Diffuse brainstem glioma in children: critical review of clinical trials

Diffuse intrinsic brainstem gliomas constitute 15-20% of all CNS tumours in children, and are the main cause of death in children with brain tumours. Many clinical trials have been done over the past three decades, but survival has remained static. More than 90% of children die within 2 years of diagnosis, and conventional fractionated radiation remains the standard treatment. However, median survival differs substantially between clinical trials, suggesting a survival benefit with some strategies. We appraised the consistency between protocols in terms of eligibility criteria, definition and assessment of response and progression, statistical design, and endpoints. Study designs varied substantially, which could explain the differences in outcome, and no treatment has shown a benefit over conventional radiotherapy. However, consistency between protocols (eg, eligibility criteria and outcome measures) is important to measure the progress in management of diffuse pontine gliomas.     

Comparison of human bronchiolar smooth muscle responsiveness in vitro with histological signs of inflammation.

A study was carried out to test the hypothesis that chronic inflammation is associated with increased sensitivity or contractility of human airway smooth muscle. Bronchiolar strips from 30 patients, 12 of whom had chronic bronchitis, were examined in the organ bath for their responses to histamine, methacholine, and leukotriene (LT) C4. The same airways were also studied histologically and small airway disease was quantified by subjective grading of the degree of inflammatory cell infiltration, smooth muscle hypertrophy, fibrosis, and goblet cell hyperplasia. The degree of small airway disease varied widely among patients both with and without chronic bronchitis. Multiple regression analysis failed to show increased sensitivity (-log EC50) to histamine, methacholine, or LTC4 in relation to small airway disease. In contrast, the only significant correlations found were between a decreased -log EC50 to histamine and methacholine and an increased small airway disease score. Contractile responses (Tmax) to histamine and methacholine in peripheral airways tended to be higher in patients with chronic bronchitis than in those without. Tmax was not related to small airway disease scores. These results suggest that chronic airway inflammation does not cause in vitro hyperresponsiveness of human small airway smooth muscle.     

Expression of the chemokine receptor CXCR3 in human renal allografts--a prospective study.

BACKGROUND: Mechanisms involved in the recruitment and activation of inflammatory cells during renal allograft injury are still incompletely understood. Since chemokines play pivotal roles in this process, our prospective study was performed to evaluate further the role of the chemokine receptor CXCR3. METHODS: A total of 138 biopsies were included from patients without rejection and unaltered morphology (according to Banff 97 classification grade 1, n = 49), with acute interstitial rejection (Banff grade 4 type I, n = 8), with acute vascular rejection (Banff grade 4 type II, n = 23), with chronic allograft nephropathy (Banff grade 5, n = 16), without rejection but with various other lesions (Banff grade 6, n = 36) and from pre-transplant kidneys (n = 6). The expression of CXCR3-, CD4- and CD8-positive cells was localized by immunohistochemistry and quantified by image analysis. RESULTS: CXCR3 was expressed by infiltrating inflammatory cells, but not by intrinsic renal structures. CXCR3-positive cells were found to be involved in tubulitis and vascular rejection. The area of CXCR3-positive staining was significantly larger in biopsies with acute interstitial rejection (P<0.001) and acute vascular rejection (P<0.001) as compared with normal renal graft biopsies. There was a strong morphological and numerical correlation between CXCR3 and both CD4- and CD8-positive T cells, respectively. CONCLUSIONS: A significant part of both CD4- and CD8-positive T cells express the chemokine receptor CXCR3. During renal allograft rejection, the number of these cells increases significantly at the site of injury and might be targeted by CXCR3 blocking agents.     

The pathogenesis and therapy of multiple sclerosis is based upon the requirement of a combination of myelin antigens for autoimmune demyelination

It is postulated that the pathogenesis of demyelination in multiple sclerosis (MS) might lie in the cooperative effect of a T cell response against one myelin antigen (e.g. myelin basic protein--MBP) and a B cell response against a second myelin component which may act as a hapten or a carrier for the primary antigen. The hypothesis is based upon recent experiments in guinea pigs in which the encephalitogenicity of MBP was enhanced by the myelin glycolipid, galactocerebroside. This pathogenetic mechanism might be analogous to antibody-dependent, cell-mediated demyelination. Based upon this assumption, therapeutic trials in MS should take into consideration the possibility that instead of MBP alone, MBP might be more effective in combination with a lipid hapten.     

