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.

Preliminary study in to the incidence of gastroesophageal reflux (GER) in high risk neonates admitted to NICU.

OBJECTIVE: To find out the incidence of Gastro-esophageal reflux (GER) in neonates at risk for it and compare this with the incidence in the controls. METHODS: This prospective case control study was conducted on 34 neonates. Twenty-four test high risk neonates comprised of preterms, neonates on mechanical ventilation neonates with ALTE(Acute Life Threatening Episode) and post-operative neonates (Tracheo-esophageal fistula, congenital diaphragmatic hernia). There were ten matched controls. Esophageal pHmetry was done using double sensor antimony pH probe and the two groups were compared. Significant reflux was defined as any reflux on pharyngeal sensor (grade 4 reflux) or a Reflux Index or RI (amount of time the esophageal pH remained <4) >20%.Analysis were done using Fisher Exact t test and Chi square test. RESULTS: Mean gestational age was 34.87(3.86) wk and 33.7(3.29) wk in the test and control groups respectively, while mean BW was 2186.02(814.57) g and 1851.2(592.93) g in each respective group. In the test group 10 were symptomatic, 5 were on mechanical ventilation, 8 were on CPAP and one was post-operation case. Difference in the incidence of significant RI in test and control group was not statistically significant. Incidence between various group of neonates in test group showed no statistical significance either. However, the incidence of grade IV reflux in test group was 8/24 and control 0/10 and this difference was statistically significant. Reflux did increase when period of gestation decreased and the difference was statistically significant. CONCLUSIONS: Clinically significant grade IV GER was more in high risk (test) neonates than control.

Revised statement on management of urinary tract infections.

JUSTIFICATION: In 2001, the Indian Pediatric Nephrology Group formulated guidelines for management of patients with urinary tract infection (UTI). In view of emerging scientific literature, the recommendations have been reviewed. PROCESS: Following a preliminary meeting in November 2010, a document was circulated among the participants to arrive at a consensus on the evaluation and management of these patients. OBJECTIVES: To revise and formulate guidelines on management of UTI in children. RECOMMENDATIONS: The need for accurate diagnosis of UTI is emphasized due to important implications concerning evaluation and follow up. Details regarding clinical features and diagnosis, choices and duration of therapy and protocol for follow up are discussed. UTI is diagnosed on a positive culture in a symptomatic child, and not merely by the presence of leukocyturia. The need for parenteral therapy in UTI in young infants and those showing toxicity is emphasized. Patients with aysmptomatic bacteriuria do not require treatment. The importance of bowel bladder dysfunction in the causation of recurrent UTI is highlighted. Infants with the first UTI should be evaluated with micturating cystourethrography. Vesicoureteric reflux (VUR) is initially managed with antibiotic prophylaxis. The prophylaxis is continued till 1 year of age in patients with VUR grades I and II, and till 5 years in those with higher grades of reflux or until it resolves. Patients and their families are counselled about the need for early recognition and therapy of UTI. Children with VUR should be followed up with serial ultrasonography and direct radionuclide cystograms every 2 years, while awaiting resolution. Siblings of patients with VUR should be screened by ultrasonography. Children with renal scars need long term follow up on yearly basis for growth, hypertension, proteinuria, and renal size and function.

Clinicopathological Spectrum of Renal Biopsies in Children.

BACKGROUND: Renal biopsy has revolutionized the study of glomerular diseases. A retrospective analysis of 104 consecutive renal biopsies performed in children at a tertiary care referral centre over five years is presented. METHODS: All the biopsies were performed non-ultrasound guided by a single consultant nephrologist. Trucut needles were used in the initial few years and a Magnum biopsy gun (Bard) over subsequent three years. There were 66 boys and 38 girls. RESULT: A male predominance occurred in the older and younger patients. The male: female ratio was 2.2:1, 1:1, and 2.7:1 for the age groups below five years, 5-10 years and above 10 years respectively. All patients tolerated the biopsy well and success rate was 94%. There were minimal complications in the form of post biopsy haematuria (33.3%). Haematuria was mild in most of the cases and settled down within 24 hours. None required transfusion. However, 60% patients had mild discomfort in the form of local pain. There was no mortality, infection or renal loss. The most common indication for a kidney biopsy was nephrotic syndrome. Out of 104 biopsies, 85 were in children with nephrotic syndrome. The commonest primary renal pathology was mesangial proliferative glomerulonephritis (38%), minimal change disease (19%), focal segmental glomerulosclerosis (15%) and membranoproliferative glomerulonephritis (7%). CONCLUSION: Renal biopsy is a safe procedure in experienced hands and the commonest indication for a biopsy in children remains nephrotic syndrome.

Growth in Children with Steroid Sensitive Nephrotic Syndrome.

