New insights from the genetic work-up in early onset nephrotic syndrome: report from a registry in western India.

BACKGROUND: Eighty-five percent of infants with congenital nephrotic syndrome (CNS) and 66% with infantile NS (INS) are likely to have a monogenic etiology. There exists a significant genetic variability between different regions and ethnic groups. This study aimed to determine the genetic defects in children with CNS and INS by establishing a registry in western India. METHODS: In this cross-sectional study, pediatric nephrologists from 13 private and government institutions shared relevant clinical data and details of the genetic evaluation of children presenting with NS within the first year of life. RESULTS: The median age at presentation was 9 months (range 1-23, IQR 3-13 months), history of consanguinity between parents existed in 14 patients (34%), family history of similar illness in 6 (15%), and extra-renal manifestations in 17 (41%). Twenty-five (61%) were confirmed to have a monogenic etiology. NPHS1 gene was the most implicated (9/25) followed by PLCE1 (5/25). There were 12 variants of uncertain significance (VUS) involving 10 genes (10/25, 40%), and no definite genetic abnormality was found in 4 (25%). A re-analysis of these VUS attempted 2-3 years later facilitated reclassification of 7/12 (58%); increasing the diagnostic yield from 61 to 68.2%. CONCLUSIONS: Consistent with worldwide data, variants in NPHS1 gene were the most common cause of NS in infancy; however, PLCE1 was implicated more frequently in our cohort. NUP93 and COL4A3 were reported in early onset NS for the first time. Reclassification of VUS should be attempted, if feasible, since it may lead to a useful revision of diagnosis.

Does deafness lead to enhancement of visual spatial cognition in children? Negative evidence from deaf nonsigners.

This study investigated whether deafness contributes to enhancement of visual spatial cognition independent of knowledge of a sign language. Congenitally deaf school children in India who were born to hearing parents and were not exposed to any sign language, and matched hearing controls, were given a test of digit span and five tests that measured visual spatial skills. The deaf group showed shorter digit span than the hearing group, consistent with previous studies. Deaf and hearing children did not differ in their performance on the visual spatial skills test, suggesting that deafness per se may not be a sufficient factor for enhancement of visual spatial cognition. Early exposure to a sign language and fluent sign skills may be the critical factors that lead to differential development of visual spatial skills in deaf people.

Thalidomide for systemic onset juvenile idiopathic arthritis.

Systemic onset juvenile idiopathic arthritis (SOJIA) is the most common autoimmune auto inflammatory disease in childhood. A sizeable number of these patients run a recalcitrant disease course, resistant to the conventional line of management, ultimately resulting in permanent disability from joint destruction, local growth deformities or iatrogenic side effects. The new biological agents although very effective, are beyond the affordability of most in our country. Thalidomide, a cheaper option has been shown to be very effective in the disease control of patients with SOJIA. We report three Indian children with a chronic refractory course of SOJIA, all of whom had failed conventional line of treatment but improved with thalidomide.

Acute renal failure secondary to ingestion of ayurvedic medicine containing mercury.

Several traditional medicines contain potentially toxic heavy metals. Heavy metal poisoning is not an uncommon cause of renal damage, although the diagnosis can be easily missed. We report a case of chronic ingestion of an ayurvedic medicine containing mercury in a 2-year-old girl, resulting in anuric renal failure due to acute interstitial nephritis.

A peroxisome proliferator-activated receptor-δ agonist provides neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.

Peroxisome proliferator-activated receptor (PPAR)-γ and PPARα have shown neuroprotective effects in models of Parkinson's disease (PD). The role of the third, more ubiquitous isoform PPARδ has not been fully explored. This study investigated the role of PPARδ in PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to model the dopaminergic neurodegeneration of PD. In vitro administration of the PPARδ antagonist GSK0660 (1 µM) increased the detrimental effect of 1-methyl-4-phenylpyridinium iodide (MPP⁺) on cell viability, which was reversed by co-treatment with agonist GW0742 (1 µM). GW0742 alone did not affect MPP⁺ toxicity. PPARδ was expressed in the nucleus of dopaminergic neurons and in astrocytes. Striatal PPARδ levels were increased (over two-fold) immediately after MPTP treatment (30 mg/kg for 5 consecutive days) compared to saline-treated mice. PPARδ heterozygous mice were not protected against MPTP toxicity. Intra-striatal infusion of GW0742 (84 µg/day) reduced the MPTP-induced loss of dopaminergic neurons (5036±195) when compared to vehicle-infused mice (3953±460). These results indicate that agonism of PPARδ provides protection against MPTP toxicity, in agreement with the effects of other PPAR agonists.

Interventions to reduce needle stick injuries at a tertiary care centre.

BACKGROUND: Occupational exposure to blood/body fluids is associated with risk of infection with blood borne pathogens like human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). MATERIALS AND METHODS: We carefully document needle stick injuries (NSI) and implement post-exposure prophylaxis (PEP). We report a four-year continuing surveillance study where 342 healthcare workers (HCWs) sustained NSI. PEP was given to HCWs injured from seropositive sources. If the source was HbsAg positive, HCWs were given a hepatitis B immunization booster. If the HCW was antiHBs negative, both hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine were administered. For HCWs who sustained injuries from HIV positive sources, antiretroviral therapy was started. Follow-up was done after three and six months of exposure. Recent interventions by the infection control committee at our hospital reduced NSI considerably during intravenous line administration and glucose monitoring. RESULTS AND DISCUSSION: Of 342 injuries, 254 were from known sources and 88 from unknown sources. From known sources, 37 were seropositive; 13 for HIV, 15 for HCV, nine for HBV. Sixty six sharp injuries were sustained through garbage bags, 43 during IV line administration, 41 during injection administration, 35 during needle recapping, 32 during blood collection, 27 during blood glucose monitoring, 24 from OT instruments, 17 during needle disposal, 16 while using surgical blade, 7 during suturing and 34 from miscellaneous sources. CONCLUSION: No case of seroconversion has taken place, so far, as a result of needle stick injuries at our centre.