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Biomedical subjects

R Patel

Publications and source records attributed to R Patel.

At least 127 records · Page 7Linked to original sources
PubMed2000

Differential anti-inflammatory effects of immunosuppressive drugs: cyclosporin, rapamycin and FK-506 on inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2 and PGE2 production.

OBJECTIVE AND DESIGN: Cyclosporin, FK-506 and rapamycin have similar but distinct modes of interaction with cyclophilins, calcineurins and transcription factors. These immunosuppressive drugs have also been shown to inhibit cytotoxic and inflammatory responses in macrophage. Therefore, we evaluated the mechanism of action of these drugs on iNOS and COX-2 expression by macrophages, the products of which (NO and PGE2) have cytotoxic and proinflammatory activities. MATERIALS AND METHODS: The murine macrophage cell line RAW 264.7 was grown as monolayer cultures. The effects of pharmacologically relevant concentrations of cyclosporin, rapamycin and FK-506 were evaluated in the presence and absence of lipopolysaccharide (LPS) which is a known inducer of iNOS and COX-2. Subsequently the expression of iNOS and COX-2 were analyzed by Western and Northern analysis. The production of NO and PGE2 were assayed by Greiss and RIA respectively. RESULTS: Cyclosporin (1-5 microg/ml) and rapamycin (1.0-10 nM) but not FK-506 (5-10 nM) inhibited both iNOS and COX-2 expression at mRNA level which led to significant inhibition of NO and PGE2 production. CONCLUSION: These studies characterize differential mechanistic capacity of the immunophilin-binding immunosuppressive drugs (comparable to hydrocortisone) to inhibit both iNOS and COX-2 expression. Inhibition of iNOS and COX-2 mRNA accumulation by cyclosporin and rapamycin seem to be distinct. These studies also highlight potential anti-inflammatory properties of these drugs in addition to their known immunosuppressive activity.

Animals↗
PubMed2000

The geographical mobility of severely mentally ill residents in London.

BACKGROUND: There is currently great concern over the demands on psychiatric services in metropolitan areas in most developed countries, and this is exemplified in capital cities. These greater demands were not anticipated by those planning psychiatric services and the consequences have led to insufficient beds in many areas. We investigated the geographical mobility (the number of changes of address in the past 2 years) of patients presenting to services in greater London, to determine whether this might be a possible factor in the increased demand. METHOD: The geographical mobility of the severely mentally ill was determined by taking a random sample of all psychiatric admissions to hospitals serving residents in the London area over the calendar year of 1994 (n = 156) and an equivalent sample of patients in an established community mental health team (n = 74) in one area (Paddington). The extent of geographical movement was determined for the 2 years prior to interview. RESULTS: Greater geographical movement in the in-patient group was found for those living in inner London compared with outer London and for patients admitted to hospitals outside their catchment area. Twenty-eight percent of the in-patient sample had changed address in the year before admission (including 13% more than once) and 39% had changed address in the 2 years prior to admission. By contrast, the patients seen by the community psychiatric team were less than half as likely to have changed address over the previous year as the in-patients, and none of the community team's patients had changed address more than once over the previous year. The geographically mobile patients had significantly longer periods in hospital than geographically stable patients. CONCLUSION: Geographical mobility of psychiatric patients in London is high and is particularly marked for those presenting for in-patient treatment. These findings suggest that greater mobility could be one of the most important reasons for the higher than expected demands on psychiatric services and the difficulties in maintaining contact with patients in London in general and inner London in particular. More attention should be paid to geographical mobility as a predictor of psychiatric service use, and it is recommended that it is recorded regularly in information systems.

Adolescent↗
PubMed2000

Long-term precision of DXA scanning assessed over seven years in forty postmenopausal women.

