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Biomedical subjects

N Gupta

Publications and source records attributed to N Gupta.

At least 19 recordsLinked to original sources

Is fluoroscopy essential for retrieval of lower ureteric stones?

INTRODUCTION: The aim of this study was to assess the efficacy of ureteroscopy for lower ureteric stones without the use of fluoroscopy. PATIENTS AND METHODS: Between June 2001 and January 2005, a total of 110 patients with a mean age of 33.5 years (range 12-65) suffering from of lower ureteral calculi (below the upper margin of the sacroiliac joint) prospectively underwent ureteroscopic removal. Retrograde pyelography was avoided, and no safety guidewire was placed. Whenever required, the ureteric meatus was dilated with a ureteric balloon under direct vision. Double-J stent placement was done with the aid of ureteroscopy. A fluoroscope was kept standby. The patients had a postoperative X-ray of the kidney-ureter-bladder region to document the stone clearance. RESULTS: The mean stone size was 8.7 mm (range 6-15). Complete clearance without the use of fluoroscopy was achieved in 99 patients (94.2%). Fluoroscopy was required in 6 patients (4%) for calcified stricture (n = 1), duplex system (n = 1), narrow and tortuous meatus causing difficulty in passing the 5-Fr balloon dilator (n = 3), and confirmation of spontaneous passage of the stone (n = 1). Of the 13 patients who required balloon dilatation it was successfully achieved without fluoroscopy. Double-J stenting was done due to mucosal ulceration (n = 3), polypoid reaction (n = 2), and perforation (n = 1). All these patients had correct placement of the stent, as confirmed by X-ray of the kidney-ureter-bladder region postoperatively. CONCLUSIONS: To uphold the notion for radiation exposure to be as low as reasonably achievable, ureteroscopic stone retrieval can safely be done without the use of fluoroscopy in a significant number of patients.

Adolescent↗

Rapid and real-time detection of Chikungunya virus by reverse transcription loop-mediated isothermal amplification assay.

The standardization and validation of a one-step, single-tube, accelerated, quantitative reverse transcription (RT) loop-mediated isothermal amplification (RT-LAMP) assay targeting the E1 gene for the rapid and real-time detection of Chikungunya virus (CHIKV) are reported. A linear relationship between the amount of template and time of positivity value over a range of 2 x 10(8) to 2 x 10(2) copies was obtained. The feasibility of CHIKV RT-LAMP for clinical diagnosis was validated with patient serum samples from an ongoing epidemic in Southern India. Optimal assay conditions with zero background were established for the detection of low levels of CHIKV in acute-phase patient serum samples. The comparative evaluation of the RT-LAMP assay with acute-phase patient serum samples demonstrated exceptionally higher sensitivity by correctly identifying 21 additional positive borderline cases that were missed by conventional RT-PCR (P < 0.0001) with a detection limit of 20 copies. The quantification of virus load in patient serum samples was also determined from the standard curve based on their time of positivity and was found to be in the range of 2 x 10(8) to 2 x 10(1) copies. In addition, the field applicability of the RT-LAMP assay was also demonstrated by standardizing SYBR Green I-based RT-LAMP wherein the amplification was carried out in a water bath at 63 degrees C for 60 min, which was followed by monitoring gene amplification with the naked eye through color changes. These findings demonstrated that the RT-LAMP assay is a valuable tool for rapid, real-time detection as well as quantification of CHIKV in acute-phase serum samples without requiring any sophisticated equipment and has potential usefulness for clinical diagnosis and surveillance of CHIKV in developing countries.

Acute Disease↗

Current insights into the regulation of programmed cell death by NF-kappaB.

