Biomedical subjects

V Jain

Publications and source records attributed to V Jain.

At least 19 recordsLinked to original sources

PubMed2003

Phase II study of gemcitabine, cisplatin, and infusional fluorouracil in advanced pancreatic cancer.

PURPOSE: This phase II study was undertaken to determine the efficacy of adding infusional fluorouracil (FU) to the chemotherapy doublet of gemcitabine and cisplatin in patients with advanced pancreatic cancer. PATIENTS AND METHODS: The eligibility criteria included histologically or cytologically confirmed adenocarcinoma of the pancreas that was either unresectable or metastatic. No prior gemcitabine therapy was allowed. Patients received a combination of gemcitabine 1000 mg/m2 intravenously (IV) on days 1, 8, and 15; cisplatin 50 mg/m2 IV on days 1 and 15; and FU 175 mg/m2/d from days 1 to 15 by continuous IV infusion. Cycles were repeated every 28 days. Objective tumor response and toxicity were evaluated according to the World Health Organization criteria. RESULTS: A total of 47 patients (median age, 57 years; males, 59%) were enrolled. Sixteen patients had locally advanced (LA) disease, and 31 patients had metastatic disease. A total of 183 cycles of chemotherapy were administered. In patients with metastatic disease (n = 31), the probability of survival at 6 and 12 months was 66% and 34%, respectively. Objective partial response or stable disease was observed in 26% (90% confidence interval [CI], 0.14 to 0.41) and 61% (90% CI, 0.45 to 0.74) of patients, respectively. In patients with LA disease (n = 16), there were three partial responses (19%; 90 CI, 0.07 to 0.39). One patient in this group was successfully resected after FU-based radiotherapy. The most common grade 3 to 4 toxicities were neutropenia (60%), thrombocytopenia (42%), and anemia (26%). Thirteen patients were hospitalized for treatment-related complications. CONCLUSION: The combination of gemcitabine, cisplatin, and infusional FU has significant activity in patients with advanced pancreatic cancer.

Adenocarcinoma↗

PubMed2003

Cellular uptake, localization and photodynamic effects of haematoporphyrin derivative in human glioma and squamous carcinoma cell lines.

Uptake, intracellular concentration, localization and photodynamic effects of a haematoporphyrin derivative (HpD, Photosan-3) were compared in human glioma (BMG-1, wild-type p53) and squamous carcinoma (4451, mutated p53) cell lines. Concentration and time dependence of cellular uptake of HpD was assayed from methanol extracts and whole cell suspension spectroscopy, while localization was studied by fluorescence microscopy-based image analysis. Colony-forming ability, apoptosis, cell-cycle progression and cytogenetic damage (micronuclei formation) were investigated as parameters of photodynamic response following irradiation with red light. BMG-1 cells were more sensitive to the photodynamic treatment than 4451 cells, although the 4451 cells accumulated a higher amount of HpD and did not differ significantly from BMG-1 cells with respect to intracellular localization. Photodynamically-induced cytogenetic damage and apoptosis were considerably higher in BMG-1 cells as compared to 4451 cells. The present results strongly suggest that manifestation of the photodynamically-induced lesions in the form of cytogenetic damage and apoptosis are among the important determinants of cellular sensitivity to HpD-PDT besides the photodynamic dose (intracellular concentration of the photosensitizer and the light dose).

Apoptosis↗

PubMed2003

A phase I clinical trial of spicamycin derivative KRN5500 (NSC 650426) using a phase I accelerated titration "2B" design.

The spicamycin derivative KRN5500 was considered as a potential anti-cancer agent based on in vitro and preclinical studies. A Phase I study involving 24 cancer patients in whom tumors were refractory to all other conventional therapies was conducted to determine the dose limiting toxicity, maximum tolerated dose, effectiveness, and pharmacokinetic parameters of this drug administered by 1-h IV infusion daily for five consecutive days every 3 weeks. Using an accelerated dose titration strategy, 8.4 mg/m2/d x 5 days was the maximum administered dose. Severe gastrointestinal and hepatic toxicities were observed at doses at or above 4.3 mg/m2/d x 5. The recommended Phase II dose i s 4.3mg/m2/d x 5. The distribution of KRN5500 followed a two-compartment model, and clearance did not decrease significantly over the dose range 0.8-8.4 mg/m2/d x 5. No significant correlation was observed between plasma levels and toxicity. No tumor responses were observed among the 14 patients evaluable for response.

