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Biomedical subjects

A Patel

Publications and source records attributed to A Patel.

At least 253 records · Page 14Linked to original sources
PubMed1997

Distinct mechanisms for the induction and maintenance of allograft tolerance with CTLA4-Fc treatment.

A murine CTLA4/Fc gamma2a heavy chain (mCTLA4-Fc) chimeric fusion molecule was used in B6AF1 recipients of BALB/c pancreatic islet allografts to study the induction and maintenance of tolerance following inhibition of the CD28-B7 pathway for T cell activation. Donor-specific tolerance was achieved by administering 100 microg of mCTLA4-Fc on alternate days for 14 days (8 total doses) or a single 500 microg dose of mCTLA4-Fc on day 2 after transplant. Tolerance was mediated by long-lived peripheral lymphocytes and showed features of organ and alloantigen specificity. Whereas tolerance could not be established in allograft recipients receiving simultaneous mCTLA4-Fc and rIL-2, previously tolerant animals did not reject their grafts when given IL-2, suggesting that the induction and maintenance phases of tolerance were distinct and separate. The maintenance of donor-specific tolerance was an active immunologic process that was CD4+ T cell dependent and could be adoptively transferred to naive lymphocytes, but could not be explained by apoptosis or deletion of alloreactive T cells. Although an IL-2-sensitive mechanism such as anergy may contribute toward the induction of tolerance, its maintenance involves active suppression.

Abatacept↗
PubMed1997

Telephone assessment and advice: a training programme.

Nurses have become increasingly involved in providing telephone assessment and advice, and telephone triage is emerging as an important part of the everyday role that nurses can play in A&E, general practice and other community settings. This article describes a project to prepare staff to fulfil this role.

Counseling↗
PubMed1997

The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis.

OBJECTIVE: To prospectively test the hypothesis that a diagnosis of deep vein thrombosis can be excluded in outpatients who present with clinical indications of deep vein thrombosis and whose results of D-dimer testing and impedance plethysmographic examination on the day of presentation are normal. DESIGN: Prospective cohort study. SETTING: Four university-affiliated hospitals. METHODS: Three hundred ninety-eight consecutive patients with clinical indications of deep vein thrombosis were included in the final analysis. All patients underwent an assessment of pretest probability, bedside D-dimer testing, and impedance plethysmographic examination. In most patients, if the results of D-dimer testing and impedance plethysmographic examination were negative for deep vein thrombosis, anticoagulants were withheld and patients were followed up for 3 months. If the results of one or both tests were abnormal, an examination using venous compression ultrasonography or phlebography was performed. RESULTS: In the majority of patients (69%), the results of D-dimer testing and impedance plethysmographic examination were normal. This combination had a negative predictive value of 98.5% (95% confidence interval, 96.3-99.6) for deep vein thrombosis. CONCLUSION: The results of the D-dimer assay and impedance plethysmographic examination on the day of presentation can be used to treat the majority of outpatients who present with clinical indications of deep vein thrombosis without further testing.

Adult↗
PubMed1997

Contraction-induced changes in acetyl-CoA carboxylase and 5'-AMP-activated kinase in skeletal muscle.