BACKGROUND: Nephrotic syndrome in children usually has an onset between 2-8 years of age and steroids form the mainstay of management. Therapy may affect growth in children with relapsing nephrotic syndrome. This study was carried out to correlate growth with the cumulative dose of steroids in children with steroid sensitive nephrotic syndrome (SSNS). METHODS: Data of 35 children with SSNS was analysed retrospectively. They were divided into two groups. Group I received prednisolone only and Group II received levamisole and or cyclophosphamide in addition to steroids. Their heights were recorded at the time of inclusion and again one year later. The SD scores for age were determined. Growth rate as a change in the SD score over one year (Δ SD score) was correlated to the cumulative dose of steroids over the same period using the Pearson's correlation. RESULT: There were 24 (68.6 %) boys and 11 (31.4 %) girls (M:F ratio 2.18:1) in the age group of 17 months to 11 years at inclusion. Group I constituted 19 (54.2 %) and Group II, 16 (45.8 %). Pearson's correlation coefficients for all children, Groups I and II were -0.341, -0.441 and -0.255 respectively indicating "Fair correlation". This indicates that as the cumulative dose of steroid increases the growth retardation becomes more apparent. CONCLUSION: Growth retardation is proportional to the cumulative dose of steroids in children with SSNS.

Spectrum of Childhood Tuberculosis in BCG Vaccinated and Unvaccinated Children.

BACKGROUND: Childhood tuberculosis remains a major public health problem in India. We evaluated the impact of BCG vaccination on childhood tuberculosis and the underlying risk factors. METHODS: 100 consecutive children below 12 years diagnosed to have tuberculosis based on the WHO and IAP consensus statement were included in the study. RESULT: Majority(42%) of children with tuberculosis were below four years of age. History of contact with a case of tuberculosis was present in 41 cases. BCG scar was present in 77 cases indicating a poor coverage/uptake of BCG vaccination. Pulmonary form of tuberculosis was seen in 52 and extra pulmonary form in 41 cases. Tubercular lymphadenitis was seen in seven cases, of which more than 70 % were in BCG vaccinated group. There was no statistically significant difference in the type of tuberculosis (pulmonary or extra pulmonary) and BCG vaccination. In the extra pulmonary form, 13 children had neuro-tuberculosis, of which 66% were in BCG unvaccinated group, which was statistically significant (p=0.011). The underlying risk factors were poor socioeconomic status (62%), malnutrition (61%) and poor immunization coverage. CONCLUSION: Higher incidence of pulmonary tuberculosis in BCG vaccinated group was not statistically significant. However, high incidence of neuro-tuberculosis in BCG unvaccinated group was statistically significant. The underlying risk factors were poor socio-economic status, malnutrition and poor immunization coverage and should be taken into consideration in order to prevent morbidity and mortality due to tuberculosis in children.

Novel role of curcumin in the prevention of cytokine-induced islet death in vitro and diabetogenesis in vivo.

BACKGROUND AND PURPOSE: Oxidative stress caused by cytokine exposure is a major cause of pancreatic islet death in vitro and of diabetogenesis. Antioxidant compounds may prevent cytokine-induced damage to islet cells. Hence, we studied the potential of curcumin, an antioxidant and anti-inflammatory compound, in vitro to protect islets against pro-inflammatory cytokines and in vivo to prevent the progression of diabetes induced by multiple low doses of streptozotocin (MLD-STZ). EXPERIMENTAL APPROACH: Pancreatic islets from C57/BL6J mice were pretreated with curcumin (10 microM) and then exposed to a combination of cytokines. Islet viability, reactive oxygen species (ROS), NO, inducible NO synthase and NF-kappaB translocation were studied. Curcumin pretreated (7.5 mg kg(-1) day(-1)) C57/BL6J mice were given MLD-STZ (40 mg kg(-1)), and various parameters of diabetes induction and progression were monitored. KEY RESULTS: Curcumin protected islets from cytokine-induced islet death in vitro by scavenging ROS and normalized cytokine-induced NF-kappaB translocation by inhibiting phosphorylation of inhibitor of kappa B alpha (IkappaBalpha). In vivo, curcumin also prevented MLD-STZ, as revealed by sustained normoglycaemia, normal glucose clearance and maintained pancreatic GLUT2 levels. Pro-inflammatory cytokine concentrations in the serum and pancreas were raised in STZ-treated animals, but not in animals pretreated with curcumin before STZ. CONCLUSIONS AND IMPLICATIONS: Here, we have demonstrated for the first time that curcumin in vitro protects pancreatic islets against cytokine-induced death and dysfunction and in vivo prevents STZ-induced diabetes.

Isolated islets in diabetes research.

This review highlights some recent developments and diversified applications of islets in diabetes research as they are rapidly emerging as a model system in biomedical and biotechnological research. Isolated islets have formed an effective in vitro model in antidiabetic drug development programme, screening of potential hypoglycaemic agents and for investigating their mechanisms of action. Yet another application of isolated islets could be to understand the mechanisms of beta cell death in vitro and to identify the sites of intervention for possible cytoprotection. Advances in immunoisolation and immunomodulation protocols have made xeno-transplantation feasible without immunosuppression thus increasing the availability of islets. Research in the areas of pancreatic and non pancreatic stem cells has given new hope to diabetic subjects to renew their islet cell mass for the possible cure of diabetes. Investigations of the factors leading to differentiation of pancreatic stem/progenitor cells would be of interest as they are likely to induce pancreatic regeneration in diabetics. Similarly search for the beta cell protective agents has a great future in preservation of residual beta cell mass left after diabetogenic insults. We have detailed various applications of islets in diabetes research in context of their current status, progress and future challenges and long term prospects for a cure.