Adult↗

PubMed2003

Effects of L-type Ca(2+)-channel blockade, K(+)(ATP)-channel opening and nitric oxide on human uterine contractility in relation to gestational age and labour.

Relative uterine inactivity during pregnancy changes to vigorous rhythmic contractility during labour. We hypothesized that mechanisms involved in the regulation of uterine quiescence and contractility differ between term and preterm myometrium and in labour and non-labour states. Myometrial strips, prepared from biopsies taken at Caesarean section from labouring and non-labouring women preterm and at term, were mounted in organ chambers for isometric tension recording. Oxytocin (10(-9) mol/l) was added to maintain stable contractions, and effects of various inhibitors of uterine contractility were studied. The inhibitory effects of L-type Ca(2+)-channel blocker nifedipine and ATP-sensitive K(+)-channel opener pinacidil were greater in myometrium from the non-labour versus the labour group, both preterm and at term. In addition, pinacidil's effect was greater at term compared with preterm in the non-labour group. Mg(2+) and the nitric oxide donor sodium nitroprusside significantly inhibited contractility in all groups without significant differences with regard to labour or gestational age. Decreased inhibition of human uterine contractility by L-type Ca(2+)-channel blockers and K(+)(ATP)-channel openers in preterm and term labour may reflect changes in expression and activity of these channels. Effects of nitric oxide and Mg(2+) are not affected by gestational age or labour.

Adult↗

PubMed2002

Further evidence for the decay K+ -->pi+nu(nu).

Additional evidence for the rare kaon decay K+-->pi+nu(nu) has been found in a new data set with comparable sensitivity to the previously reported result. One new event was observed in the pion momentum region examined, 211 pi+nu(nu)) = 1.57(+1.75)(-0.82)x10(-10).

Journal Article↗

PubMed2002

Charcoal enhancement of treatment for tricyclic-induced mania.

Induction of mania by tricyclic antidepressants (TCAs) is controversial, with indirect evidence for and against it. Unusual direct evidence of it was observed in a 77-year-old female patient having ingested an amitriptyline overdose. Mania developed while the TCA blood levels were high, and responded to a combination of charcoal and valproate. However, mania reappeared when charcoal was discontinued, and disappeared again when it was restarted. This time course suggests a therapeutic advantage for adding charcoal to valproate in treating tricyclic-induced mania. Presumably, charcoal might have removed a mania-inducing metabolite of amitriptyline. Moreover, repeated doses of oral activated charcoal accelerated the elimination of TCA from the blood stream to several times its original rate, which is consistent with interruption of the enterohepatic circulation. This enhanced elimination and improved outcome illustrate the value of repeated charcoal doses after TCA overdose, and suggest its use when mania develops in a patient who takes an antidepressant, at least amitriptyline or nortriptyline.

Aged↗

PubMed2002

Reversible brain lesions in childhood hypertension.

UNLABELLED: Posterior leukoencephalopathy syndrome is characterized by an acute, usually reversible, encephalopathy with transient occipital lobe abnormalities detected on MRI that occur mostly in association with acute hypertension. The clinical presentation includes seizures, headache, altered mental status and blindness. Disturbed autoregulation of cerebral blood flow and endothelial injury are central to the pathogenesis of this disorder. Prompt control of hypertension results in rapid and complete neurological recovery. In this report we discuss the cases of two children with acute onset hypertension of different aetiologies that presented with the characteristic features of posterior leukoencephalopathy syndrome. CONCLUSION: Early recognition of this readily treatable condition may obviate the need for extensive and invasive investigations. Despite the alarming lesions on the MRI, prompt control of hypertension carries a uniformly favourable prognosis.

Acute Disease↗

PubMed2002

A new incision for surgery on tendo Achillis using a distally-based fasciocutaneous flap.