The reproducibility of dual-energy X-ray absorptiometry (DXA) measurements of bone mineral density (BMD) is an important factor for longitudinal studies. We assessed the long-term precision of posteroanterior lumbar spine, femoral neck and total hip BMD in 40 postmenopausal women who formed the control arm of a clinical trial of tibolone. BMD was measured at 0, 6 and 12 months and thereafter every 12 months up to 7 years. For each subject the trend of BMD with time was analyzed using linear regression. Each residual was expressed as the percentage difference from predicted BMD and the validity of assuming linear change with time was checked using the mean residuals for each visit number. For spine BMD a chi-squared test showed that the mean residuals were not statistically significantly different from zero. Although statistically significant deviations from linearity were found for the femoral neck and total hip sites the weighted root mean square residuals were small compared with the precision errors. When residuals were binned into histograms a statistical test for skewness was not significant for all three sites. However, a test for kurtosis yielded a statistically significant result for each histogram due to outlying residuals. To determine the standard deviation (SD) of the core gaussian distribution, outliers were trimmed using the method of Melton et al. For lumbar spine BMD outliers with residuals exceeding +/- 3 SD arose mainly from subjects with a body mass index (BMI) >28 kg/m(2) or from subjects who had undergone a large change in BMI during the study. For femoral neck BMD and total hip BMD the outliers were frequently due to inconsistent rotation of the hip. Results for long-term precision calculated from the standard deviation of residuals using the trimmed (untrimmed) data were: lumbar spine BMD, 1.12% (1.65%); femoral neck BMD, 2.21% (2.48%); and total hip BMD, 1.32% (1.57%). These errors were only slightly worse than short-term errors despite changes of DXA scanner during the course of the study. However, obesity may have an adverse effect on precision errors in individual patients and particular care is necessary to ensure reproducible patient positioning for femur scans.

Absorptiometry, Photon↗
PubMed2000

The effect of weight change on total body dual-energy X-ray absorptiometry: results from a clinical trial.

In the past decade dual-energy X-ray absorptiometry (DXA) scanning has assumed an important role in the evaluation of new treatments for osteoporosis. Although the spine and hip are the sites usually chosen for monitoring bone mineral density (BMD) changes, total body DXA is also of interest because of the comprehensive view it gives of the whole skeleton. However, recent studies have reported anomalies in total body DXA in subjects undergoing weight change, suggesting that the technique may not be valid in this circumstance. The present study evaluated total body DXA in a trial of cyclical etidronate therapy in which many subjects underwent significant weight change. The study population was 152 postmenopausal women who had spine, hip and total body DXA scans performed at baseline, 1 and 2 years. The total body scans were analyzed using two software options referred to as 'standard' and 'enhanced'. The following variables were studied: total body BMD, total body bone mineral content (BMC), and subregional BMD values for the following seven sites: lumbar spine, thoracic spine, pelvis, head, ribs, arms and legs. The percentage change from baseline was analyzed in a multivariate regression analysis to derive the treatment effect (defined as the difference in changes between the etidronate and placebo groups) and a coefficient that described the effect of weight change on the total body DXA variable. Mean weight change after 2 years was +1.1 kg (range -9.3 to +16.8 kg). Results for the weight change coefficient were significantly different from zero for five of nine total body variables using the standard analysis and seven of nine for the enhanced analysis with values (and standard errors) that varied from +0.67 (0.04)%/kg for standard total body BMC to -0.32 (0.11)%/kg for enhanced arm BMD. Results for the treatment effect at 2 years were significantly different from zero for total body BMD, total body BMC and for the lumbar spine, thoracic spine and pelvis BMD subregions, but were not significant for head, rib, arm or leg BMD. Findings for the standard and enhanced analyses agreed closely and the size of the treatment effect was related to the proportion of trabecular bone at the measurement site. We conclude that in a randomized study the effects of weight change can be corrected and total body DXA can give useful information about the response to treatment across the whole skeleton.

Absorptiometry, Photon↗
PubMed2000

Development of an ergonomic evaluation facility for Indian tractors.

The design of tractors manufactured in low-income countries like India has not changed much in the past two decades, especially from an ergonomic point of view. Moreover, in these countries tractors are used for transportation purposes in addition to farming operations. Therefore, the design criteria for these tractors need to be different from those in high-income countries. This paper describes the development of an ergonomic facility for improvement of tractor design. An ergonomic evaluation facility has been developed consisting of a work place envelope for the Indian population, a layout measuring device and an ergonomic rig. This facility can be used for comparative evaluation of the display and control layouts of different tractors in order to develop an optimum layout. The ergonomic rig has the facility to simulate the improved layout for subjective evaluation.

Agriculture↗
PubMed2000

Catecholamine-induced hypertension in lumbosacral paraplegia: five case reports.

Hypertension in the patient with SCI is relatively rare and generally restricted to patients with high-level injuries where autonomic dysreflexia can occur. Resting blood pressure in individuals with SCI has been described as lower than that in the normal population. This report describes five previously normotensive teenagers with subsequent paraplegia as a result of gunshot wounds who presented with hypertension secondary to idiopathic elevation of plasma or urinary catecholamine levels. A clonidine suppression test was used as a neuroprobe to inhibit centrally mediated sympathetic outflow, excluding the probability of an extra-axial autonomous catecholamine-secreting tumor as the possible source of hypertension. Positive suppression was achieved in four patients (41%, 37.2%, 4.8%, and 37.2% decreases). One patient had values corresponding to orthostatic changes (an increase of 63%) because of poor compliance with the test. This patient was lost to follow-up; in the remaining four, hypertension resolved at 12, 8, 9, and 6 weeks postinjury. The increased circulating catecholamine level appears to be promoted by a centrally mediated response to the SCI. Elevated blood pressure probably results from an upgraded receptor regulation or an increased receptor sensitivity on the affected cells in the absence of restraining spinal reflexes. The pathophysiology of such hypertension seems to be secondary to autonomic dysfunction and, although it may be transient, it should be treated promptly and reevaluated periodically until stabilization is achieved.

