Efficiency of natural oils as alternative adjuvants to mineral oils in inactivated avian influenza vaccine formulation.

1. The effectiveness of inactivated vaccines depends on selecting the suitable adjuvant for vaccine formulation. The potency of vaccines with low antigen content can be improved with the appropriate adjuvant. This could allow production of more doses and lower the production cost.2. This study evaluated the efficiency of vaccines prepared using oil extracted from natural sources including argan oil, almond oil, sesame seed oil, pumpkin oil, cactus oil and black seed oil as alternative adjuvants for improving the protection capacity of inactivated influenza virus vaccine as compared to commonly used mineral oils.3. Each vaccine formulation was evaluated for stability, safety and immunogenicity in chickens, as well as for reducing the viral shedding after challenge infection.4. The cactus, sesame and pumpkin seed oil-based vaccines were found to be potent and successfully induced the production of humoral immunity in vaccinated chickens.

Availability and Access to Medications for Puberty Induction and Maintenance in Adolescents with Hypogonadism in the Arab Region.

Background: Inducing puberty in hypogonadal patients enables achieving normal final adult height and healthy bone mass accrual and improves fertility potential. Reliable availability and access to medicines remain a challenge around the world, particularly in low-income countries. Aim: We aimed to describe the availability/access to medications used for inducing and maintaining puberty in centers within the Arab region. Method: A cross-sectional survey was conducted using a link to an online questionnaire, which was emailed to paediatric endocrinologists in the Arab region. The questionnaire consisted of three questions related to the availability of various forms of sex hormones. Results: 99 physicians from 16 countries participated in the study. The commonest available form of estrogen was conjugated estrogen (29% of centers), followed by ethinylestradiol (26%). Depot estradiol was available in 11 centers, while topical estrogen preparations of gel and patches were available in 6 and 10 centers, respectively. Medroxy progesterone was available in 26% of the centers, followed by norethisterone (24%). The combined forms of oral and transdermal patches of estrogen/progesterone were available in 35% and 9% of centers, respectively. Intramuscular testosterone (Sustanon) was the most commonly available preparation of testosterone, followed by the depot injection (Nebido), oral testosterone, and testosterone gel and cream. Conclusions: We report the first available data on medications used for puberty induction and maintenance in paediatric hypogonadism in the Arab region. Recommended preparations for this purpose are not widely available. Creating an essential list of medications used in paediatric endocrinology disorders might improve availability, access, and consequently practice.

Ligation of the middle hepatic vein to increase hypertrophy induction during the ALPPS procedure.

PURPOSE: Here, we analyse the technical modification of the ALPPS procedure, ligating the middle hepatic vein during the first step of the operation to enhance remnant liver hypertrophy. METHODS: In 20 of 37 ALPPS procedures, the middle hepatic vein was ligated during the first step. Hypertrophy of the functional remnant liver volume was assessed in addition to postoperative courses. RESULTS: Volumetric analysis showed a significant volume increase, especially for patients with colorectal metastases. Pre-existing liver parenchyma damage (odds ratio = 0.717, p = 0.017) and preoperative chemotherapy were found to be significant predictors (odds ratio = 0.803, p = 0.045) of higher morbidity and mortality. In addition, a survival benefit for maintenance of middle hepatic vein was shown. CONCLUSION: This technical modification of the ALPPS procedure can accentuate future liver remnant volume hypertrophy. The higher morbidity and mortality observed are most likely associated with pre-existing parenchymal damage within this group.

Mutations in foot and mouth disease virus types A and O isolated from vaccinated animals.

Foot and mouth disease (FMD) is responsible for serious economic losses in Egypt. Although vaccination is practised as the main control strategy, failure of vaccination has been reported in many cases, which can be due to a number of factors. Selection of FMD antigenic variants under the immune pressure of partially immunised hosts has been previously recorded. This study was designed to isolate and characterise foot and mouth disease viruses (FMDVs) circulating in Egyptian vaccinated animals. Serotype O, A and Southern African Territories (SAT) 2 FMDVs were detected in different Egyptian governorates during 2015, 2016 and 2017. The successful isolation of 15 FMDVs of the three serotypes is reported in this paper. Phylogenetic analysis based on the viral protein (VP) 1 gene showed that all serotype O isolates had East Africa (EA)-3 topotypes. There was variation in 15-17 amino acids between the serotype O isolates of 2015 and those of 2016 and 2017. The serotype A isolates belonged to the A-Iran-05 lineage, with the exception of one isolate of 2016 which clustered with the African strains of G-IV. Serotype SAT2 FMDV was detected in two samples of 2017 and both were of lineage Alx-12 of topotype VII. The virus neutralisation test using sera raised against vaccine strains confirmed the serotyping of the isolates and determined the antigenic relatedness between the isolates and the currently used vaccine strains. A decrease in the neutralising antibody titre of some serotype O and A isolates could be attributed to mutation in critical amino acids in the neutralising antigenic sites. Hence, this work supports previous studies describing the significance of amino acid substitutions within the antigenic sites of the virus in antibody neutralisation and immune escape.

