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Biomedical subjects

N Shah

Publications and source records attributed to N Shah.

At least 109 records · Page 6Linked to original sources

The impact of FDG positron emission tomography imaging on the management of lymphomas.

The role of 2-(F-18)-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) imaging in the management of patients with lymphoma has been evaluated. 29 patients (12 Hodgkin's disease, 17 non-Hodgkin's lymphoma (NHL)) who underwent FDG-PET imaging during their lymphoma treatment programme were reviewed retrospectively. Correlation between FDG-PET and CT was evaluated, together with the impact upon clinical management of the findings on FDG-PET imaging. FDG-PET added extra information to the findings on clinical examination and CT in 12 patients (41%). This was seen both in patients with negative and positive CT scan. Two false positive FDG-PET scans were seen, reflecting FDG uptake in extranodal sites. Information from FDG-PET imaging resulted in a change in clinical management in 10 patients (34%); in two, initial management was altered, and in eight consolidation therapy after completion of initial chemotherapy was influenced. These changes in clinical management occurred in six patients with high grade NHL, two with low grade NHL and two with Hodgkin's disease. No specific subgroup was identified in whom FDG-PET was particularly discriminant.

Adolescent↗

A pilot study to assess the feasibility of prior scalp cooling with palliative whole brain radiotherapy.

The objective of this work was to perform a feasibility study on the use of scalp cooling during palliative whole brain radiotherapy. Seven patients (1 male, 6 female) with good performance status underwent scalp cooling prior to and during radiotherapy for cerebral metastases. Five patients were prescribed 12 Gy in two fractions and two patients were prescribed 20 Gy in five fractions. Phantom thermoluminescent dosemeter (TLD) studies to assess the build-up effect from the scalp cap were performed. Seven out of eight patients that were offered scalp cooling completed treatment uneventfully. One patient reported discomfort on application of the scalp cap and continued treatment without scalp cooling. No patients reported other adverse effects from use of the cap during treatment or at follow-up. TLD studies demonstrated a 55-80% increase in dose to the scalp after application of the scalp cap. All patients experienced hair loss. Scalp cooling caps are well tolerated through a course of palliative whole brain radiotherapy. The scalp dose is significantly increased owing to a bolus effect from the scalp cap.

Adult↗

Vasoactive agents modulate migration of monocytes across glomerular endothelial cells.

BACKGROUND: Macrophages seem to play an important role in the development of glomerulosclerosis. In both human and experimental animal models of focal glomerulosclerosis (FSGS), infiltration of macrophages in the mesangium has been considered key in the development of FSGS. METHODS: In the present study, we evaluated the effect of vasoactive agents on the migration of monocytes across a filter in a modified Boyden chamber as well as across a cultured glomerular endothelial cell layer (in vitro model of glomerular mesangium). Both light as well as scanning electron microscopic studies were performed. We evaluated the effect of vasoactive agents including histamine, prostaglandin (PG) E2, angiotensin II, endothelin-1, platelet-activating factor, and interleukin-1 (IL) on the migration of monocytes/macrophages across an endothelial cell layer as well as a gelatin-coated filter. In addition, we evaluated the effect of cyclic adenosine 3',5' cyclic monophosphate (cAMP) and PGE2 on vasoactive-induced migration of monocytes. RESULTS: Histamine increased (P < 0.003) the migration of monocytes across the filter. This effect of histamine was dose-dependent. Histamine at concentrations of 10(-8) to 10(-5) mol/L induced optimal migration across the filter (control, 16.6 +/- 1.1 vs histamine, 10(-8) mol/L, 40.9 +/- 0.9 monocytes/high power field). Cimetidine, an H2 receptor blocker, attenuated (P < 0.001) the effect of histamine on the migration of monocytes. PGE2 inhibited the migration of monocytes in a dose-dependent manner. Histamine increased (P < 0.001) the passage of monocytes across the glomerular endothelial cell layer (control, 1012 +/- 37 vs 1711 +/- 163 cpm/well). Histamine also increased the migration of murine macrophages across the glomerular endothelial cell layer. PGE2 inhibited the migration of monocytes across the endothelial cell layer under basal as well as histamine-stimulated states. Dibutyryl cyclic (DBc) AMP also attenuated the migration of monocytes under basal as well as histamine-stimulated states. Both PGE2 and DBcAMP also attenuated the IL-1 beta-stimulated migration of monocytes. Angiotensin II, endothelin-1, and platelet-activating factor did not modulate the migration of monocytes. CONCLUSIONS: Vasoactive agents directly modulate the transmigration of monocytes. The present in vitro study provides a basis for a hypothesis that vasoactive agents may also be modulating the migration of monocytes across the glomerular endothelial cell layer (into the mesangium).