Adolescent↗
PubMed2000

Double-blind randomized comparison of single-dose ciprofloxacin versus intravenous cefazolin in patients undergoing outpatient endourologic surgery.

OBJECTIVES: To compare the efficacy of single-dose oral ciprofloxacin with intravenous cefazolin as a prophylactic agent in patients undergoing outpatient endourologic surgery. METHODS: One hundred patients were enrolled in a double-blind, randomized study to receive either ciprofloxacin (500 mg) or cefazolin (1 g) before surgery. A postoperative clinical evaluation and urine cultures were performed 5 to 10 days after surgery. Patients undergoing ureteral stent insertion or exchange, ureteroscopy, bladder biopsy, retrograde pyelography, collagen injection, and internal urethrotomy were included. RESULTS: Postoperative urinary tract infection occurred in 7 (9.1%) of 77 patients, including 3 (8.1%) of 37 and 4 (10.0%) of 40 of those who received ciprofloxacin and cefazolin, respectively (P = 0.77). There were no episodes of sepsis, and no patient with infection required hospitalization. The total cost associated with the administration of prophylactic antibiotics in the study population was $3657 less in those 50 patients who received ciprofloxacin than in the 50 patients who received cefazolin. CONCLUSIONS: A single oral dose of ciprofloxacin in patients undergoing outpatient endourologic surgery was equally effective as cefazolin in preventing postoperative urinary tract infection, but was associated with markedly lower overall costs.

Adult↗
PubMed2000

Vasopressin-induced neurotrophism in cultured neurons of the cerebral cortex: dependency on calcium signaling and protein kinase C activity.

Neuronal process outgrowth has been postulated to be one of the fundamental steps involved in neuronal development. To test whether vasopressin can influence neuronal development by acting on the outgrowth of neuronal processes, we determined the neurotrophic action of the memory-enhancing peptide, vasopressin, in neurons derived from the cerebral cortex, a site of integrative cognitive function and long-term memory. Exposure to V(1) receptor agonist significantly increased multiple features of nerve cell morphology, including neurite length, number of branches, branch length, number of branch bifurcation points and number of microspikes. The dose-response profile of V(1) receptor agonist-induced neurotrophism exhibited a biphasic function, with lower concentrations inducing a significant increase while higher concentrations generally induced no significant effect. The neurotrophic effect of V(1) receptor activation did not require growth factors present in serum. Analysis of the regional selectivity of the vasopressin-induced neurotrophic effect revealed significant V(1) receptor agonist-induced neurotrophism in occipital and parietal neurons, whereas frontal and temporal neurons were unresponsive. Results of experiments to determine the mechanism of vasopressin-induced neurotrophism demonstrated that vasopressin-induced neurotrophism is dependent on V(1)a receptor activation, requires L-type calcium channel activation and activation of both pathways of the phosphatidylinositol signaling cascade, inositol trisphosphate and protein kinase C. These studies are the first to describe a functional cellular response for vasopressin in the cerebral cortex. The findings are discussed with respect to their implications for understanding the role of vasopressin-induced neurotrophism, the associated signaling pathways required for this response, and the ability of vasopressin to enhance memory function.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

In vitro activity of GAR-936 against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae.

We report the activity of the new glycylcycline antimicrobial agent GAR-936 against 37 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes), 26 clinical isolates of methicillin-resistant S. aureus and 30 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci, methicillin-resistant S. aureus, and penicillin-resistant S. pneumoniae were inhibited by < or = 1, < or = 2, or < or = 0.25 microg/ml of GAR-936, respectively. Time kill experiments using vancomycin-resistant enterococci did not demonstrate synergy or antagonism between 2 microg/ml of GAR-936 and 0.25 microg/ml of quinupristin/dalfopristin.

Anti-Bacterial Agents↗
PubMed2000

Recommendations of the British Paediatric Cardiac Association for therapeutic cardiac catheterisation in congenital cardiac disease.

