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Biomedical subjects

P Shah

Publications and source records attributed to P Shah.

At least 55 records · Page 3Linked to original sources
PubMed2002

Open-label, multicentre, emergency-use study of clinafloxacin (CI-960) in the treatment of patients with serious life-threatening infections.

In an open-label emergency-use study, 23 patients with bacterial infections caused by multiply drug resistant pathogens were treated with clinafloxacin. Efficacy and safety were evaluated by tabulating investigators' assessments at the end of treatment, treatment discontinuations and adverse event data. Most of the patients were seriously ill and had multi-organ infections, primarily respiratory tract infections such as nosocomial pneumonia and gastrointestinal infections. Eleven patients were successfully treated, two had treatment failure and 10 were not evaluable because the patients died of their underlying disease. Considering that most of the patients had several infections caused by multiply resistant pathogens, clinafloxacin may be useful for the treatment of such life-threatening episodes.

Adult↗
PubMed2002

Differences in body mass index and waist: hip ratios in North Indian rural and urban populations.

Overweight could be a major factor in determining the increasing rates of coronary heart disease in the Indian population, by its influence on blood pressure, diabetes and insulin resistance. We studied the prevalence of overweight in north Indian urban and rural population samples. The urban sample population (n = 3050) was selected using a multistage sampling with stratification for geographical zone and the type of residential colony and cluster sampling of urban blocks in each stratum. The rural sample (n = 2487) was selected by random sampling of villages stratified for population size followed by coverage of all eligible persons in the village. All participating individuals were 35-64 years of age. Women constituted 52.2% (n = 1594) and 57% (n= 1417) of urban and rural samples, respectively. The study reveals that overweight is widely prevalent in the adult urban Delhi population, whereas underweight is a significant problem in the rural population. This was noted across all the age groups in both men and women. We estimated 'comprehensive coronary risk estimates' based on the New Zealand Heart foundation guidelines and noted that the proportion of high and very high risk subjects increased in a continuous manner even within the 'normal' ranges of BMI. This difference in prevalence in the urban population could represent the demographic transition in the Indian population.

Adult↗
PubMed2002

Cutaneous vascular function during acute hyperglycemia in healthy young adults.

Although it is well established that severe chronic hyperglycemia is associated with microvascular disease, it is not known whether transient hyperglycemia similar to that observed with impaired glucose tolerance or early Type 2 diabetes contributes to this pathology by altering microvascular function. To test the hypothesis that acute hyperglycemia decreases microvascular vasodilator responsiveness in human skin, we measured the cutaneous vasodilator response to local warming. This response can be divided into two phases, an initial peak that relies predominantly on local sensory nerves and a second slower phase that is largely dependent on endothelial nitric oxide. We reasoned that a change in one or both phases would indicate a change in the corresponding mechanism(s) with hyperglycemia. Twenty-eight healthy volunteers (14 women, 14 men) were randomly divided into three groups, corresponding to 6 h of euglycemia (n = 8), 6 h when glucose was clamped at approximately 7 mmol/l (n = 10), or 6 h when glucose was varied to mimic a postprandial pattern (i.e., peak glucose approximately 11.1 mmol/l) commonly observed in individuals with impaired glucose tolerance (n = 10). Insulin concentrations in all instances were maintained at approximately 65 pmol/l by means of continuous infusions of somatostatin and insulin. Glucagon and growth hormone were also continuously infused to maintain their basal concentrations. Despite substantial differences in both the level and pattern of glucose concentrations, neither maximum cutaneous vasodilation nor the pattern of the vasodilator response to local warming differed over the 6 h of study. We conclude that acute hyperglycemia similar to levels commonly observed in people with either early Type 2 diabetes or impaired glucose tolerance does not alter the vasodilator response to local warming of the skin in humans.

Acute Disease↗
PubMed2001

Advances in the stable isotope-mass spectrometric measurement of DNA synthesis and cell proliferation.

