Search

DEBRA International is undertaking a long-term initiative to develop clinical practice guidelines (CPGs) for epidermolysis bullosa (EB), to -improve the clinical care of people living with EB. Current neonatal care is based on evidence, clinical expertise and trial and error, with collaboration between the EB specialist team, parent or carer and patient, and is dependent on the neonate's individual presentation and type of EB. Early intervention based on research and clinical practice is needed to establish a foundation of knowledge to guide international practitioners to create and improve standards of care and to be able to work effectively with those newly diagnosed with EB. This CPG was created by an international panel with expertise working with persons with EB. The CPG focuses on neonatal care using a systematic review methodology covering four key areas: (i) diagnosis and parental psychosocial support; (ii) hospital management: medical monitoring, wound care and pain; (iii) feeding and nutrition; and (iv) discharge planning and EB education. These four areas highlight the importance of a multidisciplinary team approach, to provide a patient-specific holistic care model that incorporates the needs and wishes of the parents and carers. The Hospital Implementation Tool included promotes transfer of theory to clinical practice., Competing Interests: Conflicts of interest With one exception (K.M.-C.), this panel of researchers claims no financial conflicts of interest. K.M.-C. declared a potential conflict from her professional work coordinating guideline development for DEBRA International between 1 February 2016 and 6 February 2023. This author was therefore not involved in the final editions of the recommendations after review panel feedback. All other panel members and reviewers self-declared no potential conflicts of interest with respect to the publication of this guideline., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Study Objectives: Narcolepsy is associated with cardiovascular risk factors; however, the risk of new-onset cardiovascular events in this population is unknown. This real-world study evaluated the excess risk of new-onset cardiovascular events in U.S. adults with narcolepsy., Methods: A retrospective cohort study using IBM MarketScan administrative claims data (2014-2019) was conducted. A narcolepsy cohort, comprising adults (≥18 years) with at least two outpatient claims containing a narcolepsy diagnosis, of which at least one was non-diagnostic, was matched to a non-narcolepsy control cohort (1:3) based on cohort entry date, age, sex, geographic region, and insurance type. The relative risk of new-onset cardiovascular events was estimated using a multivariable Cox proportional hazards model to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: The narcolepsy and matched non-narcolepsy control cohorts included 12 816 and 38 441 individuals, respectively. At baseline, cohort demographics were generally similar; however, patients with narcolepsy had more comorbidities. In adjusted analyses, the risk of new-onset cardiovascular events was higher in the narcolepsy cohort compared with the control cohort: any stroke (HR [95% CI], 1.71 [1.24, 2.34]); heart failure (1.35 [1.03, 1.76]); ischemic stroke (1.67 [1.19, 2.34]); major adverse cardiac event (1.45 [1.20, 1.74]); grouped instances of stroke, atrial fibrillation, or edema (1.48 [1.25, 1.74]); and cardiovascular disease (1.30 [1.08, 1.56])., Conclusion: Individuals with narcolepsy are at increased risk of new-onset cardiovascular events compared with individuals without narcolepsy. Physicians should consider cardiovascular risk in patients with narcolepsy when weighing treatment options., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society.)

