Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy

Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profound hypoglycemia due to inappropriate hypersecretion of insulin. An important diagnostic goal is to distinguish patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ significantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic venous sampling coupled with peroperative surgical examination and analysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the pancreas but not in normal pancreatic cells. This somatic event is consistent with a proliferative monoclonal lesion. It involves disruption of the balance between monoallelic expression of several maternally and paternally expressed genes. Thus, we provide the first molecular explanation of the heterogeneity of sporadic forms of PHHI such that it is possible to perform only partial pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia.     

Development of severe secondary hypertension in a patient with systemic entomophthoromycosis

The sudden onset of hypertension mandates investigation for secondary causes. We report the case of a young man with a very rare systemic fungal disease that included massive unilateral perirenal adenopathy. Treatment was associated with the abrupt onset of severe hypertension. Imaging studies suggested progressive constriction of one kidney with treatment, presumably as a result of healing adenopathy. We suggest that this case is a new example of hypertension secondary to constrictive perinephritis (Page kidney).     

Cathepsin E expression by normal and premalignant cervical epithelium

We have investigated the expression of the aspartic proteinase cathepsin E and HLA-DR and the presence of HPV16 in normal squamous epithelium (n = 8) and low-grade (n = 21) and high-grade (n = 14) intraepithelial squamous lesions of the uterine cervix. Immunohistochemistry of cervical biopsies revealed that up-regulation of cathepsin E expression was related to increasing severity of the cervical intraepithelial neoplasia (CIN). Up-regulation of protein was associated with increased message as assessed by in situ hybridization. Langerhans cells and the majority of koilocytes did not express detectable cathepsin E levels. Although there was also an up-regulation of HLA-DR expression by cervical keratinocytes in cervical intraepithelial neoplasia lesions, as determined by immunohistochemistry, no significant correlation was found between HLA-DR and cathepsin E expression in these lesions; neither was expression of cathepsin E correlated to the presence of HPV16, detected by polymerase chain reaction. The expression of cathepsin E, an aspartic proteinase that is reported to play a role in antigen processing for presentation by class II major histocompatibility complex molecules, is associated with cellular dedifferentiation in cervical intraepithelial neoplasia.     

35S]Guanosine-5''-O-(3-thio)triphosphate binding as a measure of efficacy at human recombinant dopamine D4.4 receptors: actions of antiparkinsonian and antipsychotic agents

Great progress has been made in the last 10 years in the understanding of the various types of viral hepatitis, and new viruses, concepts, therapies, preventive measures, and control strategies have been recognized. Even more agents, vaccines, and drugs will be discovered or developed in the future, and pediatricians increasingly will be expected to provide guidance to patients and to the community on the importance and use of these new tools.     

Effect of shigella enterotoxin 1 (ShET1) on rabbit intestine in vitro and in vivo

The purpose of this study was to identify the optimal knot construction for interrupted dermal sutures. A synthetic braided absorbable suture, sizes 3-0 and 5-0, was selected for this evaluation. With reproducible mechanical performance tests, we determined that the construction of secure knots without ears required one additional throw as compared with secure knots with 3-mm ears. The direction of applied tension did not alter knot security, with the exception of granny knots, which required an extra throw when tension was applied parallel to the suture loop. Because interrupted dermal knot construction is accomplished without knot ears and with an applied tension parallel to the wound, one additional throw must be added to the knot to ensure knot security.     

Autoimmunity caused by disruption of central T cell tolerance. A murine model of drug-induced lupus

A side effect of therapy with procainamide and numerous other medications is a lupus-like syndrome characterized by autoantibodies directed against denatured DNA and the (H2A-H2B)-DNA subunit of chromatin. We tested the possibility that an effect of lupus-inducing drugs on central T cell tolerance underlies these phenomena. Two intrathymic injections of procainamide-hydroxylamine (PAHA), a reactive metabolite of procainamide, resulted in prompt production of IgM antidenatured DNA antibodies in C57BL/6xDBA/2 F1 mice. Subsequently, IgG antichromatin antibodies began to appear in the serum 3 wk after the second injection and were sustained for several months. Specificity, inhibition and blocking studies demonstrated that the PAHA-induced antibodies showed remarkable specificity to the (H2A-H2B)-DNA complex. No evidence for polyclonal B cell activation could be detected based on enumeration of Ig-secreting B cells and serum Ig levels, suggesting that a clonally restricted autoimmune response was induced by intrathymic PAHA. The IgG isotype of the antichromatin antibodies indicated involvement of T cell help, and proliferative responses of splenocytes to oligonucleosomes increased up to 100-fold. As little as 5 microM PAHA led to a 10-fold T cell proliferative response to chromatin in short term organ culture of neonatal thymi. We suggest that PAHA interferes with self-tolerance mechanisms accompanying T cell maturation in the thymus, resulting in the emergence of chromatin-reactive T cells followed by humoral autoimmunity.     

Behavioural effects induced by nitrous oxide in rats performing a vigilance task

Nitrous oxide (N2O) effects were evaluated, as a behavioural model of inert gas narcosis, in rats performing a vigilance task in which they were required to respond to a slight luminous increment of the house-light. A dose-related decrease of correct responses was produced by the tested range of concentrations of N2O (from 30 to 70% N2O), with a parallel increase of anticipatory responses up to 60% N2O and a dramatic increase of omissions at 70% N2O. The influence of preparatory period duration on hits delays suggested a 'conditional probability effect' conserved under N2O. Pretreatment of animals with flumazenil (a central benzodiazepine receptor antagonist) did not improve performance under 40% N2O. Naltrexone, an opiate receptor antagonist, however, increased the N2O-induced deficits. These results suggest that benzodiazepine receptors are not involved in N2O-induced impairments in this attentional task, but opiate mechanisms may be implicated.     

Epidemiological study of hypertension and its determinants in an urban population of North India

OBJECTIVES: To determine age-specific prevalence of hypertension and blood pressure (BP) levels in relation to diet and lifestyle factors in North Indians. DESIGN AND SETTING: Cross-sectional survey in 20 randomly selected streets in Moradabad, North India. SUBJECTS AND METHODS: A total of 1806 subjects from North India (904 males and 902 females) age range 25-64 years. The survey methods were as follows: dietary diaries for 7 days food intake record; BP measurements; physician administered questionnaire and anthropometric measurements. Diagnosis of hypertension was based on new World Health Organization/International Society of Hypertension (WHO/ISH) criteria. Risk factors were assessed based on WHO guidelines. RESULTS: The prevalence of hypertension according to WHO/ISH criteria was 23.7% and by old WHO criteria 13.3%. In the WHO/ISH hypertensive group, isolated diastolic hypertension was present in 47.3% males and 40.6% females. Males have a slightly higher prevalence than females in the young age group, however, the prevalence rates are comparable in the older age groups. In both sexes, the prevalence rates and BP level increased with older age. Multivariate analysis revealed that age, higher body mass index, central obesity and higher socioeconomic status were independently and strongly associated with hypertension in both sexes. Higher dietary fat and salt intake and lower physical activity were weakly but significantly associated with hypertension. CONCLUSION: Association of higher socioeconmic status, higher body mass index and central obesity in North Indian adults with higher fat intake, lower physical activity and higher prevalence and level of hypertension indicate that these populations may benefit by decreasing the dietary fat intake and increasing physical activity, with an aim to decrease central obesity for decreasing hypertension in North Indians.