The nuclear factor-kappaB (NF-kappaB) transcription factors have emerged as major regulators of programmed cell death (PCD) whether via apoptosis or necrosis. In this context, NF-kappaB's activity has important ramifications for normal tissue development, homoeostasis and the physiological functions of various cell systems including the immune, hepatic, epidermal and nervous systems. However, improper regulation of PCD by NF-kappaB can have severe pathologic consequences, ranging from neurodegeneration to cancer, where its activity often precludes effective therapy. Although NF-kappaB generally protects cells by inducing the expression genes encoding antiapoptotic and antioxidizing proteins, its role in apoptosis and necrosis can vary markedly in different cell contexts, and NF-kappaB can sensitize cells to death-inducing stimuli in some instances. This article describes our current knowledge of the role of NF-kappaB in apoptosis and necrosis, and focuses on the many advances since we last reviewed this rapidly evolving topic in Oncogene 3 years ago. There has been substantial progress in understanding NF-kappaB's mode of action in apoptosis and necrosis and the mechanisms that regulate its anti- vs proapoptotic activities. These recent developments shed new light on the role of NF-kappaB in many disease conditions including tumor development, tumor progression and anticancer treatment.

Animals↗

Fluorotoxic metabolic bone disease: an osteo-renal syndrome caused by excess fluoride ingestion in the tropics.

BACKGROUND: There is scant data available on the pathogenetic mechanisms of varied clinical presentation of bone disease in patients with excess fluoride ingestion in the Indian subcontinent. The present study is comprehensive and state of the art, incorporating all essential elements of bone mineral metabolism in patients with excess fluoride ingestion. METHODS: We studied 24 patients (age 31 +/- 16 years) with fluorotoxic metabolic bone disease (FMBD) for their clinical, radiological and biochemical parameters like serum calcium, phosphorous, alkaline phosphatase (SAP), 25-hydroxyvitamin D, 1,25 dihydroxyvitamin D, and parathyroid hormone levels, nephrologic parameters that assess renal handling of calcium and phosphorous and skeletal dynamics as revealed by bone histomorphometry. FINDINGS: Major clinical manifestations were bone pain (79%), Tetany (12.5%) and dental mottling (38%). Radiological findings included osteosclerosis (96%), pseudofracture and ligamentous calcification (50%). These patients manifested hypocalcemia and raised SAP with normal serum phosphorus. There was a positive correlation between serum creatinine and phosphorous excretion index (PEI) and a negative correlation between declining endogenous creatinine clearance (Cr.Cl) and increasing renal loss of calcium and phosphorus as indicated by increased calcium to creatinine ratio and PEI. Bone histomorphometry revealed impairment of primary mineralization with hypomineralized lacunae, interstitial mineralization defects and very thick and extended osteoid seams. Autopsy findings in a patient who died of azotemia showed tubular atrophy with secondary glomerular changes. INTERPRETATION: Fluoride intoxication plays an important role in the pathogenesis of the unique osteo-renal syndrome.

Adolescent↗

Depth perception deficits in glaucoma suspects.

AIM: To investigate depth perception in glaucoma suspects compared to glaucoma patients and controls. METHODS: Glaucoma suspects (n = 16), patients (n = 18), and normal age matched controls (n = 19) aged 40-65 years were prospectively evaluated for depth perception deficits using the Frisby test. Stereoacuity was measured by stereothreshold in seconds of arc for each group. RESULTS: Glaucoma suspects showed significantly increased mean stereothreshold compared to age matched normals (144.1 (SE 35.2) v 26.6 (3.7) seconds of arc; p = 0.0004). The mean stereothreshold in glaucoma patients was also increased compared to age matched normals 148.1 (33.8) v 26.6 (3.7) seconds of arc; p = 0.0004). CONCLUSIONS: Glaucoma suspects show depth perception deficits. The impaired stereovision in glaucoma suspects suggests that binocular interactions can be disrupted in the presence of normal visual fields by standard achromatic automated perimetry.

Adult↗

Mutational analysis of the betaglycan gene-coding region in susceptibility for ovarian failure.

