Cardiovascular outcomes of Nephrotic syndrome in childhood (CVONS) study: a protocol for prospective cohort study.

BACKGROUND: Nephrotic syndrome (NS) is characterized by dyslipidemia which is a well-known risk factor for atherogenesis. Atherosclerosis in childhood is mostly subclinical and endothelial dysfunction is known to precede this. Evidence for screening for endothelial dysfunction and cardiovascular risk factors and early identification of premature onset of atherosclerosis in childhood NS remains tenuous in the absence of well-designed prospective studies addressing cardiovascular comorbidity in NS. The objective of our study is to examine endothelial dysfunction and short-term cardiovascular outcomes in a carefully phenotyped cohort of patients with Nephrotic syndrome as compared to healthy controls. METHODS: In a multi-centric prospective cohort study, 70 Steroid Resistant NS (SRNS), 70 Steroid Sensitive (SSNS) patients along with 70 Healthy Controls are being recruited. After a baseline assessment of functional and structural status of heart (2D Echocardiography), arteries (Carotid Doppler and Intima Media Thickness measurements) and microcirculation [a combination of 2D Echocardiography, Laser Doppler Flowmetry (LDF) and Brachial Artery Flow mediated dilation (FMD) and Nail Fold Capillaroscopy (NFC)], the patients are being investigated for endothelial dysfunction. Venous blood sample (15 ml) is being collected for routine investigations and assay of biochemical endothelial markers through Flow Cytometry. The patients will be followed up at 12 months and 24 months after the recruitment to look for any change from baseline period. DISCUSSION: This study will able to provide a better understanding of the epidemiology of endothelial dysfunction and associated subclinical cardiovascular co-morbidity in childhood NS. Findings on characterization of prevalence of endothelial dysfunction and subclinical markers may be used to design future randomized controlled trials for evaluating the efficacy of preventive and therapeutic interventions in reducing the incidence of cardiovascular disease.

Posttransplant Lymphoproliferative Disorder: Experience from a Pediatric Nephrology Unit in North India.

Posttransplant lymphoproliferative disorder (PTLD) is reported in 1%-3% among pediatric renal allograft recipients. We report the experience of PTLD among pediatric renal allograft recipients at a pediatric nephrology center in North India. Four cases of PTLD were identified from among records of 95 pediatric renal allograft recipients over a period of 21 years. Constitutional and localizing symptoms were present in three patients each. The diagnosis was suggested on positron emission tomography in three patients and confirmed by histopathology in all. Sites affected included tonsils, cervical lymph nodes, duodenum, and para-aortic lymph nodes in one patient each. The lymphocytic infiltrate was polymorphic in three patients and monomorphic in one. Immunostaining suggested B-cell origin in all patients. There was evidence of Epstein-Barr virus infection in only one patient. The patients were successfully managed with reduction of immunosuppression (in all), rituximab (in 3), and excision of affected tissue (in 1). Over a follow-up period of 30-88 months, there were no episodes of disease recurrence or allograft rejection, and renal function was preserved.

Fluoride-associated ultrastructural changes and apoptosis in human renal tubule: a pilot study.

The susceptibility of the kidneys to fluoride toxicity can largely be attributed to its anatomy and function. As the filtrate moves along the complex tubular structure of each nephron, it is concentrated in the proximal and distal tubules and collecting duct. It has been frequently observed that the children suffering from renal impairments also have some symptoms of dental and skeletal fluorosis. The findings suggest that fluoride somehow interferes with renal anatomy and physiology, which may lead to renal pathogenesis. The aim of this study was to evaluate the fluoride-associated nephrotoxicity. A total of 156 patients with childhood nephrotic syndrome were screened and it was observed that 32 of them had significantly high levels ( p ≤ 0.05) of fluoride in urine (4.01 ± 1.83 ppm) and serum (0.1 ± 0.013 ppm). On the basis of urinary fluoride concentration, patients were divided into two groups, namely group 1 (G-1) ( n = 32) containing normal urine fluoride (0.61 ± 0.17 ppm) and group 2 (G-2) ( n = 32) having high urine fluoride concentration (4.01 ± 1.83 ppm). Age-matched healthy subjects ( n = 33) having normal levels of urinary fluoride (0.56 ± 0.15 ppm) were included in the study as control (group 0 (G-0)). Kidney biopsies were taken from G-1 and G-2 only, who were subjected to ultrastructural (transmission electron microscopy) and apoptotic (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling) analysis. Various subcellular ultrastructural changes including nuclear disintegration, chromosome condensation, cytoplasmic ground substance lysis, and endoplasmic reticulum blebbing were observed. Increased levels of apoptosis were observed in high fluoride group (G-2) compared to normal fluoride group (G-1). Various degrees of fluoride-associated damages to the architecture of tubular epithelia, such as cell swelling and lysis, cytoplasmic vacuolation, nuclear condensation, apoptosis, and necrosis, were observed.