Background: Malignant hypertension is macrovascular and microvascular endothelial injury responsible for multiple organ damage. Considering the anatomical and functional homologies between the posterior pole of the eye and the kidney, ophthalmological explorations may inform clinicians on the mechanisms underpinning concurrent kidney injury in this condition. More specifically, we investigated whether the wall-to-lumen ratio (WLR) of retinal arterioles measured by adaptive optics ophthalmoscopy could be correlated to WLR of kidney arterioles as determined by pathology. We sought to estimate the incidence of retinal arteriole occlusion a supposedly uncommon complication of malignant hypertension., Methods: All patients hospitalized in our renal Intensive Care Unit for malignant hypertension between 2016 and 2019 were referred to ophthalmological examinations., Results: Twenty-seven patients were included. Median retinal WLR was 0.39 [0.31-0.47] and was correlated with initial systolic (r = 0.56, P = 0.003) and mean blood pressure (r = 0.46, P = 0.02) upon admission. The retinal WLR was not correlated to renal pathological findings, as assessed by juxtaglomerular WLR (r = 0.38, P = 0.2), ratio of glomerulosclerosis (r = -0.39, P = 0.2), or tubulointerstitial fibrosis (r = -0.45, P = 0.08). Retinal WLR was not associated with neurological or cardiovascular end-organ damage. Branch retinal artery occlusion was detected in 18.5% of patients and exudative retinal detachment (ERD) in 29.6% of patients, without any significant correlation with canonical signs of retinal hypertension including optic disc swelling., Conclusions: In the setting of malignant hypertension, we failed to demonstrate a significant relationship between WLR and other meaningful end-organ injuries. However, branch retinal artery occlusion and ERD may have been hitherto underestimated., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Understanding the molecular evolutionary basis of social behavior is a major challenge in evolutionary biology. Social insects evolved a complex language of chemical signals to coordinate thousands of individuals. In the fire ant Solenopsis invicta, chemical signals are involved in the determination of a polymorphic social organization. Single-queen (monogyne) or multiqueen (polygyne) social structure is determined by the "social chromosome," a nonrecombining region containing ∼504 genes with two distinct haplotypes, SB and Sb. Monogyne queens are always SBB, while polygyne queens are always SBb. Workers discriminate monogyne from polygyne queens based on olfactory cues. Here, we took an evolutionary genomics approach to search for candidate genes in the social chromosome that could be responsible for this discrimination. We compared the SB and Sb haplotypes and analyzed the evolutionary rates since their divergence. Notably, we identified a cluster of 23 odorant receptors in the nonrecombining region of the social chromosome that stands out in terms of nonsynonymous changes in both haplotypes. The cluster includes twelve genes formed by recent Solenopsis-specific duplications. We found evidence for positive selection on several tree branches and significant differences between the SB and Sb haplotypes of these genes. The most dramatic difference is the complete deletion of two of these genes in Sb. These results suggest that the evolution of polygyne social organization involved adaptations in olfactory genes and opens the way for functional studies of the molecular mechanisms underlying social behavior.

Chemical communication is fundamental for the operation of insect societies. Their diverse vocabulary of chemical signals requires a correspondingly diverse set of chemosensory receptors. Insect olfactory receptors (ORs) are the largest family of chemosensory receptors. The OR family is characterized by frequent expansions of subfamilies, in which duplicated ORs may adapt to detect new signals through positive selection on their amino acid sequence. Ants are an extreme example with ∼400 ORs per genome-the highest number in insects. Presumably, this reflects an increased complexity of chemical communication. Here, we examined gene duplications and positive selection on ant ORs. We reconstructed the hymenopteran OR gene tree, including five ant species, and inferred positive selection along every branch using the branch-site test, a total of 3326 tests. We find more positive selection in branches following species-specific duplications. We identified amino acid sites targeted by positive selection, and mapped them onto a structural model of insect ORs. Seventeen sites were under positive selection in six or more branches, forming two clusters on the extracellular side of the receptor, on either side of a cleft in the structure. This region was previously implicated in ligand activation, suggesting that the concentration of positively selected sites in this region is related to adaptive evolution of ligand binding sites or allosteric transmission of ligand activation. These results provide insights into the specific OR subfamilies and individual residues that facilitated adaptive evolution of olfactory functions, potentially explaining the elaboration of chemical signaling in ant societies.

