Disseminated vitiligo associated with AIDS

We report a case of vitiligo arising one year after human immunodeficiency virus (HIV) seropositivity but before clinical onset of acquired immunodeficiency syndrome (AIDS). To our knowledge, this specific time sequence has not been described. Generalization of such lesions began during a period of medical noncompliance, increasing viral load, rising CD8+ count, and markedly decreased CD4+ count. These findings suggest new mechanisms of autoimmune and infectious pathogenesis.     

The effects of long- and short-term maternal caffeine ingestion on human fetal breathing and body movements in term gestations

The possible effects of long- and short-term maternal ingestion of caffeine during normal human pregnancy on the breathing and body movements of third-trimester fetuses were studied in 14 patients, selected by a dietary questionnaire, and divided into two equal groups: high consumers (greater than 500 mg/day) (group 1) and low consumers (less than 250 mg/day) (group 2). All mothers followed a standard study protocol and underwent overnight fasting; studies began with a 30-minute control period, followed by oral administration of 200 mg caffeine, and a 180-minute subsequent observation period with continued maternal fasting. Blood samples for glucose and caffeine were obtained every 30 minutes and continuous recording of fetal breathing and body movements were entered on a microcomputer for off-line analysis. The two groups were similar for all obstetric outcome features. Plasma glucose levels were similar and constant in both groups whereas caffeine levels increased significantly at 60 minutes after administration; mean plasma caffeine levels were significantly higher in group 1 than in group 2 at all intervals. Fetal breathing rates and body movement incidences were similar in both groups before and after caffeine administration. Fetal breathing movement incidence decreased significantly in group 2 but was sustained at baseline levels in group 1 throughout the study. High long-term ingestion of caffeine during pregnancy is associated with higher maternal plasma caffeine levels and fetal breathing activity when compared with low caffeine ingestion. Short-term administration of 200 mg caffeine does not appear to have a significant physiologic impact on these activities.     

Coagulation factor abnormalities in patients with single-ventricle physiology immediately prior to the Fontan procedure

Background. Coagulation abnormalities have been reported following the Fontan operation and have been attributed to various aspects of Fontan-associated physiology. Using age-matched controls, this study evaluated coagulation abnormalities in children who had undergone a bidirectional Glenn procedure to test the hypothesis that coagulation abnormalities are present before the Fontan operation.

Methods. Coagulation factors were assayed in 38 children (mean age 34.4 ± 15 months) immediately before the Fontan operation; 37 healthy children (mean age 33 ± 17 months) were assayed as controls. Concentration of factors II, V, VII, VIII, IX, and X and of antithrombin III, plasminogen, proteins C and S, fibrinogen, serum albumin, and liver enzymes were measured. Normal reference intervals based on the control patients were determined using 95% confidence limits. Patient demographic data, hemodynamic variables, and elapsed time after the Glenn procedure were evaluated as possible predictors of coagulation abnormalities.

Results. Concentrations of protein C; factors II, V, VII, and X; plasminogen; and antithrombin III were significantly lower before the Fontan operation compared with age-matched controls (p < 0.01); no specific hemodynamic variables were predictive of a pro- or anticoagulant deficiency. There were significant positive correlations between patients who had abnormally low factor VII, protein S, and protein C levels and a longer interval between the bidirectional Glenn procedure and the Fontan operation (p < 0.001).

Conclusions. Coagulation abnormalities that could predispose patients to increased risk for clotting or bleeding are evident early in the course of staged single-ventricle repair.     

Selective disruption of the recognition of facial expressions of anger

Appetitive aggression occurs in the context of resource/dominance disputes in a wide variety of species. Hence, the possibility arises that a specific neural system may have evolved to detect and coordinate responses to this specific form of challenge or threat. The dopamine system has been implicated in the processing of signals of aggression in social-agonistic encounters in several species. Here we report that dopaminergic antagonism in healthy male volunteers, following acute administration of the dopamine D2-class receptor antagonist sulpiride, leads to a selective disruption in the recognition of facial expressions of anger (signals of appetitive aggression in humans), but leaves intact recognition of other emotions and the matching of unfamiliar faces.     

Modification of glutamate binding sites in newborn brain during hypoglycemia

We have shown that acute insulin-induced hypoglycemia leads to specific changes in the cerebral NMDA receptor-associated ion channel in the newborn piglet. The present study tests the hypothesis that exposure to acute hypoglycemia in the newborn will alter the glutamate binding site of both NMDA and kainate receptors. Studies were performed in 3-6 days-old piglets randomized to control (n=6) or hypoglycemic (n=6) groups. Hypoglycemia was maintained for 120 min using insulin infusion. Saturation binding assays were performed in cerebral cell membranes using (3)H-glutamate or (3)H-kainate to determine the characteristics of the glutamate binding sites of the NMDA and kainate receptors, respectively. The concentration of glucose in cerebral cortex was 10-fold less in hypoglycemic piglets than in controls (P<0.05). Brain ATP was not significantly decreased during hypoglycemia, but phosphocreatine decreased from control of 6.6 +/- 1.3 micromoles/g brain to 3.2 +/- 1.9 micromoles/g brain in hypoglycemic piglets. The B(max) for NMDA-displaceable (3)H-glutamate binding was 992 +/- 64 fmol/mg protein in hypoglycemic animals, significantly higher than the control value of 746 +/- 42 fmol/mg protein. However, the dissociation constant for glutamate was unchanged during hypoglycemia. The (3)H-kainate binding studies demonstrated no change in B(max) of high-affinity kainate receptors during hypoglycemia. In contrast, the affinity of the kainate receptor glutamate binding site significantly increased compared to control. Thus, acute hypoglycemia in the newborn piglet had specific effects on the glutamate binding sites of the NMDA and kainate receptors that could be due to alterations in cell membrane lipids or modification of receptor proteins.     