Methods for measuring rates of DNA synthesis, and thus cell proliferation, in humans had not been available until recently. We (D. C. Macallan, C. A. Fullerton, R. A. Neese, K. Haddock, S. S. Park, and M. K. Hellerstein, 1998, Proc. Natl. Acad. Sci. USA 95, 708-713) recently developed a stable isotope-mass spectrometric technique for measuring DNA synthesis by labeling the deoxyribose (dR) moiety of purine deoxyribonucleotides through the de novo nucleotide synthesis pathway. The original analytic approach had limitations, however. Here, we describe technical improvements that increase yield, stability, sensitivity, and reproducibility of the method. The purine deoxyribonucleoside, deoxyadenosine (dA), is directly isolated from hydrolysates of DNA by using an LC18 SPE column. Two derivatives were developed for analyzing the dR moiety of dA alone (without the base), an aldonitrile-triacetate derivative, and a reduced pentose-tetraacetate (PTA) derivative. The PTA derivative in particular exhibited greater stability (no degradation after several weeks), greater GC/MS signal, and much less abundance sensitivity of isotope ratios (i.e., less dependence of mass isotopomer abundances on the amount of material injected into the mass spectrometer source), compared to previous derivatives of dA. The need for complex, multidimensional abundance corrected standard curves was thereby avoided. Using the PTA derivative, dR enrichments from DNA of fully turned over cells of rodents with 2H2O enrichments in body water of 2.2-2.8% were 9.0-9.5%, and less than 1.0 microg DNA (ca. 2 x 10(5) cells) was required for reproducible analyses. In summary, these methodologic advances allow measurement of stable isotope incorporation into DNA and calculation of cell proliferation and death rates in vivo in humans and experimental animals, with fewer cells, greater reproducibility, and less labor. Many applications of this approach can be envisioned.

Animals↗
PubMed2001

Chronic atrial fibrillation in patients with rheumatic heart disease: mapping and radiofrequency ablation of flutter circuits seen at initiation after cardioversion.

BACKGROUND: There is little information concerning mapping and radiofrequency ablation (RFA) of arrhythmias seen during reinduction of atrial fibrillation (AF) after pharmacological and/or electrical cardioversion in patients with chronic AF and rheumatic heart disease. METHODS AND RESULTS: Seventeen patients with rheumatic heart disease and symptomatic chronic AF underwent multisite atrial mapping during reinduction of AF after cardioversion. An organized atrial arrhythmia of varying duration was seen to precede the AF in all patients. The earliest atrial activity during this organized rhythm was near the coronary sinus ostium (CS OS) in 14 patients and along the left side of the interatrial septum (IAS) in 3 patients. RFA was performed in 16 patients (14 near the CS OS and 2 along the IAS). Postablation AF was inducible in 1 patient in whom RFA was preformed near the CS OS and in both patients when it was performed along the IAS. At a follow-up of 6 to 56 weeks (mean, 32 weeks), 10 of the 13 patients who had successful ablation were in sinus rhythm. All patients in whom AF was reinducible immediately after RFA continue to be in AF. CONCLUSIONS: Induced AF in patients with rheumatic heart disease begins as a rapid organized arrhythmia with earliest atrial activity near the CS OS in most patients. RFA targeting the region of the CS OS is successful in suppressing the arrhythmia immediately in most of the patients and in most on follow-up.

Adult↗
PubMed2001

Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.

PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. RESULTS: Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. CONCLUSION: Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.

Adult↗
PubMed2001

Intracellular inhibition of human neutrophil elastase by orally active pyrrolidine-trans-lactams.

Described are the acylation binding of trans-lactam 1 to porcine pancreatic elastase, the selection of the SO2Me activating group for the lactam N which also confers metabolic stability in hamster liver microsomes, the introduction of aqueous solubility through the piperidine salt 9, the in vivo oral activity of 9 and its bioavailability, and the introduction of 9 as an intracellular neutrophil elastase inhibitor.

Acylation↗
PubMed2001

Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters.

