Tubular expression of angiotensin II receptors and their regulation in IgA nephropathy

Enhanced renal expression for the renin-angiotensin system (RAS) is detected in IgA nephropathy (IgAN). Previous data showed an altered glomerular expression of angiotensin II type 1 receptor (AT1R), suggesting a regulatory response to high intrarenal angiotensin II (Ang II) concentration in IgAN. In this study, the expression and regulation of Ang II receptors were examined in human proximal tubular epithelial cells (PTEC) in IgAN. Tubular expression of AT1R and Ang II type 2 receptor (AT2R) was increased in IgAN. In vitro culture experiment showed that the upregulation of Ang II receptors was not due to the direct effect of IgA but the indirect effect after IgA deposition on human mesangial cell. When PTEC were cultured with conditioned culture medium from human mesangial cells activated with IgA, Ang II production was upregulated, leading to inflammation and apoptosis via the AT1R and AT2R, respectively. Sequential expression of Ang II receptors determined the injury of PTEC induced by mediators in the conditioned medium. The initial interaction between Ang II and AT1R activated both protein kinase C and mitogen-activated protein kinase pathways, leading to inflammatory responses. This early AT1R-dependent event was followed by upregulation of AT2R expression and continued Ang II release. The interaction between Ang II and AT2R subsequently led to expression of cleaved poly[ADP-ribose] polymerase through downregulation of the mitogen-activated protein kinase pathway. The data suggest that appropriate control of Ang II receptor activities in PTEC may ameliorate tubulointerstitial injury in IgAN.     

Synthesis and antimalarial activities of some furoxan sulfones and related furazans

Furoxan derivatives bearing a sulfone moiety at position 3 or 4 were synthesized and tested for their antimalarial action on the chloroquine-sensitive D10 and the chloroquine-resistant W2 strains of Plasmodium falciparum. The furazan analogues were considered for comparison. The most active compounds were the products in which the -SO2R groups are at the 3-position of the furoxan system. These latter substances displayed an antimalarial activity in the microM range, possibly related in part to their ability to release NO.     

Reproducibility and accuracy of a food frequency questionnaire used for diet intervention studies

The purpose of the present investigation was to determine whether altering the format of a food frequency questionnaire affected its accuracy and reproducibility. Three questionnaires were tested at one-month intervals. Questionnaire I contained 39 food items listed according to food categories. Questionnaire II contained 55 food items, presented according to the meal in which they were consumed. Questionnaire III contained 31 food items presented in a similar order to that in Questionnaire II. To determine the accuracy of the food frequency questionnaire, results were compared to those obtained from a simultaneously administered seven-day diet diary. Results from this study showed that food frequency questionnaires containing broad categories of food items presented in order of the meals in which they are consumed are the most reproducible. Highly reproducible results also can be obtained from seven-day diet diary, if data are calculated in terms of nutrients (i.e. carbohydrates, fats, proteins, etc.) and not specific food items. Finally, this study suggests that individuals more closely maintain their intake of nutrients, rather than specific food items.     

The effects of maternal drug dependence on neonatal mortality

Addiction in pregnancy has become an important health problem owing to the tendency of drug-dependent women to neglect general health care and to avoid seeking prenatal care. In addition, continued heroin administration during pregnancy carries additional risks for the maternal-fetal unit. Thus, there is an increased incidence of obstetrical and medical complications in these mothers, resulting in high incidences of prematurity, low birth weight and mortality in their infants. Therefore, there is a high neonatal mortality rate due to clinical conditions most commonly seen among premature infants. Data from three groups of drug-dependent women and their infants and one control group demonstrate that the high mortality rate, as well as the incidence of low birth weight, can be reduced to a rate similar to the control group in infants of mothers who receive comprehensive services that include prenatal care in conjunction with methadone maintenance.     