Animals↗

Effect of yogic practices on subjective well being.

Forty eight healthy volunteers who participated in the practice of yoga over a period of 4 months were assessed on Subjective Well Being Inventory (SUBI) before and after the course in order to evaluate the effect of practice of yoga on subjective feelings of well-being and quality of life. A significant improvement in 9 of the 11 factors of SUBI was observed at the end of 4 months, in these participants. The paper thus, reiterates the beneficial effects of regular practice of yoga on subjective well being.

Adult↗

Age related seroprevalence of antibodies to varicella in India.

OBJECTIVE: To determine the age related prevalence of Varicella Zoster Virus (VZV) antibodies in India. SETTING: This was a cross sectional multicentric study performed in 4 major cities of India: Calcutta (outpatients), Mumbai (outpatients), Lucknow (walk-in patients to a diagnostic laboratory, orphanage and factory workers) and Bangalore (outpatients and walk-in patients to a diagnostic laboratory). METHODS: A total of 1609 volunteers from birth to 40 years of age were included into the study. IgG antibodies against VZV were determined using commercial kits (ELISA-Enzygnost). RESULTS: Overall seroprevalence of anti VZV antibodies was 68. 22percnt. The age related seroprevalence rate of anti VZV antibodies was 29percnt in the age group of 1-5 years, 51.1percnt in 5-10 years, 71.7percnt in 11-15 years, 79.8percnt in 16-20 years, 88.1percnt in 21-30 years and 91.1percnt in 31-40 years. CONCLUSION: A significant proportion of adolescents and adults are susceptible to varicella in India, as in other tropical countries

Adolescent↗

Microenvironmental influences on human B-cell development.

Mammalian B-cell development can be viewed as a developmental performance with several acts. The acts are represented by checkpoints centered around commitment to the B-lineage and functional Ig gene rearrangement--culminating in expression of the pre-B-cell receptor (pre-BCR) and the BCR. Progression of cells through these checkpoints is profoundly influenced by the fetal liver and adult bone marrow (BM) stromal cell microenvironments. Our laboratory has developed a model of human B-cell development that utilizes freshly isolated/non-transformed human BM stromal cells as an in vitro microenvironment. Human CD34+ hematopoietic stem cells plated in this human BM stromal cell microenvironment commit to the B lineage and progress through the pre-BCR and BCR checkpoints. This human BM stromal cell microenvironment also provides survival signals that prevent apoptosis in human B-lineage cells. Human B-lineage cells exhibit differential expression of Notch receptors and human BM stromal cells express the Notch ligand Jagged-1. These results suggest a potential role for Notch in regulating B-lineage commitment and/or progression through the pre-BCR and BCR checkpoints.

Apoptosis↗

Activation of nuclear factor kappaB by polyamines in breast cancer cells.