Objectives: In emphysema, air can flow preferentially via collateral pathways, which can connect an entire lung when incomplete fissures are present. Spiracles are openings through the chest wall into the lung parenchyma. We previously observed increased alveolar ventilation (VA) in subjects with severe emphysema, when spiracles occurred during lung transplant operations. In this study, we set out to identify a computed tomography (CT) imaging phenotype associated with improved VA via spiracles in severe emphysema., Methods: We retrospectively reviewed 4 patients with severe emphysema who exhaled ≥75% of the inhaled tidal volume via transpleural spiracles during a lung transplant operation. We used quantitative image analysis via VIDA VISION CT software to describe emphysema severity and distribution and fissure integrity from pretransplant CT scans of the chest. We analysed partial pressure of carbon dioxide and calculated estimates of VA at baseline and during spiracle ventilation., Results: All 4 subjects demonstrated severe hyperinflation (total lung capacity 148 ± 24%predicted, residual volume 296 ± 79% predicted). On CT imaging, severe emphysema was present, with an average 38.7 ± 9% (range 28-50%) of lung parenchyma showing low-attenuation areas of - 950 Hounsfield units or less. Lung fissure integrity analysis demonstrated evidence of incomplete fissures (average detectable fissure integrity 67 ± 19%, range 40 ± 11-90 ± 10%). During spiracle ventilation on unchanged ventilator settings, there was a significant reduction in partial pressure of carbon dioxide (61 ± 4-35 ± 4 mmHg, P < 0.001) and increase in estimated VA (2.1 ± 0.5-3.8 ± 0.8 l/min, P < 0.001)., Conclusions: Incomplete lung fissures on quantitative CT analysis seem to be a key image phenotype associated with substantial improvements in VA during transpleural ventilation via spiracles in severe emphysema., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background and Aims: Both adalimumab [ADA] and infliximab [IFX] seem to be effective in the prevention of early postoperative endoscopic recurrence [EPER] after ileocaecal resection in Crohn's disease [CD] patients. There is lack of data with direct comparison between the two agents in the postoperative scenario. The aim of this study was to compare the rates of EPER in patients treated with ADA and IFX after ileocaecal resection for CD., Methods: This was a multicentre retrospective analysis of EPER rates in CD patients after ileocaecal resections, from seven referral centres in three countries. Endoscopic recurrence was defined as Rutgeerts' score ≥ i2. The patients were allocated according to treatment to two groups: ADA or IFX. The EPER rates were compared between the two treatment groups., Results: Among the 168 patients included in the database, 96 received anti-tumour necrosis factor [TNF] agents after resection [37 in the ADA and 59 in the IFX groups] and were included in this comparative study. The groups were comparable in all baseline characteristics, mainly age, gender, previous resections, perianal CD, and mono or combination therapy. EPER was identified in 9/37 [24.32%] in the ADA group vs 16/59 [27.12%] in the IFX group [p = 0.815]., Conclusions: In this retrospective direct comparison between ADA and IFX therapy after ileocaecal resection, there was no significant difference between the two anti-TNF agents in terms of EPER rates. However, prospective randomised studies are needed to confirm these data and better define the role of each agent in the prevention of EPER., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study is aimed at drawing the profile of the Brazilian general thoracic surgeon. This experience has been fruitful in other areas, helping attract manpower and to better serve the interests of other Societies. This is the first survey of this kind in Brazil and in Latin America., Methods: An electronic invitation was sent to the members of the Brazilian Society of Thoracic Surgery to answer a web-based questionnaire and physicians potentially practising thoracic surgery, with 82 questions including demographic data, medical education, training in general and thoracic surgery, continued professional education, practice profile, research activities and certifications, participation in medical societies, income/compensation and career satisfaction. Quantitative and qualitative analyses are presented., Results: The estimated level of participation was 82% (468). The mean age of the active general thoracic surgeon is 43.2 (range 45.3±11.4) years. Women comprised 8% (37) of respondents, and 60% (277) of the participants had graduated from public medical schools. Four states nationwide trained 88% (391) of the thoracic surgeons. Only 32% (149) of the surgeons work exclusively with thoracic surgery. The public health system is the main provider of income for thoracic surgeons. Only 11 of 27 states have an adequate, although poorly distributed, number of thoracic surgeons., Conclusions: Although Brazil has a reasonable number of general thoracic surgeons, inequalities in their distribution through the country arise as one of the most concerning problems of the speciality. The results of this study show that leadership actions and consistent government policies are required to improve work conditions and provide efficient workforce planning., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Paradoxical cases of psoriatic lesions induced or exacerbated by anti-tumor necrosis factor (TNF)-α therapy have been reported more frequently in recent years, but data related to inflammatory bowel disease (IBD) are rare. A systematic literature review was performed to provide information about this adverse effect in patients with IBD who receive anti-TNF therapy., Methods: Published studies were identified by a search of Medline, Embase, Cochrane, SciELO, and LILACS databases., Results: A total of 47 studies (222 patients) fulfilled the inclusion criteria and were selected for analysis. Clinical and therapeutic aspects varied considerably among these reports. Of the 222 patients, 78.38% were diagnosed with Crohn's disease, and 48.20% were female. The mean patient age was 26.50 years, and 70.72% of patients had no history of psoriasis. Patients developed psoriasiform lesions (55.86%) more often than other types of psoriatic lesions, and infliximab was the anti-TNF-α therapy that caused the cutaneous reaction in most patients (69.37%). Complete remission of cutaneous lesions was observed in 63.96% of the cases., Conclusions: We found that psoriatic lesions occurred predominantly in adult patients with Crohn's disease who received infliximab and had no previous history of psoriasis. Most patients can be managed conservatively without discontinuing anti-TNF-α therapy., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Although therapy with tumor necrosis factor-alpha inhibitors (anti-TNF) provides beneficial effects in different immune inflammatory disorders, paradoxical cases of anti-TNF-induced psoriasis have increasingly been reported, mostly in the setting of rheumatologic diseases. To date, less than 50 cases of infliximab-induced psoriasis in inflammatory bowel disease patients have been described. The present report was aimed at describing two new cases of infliximab-induced psoriasis during therapy for Crohn's disease and at carrying out a review on this intriguing phenomenon., (Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Objective: The study aimed to investigate the safety of including patients ≥ 80 years of age at the start of a video-assisted thoracic surgery major pulmonary resection (VMPR) programme., Methods: Patients were considered for VMPR if the computed tomography/positron emission tomography (CT/PET) was suggestive of T1-3, N0-1 and M0 lesion. Age was not a criterion for exclusion at the very start of the programme. Data were collected prospectively and comparison made between two groups, (A) <80 years of age and (B) ≥ 80 years, in terms of preoperative risk factors, oncological and functional data, operative results, postoperative complications and survival., Results: Between April 2005 and January 2011, 200 consecutive patients were considered for VMPR. A total of 160 had non-small-cell lung cancer, of whom 136 were in group A, with a median age of 66.5 (range: 42.8-79.4 years) and 24 in group B with a median age of 82 (range: 80-85.5 years). In group B, 13 were men and 11 were women. Rate of conversion to thoracotomy was similar (3 (12.5%) in group B vs 17 (12.5%) in group A, p = 0.65), and so was the mean hospital stay (5.8 ± 3.3 days in group B vs 5.9 ± 4.6 days in group A, p = 0.899). Admission to intensive care unit and atrial fibrillation were significantly higher in octogenarians (six (25%) and six (25%) in group B vs eight (5.9%) and nine (6.6%) in group A, p = 0.008 and p = 0.012, respectively). There was significantly less mean days of air leak in octogenarians (0.06 ± 0.3 days in group B vs 2.8 ± 5.6 days in group A, p = 0.000). Otherwise, there were no age-related differences in relation to morbidity, mortality and the 3-year survival rate., Conclusion: Octogenarians undergoing VMPR have a higher incidence of atrial fibrillation and admission to the intensive care unit for cardiopulmonary support but otherwise are no different from younger age groups when it comes to rate of conversion to thoracotomy, hospital stay, morbidity and mortality. Age should not be an excuse to deny the elderly curative VATS resection. In our experience, accepting octogenarians early in the VMPR programme did not compromise the outcome results.