The aims of these recommendations are to improve the outcome for patients after, and to provide acceptable standards of practice of therapeutic cardiac catheterisation performed to treat congenital cardiac disease. The scope of the recommendations includes all interventional procedures, recognising that for some congenital malformations, surgical treatment is equally as effective as, or occasionally preferable to, interventional treatment. The limitations of the recommendations are that, at present, no data are available which compare the results of interventional treatment with surgery, and certainly none which evaluate the numbers and types of procedures that need to be performed for the maintenance of skills. Thus, there is a recognised need to collect comprehensive data with which these recommendations could be reviewed in the future, and re-written as evidence-based guidelines. Such a review will have to take into account the methods of collection of data, their effectiveness, and the latest developments in technology. The present recommendations should, therefore, be considered as consensus statements, and as describing accepted practice, which could be used as a basis for ensuring and improving the quality of future care.

Cardiac Catheterization↗
PubMed2000

Dendritic cells can be successfully generated from CD34+ cord blood cells in the presence of autologous cord blood plasma.

Dendritic cells (DCs) are currently being considered as adjuvants in immunotherapy. Depending on their source and culture conditions, they show different features and maturation states. Dendritic cells can be generated from monocytes and CD34+ haematopoietic stem cells, from both adult and cord blood. Here, we report the generation of mature DCs from enriched CD34+ cord blood (CB) cells using autologous cord blood plasma (ACBP) as a source of serum proteins and factors. In the presence of ACBP, CD34+ cells proliferated and differentiated resulting in a population of cells with a dendritic phenotype as assessed by morphology and flow cytometry analyses. The DC population obtained using ACBP showed higher levels of HLA class II molecules, co-stimulatory molecules including CD40, CD80 or CD86, and the dendritic cell marker CD83, compared with those generated in adult blood serum (ABS). Furthermore, the DCs generated in the presence of ACBP were more potent stimulatory cells in the mixed lymphocyte:dendritic cell reactions (MLDCR), compared to cells generated in ABS. Similar results were obtained using homologous cord blood plasma (HCBP). These results show that ACBP can support the generation of DCs from CD34+ progenitor cells when only GM-CSF and TNFalpha are used as differentiating cytokines.

Adult↗
PubMed2000

Efficient and sustained transgene expression in human corneal cells mediated by a lentiviral vector.

The development of vectors and techniques able to transfer potentially therapeutic genetic information to corneal tissues efficiently may have broad clinical applications. Although a variety of vectors have been tested for their ability to transduce corneal tissue, these systems have been ineffective at transducing all cell types or have been associated with a relatively short duration of transgene expression. Towards the implementation of efficient, long-term transgene expression in all corneal cell types, we have studied the ability of a recombinant lentiviral vector, containing the enhanced green fluorescent protein (eGFP), to mediate gene transfer into human corneal tissue in vitro and in situ. Human primary keratocytes, cultured in vitro, were efficiently transduced by a lentiviral vector as determined by fluorescent-activated cell sorting (FACS) and by fluorescent microscopy. Transduction efficiency was found to be dependent upon multiplicity of infection (MOI); 92% of keratocytes were transduced at an MOI of 1000. The proportion of eGFP-positive cells remained unchanged throughout continuous culture for 60 days, indicating stable expression and a lack of selective pressure for or against transduced cells. Human corneal tissue, obtained at the time of penetrating keratoplasty, demonstrated efficient in situ transduction with this vector. Endothelial cells, epithelial cells and stromal keratocytes at the exposed cut edge of the corneal tissue in situ demonstrated eGFP expression. Underlying stromal cells not in direct contact with vector-containing media, were not transduced, implying that virus-cell contact is required for transduction. Transduced corneal tissues expressed eGFP in situ for the life of the corneal button in extended organ culture (60 days). These results imply that lentiviral vectors may prove to be useful tools, able to transduce corneal tissue efficiently, and that transgene expression is temporally stable. Gene Therapy (2000) 7, 196-200.

Cells, Cultured↗
PubMed2000

The mechanics of corporal veno-occlusion in penile erection: a theory on the effect of stretch-associated luminal constrictability on outflow resistance.