Acute phase response in lame crossbred dairy cattle.

AIM: The study was undertaken to study acute phase response based on acute phase proteins (APPs) such as C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA), and fibrinogen in lame crossbred dairy cattle. MATERIALS AND METHODS: Lame animals (n=30) were selected within 3-7 days of being noticed as lame by the farm veterinarian, from a local dairy farm in southeast Ludhiana over a period of 6 months, stratified proportionately with respect to stage of lactation with non-lame healthy cows (n=10). All the cows were otherwise healthy and did not have any other inflammatory problems such as pneumonia, enteritis, mastitis, or any kind of acute uterine inflammation. Blood samples were collected from all the animals; serum and plasma samples were separated and stored at -20°C. The levels of CRP, Hp, and SAA were estimated using Sandwich ELISA, whereas fibrinogen was estimated by heat precipitation method. RESULTS: SAA levels in lame cows were significantly higher (22.19±0.85 µg/ml), approximately 3 times as compared to non-lame cows (8.89±0.72 µg/ml), whereas serum Hp concentration was approximately 20 times higher in the lame cattle (21.71±3.32 mg/dl) as compared to non-lame cows (1.17±0.07 mg/dl). Fibrinogen also increased in the lame cattle (3.97±0.22 g/L) as compared to non-lame group (1.40±0.17 g/L). Serum CRP levels analyzed in the lame cattle for the first time in the present study, and significant high concentration was appreciated in lame cattle (4.41±0.33 mg/L) as compared to non-lame cattle (0.61±0.14 mg/L). Lame cattle were having more of sole hemorrhages, sole ulcers, and white line lesions as compared to non-lame cattle. CONCLUSION: It can be concluded that lame cattle exhibit high levels of APPs including CRP, Hp, SAA, and fibrinogen as compared to non-lame cattle.

Parvovirus B19 infection-related complications in renal transplant recipients: treatment with intravenous immunoglobulin.

BACKGROUND: Chronic red cell aplasia can develop in immunocompromised patients including transplant recipients infected with parvovirus B19 (PV B19). Renal involvement with PV B19 infection is not well-recognized. METHODS: We diagnosed erythroid hypoplasia associated with PV B19 infection in three renal transplant recipients; one of them developed de novo collapsing glomerulopathy. These patients were treated with intravenous immunoglobulin (IVIG). RESULTS: In two patients, anemia responded promptly to IVIG therapy. One of them had recurrence of anemia that responded to a second course of IVIG. Despite IVIG treatment, persistent infection with PV B19, recurrent anemia, and de novo collapsing glomerulopathy leading to allograft failure developed in the third patient, who had received the most intense immunosuppression. CONCLUSIONS: These findings indicate that PV B19 infection in transplant recipients can cause chronic red cell aplasia that generally responds to IVIG therapy. In some patients, particularly those who are heavily immunosuppressed, infection may persist despite treatment. As the cellular receptor for PV B19 is expressed in the kidney, persistent infection may result in development of glomerulopathies in these patients.

Lung allograft dysfunction correlates with gamma-interferon gene expression in bronchoalveolar lavage.

