Effect of age on auditory evoked responses (AER) and augmenting-reducing

Auditory evoked responses (AER) were obtained from Cz and Fz in 30 adults (14 male, 16 female) from 20-80 years old. Sound bursts (1000 Hz-200 msec) of four different intensities were used. Peak to trough amplitudes of P1N1 and N1P2 and latencies of P1, N1 and P2 peaks were measured with increasing stimulus intensity and slopes of amplitude - intensity and latency - intensity curves were analysed for assessment of an age effect. The main result is that the increase in P1N1 amplitude with increasing stimulus intensity is more pronounced in older persons. Previous studies have established a negative correlation between the augmenting-reducing responses and HVA levels in the CSF (with lower amounts of HVA in the CSF of "augmenters"). Decreased dopamine metabolism in old subjects could account for our results, so further studies should focus on patients with pathological dopamine deficiencies.     

Chronic Granulomatous Disease: Two Decades of Experience From a Tertiary Care Centre in North West India

Chronic granulomatous disease (CGD) results from an inherited defect in the phagocytic cells of the immune system. It is a genetically heterogenous disease caused by defects in one of the five major subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. There is a paucity of data from India on CGD. We herein describe the clinical features in 17 children with CGD from a single tertiary referral center in India. A detailed analysis of the clinical features, laboratory investigations and outcome of 17 children 7 with X-linked (XL) and 10 with autosomal recessive (AR) form was performed. Diagnosis of CGD was based on an abnormal granulocyte oxidative burst evaluated by either Nitroblue Tetrazolium (NBT) test or flow cytometry based Dihyrorhodamine 123 assay or both. The molecular diagnosis was confirmed by genetic mutation analysis in 13 cases. The mean age at diagnosis and the age at onset of symptoms was significantly lower in children diagnosed with XL- CGD compared those with AR disease. Mutations were detected in CYBB gene in 6 patients with XL-CGD and NCF-1 gene mutations were observed in 7 cases of AR- CGD. The course and outcome of the disease was much worse in children diagnosed with X-linked form of disease compared to AR forms of the disease; 4/7 (57 %) children with X-CGD were dead at the time of data analysis. This is one of the largest series on chronic granulomatous disease from any developing country.     

Frosted branch angiitis associated with rapidly progressive glomerulonephritis

Simultaneous occurrence of frosted branch angiitis and immune-mediated rapidly progressive glomerulonephritis is reported. The two diseases possibly share a common immune mechanism. Patients of frosted branch angiitis should undergo complete systemic evaluation including renal function tests even if the patient is systemically asymptomatic.     

Clinico-immunological profile of juvenile rheumatoid arthritis at Chandigarh

OBJECTIVE: To study the clinical and immunological profile of children with juvenile rheumatoid arthritis (JRA). DESIGN: Retrospective hospital based study. SETTING: Tertiary level center of North India. SUBJECTS:74 patients attending the Pediatric Rheumatology and Immunology Clinic over last 5 years. RESULTS: The patients were aged between 9 months to 12 years with male female ratio of 1.8:1. Eleven (14.9%) patients had systemic onset JRA, 28 (37.8%) had polyarticular onset type and 35(47.3%) had pauciarticular onset type JRA. Uveitis was present only in one patient and rheumatoid nodules were present in 4(5.4%) patients. Rheumatoid factor was positive in 2(2.7%) and antinuclear antibody was present in one patient only. HLA-B27 was positive in 4 children. Two patients developed amyloidosis. CONCLUSION:The clinico-immunological profile of JRA at Chandigarh appears to be some what different from that reported from other centers in India.     

Protective effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on glomerular protein permeability barrier

BACKGROUND: Proteinuria is a significant problem in medicine today, although glomerular events underlying it are unknown. Products of cytochrome P450 (CYP450) pathway of arachidonic acid metabolism are increasingly recognized as playing major roles in renal function. We used in vitro albumin permeability (P(alb)) as a measure of injury and puromycin aminonucleoside (PAN) as an injurious agent to test the hypothesis that 20-hydroxyeicosatetraenoic acid (20-HETE) protects the glomerular filtration barrier from increased P(alb). METHODS: We determined P(alb) in the following experimental groups: (1) isolated rat glomeruli incubated with PAN (5 microg/mL) for 5, 15, 30 or 60 minutes; (2) isolated glomeruli preincubated with 20-HETE (1.0 nmol/L to 100 nmol/L) for 15 minutes followed by additional incubation with PAN (5 microg/mL) for 15 minutes; (3) isolated glomeruli from rats treated with the CYP450 4A inducer clofibrate, and incubated with PAN (5 microg/mL) for 15 minutes; and (4) appropriate controls for each group. CYP450 4A levels were measured in glomeruli isolated from rats treated with clofibrate or vehicle. RESULTS: PAN increased P(alb) of isolated glomeruli as early as 5 minutes (P(alb) 0.33 +/- 0.21, P < 0.05 vs. control). Maximal effect occurred at 30 minutes (P(alb) 0.75 +/- 0.16, P < 0.001 vs. control). Inclusion of 20-HETE (100 nmol/L) blocked the increased P(alb) caused by PAN (P(alb) 0.05 +/- 0.13). Likewise, glomeruli isolated from rats treated with clofibrate were protected from PAN-induced increase in P(alb) (P(alb) 0.19 +/- 0.03). Treatment with clofibrate significantly increased glomerular CYP450 4A expression. CONCLUSION: PAN directly and immediately affects the glomerular permeability barrier. Furthermore, exogenous 20-HETE or clofibrate treatment protects glomeruli from increased P(alb) caused by PAN. Relative lack of 20-HETE may be a general characteristic of proteinuric states. Conversely, measures used to treat and/or prevent proteinuria may act to restore or increase glomerular 20-HETE levels.