The consequences of breakdown of the wound after surgery to tendo Achillis are considerable. Complex surgery is often required to reconstruct the tendon and to provide soft-tissue cover. We describe a new incision which approaches the tendon by using a distally-based fasciocutaneous flap. This reduces the risk of breakdown of the wound since it avoids making an incision directly over the tendon, provides good exposure, and maintains the vascularity of the skin overlying the tendon.

Achilles Tendon↗

PubMed2001

First measurement of gamma(D*(+)).

We present the first measurement of the D*(+) width using 9/fb of e(+)e(-) data collected near the Upsilon(4S) resonance by the CLEO II.V detector. Our method uses advanced tracking techniques and a reconstruction method that takes advantage of the small vertical size of the Cornell Electron-positron Storage Ring beam spot to measure the energy release distribution from the D*(+)-->D(0)pi(+) decay. We find gamma(D*(+)) = 96+/-4 (stat)+/-22 (syst) keV. We also measure the energy release in the decay and compute Delta m identical with m(D*(+))-m(D(0)) = 145.412+/-0.002 (stat)+/-0.012 (syst) MeV/c(2).

Journal Article↗

PubMed2001

Heterogeneity in 2-deoxy-D-glucose-induced modifications in energetics and radiation responses of human tumor cell lines.

PURPOSE: The glucose analog and glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has been shown to differentially enhance the radiation damage in tumor cells by inhibiting the postirradiation repair processes. The present study was undertaken to examine the relationship between 2-DG-induced modification of energy metabolism and cellular radioresponses and to identify the most relevant parameter(s) for predicting the tumor response to the combined treatment of radiation + 2-DG. METHODS AND MATERIALS: Six human tumor cell lines (glioma: BMG-1 and U-87, squamous cell carcinoma: 4451 and 4197, and melanoma: MeWo and Be-11) were investigated. Cells were exposed to 2 Gy of Co-60 gamma-rays or 250 kVP X-rays and maintained under liquid-holding conditions 2-4 h to facilitate repair. 2-DG (5 mM, equimolar with glucose) that was added at the time of irradiation was present during the liquid holding. Glucose utilization, lactate production (enzymatic assays), and adenine nucleotides (high performance liquid chromatography and capillary isotachophoresis) were investigated as parameters of energy metabolism. Induction and repair of DNA damage (comet assay), cytogenetic damage (micronuclei formation), and cell death (macrocolony assay) were analyzed as parameters of radiation response. RESULTS: The glucose consumption and lactate production of glioma cell lines (BMG-1 and U-87) were nearly 2-fold higher than the squamous carcinoma cell lines (4197 and 4451). The ATP content varied from 3.0 to 6.5 femto moles/cell among these lines, whereas the energy charge (0.86-0.90) did not show much variation. Presence of 2-DG inhibited the rate of glucose usage and glycolysis by 30-40% in glioma cell lines and by 15-20% in squamous carcinoma lines, while ATP levels reduced by nearly 40% in all the four cell lines. ATP:ADP ratios decreased to a greater extent ( approximately 40%) in glioma cells than in squamous carcinoma 4451 and MeWo cells; in contrast, presence of 2-DG reduced ADP:AMP ratios by 3-fold in the squamous carcinoma 4451, whereas an increase was noted in the glioma cell line BMG-1. 2-DG significantly reduced the initial rates of DNA repair in all cells, resulting in an excess residual damage after 2 h of repair in BMG-1, U-87, and 4451 cell lines, whereas no significant differences could be observed in the other cell lines. Recovery from potentially lethal damage was also significantly inhibited in BMG-1 cells. 2-DG increased the radiation-induced micronuclei formation in the melanoma line (MeWo) by nearly 60%, while a moderate (25-40%) increase was observed in the glioma cell lines (BMG-1 and U-87). Presence of 2-DG during liquid holding (4 h) enhanced the radiation-induced cell death by nearly 40% in both the glioma cell lines, while significant effects were not observed in others. CONCLUSIONS: The modifications in energetics and radiation responses by 2-DG vary considerably among different human tumor cell lines, and the relationships between energy metabolism and various radiobiologic parameters are complex in nature. The 2-DG-induced modification of radiation response does not strictly correlate with changes in the levels of ATP. However, a significant enhancement of the radiation damage by 2-DG was observed in cells with high rates of glucose usage and glycolysis, which appear to be the two most important factors determining the tumor response to the combined treatment of 2-DG + radiation therapy.