Polyamines-putrescine, spermidine, and spermine-are involved in the growth of breast cancer cells. A possible target of polyamine action is at the site of interaction of transcription factors with their response elements. NF-kappaB is a member of the rel family of transcription factors that regulate transcription of genes in the proliferative/anti-apoptotic pathways. We performed electrophoretic mobility shift assays to study the role of polyamines in NF-kappaB binding to NF-kappaB response elements (NREs), the consensus sequence of which is GGGGAATTCCCC. Using cellular extract from MCF-7 breast cancer cells, we found very little binding of NF-kappaB to NRE in the absence of polyamines. Addition of 1 mM spermidine or spermine caused a 4- and 6-fold increase in NF-kappaB-NRE binding, respectively. Putrescine induced a 2-fold increase in the binding at 2 mM concentration. Using antibody supershift assays, we identified the p50 subunit of NF-kappaB to be a major component in NF-kappaB-NRE complex formation in the presence of polyamines. However, the decreased intensity of the band corresponding to NF-kappaB-NRE complex in the presence of anti-p65, c-rel, relB and p52 antibodies suggested the participation of these subunits also. Spermine also stimulated NF-kappaB-NRE binding using cellular extracts from other breast cancer cell lines and a normal breast epithelial cell line. A differential effect of spermine analogues on NF-kappaB-NRE binding was observed, with spermine exerting the maximal effect. CD spectra of NRE containing oligonucleotides was asymmetric and distinct from that of a typical B-DNA CD spectrum. A concentration-dependent increase in T(m) of the duplex NRE was seen in the presence of polyamines. In transient transfection experiments using an NF-kappaB driven secreted alkaline phosphatase (SEAP) reporter, spermine induced NF-kappaB activity by approximately 2-fold as compared to controls. Spermine induced activation of NF-kappaB was also confirmed using an NF-kappaB-EGFP (enhanced green fluorescent protein) vector in transient transfections in which expression of the green fluorescent protein was visualized by fluorescence microscopy. These data show a gene regulatory function of polyamines involving enhanced binding of NF-kappaB to NRE and a possible mechanism for the action of polyamines in breast cancer cell proliferation.

Breast Neoplasms↗

Antitumor effects of bis(ethyl)polyamine analogs on mammary tumor development in FVB/NTgN (MMTVneu) transgenic mice.

We studied the therapeutic potential of two polyamine analogs on breast cancer using FVB/NTgN (MMTVneu), a transgenic mouse model with neu/erb-B2 oncogene overexpression. Treatment was initiated at 31 weeks of age with bis(ethyl)norspermine (BE333) and its higher homolog, BE3333 as i.p. injections once weekly. There was a 40% reduction in the average number of tumors per mouse in both treatment groups, by 10 weeks of treatment. BE3333-treated mice had 70-75% lower tumor volume than controls. Spermidine/spermine acetyl transferase activity was significantly higher in tumor tissues and kidneys of treated animals, whereas polyamine levels were lower than controls. Beneficial effects were also evident from the mortality rates in control and treatment groups. Our results suggest a potential use of selected bis(ethyl) polyamine analogs as antitumor agents in breast cancer.

Acetyltransferases↗

Carbamazepine pharmacokinetics-pharmacodynamics in genetically epilepsy-prone rats.

Carbamazepine produces dose-related anticonvulsant effects in epilepsy models including the genetically epilepsy-prone rat (GEPR) model and the rat maximal electroshock model. Dose-response relationships are quantitatively different among the models. Against electroshock seizures in Sprague-Dawley rats the ED50 dose is 7.5 mg/kg whereas the ED50 against audiogenic seizures in severe seizure GEPRs (GEPR-9s) is 3 mg/kg. In contrast, the ED50 in moderate seizure GEPRs (GEPR-3s) is 25 mg/kg. The present study was designed to ascribe dose-response differences among the three rat strains to pharmacokinetic or pharmacodynamic factors. After systemic carbamazepine, pharmacokinetic studies revealed differences in area under the concentration-vs.-time curve. In other experiments, carbamazepine-induced serotonin release from hippocampus was used as a pharmacodynamic marker. In a concentration-controlled design using intracerebral microdialysis, hippocampal carbamazepine infusions produced similar concentration-response relations for the three rat strains. These data support the hypothesis that dose-response differences among the three rat strains are primarily pharmacokinetic in nature.

