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Biomedical subjects

A Patel

Publications and source records attributed to A Patel.

At least 127 records · Page 7Linked to original sources

Age-dependent renal responses to the bradykinin B(2)- receptor antagonist icatibant in conscious lambs.

To investigate the role of endogenously produced bradykinin in modulating renal function during postnatal maturation, various parameters of glomerular and tubular function were measured for 1 h before and after intravenous injection of 12.5 microg/kg of the specific B(2)-receptor antagonist icatibant to conscious, chronically instrumented lambs aged approximately 1 (n = 7) and approximately 6 wk (n = 7). In response to icatibant, and in the absence of any changes in renal hemodynamics, there was an approximately 80% decrease in glomerular filtration rate (GFR) at 20 min in 1-wk-old lambs that was sustained for 60 min; in 6-wk-old lambs, there was an approximately 70% decrease in GFR by 20 min, with control levels being reached by 40 min. Icatibant administration was also associated with significant decreases in urinary flow, Cl(-), and K(+) excretion rates that were similar in both groups of lambs, whereas Na(+) excretion decreased only in 6-wk-old lambs. We conclude that bradykinin modulates glomerular and tubular function in an age-dependent manner.

Aging↗

Costs and characteristics of heavy inpatient service users in outer London.

"Heavy users" is a new term often used to describe those who occupy a disproportionate number of psychiatric beds. In this study we identified the heaviest 10% (193) inpatient service users in one London borough over a 6 year period and compared these with a control group of 400 ordinary inpatient users. A weighting index was used to combine frequency of admission with duration. Heavy users were diagnostically and demographically similar to ordinary inpatient service users and only differed by their extensive use of services, about 3 times more than ordinary users in terms of health care costs, during the measured year. Their heavy use mainly depended on occupying hospital beds, and their use of outpatient, day patient and community services was relatively light.

Adult↗

An evaluation of on-site testing for syphilis.

One of the major obstacles to the eradication of perinatal transmission of syphilis is the delay in obtaining the results of syphilis serological tests. The availability of on-site syphilis testing lead to this study which attempted to evaluate on-site syphilis testing performed by nursing staff. The seroprevalence of syphilis by laboratory rapid plasma reagin (RPR) was 8.2% (n=42). Twenty-one of the 42 women were correctly identified by the on-site test. The overall sensitivity of on-site testing was 50% [95% confidence interval (CI)=34.4-65.6]; specificity of 90.9% (95% CI=87.8-93.2). The on-site test correctly identified as uninfected 429 of the 471 women reported as RPR negative by the laboratory, giving a specificity of 91.1% (95% CI=88.1-93.4). The results of the study show that on-site RPR test had a sensitivity of 75% in respect of the clinically important titres of > or = 1:8. The specificity of the on-site test was 91.1% and on-site testing only failed to detect syphilis in those patients with titres of 1:1 and 1:2. On-site testing is a practical and cost-effective option to prevent congenital syphilis, in settings of a high prevalence of syphilis and using skilled testers.

Adolescent↗

Infiltration of differentiated thyroid carcinoma by proliferating lymphocytes is associated with improved disease-free survival for children and young adults.

An immune response directed against thyroid cancer might be important in preventing metastasis and recurrence. This idea is supported by previous observations showing that adults with autoimmune thyroiditis or lymphocytic infiltration surrounding papillary thyroid carcinoma (PTC) have improved disease-free survival. The long-term outcome for differentiated thyroid cancer is even more favorable for children and young adults. If the immune response is important, we hypothesized that tumor-associated lymphocytes with a high proliferation index would be found in thyroid cancers from children and young adults and would be associated with improved disease-free survival. Using immunohistochemistry, we examined 39 childhood PTC, 9 follicular thyroid carcinomas, 2 medullary thyroid carcinomas, 11 benign thyroid lesions, and 2 normal thyroid glands for the presence of lymphocytes (leukocyte common antigen) and lymphocyte proliferation (proliferating cell nuclear antigen, Ki-67). The majority of PTC (65%) and follicular thyroid carcinomas (75%) from children and young adults contained lymphocytes in the immediate vicinity of thyroid cancers, but only 7 (18%) patients with PTC also had a diagnosis of autoimmune thyroiditis. Disease-free survival did not correlate with the presence or number of lymphocytes per high power field. In contrast, disease-free survival was significantly improved (P = 0.01) for thyroid cancers with the greatest number of Ki-67-positive lymphocytes per high power field. The number of lymphocytes per high powered field was greater for multifocal PTC (P: = 0.023), and the number of proliferating lymphocytes was greatest for PTC with regional lymph node involvement (30.5 +/- 12.3 vs. 6.8 +/- 5.0; P = 0.047). We conclude that proliferation of tumor-associated lymphocytes is associated with improved disease-free survival for children and young adults with thyroid cancer.