The concentration of malonyl-CoA, a negative regulator of fatty acid oxidation, diminishes acutely in contracting skeletal muscle. To determine how this occurs, the activity and properties of acetyl-CoA carboxylase beta (ACC-beta), the skeletal muscle isozyme that catalyzes malonyl-CoA formation, were examined in rat gastrocnemius-soleus muscles at rest and during contractions induced by electrical stimulation of the sciatic nerve. To avoid the problem of contamination of the muscle extract by mitochondrial carboxylases, an assay was developed in which ACC-beta was first purified by immunoprecipitation with a monoclonal antibody. ACC-beta was quantitatively recovered in the immunopellet and exhibited a high sensitivity to citrate (12-fold activation) and a Km for acetyl-CoA (120 microM) similar to that reported for ACC-beta purified by other means. After 5 min of contraction, ACC-beta activity was decreased by 90% despite an apparent increase in the cytosolic concentration of citrate, a positive regulator of ACC. SDS-polyacrylamide gel electrophoresis of both homogenates and immunopellets from these muscles showed a decrease in the electrophoretic mobility of ACC, suggesting that phosphorylation could account for the decrease in ACC activity. In keeping with this notion, citrate activation of ACC purified from contracting muscle was markedly depressed. In addition, homogenization of the muscles in a buffer free of phosphatase inhibitors and containing the phosphatase activators glutamate and MgCl2 or treatment of immunoprecipitated ACC-beta with purified protein phosphatase 2A abolished the decreases in both ACC-beta activity and electrophoretic mobility caused by contraction. The rapid decrease in ACC-beta activity after the onset of contractions (50% by 20 s) and its slow restoration to initial values during recovery (60-90 min) were paralleled temporally by reciprocal changes in the activity of the alpha2 but not the alpha1 isoform of 5'-AMP-activated protein kinase (AMPK). In conclusion, the results suggest that the decrease in ACC activity during muscle contraction is caused by an increase in its phosphorylation, most probably due, at least in part, to activation of the alpha2 isoform of AMPK. They also suggest a dual mechanism for ACC regulation in muscle in which inhibition by phosphorylation takes precedence over activation by citrate. These alterations in ACC and AMPK activity, by diminishing the concentration of malonyl-CoA, could be responsible for the increase in fatty acid oxidation observed in skeletal muscle during exercise.

AMP-Activated Protein Kinases↗
PubMed1997

The Diabetes Care Support Service for general practitioners in Auckland.

AIMS: Diabetic complications can often be prevented by timely detection and intervention. Optimising diabetes care requires effective monitoring of risk factors at both practice and district level. We describe a novel method which combines district monitoring of diabetes with enhanced diabetes care by individual general practitioners. METHODS: All general practitioners in south and west Auckland (n = 291) were invited to join the Diabetes Care Support Service (DCSS). This involved the identification of all diabetic patients within the practice and the completion of an audit from with key measures of diabetes and its care. RESULTS: Audit was completed for 217 (75%) of general practitioners and 4611 diabetic patients: 39% of general practitioners completed their own audit. The proportion of completed patient assessments ranged between 35% (foot pulses) and 89% (blood pressure). The process was found to be helpful by 88% of general practitioners (who commented). CONCLUSION: The DCSS is a seamless, service-orientated approach to the delivery of diabetes care by primary and secondary services and is likely to improve care district-wide and identify the need for further interventions. Subsequent audit passes will allow the demonstration and monitoring of any changes that occur, as well as the demonstration of its feasibility and acceptability on an ongoing basis.

Blood Pressure↗
PubMed1997

A bacterial basic region leucine zipper histidine kinase regulating toluene degradation.

The two-component signal transduction pathways in bacteria use a histidine-aspartate phosphorelay circuit to mediate cellular changes in response to environmental stimuli. Here we describe a novel two-component todST system, which activates expression of the toluene degradation (tod) pathway in Pseudomonas putida F1. The todS gene is predicted to encode a sensory hybrid kinase with two unique properties--a basic region leucine zipper dimerization motif at the N terminus and a duplicated histidine kinase motif. Evidence from a synthetic peptide model suggests that TodS binds as a dimer to a pseudopalindromic sequence (5'-TGACTCA), which resembles the recognition sequence of the eukaryotic transcription factors Fos and Jun. These results provide additional evidence that bacteria and eukaryotes share common regulatory motifs. The todT gene product, a response regulator, was overproduced as a fusion protein in Escherichia coli, and the purified protein was found to bind specifically to a 6-bp palindromic DNA structure in the tod control region. The phosphorylated form of TodT appears to be the activator of tod structural genes. This is the first report of a two-component system that regulates aromatic metabolism in bacteria.

Amino Acid Sequence↗
PubMed1997

Mice lacking transforming growth factor alpha have an increased susceptibility to dextran sulfate-induced colitis.