Multiple sclerosis: magnetization transfer histogram analysis of segmented normal-appearing white matter

PURPOSE: To investigate and characterize the global distribution of magnetization transfer (MT) ratio values of normal-appearing white matter (NAWM) in patients with relapsing-remitting multiple sclerosis (MS) and test the hypothesis that the MT histogram for NAWM reflects disease progression. MATERIALS AND METHODS: Conventional and MT magnetic resonance (MR) images were obtained in 23 patients and 25 healthy volunteers. Clinical tests for comparison with the MT histogram parameters included the Extended Disability Status Scale and the ambulation index. Lesion load calculated with T2-weighted MR images and whole-brain and white matter volumes were measured. RESULTS: The location of the MT histogram peak and the mean MT ratio for NAWM were significantly lower in patients with MS than in control subjects. In longitudinal studies, the histogram peak location and mean MT ratio shifted in the direction of normal values as the duration of disease increased. A mean of 26.5% of the volume of new lesions identified on the later studies were demonstrated to have originated in NAWM corresponding to "lost" pixels on the histogram. CONCLUSION: MT histogram analysis of NAWM, including longitudinal analysis, may provide new prognostic information regarding lesion formation and increase understanding of the course of the disease.     

Expression of lipoprotein receptor and apolipoprotein E genes by perinatal rat lipid-laden pulmonary fibroblasts

Lipid-laden interstitial fibroblasts (LIFs) are abundant during alveolar septal formation in rats and accumulate droplets of neutral lipids. The mechanisms controlling lipid acquisition by LIFs are incompletely understood and accumulation varies during postnatal development, because lipid droplets are usually a transient phenotype. We hypothesized that plasma lipoproteins may be an important source of lipids and that the cells may alter their acquisition of lipoproteins by changing the expression of lipoprotein receptors and apolipoprotein E. We quantified the accumulation low-density lipoproteins (LDLs) and very-low-density lipoproteins (VLDLs) by LIFs and the expression of LDL and VLDL receptors mRNA and protein at various perinatal ages and found no significant age-related differences. Apolipoprotein E mRNA was maximal at postnatal day 15, whereas immunoreactive apolipoprotein E protein was maximal at gestational day 21, suggesting complex regulation. Our findings indicate that the age-related difference in the lipid droplet contents of LIFs is not primarily related to differences in LDL or VLDL receptor expression. They suggest that changes in the quantities of plasma lipoproteins, which are presented to LIFs in the lung at various perinatal ages, are more likely to be responsible for age-related alterations in lipid droplet size and abundance.     

Cognitive functioning in children on dialysis and post-transplantation

We studied 124 children, 62 patient-subjects who had end-stage renal disease (ESRD) and 62 sibling-controls who closely matched the patient-subjects in terms of their ethnicity and their socioeconomic status, to discern whether children with ESRD would perform less well than their siblings on standardized achievement and intelligence quotient (IQ) tests, and to determine whether ethnicity would influence such results. The subjects were recruited from nine pediatric transplant and dialysis centers across the United States. Thirty-one subjects were white (Euro-American), 17 were African-American, and 14 were categorized as 'other'. The average age of the patient-subjects was 13.7 +/- 0.44 yr; and of the sibling-controls 13.7 +/- 0.38 yr. Most patients (61%) and siblings (84%) were in regular school classes, and most (87% and 92%, respectively) attended school full-time. The average IQ percentile rank for the patients was significantly lower than their siblings (31 +/- 4 vs. 44 +/- 5, respectively, with normal = 50). Patients tended to score lower on achievement tests compared with their siblings (spelling: 88.7 +/- 4 vs. 94.6 +/- 2; arithmetic: 88.5 +/- 2 vs. 94.0 +/- 2; reading: 91.9 +/- 2 vs. 100 +/- 3, respectively). Patients scores on achievement tests were influenced by age at diagnosis and by the mother/caregiver's lower achievement. Also, increased time on dialysis predicted lower scores on achievement tests. Neither dialysis/transplant status nor ethnicity significantly affected outcome. Our data suggest that ESRD, but not ethnicity or dialysis/transplant status, is a risk factor for lower IQ and academic achievement, especially in younger children, in children who spend more time living with ESRD, and in children whose mother's/caregiver's have lower educational levels.