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Biomedical subjects

S Patel

Publications and source records attributed to S Patel.

At least 271 records · Page 15Linked to original sources
PubMed1999

National survey of stress ulcer prophylaxis.

OBJECTIVE: To determine the rationale for using stress ulcer prophylaxis (SUP) among clinicians; to assess criteria used to define failure of SUP; and to evaluate the decision-making process in the selection of a prophylactic agent. DESIGN: A cross-sectional national mail survey. SETTING: Random sample of the members of the Society of Critical Care Medicine who identified anesthesiology, surgery, or internal medicine as their primary specialty area. PATIENTS: None. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Questionnaires consisting of multiple-choice and short-answer questions were sent to a simple random sample of 1,268 physicians to assess the current practice of SUP. A total of 328 usable questions were returned, resulting in a response rate of 26%. All percentages reported in the results are based on the total number of responses. The risk factors for SUP that were most commonly identified were burns (91%), shock (90%), and sepsis (88%). These were also risk factors for which the respondents most commonly started SUP. Histamine-2-receptor (H2)-antagonists as a class, were the most commonly used prophylactic agents (67%). The most commonly used agents for SUP were ranitidine (31%), famotidine (24%), sucralfate (24%), and cimetidine (12%). Most respondents selected ranitidine for ease of administration, famotidine because of formulary availability, sucralfate for a better side effects profile, and cimetidine for cost-effectiveness. Eighty-two percent of respondents considered the presence of bright red blood in the nasogastric tube as failure of SUP. In cases where SUP failed, most respondents would add a second agent from a different therapeutic class. Of those respondents who used an H2-antagonist initially, 48% would add sucralfate, 36% would add antacid, and 13% would add omeprazole. Of those respondents who used sucralfate, 77% would add an H2-antagonist when SUP failed. For those respondents who would switch to another agent when the H2-antagonist failed, 52% would change to omeprazole, whereas 67% would change to an H2-antagonist when sucralfate failed. Only eight respondents would discontinue SUP when risk factors were resolved. Most respondents would discontinue SUP when the patient was no longer in the "nothing by mouth" status (28%), started on enteral feeding (23%), or discharged from the intensive care unit (21%). The mean duration of SUP was 6.3+/-4.5 (SD) days. CONCLUSIONS: This survey highlighted the lack of consensus in the use of SUP. Many patients receive SUP for an extended period, without clear-cut indications or documented benefit. The cost of unwarranted SUP in patients with low risk of stress ulcer gastrointestinal bleeding is prohibitive. Treatment algorithms or protocols for SUP based on prescribing patterns, hospital formulary restrictions, and cost-analysis should be considered for each institution to guide critical care physicians on the proper use of SUP therapies.

Anti-Ulcer Agents↗
PubMed1999

Comparison of letter and Vernier acuities with dioptric and diffusive blur.

We assessed the influence of dioptric and diffusive blur on normal subjects' letter and Vernier acuity in two experiments. In the first experiment, letter acuity was measured for isolated black Sloan letters and Vernier acuity was determined for a pair of black vertical abutting or nonabutting lines. Targets were viewed through plus lenses that produced 0, 1, 2, 4, and 8 D of dioptric blur. In the second experiment, letter acuity was determined for bright 4-position Ts and Vernier acuity was measured for a pair of bright abutting vertical lines. Six levels of imposed diffusive blur were produced by varying the distance between a ground glass screen and the oscilloscope on which the targets were presented. The results of both experiments indicate that letter and Vernier acuity for abutting or closely separated lines worsen in parallel curvilinear fashion, as long as the lines comprising the Vernier targets remain equally detectable when various amounts of dioptric and diffusive blur are imposed. We conclude that both dioptric and diffusive blur introduce common processing limitations for letter and Vernier acuity.

Form Perception↗
PubMed1999

Tear thinning time and topical anesthesia as assessed using the HIRCAL grid and the NCCA.

