Effectiveness of a comprehensive educational programme for Accredited Social Health Activists (ASHAs) to identify individuals in the Udupi district with bleeding disorders: A community-based survey.

INTRODUCTION: The awareness and knowledge on bleeding disorders is generally poor among the rural population. Accredited Social Health Activists (ASHAs) serve as the facilitators between the rural community and the health care system. Training of ASHAs in screening of rural population for early identification of bleeding disorders can enable prompt referral, timely detection and management of bleeding disorders. AIM: The aim of the study was to evaluate the effectiveness of an ASHA training programme for identification of suspected bleeding disorder cases. METHODS: A population-based, cross-sectional survey was implemented by 586 Accredited Social Health Activists (ASHAs) in rural Udupi district, who underwent a structured training programme on identification of bleeding disorders. A survey record book with a screening tool on assessment of bleeding symptoms was given to each ASHA. The screening tool consisted of symptoms related to bleeding disorders and family history of bleeding disorders. Using the screening tool, ASHAs carried out a door-to-door survey. After screening, those who reported with bleeding symptoms were referred by the ASHAs to the investigator, who conducted further assessment. A detailed bleeding history was documented and bleeding symptom assessment was carried out using bleeding assessment tool (BAT) at the haemophilia treatment centre. Further coagulation assessments were carried out as per the treatment centre protocol. This paper highlights the evaluation of an ASHA training programme on identification of individuals with bleeding symptoms in the rural population. RESULTS: A total of 586 trained ASHAs surveyed a population of 318 214 in rural Udupi district. Out of the 124 cases reported by ASHAs, 29 bleeding disorder cases were identified; haemophilia (A and B) was the most commonly found bleeding disorder 22 (75.8%), followed by von Willebrand disease (vWD) 3 (10.3%) and 4 (13.8%) immune-mediated thrombocytopenic purpura (ITP), with an overall prevalence of 2.2/10 000 population. CONCLUSION: Training ASHA health care workers, who are the most important link between the community and health services, resulted in increased awareness among the public for the early detection of bleeding disorders.

Vitamin D status and adequacy of standard supplementation in preterm neonates from South India.

OBJECTIVE: The aim of this study was to assess vitamin D status of preterm babies at birth and adequacy of daily supplementation with vitamin D. METHODS: This prospective cohort study recruited 111 preterm babies, 25 to 32 weeks' gestation from a tertiary care perinatal center in south India. Cord blood was assayed for serum calcium, phosphate, alkaline phosphatase, and 25-hydroxyvitamin D (25(OH)D). All of the babies were fed unfortified breast-milk and supplemented daily with calcium, phosphate, and 400 IU of vitamin D. At 6 weeks serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, and 25(OH)D levels were estimated. RESULTS: Of 111 preterm babies recruited, a total of 90 (81%) of the preterm babies were followed up until 6 weeks. The median (interquartile range) vitamin D level in the preterm group was 34.7 (25.6-50.1) and 19.3 (13.9-27.1) ng/mL at birth and 6 weeks, respectively. Using a cutoff value of <20 ng/mL to determine vitamin D insufficiency (VDI), it was observed that 12.6% of the babies were vitamin D insufficient at birth. This increased to 52.2% at 6 weeks despite the recommended supplementation with vitamin D (P < 0.001). CONCLUSIONS: The prevalence of VDI was not high at birth; however, a large proportion of preterm babies were vitamin D insufficient at 6 weeks despite being supplemented with vitamin D 400 IU/day. The recommended vitamin D supplementation of 400 IU appears to be inadequate to prevent VDI, and hence randomized controlled trials looking at higher doses of vitamin D supplementation are needed.

Cytomegalovirus Induced Collapsing Glomerulopathy and Necrotizing Glomerulonephritis in a Renal Allograft Recipient.

In renal allograft recipients, cytomegalovirus (CMV) typically causes tubulointerstitial nephritis. Only rarely glomeruli are involved. We present a rare case of CMV with collapsing glomerulopathy, necrotizing glomerulonephritis, and crescent formation in a renal allograft recipient. Immunohistochemistry confirmed CMV infection. The patient was started on valganciclovir and his renal function remained stable. A repeat renal biopsy performed three months later showed morphologically normal glomeruli and CMV immunostaining was also negative. Nephropathologists have to carefully screen for CMV in cases with crescentic or collapsing glomerulopathy as the later lesions resolve after treating the underlying viral infection. This study will add on to the various glomerular changes associated with CMV infection.

Task completion time: Objective tool for assessment of technical skills in laparoscopic simulator for urology trainees.