La fièvre aphteuse est à l'origine d'importantes pertes économiques en Égypte. Si la vaccination constitue la principale stratégie de lutte contre cette maladie, de nombreux échecs vaccinaux ont été rapportés, dus à différents facteurs. Il a été constaté par le passé que la pression immunitaire exercée par des hôtes partiellement immunisés contre la fièvre aphteuse entraînait une sélection de variants antigéniques du virus. La présente étude avait donc pour objet d'isoler et de caractériser les virus de la fièvre aphteuse présents en Égypte chez les animaux vaccinés. Les sérotypes O, A et Southern African Territories (SAT) 2 du virus de la fièvre aphteuse ont été détectés dans plusieurs gouvernorats égyptiens en 2015, 2016 et 2017. Les auteurs font état de 15 isolements réussis de souches virales appartenant à chacun des trois sérotypes. Il ressort de l'analyse phylogénétique basée sur le gène de la protéine virale 1 (PV1) que tous les isolats de sérotype O correspondaient au topotype East Africa (EA) 3. Une variation de 15 à 17 acides aminés a été observée entre les virus de sérotype O isolés en 2015 et ceux du même sérotype isolés en 2016 et en 2017. Les isolats de sérotype A appartenaient tous à la lignée A-Iran-05, à l'exception d'un isolat de 2016 qui était proche des souches africaines du lignage G-IV. Le sérotype SAT-2 du virus de la fièvre aphteuse a été détecté dans deux échantillons prélevés en 2017. Les deux souches isolées appartenaient à la lignée Alx-12 du topotype VII. La neutralisation virale utilisant des antisérums produits contre les souches vaccinales a permis de confirmer le sérotypage des souches isolées et de déterminer le degré de similitude entre les isolats et les souches vaccinales utilisées actuellement. La diminution du titre d'anticorps neutralisants dirigés contre certains isolats des sérotypes O et A est probablement imputable à une mutation d'acides aminés déterminants au sein des sites de neutralisation des antigènes. Ce travail corrobore les résultats d'études antérieures qui avaient révélé que les substitutions d'acides aminés au sein des sites antigéniques du virus peuvent avoir un rôle dans la neutralisation d'anticorps et dans l'échappement du virus au système immunitaire.

La fiebre aftosa es causante de graves pérdidas económicas en Egipto. Aunque la vacunación viene siendo la principal estrategia de lucha, se han descrito numerosos casos en los que ha resultado ineficaz, hecho que puede deberse a varios factores. Anteriormente ya se había observado que la presión inmunitaria de hospedadores parcialmente inmunizados conduce a la selección de determinadas variantes antigénicas de la fiebre aftosa. Los autores exponen un estudio encaminado a aislar y caracterizar los virus de la fiebre aftosa circulantes en los animales egipcios vacunados. En los años 2015, 2016 y 2017 se detectaron en diferentes provincias del país los serotipos víricos O, A y SAT (Southern African Territories) 2. Los autores dan cuenta del aislamiento de 15 virus de la fiebre aftosa pertenecientes a uno u otro de estos tres serotipos. El análisis filogenético basado en el gen de la proteína vírica (VP) 1 demostró que todos los virus del serotipo O aislados correspondían al topotipo EA (East Africa)-3, con diferencias localizadas en los aminoácidos 15 a 17 entre los virus aislados en 2015 y los de 2016 y 2017. Los virus del serotipo A pertenecían al linaje A-Iran-05, con la excepción de uno de los de 2016, que formaba un conglomerado con las cepas africanas del linaje G-IV. El serotipo SAT2, por su parte, estaba presente en dos muestras de 2017, pertenecientes ambas al linaje Alx-12 del topotipo VII. Empleando la prueba de neutralización vírica con sueros sensibilizados contra cepas vacunales se confirmó el serotipo de los virus aislados y se determinó el grado de parentesco antigénico entre esos virus y las cepas vacunales utilizadas actualmente. El decremento observado en el título de anticuerpos neutralizantes frente a algunos de esos virus de los serotipos O y A podría explicarse por la mutación de aminoácidos fundamentales de los sitios antigénicos neutralizantes. Este trabajo, por lo tanto, viene a corroborar anteriores estudios que señalaban la gran influencia de la sustitución de aminoácidos en los sitios antigénicos del virus en los procesos de neutralización de anticuerpos y escape inmunitario.