Background: Differences in epidemiology of kidney disease across the Middle East may arise from variations in indication for biopsy, environmental exposure and socio-economic status. The Lebanese population is composed of different ethnicities, with distinct ancestry and religion, enabling comparison of their effect on the prevalence of kidney disease within a confined geographic setting and uniform practices. Here we report 5 years' detailed epidemiology of renal diseases, based on histological diagnosis, in a sample from three large pathology centres in Lebanon., Methods: Records of renal biopsies analysed at the American University of Beirut Medical Center, Hotel Dieu de France Hospital and the Institut National de Pathologie from January 2003 till December 2007 were retrospectively examined. We recorded the following data for each patient: age, gender, indication for renal biopsy and histopathological diagnosis. Religious affiliation and parents' consanguinity were recorded when feasible., Results: The mean age at renal biopsy was 36.76 ± 20 years (range 1-84). The most common diagnosis was mesangioproliferative glomerulonephritis (GN; 20%), followed by focal segmental glomerulosclerosis (13.2%). While there were no differences in age, gender or indications for biopsy among different religious affiliations, mesangioproliferative GN was significantly more frequent among Muslims (P = 0.039) and offspring of consanguineous unions (P = 0.036). On the other hand, focal segmental glomerulosclerosis was most prevalent in Christians (P < 0.001)., Conclusions: Variation in the distribution of diagnoses between Muslim and Christian groups likely reflects differences in population structure and ancestry. In particular, the increased prevalence of mesangioproliferative GN among offspring of consanguineous unions in Muslims suggests a recessive genetic component to this disease which may be identified via homozygosity mapping. These findings have important implications for formulating renal health policies and designing research studies in this population.