CONTEXT: Laparoscopic surgical simulation is a valuable training tool for urology trainees. AIMS: We assessed the validity of task completion time (TCT) as an objective tool for practicing and acquiring technical skills in a simulated laparoscopy environment. MATERIALS AND METHODS: Fifteen participants comprising postgraduate urology trainees from first to third year (n = 12), urology fellow (n = 1) and consultants (n = 2) underwent basic laparoscopic training on the "Beetle Universal" endotrainer. Training included 10 attempts each comprising four tasks; placing a ball in a cup (Task 1), threading five rings (Task 2), threading five balls (Task 3) and tying a suture (Task 4). Individual task (IT) time was measured. The TCT was defined as sum of IT time for a single attempt. STATISTICAL ANALYSIS USED: Statistical analysis was done by Pearson's correlation coefficient and student's t test using SPSS software 10. RESULTS: The average TCT for the first attempt to complete the four tasks by the participants was 76.5 +/- 13.0 min (range 38 to 92.5, skew -1.8), compared to the 10(th) attempt 33 +/- 4.23 min (range 25 to 38.5, skew -0.5). There was statistically significant correlation (r = mean -0.91, range -0.97 to -.83, skew -0.5), (P = < 0.001) between the number of attempts and decreasing TCT for all participants. Correlation decreased when TCT between the sixth to 10(th) attempt was compared (r = mean -0.67, range -0.99 to 0.76). CONCLUSIONS: The TCT is practical, easy and a valid objective tool for assessing acquired technical skills of urology trainees in a laparoscopic simulated environment.

Adenovirus Interstitial Nephritis: An Unusual Cause for Early Graft Dysfunction.

We describe a rare case of adenovirus interstitial nephritis in a 37-year-old man, 4 weeks following deceased donor renal transplantation. He presented with gross hematuria and acute graft dysfunction. A renal biopsy revealed necrotizing tubulointerstitial nephritis with intranuclear viral inclusions in the tubular epithelial cells. Immunohistochemistry and polymerase chain reaction confirmed adenovirus infection. Reduction in immunosuppression alone resulted in rapid improvement of graft function. Awareness of the clinical and characteristic biopsy findings may help establish the correct diagnosis, which is crucial as disseminated infection, if left untreated, is associated with a high mortality rate in renal allograft recipients.

Amyloid Proximal Tubulopathy and Amyloid Casts: An Unusual Finding in Multiple Myeloma.

Patients with multiple myeloma (MM) often develop renal manifestations. The majority of cases present as cast nephropathy, amyloid light-chain (AL) amyloidosis, and monoclonal immunoglobulin deposition disease. AL amyloidosis usually involves the glomeruli, blood vessels, and interstitium. It is extremely uncommon to find isolated intratubular deposition of AL amyloid. Our patient presented with rapid worsening of renal function due to isolated intratubular deposition of AL amyloid, where the biopsy revealed amyloid proximal tubulopathy and amyloid cast nephropathy. Our case provides new insights into the complicated pathophysiology of the abnormal light chains in MM. This case is, to our knowledge, the second case of amyloid proximal tubulopathy reported in literature.

Collapsing Glomerulopathy and Thrombotic Microangiopathy in Postpartum Period: Two Case Reports.

Collapsing glomerulopathy (CG) is a distinct histopathologic pattern of glomerular injury characterized by global/segmental wrinkling of the glomerular basement membrane with podocyte hyperplasia and hypertrophy along with tubulointerstitial changes. There is no specific treatment for CG due to etiological heterogeneity, and newer insights into the pathogenesis may lead to the development of targeted therapy. The most common form of CG is the primary or idiopathic followed by secondary (due to viral infections, autoimmune disease, drugs, etc.) and genetic causes. Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ failure of variable severity. We here present two young women with preeclampsia who presented with acute kidney injury, anemia, and schistocytes in peripheral smear suggestive of TMA. Renal biopsy showed interesting histopathology of CG in addition to TMA in the first patient and CG alone in the second. Both the patients received supportive therapy while the first patient also received plasmapheresis. One patient had complete recovery, and other had partial recovery of renal function at last follow-up. Combined histopathological lesion of CG with TMA has never been reported in postpartum period so far in literature.

The Spectrum of Focal Segmental Glomerulosclerosis from Eastern India: Is It Different?