BACKGROUND: The literature contains conflicting reports of the effects of topical anesthetics on tear film stability, with some consensus that unpreserved topical anesthetics are less likely to reduce tear film stability than preserved preparations. This experiment investigated the effect of unpreserved 0.4% benoxinate hydrochloride on tear thinning time (TTT), in parallel with "real time" corneal sensitivity assessment. METHODS: Tear film stability was assessed (HIRCAL grid) in parallel with real time assessment of the pharmacological activity (NCCA) of unpreserved 0.4% benoxinate hydrochloride in normal eyes. RESULTS: The anesthetic used did not significantly affect tear film stability. This finding is in agreement with previous investigators. CONCLUSIONS: Unpreserved 0.4% benoxinate hydrochloride could be used to facilitate tear film stability assessment. The experimental protocol used could also be applied to investigate the temporal relationship between anesthesia and tear film stability with preserved topical anesthetics that have been found to decrease tear film stability.

Adult↗
PubMed1999

Clinical study of combined penetrating keratoplasty, pars plana vitrectomy with temporary keratoprosthesis, and pars plana seton implant.

PURPOSE: To assess the effectiveness of a combined procedure (pars plana vitrectomy with temporary keratoprosthesis, penetrating keratoplasty, and pars plana seton implant) in preserving vision and controlling intraocular pressure (IOP). METHODS: We reviewed the course of visual acuity, IOP, graft clarity, retinal status, and complications in 18 patients who underwent the above procedure during one operating sitting. RESULTS: Preoperative diagnoses were varied. The majority of patients had pseudophakic bullous keratopathy and failed corneal transplants with glaucoma. Preoperative mean visual acuity was hand motions. Preoperative mean IOP was 27+/-13 mm Hg. Initially, all patients had attached retina. With a mean follow-up of 17+/-9 months, six patients had improved vision greater than 2 lines and 10 had unchanged vision. Only two patients lost vision greater than 2 lines. The final average IOP was 16+/-6 mm Hg and only one eye had a pressure above 22 mm Hg. Three eyes were classified as complete failures; two of the three became phthisical. Two patients developed rhegmatogenous detachments requiring further surgery. CONCLUSION: The combined procedure offers reasonable improvement in vision, good pressure control, and a tolerable number of complications. It is a useful procedure in eyes that probably would not have been treatable otherwise.

Adolescent↗
PubMed1999

HLA class II transgenic mice: models of the human CD4+ T-cell immune response.

This review examines the field of current HLA class II transgenic mouse models and the individual approaches applied in production of these mice. The majority of these mice have been created with the objective of obtaining a disease model with clinical features mimicking human autoimmune disease. The development process of a different type of HLA class II transgenic mice, which are designed to function as a substitute for a normal human immune system in studies of human autoantigens, is described. Several HLA-DR4 transgenic lines with normally expressed HLA-DR4 molecules have been produced. To obtain adequate positive selection of the HLA-DR4-restricted CD4+ T-cell repertoire in these mice it is essential both to introduce a human CD4 transgene, and to delete the murine major histocompatibility complex (MHC) class II molecules. These HLA-DR4 transgenic mice have been used to determine the immunogenic CD4+ T-cell epitopes of several human autoantigenic proteins.

Animals↗
PubMed1999

Hypersensitive site 2 specifies a unique function within the human beta-globin locus control region to stimulate globin gene transcription.

The human beta-globin locus control region (LCR) harbors both strong chromatin opening and enhancer activity when assayed in transgenic mice. To understand the contribution of individual DNase I hypersensitive sites (HS) to the function of the human beta-globin LCR, we have mutated the core elements within the context of a yeast artificial chromosome (YAC) carrying the entire locus and then analyzed the effect of these mutations on the formation of LCR HS elements and expression of the genes in transgenic mice. In the present study, we examined the consequences of two different HS2 mutations. We first generated seven YAC transgenic lines bearing a deletion of the 375-bp core enhancer of HS2. Single-copy HS2 deletion mutants exhibited severely depressed HS site formation and expression of all of the human beta-globin genes at every developmental stage, confirming that HS2 is a vital, integral component of the LCR. We also analyzed four transgenic lines in which the core element of HS2 was replaced by that of HS3 and found that while HS3 is able to restore the chromatin-opening activity of the LCR, it is not able to functionally replace HS2 in mediating high-level globin gene transcription. These results continue to support the hypothesis that HS2, HS3, and HS4 act as a single, integral unit to regulate human globin gene transcription as a holocomplex, but they can also be interpreted to say that formation of a DNase I hypersensitive holocomplex alone is not sufficient for mediating high-level globin gene transcription. We therefore propose that the core elements must productively interact with one another to generate a unique subdomain within the nucleoprotein holocomplex that interacts in a stage-specific manner with individual globin gene promoters.