Adenosine Diphosphate↗

PubMed2001

Genotoxic effect of hydroquinone on the cultured mouse spleenocytes.

The daily administration of 0, 0.5, 1, 2, 4 and 8 mg/kg b. wt. of hydroquinone (HQ) to Swiss albino mice, consecutively for 6 days resulted in a dose dependent elevation in the frequency of micronucleated binucleate spleenocytes (MNBNS). This increase in the frequency of MNBNS was significantly higher than that of non-drug treated controls (0 mg/kg). The daily administration of various doses of HQ for 6 days not only increased the frequency of binucleated spleenocytes bearing one micronuclei (MN), but also the BNS bearing two, three, and four MN. The study demonstrates that the daily administration of various doses of HQ for 6 days increases the genotoxic and mutagenic potential in mice.

Animals↗

PubMed2001

Functional magnetic resonance imaging of the primary motor cortex in humans: response to increased functional demands.

Functional magnetic resonance imaging (fMRI) studies have been performed on 20 right handed volunteers at 1.5 Tesla using echo planar imaging (EPI) protocol. Index finger tapping invoked localized activation in the primary motor area. Consistent and highly reproducible activation in the primary motor area was observed in six different sessions of a volunteer over a period of one month. Increased tapping rate resulted in increase in the blood oxygenation level dependent (BOLD) signal intensity as well as the volume/area of activation (pixels) in the contralateral primary motor area up to tapping rate of 120 taps/min (2 Hz), beyond which it saturates. Activation in supplementary motor area was also observed. The obtained results are correlated to increased functional demands.

Adult↗

PubMed2001

Post-neonatal tetanus: issues in intensive care management.

Tetanus is an acute neurological disease characterized by muscle rigidity and spasms, autonomic dysfunction and in severe forms requires respiratory and hemodynamic support. Though it is entirely preventable by immunization, it still occurs in developing countries causing significant morbidity and mortality. Intensive care management of tetanus is fraught with problems of ventilator-associated pneumonia, nosocomial sepsis and a variety of other complications. Various treatment protocols have been tried in managing diverse manifestations of severe tetanus but the consensus is yet to emerge. In this review we have discussed the pathophysiology, clinical features and management controversies and suggest on basis of our experience use of high dose diazepam (20-120 mg/kg/day) and vecuronium with mechanical ventilation if required for control of spasms, and early detection of autonomic dysfunction and use of propranolol, in our circumstances.

Child↗

PubMed2001

Strangulation injury, a fatal form of child abuse.

Strangulation is a common method of committing murder, though underreported in Indian literature. We managed a girl child, victim of child abuse who later succumbed to its neurological complications. This case report describes the clinical features associated with such injuries and complications which should be anticipated in such cases.

Asphyxia↗

PubMed2001

Epidemiology of rotavirus in India.

Rotavirus is the leading cause of childhood diarrhea worldwide, causing an estimated 600,000 deaths each year. To assess the potential benefits of a national rotavirus immunization program in India, we analyzed 40 published studies of rotavirus that were conducted between 1976 and 1997 and included a total of approximately 13,000 Indian pediatric inpatients. Pediatric studies featuring 100 or more patients and lasting at least 12 months in duration and all neonatal studies were analyzed. Rotavirus was detected in a median of 18% of pediatric patients and 28% of neonates surveyed. Fifty percent of all children hospitalized with rotavirus by age 5 were hospitalized by the age of 6 months, 75% by the age of 9 months, and almost 100% by the age of 2 years. Rotavirus was most prevalent (31%) in children between 7 and 12 months of age, followed by children between 1 and 2 years of age (20%), and children < 7 months of age (13%). VP7 genotypes G1 and G2 were most commonly isolated although significant heterogeneity of serotypes was observed. P[11], G9 strains were most frequently isolated among neonates. In 1998; approximately 98,000 childhood deaths were caused by rotavirus. These data underscore the urgent need for safe and effective interventions against rotavirus such as vaccines. The significant diversity of rotavirus strains and young age of hospitalization pose unique challenges to the formulation of a rotavirus immunization program in India, but raise the possibility of utilizing a neonatal vaccine to provide effective coverage.