Protective efficacy of a prime-boost protocol using H5-DNA plasmid as prime and inactivated H5N2 vaccine as the booster against the Egyptian avian influenza challenge virus.

In this study, a recombinant DNA plasmid was constructed, encoding for HA1 of a selected Egyptian H5N1 virus (isolated during the 2012 outbreaks). In the immunization and challenge experiments, SPF chickens received 1 or 2 doses of H5-DNA plasmid prime, and boosted with the inactivated H5N2 vaccine. Haemagglutination inhibition (HI) titers, protection levels, and the magnitude of virus shedding were compared to that of the chickens that received either DNA plasmid or inactivated H5N2 vaccine alone. H5N1 virus A/chicken/Egypt/128s/2012 (H5N1) highly pathogenic avian influenza (HPAI) clade 2.2.1/C was used for the challenge. Chickens immunized with 1 or 2 doses of H5-DNA vaccine failed to overcome the challenge with 0% and 10% protection, respectively. Quantitative real-time reverse transcription-PCR revealed virus shedding of 2.2 x 104 PCR copies/ml 3 days post challenge (dpc) in the only surviving bird from the group that received 2 doses of plasmid. However, chickens immunized with 1 or 2 doses of H5-DNA plasmid as prime and inactivated H5N2 vaccine as booster, showed 80% protection after challenge, with a viral shedding of 1.2 x 104 PCR copies/ml (1 dose) and 1.6 x 104 PCR copies/ml (2 doses) 3 dpc. The surviving birds in both groups did not shed the virus at 5 and 7 dpc. In H5N2-vaccinated chickens, protection levels were 70% with relatively high virus shedding (1.8 x 104 PCR copies/ml) 3 dpc. HI titers were protective to the surviving chickens. This study reports the efficacy of H5-DNA plasmid to augment reduction in viral shedding and to provide better protection when applied in a prime-boost program with the inactivated AI vaccine.

[Sarcoma of the spleen with MDM2 expression]. / Sarkom der Milz mit MDM2-Expression.

Primary sarcomas and sarcoma metastases are a rarity in the spleen. We report on the case of a 69-year-old male patient presenting with unclear abdominal symptoms and computed tomography (CT) revealed a tumor mass in the spleen. Histologically the tumor mass predominantly showed features of a spindle cell sarcoma with lymphoid infiltrates. The expression and amplification of MDM2 could be demonstrated by means of immunohistochemistry and fluorescence in situ hybridization (FISH). Furthermore, staging examinations did not reveal indications of any other primary tumors. These preliminary findings were suggestive of a dedifferentiated liposarcoma; however, in the further diagnostic work-up the tumor showed strong expression of CD21 and CD23 and was ultimately diagnosed as a follicular dendritic cell sarcoma (FDCS). The case emphasizes that MDM2 expression represents a possible pitfall in the diagnosis of spindle cell tumors. The differential diagnostic distinction between FDCS and a dedifferentiated liposarcoma is discussed.

Effect of aerobic exercise on premenstrual symptoms, haematological and hormonal parameters in young women.

The objective of this study was to investigate the effect of aerobic exercise on premenstrual symptoms, haematological and hormonal parameters in young women. A total of 30 participants aged 16-20 years and complaining of premenstrual syndrome (PMS) were randomly assigned into two groups: a control group received vitamin B6 and Ca supplements once daily and a study group received the same medical treatment and participated in treadmill training three times per week for 3 months. A premenstrual syndrome questionnaire (MSQ), complete blood picture and hormone assays were performed for the assessment of all participants at the start and after the end of the treatment course. The study group showed a significant decrease in all post-treatment subscale symptoms, scores and total score. Haemoglobin, haematocrit, red cell count and platelet count were significantly increased, while mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and white blood cell count showed no significant differences. There was also a significant decrease in prolactin, oestradiol and progesterone levels. In conclusion, aerobic exercise increases haemoglobin, haematocrit, red cell count and platelet count, and decreases levels of prolactin, oestradiol and progesterone, resulting in improvement of fatigue, impaired concentration, confusion and most premenstrual symptoms.

