Cutaneous phenotype and MC1R variants as modifying factors for the development of melanoma in CDKN2A G101W mutation carriers from 4 countries

The G101W founder mutation is the most common CDKN2A mutation in Italy, Spain, and France. As the background of modifying genes, environmental exposures, and sun behavior vary across countries, studying G101W carriers from distinct countries offers a unique opportunity to evaluate possible modifying factors in melanoma development. We evaluated 76 G101W cases and 59 carrier controls from France, Italy, Spain, and the United States. Hair color and dysplastic nevi distributions differed significantly in cases and controls across the 4 study groups. Cases also varied significantly for eye color, freckling, and nevi. The distribution of MC1R variants in cases differed significantly across study groups because 12% of Italian melanoma patients had > or =2 MC1R variants vs. >50% for the other case groups. Several MC1R covariates showed significant associations with melanoma risk in all groups combined and in the American, French, and Spanish samples; no significant findings were observed in the Italian sample. In multiple-case families, the number and type of MC1R variants varied significantly between multiple-primary-melanoma and single-primary-melanoma patients from the 4 groups; there was also a significant decrease in median age at melanoma diagnosis as the number or type of MC1R variants increased. The variation in the effects of the cutaneous phenotypic and MC1R factors across the study sample suggests that these factors differentially contribute to development of melanoma even on a common genetic background of a germline CDKN2A mutation. Differences in melanoma risk across geographic regions justify the need for individual studies in each country before counseling should be considered.     

Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review

Background

Transcutaneous Vagus Nerve stimulation (tVNS) may be an alternative to surgically implanted VNS for epilepsy and other diseases. However, its safety and tolerability profile is unclear.

Assesssing Herbal Medical Practitioners in Professional Qualifying Examination in Ghana, a Model

About 70% of Ghanaians depend on Alternative health practice for their primary health care needs. Hence, there is the need to streamline and regulate these practices. Graduates from the Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology (K.N.U.S.T), Kumasi-Ghana were assessed by the Professional Qualifying Examination Board of the Traditional Medicine Practice Council (TMPC), Ghana, after two years of internship training. A model of assessment took into consideration, the scope of the university training, internship and the primary health care needs of the society.     

Sex differences in outcomes of sinus surgery

PURPOSE: Sex has been demonstrated to affect outcome in many diseases. Our current aim is to investigate the relationship between sex and outcomes of endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). METHODS: Forty-four males and 73 females undergoing ESS for CRS with a mean follow-up of 1.4 years were evaluated prospectively. Computed tomography (CT), endoscopy, and quality of life (QOL) assessment was performed. Univariate analyses were performed to evaluate whether sex was predictive of outcome. Multiple logistic regression analysis was performed to evaluate sex association with patient factors predictive of outcome. RESULTS: Although no sex differences in CT and endoscopy were observed (CT, P=.107 and endoscopy, P>.1), females consistently scored worse than males on disease-specific QOL pre- and postoperatively. Importantly, there was no effect of sex on improvement/change scores for the QOL instruments. PREDICTIVE MODELS AND MULTIPLE LOGISTIC REGRESSION ANALYSIS: Sex was not found to be predictive of QOL or endoscopic outcome. Female sex was, however, associated with acetylsalicylic acid (ASA) intolerance and depression, both factors that have been associated with poorer outcome. CONCLUSION: Despite similarities in objective disease measures, females report significantly worse QOL scores pre- and postoperatively. Postoperative improvement did not differ by sex, nor was sex predictive of postoperative outcome. Sex differences in QOL reflect sex differences in ASA intolerance and depression, both more prevalent in females.     

Multicystic dysplastic kidney: observations of contralateral disease in the fetal population

To evaluate multicystic dysplastic kidney (MDK) and associated contralateral renal abnormalities in the fetal population, 27 cases detected and followed in utero were reviewed retrospectively. The sonographic assessment included estimation of amniotic fluid volume and interval growth, evaluation for non-genitourinary anomalies, and postnatal follow-up study. Contralateral renal anomalies were detected in 41% of the fetuses and included obstruction of the ureteropelvic junction, renal agenesis, renal hypoplasia, and bilateral MDK. The incidences of these malformations were compared with results of earlier studies of MDK in the pediatric and adult populations. Lethal anomalies, such as bilateral MDK and MDK associated with contralateral agenesis, are common (19% and 11%, respectively) in the fetal population; obstruction of the contralateral ureteropelvic junction, a nonlethal anomaly, was seen less commonly (7%). Perinatal death from lethal abnormalities may spuriously raise the incidence of nonlethal contralateral abnormalities in the pediatric and adult populations. Contralateral mild fetal pyelectasis, found in 15% of fetuses with MDK, was not clinically significant.     