Animals↗
PubMed1999

Association of fever and severe clinical course in bronchiolitis.

Little attention has been given to the relation between fever and the severity of bronchiolitis. Therefore, the relation between fever and the clinical course of 90 infants (59 boys, 31 girls) hospitalised during one season with bronchiolitis was studied prospectively. Fever (defined as a single recording > 38.0 degrees C or two successive recording > 37.8 degrees C) was present in 28 infants. These infants were older (mean age, 5.3 v 4.0 months), had a longer mean hospital stay (4.2 v 2.7 days), and a more severe clinical course (71.0% v 29.0%) than those infants without fever. Radiological abnormalities (collapse/consolidation) were found in 60. 7% of the febrile group compared with 14.8% of the afebrile infants. These results suggest that monitoring of body temperature is important in bronchiolitis and that fever is likely to be associated with a more severe clinical course and radiological abnormalities.

Age Factors↗
PubMed1999

Subcallosal striations: early findings of multiple sclerosis on sagittal, thin-section, fast FLAIR MR images.

PURPOSE: To determine how sensitive and specific the magnetic resonance (MR) imaging finding of subcallosal striations is for multiple sclerosis (MS). MATERIALS AND METHODS: In 18 patients with clinically suspected MS and 32 age-matched patients without MS, sagittal 2-mm fast fluid-attenuated inversion-recovery (FLAIR) imaging was added to the routine MR studies of the brain. The images were reviewed for the presence of subcallosal striations, that is, linear, 1-mm-thick foci of hyperintensity perpendicular to the ependyma, like a stack of coins. The images were masked to exclude the hemispheric white matter and were interpreted without knowledge of patient age or medical history. RESULTS: Seventeen patients with clinical MS had subcallosal striations; one did not. Of the 32 patients without MS, five had subcallosal striations and 27 did not. Subcallosal striations were highly associated (P < .001) with clinical MS. CONCLUSION: Subcallosal striations are thought to represent perivenular demyelination, that is, the same process that later produces the "ovoid" lesions visible on routine MR images. Subcallosal striations are not seen on routine axial MR images and can be seen only on 2-mm sagittal FLAIR images.

Adult↗
PubMed1999

Role of matrix metalloproteinases and their tissue inhibitors in the regulation of coronary cell migration.

The migration of vascular cells is regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Because the activation of adventitial fibroblasts has been implicated in coronary repair, we have examined regional differences in cell outgrowth and the synthesis of MMPs/TIMPs in different layers of porcine coronary arteries. Coronary medial explants demonstrated significantly slower cell outgrowth than coronary adventitia in culture (P<0.001). These observations were paralleled by the predominant expression of TIMP-1 and -2 in the media (14-fold and 37-fold higher than in adventitia, respectively, P<0.001), whereas higher gelatinolytic activities (MMP-2 and -9) were released from adventitial explants. Smooth muscle cell outgrowth from the media was regulated by endogenous TIMPs, since TIMP inhibition (recombinant MMP-2 or neutralizing anti-TIMP antibodies) facilitated cell outgrowth (P<0.001). In contrast, the addition of recombinant TIMP-1 or -2 decreased adventitial cell outgrowth. In the coculture experiments, the presence of coronary media retarded adventitial cell outgrowth, whereas medial damage abrogated these effects, allowing for fibroblast migration (P<0.001). In conclusion, this study demonstrated differential migratory properties and distinct MMP/TIMP synthesis by coronary fibroblasts and smooth muscle cells. Endogenous TIMPs in the media may play an important role in maintaining coronary arterial wall homeostasis, whereas high levels of matrix-degrading activities confer the "invasive" characteristics of adventitial fibroblasts.

Animals↗
PubMed1999

Evaluation of early computed tomographic findings in acute ischemic stroke.