BACKGROUND: Elevation of FSH is frequently a consequence of impaired ovarian follicle growth. Down-regulation of the FSH levels by inhibins is mediated through its receptor betaglycan in the gonadotrophs. Understanding of germline status of the betaglycan gene (TGFBR3) is essential for ovarian failure pathophysiology. METHODS: Sequence analysis was performed for the coding region of TGFBR3 gene in a cohort of 196 ovarian failure cases that include 133 premature ovarian failure (POF) cases, 63 primary amenorrhoea (PA) cases compared with 200 controls. RESULTS: Forty-six variants including six novel exonic variants and 16 novel intronic variants were revealed. Two variants were missense: (i) p.Iso184Val in a control and (ii) p.Pro775Ser in a POF case. Genotypic distribution of three variants (c.382-81C>T, c.382-77T>C and c.1200G>A) was significantly different in the patients as compared with the controls. Five variants c.382-81C>T, c.382-77T>C, c.566-216G>A, c.1200G>A and c.2022T>C were chosen for haplotyping. The CCAAT haplotype was significantly higher in the patient population as compared with the controls (P = 0.00007). CONCLUSION: This study establishes the first mutational report of the TGFBR3 gene in correlation with ovarian failure. Significant diversity of genotype distribution and haplotype analysis suggested susceptibility of the TGFBR3 gene for ovarian failure aetiology.

Adult↗

Human glaucoma and neural degeneration in intracranial optic nerve, lateral geniculate nucleus, and visual cortex.

The pathology of glaucoma has been extensively studied at the level of the retina and optic nerve head. Here the first clinicopathological case of human glaucoma is reported demonstrating degenerative changes in the brain involving the intracranial optic nerve, lateral geniculate nucleus, and visual cortex. Pathological evidence of neural degeneration in this patient is correlated with clinical, optic nerve head, visual field, and neuroradiology findings. Neuropathology in the glaucoma brain is compared to age matched controls. In the presence of advanced human glaucoma with 50% visual field loss, neural damage is evident in multiple vision stations within the brain.

Aged↗

Pharmacokinetic/pharmacodynamic insulin-glucose analysis for differentiation of beta-cell function: an 18 month follow-up study in pre-pubertal lean and obese children.

The objective of this study was to analyse the PK/PD of the insulin-glucose physiology for glucose stimulated insulin secretion from beta-cells between lean and obese pre-pubertal children in an 18 month study. The subjects were divided into two groups of six children according to their body mass index (BMI). Each subject was assessed on four occasions: on admission and at 6, 12 and 18 month follow-ups. Each time, 23 blood samples were obtained from the subjects according to the frequently sampled intravenous glucose tolerance test involving a bolus of 250 mg/kg dextrose. For the obese group, a significant difference (p <0.05) was found in the rate constant for the first phase secretion of insulin between the time of admission (1.73 +/- 0.372 min(-1)) and the 18 month follow-up (3.08 +/- 0.391 min(-1)). Additionally, the lean vs obese group comparisons showed a higher first phase insulin secretion rate constant (p <0.05) in the obese group on admission (1.73 +/- 0.372 vs 1.29 +/- 0.278 min(-1)), 6 months (1.96 +/- 0.317 vs 1.32 +/- 0.444 min(-1)), 12 months (2.33 +/- 0.621 vs 1.57 +/- 0.435 min(-1)) and 18 months (3.08 +/- 0.391 vs 1.83 +/- 0.587 min(-1)). The proposed PK/PD model for the insulin secretion from beta-cells is able to identify kinetic differences in first phase insulin secretion between lean and obese non-diabetic pre-pubertal children in this 18 month follow-up study.

Child↗

Intravenous administration of darbepoetin to NICU patients.