Acoustic Stimulation↗

Ethanol-induced neutrophil apoptosis is mediated through nitric oxide.

Clinical reports indicate that acute ethanol intoxication in chronic ethanol abusers is associated with neutropenia. We hypothesize that ethanol accelerates the apoptosis of neutrophils thus decreasing the peripheral blood count of neutrophils. We studied the effect of ethanol on neutrophil apoptosis in vivo as well as in vitro. Human neutrophils harvested from healthy subjects after an alcohol drinking binge showed enhanced apoptosis (before, 0.5+/-0.25 vs. after, 26.1+/-2.6% apoptotic neutrophils/field). Peritoneal neutrophils isolated from ethanol-treated rats also showed increased (P < 0.0001) apoptosis when compared with neutrophils isolated from control rats (control, 0.8+/-0.2% vs. ethanol, 11.8+/-0.7% apoptotic neutrophils/field). In in vitro studies, ethanol in concentrations of 50 mM and higher accelerated the apoptosis of human and rat neutrophils. This effect of ethanol on human neutrophils was time dependent. DNA isolated from ethanol-treated human neutrophils displayed integer multiples of 180 base pairs (ladder pattern), further confirming the effect of ethanol on neutrophil apoptosis. N(G)-monomethyl-L-arginine monoacetate and N(G)-nitro-L-arginine methyl ester, inhibitors of nitric oxide (NO) synthase, attenuated the ethanol-induced neutrophil apoptosis. Sodium nitroprusside, a NO donor, also promoted neutrophil apoptosis. Moreover, ethanol enhanced neutrophil expression of inducible NO synthase. In addition, ethanol stimulated neutrophil NO generation. These results suggest that ethanol accelerates neutrophil apoptosis. This effect of ethanol on neutrophil apoptosis seems to be mediated through the generation of NO.

Animals↗

Needle-exchange attendance and health care utilization promote entry into detoxification.

This study was undertaken to identify factors associated with entry into detoxification among injection drug users (IDUs), and to assess the role of needle-exchange programs (NEPs) as a bridge to treatment. IDUs undergoing semiannual human immunodeficiency virus (HIV) tests and interviews were studied prospectively between 1994 and 1998, during which time an NEP was introduced in Baltimore. Logistic regression was used to identify independent predictors of entry into detoxification, stratifying by HIV serostatus. Of 1,490 IDUs, similar proportions of HIV-infected and uninfected IDUs entered detoxification (25% vs. 23%, respectively). After accounting for recent drug use, hospital admission was associated with four-fold increased odds of entering detoxification for HIV-seronegative subjects. Among HIV-infected subjects, hospital admission, outpatient medical care, and having health insurance independently increased the odds of entering detoxification. After accounting for these and other variables, needle-exchange attendance also was associated independently with entering detoxification for both HIV-infected (adjusted odds ratio [AOR] = 3.2) and uninfected IDUs (AOR = 1.4). However, among HIV-infected subjects, the increased odds of detoxification associated with needle exchange diminished significantly over time, concomitant with statewide reductions in detoxification admissions. These findings indicate that health care providers and NEPs represent an important bridge to drug abuse treatment for HIV-infected and uninfected IDUs. Creating and sustaining these linkages may facilitate entry into drug abuse treatment and serve the important public health goal of increasing the number of drug users in treatment.

Adult↗

Nitroglycerin is superior to diltiazem as a coronary bypass conduit vasodilator.