Child, Preschool↗

PubMed2001

Radiotherapeutic response of Ehrlich ascites tumor cells perfused in agarose gel threads and implanted in mice. A 31P MR spectroscopy study.

AIM: In order to obtain better understanding of radiation-induced alterations in intracellular metabolism, a dynamic and non-invasive experimental model system is required. A serial study in cultured tumor cell line followed by verification in the in vivo samples may be of considerable value for non-invasive prediction and/or detection of tumor response to therapy. The present study was undertaken to evaluate the radiation response of perfused Ehrlich ascites tumors cells (EATC) immobilized in agarose gel matrix to that observed in mouse bearing EATC tumor, in order to identify biomarkers of radiation response. MATERIALS AND METHODS: Perfused EAT cells, entrapped in agarose gel threads were irradiated in the perfusion assembly outside the magnet with fast electrons (6 Gy, 1 Gy/min) using 30 MeV Betatron. Solid EATC tumors implanted subcutaneously onto right hand limb of Swiss-albino strain "A" mice, were focally irradiated using 60Co teletherapy (10 Gy, 0.4 Gy/min). Metabolites changes were monitored by 31P MR spectroscopic techniques. RESULTS: A post-irradiation decrease in the levels of ATP and ADP along with an increase in inorganic phosphate and glycerophosphocholine levels was observed. The ratios of beta-phosphate of ATP to inorganic phosphate (beta-ATP/Pi), and phosphocholine to glycerophosphocholine (PC/GPC), declined during 1-5 hours following irradiation, in perfused EAT cells and in the solid tumors implanted in mice. CONCLUSION: Perfused cells could be used as a simple model of tumor for prediction of clinical radiotherapeutic response. The present study demonstrates that radiation damage may be occurring both at the DNA protein as well as the membrane lipid levels. Therefore, the bioenergetics and phospholipid profiles of tumor cells could be used as complimentary, reliable and sensitive indirect indicators for devising predictive assays for assessment and monitoring of radiation response, which will also facilitate the individualization and optimization of tumor radiotherapy.

Adenosine Diphosphate↗

PubMed2001

Keratonconjunctivitis sicca is not uncommon in children with juvenile rheumatoid arthritis.

Keratoconjunctivitis sicca (KCS), characterised by aqueous tear deficiency, is the most common ocular complication in adult rheumatoid arthritis (RA). In juvenile rheumatoid arthritis (JRA), however, it remains under-reported. For this prospective study, 50 children with JRA were examined clinically and underwent tests for KCS (Schirmer's I and rose bengal tests, fluorescein staining, and tear film breakup time). Six children (12%) with two or more abnormal tests were diagnosed as having definite KCS, while one child with only one abnormal test was labelled with probable KCS. Five of the six (83.3%) with definite KCS were males, and three (50%) had a pauciarticular form of the disease. Two children (33.3%) with definite KCS had no ocular symptoms, five were receiving only nonsteroidal anti-inflammatory drugs, and one was additionally on methotrexate. Keratoconjunctivitis sicca appears to be a common ocular complication and all children with JRA should be screened for it with a comprehensive battery of tests.

Adolescent↗

PubMed2001

Laser Raman and IR spectra and force fields for 2,4-dichlorobenzonitrile.

Raman spectrum of 2,4-dichlorobenzonitrile (2,4-DCBN) in powder form has been recorded in the region 50-4000 cm(-1) on a Jasco K-500 Raman spectrophotometer using the 488.0 nm radiation from an argon laser. FTIR spectra in the region 200-4000 cm(-1) have been recorded in KBr pellet and nujol mull on a Nicolet DX spectrometer. Using the observed Raman and IR frequencies, normal co-ordinate analysis has been carried out to support the vibrational analysis and to determine the planar and non-planar force fields.

Chlorine Compounds↗