BACKGROUND: Peripherally placed percutaneous central venous catheters (PCVC) are used in neonates to provide long-term vascular access. Major complications associated with these catheters include mechanical complications (catheter thrombosis, occlusion or dislodgement) and infection. Strategies to prevent catheter thrombosis and occlusion include the use of heparin. Systematic review has revealed that heparin is effective in prolonging the umbilical arterial catheter stay in neonates. However, heparin is known to be associated with complications such as bleeding and thrombocytopenia which may result in serious long-term sequelae. OBJECTIVES: The primary objective is to assess the effectiveness of heparin for prevention of catheter related thrombosis. The secondary objectives are to assess the effectiveness of heparin on catheter occlusion, duration of catheter patency, catheter related sepsis and complications associated with the use of heparin. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966- February 2001), EMBASE (1980-February 2001), CINAHL (1982-February 2001) and the Cochrane Controlled Trials Register ((Issue 1, 2001 of Cochrane Library) and abstracts from the annual meetings of the Society for Pediatric Research/American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2000). No language restrictions were applied. SELECTION CRITERIA: Selection criteria applied to the clinical trials were: the population had to be neonates, intervention had to be heparin infusion compared to placebo or no treatment for prevention of any of the complications related to peripherally placed PCVC, the trial had to be randomized or quasi-randomized and at least one of the primary or secondary outcomes reported. DATA COLLECTION AND ANALYSIS: The methodological quality of included trials was assessed using criteria for masking of randomization, masking of intervention, completeness of follow-up and masking of outcome measurement. Data on relevant outcomes were extracted and the effect size was estimated by calculating relative risk (95% CI) and risk difference (95% CI). MAIN RESULTS: One randomized trial on the use of heparin for peripherally placed PCVC was identified. The trial was excluded due to several methodological issues: 1. randomization was at the time of umbilical catheter placement rather than later PCVC placement 2. multiple PCVC were used in some infants, with reported results based on number of catheters rather than infants. Thus, the trial was not included in the review. REVIEWER'S CONCLUSIONS IMPLICATIONS FOR PRACTICE: Prophylactic use of heparin for prevention of complications related to peripherally placed PCVC has not been studied in well designed randomized controlled clinical trials. With the current state of knowledge routine use of heparin for this purpose cannot be recommended. Implication for research: Increasing survival of extremely low birth weight infants may be accompanied by prolonged intravenous access for nutrition. Well designed randomized controlled trials of sufficient power to determine the benefits and risks of continuous infusion of heparin in neonates with peripherally inserted PCVC are warranted.

Anticoagulants↗
PubMed2001

Alpha-1 proteinase inhibitor (a1PI) for preventing chronic lung disease in preterm infants.

BACKGROUND: Inflammation of the pulmonary parenchyma is one of the important mechanisms implicated in development of chronic lung disease (CLD) in preterm neonates. Release of enzymes and other anti - oxidants following cell damage is considered to be responsible for the damage to lung tissue. Various strategies have been attempted to counteract enzymatic damage to pulmonary parenchyma and to prevent CLD. OBJECTIVES: This review examines the effectiveness of alpha 1 proteinase inhibitor (a1PI) for the prevention of CLD defined as requirement of supplemental oxygen at 36 weeks post menstrual age (PMA) in preterm neonates. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966 - February 2001), EMBASE (1980 -February 2001), CINAHL (1982 - February 2001), Cochrane Controlled Trials Register (Issue 1, 2001 of Cochrane Library) and abstracts from the annual meetings of the Society of Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2000). No language restrictions were applied. SELECTION CRITERIA: Selection criteria applied to the clinical trials were: 1. The population had to be preterm neonates 2. The intervention had to be administration of a1PI compared to placebo or no treatment within the first week of life 3. The eligible studies had to include any of the following outcomes: a. prevention of CLD b. reduction in duration of assisted ventilation c. reduction in the duration of oxygen requirement d. reduction in the need for systemic antiinflammatory therapy e. reduction in mortality or f. reduction in long term adverse neurological sequelae. 4. The trial had to be randomized or quasi-randomized. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the authors. Data on relevant outcomes were extracted and the effect size was estimated and reported as pooled relative risk (RR), risk difference (RD) and weighted mean difference (WMD) as appropriate. Two strategies were used for analysis : 1. Comparison of 60 mg/kg/dose of a1PI administered for 4 days in first 2 weeks after birth, versus placebo and 2. Comparison of any dose of a1PI administered in first 2 weeks after birth, versus placebo. MAIN RESULTS: Two eligible studies were identified. The methodological qualities of identified studies were good. One study randomized infants to either placebo, or a1PI 60 mg/kg/dose for four doses while in the second study the same investigators explored the efficacy of different dose regimens of a1PI compared to placebo. There was no statistically significant difference in the development of CLD at 36 weeks PMA amongst all randomized infants. For 60 mg/kg/dose for four doses of a1PI compared to placebo the pooled RR was 0.64 [95% CI 0.35, 1.18] and RD was -0.10 [95% CI -0.23, 0.03] while for any doses of a1PI the pooled RR was 0.79 [95% CI 0.44, 1.41], RD was -0.05 [95% CI -0.17, 0.06]. There was a trend towards reduced risk of development of oxygen dependency at 28 days postnatal age, pooled RR 0.81 [95% CI 0.64, 1.01], RD -0.14 [95% CI -0.29, 0.00] for 60 mg/kg/dose for four doses of a1PI compared to placebo. The pooled RR was statistically significant, RR 0.80 [95% CI 0.65, 0.98], RD -0.15 (95 % CI -0.29, -0.01) when any doses of a1PI were combined. The number of patients needed to treat (NNT) with a1PI to prevent one infant developing oxygen dependency at 28 weeks was 7. The benefits of short-term outcomes did not remain for long-term outcomes such as CLD and/or death at 36 weeks post menstrual age (pooled RR 0.84 [95% CI 0.53, 1.34], RD -0.06 [95% CI -0.20, 0.09] for 60 mg/kg/dose and pooled RR 0.95 [95% CI 0.61, 1.49], RD -0.02 [95% CI -0.15, 0.12] for any dose) or risk of development of long term neurodevelopmental abnormalities (pooled RR 1.29 [95% CI 0.43, 3.90], RD 0.03 [95% CI -0.11, 0.18]). In addition, no statistically significant difference was noted in other respiratory parameters such as duration of oxygen requirement or respiratory support. REVIEWER'S CONCLUSIONS: Prophylactic administration of a1PI did not reduce the risk of CLD at 36 weeks or long term adverse developmental outcomes in preterm neonates.