BACKGROUND AND PURPOSE: Detection of large, hypoattenuated brain-tissue volume on hyperacute CT scan has been suggested as an exclusion criterion for early intravenous tissue plasminogen activator (IV-tPA) treatment. This study assessed the reliability of detection for these findings and their relationship to outcome. METHODS: Fifty hyperacute CT scans (<6 hours after ictus) were selected from a randomized trial evaluating IV-tPA (ATLANTIS trial). Three neuroradiologists blinded to all clinical information evaluated scans for degree of MCA territory involvement (<33% or >33%) and the presence of a hyperdense MCA. Evaluations were compared with 24-hour scan results, 30-day infarct volumes, and baseline NIH stroke scale scores (NIHSS). RESULTS: Readers reliably evaluated the degree of MCA territory hypodensity (intraclass correlation=0.53, P<0.001), with all 3 readers agreeing in 36 of 50 cases (72%). They correctly called >33% involvement with a sensitivity of 60% to 85% and a specificity of 86% to 97%. The baseline NIHSS was higher when >33% MCA hypodensity was seen (P=0. 021). Detection of significant hypodensity (>33%) correlated with poorer outcome. When >33% hypodensity was not detected, mean 30-day infarct volumes were 27.0 to 33.0 cm3, versus 84.3 to 123.1 cm3 when >33% hypodensity was present (P=0.002). CONCLUSIONS: Detection of MCA territory hypodensity on hyperacute CT scans is a sensitive, prognostic, and reliable indicator of the amount of MCA territory undergoing infarction.

Acute Disease↗
PubMed1999

Agreement and variability in the interpretation of early CT changes in stroke patients qualifying for intravenous rtPA therapy.

BACKGROUND AND PURPOSE: Ischemic changes identified on CT scans performed in the first few hours after stroke onset, which are thought to possibly represent early cytotoxic edema and development of irreversible injury, may have important implications for subsequent treatment. However, insecurity and conflicting data exist over the ability of clinicians to correctly recognize and interpret these changes. We performed a detailed review of selected baseline CT scans from the NINDS rt-PA Stroke Trial to test agreement among experienced stroke specialists and other physicians on the presence of early CT ischemic changes. METHODS: Seventy baseline CT scans from the NINDS Stroke Trial were read and classified for the presence or absence of various early findings of ischemia by 16 individuals, including NINDS trial investigators, other neurologists, other emergency medicine physicians, and radiology or stroke fellows. CT scans included normal scans and scans from patients who later developed symptomatic intracranial hemorrhage, as well as scans on which the NINDS rt-PA Stroke Trial neuroradiologist identified clear-cut early CT changes. For each CT finding, kappa-statistics were used to assess the proportion of agreement beyond chance. RESULTS: kappa-Values (95% confidence interval [CI]) ranged from 0.20 (-0.20, 0.61) (fair agreement) to 0.41 (0.37, 0.45) (moderate agreement) among the 16 viewers, and the kappa-value was only 0.39 (0.29, 0.49) (fair) in answer to the question "do early CT changes involve more than one third of the MCA [middle cerebral artery] territory?" There was substantial variability within each specialty group and between groups. kappa-Values were only fair to moderate even among physicians experienced in selecting and treating acute stroke patients with rtPA. Observed agreement ranged from 68% to 85%. Physicians agreed on the finding of early CT changes involving >33% of the MCA territory 77% of the time, although the kappa-value of 0.39 suggested only moderate agreement beyond chance. CONCLUSIONS: There is considerable lack of agreement, even among experienced clinicians, in recognizing and quantifying early CT changes. Improved methods of recognizing and quantifying early ischemic brain damage are needed.

Cerebrovascular Disorders↗
PubMed1999

Reasoning with uncertainty in pathology: artificial neural networks and logistic regression as tools for prediction of lymph node status in breast cancer patients.

Axillary lymph node status is an important prognostic feature for patients with breast cancer, but the therapeutic value of axillary lymphadenectomy is controversial. It would be useful to be able to predict the status of axillary lymph nodes before lymphadenectomy from prognostic features evaluated in a previous breast biopsy. This prediction would be useful to optimize the treatment of patients with breast cancer who are unlikely to have nodal metastases. We studied 279 patients with invasive breast carcinoma treated with modified radical mastectomy or with lumpectomy combined with axillary lymph node dissection. Prognostic factors evaluated were age, histologic type of invasive tumor, presence of associated ductal and/or lobular carcinoma in situ, lesion size, histologic and nuclear grades, DNA index, presence of multiploidy by flow cytometric analysis, and immunocytochemical expression of estrogen and progesterone receptors, proliferating nuclear cell antigen, and HER-2/neu oncogene. Several probabilistic neural networks (NNs) with genetic algorithms were developed using prognostic features as input neurons and lymph node status (positive or negative) as output neurons. The data were also studied with multiple regression and logistic regression analysis. The best NN model trained with 224 cases using 19 input neurons. It classified correctly 49 (89.0%) of 55 unknown cases (specificity, 97.2%; sensitivity, 80.0%; positive predictive value, 93.8%; negative predictive value, 87.5%). Several statistically significant models could be fitted with both multiple regression and logistic regression. The logistic regression model fitted with 240 cases using 6 independent variables estimated correctly 26 (66%) of 39 holdout cases. NNs and logistic regression models offer potentially useful tools to estimate the status of axillary lymph nodes of breast cancer patients before axillary lymphadenectomy. Future prospective studies with larger groups of patients and perhaps better prognostic markers are needed before these predictive multivariate models become ready for clinical use.