Acute neonatal effects of cocaine exposure during pregnancy

OBJECTIVE: To identify associations between cocaine exposure during pregnancy and medical conditions in newborn infants from birth through hospital discharge. DESIGN: Multisite, prospective, randomized study. SETTING: Brown University, University of Miami, University of Tennessee (Memphis), and Wayne State University.Subjects A total of 717 cocaine-exposed infants and 7442 nonexposed infants. MAIN OUTCOME MEASURES: Results of physical examination and conditions observed during hospitalization. RESULTS: Cocaine-exposed infants were about 1.2 weeks younger, weighed 536 g less, measured 2.6 cm shorter, and had head circumference 1.5 cm smaller than nonexposed infants (all P<.001). Results did not confirm previously reported abnormalities. Central and autonomic nervous system symptoms were more frequent in the exposed group: jittery/tremors (adjusted odds ratio, 2.17; 99% confidence interval, 1.44-3.29), high-pitched cry (2.44; 1.06-5.66), irritability (1.81; 1.18-2.80), excessive suck (3.58; 1.63-7.88), hyperalertness (7.78; 1.72-35.06), and autonomic instability (2.64; 1.17-5.95). No differences were detected in organ systems by ultrasound examination. Exposed infants had more infections (3.09; 1.76-5.45), including hepatitis (13.46; 7.46-24.29), syphilis (8.84; 3.74-20.88), and human immunodeficiency virus exposure (12.37; 2.20-69.51); were less often breastfed (0.26; 0.15-0.44); had more child protective services referrals (48.92; 28.77-83.20); and were more often not living with their biological mother (18.70; 10.53-33.20). CONCLUSIONS: Central and autonomic nervous system symptoms were more frequent in the exposed cohort and persisted in an adjusted analysis. They were usually transient and may be a true cocaine effect. Abnormal anatomic outcomes previously reported were not confirmed. Increased infections, particularly sexually transmitted diseases, pose a serious public health challenge. Exposure increased involvement of child protective services and out-of-home placement.     

The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in north India

The aim of this study was to find predictors of neuropathy and reactions, determine the most sensitive methods for detecting peripheral neuropathy, study the pathogenesis of neuropathy and reactions and create a bank of specimen, backed up by detailed clinical documentation. A multi-centre cohort study of 303 multibacillary leprosy patients in Northern India was followed for 2 years. All newly registered MB patients requiring a full course of MDT, who were smear positive and/or had six or more skin lesions and/or had two or more nerve trunks involved, were eligible. A detailed history was taken and physical and neurological examinations were performed. Nerve function was assessed at each visit with nerve conduction testing, warm and cold detection thresholds, vibrometry, dynamometry, monofilaments and voluntary muscle testing. Because the latter two are widely used in leprosy clinics, they were used as 'gold standard' for sensory and motor impairment. Other outcome events were type 1 and 2 reactions and neuritis. All subjects had a skin biopsy at registration, repeated at the time of an outcome event, along with a nerve biopsy. These were examined using a variety of immunohistological techniques. Blood sampling for serological testing was done at every 4-weekly clinic visit. At diagnosis, 115 patients had an outcome event of recent onset. Many people had skin lesions overlying a major nerve trunk, which were shown to be significantly associated with an increased of sensory or motor impairment. The most important adjusted odds ratios for motor impairment were, facial 4.5 (1.3-16) and ulnar 3.5 (1.0-8.5); for sensory impairment they were, ulnar 2.9 (1.3-6.5), median 3.6 (1.1-12) and posterior tibial 4.0 (1.8-8.7). Nerve enlargement was found in 94% of patients, while only 24% and 3% had paraesthesia and nerve tenderness on palpation, respectively. These increased the risk of reactions only marginally. Seven subjects had abnormal tendon reflexes and seven abnormal joint position sense. In all but one case, these impairments were accompanied by abnormalities in two or more other nerve function tests and thus seemed to indicate more severe neuropathy. At diagnosis, 38% of a cohort of newly diagnosed MB leprosy patients had recent or new reactions or nerve damage at the time of intake into the study. The main risk factor for neuropathy found in this baseline analysis was the presence of skin lesions overlying nerve trunks. They increased the risk of sensory or motor impairment in the concerned nerve by 3-4 times. For some nerves, reactional signs in the lesions further increased this risk to 6-8 times the risk of those without such lesions. Patients with skin lesions overlying peripheral nerve trunks should be carefully monitored for development of sensory or motor impairment.     

Factors influencing survival in children with recurrent neuroblastoma

Despite advances in multimodal therapy for neuroblastoma, survival from advanced disease remains poor. Children are now offered a wide variety of salvage regimens following relapse. A retrospective review was performed on 31 patients with recurrent neuroblastoma treated at one institution between 1995 and 2001. At initial diagnosis, 27 patients had metastatic disease and 11 had N-myc amplification (NMA). The median time to recurrence from diagnosis was 16.1 months. Seventeen patients received salvage therapy, with a median of three salvage regimens per patient. The median survival time from relapse was 8.4 months. The median survival time was significantly shorter for recurrence less than 6 months after stem cell transplantation (2.9 vs. 13.3 months; P = 0.003) and for patients with NMA (2.7 vs. 15.1 months; P < 0.0001). Overall, salvage therapy led to a significantly longer median survival time (22.4 vs. 3.3 months; P = 0.0003); however, salvage therapy extended the median survival time only from 2.2 to 3.2 months for patients with NMA and from 0.7 to 5.8 months for patients with early relapse after stem cell transplantation. Multiple salvage regimens prolong survival significantly, especially for patients with no NMA and for relapses more than 6 months after stem cell transplantation, but the long-term disease-free survival after recurrent disease remains dismal.