Many studies have shown important changes in lung function tests after coronary artery surgeries. It is controversial if off-pump surgery can give a better and shorter recovery than the on-pump. A prospective study was conducted on 42 patients submitted to coronary artery surgery and divided into two groups: 21 off-pump using intraluminal shunt (G (I)) and 21 on-pump (G (II)), matched by the anatomical location of the coronary arteries lesions. All patients had spirometric evaluation, blood gas measurements and alveolo-arterial oxygen gradient (A-aDO(2)), at the fourth and 10th postoperative days (PO(4) and PO(10)). Preoperatively, G(I) and G(II) had similar results (P>0.372). Spirometry showed decreases at PO(4) and remained decreased until PO(10) for both groups, with significant differences between the groups. The blood gas measurements showed reduction in arterial oxygen pressure (PaO(2)) and carbon dioxide pressure (PaCO(2)), while there was an increase in A-aDO(2) at PO(4) and PO(10) in both groups. The results suggest that different changes occur in pulmonary function when the surgery is performed with or without cardiopulmonary bypass. The off-pump patients showed significantly greater improvement than the on-pump group.

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP) could be a useful alternative diuretic for patients post cardiac surgery. Altogether more than 250 papers were found using the reported search, of which eight RCTs represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that the RCTs consistently showed a diuretic effect with increased creatinine clearance, and increased urine volume and reduced usage of conventional diuretics. Lower urea and creatinine levels were also found postoperatively and also reduced decreases in glomerular filtration rate compared to placebo, both in studies of patients with preoperatively normal renal function and those who had impaired function. In addition, two studies found a reduction in the incidence of AF, and renin/aldosterone levels were lower. The NAPA trial of 272 CABG patients with LV dysfunction was the only study to show a shorter ICU stay and reduced early mortality with nesiritide compared to placebo.

Background: Patients differ in responses to warfarin, which is commonly prescribed to treat thromboembolic events. Genetic variations in the cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9), vitamin K epoxide reductase complex, subunit 1 (VKORC1), and gamma-glutamyl carboxylase (GGCX) genes have been shown to contribute to impaired metabolism of warfarin., Methods: We designed a custom multiplex single-nucleotide polymorphism (SNP) panel to interrogate the CYP2C9 *2, *3, VKORC1 (-1639G-->A), and GGCX (1181T-->G) alleles simultaneously in a single sample by use of single-base extension and capillary electrophoresis after genomic DNA extraction and PCR amplification., Results: Our assay successfully detected various genotypes from known controls and 24 unknown samples. It was found to be 100% concordant with sequencing results., Conclusions: Our multiplexed SNP panel can be successfully used in genotyping of patient blood samples. Results can be combined with other clinical parameters in an algorithm for warfarin dosing. These data provide a proof-in-principle of multiplexed SNP analysis using rapid single-base extension and capillary electrophoresis, and warrant additional validation using a larger cohort of patient samples.

The incidence of type 2 diabetes mellitus in children is increasing with the increasing prevalence of obesity, particularly in African-American children. We hypothesized that African-American obese adolescents are more insulin resistant than their white peers, but have lower insulin secretion, thus increasing their risk of type 2 diabetes mellitus. The present study investigated insulin sensitivity and secretion, visceral adiposity (VAT), and cardiovascular disease (CVD) risk profile in black obese adolescents (BOA) vs. white obese adolescents (WOA). Twenty-four BOA and 26 WOA underwent a hyperinsulinemic-euglycemic clamp to assess insulin sensitivity, a hyperglycemic clamp to determine insulin secretion, dual energy x-ray absorptiometry for body composition and computed tomography scan at L4-L5 to measure VAT and sc abdominal adipose tissue. Fasting lipid and automated blood pressure measurements were obtained. The WOA and BOA groups were divided into low VAT and high VAT groups. BOA compared with WOA of similar body mass index and percent body fat had less visceral adiposity, lower hepatic glucose production, and lower lipid levels. Visceral adiposity was associated with lower insulin sensitivity in both groups [low vs. high VAT; BOA, 2.9 +/- 0.4 vs. 1.7 +/- 0.2 micromol/kg x min per pmol/liter (P = 0.016); WOA, 2.6 +/- 0.5 vs. 1.5 +/- 0.1 (P = 0.032)]. However, this was compensated by higher insulin secretion in whites (low VAT, 934.8 +/- 121.8; high VAT, 1590.6 +/- 232.8 pmol/liter; P = 0.037), but not in blacks (low VAT, 1398.9 +/- 214.0; high VAT, 1423.7 +/- 108.7 pmol/liter). Glucose disposition index (insulin sensitivity x first phase insulin) was lower in high VAT vs. low VAT BOA, but not in WOA. In each racial group, high VAT groups had elevation of systolic and diastolic blood pressure, but dyslipidemia was worse in WOA with high VAT. In conclusion, a given level of body mass index confers different metabolic risks for WOA vs. BOA. Although differences in fat patterning may help explain the more atherogenic risk profile in whites, the cause of the more diabetogenic insulin sensitivity/secretion profile in blacks remains unknown and needs to be investigated further.