Adenocarcinoma, Follicular↗

Prevalence and location of peripheral nerve found on prostate needle biopsy.

We examined 238 prostate biopsy cores from 40 sextant biopsies by routine H&E stain to determine the presence of prostatic adenocarcinoma (PCa), perineural invasion (PNI), and nerves. Step sections were immunostained for S-100 protein to confirm the presence of nerves. Nerves were distributed evenly in specimens from apex, mid gland, and base. No significant difference was observed in the number of nerves in these areas. Significantly more nerves were found using the S-100 stain than the H&E stain. There was no significant difference between cancerous and benign specimens. However, there was a significant reduction in the nerve density in cancerous compared with benign specimens. PNI was identified in 3 of 11 PCas. All foci of PNI were identified on H&E stain. The S-100 immunostain detected no additional foci of PNI. Nerves are distributed evenly in standard sextant biopsy specimens from prostatic apex, mid gland, and base. In addition, the specimens with PCa have nerve distribution similar to that of benign specimens, suggesting that finding no PNI may represent true absence of PNI in the specimens. Careful examination of routine H&E-stained specimens is sufficient to detect all important PNI.

Adenocarcinoma↗

Risk-taking, death anxiety, and dreaming.

Dream characteristics of 29 women from a graduate program were correlated with scores on the Sensation-Seeking and Death Anxiety scales. Significant positive correlations were obtained between Sensation Seeking and dream frequency (.38), meaningful dreams (.38), and Openness and depth of dreaming (.39) as well as between Thrill-seeking and dream frequency (.41) and meaningful dreams (.41). Death Anxiety scores positively related to the occurrence of nightmares (.37), representations of death in dreams (.55), and recurring nightmares (.38), but no support was found for a relationship between death anxiety and Sensation Seeking.

Adult↗

Condylar prostheses in head and neck cancer reconstruction.

OBJECTIVE: To discuss the use of condylar prostheses after mandibular resection for tumor. DESIGN: Case series and literature review. SETTING: Tertiary referral center. PATIENTS: Four patients underwent condylar reconstruction with metallic condylar prostheses after hemimandibulectomy for either squamous cell cancer or Ewing sarcoma. MAIN OUTCOME MEASURE: Complications related to the condylar prostheses. RESULTS: Clinical and radiological follow-up in these patients revealed several complications, including exposure or extrusion of the prosthesis and migration of the prosthesis into the epitympanum, resulting in profound sensorineural hearing loss owing to bony destruction of the cochlea. Two of our patients required removal of the mandibular hardware because of the seriousness of the complications, and 1 of the 2 underwent reconstruction of the condyle with a fibular free flap. CONCLUSIONS: Metallic condylar prostheses in the setting of tumor resection and reconstruction involve significant risks. Autogenous materials, such as vascularized bone grafts, should be used whenever possible.

Carcinoma, Squamous Cell↗

Nuclear localization of thyroid transcription factor-1 correlates with serum thyrotropin activity and may be increased in differentiated thyroid carcinomas with aggressive clinical course.

Thyroid transcription factor 1 (TTF-1) is essential for thyroid differentiation and regulates expression of thyroglobulin, thyroid peroxidase, sodium/iodide symporter, and thyrotropin receptor (TSH-R) genes. Because thyrotropin (TSH) upregulates these same genes, we hypothesized TSH-R activation might increase TTF-1 and that TTF-1 might be differentially expressed in benign and malignant thyroid disease. TTF-1 expression and sub-cellular localization were determined by immunohistochemistry in 62 thyroid carcinomas, 15 benign lesions, and 2 normal thyroids. Nuclear TTF-1 was detected in benign (77%) and malignant lesions (69%), with similar intensity in both (1.1+/-0.19 versus 1.0+/-0.10). Nuclear TTF-1 staining correlated with the effective serum TSH level (p = 0.02) and patient age (p < 0.05). Nuclear TTF-1 was detected in 35 papillary thyroid carcinomas (PTC), of which 23% developed recurrent or persistent disease, and was absent from 18 PTC, of which only 6% recurred (p = 0.06). We conclude that nuclear TTF-1 correlates with serum TSH activity, increases with age, and may be increased in persistent or recurrent PTC.

Adolescent↗

A probability based system for combining simple office parameters as a predictor of bladder outflow obstruction.