Chronic Disease↗
PubMed2001

Type I diabetes mellitus does not alter initial splanchnic glucose extraction or hepatic UDP-glucose flux during enteral glucose administration.

AIMS/HYPOTHESIS: Our aim was to determine whether an alteration in splanchnic glucose metabolism could contribute to postprandial hyperglycaemia in people with Type I (insulin-dependent) diabetes mellitus. METHODS: Splanchnic glucose extraction, hepatic glycogen synthesis and endogenous glucose production were compared in 8 Type I diabetic patients and in 11 control subjects. Endogenous hormone secretion was inhibited with somatostatin while insulin (approximately 550 pmol/l) and glucagon (approximately 130 ng/l) concentrations were matched with exogenous hormone infusions. Glucose containing [3-3H] glucose was infused into the duodenum at a rate of 20 micromol.kg(-1).min(-1). Plasma glucose concentrations were maintained at about 8.5 mmol/l in both groups by means of a separate variable intravenous glucose infusion. RESULTS: Initial splanchnic glucose uptake, calculated by subtracting the systemic rate of appearance of [3-3H] glucose from the rate of infusion of [3-3H] glucose into the duodenum, did not differ in the diabetic and non-diabetic patients (4.1 +/- 0.8 vs 3.0 +/- 1.0 micromol/kg/min). In addition, hepatic glycogen synthesis, measured using the acetaminophen glucuronide method did not differ (10.7 +/- 2.4 vs 10.1 +/- 2.7 micromol.kg(-1).min(-1)). On the other hand, suppression of endogenous glucose production, measured by an intravenous infusion of [6,6-2H2] glucose, was greater (p < 0.05) in the diabetic than in the non-diabetic subjects (1.7 +/- 1.6 vs 5.8 +/- 1.9 micromol.kg(-1).min(-1)). CONCLUSION/INTERPRETATION: When glucose, insulin and glucagon concentrations are matched in individuals with relatively good chronic glycaemic control, Type I diabetes does not alter initial splanchnic glucose uptake of enterally delivered glucose or hepatic glycogen synthesis. Alterations in splanchnic glucose metabolism are not likely to contribute to postprandial hyperglycaemia in people with well controlled Type I diabetes.

Blood Glucose↗
PubMed2001

Cyclodiode photocoagulation for refractory glaucoma after penetrating keratoplasty.