A comparison of two methods of measuring food group intake: grams vs servings

Different measurements can be used to quantify food group intake, such as servings, cups, or grams. Dietary recommendations are given in terms of servings (recently expressed as cup and ounce measurements), but research on disease risks often uses grams as the intake measure. Because serving sizes vary among foods within a food group, the method of expressing food group intake (grams vs servings) may impact disease risk analyses. Daily consumption of eight food groups was calculated as both Food Guide Pyramid servings and grams for 206,721 participants in the Multiethnic Cohort Study who completed a quantitative food frequency questionnaire between 1993 and 1996. Mean grams per serving ranged from 25 g for red meat to 172 g for dairy products. Spearman correlation coefficients between intakes as grams per day and servings per day were 0.85 for grains, 0.97 for vegetables, 0.99 for fruit, 0.95 for dairy products, 0.98 for red meat, 0.93 for processed meat, 1.00 for poultry, and 1.00 for fish. Because there was little effect on the ranking of study participants' intakes due to the method of calculating food group consumption, the two measures are interchangeable in disease risk models.     

"Any decision is better than none" decision-making about sex of rearing for siblings with 17beta-hydroxysteroid-dehydrogenase-3 deficiency

Children with 17beta-hydroxysteroid-dehydrogenase-3 (17beta-HSD-3) deficiency have a defect of testosterone biosynthesis with subsequent diminished virilization in XY individuals. Some are raised as girls and some as boys. There were two purposes of this case report: First, it analyzed the process of decision-making in a family with a pair of siblings with identical mutations leading to 17beta-HSD-3 deficiency whose parents chose to raise one child as a boy and one as a girl. This analysis was based on narrative interviews with the parents. Second, we assessed the gender role behavior and gender identity in the children to examine if the psychosexual development of these children correspond with the sex of rearing their parents chose. When participating in the study, the children were 7 (boy) and 5 (girl) years old. Parents described a difficult process of decision-making and voiced concerns about lack of appropriate and understandable information, and anticipated decision regret. However, they did not feel that the decision to "normalize" the external genitalia should have been deferred. Both children appeared to show age-typical gender-related behavior and did not show any signs of physical or mental distress.     

Clinical predictors for a high risk for the development of diabetes mellitus in the early puerperium in women with recent gestational diabetes mellitus

OBJECTIVE: The purpose of this study was to identify which maternal, antepartum, or neonatal clinical parameters were predictive for a high risk of diabetes mellitus in the puerperium in women with recent gestational diabetes mellitus and to calculate the associated diabetes mellitus rates and odds ratios. STUDY DESIGN: One thousand six hundred thirty-six women underwent an oral glucose tolerance test within 1 to 4 months of delivery. Demographic, historic, and antenatal glycemic parameters and neonatal outcome parameters were tested by univariate and multivariate logistic regression for risk of postpartum diabetes mellitus. Continuous variables were divided into quartiles that compared the upper to lower quartile adjusted odds ratio and prevalence of diabetes mellitus. RESULTS: Postpartum diabetes mellitus was diagnosed in 230 women (14.1%) according to the American Diabetes Association criteria (1997). No maternal demographic or neonatal parameters were significantly associated with diabetes mellitus. The final model of independent predictors in decreasing significance included the highest fasting plasma glucose level during pregnancy, any fasting plasma glucose level of > or = 105 mg/dL (class A(2)), the area under the curve of pregnancy oral glucose tolerance test, gestational age at diagnosis, previous gestational diabetes mellitus history, and 50-g glucose challenge test results. The fasting plasma glucose level was the best discriminator, with a 21-fold (95% CI, 4.6-96.3) increased odds ratio comparing the 4th quartile (fasting plasma glucose level, >121 mg/dL; diabetes mellitus rate, 36.7%) to 1st quartile (fasting plasma glucose level, < 95 mg/dL; diabetes mellitus rate, 0.5%). The presence of previous gestational diabetes mellitus or current class A(2) gestational diabetes mellitus approximately doubled the odds ratio for diabetes mellitus. The odds ratio increased 3- to 4-fold when the area under the curve was > or = 33.36 min small middle dot g/dL (4th quartile) or the glucose challenge test was > or = 155 mg/dL (2nd-4th quartiles) and decreased > 50% if gestational diabetes mellitus was diagnosed at > 27 weeks (3rd-4th quartile). CONCLUSION: During pregnancy, the highest fasting glucose level, followed by the severity of glucose intolerance, and earlier gestational diabetes mellitus diagnosis were the best predictors for postpartum diabetes mellitus. Diabetic education should begin during pregnancy, especially for women who are identified to be at a high risk when they are highly motivated and under medical care.