In order to further our understanding of the physiology of corporal veno-occlusion, we developed a theory of a possible contribution to corporal venous outflow resistance which occurs as the result of venule stretching with resultant luminal narrowing when penile volume increases during the erection process. We stretched non-biological tubes and rabbit abdominal vena cava segments, performed flow-based and volume-based experiments to calculate the magnitude of N, the newly defined 'stretch-associated luminal constrictability' factor. We solved for (R(s)/R(u)), the ratio of the venule fluid resistance in the stretched state (R(s)) to the unstretched state (R(u)), to quantify the projected increases in fluid resistance as well as Q.R(u) where Q is the subtunical venule flow rate. For a given tube, N was found to be essentially constant for different amounts of stretch. A theory was formulated which predicted R(s) and Q as a function of N, DeltaP (intracavernosal pressure increase); V(E)/V(F) (tunical distensibility); X (cavernosal expandability) and R(u). Based on the magnitude of N=2, this theory predicts that patients with the highest values of both V(E)/V(F) and X would have maximal R(s) values, approaching infinity (complete occlusion) at a low DeltaP near 5 mmHg. In contrast, patients with low values of both V(E)/V(F) (eg Peyronie's disease) and X (eg corporal fibrosis), would be predicted to have minimal R(s) values. For example, a hypothetical patient with the lowest values of V(E)/V(F) and X would yield R(s) values only approaching 7.9 times that of unstretched values at a DeltaP increase of 90 mmHg. We concluded to that stretch-associated venule resistance may occur as a result of decreased sub-tunical venule diameter and increased sub-tunical venule length. In individual patients, stretch-associated venule resistance may either dominate or be a minor component of the overall mechanism of corporal veno-occlusion.

Animals↗
PubMed2000

Purification, cloning, and characterization of an arylsulfotransferase from the anaerobic bacterium Eubacterium rectale IIIH.

A bacterium, Eubacterium rectale IIIH, which possessed arylsulfotransferase (ASST) activity was isolated from human feces. The ASST gene (astA) was cloned and the corresponding protein partially characterized. This gene shows only moderate homology to the previously sequenced ASST genes of Klebsiella and Enterobacter, which are very closely related to each other.

Journal Article↗
PubMed2000

Cytoprotection by WR-1065, the active form of amifostine, is independent of p53 status in human malignant glioma cell lines.

PURPOSE: This study tests the hypothesis that p53 status, i.e. wild type versus mutant form, is a determinant in radiation protection of human glioma cells by WR-1065, the active thiol form of amifostine (WR-2721). MATERIALS AND METHODS: The cytoprotective effectiveness of WR-1065 when present during irradiation was investigated using four well-characterized human glioma cell lines. The p53 positive lines were U87 and D54, and the mutant p53 lines were U251 (mutant at codon 273; CGT/CAT; Arg/His) and A172 (mutant at codon 242; TGC/TTC; Cys/Phe). Treatment conditions included exposure of cells to a range of doses (0-10Gy) alone or in combination with 4mM of WR-1065 added 30min prior to irradiation. Resultant survival curves were obtained using a clonogenic assay and protection factors, the ratio of terminal slopes +/- WR-1065, were determined for each glioma cell line. RESULTS: The Do values of wild-type U87 and D54 were 1.62 and 1.89Gy while those of p53 mutants U251 and A172 were 1.64 and 1.68 Gy, respectively. Protection factors were determined to be 2.4 and 1.9 for U87 and D54, and 2.6 and 2.8 for U251 and A172, respectively. CONCLUSIONS: The p53 status of the four human glioma cell lines tested was not a predictor for either their relative sensitivity to ionizing radiation or ability to be protected by WR-1065. It is concluded that cytoprotection exhibited by cells exposed to WR-1065 during irradiation is independent of their p53 status.

Amifostine↗
PubMed2000

Lack of benefit of intravenous immune globulin in a murine model of group A streptococcal necrotizing fasciitis.

Penicillin, clindamycin, and intravenous immune globulin (Venoglobulin-S; IVIG) alone and in combination were studied in a murine model of group A streptococcal necrotizing fasciitis. As assessed by bacterial clearance, treatment with IVIG was not significantly different from no treatment. All treatment regimens that contained penicillin or clindamycin were more effective (P<.05) than no treatment or treatment with IVIG alone. No significant differences were detected among results of treatment with penicillin, penicillin/clindamycin, penicillin/IVIG, clindamycin/IVIG, or all agents combined. Clindamycin alone was less effective than penicillin/IVIG (P=.02), penicillin/clindamycin (P=.009), clindamycin/IVIG (P=.04), or all agents combined (P=.02). No antagonism was observed with the addition of clindamycin or IVIG to penicillin.

Animals↗
PubMed2000

Death from inappropriate therapy for Lyme disease.

A 30-year-old woman died as a result of a large Candida parapsilosis septic thrombus located on the tip of a Groshong catheter. The catheter had been in place for 28 months for administration of a 27 month course of intravenous cefotaxime for an unsubstantiated diagnosis of chronic Lyme disease.

Adult↗