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Biomedical subjects

R Patel

Publications and source records attributed to R Patel.

At least 73 records · Page 4Linked to original sources

Solitary melanoma confined to the dermal and/or subcutaneous tissue: evidence for revisiting the staging classification.

BACKGROUND: Several patients presented with a single focus of presumed cutaneous metastatic melanoma with an unknown primary tumor based on clinical and histologic staging criteria of the American Joint Committee on Cancer (AJCC). This population is classified as having stage IV disease by the current AJCC staging system, which carries a dismal prognosis (5%-18% 5-year survival). Our clinical observation was that these patients had a higher survival rate than would be expected for stage IV disease. We believe this population represents a subgroup of primary dermal- and or subcutaneously-derived melanoma that simulates cutaneous metastatic melanoma in histologic and clinical presentation but may differ in behavior. OBSERVATIONS: The database records of 1800 patients from the University of Michigan Melanoma Clinic, Ann Arbor, were retrospectively reviewed to identify the prevalence and survival for patients diagnosed with a single focus of presumed metastatic melanoma to the skin based on accepted histologic and clinical parameters. The prevalence of this population was 0.61% (11 of 1800 patients). The Kaplan-Meier 8-year survival estimate was 83% (95% confidence interval, 58%-100%). CONCLUSIONS: By AJCC convention, these cases are classified as stage IV metastatic disease. Our data suggest that these presumed metastatic tumors do not behave like stage IV metastatic disease to the skin via lymphatic or hematogenous spread from an unknown primary site; rather, they are behaving like primary tumors originating in the dermal and/or subcutaneous tissue.

Adult↗

Isoflavonoids and chronic disease: mechanisms of action.

Soy and its isoflavones are associated with a reduced risk of chronic disease. The mechanisms of action of isoflavones include their roles as weak estrogens, inhibitors of tyrosine kinase-dependent signal transduction processes and as cellular antioxidants. Although estrogen receptor beta binds genistein with an affinity close to that of 17beta-estradiol, it remains to be determined whether it is a mediator of genistein's activity in vivo. Genistein's inhibition of protein tyrosine kinases is not limited to direct effect on these kinases, but may result from alteration in kinase expression. Genistein is not a particularly good scavanger of cellular oxidants; however, it reacts vigorously with the prooxidant hypochlorous acid, produced by neutrophils as part of the inflammatory response. The chlorinated isoflavones may have altered biochemical and biological effects compared to their parent compounds and may provide increased protection against inflammatory disease.

Animals↗

Paenibacillus associated with milky disease in Central and South American scarabs.

Thirty-one isolates of bacteria causing milky disease in scarab larvae collected in Central and South America were identified as Paenibacillus popilliae or Paenibacillus lentimorbus by use of DNA similarity analysis. The isolates were more similar to each other than to the North American isolates that are the type strains of the species. All of the bacteria of both species produced parasporal bodies, a characteristic previously believed to be unique to P. popilliae. Screening of the bacteria using PCR with parasporal protein primers revealed differences among the parasporal protein genes of P. popilliae isolates and between the parasporal genes of P. popilliae and P. lentimorbus. In contrast to P. popilliae from North America, none of the isolates from Central and South America was resistant to vancomycin, an indication of an interesting geographic distribution of the resistance genes.

Animals↗

Variants of trophic factors and expression of cardiac hypertrophy in patients with hypertrophic cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HCM) exhibit variable expression of left ventricular hypertrophy (LVH), a major determinant of mortality and morbidity, which is partly due to the diversity of causal mutations, genetic background (modifier genes), and probably environmental factors. We determined association of functional variants of tumor necrosis factor (TNF)- alpha, interleukin-6 (IL6), insulin-like growth factor-2 (IGF2), transforming growth factor- beta 1 (TGFB1), and aldosterone synthase (CYP11B2) genes, all previously implicated in cardiac hypertrophy, with the severity of LVH in patients with HCM. Two-dimensional echocardiography was performed and demographic variables were recorded in 142 genetically independent patients. Indices of LVH including interventricular septal thickness (IVST), left ventricular mass index (LVMI), and LVH score were measured/calculated. TNF-alpha-308G/A, IL6-174G/C, IGF2 820G/A, TGFB1-509C/T, and CYP11B2-344T/C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were identified by the presence of specific electrophoretic patterns and their distributions were according to the Hardy-Weinberg equilibrium. Demographic variables were not significantly different among the genotypes. Subjects with the AA genotype of TNF-alpha (n=8) were approximately 13 years younger at the time of clinical diagnosis. Despite a younger age, they had a greater mean LVMI than those with the GG (n=94) or GA (n=33) genotypes (191.8+/-59.5 v 139.1+/-47.3 v 132.1+/-34.3, respectively, P=0.004). TNF-alpha-308G/A genotypes accounted for 6.0% of variability of LVMI (P=0.002). Mean IVST, LVEDD, and LVH score were not significantly different. Variants of IL6, IGF2, TGFB1, and CYP11B2 were not associated with indices of LVH. The uncommon allele of TNF-alpha-308G/A polymorphism, known to produce more TNF- alpha, was associated with greater LVMI and clinical diagnosis at a younger age in patients with HCM. Functional variants of other trophic factors, previously implicated in cardiac hypertrophy, were not associated with the indices of LVH. These results suggest that TNF-alpha is a modifier gene for HCM.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