Adult↗
PubMed1999

The prognostic impact of BCL2 protein expression in acute myelogenous leukemia varies with cytogenetics.

BCL2 protein exerts an antiapoptotic effect on cells and decreases chemosensitivity. To determine whether BCL2 expression is prognostic of patient outcome in acute myelogenous leukemia (AML), we measured its level in 198 newly diagnosed, untreated AML patients by Western blotting using whole-cell lysates from low-density peripheral blood cells. BCL2 expression was not associated with the percentage of blasts (R2 = 0.10), French-American-British classification type, or cytogenetic abnormality. Smoothed martingale residual plots indicated that high BCL2 protein level was an adverse prognostic factor for patients with either favorable or intermediate prognosis cytogenetics [FIPC; inv(16), t(8:21), t(15:17), or diploid or insufficient metaphases] but was a favorable prognostic factor for patients with unfavorable prognosis cytogenetics (UC; -5, -7, +8, 11q23, Ph1, or miscellaneous changes). Patients with FIPC and high BCL2 (highest quartile) had a significantly shorter median survival (78 weeks versus not reached; P = 0.009) than did those with lower (lower three quartiles) levels of BCL2. Among those with UC, as BCL2 level decreased from the fourth quartile to the third or the combined first and second quartiles, the median survival decreased (from 94 to 45 or 17 weeks, respectively; P = 0.003). Lower expression of BCL2 in UC was associated with shorter remission duration (P = 0.05). In multivariate analyses performed using either overall or event-free survival as the end point, for either all patients or within either cytogenetic subgroup, BCL2 level was an independent prognostic factor. Similar analysis revealed that BCL2 level was an independent predictor of remission duration for UC patients as well. These data suggest that BCL2 is involved differently in different types (favorable versus unfavorable) of AML and that therapeutic strategies aimed at modulating BCL2 function may be more likely to work in patients with favorable cytogenetic abnormalities.

Adolescent↗
PubMed1999

Enhancement of tumor-to-nontumor localization ratios by hepatocyte-directed blood clearance of antibodies labeled with certain residualizing radiolabels.

UNLABELLED: To increase tumor-to-nontumor localization ratios of injected radiolabeled antibodies (Abs), several interrelated methods were used. METHODS: The model systems used were two human carcinoma xenografts grown in nude mice, targeted by antibodies RS11 (antiepithelial glycoprotein-2) or MN-14 (anticarcinoembryonic antigen). The Abs were conjugated with biotin and 111In-benzyl diethylenetriamine pentaacetic acid, and, at various times after injection, were cleared by intraperitoneal injection of galactosylated streptavidin, which delivers the complexes to hepatocytes. The radiolabel used was selected because it is retained within tumors after catabolism of the Ab by the tumor cell but is quite rapidly excreted from hepatocytes into bile. RESULTS: With blood clearance induced at 24 h, and dissection 5 h later, high tumor-to-nontumor ratios were attained. Depending on the model used, tumor-to-blood ratios were 16:1 to 31:1, and tumor-to-nontumor ratios for the kidney, lungs and bone were also high and greatly increased by the clearance regimen. Despite clearance into the liver, tumor-to-liver ratios remained >1, due to fairly rapid biliary excretion of the label. The absolute antibody uptake by the tumors was also high, because 24 h was allowed for the Ab to penetrate and bind to cells within the subcutaneous tumors. CONCLUSION: The method described produced high tumor-to-nontumor ratios at 1 d after injection and may be advantageous for tumor imaging with antibodies. Radiation dosimetry calculations indicate that there is only a slight advantage with this approach for radioimmunotherapy.

Animals↗