Resolving duodenal-jejunal hematoma in abused children

Acute intramural duodenal-jejunal hematoma is a classical finding in the battered child syndrome. The radiographic findings of a large obstructing intramural mass associated with the "coiled-spring" appearance generally raise the question of child abuse in any patient without appropriate accidental injury. In this study the radiologic features of resolving duodenal-jejunal hematoma are detailed in five abused children. The results show that the coiled-spring appearance is an acute phenomenon associated with a well-localized intramural hematoma. In the resolving phase, localized mural masses in the lateral aspect of the descending duodenum and fold thickening are indications of prior intramural hemorrhage. When these radiologic features are encountered in a child with nonspecific abdominal complaints, child abuse should be suspected. Furthermore, in patients with suspected occult trauma, resolution of abdominal symptoms should not deter the radiologist from performing an upper gastrointestinal tract series, which may provide evidence of child abuse.     

Increased plasma thyroid stimulating hormone in treated congenital hypothyroidism: relation to severity of hypothyroidism, plasma thyroid hormone status, and daily dose of thyroxine

Plasma thyroid stimulating hormone (TSH) concentrations obtained during the first four years of treatment in 418 children with congenital hypothyroidism, identified by neonatal screening, were examined in relation to paired measurements of plasma thyroxine (n = 1945), free thyroxine (n = 836), triiodothyronine (n = 480), and free triiodothyronine (n = 231), and estimated daily dose of thyroxine at the time of blood sampling. Overall, plasma TSH was above 7 mU/l in 1280 out of 2960 samples (43%); the percentage was not related to severity of hypothyroidism at diagnosis. Mean values for thyroxine and free thyroxine, and to a lesser extent free triiodothyronine, were consistently lower in samples with TSH concentrations over 7 mU/l and this was the case in patients with either severe or less severe hypothyroidism. Raised TSH concentrations were also associated with lower mean doses of thyroxine (micrograms/kg/day) but here the mean doses of thyroxine in children with severe hypothyroidism were higher than in the children with less severe hypothyroidism. The mean dose of thyroxine associated with low/normal TSH values was highest in the first 6 months and fell progressively. Thyroxine dose was significantly related to thyroxine and free thyroxine concentrations but not to triiodothyronine and free triiodothyronine and the latter appeared to be of limited value as measures of plasma thyroid hormone status during treatment.     

Thrombomodulin, an endothelial anticoagulant protein, is absent from the human brain

Protein C activation by thrombin is significantly accelerated by the endothelial cell cofactor, thrombomodulin. In this study, we have developed a radioimmunoassay for thrombomodulin and have measured the cofactor content in several human tissues. The assay method detects as little as 2 ng of thrombomodulin. The highest thrombomodulin content was found in lung and placenta, but the antigen was also detected in spleen, pancreas, liver, kidney, skin, heart, and aorta. Unexpectedly, thrombomodulin was absent from brain. Extracts from cerebral cortex, cerebellum, centrum semiovale, midbrain, basal ganglia, pons, and medulla were devoid of thrombomodulin. In contrast, thrombomodulin antigen is present in extracerebral intracranial vessels, including basilar and internal carotid arteries and choroid plexus, as well as in endothelium of the pia-arachnoid.     

Isolation and structural characterization of the polypeptide subunits of membrane glycoprotein IIb-IIIa from human platelets

We have previously demonstrated the isolation of platelet membrane glycoprotein IIb-IIIa by affinity chromatography with a specific monoclonal antibody. We have now separated the polypeptide subunits IIb and IIIa of the isolated glycoprotein by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis and have compared their structural features. Both IIb and IIIa contain approximately 15% carbohydrate, but IIIa contains a larger percentage of mannose residues, suggesting the presence of high mannose as well as complex N- linked oligosaccharide chains. The amino acid compositions are sufficiently similar to imply areas of sequence homology between the two subunits. To examine further the relationship between the subunits, we digested a mixture of 125I-IIb and 131I-IIIa with trypsin and then separated the radiolabeled peptides by high performance liquid chromatography. The resultant peptide maps of IIb and IIIa are completely different. This indicates that neither subunit is derived from the other and suggests that polypeptides IIb and IIIa are products of separate genes.