OBJECTIVE: Darbepoetin can be administered either intravenously (i.v.) or subcutaneously (s.c.). However, no information is available regarding pharmacokinetics and pharmacodynamics following its i.v. administration to neonates. STUDY DESIGN: We administered a single i.v. dose (4 microg/kg) of darbepoetin to 10 neonates who had a hemoglobin < or =10.5 g/dl. Blood was obtained for immature reticulocyte fraction (IRF) and absolute reticulocyte count (ARC), before and 48 h following the dose. Blood was also drawn for pharmacokinetic analysis once before and at four pre-set intervals after dosing. RESULTS: The study subjects ranged from 704 to 3025 g (median, 1128 g) birth weight, and were 26.0-40.0 weeks (median, 29.2 weeks) gestation at delivery. When the darbepoetin dose was given, ages ranged from 3 to 28 days (median, 8.5 days) with a hemoglobin of 9.8 +/- 0.7 g/dl (mean +/- s.d.). Doses were administered by i.v. infusion over 4 h. No adverse effects of the infusions were detected. The half-life of darbepoetin (t (1/2)) was 10.1 h (range 9.0-22.7 h), the volume of distribution was 0.77 l/kg (range 0.18-3.05 l/kg) and the clearance was 52.8 ml/h/kg (range 22.4-158.0 ml/h/kg). In the preterm neonates, there was no significant correlation between gestational age, or age at darbepoetin administration, and pharmacokinetic parameters. However, in the term and near-term neonates, volume of distribution correlated significantly with both gestational and age at darbepoetin administration (P < 0.05). Forty-eight hours after dosing, the IRFs and ARCs were elevated in six subjects and not in four. Those with predosing reticulocyte counts >200,000/microl did not have an increase in reticulocytes by 48 h (P < 0.05). CONCLUSIONS: Darbepoetin administered i.v. to neonates had a shorter t (1/2), a larger volume of distribution and more rapid clearance than reported in children. We observed a significantly shorter t (1/2) and a less consistent rise in IRF and ARC after i.v. dosing than we previously reported following 4 microg/kg administered SC.

Birth Weight↗

Body mass index in spinal cord injury -- a retrospective study.

STUDY DESIGN: Retrospective chart review. OBJECTIVE: To identify the prevalence of overweight and severely overweight (obese) in veterans with spinal cord injury. SETTING: Veterans Administration Hospital in Wisconsin. METHODS: A retrospective chart review of all the patients registered in the current database with the Spinal Cord Injury Unit in the Veterans Administration Hospital was undertaken Data collected for each patient included age, sex, height, date of assessment of the height, weight, date of assessment of the weight, duration of spinal cord injury and the type of spinal cord injury -- paraplegia versus quadriplegia. The body mass index (BMI) was subsequently calculated for each patient and the prevalence of overweight and obesity were determined. RESULTS: There were a total of 408 patients registered in the database with the Spinal Injury Unit. The median age was 56 years, and the mean age 55.8 years. Of all patients with spinal cord injury, 52.2% patients had paraplegia and 47.7% had quadriplegia. The mean duration of injury was 19 years. Of the total number of patients, 46.0% were ASIA A, 11.0% were ASIA B, 12.7% were ASIA C and 29.1% were ASIA D. In all, 27.9% patients had a normal BMI and 3.6% patients were undernourished (BMI less than 18.5 kg/m(2)). The prevalence of overweight was 65.8% and 29.9% patients were obese. CONCLUSION: Overweight and obesity are problems of a significant magnitude in veterans with spinal cord injury.

Adult↗

Endocrine regulation in asymmetric intrauterine fetal growth retardation.

OBJECTIVE: The ponderal index (PI) is a widely accepted measure of disproportionate growth or asymmetrical growth retardation by pediatricians worldwide. Identification of disproportionately grown small for gestational age (SGA) neonates by using the ponderal index as a measure of the nutritional status at birth, is important because they constitute a high-risk group among SGA neonates. Poor nutritional status of the mother could have a direct effect on the organs of the developing fetus and/or affect the endocrine milieu in the maternal feto-placental unit resulting in an increased incidence of intrauterine growth-retarded (IUGR)/SGA births. IUGR is a significant risk factor for adult disease. In this study, we have investigated the endocrine adaptation by the fetus to overcome the growth disadvantage caused due to poor nutritional status of the mother. MATERIALS AND METHODS: We examined the quantitative variations in hormonal and growth factor profiles in paired maternal and cord blood samples obtained from mothers and their neonates who were classified based on their growth status into SGA and appropriate for gestational age (AGA). RESULTS: (1) A total of 24.7% neonates had a PI < 2, indicating a high incidence of asymmetric IUGR in the population studied. (2) Anthropometric parameters measured in the mothers indicate that the mothers giving birth to neonates with a PI < 2 had poor nutritional status, both prior to and during pregnancy. (3) We observed increased levels of placental lactogen and prolactin and decreased levels of insulin in the cord blood of neonates with PI < 2, while lower levels of insulin-like growth factor 1 (IGF-1) and higher levels of epidermal growth factor (EGF) were observed in their mothers. CONCLUSION: Poor maternal nutritional status results in fetal adaptation to a growth restricted environment via the modulation of the pituitary-thyroid axis thereby altering the endocrine milieu, thus affecting fetal growth.