Focal segmental glomerulosclerosis (FSGS) is a disease that is defined entirely by its histopathological appearance. The recent Columbian classification has grouped this disease into various types based on the light microscopic description. There is a paucity of data describing the distribution of its various subtypes from the Indian subcontinent. This study was undertaken with the aim to throw light on the epidemiology and clinical features of primary FSGS in Eastern India. This retrospective study includes our cohort of biopsy-proven FSGS who presented to us from June 2009 to July 2011 and the analysis of their presenting clinical and histopathological features from our center in East India. Out of 347 patients diagnosed with FSGS in this period, 224 patients were included in the study. A total of 167 cases were of not otherwise specified (NOS) variant (74.5%), 30 tip variant (13.39%), 14 perihilar (6.25%), 8 cellular (3.57%), and 5 to the collapsing variant (2.23%). The maximum proteinuria at presentation was seen with the tip variant (7.98 ± 6.6 g/24 h), and the renal functions were most deranged at presentation with the collapsing variant. These findings were different from those described in other populations including higher prevalence of the tip and the perihilar variant, significant difference in the degree of hypertension, proteinuria, and renal dysfunction among the different variants. The Columbian classification has helped to stratify the outcomes of this glomerular disease with respect to its clinical presentation as well as histopathological features. However, the characteristics of the various variants do show a distinctive pattern in various populations based on ethnicities.

Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection.

Neonatal rotavirus infections are predominantly asymptomatic. While an association with gastrointestinal symptoms has been described in some settings, factors influencing differences in clinical presentation are not well understood. Using multidisciplinary approaches, we show that a complex interplay between human milk oligosaccharides (HMOs), milk microbiome, and infant gut microbiome impacts neonatal rotavirus infections. Validating in vitro studies where HMOs are not decoy receptors for neonatal strain G10P[11], population studies show significantly higher levels of Lacto-N-tetraose (LNT), 2'-fucosyllactose (2'FL), and 6'-siallylactose (6'SL) in milk from mothers of rotavirus-positive neonates with gastrointestinal symptoms. Further, these HMOs correlate with abundance of Enterobacter/Klebsiella in maternal milk and infant stool. Specific HMOs also improve the infectivity of a neonatal strain-derived rotavirus vaccine. This study provides molecular and translational insight into host factors influencing neonatal rotavirus infections and identifies maternal components that could promote the performance of live, attenuated rotavirus vaccines.

Structural compromise of disallowed conformations in peptide and protein structures.

Using a data set of 454 crystal structures of peptides and 80 crystal structures of non-homologous proteins solved at ultra high resolution of 1.2 A or better we have analyzed the occurrence of disallowed Ramachandran (phi, psi) angles. Out of 1492 and 13508 non-glycyl residues in peptides and proteins respectively 12 and 76 residues in the two datasets adopt clearly disallowed combinations of Ramachandran angles. These examples include a number of conformational points which are far away from any of the allowed regions in the Ramachandran map. According to the Ramachandran map a given (phi, psi) combination is considered disallowed when two non-bonded atoms in a system of two-linked peptide units with ideal geometry are prohibitively proximal in space. However, analysis of the disallowed conformations in peptide and protein structures reveals that none of the observations of disallowed conformations in the crystal structures correspond to a short contact between non-bonded atoms. A further analysis of deviations of bond lengths and angles, from the ideal peptide geometry, at the residue positions of disallowed conformations in the crystal structures suggest that individual bond lengths and angles are all within acceptable limits. Thus, it appears that the rare tolerance of disallowed conformations is possible by gentle and acceptable deviations in a number of bond lengths and angles, from ideal geometry, over a series of bonds resulting in a net gross effect of acceptable non-bonded inter-atomic distances.

The Epidemiology, Clinical Features, and Outcome of Infection-related Glomerulonephritis from East India: A Single Center Experience.

Infection-related glomerulonephritis (IRGN) is an example of immunological renal injury due to non-renal infections. With the changing face of IRGN over the years, renal biopsy definitely has an important role to play in differentiating this disease from the other masquerades and helps in prognosticating the long-term outcomes. This prospective study includes biopsy-proven IRGN cases who presented to us from July 2010 to July 2013 from a single center in East India. Of the 168 patients suspected and screened, 137 patients were proved to have IRGN. About 11.67% cases were proven to be immunoglobulin A-IRGN variant. The mean age of presentation was 22.7 ± 15.8 years with a slight male preponderance. A nephrotic range of proteinuria was seen in 13.8% cases and 17.5% patient required renal replacement therapy at presentation. Around 8.75% patients had persistent proteinuria despite normal renal function beyond 6 months of follow-up and 8.09% patients progressed to chronic kidney disease. It may no longer be classified as a glomerular disease with the definite favorable outcome as an important number of patients may progress to chronicity following this disease. Renal biopsy plays an important role in the assessment of prognosis of IRGN and detection of the presence of other underlying glomerulonephritis and should be considered early, especially in patients with atypical presentation.

Thrombotic microangiopathy due to Viperidae bite: Two case reports.