BACKGROUND: Preceding episodes of acute cellular rejection (ACR) may predispose lung allografts to the subsequent development of irreversible dysfunction or bronchiolitis obliterans syndrome (BOS). Other histologic patterns such as bronchiolitis obliterans with organizing pneumonia (BOOP), organizing pneumonia, lymphocytic bronchiolitis and diffuse alveolar damage (DAD) may also adversely affect allograft function. We have previously reported the predominant expression of Th1 cytokines (IL-2 and interferon gamma) in rejecting and Th2 (IL-10) in a tolerant model of rat lung transplantation. Here we correlate the "Th1/Th2 paradigm" in clinical lung transplantation with histologic findings and assess the effect on serial spirometric function. METHODS: We examined the mRNA expression of IL-2, interferon gamma, IL-10 and ICAM-1 in 53 bronchoalveolar lavage (BAL) specimens from 23 lung transplant (LT) recipients utilizing qualitative "nested" reverse transcriptase polymerase chain reaction (RT-PCR). We also measured IgG1 and IgG2 levels in 44 BAL specimens by ELISA. The mRNA expression for cytokines, ICAM-1 and the IgG2/IgG1 ratios were correlated with the presence or absence of ACR and alternate "histologic patterns". Serial spirometry were analyzed for the 2-3 month interval before bronchoscopic (FOB) assessment to derive "baseline" forced expiratory volume-one second (FEV1) values. The change in FEV1 coincident with (deltaFEV1 pre) and for the 2-3 month interval subsequent to (deltaFEV1 post) FOB were expressed relative to "baseline" spirometric indexes. RESULTS: Detection of mRNA for interferon gamma and ICAM-1 correlated significantly with ACR, whereas IL-2 and IL-10 expression did not correlate. IL-10 was virtually "ubiquitous" in most BAL samples irrespective of the presence or absence of ACR. The highest correlation was observed with interferon gamma for acute cellular rejection whereupon the sensitivity was 77.7%, specificity 87.7%, positive predictive value 73.6% and negative predictive value 88.2%, although for ICAM-1 these values were 75%, 65.7%, 50.0% and 85.0%, respectively. Nevertheless, 4 of 5 episodes of respiratory tract infection (bacterial, CMV, Aspergillus spp.) were similarly associated with cytokine mRNA. The ratios of IgG2 to IgG1, a reflection of Th1/Th2 influence, were not statistically different when analyzed for the presence or absence of ACR (0.91+/-0.53 vs. 1.02+/-0.70, respectively; p = NS). By analysis of FEV1 trends, expression of interferon gamma was associated with a greater and persistent decrement (deltaFEV1 pre: -0.265+/-0.78 liters, and post: -0.236+/-0.1161; mean +/- SE) than ACR in the absence of interferon gamma expression (+0.158 +/- +0.065 and +0.236+/-0.007 liters, respectively) (Student-Newman-Keuls, p<.05). CONCLUSION: Our findings suggest that interferon gamma mRNA expression and ICAM-1 may be valuable in both the diagnosis and prognosis for lung allograft ACR. IL-10, a Th2 cytokine, was locally expressed both in the presence and absence of ACR. Expression of mRNA for interferon y in BAL and, to a lesser extent ICAM-1, were associated with increased lung allograft dysfunction. Whether BAL cytokine "immunosurveillance" would complement or possibly supplant a specific "histologic pattern" and thereby direct different therapies after lung transplantation, may be potentially rewarding areas of further investigation.

Serum antibodies to verotoxin-producing Escherichia coli (VTEC) strains in patients with haemolytic uraemic syndrome.

Serological evidence of infection with verotoxin-producing Escherichia coli (VTEC) was sought in 28 patients suffering from haemolytic uraemic syndrome (HUS) and 25 age- and sex-matched controls. ELISA was used to detect anti-lipopolysaccharide (LPS) antibodies to E. coli strains O157, O111, O26 and NCTC 10418, a non-VTEC strain, and Shigella dysenteriae O1. Sera from 19 of the HUS patients but from none of the 25 controls had significant antibody levels to the verotoxin-producing bacteria. Sera from 13 patients reacted with only one LPS of the four verotoxin-producing bacteria; sera from six reacted with more than one LPS antigen but not with LPS of E. coli NCTC 10418. Paired sera taken 2-3 weeks apart were obtained from 20 HUS patients; 14 of these had high levels of antibody in the acute phase sample. Analysis of antibody levels in the convalescent sera showed that one patient had an increase, one was unchanged and 12 patients had a decrease in antibody to the verotoxin-producing bacteria.