Adult↗

Pathology of supraclavicular lymphadenopathy in Chandigarh, north India: an audit of 200 cases diagnosed by needle aspiration.

OBJECTIVE: Fine needle aspiration cytology (FNAC) of lymph nodes can be used routinely as a first-line diagnostic test. The majority of studies reveal a malignant cause for palpable supraclavicular lymph nodes. The present audit further emphasizes the use of FNAC as a first-line investigation for the evaluation of enlarged supraclavicular lymph nodes. METHODS: A total of 200 cases of palpable supraclavicular lymph node(s) were included in the present study. RESULTS: Left supraclavicular lymph nodes were found to be more commonly involved (59.5% cases). Sixty-four per cent cases showed metastatic deposits and 13.5% cases were diagnosed as tuberculosis. Ten per cent cases showed reactive lymphoid hyperplasia; 0.5% (one) case showed only necrosis and on autopsy, a microscopic focus of choriocarcinoma was found in the testis. In 7.5% cases, diagnostic material could not be aspirated despite repeated attempts. Common metastatic tumours were from lung (22% cases), breast (16.4% cases), cervix (11% cases) and oesophagus (8.6% cases). In 13.3% cases the primary site was unknown and the diagnosis of malignancy first came from FNAC. CONCLUSION: The present study further highlights the importance of FNAC as a first-line diagnostic modality in the evaluation of supraclavicular lymphadenopathy. A full history, radiological findings and immunochemistry in difficult cases can help to arrive at a definitive diagnosis.

Adolescent↗

Fine needle aspiration of epididymal nodules in Chandigarh, north India: an audit of 228 cases.

BACKGROUND: Epididymal nodules are not infrequently encountered in surgical practice. These are generally small and slippery and fine needle aspiration cytology (FNAC) is not easy. But as it is rapid and less traumatic than a biopsy, this is a favoured technique in the assessment of epididymal nodules. PATIENTS AND METHODS: In the present study, all the cases of epididymal nodules aspirated from January 1998 to August 2004 were retrieved from the cytology files of the Department of Cytology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. RESULTS: A total of 228 cases were retrieved and divided as follows: tuberculous epididymitis 70 (30.7%), non-specific inflammation 10 (4.4%), microfilaria 2 (0.9%), hydrocele 26 (11.4%), spermatocele 42 (18.4%), spermatic granulomas 12 (5.3%), adenomatoid tumour 3 (1.3%), leiomyosarcoma 1 (0.4%) and lipoma 1 (0.4%). Thirty-six (15.8%) cases were labelled as benign aspirate not otherwise specified. FNAC material was inadequate for opinion in 22 (9.65%) cases and three (1.3%) cases revealed evidence of a haematoma. CONCLUSIONS: FNAC was useful in the diagnosis of 90.3% of cases, thereby avoiding surgical biopsy and other investigations. Therefore, FNAC has an important role in the differential diagnosis of epididymal nodules as it can detect malignancy and benign conditions such as tuberculosis and acute and chronic epididymo-orchitis.

Biopsy, Fine-Needle↗

Correlates of Type 2 diabetes mellitus in children, adolescents and young adults in north India: a multisite collaborative case-control study.