Snake bite is mainly an occupational hazard and causes serious health problems in rural India. Acute kidney injury (AKI) occurs in 5-30% cases. Renal pathologic findings include acute tubular necrosis, cortical necrosis, interstitial nephritis, glomerulonephritis, and vasculitis. Thrombotic microangiopathy (TMA) occurrence after a snake bite is reported rarely. Here, we present two patients who developed TMA after viper bite treated with hemodialysis and plasmapheresis. Renal biopsy showed fibrin thrombi in glomeruli and arterioles with cortical necrosis. One patient progressed to end-stage renal disease and other was lost to follow-up. TMA should be considered as a possible pathogenesis of AKI after snake bite. The role of plasma exchanges in snake bite TMA is yet to be defined.

Lupus podocytopathy: An important differential diagnosis of nephrotic syndrome in systemic lupus erythematosus.

Some patients with systemic lupus erythematosus (SLE) present with sudden onset of nephrotic syndrome and biopsy findings may be of minimal change disease or focal segmental glomerulosclerosis with diffuse foot process effacement on electron microscopy but without significant immune deposits. This entity is termed lupus podocytopathy. Clinicians and renal pathologists need to be aware of this condition. Though steroid sensitive, it needs follow-up to recognize flare and class change, thereby optimizing therapy.

Lymphoblastic lymphoma presenting as bilateral renal enlargement diagnosed by percutaneous kidney biopsy: Report of three cases.

Renal involvement by lymphoma can be a diagnostic challenge. Acute kidney injury (AKI) is an unusual manifestation of lymphomatous infiltration in the kidneys. We report three cases of lymphoblastic lymphoma, a very rare form of lymphoma, presenting with AKI and bilateral enlargement of kidneys, diagnosed by percutaneous kidney biopsy. Lymphomatous infiltration should be suspected with such clinical presentation. Kidney biopsy is a valuable diagnostic tool, to establish the correct diagnosis and subtype of lymphoma for timely initiation of therapy for these aggressive hematological malignancies.

Membranous nephropathy as a rare renal manifestation of IgG4-related disease.

IgG4-related disease, a newly described immune-mediated disorder with tissue infiltration of IgG4-positive plasma cells, has been reported in nearly every organ. In the kidney, it manifests as IgG4-related tubulointerstitial nephritis (TIN) but may also present as membranous nephropathy. We report a patient with IgG4 renal disease who had membranous nephropathy as well as TIN.

The bone marrow in Hodgkin's disease--a two year study.

A total of forty bone marrow trephine biopsies and aspirates were studied from thirty five patients suffering from Hodgkin's disease during the two year period 1994 and 1995. Of these twenty five were at the time of diagnosis of the disease and fifteen after treatment. The biopsies were studied for incidence of involvement as well as associated findings in both the positive and negative biopsies. A comparison of the trephine biopsy with marrow aspirate with respect to yield of positivity was made. Five patients (20%) at the time of diagnosis and two (13.33%) after treatment showed involvement of the marrow. None of the seven corresponding aspirates were positive for involvement showing that biopsies were superior to aspirates in detecting marrow infiltration in Hodgkin's disease. Suppression of the marrow, fibrosis and lymphocytic aggregates were the other findings in positive biopsies. Eosinophilia and myelosuppression were notable changes in the negative biopsies. One biopsy also showed granulomas. The probable significance of these findings are also discussed.

Seasonality and other epidemiological features of haemolytic uraemic syndrome and E. coli O157 isolates in Scotland.

The main objective was to determine whether there was seasonality in presentation of haemolytic uraemic syndrome (HUS) in children and adults, and compare this with the reporting of E. coli O157. The data came from Scotland, examining admissions during 1980-95 and E. coli isolates 1984-95. Seasonality was sought by fitting a sine curve to monthly or four-weekly data throughout the year. Seasonality was present for HUS and E. coli isolates in patients under 15 years of age but not in those above that age. The highest point of the sine curve was in July/August but there was a high plateau from June to September. The timing was similar to other diarrhoeal disease. This is an epidemiological study, the purpose being to clarify the seasonal features of HUS. E. coli infection is an important food hazard and a sound knowledge of the epidemiology, could lead to optimal control. The Scottish geographic distribution is illustrated.

IgA dominant postinfectious glomerulonephritis: Report of two cases.

Immunoglobulin A (IgA) dominant postinfectious glomerulonephritis (IgA PIGN) is a distinct clinical entity increasingly recognized in adult. It usually presents with reduced glomerular filtration rate, heavy proteinuria, and has unfavorable prognosis. Immunofluorescence study of renal biopsy specimens have IgA as dominant or codominant antibody. We encountered two cases of IgA dominant PIGN recently presenting as rapidly progr essive glomerulonephritis and managed conservatively. Both the patients are on follow-up and do not have complete recovery of renal function till date. Long-term follow-up is needed to assess the progression of the disease in these patients.