth questionnaire, as well as clinical and sociodemographic data. Our results showed that the physical, social, and emotional health-related quality of life of children treated with human growth hormone significantly increased, while untreated patients with idiopathic short stature reported a decrease in these domains. Along with this, a statistically significant increase in height in the treated group can be observed, while the slight increase in the untreated group was not significant. In conclusion, the results showed that human growth hormone treatment may have a positive effect not only on height but also in improving patient-reported health-related quality of life of children with idiopathic growth hormone deficiency and children born small for gestational age

Characterisation of three novel CYP11B1 mutations in classic and non-classic 11 beta-hydroxylase deficiency

Background: Congenital adrenal hyperplasia (CAH) is one of the most common autosomal recessive inherited endocrine diseases. Steroid 11 beta-hydroxylase (P450c11) deficiency (11OHD) is the second most common form of CAH. Abstract Background: Congenital adrenal hyperplasia (CAH) is one of the most common autosomal recessive inherited endocrine diseases. Steroid 11b-hydroxylase (P450c11) deficiency (11OHD) is the second most common form of CAH. Aim: The aim of the study was to study the functional consequences of three novel CYP11B1 gene mutations (p.His125Thrfs*8, p.Leu463_Leu464dup and p.Ser150Leu) detected in patients suffering from 11OHD and to correlate this data with the clinical phenotype. Methods: Functional analyses were done by using a HEK293 cell in vitro expression system comparing WT with mutant P450c11 activity. Mutant proteins were examined in silico to study their effect on the three-dimensional structure of the protein. Results: Two mutations (p.His125Thrfs*8 and p.Leu463_Leu464dup) detected in patients with classic 11OHD showed a complete loss of P450c11 activity. The mutation (p.Ser150Leu) detected in a patient with non-classic 11OHD showed partial functional impairment with 19% of WT activity. Conclusion: Functional mutation analysis enables the correlation of novel CYP11B1 mutations to the classic and non-classic 11OHD phenotype respectively. Mutations causing a non-classic phenotype show typically partial impairment due to reduced maximum reaction velocity comparable with non-classic mutations in 21-hydroxylase deficiency. The increasing number of mutations associated with non-classic 11OHD illustrate that this disease should be considered as diagnosis in patients with otherwise unexplained hyperandrogenism. European Journal of Endocrinology (2014) 170, 697&ndash;706 Introduction Congenital adrenal hyperplasia (CAH), one of the most common autosomal recessive inherited endocrine diseases, is characterised by complete or partial impairment of adrenal steroidogenesis (1, 2). Although over 90% of cases of CAH are caused by 21-hydroxylase deficiency, steroid 11b-hydroxylase (P450c11, EC 1.14.15.4) deficiency (11OHD) accounts for 5&ndash;8% of cases, reflecting a frequency of w1:100 000&ndash;1:200 000 live births in non-consanguineous populations (3, 4, 5). The 11b-hydroxylase belongs to the cytochrome P450 system (P450c11) that facilitates the conversion of 11-deoxycortisol (S) to cortisol (F) and 11-deoxycorticosterone (DOC) to corticosterone (B) in the mitochondria of the adrenal cortex. 11OHD is characterised by deficient European Journal of Endocrinology Clinical Study S Polat and others Three novel CYP11B1 mutations 170:5 697&ndash;706 www.eje-online.org 2014 European Society of Endocrinology DOI: 10.1530/EJE-13-0737 Printed in Great Britain Published by</p

Histology Laboratory Guide Book

Histology and Embryology education and research are fundamental cornerstones of medical science. Histology, which is the basis of many fields of preclinical and clinical medicine, defines the visual components of cells, tissues and organs at the microscope level. This book, which we have published in the third extended version, provides students with a selection of micrographs created from archive preparations that Hacettepe University Faculty of Medicine Department of Histology and Embryology has been carefully created for more than 50 years. This selection has been prepared with the common effort of our academic staff, research assistants and technicians. The purpose of the book is to guide medical and health sciences students while examining the original preparations under the microscope in the laboratory, to match the functional properties associated with the structure of healthy cells with histochemical staining properties. Each chapter in the book contains brief information of micrographs on the basis of organs, tissues and cells under the relevant technical title. In this edition; we would respectfully like to thank the founder of our department and the first woman dean of medical school of our country, Prof. İlhan Kerse and, all of our retired professors who greatly contributed to our education by showing us the way of science. We also thank our former heads of department Prof. Ülken Örs, Prof. Esin Aşan, Prof. Ayşe Nur Çakar, Prof. Attila Dağdeviren, Prof. Sevda Fatma Müftüoğlu and Prof. Fevziye Figen Kaymaz. On behalf of our department, we wish all our students sincere success.Histoloji ve Embriyoloji, tıp biliminin vazgeçilmez temel taşlarından birisini oluşturur. Tıbbın birçok preklinik ve klinik alanına esas oluşturan histoloji, hücre, doku ve organların mikroskop düzeyinde görsel bileşenlerini tanımlar. Beşinci genişletilmiş basımını yaptığımız bu kitap, Hacettepe Üniversitesi Tıp Fakültesi Histoloji ve Embriyoloji Anabilim Dalı’nın 50 yılı aşkın süredir özenle oluşturduğu arşiv preparatlarından derlenmiş mikrograf seçkisini öğrencilere sunmaktadır. Bu seçki, anabilim dalımız öğretim üyeleri, araştırma görevlileri ve teknisyenlerinin ortak emeği ile hazırlanmıştır. Kitabın amacı; tıp ve sağlık bilimleri öğrencilerine laboratuvarda bu preparatları mikroskop altında incelerken rehberlik etmek, sağlıklı hücrelerin yapıları ile ilişkili işlevsel özelliklerini, histokimyasal boyanma özellikleriyle eşleştirmelerini sağlamaktır. Kitaptaki her bölüm, ilgili teknik başlık ya da sisteme ait preparat mikrografları hakkında organ, doku, hücre temelinde kısa bilgiler vermektedir. Bu baskıda; anabilim dalımızın kurucusu ve ülkemizin ilk kadın tıp fakültesi dekanı Sn. Prof. Dr. İlhan Kerse başta olmak üzere, bizlere bilimin yolunu göstererek yetişmemize katkıda bulunan anabilim dalı başkanlarımız Sn. Prof. Dr. Ülken Örs, Sn. Prof. Dr. Esin Aşan, Sn. Prof. Dr. Ayşe Nur Çakar, Sn. Prof. Dr. Attila Dağdeviren, Sn. Prof. Dr. Sevda Fatma Müftüoğlu, Sn. Prof. Dr. Fevziye Figen Kaymaz’a ve tüm emekli hocalarımıza teşekkür ediyoruz. Anabilim dalımız adına tüm öğrencilerimize içten başarı dileklerimizle

Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study

Background: KCNJ11 mutations cause permanent neonatal diabetes through pancreatic ATP-sensitive potassium channel activation. 90% of patients successfully transfer from insulin to oral sulfonylureas with excellent initial glycaemic control; however, whether this control is maintained in the long term is unclear. Sulfonylurea failure is seen in about 44% of people with type 2 diabetes after 5 years of treatment. Therefore, we did a 10-year multicentre follow-up study of a large international cohort of patients with KCNJ11 permanent neonatal diabetes to address the key questions relating to long-term efficacy and safety of sulfonylureas in these patients. Methods: In this multicentre, international cohort study, all patients diagnosed with KCNJ11 permanent neonatal diabetes at five laboratories in Exeter (UK), Rome (Italy), Bergen (Norway), Paris (France), and Krakow (Poland), who transferred from insulin to oral sulfonylureas before Nov 30, 2006, were eligible for inclusion. Clinicians collected clinical characteristics and annual data relating to glycaemic control, sulfonylurea dose, severe hypoglycaemia, side-effects, diabetes complications, and growth. The main outcomes of interest were sulfonylurea failure, defined as permanent reintroduction of daily insulin, and metabolic control, specifically HbA1c and sulfonylurea dose. Neurological features associated with KCNJ11 permanent neonatal diabetes were also assessed. This study is registered with ClinicalTrials.gov, number NCT02624817. Findings: 90 patients were identified as being eligible for inclusion and 81 were enrolled in the study and provided long-term (&gt;5·5 years cut-off) outcome data. Median follow-up duration for the whole cohort was 10·2 years (IQR 9·3–10·8). At most recent follow-up (between Dec 1, 2012, and Oct 4, 2016), 75 (93%) of 81 participants remained on sulfonylurea therapy alone. Excellent glycaemic control was maintained for patients for whom we had paired data on HbA1c and sulfonylurea at all time points (ie, pre-transfer [for HbA1c], year 1, and most recent follow-up; n=64)—median HbA1c was 8·1% (IQR 7·2–9·2; 65·0 mmol/mol [55·2–77·1]) before transfer to sulfonylureas, 5·9% (5·4–6·5; 41·0 mmol/mol [35·5–47·5]; p&lt;0·0001 vs pre-transfer) at 1 year, and 6·4% (5·9–7·3; 46·4 mmol/mol [41·0–56·3]; p&lt;0·0001 vs year 1) at most recent follow-up (median 10·3 years [IQR 9·2–10·9]). In the same patients, median sulfonylurea dose at 1 year was 0·30 mg/kg per day (0·14–0·53) and at most recent follow-up visit was 0·23 mg/kg per day (0·12–0·41; p=0·03). No reports of severe hypoglycaemia were recorded in 809 patient-years of follow-up for the whole cohort (n=81). 11 (14%) patients reported mild, transient side-effects, but did not need to stop sulfonylurea therapy. Seven (9%) patients had microvascular complications; these patients had been taking insulin longer than those without complications (median age at transfer to sulfonylureas 20·5 years [IQR 10·5–24·0] vs 4·1 years [1·3–10·2]; p=0·0005). Initial improvement was noted following transfer to sulfonylureas in 18 (47%) of 38 patients with CNS features. After long-term therapy with sulfonylureas, CNS features were seen in 52 (64%) of 81 patients. Interpretation: High-dose sulfonylurea therapy is an appropriate treatment for patients with KCNJ11 permanent neonatal diabetes from diagnosis. This therapy is safe and highly effective, maintaining excellent glycaemic control for at least 10 years. Funding: Wellcome Trust, Diabetes UK, Royal Society, European Research Council, Norwegian Research Council, Kristian Gerhard Jebsen Foundation, Western Norway Regional Health Authority, Southern and Eastern Norway Regional Health Authority, Italian Ministry of Health, Aide aux Jeunes Diabetiques, Societe Francophone du Diabete, Ipsen, Slovak Research and Development Agency, and Research and Development Operational Programme funded by the European Regional Development Fund