Acute renal failure in north Indian children.

The spectrum and outcome of acute renal failure (ARF) were studied in 205 children aged between 1 month and 12 yr. There were 145 boys and 60 girls; 23 per cent were below 1 yr and 49 per cent between 1 and 4 yr. The main causes of ARF were haemolytic uraemic syndrome (HUS) in 36 per cent, serious infections in 19 per cent, acute gastroenteritis and dysentery in 17 per cent, glomerulonephritis (GN) in 13 per cent and intravascular haemolysis (IVH) in 6 per cent. Most patients with HUS, serious infections and gastroenteritis were below 5 yr, whereas GN and IVH occurred in older children. HUS was mostly associated with dysentery; Shigella and several other pathogens were isolated from stools in 35 per cent. In most patients with HUS disseminated intravascular coagulation and renal cortical necrosis were present, with a high mortality. The outcome was also poor in infants with serious infections. IVH occurred in patients with G-6-PD deficiency. In such patients and in those with post-streptococcal GN the prognosis was good. Crescentic GN had a poor outcome. Our observations highlight the common and serious nature of ARF in India. However, most of the underlying causes are preventable.

Peripheral blood lymphocyte subsets in idiopathic nephrotic syndrome of childhood.

Lymphocyte subsets in the peripheral blood were examined in 34 patients with nephrotic syndrome [27 with minimal change nephrotic syndrome (MCNS), 7 with significant lesions] and 10 normal children. The investigations were done at the onset of disease before administering corticosteroids (n = 34), during the subsequent remission (n = 27), and the first relapse (n = 12). The proportions of T cell subsets (CD3, CD4 and CD8) were determined by immuno-alkaline phosphatase staining; interleukin-2 receptor (IL-2 R) positive cells, natural killer (NK) cells and B cells were studied by indirect immunofluorescence. No significant differences were found in the proportion of CD3, CD4, CD8 and IL-2 R positive cells in patients with MCNS as compared to controls. An increased proportion of NK and B cells was not specific to MCNS and was detected even in those with significant renal lesions. Our findings suggest that T lymphocyte subsets in MCNS are similar to those in normal children.

Intracranial tuberculoma. Evaluation and treatment.

We used computerized tomography (CT) to screen 83 patients with partial seizures who had 1) increased intracranial pressure; 2) evidence of systemic tuberculosis; or 3) focal neurological deficit. We found intracranial tuberculoma in 20 (24%). In addition, of 55 patients with tuberculous meningitis, 12 had associated tuberculoma. The image morphology on CT scans showed ring lesions (14), discs (10), and irregular coalescing masses (8). Perilesional edema frequently was present. After appropriate antitubercular therapy, clinical outcome for seizures, neurological deficit, and increased intracranial pressure was satisfactory. CT lesions regressed within 12 weeks of inauguration of medical therapy in most patients. Medical management of tuberculoma is advocated, with surgery limited to those in whom such treatment is ineffective.

Clinical profile of pulmonary nocardiosis.

Pulmonary nocardiosis mimics pulmonary tuberculosis in both clinical symptoms, being chronic in nature and radiological characteristics, and it is often wrongly treated with anti-tuberculosis drugs. The present study was undertaken to determine the prevalence of pulmonary nocardial infection in patients having chronic chest symptoms and to study their clinical response to specific chemotherapeutic agents. All the patients, who had a negative sputum for AFB on direct smear examination consecutively, were investigated for nocardiosis by examining the sputum with KOH preparation and modified Ziehl-Neelsen method. This was later confirmed by fungal culture of the sputum and inoculation on McClung's broth for paraffin baiting technique. Fibreoptic bronchoscopy was performed on all the suspected cases and the bronchial aspirate was examined similarly. The confirmed cases of nocardiosis were treated with cotrimaxazole and doxycycline for a total duration of six months. The prevalence of pulmonary nocardiosis in the present study was 1.9 percent. All the patients were immunocompetent. All the patients showed a good clinical response to chemotherapy at the end of six months of treatment. No relapse has been observed on follow up.

