Search PubMed⌕ Search

Biomedical subjects

S Patel

Publications and source records attributed to S Patel.

At least 199 records · Page 11Linked to original sources
PubMed2000

Conditionally immortal neuroepithelial stem cell grafts reverse age-associated memory impairments in rats.

In order to investigate the effects of stem cell grafts on water maze deficits in aged (22-month-old) rats, three groups of aged rats, assigned by pre-training latency scores to unimpaired, impaired control and impaired grafted groups, were compared with young (five-month-old) controls, six to eight weeks after implantation of cells from the conditionally immortal Maudsley hippocampal stem cell line, clone 36 (MHP36 stem cell line), in the cortex, striatum and hippocampus. Grafted rats were substantially superior to their matched impaired aged controls, and learned to find the platform as rapidly as unimpaired aged rats, although young controls were more efficient than all aged groups in several measures of spatial search during training. On the probe trial, however, aged rats with grafts showed significantly better recall of the precise position of the platform than any other group, including young controls, possibly indicating some perseveration. A further comparison found that groups of unimpaired and moderately impaired aged rats showed far less improvement from water maze pre-training to acquisition phases than young controls, indicative of progressive deficits over time. Histological investigation showed that beta-galactosidase-positive MHP36 cells migrated widely from the implantation sites to infiltrate the striatal matrix, all hippocampal fields and areas of the cortex. Grafted cells showed both astrocytic and neuronal morphologies, with cells of pyramidal and granular appearance in appropriate hippocampal strata.Taken together, these results indicate that neuroepithelial stem cell grafts extensively colonize the aged rat brain and substantially reverse progressive cognitive decline associated with ageing.

Aging↗
PubMed2000

Analysis of promoter region polymorphism in the aldosterone synthase gene (CYP11B2) as a risk factor for myocardial infarction.

Several polymorphisms in genes of the reninangiotensin-aldosterone system have been found to have pleiotropic effects on cardiovascular disorders. Recently, a polymorphism (-344 C/T) in the promoter region of the aldosterone synthase gene (CYP11B2), which may influence plasma aldosterone levels, has been reported to strongly influence left ventricular diameters and mass in young adults and arterial stiffness in essential hypertensives. We investigated any association with risk of myocardial infarction (MI). CYP11B2 -344 polymorphism genotypes were determined by polymerase chain reaction (PCR) in 542 acute MI cases and 500 control subjects without history of coronary disease. All subjects were white and <75 years old. There was no significant difference in either genotype distributions (cases CC 17%, CT 52%, TT 31%; controls CC 22%, CT 47%, TT 31%, P = .10) or allele frequencies (cases C/T 0.43/0.57, controls C/T 0.46/0.54, P = .39) between cases and controls. The odds ratio (OR) for MI associated with the CC genotype was 0.75 (0.54-1.05), and remained insignificant when analysis was restricted to the 129 (24%) cases and 193 (37%) controls < 55 years of age (OR 0.68 [0.36-1.27], P = .20). In further analyses, there was no interaction of the polymorphism with other cardiovascular risk factors (smoking, hypertension, diabetes, body mass index, or cholesterol level) in determining MI risk, and the polymorphism did not influence the frequency of these risk factors in either cases or controls. In the case cohort, age at MI was not significantly different in subjects with the three genotypes (CC 61.2 +/- 9.8 years, CT 61.8 +/- 9.1 years, TT 62.2 +/- 9.0 years, P = .69). We conclude that the aldosterone synthase -344 promoter region polymorphism does not significantly influence the risk of MI either directly or via interaction with other risk factors.

Alleles↗
PubMed2000

Topical hepatic hypothermia attenuates pulmonary injury after hepatic ischemia and reperfusion.