Structural, radiation shielding, thermal and dynamic mechanical analysis for waste rubber/EPDM rubber composite loaded with Fe2O3 for green environment.

Increasing waste rubber recycling produces a specious range of products for many valuable applications. Waste Rubber/EPDM composite with different concentrations was prepared. Infrared spectroscopy (FTIR) is used to identify the chemical composition. A water absorption test, Dynamic mechanical analysis (DMA), and Thermal Gravimetric Analysis (TGA) were performed. The (75/25) WR/EPDM rubber composite exhibited the best behavior with the highest mechanical performance. Fe2O3 was added to (75/25) WR/EPDM rubber composite. Water absorption, FTIR, TGA, and DMA were investigated. The composite performance was improved with increasing Fe2O3 content. The linear attenuation coefficients (µ) were also measured as a function of the concentrations of Fe2O3 for γ-ray energy 662 keV by using 137Cs point source; the radiation shielding can be denoted by numbers of parameters like mass attenuation coefficient (µm), half value layer (HVL), Tenth value layer TVL and radiation protection efficiency (RPE%), radiation protection efficiency increased as Fe2O3 increased.

Association between operative approach and complications in patients undergoing Hartmann's reversal.

BACKGROUND: Complications following reversal of Hartmann's procedure are common, with morbidity rates of up to 50 per cent, and a mortality rate as high as 10 per cent. This is based on case series with heterogeneous data collection and analysis. This study determined risk factors for complications following Hartmann's reversal. METHODS: Patients who underwent elective open and laparoscopic Hartmann's reversal were identified from the American College of Surgeons National Surgical Quality Improvement Program database (2005-2010). The programme collects patient demographics, preoperative medical history, clinical findings and laboratory investigations. Postdischarge data were obtained by a certified reviewer. Complications were categorized as major, septic or incisional. Risk-adjusted 30-day outcomes were assessed by univariable and multivariable analyses, adjusting for patient characteristics, co-morbidity and operative approach. RESULTS: During the study period 7996 patients had a Hartmann's procedure and 2567 cases of Hartmann's reversal were identified, including 336 laparoscopic procedures (13·1 per cent). Major, septic and incisional complication rates were 13·3, 8·5 and 15·7 per cent respectively, with a mortality rate of 0·5 per cent. A laparoscopic approach was found to be independently associated with fewer major (odds ratio (OR) 0·53, 95 per cent confidence interval 0·34 to 0·81), septic (OR 0·48, 0·27 to 0·83) and incisional (OR 0·54, 0·37 to 0·80) complications. A history of chronic obstructive pulmonary disease (OR 1·78-2·00), steroid use (OR 1·75), body mass index at least 30 kg/m² (OR 1·48), diabetes (OR 1·40), smoking (OR 1·33-1·40), American Society of Anesthesiologists fitness grade III and IV (OR 1·46-1·48) and prolonged operating time (OR 1·02) were other factors associated with complications. CONCLUSION: A laparoscopic approach to Hartmann's reversal was associated with fewer complications than open surgery in this highly selected group of patients.

Closure of defunctioning loop ileostomy is associated with considerable morbidity.

AIM: An elective defunctioning ileostomy is commonly employed to attenuate the morbidity that may arise from distal anastomotic leakage. The magnitude of risk associated with subsequent ileostomy closure is difficult to estimate as many of the data arise from small series. This study looked at the rate of complications and predictive factors in a large series of patients. METHODS: The National Surgical Quality Improvement Program database was queried for patients who had an elective closure of ileostomy between 2005 and 2010. Patient demographics, preoperative risk factors and operative variables were recorded. The primary outcome was occurrence of major (mortality, sepsis, return to the operating room, renal failure, major cardiac, neurological or respiratory episode) or minor (wound infection, urinary tract infection) complications within 30 days. Univariate and multivariate regression was used to evaluate the effect of these clinical factors on the complication rate. RESULTS: In total, 5401 patients underwent closure of ileostomy, of whom 502 (9.3%) patients had major complications. The incidence of minor complications was 8.4% (452 patients). There were 32 (0.6%) deaths. American Society of Anesthesiologists grade, functional status, prolonged operative time, history of chronic obstructive pulmonary disease, dialysis and disseminated cancer were independent predictors of major complications. There was no significant increase in complication rates in patients over the age of 80. Major complications were associated with a significant increase in postoperative stay (13.9 vs 4.7 days, P < 0.0001). CONCLUSION: Closure of ileostomy is associated with a significant complication rate. It may use as many resources as the primary surgery and is not a minor follow-up operation.