Spontaneous lung hernia.

A case of spontaneous thoracic type of acquired lung hernia in a diabetic obese patient is presented in this report. The patient has been on conservative medical therapy for the last six months.

Traditional Indian systems of medicine.

INTRODUCTION: A number of traditional systems of medicine exist in India of which Ayurveda is the most popular. Despite being in use for more than 3000 years, few properly designed trials have scientifically examined the clinical potential of Ayurvedic and other medications. METHODS: We reviewed the MEDLINE database to identify clinical trials conducted using traditional Indian medicines. Single case reports were excluded. RESULTS: Ayurvedic preparations have been successfully used for the treatment of bronchial asthma, ischaemic heart disease and hyperlipidaemia. Formulations containing curcumin were reported to reduce inflammation and disability in double-blind clinical trials on patients with rheumatoid arthritis. A number of products are reported to be useful in patients with acute viral hepatitis. A multicentric study by the Indian Council of Medical Research showed that a preparation from Pterocarpus marsupium was effective in reducing levels of blood glucose and glycosylated haemoglobin in patients with non-insulin-dependent diabetes mellitus. In another multicentric trial, patients with fistula-in-ano were randomised to surgery or application of medicated seton (Ksharsootra). Surgical treatment led to a faster cure but recurrence rates were lower with medicated seton. Administration of extract from Bacopa monnieri, to children with mental retardation, was reported to significantly improve short-term and long-term memory. CONCLUSIONS: Evidence-based studies on the efficacy and safety of traditional Indian medicines are limited. The essential ingredient in most formulations is not precisely defined. High quality studies are necessary to evaluate and compare the value of traditional Indian drugs to modern medicine.

Role of supravital staining of urine sediment and bright field microscopy in diagnosis of acute renal failure in bedside medicine.

BACKGROUND: An early accurate etiological categorization of acute renal failure (ARF) into acute glomerulonephritis (AGN), acute tubular necrosis (ATN) and acute interstitial nephritis (AIN) is very important in clinical medicine. METHODS: To evaluate the efficacy of a simple, cheap supravital staining method developed in our laboratory, we examined urine of 32 cases of ARF at their initial presentation in oliguric phase, which were later biopsied. The stain consisted of 1% crystal violet and 0.5% safranin in normal saline. The coverslip preparations of coded and stained urine sediments were examined under ordinary bright field microscope (BFM) by two independent observers. RESULTS: The renal biopsy showed 12 cases of AGN, 12 ATN and 8 AIN. The diagnosis could be predicted by supravital staining method in 75% cases with 95% uniformity among two observers with a sensitivity of 85.7% for AGN followed by AIN (80%) and ATN (75%). CONCLUSION: Thus this simple supravital staining technique can be used with ordinary BFM for accurate urine sediment analysis in cases of ARF in bedside medicine.

Management of acute renal failure.

Acute renal failure (ARF) is defined as an abrupt decline in the renal regulation of water, electrolytes, and acid-base balance. It continues to be an important factor contributing to the morbidity and mortality of critically ill infants and children. The frequency of specific diseases that result in ARF differs among different age-groups and geographical areas. The common causes in Indian children include hemolytic uremic syndrome, acute tubular necrosis, glomerulonephritis and urinary tract obstruction. Though the hallmark of renal failure is oliguria, there is increasing recognition of non-oliguric ARF often associated with the use of nephrotoxic drugs. The basic principles of management are avoidance of life-threatening complications, maintenance of fluid and electrolyte balance and nutritional support. Specific management of the underlying disorder is possible only in a minority of cases. All the major dialysis modalities--peritoneal dialysis (PD), hemodialysis (HD) and continuous hemofiltration--can be used to provide equivalent solute clearance and ultrafiltration. Peritoneal dialysis requires minimal equipment and infrastructure, and is easy to perform; this makes it the favoured modality in developing countries where resources for HD or continuous therapies may not be accessible. However, continuous hemofiltration is an excellent alternative to PD in patients with ARF and severe fluid overload. The prognosis of children with renal failure depends on the underlying condition and associated medical complications.

Urinary tract infections: evaluation and treatment.