BACKGROUND: Prolonged periods of hepatic ischemia are associated with hepatocellular injury and distant organ dysfunction in experimental models. Neutrophils (PMN) and tumor necrosis factor (TNF)-alpha have been implicated, mostly because of their local deleterious effects on the hepatocyte after hepatic ischemia and reperfusion (I/R) injury. We hypothesize that topical hepatic hypothermia (THH) reduces ischemia and reperfusion-induced hepatic necrosis, PMN infiltration, TNF-alpha release, and consequent acute pulmonary injury. STUDY DESIGN: Sprague-Dawley rats (250 to 300g) were evenly divided into three groups: 90 minutes of normothermic (37 degrees C) partial hepatic ischemia (normothermic I/R), 90 minutes of hypothermic (25 degrees C) partial hepatic ischemia (hypothermic I/R), and sham laparotomy (without ischemia). There were six animals in each experimental group per time point unless otherwise specified. Hepatic necrosis and PMN infiltration were evaluated and scored on hematoxylin and eosin-stained liver specimens 12 hours after reperfusion. Serum TNF-alpha levels were determined by ELISA at 0 minutes, 15 minutes, 30 minutes, 1 hour, and 12 hours postreperfusion. Pulmonary PMN infiltration and vascular permeability were measured by myeloperoxidase activity and Evans blue dye extravasation, respectively, to quantitate pulmonary injury 12 hours after reperfusion. RESULTS: Normothermic I/R results in a significant increase in TNF-alpha at 15 and 30 minutes (p < 0.005), PMN infiltration (p < 0.001), and hepatic necrosis (p < 0.001), compared with sham. Institution of THH reduced peak serum TNF-alpha levels by 54% at 15 minutes (p < 0.005) and by 73% at 30 minutes (p < 0.001) postreperfusion compared with normothermic I/R. Similarly, hepatic PMN infiltration and necrosis at 12 hours were reduced by 60% (p < 0.05) and 47% (p < 0.05), respectively. Myeloperoxidase activity and Evans blue extravasation (measures of acute lung injury) were reduced by 42% and 39%, respectively, with institution of THH compared with animals undergoing normothermic I/R (p < 0.001). CONCLUSIONS: These results demonstrate that THH protects the liver from ischemia and reperfusion-induced necrosis and PMN infiltration. In addition, THH reduces the serum levels of TNF-alpha and associated pulmonary injury. These data suggest that the ischemic liver is a potential source of inflammatory mediators associated with hepatic ischemia and reperfusion-induced pulmonary injury.

Analysis of Variance↗
PubMed2000

Age, stability of the precorneal tear film and the refractive index of tears.

PURPOSE: To investigate the relationship between age, stability of the precorneal tear film and refractive index of tear samples drawn from a normal population. METHODS: The stability of the precorneal tear film was estimated by measuring the Tear Thinning Time MT) using the Bausch and Lomb keratometer. Microlitre tear samples were obtained from the lower tear meniscus using glass capillary tubes. The refractive index (RI) was measured using a digital electronic Abbe refractometer with an accuracy of +/- 0.00005 units. Measurements were obtained from the right eyes of 110 subjects (55 male and 55 female) ranging in age from 18 to 89 years. They were all healthy, non-contact lens wearing individuals with no history of ocular disease or dry eye symptoms. RESULTS: A significant relationship was found between age (x) and tear stability (TTT) in both genders. Females, TTT = 32.89-0.33x, (Spearman correlation coefficient, r = -0.537, P = 0.0001). Males, TTT = 29.25-0.29x (Spearman correlation coefficient, r = -0.353, P = 0.008). A significant correlation was found between age (x) and refractive index (RI) in females only RI = 1.33815-0.000023x, (Spearman correlation coefficient, r = -0.299, P = 0.027). CONCLUSION: Tear stability is lower in the aged eye regardless of gender. Tear refractive index is lower in the older female eye.

Journal Article↗
PubMed2000

Combination gene therapy using multiple immunomodulatory genes transferred by a defective infectious single-cycle herpes virus in squamous cell cancer.

Herpes simplex type 2-defective infectious single-cycle (DISC) viruses are attenuated viruses that were originally produced as viral vaccines; however, these viruses are also efficient gene transfer vehicles. The main goals of this study were to examine determinants of the gene transfer by using DISC virus for squamous cancer and to evaluate the antitumoral efficacy of vaccination with tumor cells modified by DISC viruses carrying a combination of immunomodulatory genes (interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF), B7-1) in a model of squamous cell cancer (SCCVII) in C3H/HeJ mice. SCCVII cells transduced by DISC viruses (multiplicity of infection of 10) carrying the IL-2 or GM-CSF gene produced nanogram quantities of IL-2 or GM-CSF per 10(6) cells. Irradiated (5,000 cGy, 10,000 cGy) cells secreted levels of GM-CSF or IL-2 that were comparable with nonirradiated cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-IL2 or DISC-GMCSF resulted in protection against subsequent tumor challenge (P < .01), with DISC-GMCSF-transduced, irradiated tumor cells showing the greatest effects (P < .001). Marked growth arrest also was noted in established tumors after direct injection of DISC-GMCSF (P < .001). These data demonstrate that (a) DISC virus is capable of efficient gene transfer, (b) GM-CSF-secreting genetically modified tumor vaccine protects against tumor cell challenge and suppresses tumor growth, and (c) intratumoral injection of DISC-GMCSF significantly suppresses the growth of established tumors. These results not only confirm clinically relevant gene transfer but also demonstrate that the gene transfer is an effective anti-cancer therapy.