A double-blinded randomised controlled study of the value of sequential intravenous and oral magnesium therapy in patients with chronic low back pain with a neuropathic component.

Persistent mechanical irritation of the nerve root sets up a series of events mediating sensitisation of the dorsal roots and dorsal horns in the spinal cord. Current evidence supports the role of magnesium in blocking central sensitisation through its effect on N-methyl-d-aspartate receptors. We studied the role of sequential intravenous and oral magnesium infusion in patients with chronic low back pain with a neuropathic component. We recruited a cohort of 80 patients with chronic low back pain with a Leeds Assessment of Neuropathic Signs and Symptoms pain scale score ≥ 12, who were receiving a physical therapy programme. All patients were treated with anticonvulsants, antidepressants and simple analgesics; in addition 40 patients received placebo for 6 weeks (control group), while the other 40 patients received an intravenous magnesium infusion for 2 weeks followed by oral magnesium capsules for another 4 weeks (magnesium group). Patients were asked to rate their pain using a numerical rating scale. Lumbar spine range of motion was also determined using a long-arm goniometer. In the magnesium group, the patients' numerical rating scales revealed a significant reduction in pain intensity. The mean (SD) pre-treatment value was 7.5 (2.2) compared with 4.7 (1.8) at 6 months (p = 0.034). The reduction in pain intensity was accompanied by significant improvement in lumbar spine range of motion during the follow-up period. The mean (SD) values of flexion, extension and lateral flexion movements before treatment and at 6-month follow up were 22.2 (8.4) vs 34.7 (11.5) (p = 0.018), 11.8 (3.4) vs 16.9 (3.5) (p = 0.039), 11.4 (3.6) vs 17.2 (4.4) (p = 0.035), respectively. Our findings show that a 2-week intravenous magnesium infusion followed by 4 weeks of oral magnesium supplementation can reduce pain intensity and improve lumbar spine mobility during a 6-month period in patients with refractory chronic low back pain with a neuropathic component.

A laparoscopic approach reduces short-term complications and length of stay following ileocolic resection in Crohn's disease: an analysis of outcomes from the NSQIP database.

AIM: Studies to date examining the impact of laparoscopy in resection for Crohn's disease on short-term morbidity have been limited by small study populations. The aim of this study was to establish the impact of the operative approach (laparoscopic or open) on outcomes after ileocolic resection for Crohn's disease. METHOD: Ileocolic resections for Crohn's disease were identified using Current Procedural Terminology (CPT) and International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes from the National Surgical Quality Improvement Program (NSQIP) database (2005-2009). Complications were categorized as major (organ system damage and systemic sepsis) or minor (incisional and urinary infections). Multivariate 30-day outcomes and length of stay were determined using linear models adjusting for patient characteristics, comorbidities and operative approach. RESULTS: Of 1917 ileocolic resections, 644 (34%) were performed laparoscopically. At baseline, the open group was significantly older, had more comorbidities, higher American Society of Anesthesiology (ASA) classes, and more intra-operative transfusions (all variables, P<0.05). On multivariate analysis, laparoscopic ileocolic resections were associated with a decrease in major (OR=0.629, 95% CI: 0.430-0.905, P=0.014) and minor (OR=0.576, 95% CI: 0.405-0.804, P=0.002) complications compared with open resections. Laparoscopy was associated with a significant reduction in adjusted length of stay compared with the open approach (-1.08±0.29 days, P=0.0002). CONCLUSION: After adjusting for comorbidities and perioperative factors, such as preoperative sepsis, higher ASA class and higher transfusion rates in the open group, laparoscopic ileocolic resection for Crohn's disease was found to be a safer choice than the open approach, resulting in fewer complications and length of stay. All other things being equal, such patients should be offered the laparoscopic approach as a first-choice option.

Assessment and referral of patients with short stature by primary care physicians in the Arabian gulf region: Current perspectives from a regional survey.