Urinary tract infections (UTI) are the second most common bacterial infection in children after those of the respiratory tract. These infections are important in view of their acute morbidity and the long-term risk of renal scarring. Occurrence of UTI below two years of age, delay in starting treatment and presence of vesicoureteric reflux or obstruction are the chief risk factors associated with renal scarring. The classical features of UTI are absent in young children, who often present with few signs or symptoms other than fever. Since the diagnosis of UTI warrants a thorough evaluation subsequently, empiric treatment based on symptoms or urinalysis alone should be avoided. Therapy with appropriate antibiotics is started only after obtaining a urine culture. The distinction between upper and lower urinary tract infections is difficult and the choice of therapy guided by the patient's age and severity of clinical manifestations. All children with UTI should be investigated to identify those with an underlying urinary tract anomaly.

The profile and outcome of patients admitted to a pediatric intensive care unit.

The records of all admissions to a 6-bed pediatric intensive care unit (PICU) over a period of 6 years were reviewed. The age, diagnosis, clinical service provided, duration of stay and outcome were recorded. Of the 3025 children admitted, 2092 (69.2%) were males. Neonates constituted 13.1% (400) and infants 57.1% (1727) of total admissions. The duration of stay ranged from 6 hours to 46 days, and 61 patients stayed for longer than 13 days (long-stay patients). The most common cause for admission was septicemia, seen in 459 patients (14.8%); 418 (13.8%) children had congenital heart disease, 407 (13.5%) lower respiratory tract infections (LRTI) and 261 (8.6%) meningitis. The most common conditions necessitating long-stay in the PICU were meningitis (20%), Landry-Guillain-Barre syndrome (16.6%), acute renal failure (20%), and septicemia (16.6%). There were 721 deaths giving a mortality of 23.5%. Of these 134 (18.6%) were due to septicemia, 103 (14.2%) due to congenital heart disease, 77 (10.6%) due to meningitis and 55 (7.6%) due to LRTI. The highest case fatality rate was seen with encephalitis (52.6%), followed by hepatic coma (51.3%), malignancies (43.2%), septicemia (29.1%) and meningitis (29.5%). The mortality was lower (9.8%) in long-stay patients than in short-stay patients (24.6%). There was gradual increase in proportion of cases requiring interventions including artificial ventilation (1% to 35%), peritoneal dialysis (1.5% to 11%), insertion of central venous pressure lines (0 to 10%), over the last 6 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation and treatment of chronic renal failure.

Chronic renal failure (CRF) is the irreversible deterioration of renal function that gradually progresses to end stage renal disease (ESRD). The chief causes of CRF include obstructive uropathy, primary glomerular diseases, reflux nephropathy and hypoplastic or dysplastic kidneys. Progressive hyperperfusion and hyperfiltration causes increasing glomerular injury and further renal damage. Symptoms of CRF are usually seen when GFR is between 10-25% of normal. Children with severe CRF often suffer from failure to thrive, growth retardation, acidosis, anemia and renal osteodystrophy. Management of CRF aims at retarding progression of renal damage and treatment of complications related to renal dysfunction. Measures suggested to retard progression include protein restriction, strict control of hypertension, use of angiotensin converting enzyme inhibitors and control of hyperlipidemia. Appropriate amounts of protein and calories are recommended to prevent growth failure. Nutritional supplements are often required. The availability of recombinant erythropoietin, calcitriol and human growth hormone has significantly improved the management of these patients. Once ESRD supervenes, renal replacement therapy in the form of chronic peritoneal or hemodialysis and transplantation is necessary.

McCune Albright syndrome and hypophosphatemic rickets.

A 4 year-old girl had coxa vara, tibial bowing and hyperpigmented macules. The x-ray showed polyostotic fibrous dysplasia and evidence of rickets. Biochemical investigations confirmed hyperphosphaturic hypophosphatemic rickets. The literature has been reviewed.

Failure to isolate verotoxin producing Escherichia coli from patients of haemolytic uremic syndrome.

Haemolytic Uremic Syndrome (HUS) been defined as the simultaneous occurrence of acute renal failure in children with haemolytic anemia and thrombocytopenia. This clinical condition that has been recognized is an important cause of acute renal failure in children.