Animals↗
PubMed2000

Effects of lipids in patients with familial hypercholesterolaemia on the kinetics of the sodium-lithium countertransporter.

Sodium-lithium countertransport kinetics were measured in 87 patients (50 male; 37 female) with heterozygous familial hypercholesterolaemia (FH) and a group of 38 age range and sex-distribution matched controls. Basic clinical data including basic anthropometry, blood pressure were obtained and blood was taken for detailed lipid biochemistry, glucose and insulin measurement. Patients with FH had elevated total cholesterol, low-density lipoprotein (LDL)-cholesterol and apolipoprotein B concentrations compared to controls. The activity and log transformed maximal velocity (Vmax) of the sodium-lithium countertransporter unlike the affinity (Km) were reduced in patients with FH compared to controls (geometric means 0.172 vs 0.217 mmol Li+/L.RBC.hr; P = 0.02; 0.237 vs. 0.317 mmol Li+/L.RBC.hr; P = 0.009 respectively). In multiple regression analysis, log normalised SLC activity correlated weakly with log triglyceride (beta = 0.225; P = 0.06) and cholesterol (beta = -0.112 P = 0.06). Log Vmax correlated with log triglyceride (beta = 0.307; P = 0.02), and high-density lipoprotein (HDL) (beta = 0.74; P = 0.03) whilst Km correlated with HDL (beta = 1.73; P<0.001) and apoAI (beta = -1.76; P = 0.0048), LDL (beta = -0.14; P = 0.05), and creatine kinase (beta = 0.003; P = 0.01). Cholesterol and triglyceride concentrations rather than insulin resistance seem to be the key features affecting the environmental alteration of sodium lithium countertransporter Vmax in patients with familial hypercholesterolaemia.

Adult↗
PubMed2000

Gene identification using exon amplification on human chromosome 18q21: implications for bipolar disorder.

We previously reported linkage between bipolar disorder and a region on human chromosome (HC) 18q21. To identify genes in this region, exon trapping was performed on cosmids isolated from an HC18-specific cosmid library (LL18NC02) using 47 sequence tagged site (STS) markers from 18q21 as hybridization probes. A total of 285 unique sequences (exons) were obtained from 850 sequenced clones. Homology searching of the databases using NCBI's BLAST algorithms revealed that 31 exons have identity to known genes and/or ESTs, seven are identical to regions of finished genomic sequences in the 18q21 region, 20 have significant similarity (>30% sequence identity) to genes from human and/or other species, 19 were repetitive sequences, and 208 sequences (72%) are novel. Seventy per cent of the trapped sequences were predicted to be derived from genes using library screening and RT-PCR analyses. This represents an initial stage in characterizing genes in a susceptibility region for further study in bipolar disorder or other diseases that map to this region.

Animals↗
PubMed2000

Increase in the incidence of oesophagogastric carcinoma in the south thames region: an epidemiological study