Children with short stature are frequently referred late to pediatric endocrinologists in the Arabian Gulf region. This is likely a contributing factor to late initiation of treatment despite current evidence suggesting that children with short stature have better outcomes with earlier treatment. This delay in referral could be due to a lack of identification or proper assessment of short stature by front-line physicians. To analyze the assessment and perception of short stature in this group of physicians, an expert group of pediatric endocrinologists developed and disseminated an anonymous online survey of 22 multiple choice questions amongst general pediatricians, pediatric subspecialists, and family medicine physicians in the Arabian Gulf region. Of the 640 respondents, 450 completed the survey (70.3% completion rate). While most surveyed physicians use the correct definition for short stature in children, only 24% reported a consistent use of a wall-mounted stadiometer. Of the respondents, 50% or less would consider referring clinical conditions other than growth hormone (GH) deficiency or idiopathic short stature, 41% would refer a child with short stature as soon as height dropped below the 5th percentile, 57% considered GH a treatment option for short stature, and only 60% consider GH treatment safe. The results of this survey demonstrate knowledge gaps in short stature assessment and referral that need to be addressed through education on short stature amongst target physicians, and lay groundwork for future recommendations to address those gaps in the Arabian Gulf region.

Intra-articular injection of etanercept versus glucocorticoids in rheumatoid arthritis patients.

OBJECTIVES: This study was conducted to assess the safety and efficacy of intra-articular injection of etanercept and compare it with corticosteroid injection in rheumatoid arthritis (RA) patients. METHODS: Fifty patients with RA who suffered from activity in one joint were randomized into two groups, received an intra-articular injection of either etanercept or corticosteroid guided by musculoskeletal ultrasound. All patients were assessed for disease activity by disease activity score (DAS28), functional assessment using the Modified Health Assessment Questionnaire (MHAQ), and laboratory investigations (erythrocyte sedimentation rate and C-reactive protein). Joints affected were evaluated for pain by visual analog scale (VAS), tenderness, and swelling scores and by ultrasound for estimation of synovial hypertrophy, synovial effusion, and power Doppler. Follow-up of the patients was done at weeks 1, 4, and 12 after injection by clinical assessment and ultrasound. RESULTS: There was a significant improvement of joint pain assessed by VAS, tenderness, and swelling scores in the etanercept group at week 1 and week 4 follow-up periods but there were insignificant changes at week 12. There was a significant decrease in synovial effusion at week 1 and week 4 and in power Doppler at week 1 but no significant change was noticed in synovial hypertrophy during the follow-up periods. In comparison of the two groups, etanercept has shown better results on joint scores at week 1; however, glucocorticoid had more sustained effects. No major or life-threatening side effects were noticed following intra-articular injection of etanercept. CONCLUSION: Intra-articular injection of etanercept is a safe and promising option; with comparable results to intra-articular injection of corticosteroid; however, its rapid absorption from the synovium may necessitate frequent injections. Key Points • Persistent inflammatory mono-arthritis is a common clinical problem that is often difficult to treat; it is a debilitating and destructive condition. • Intra-articular injection of TNF inhibitors is an encouraging treatment modality in managing refractory mono-arthritis in rheumatoid arthritis.

Insulin sensitivity and body composition in children with classical and nonclassical congenital adrenal hyperplasia.

BACKGROUND: Reduced insulin sensitivity and increased fat mass have been reported in children and adults with congenital adrenal hyperplasia (CAH). To understand the potential mechanisms underlying these differences, we assessed insulin sensitivity and body composition in children with classical or nonclassical (late-presenting) CAH compared with normal controls. SUBJECTS AND METHODS: Thirty-seven children with CAH (26 classical and 11 nonclassical) median (range) age 9.4 year (0.5-15.8) were compared with 41 healthy control children age 11.0 year (3.2-17.1). All children had an overnight fasting blood sample and body composition assessed by DEXA. Pubertal children (14 CAH and 19 controls) also had an oral glucose tolerance test. Classical and nonclassical CAH groups were each compared with controls, adjusting for age, gender and pubertal status. Results Classical CAH children had more fat mass than controls (P = 0.03), while nonclassical CAH children had more lean mass (P = 0.006) and higher systolic blood pressure (P = 0.003) than control children. Among pubertal children, nonclassical CAH children had higher mean insulin (0-120 min; P = 0.04), stimulated insulin (0-30 min; P = 0.02), 120 min insulin (P = 0.004) and 120 min glucose levels (P = 0.03) than controls, but no difference in disposition index. DISCUSSION: Greater body fat in classical (early-presenting) CAH children could reflect the effects of lifetime glucocorticoid therapy. In contrast, the greater lean mass and parameters of insulin resistance in nonclassical (late-presenting) CAH children likely indicate the adverse metabolic effects of prolonged postnatal androgen excess.