PURPOSE: We explored the relationships of office assessment of lower urinary tract symptoms, transrectal ultrasound measurement and the bladder outlet obstruction index, as derived from pressure flow studies. We also developed and validated a multivariate analysis for predicting the bladder outlet obstruction index. MATERIALS AND METHODS: We evaluated 384 men with lower urinary tract symptoms using the International Prostate Symptom Score, maximum urine flow, post-void residual urine, transrectal ultrasound and urodynamic studies. Data were analyzed by multiple linear regression with continuous variables. A simple algorithm, that is the predicted bladder outlet obstruction index, was created using the best fit variables identified from a derivation set and assessed in a separate validation set. The predicted index was applied to predict the probability of actual obstruction according to office parameters. RESULTS: Maximum urine flow and total prostate volume predicted the bladder outlet obstruction index most completely (adjusted R2 = 0.50, F 75.9, p <0.0001), while other variables were not helpful. These variables were used to create the predicted bladder outlet obstruction index algorithm, antilog10 (2.21 - 0.50 log maximum urine flow + 0.18 log total prostate volume) - 50. In the 42% of patients with a predicted index of greater than 40 there was a 92% risk or positive predictive value of equivocal or worse obstruction, whereas a predicted index of less than 20 in 23% indicated a 4% risk of significant obstruction. CONCLUSIONS: The bladder outlet obstruction index can be predicted from maximum urine flow and prostate volume. Development of the predicted bladder outlet obstruction index algorithm enables the mathematical prediction of obstruction from these simple measures. Using the predicted bladder outlet obstruction index clinicians can determine the risk of obstruction in individuals. In 65% of patients we predicted equivocal or worse obstruction with greater than 90% confidence.

Aged↗

Striated muscle preferentially expressed genes alpha and beta are two serine/threonine protein kinases derived from the same gene as the aortic preferentially expressed gene-1.

Aortic preferentially expressed gene (APEG)-1 is a 1.4-kilobase pair (kb) mRNA expressed in vascular smooth muscle cells and is down-regulated by vascular injury. An APEG-1 5'-end cDNA probe identified three additional isoforms. The 9-kb striated preferentially expressed gene (SPEG)alpha and the 11-kb SPEGbeta were found in skeletal muscle and heart. The 4-kb brain preferentially expressed gene was detected in the brain and aorta. We report here cloning of the 11-kb SPEGbeta cDNA. SPEGbeta encodes a 355-kDa protein that contains two serine/threonine kinase domains and is homologous to proteins of the myosin light chain kinase family. At least one kinase domain is active and capable of autophosphorylation. In the genome, all four isoforms share the middle three of the five exons of APEG-1, and they differ from each other by using different 5'- and 3'-ends and alternative splicing. We show that the expression of SPEGalpha and SPEGbeta is developmentally regulated in the striated muscle during C2C12 myoblast to myotube differentiation in vitro and cardiomyocyte maturation in vivo. This developmental regulation suggests that both SPEGalpha and SPEGbeta can serve as sensitive markers for striated muscle differentiation and that they may be important for adult striated muscle function.

Amino Acid Sequence↗

ESE-1 is a novel transcriptional mediator of inflammation that interacts with NF-kappa B to regulate the inducible nitric-oxide synthase gene.

Inflammation is a hallmark of several vascular diseases. The nuclear factor kappaB (NF-kappaB) transcription factors are dimeric proteins involved in the activation of a large number of genes in response to inflammatory stimuli. We report the involvement of a novel member of the ETS transcription factor, ESE-1, in mediating vascular inflammation. ESE-1 is induced in response to inflammatory cytokines and lipopolysaccharide in vascular smooth muscle cells, endothelial cells, and cells of the monocyte-macrophage lineage. This induction occurs within hours of stimulation and is mediated by NF-kappaB transactivation of the ESE-1 promoter. We have identified the inducible form of nitric-oxide synthase (NOS2) as a putative target for ESE-1. ESE-1 can bind to the p50 subunit of NF-kappaB, and cotransfection of ESE-1 with the p50 and p65 subunits of NF-kappaB synergistically enhances transactivation of the NOS2 promoter by ESE-1. An ESE-1-binding site within the NOS2 promoter has been identified, the site-directed mutagenesis of which completely abolishes the ability of ESE-1 to transactivate the NOS2 promoter. Finally, in a mouse model of endotoxemia, associated with acute vascular inflammation, ESE-1 is strongly expressed in vascular endothelium and smooth muscle cells. In summary, ESE-1 represents a novel mediator of vascular inflammation.

Binding Sites↗

CD8+ T cells are capable of rejecting pancreatic islet xenografts.