Aims: There is some evidence to indicate that the incidence of gastric and oesophageal carcinoma is changing rapidly in the West. However, to study the true magnitude of the problem (to help in planning health and cancer strategies over the next decades), this epidemiological study was performed. METHODS: The Thames Cancer Registry database for the years 1960-1995 was searched for all oesophageal and gastric cancers in the South Thames region, and was analysed for all subsites for both sexes separately. Statistical analysis using the age-standardized ratio (ASR) (world) and chi2 test for trend for each subgroup was performed. RESULTS: The overall incidence of carcinoma of the oesophagus for both sexes saw a marked rise in the period studied, while the overall incidence of gastric cancer fell. In the upper two-thirds of the oesophagus, the increase in incidence was more dramatic for women (from 0.30 in 1960 to 0.70 in 1996; chitrend2 = 18.7, P = 0.00015) than men (from 0.59 in 1960 to 1.09 in 1996; chitrend2 = 4.4, P = 0.0354). In the lower third of the oesophagus, there was a rise in men (ASR from 0.93 in 1960 to 3. 43 in 1996; chitrend2 = 466.3, P < 0.0001) as well as in women (ASR from 0.42 in 1960 to 0.91 in 1996; chitrend2 = 51.4, P < 0.0001). For the gastric cardia, the incidence in men increased (ASR from 1. 24 in 1960 to 2.41 in 1996; chitrend2 = 109.8, P < 0.0001), while in women it remained unchanged (ASR from 0.33 in 1960 to 0.55 in 1996; chitrend2 = 0.0, P = 0.8281). The incidence of distal gastric carcinoma has decreased in men (ASR from 2.47 in 1980 to 0.63 in 1996; chitrend2 = 264.7, P < 0.0001) and women (from 1.14 in 1980 to 0.43 in 1996, chitrend2 = 131.8, P < 0.0001). For cancers of other subsites of the stomach (fundus, lesser and greater curvature, and body), there was a fall in incidence in both sexes. CONCLUSION: There has been a twofold to threefold increase over 36 years in the incidence of cancer of the oesophagogastric junction with a decreasing incidence in the distal stomach. There was also an increase in the incidence of upper oesophageal cancers, and a decrease in the incidence of cancers of other subsites of the stomach. Studies to cope with this increase and resources to cope with the treatment of these patients are required.

Journal Article↗
PubMed2000

Haemolytic disease of the newborn due to anti-Ce.

A baby was readmitted to the hospital 3 days after delivery when she developed jaundice. At admission, the direct antiglobulin test was also found to be positive. The baby required emergency exchange transfusion. A strongly reacting IgG anti-Ce (Rh7) was found in the serum of the mother. Severe haemolytic disease of the newborn due to anti-Ce is very rare. The mother's serum had been screened and found negative for red cell antibodies at 16 weeks gestation but the test was not repeated later in pregnancy when this antibody might have been detected.

Adult↗
PubMed2000

Transvaginal ultrasound examination of women with and without pelvic venous congestion.

AIM: To determine if transvaginal ultrasound, including power Doppler examination, can distinguish between women with and without pelvic congestion. MATERIALS AND METHODS: Thirty-six women with pelvic congestion were prospectively examined using transvaginal ultrasonography and standard uterine and ovarian measurements made. Additionally, planimetric measurements of each ovary were taken using an image analysis program to determine the cross-sectional area of ovarian stroma and follicles, if any. Power Doppler images of adnexal vessels were obtained and planimetric estimates of surface area calculated. A congestion score was assigned to each patient, based on vein number, diameter and morphology on grey-scale scanning. Identical measurements were obtained from 19 asymptomatic women and results compared. RESULTS: There was no significant difference between women with pelvic congestion and controls with respect to power Doppler or grey-scale images of adnexal vessels, or congestion score. However, women with pelvic congestion had significantly larger and multicystic ovaries when compared to controls. CONCLUSIONS: Transvaginal ultrasound measurements of adnexal vasculature, including power Doppler measurements, cannot reliably distinguish women with pelvic congestion from controls. However, ultrasound may remain useful for diagnosis of pelvic congestion, predominantly because it is able to visualize multi-cystic ovaries in these patients.

Adult↗
PubMed2000

Intrathecally administered endotoxin or cytokines produce allodynia, hyperalgesia and changes in spinal cord neuronal responses to nociceptive stimuli in the rat.