BACKGROUND: Recent reports of improved radial artery patency have been attributed, in part, to routine use of diltiazem to prevent vasospasm. However, diltiazem is costly, and its use may be associated with negative inotropic and chronotropic side effects. This study compares the vasodilatory properties of diltiazem to those of nitroglycerin. METHODS: In vitro, with the use of organ chambers, the vasodilatory properties of diltiazem and nitroglycerin were compared in matched segments of radial artery, internal thoracic artery, and saphenous vein that were harvested from the same patients (n = 11). The vasodilatory response of the radial artery to intravenous diltiazem or nitroglycerin was compared in vivo (n = 10) with the use of ultrasonographic measurements of radial artery diameter. RESULTS: The maximum relaxation of radial artery (100% +/- 4%), internal thoracic artery (96% +/- 4%), and saphenous vein (100% +/- 3%) to nitroglycerin were significantly greater than the response to diltiazem (33% +/- 6%, 22% +/- 7%, and 34% +/- 5%, respectively; P <.001). The thromboxane mimetic, U46619, induced radial artery spasm with a median effective concentration of 3.7 +/- 0.8 nmol/L. Physiologic concentrations of nitroglycerin (0.1+/- micromol/L) significantly inhibited the radial artery response to U46619 (median effective concentration, 6.2 +/- 1.1 nmol/L; P =.046), whereas diltiazem (1 micromol/L) did not (median effective concentration, 3.7 +/- 0.8 nmol/L; P =.64). In vivo, nitroglycerin increased radial artery diameter 22% +/- 3%, which was significantly greater than diltiazem (3% +/- 0.5%; P =.001). CONCLUSION: Nitroglycerin is a superior conduit vasodilator and is more effective in preventing graft spasm than diltiazem. Nitroglycerin should be strongly considered as the drug of choice to prevent conduit spasm after coronary bypass grafting.

Adult↗

Prevalence of smoking among currently married Kuwaiti males and females.

A structured questionnaire was administered to a random sample of 608 Kuwaiti couples through a household face-to-face interview. Both spouses were non-smokers in more than half (50.8%) of all the couples, and there was a single couple (0.2%) with both spouses currently smoking. Only 0.5% of the wives reported current smoking. The prevalence of smoking was 3.2% among divorced/widowed women from the same households. The difference between the two groups of women remained significant upon controlling for the confounding effect of age. Among the husbands, frequencies of current and ex-smokers were 37% and 11%, respectively. Younger respondents consumed more tobacco and were initiated to smoking at an earlier age. Logistic regression showed that people with one to 11 years of formal education were more likely to be current smokers as compared to the rest of the respondents (adjusted relative risk: 2.07, 95% confidence interval (CI): 1.46-2.93). Reasons for the observed findings have been discussed.

Adult↗

Does wound healing contribute to the eradication of basal cell carcinoma following curettage and electrodessication?

BACKGROUND: Histologic studies indicate that C&D fails to mechanically remove all the tumor in a percentage of cases that far exceeds the 5-year recurrence rate. This raises the question that if C&D does not mechanically remove the tumor in a significant number of patients, why don't we observe tumor recurrence in most of these patients? Our previous study indicates that inflammation occurring over 1 month following C&D does not clear residual tumor. It may be some other process, requiring more time, that clears the residual tumor. Perhaps the proliferative or maturation phase of wound healing or, alternatively, a slow-acting process such as a low-grade immune response set in motion earlier, clears the residual tumor. OBJECTIVE: To test the hypothesis that wound healing and maturation following C&D clear residual tumor that has not mechanically removed by the procedure. METHODS: The frequency of residual BCC detected histologically immediately following C&D was compared with the frequency 3 months after the C&D, an amount of time in which the maturation phase of wound healing is well under way. RESULTS: Twenty-two of 29 primary BCC less than 1 cm in size were tumor-free immediately following the procedure (clearance rate 75.9%). Twelve primary BCC <1 cm were treated by C&D, allowed to heal for 3 months, and then excised and checked histologically. Ten of the twelve BCC were free of tumor, for a clearance rate of 83.3%, which is not a statistically significant difference (p = 0.7187). CONCLUSION: By 3 months, the proliferative phase of wound healing is complete, and our study indicates that this phase has no effect on clearing the tumor. The maturation phase is well under way three months following C&D, and no statistically significant effect was observed.