OBJECTIVE: This study analyzes the results of intraocular pressure (IOP) reduction by contact diode cycloablation (cyclodiode) in cases of refractory glaucoma after penetrating keratoplasty. DESIGN: Retrospective noncomparative, interventional case series. PARTICIPANTS: Twenty-eight eyes in 28 patients attending the Moorfields Eye Hospital. INTERVENTION: Cyclodiode (40 applications x 1.5 W x 1.5 seconds over 270-300 degrees ) was used to control the IOP in refractory glaucoma after penetrating keratoplasty. MAIN OUTCOME MEASURES: Postoperative IOP, graft status, visual acuity, and number of antiglaucoma medications were recorded after cyclodiode treatment. RESULTS: Cyclodiode resulted in a reduction of IOP from a median of 33 mmHg (interquartile range [28, 40.5]) to a median of 15 mmHg (interquartile range [12, 20.5]). Most patients had a significant lowering in IOP with a median reduction of 16 mmHg (interquartile range [12, 25]; P < 0.0001). IOPs of 6 to 21 mmHg were achieved in 22 patients (79%). Sixteen patients (57%) required more than one treatment with cyclodiode to control the IOP, with three patients (11%) requiring three treatments and two patients (7%) requiring four treatments. Visual acuity improved (> two Snellen lines of acuity) in three patients (11%) and remained the same (+/- one Snellen line) in 17 patients (61%). The mean number of antiglaucoma medications before cycloablation was 2.6 and was 1.8 after treatment (P < 0.001). Of the 19 patients (68%) with originally clear grafts, three grafts (16%) developed opacification. One patient (4%), with a history of nanophthalmos and recurrent uveal effusion, had delayed hypotony (IOP < 6 mmHg) occurring 46 months after the diode treatment. All patients had at least 6 months follow-up. CONCLUSIONS: These patients have often undergone multiple previous complicated ocular interventions and are often not suitable for filtration surgery. Reduction of IOP with maintenance of visual acuity and a good safety profile was achieved in most patients in this study but may require multiple treatments. We propose cyclodiode as an effective treatment for many patients in the management of refractory glaucoma after penetrating keratoplasty.

Adult↗
PubMed2001

Exercise-induced visual loss associated with advanced glaucoma in young adults.

PURPOSE: To highlight the phenomenon of exercise-induced visual loss associated with advanced glaucoma and to discuss the possible underlying mechanisms. METHODS: Three young adult patients with congenital or juvenile-onset glaucoma presenting with visual loss which occurred during exercise underwent ophthalmic examination. In 2 cases, visual function parameters, including visual fields (Humphrey full threshold perimetry) were measured before and after exercise. RESULTS: All patients clearly described visual loss during exercise. In the 2 cases in which data were available, significant impairment in central visual acuity and reduced foveal sensitivity and mean deviation on visual field analysis occurred during exercise of mild to moderate intensity with complete or near complete recovery of visual function upon cessation of exercise. CONCLUSION: Young patients with advanced glaucomatous optic neuropathy should be questioned regarding exercise-induced visual disturbance. We hypothesise that a 'vascular steal' is the likely mechanism underlying this phenomenon. Patients should be advised to limit activities which induce their symptoms, and therapeutic measures to promote ocular blood flow should be considered.

Adult↗
PubMed2001

Pituitary-adrenal function following dexamethasone-cyclophosphamide pulse therapy for pemphigus.

BACKGROUND: Systemic corticosteroid therapy is known to lead to pituitary-adrenal (PA) suppression. Although patients treated for pemphigus with dexamethasone-cyclophosphamide pulse (DCP) therapy have shown no evidence of PA suppression, no study has been conducted to study this possible side-effect of DCP therapy. OBJECTIVES: To study the effect of DCP therapy for pemphigus on PA function. METHODS: A cross-sectional study was carried out in 33 patients who completed phase II of DCP therapy in a single centre, a large teaching hospital in New Delhi, India. Serum cortisol levels following adrenocorticotrophic hormone stimulation were analysed in 31 patients. RESULTS: Seventeen (55%) patients showed suppressed PA function. Suppressed function occurred more frequently in patients who had received pulses of dexamethasone in addition to DCP therapy in the first phase of treatment (P = 0.055). CONCLUSIONS: Suppressed PA function occurs in about half of patients who receive DCP therapy for pemphigus. These patients probably do not require routine replacement therapy with corticosteroids but may need supplementation during periods of stress.

Adolescent↗