[Living related liver transplantation]. / Lebertransplantation durch Lebendspende.

Liver transplantation has become established as a standard procedure in the treatment of end-stage liver diseases. Despite intense efforts by all parties involved up to the amendment of the German Transplantation Act, the lack of suitable donor organs was still one of the limiting factors of this therapeutic procedure. One way out of this problem is to make so-called marginal organs usable, e.g. with the help of machine perfusion or by utilizing living liver donation, which are used in some countries for more than 90% of organ donations. In general, there is no difference in the indications for liver transplantation between a (partial) organ obtained by post-mortem or living donation. Before any living donation, a thorough evaluation of the donor is carried out in order to minimize postoperative morbidity as far as possible. Technically the partial liver donation is based on the oncological liver resection, while the partial liver transplantation is a further development of split liver transplantation after post-mortem liver donation. In specialized centers comparable or even better results can nowadays be achieved using living liver donation instead of post-mortem donation.

Novel ambulatory glucose-sensing technology improves hypoglycemia detection and patient monitoring adherence in children and adolescents with type 1 diabetes.

PURPOSE: Glucose monitoring [GM] is a mainstay of diabetes control and management. Improving glycemic control is essential to prevent microvascular complications. However, adherence to GM can be a challenge in children and adolescents. Detecting hypoglycemia is essential for its prevention and treatment. We aim to study the impact of the flash ambulatory glucose monitoring in detecting hypoglycemia and enhancing adherence in children and adolescents with type 1 diabetes. METHODS: The study is prospective involving 3 hospital visits. Children and adolescents with diabetes were enrolled in the study which involved a period on conventional glucose self-monitoring [glucometers] followed by a similar period of monitoring using the flash glucose monitoring device (FreeStyle Libre). Frequency of GM, duration and frequency of hypoglycemia were compared on conventional and the flash monitoring. RESULTS: 75 subjects were studied. Age mean (range) was 11.9 years (2-19). Significant difference was seen in hypoglycemia detection between both testing devices. 68 (94%) and 65 (90%) patients detected nocturnal and diurnal hypoglycemia respectively on Flash monitoring compared to 12 (16.6%) and 30 (41%) on glucometer testing (p < 0.00). Mean (range) duration of hypoglycemia was 95 min (15-330). Statistically-significant difference was found between the frequency of GM on glucometer testing compared with Flash monitoring (2.87 and 11.6/day) (p < 0.001). CONCLUSIONS: Flash monitoring is a useful tool to improve adherence to GM and detecting hypoglycemia [diurnal and nocturnal] in children and adolescents with type 1 diabetes.

A novel mutation in the human androgen receptor suggests a regulatory role for the hinge region in amino-terminal and carboxy-terminal interactions.

CONTEXT: The androgen insensitivity syndrome (AIS) is caused by molecular defects in the androgen receptor (AR). Clinically, the partial AIS has a variable phenotype. Many mechanisms explain the phenotype in the AIS. A crucial step in AR action is the interaction of the N and C termini. OBJECTIVE: The role of the hinge region of the AR is not as well understood as other parts of the receptor. We aim to study the role of this region in the N/C-termini interaction. PATIENT AND METHOD: We report a patient with severe undermasculinization and poor response to exogenous androgens. Androgen binding was performed, and the AR gene was sequenced. The mutation was recreated and transfected in COS-1 cells. Transactivation was studied. N/C-termini interaction was studied using a mammalian two-hybrid assay. A nuclear localization study was performed. RESULTS: Androgen binding was normal, and a novel mutation (Arg629Trp) in the AR hinge region was identified. Mutant AR transactivation was 40% higher compared with wild type (WT). A 3-fold increase in transcription occurred when both WT N and C-terminal domains were cotransfected; no response occurred when the mutated region of the AR was included (P < 0.001). Cells with mutant AR showed a comparable nuclear localization to the WT AR. CONCLUSIONS: A mutation in the hinge region impaired N/C-domain interaction in the presence of normal AR binding and nuclear localization. It resulted in severe undermasculinization at birth and resistance to androgens. The findings confirm a unique regulatory role for the hinge region in AR function.