Basal Cell Carcinoma↗

Neurally mediated syncope: pathophysiology and implications for treatment.

Neurally mediated syncope may occur in patients whose hemodynamic picture does not fit the characteristics of orthostatic intolerance as described elsewhere in this issue. Nonetheless, patients who suffer from neurocardiogenic or vasovagal syncope may be seriously incapacitated by their episodes of syncope or presyncope. Although it has been assumed that vagal activation as a result of stimulation of ventricular mechanoreceptors is essential to the production of these episodes, several critical observations are presented that suggest that other mechanisms may also be operative in some patient subsets. In addition, evidence is presented that the sympathetic responses of many of these patients may be reduced rather than increased and that abnormal baroreflex responsiveness may also play an causative role. These findings suggest new avenues for therapy in this field in which carefully controlled, randomized, double-blind trials are scarce.

Autonomic Nervous System↗

Feeding difficulties and foregut dysmotility in Noonan's syndrome.

PURPOSE: Noonan's syndrome is a common dysmorphic syndrome in which failure to thrive and gastrointestinal symptoms are frequent but poorly understood. DESIGN: Twenty five children with Noonan's syndrome were investigated by contrast radiology, pH monitoring, surface electrogastrography (EGG), and antroduodenal manometry (ADM). RESULTS: Sixteen had poor feeding and symptoms of gastrointestinal dysfunction. All 16 required tube feeding. Seven of 25 had symptoms of foregut dysmotility and gastro-oesophageal reflux. In the most symptomatic children (four of seven) EGG showed fasting frequency gradient loss along the stomach fundus and pylorus with antral postprandial frequency loss. ADM showed shortened fasting cycle length, with abnormal phase III and shortened postprandial activity containing phasic contractions. IMPLICATIONS: Gastroduodenal motor activity was reminiscent of 32-35 week preterm patterns. The feeding difficulties appear to resolve as gut motility matures. In Noonan's syndrome, feeding problems appear to be the result of delayed gastrointestinal motor development.

Barium Sulfate↗

Actions of estrogen on pulsatile, nyctohemeral, and entropic modes of growth hormone secretion.

The neuroendocrine mechanisms by which estradiol drives growth hormone (GH) secretion in the human are poorly defined. Here we investigate estrogen's specific regulation of the 24-h pulsatile, nyctohemeral, and entropic modes of GH secretion in healthy postmenopausal women. Volunteers (n = 9) received randomly ordered placebo versus estradiol-17beta (1 mg micronized steroid twice daily orally) treatment for 7-10 days and underwent blood sampling at 10-min intervals for 24 h to capture GH release profiles quantitated in a high-sensitivity chemiluminescence assay. Pulsatile GH secretion was appraised via deconvolution analysis, nyctohemeral GH rhythms by cosinor analysis, and the orderliness of GH release patterns via the approximate entropy statistic. Mean (+/-SE) 24-h serum GH concentrations approximately doubled on estrogen treatment (viz., from 0.31 +/- 0.03 to 0.51 +/- 0.07 microgram/l; P = 0.033). Concomitantly, serum insulin-like growth factor-I (IGF-I), luteinizing hormone, and follicle-stimulating hormone concentrations fell, whereas thyroid-stimulating hormone and prolactin levels rose (P < 0.01). The specific neuroendocrine action of estradiol included 1) a twofold amplified mass of GH secreted per burst, with no significant changes in basal GH release, half-life, pulse frequency, or duration; 2) an augmented amplitude and mesor of the 24-h rhythm in GH release, with no alteration in acrophase; and 3) greater disorderliness of GH release (higher approximate entropy). These distinctive and dynamic reactions to estrogen are consistent with partial withdrawal of IGF-I's negative feedback and/or accentuated central drive to GH secretion.

Aged↗