BACKGROUND: In this study, the capacity of CD8+ T cells to act as a potential effector mechanism in pancreatic xenograft rejection was examined. METHODS: The fate of pancreatic islet xenografts was studied in mice deficient in MHC class II molecules and CD4+ T cells. Fetal pig pancreas (FPP) or Wistar rat islets (RI) were transplanted into nondiabetic or streptozotocin-induced diabetic I-A knock-out (CII K/O) mice. RESULTS: CII K/O mice were capable of rejecting both RI and FPP grafts. RI graft survival was not prolonged compared with wild type C57BL/6 controls. However, FPP grafts did survive longer in CII K/O recipients than in C57BL/J6 mice. Both RI and FPP graft rejection were CD8+ T-cell phenomena in CII K/O mice, as anti-CD8 monoclonal antibody prolonged graft survival, there were increased CD8+ T cells in the grafts and spleens of CII K/O recipients, and cell-mediated cytotoxicity was a CD8+ T-cell phenomenon associated with activation of the perforin/granzyme B system. By contrast, RI and FPP graft rejection was a CD4+ T cell-dependent phenomenon in wild type C57BL/6 mice with graft survival prolonged by anti-CD4 monoclonal antibody. There were increased numbers of CD4+ T cells, and cell-mediated cytotoxicity was a CD4+ T-cell phenomenon associated with activation of the Fas/FasL lytic pathway. CONCLUSIONS: The results demonstrate that, in the absence of CD4+ T cells, CD8+ T cells were capable of rejecting both rat and pig pancreatic islet xenografts.

Animals↗

Breakdown of stabilization of atoms interacting with intense, high-frequency laser pulses

An analysis of the influence of the magnetic field of an intense, high-frequency laser pulse on the stabilization of an atomic system is presented. We demonstrate that at relatively modest intensities the magnetic field can significantly alter the dynamics of the system. In particular, a breakdown of stabilization occurs, thereby restricting the intensity regime in which the atom is relatively stable against ionization. Counterpropagating pulses do not negate the detrimental effects of the magnetic field. We compare our quantum mechanical results with classical Monte Carlo simulations.

Journal Article↗

Decision making for patients with multiple brain metastases: radiosurgery, radiotherapy, or resection?

OBJECT: Multiple brain metastases are a common health problem, frequently found in patients with cancer. The prognosis, even after treatment with whole-brain radiation therapy (WBRT), is poor, with an average expected survival time of less than 6 months. Investigators at numerous centers have evaluated the role of stereotactic radiosurgery in retrospective case series of patients harboring solitary or multiple tumors. Tumor resection is used mainly for patients with large tumors that cause acute neurological syndromes. The authors conducted a randomized trial in which they compared radiosurgery combined with WBRT with WBRT alone. METHODS: Twenty-seven patients were randomized (14 to recieve WBRT alone and 13 to receive WBRT combined with radiosurgery). The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients in whom boost radiosurgery was performed. The median time to local failure was 6 months after WBRT alone (95% confidence interval (CI) 3.5-8.5) in comparison to 36 months (95% CI 15.6-57) after WBRT and radiosurgery (p = 0.0005). The median time to the development of any brain failure was improved in the combined modality group (p = 0.002). Survival was shown to be related to the extent of extracranial disease (p = 0.02). CONCLUSIONS: Combined WBRT and radiosurgery for the treatment of patients with two to four brain metastases significantly improves control of brain disease. Whole-brain radiation therapy alone does not provide lasting and effective care when treating most patients. Surgical resection remains important for patients with large symptomatic tumors and in whom limited extracranial disease has been demonstrated.

Adult↗

Comparison of percent free PSA, PSA density, and age-specific PSA cutoffs for prostate cancer detection and staging.

OBJECTIVES: Various methods have been proposed to increase the specificity of prostate-specific antigen (PSA), including age-specific PSA reference ranges, PSA density (PSAD), and percent free PSA (%fPSA). In this multicenter study, we compared these methods for their utility in cancer detection and their ability to predict pathologic stage after radical prostatectomy in patients with clinically localized, Stage T1c cancer. METHODS: Seven hundred seventy-three men (379 with prostate cancer, 394 with benign prostatic disease), 50 to 75 years old, from seven medical centers were enrolled in this prospective blinded study. All subjects had a palpably benign prostate, PSA 4.0 to 10.0 ng/mL, and a histologically confirmed diagnosis. Hybritech's Tandem PSA and free PSA assays were used. RESULTS: %fPSA and age-specific PSA cutoffs enhanced PSA specificity for cancer detection, but %fPSA maintained significantly higher sensitivities. Age-specific PSA cutoffs missed 20% to 60% of cancers in men older than 60 years of age. %fPSA and PSAD performed equally well for detection (95% sensitivity) if cutoffs of 25% fPSA or 0.078 PSAD were used. The commonly used PSAD cutoff of 0.15 detected only 59% of cancers. %fPSA and PSAD also produced similar results for prediction of the post-radical prostatectomy pathologic stage. Patients with cancer with higher %fPSA values (greater than 15%) or lower PSAD values (0.15 or less) tended to have less aggressive disease. CONCLUSIONS: The results of this study demonstrated that cancer detection (sensitivity) is significantly higher with %fPSA than with age-specific PSA reference ranges. %fPSA and PSAD provide comparable results, suggesting that %fPSA may be used in place of PSAD for biopsy decisions and in algorithms for prediction of less aggressive tumors since the determination of %fPSA does not require ultrasound.

Age Factors↗