Functional adrenal hyperandrogenism occurs in women with polycystic ovary syndrome (PCOS). Insulin, similar to its ovarian effect, may impact the regulation of adrenal steroidogenesis by modulating the activity of P450c17alpha, the rate-limiting enzyme in androgen biosynthesis. We previously demonstrated that obese adolescents with PCOS are severely insulin resistant and are at heightened risk for impaired glucose tolerance and type 2 diabetes. In the present study we tested the hypothesis that metformin therapy in obese adolescents with PCOS will attenuate the adrenal steroidogenic response to ACTH, with reduction of insulin resistance/insulinemia. Fifteen adolescents with PCOS and impaired glucose tolerance received 3 months of metformin (850 mg, twice daily) therapy. Pre- and posttherapy they had oral glucose tolerance testing, ACTH stimulation test, a 3-h hyperinsulinemic (80 mU/m(2).min)-euglycemic clamp to assess insulin sensitivity and a hyperglycemic clamp to assess insulin secretion. After 3 months of metformin treatment, glucose intolerance improved, with eight subjects having normal glucose tolerance. Total and free T decreased [1.5 +/- 0.2 vs. 1.0 +/- 0.1 nmol/liter (P = 0.022) and 41.3 +/- 8.3 vs. 22.2 +/- 2.1 pmol/liter (P = 0.028), respectively]. Insulin-stimulated glucose disposal increased (21.5 +/- 2.2 vs. 25.0 +/- 2.2 micromol/kg.min; P = 0.041). Fasting insulin and oral glucose tolerance test insulin and glucose area under the curve decreased significantly. ACTH-stimulated increases in androstenedione, 17-hydroxyprogesterone, and 17-hydroxypregnenelone were lower after metformin treatment [2.8 +/- 0.4 vs. 1.7 +/- 0.3 nmol/liter (P = 0.014), 7.0 +/- 0.6 vs. 5.3 +/- 0.5 nmol/liter (P = 0.011), and 30.4 +/- 3.7 vs. 25.7 +/- 4.2 nmol/liter (P = 0.054)]. Fasting insulin correlated with the 17-hydroxypregnenelone response to ACTH stimulation (r = 0.52; P = 0.008). In summary, metformin treatment of obese adolescents with PCOS and impaired glucose tolerance is beneficial in improving glucose tolerance and insulin sensitivity, in lowering insulinemia, and in reducing elevated androgen levels. Moreover, metformin therapy is associated with attenuation of the adrenal steroidogenic response to ACTH. Metformin therapy was well tolerated. In conclusion, double blind, placebo-controlled studies will determine whether insulin-sensitizing therapy corrects not only ovarian hyperandrogenism but also functional adrenal hyperandrogenism in adolescents with PCOS.

AIMS: The aim of this study was to assess the risk and progress of portal vein thrombosis (PVT) after splenectomy. METHODS: A prospective study was conducted in which two groups of patients were compared; each group comprised 50 patients (27 men, 23 women). Patients in the splenectomy group were of mean age 46.3 years. A second group of patients (mean age 48.5 years) had upper abdominal surgery other than splenectomy. All patients were examined before and 2 weeks after operation by duplex Doppler ultrasonography (DDUS) of the portal system. Those who developed PVT were followed up by DDUS at 6 and 12 months. RESULTS: PVT developed in 10 per cent of patients who underwent splenectomy. The portal vein was completely occluded by thrombus in 4 per cent and partially occluded in 6 per cent of patients. Symptoms and signs attributable to PVT (abdominal pain, diarrhoea, nausea, vomiting and mild fever) were found in 80 per cent of those who developed this complication. Follow-up of such patients revealed complete recanalization of portal vein in 40 per cent and partial recanalization in 60 per cent after treatment with antibiotics and long-term anticoagulation therapy. No patient who underwent upper abdominal surgery (other than splenectomy) developed PVT afterwards. CONCLUSIONS: Splenectomy (compared with other upper abdominal surgery) is followed by PVT in 10 per cent of patients but can be treated successfully.