An Initial Experience of Continuous Peritoneal Dialysis in Children in the Armed Forces.

BACKGROUND: Continuous peritoneal dialysis (CPD) is a modality of renal replacement therapy in children with renal failure. A retrospective study analysis of CPD data over four years at our center was carried out. METHODS: Ten children with renal failure on CPD were included. Depending on the supply, peritoneal dialysis (PD) fluids of two different brands were used in the same patients over time. The patient months of CPD were divided into two groups based on the brand of PD fluid used. The rates of complications with the two different fluid brands were compared. RESULTS: The mean age of our patients was 8.8 ± 2.51 years (range 4 - 13), with a total of 141 patient months of CPD. The mean follow up period was 13.6 months (range 1- 48). The commonest underlying renal pathology was focal segmental glomerulosclerosis in 30%, followed by cresentric glomerulonephritis in 20%. Peritonitis rate was 0.48 episodes per patient year. Patients in Group I had one episode of peritonitis per 53.5 patient months and Group II had one episode per 7.25 patient months (p= 0.021, relative risk of 7.3). Patients in Group I had one episode of hypertensive encephalopathy per 107 patient months and Group II had one episode per 4.8 patient months (p= 0.001, relative risk of 21.9). On analyzing the outcome, four patients were eventually transplanted, three continued on CPD awaiting a renal transplant, two died and one recovered spontaneously. CONCLUSION: CPD is an effective bridge to renal transplant in children with end stage renal disease. The risk of developing peritonitis and hypertensive encephalopathy varied with the brand of fluid used over time in the same set of patients.

Use of the Internet as a resource of health information by patients: a clinic-based study in the Indian population.

BACKGROUND: There is abundant literature documenting that the Internet is fast changing the way patients access health-related information, learn about their illnesses, and make healthcare-related decisions. However, there is hardly any data regarding Indian patients accessing health-related information available on the Internet. AIMS: To determine patients' use of the Internet as a medical information resource and to determine their experience, their perceptions of the quality and reliability of the information available. SETTING: The study was carried out in the outpatient clinic of an urban, tertiary care private sector hospital in November 2004. MATERIAL AND METHODS: Our survey instrument consisted of an anonymous single-page questionnaire. Eight hundred and eighty consecutive adults aged 18-70 years, attending the general outpatient clinic of a tertiary care private hospital completed the questionnaire. RESULTS: Two hundred and eighty-one (32%) patients acknowledged surfing the Internet, while 75% (212/281) of them acknowledged that they accessed health-related information. Amongst those who accessed the Internet, 130 (61%) found the information on the net to be of average quality. Almost all patients (211/212) felt that the information served the purpose and 95% (201/212) also found also found it to be reliable. Only 7% (21/281) patients were aware of the presence of any quality standards pertaining to health information sites and none could name any accreditation standard. CONCLUSIONS: One in four patients attending the private set-up is using the Internet for health information. A majority of patients find the information on the net reliable and of good quality. Awareness about health information quality standards is a rarity.

Renovascular hypertension.

Renovascular hypertension results from a lesion that impairs blood flow to a part or all, of one or both kidneys. 3-10% of children referred for the evaluation of severe hypertension are subsequently found to have clinically significant renovascular lesions Renovascular hypertension is the second most common cause of correctable hypertension in children second only to coarctation of the aorta. Specific therapeutic options now available, justify the often-invasive investigations required to confirm the diagnosis of renovascular hypertension. A systematic evaluation of the child with hypertension will help the pediatrician select correctly, the child most likely to have renovascular hypertension, thus reducing the number of children exposed to the risks involved with diagnostic but invasive investigations like renal arteriography which remains the gold standard Other non-invasive newer modalities like doppler ultrasonography, computed duplex sonography, ACE inhibited radionuclide imaging, and MR/CT/spiral CT angiography may be used depending on the availability of the facilities. Definite therapeutic options for renal artery stenosis include angioplasty, stenting and surgical re-vascularization using a bypass graft.

Status Epilepticus in Children.

Status epilepticus (SE) is a life-threatening emergency that requires prompt treatment, including basic neuroresuscitation principles (the ABCs), antiepileptic drugs to stop the seizure and identification of etiology. It results from an inability to normally abort an isolated seizure either due to ineffective inhibition, or due to abnormally persistent excessive excitation. Symptomatic SE is more common in younger children and the likely etiology depends on the age of the child. Treating the precipitating cause may prevent ongoing neurologic injury and facilitates seizure control. Benzodiapenes, phenytoin and phenobarbital form the mainstay of treatment. A systematic treatment regimen, planned in advance, is needed, including one for refractory status epilepticus (RSE). Patient education and home management of seizures is important to reduce the morbidity and mortality associated with SE.