AIMS: In this study we describe the clinical, anthropometric and biochemical characteristics of patients with early onset Type 2 diabetes mellitus (T2DM) (< 30 years of age) and compare them with healthy, non-diabetic individuals. METHODS: In this multisite collaborative study, 51 patients with T2DM (40 male, 11 female) and 69 non-diabetic individuals of similar age and gender distribution (controls) as the cases (46 male and 23 female) were investigated. The following parameters were measured; anthropometry [body mass index (BMI), waist circumference, waist-hip ratio (WHR) and skin-fold thickness at four sites], percentage body fat (%BF) and lipid profile. RESULTS: The mean (SD) age of diagnosis of T2DM was 21.4 (6.1) years. A significantly higher number of cases had a history of T2DM in first-degree relatives as compared with controls (82.3 vs. 23.2%, P < 0.001). The mean values and the prevalence of abnormal values of measures of generalized obesity (BMI and %BF) and abdominal obesity (waist circumference and WHR) were significantly higher in cases as compared with controls. Hypertriglyceridaemia [OR (95% CI): 4.6 (1.1-20.0)], high WHR [7.9 (2.5-24.4)] and family history of T2DM [7.3 (2.3-23.0)] were independently associated with T2DM. Age and gender adjusted odds ratios of T2DM were 23.3 (5.2-103.6), 37.7 (9.0-158.5) and 86.4 (17.0-438.5), respectively, with the following set of risk factors; hypertriglyceridaemia and high WHR, hypertriglyceridaemia and family history of T2DM, and high WHR and family history of T2DM. Finally, the presence of all three risk factors increased the odds of T2DM to 112.1 (10.8-1164.7). CONCLUSIONS: Early identification of the simple clinical, anthropometric and biochemical parameters which are strongly associated with early onset T2DM in young Asian Indians may be useful for primary prevention.

Adolescent↗

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene R620W variant and sporadic idiopathic hypoparathyroidism in Asian Indians.

Recently, a gain of function variant C1858T of the lymphoid-specific protein tyrosine phosphatase non-receptor (LYP, PTPN22) gene has been reported to be associated with several autoimmune disorders including Graves' disease, type 1 diabetes, rheumatoid arthritis and vitiligo. The present study was carried out in 80 patients with sporadic idiopathic hypoparathyroidism (SIH) [43 males and 37 females, mean +/- SD age and duration of symptoms 32.5 +/- 14.1 years and 6.7 +/- 7.2 years (range 1 day to 35 years), respectively] and 193 healthy controls (male : female ratio 91:102, mean +/- SD age, 43.1 +/- 11.6 years) to assess association of 1858T allele with the disease. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed to genotype C1858T variant. The frequency of occurrence of 1858T allele was 4/160 (2.5%) in SIH and 5/386 (1.3%) in the control alleles (odds ratio 1.95, 95% CI 0.51-7.37). Thus, the present study reveals that 1858T allele is rare (1.3%) in Asian Indians. The trend of higher prevalence of 1858T allele in patients with SIH needs to be studied further in other population with higher rate of the allele to support the autoimmune basis of the disease.

Adult↗

New tobacco products: do smokers like them?

BACKGROUND: There is little information about smokers who tried potentially reduced exposure products (PREPs) (Eclipse, Omni, Advance Lights, Accord, or Ariva), why they tried them, if they liked these products, and if they will continue to use them. OBJECTIVES: The objectives of this qualitative study were to understand: (1) how smokers who tried PREPs learned about them, (2) reasons for first trying PREPs, (3) which PREP(s) they tried, (4) what they thought of the product at first trial, (5) reasons for continuing or discontinuing use, and (6) whether they would recommend PREPs to others. DESIGN: In October 2002, 16 focus group sessions were conducted with current cigarette smokers aged 30-50 years: eight groups in Chattanooga, Tennessee, and eight in Dallas, Texas. Specific focus groups were composed of white men, white women, African American men, African American women, Hispanic men, or Hispanic women. RESULTS: The majority of the participants learned about PREPs through advertising or promotion, family, friends, and co-workers; major reasons given for first trying PREPs were that the products were free or inexpensive, they wanted to stop smoking, they believed the product claims of fewer health risks, or they were curious; most of them tried Eclipse probably because the focus groups were conducted in the same cities where Eclipse was introduced; most participants did not like PREPs; most discontinued the use of PREPS, some who continued to use them did so infrequently and also kept smoking their regular brands of cigarettes; and most would not recommend PREPs, although a few might recommend them to specific groups (for example, new smokers, the young, women, curious or health conscious people). CONCLUSIONS: Although most established smokers did not like the PREPs they tried and will not recommend them to anyone, a minority of established smokers believe that there may be a market for these products.

Adult↗