Inflammatory processes occurring within the central nervous system (CNS) can produce 'illness induced behaviours' which include fever, sleep and the development of allodynia and hyperalgesia. Here we demonstrate the effects of the pro-inflammatory mediators, bacterial endotoxin, and rat recombinant interleukin 1 beta (rrIL-1 beta) or tumour necrosis factor-alpha (rrTNF alpha) on the integration of somatosensory information at the single neuronal level, via recordings from wide-dynamic range neurones in the dorsal horn of the spinal cord in anaesthetized rats. Intrathecal administration of E. coli lipopolysaccharide (LPS, 10 and 100 microg, i.t.) enhanced the activity of dorsal horn neurones, including facilitation of neuronal post-discharge. Intrathecal administration of IL-1 beta (5-5000 pg) or TNF-alpha (5-5000 pg) enhanced dorsal horn neuronal responses, including the acute responses to C-fibre stimulation, wind-up and post-discharge, however, the effects of IL-1 beta were more robust than those of TNF alpha. Intrathecal administration of IL-1 beta (1-1000 pg) also leads to the development of mechanical allodynia and hyperalgesia. On the other hand intrathecal application of TNF alpha did not produce changes in sensitivity to mechanical stimuli. Changes in the activity of spinal wide-dynamic range neurones induced by local inflammation may provide a pathomechanism for the clinical pathology of central pain syndrome, which can accompany CNS disease or acute CNS injury.

Animals↗
PubMed2000

Survey for aflatoxins, ochratoxin A, zearalenone and fumonisins in maize imported into the United Kingdom.

This survey examined 140 samples of raw maize as received at ports or at major maize mills in the UK and 12 after initial cleaning. Samples were examined for aflatoxins B1, B2, G1 and G2, ochratoxin A, zearalenone and fumonisins B1, B2 and B3 using fully validated analytical HPLC methods with detection limits of 0.1 microgram/kg for each aflatoxin and ochratoxin A, 4 micrograms/kg for zearalenone and 10 micrograms/kg for each fumonisin. 95.0% and 92.1% of samples met the new EC statutory maximum permissible level for total aflatoxins and aflatoxin B1 respectively. The maximum concentration of ochratoxin A found was 1.5 micrograms/kg. Zearalenone and fumonisins were detected in almost every sample with 41.7% of maize containing more than 100 micrograms/kg of zearalenone and 48% of samples containing more than 1000 micrograms/kg total fumonisins. Initial cleaning of raw maize reduced aflatoxin concentrations by about 40% and total fumonisins by 32%.

Aflatoxins↗
PubMed2000

Neural network analysis of oxygenation signals in infants during sleep.

The use of artificial neural networks (ANNs) to interpret sleep monitoring signals is described. Recordings from ten infants with apparent life threatening episodes were assigned into training feedforward R-PROP networks. In order to separate good signal from artefact, 60 second time frames of SaO2 and TcPO2 signals were processed and the mean and standard deviation values were used as inputs to the networks. Intra-human errors were minimized using this method whilst inter-human errors remained significant. To decrease the latter, the number of hidden units was increased to eight. Sensitivity figures of the SaO2 network were 0.93 and 0.9 for the training and test sets respectively whilst the specificity figures were 0.7 and 0.65 respectively. For the TcPO2 signals the above figures were 0.92, 0.85, 0.77 and 0.61 respectively.

Apnea↗
PubMed2000

Permanent iodine-125 interstitial implants for the treatment of recurrent glioblastoma multiforme.

OBJECTIVE: Brachytherapy with temporary implants may prolong survival in patients with recurrent glioblastoma multiforme (GBM), but it is associated with relatively high costs and morbidity. This study reports the time to progression and survival after permanent implantation of iodine-125 seeds for recurrent GBM and examines factors predictive of outcome. METHODS: Forty patients with recurrent GBM were treated with maximal resection plus permanent placement of iodine-125 seeds into the tumor bed. A total dose of 120 to 160 Gy was administered, and patients were followed up with magnetic resonance imaging scans every 2 to 3 months. RESULTS: Actuarial survival from the time of implantation was 47 weeks, with 7 of 40 patients still alive at a median of 59 weeks after implantation. Survival was significantly better for patients younger than 60 years, and a trend for longer survival was demonstrated with gross total resection and tumors with a low MIB-1 (a nuclear antigen present in all cell cycles of proliferating cells) staining index. Median time to progression was 25 weeks and, on multivariate analysis, was favorably influenced by gross total resection and patient age younger than 60 years. After implantation, 27 of 30 patients with failure had a local component to the failure. No patient developed symptoms attributable to radiation necrosis or injury. CONCLUSION: Permanent iodine-125 implants for recurrent GBM result in survival comparable with that described in previous reports on temporary implants, but with less morbidity. Results are most favorable for patients who are younger than 60 years, and who undergo gross total resection. Despite this aggressive treatment, most patients die as a consequence of locally recurrent disease.

Adult↗