BACKGROUND & AIMS: There is indirect evidence that transforming growth factor alpha (TGF-alpha) is an important mediator of mucosal defense and repair. TGF-alpha knockout mice and TGF-alpha-deficient mice (wa-1) provide novel approaches to evaluate the role of TGF-alpha in preserving the integrity of the colon. METHODS: Colitis was induced by oral administration of dextran sodium sulfate (DSS, 5 g/dL) to knockout mice, their genetic controls (GC), wa-1 mice, and BALB/c mice. TGF-alpha was also administered intraperitoneally to wa-1 mice to evaluate the effect of exogenous TGF-alpha in DSS colitis. RESULTS: In response to DSS, nearly 60% of the entire colonic mucosa was destroyed in knockout and wa-1 mice, compared with 22% in GC mice and 16% in BALB/ c mice. Body weight loss was doubled in knockout (28%) and wa-1 mice (23%) compared with GC (11%) and Balb/c mice (12%). TGF-alpha application to wa-1 mice reduced the severity of mucosal injury by almost 70% compared with controls. CONCLUSIONS: The marked susceptibility of TGF-alpha knockout and wa-1 mice to DSS and the obvious amelioration of the colonic injury by exogenous TGF-alpha application in wa-1 mice suggest that TGF-alpha is a mediator of protection and/or healing mechanisms in the colon.

Animals↗
PubMed1997

Recurrence patterns after radical retropubic prostatectomy: clinical usefulness of prostate specific antigen doubling times and log slope prostate specific antigen.

PURPOSE: We studied the correlation between prostate specific antigen (PSA) doubling time or, equivalently, log slope PSA and clinical recurrence in patients with detectable PSA after radical retropubic prostatectomy who were followed expectantly. MATERIALS AND METHODS: In patients with PSA recurrence after radical retropubic prostatectomy log slope PSA was determined from the difference in the 2 log PSA values divided by the time between readings in months. For a given slope the corresponding PSA doubling time was calculated as log x 2 divided by the slope of the log PSA line. When the initial PSA value was considerably greater than 0.4 ng./ml., the log slope PSA plot was extrapolated to determine the time point at which PSA would have become detectable (0.4 ng./ml.). The relationship between these values, and the time and pattern of clinical recurrence were studied. RESULTS: In this series of 77 patients 80% with PSA doubling time of 6 months or greater remained clinically disease-free compared to 64% with PSA doubling time less than 6 months. PSA doubling time had better correlation with time to clinical recurrence after PSA became detectable (p <0.001 Cox proportional hazards model) than Gleason sum, pathological stage or margin status. Biochemical recurrence within 3 months was associated with early clinical recurrence (p <0.002). In addition, short PSA doubling time, that is a high log slope, regardless of the time at which PSA became positive was strongly associated with clinical recurrence (p <0.001). Distant recurrence was invariably associated with short PSA doubling time. Conversely, local recurrence reliably correlated with long PSA doubling time, that is a low log slope. CONCLUSIONS: After PSA became detectable PSA doubling time or, equivalently, log slope PSA, was a better indicator of the risk and time to clinical recurrence after radical retropubic prostatectomy than preoperative PSA, specimen Gleason sum or pathological stage. Hormone treatment may be targeted to patients at high risk for early metastatic clinical recurrence, appropriately timed radiation can be offered for proved local recurrence in those with long PSA doubling time and expectant treatment may be proposed for those with long PSA doubling time who remain clinically disease-free. Frequent and expensive imaging does not appear to be cost-effective in this latter group.

Adult↗
PubMed1997

Quantitative assessment of variables that influence soft-tissue electrovaporization in a fluid environment.

OBJECTIVES: To evaluate the process of soft-tissue electrovaporization and to study variables that affect tissue clearance rates in a laboratory setting, in order to identify parameters that can optimize transurethral electrovaporization of the prostate. METHODS: Fresh bovine skeletal muscle, equivalent in impedance and surface properties to the human prostate, was submerged in 3.3% sorbitol solution and electrovaporized with a grooved monopolar electrode attached to the weighted arm of a linear actuator. The effects of excursion rate, applied mechanical load, power setting, electrode configuration, and generator performance on the volume of tissue removed, were assessed. RESULTS: Tissue removal increased significantly when electrode excursion rate was slowed from 25 to 15 mm/s (P < 0.05) and then to 10 mm/s (P < 0.05); when the load was increased from 20 to 50 g (P < 0.005); and when dial power was increased from 120 to 150 W (P < 0.01). Tissue removal was generator dependent. There was no significant difference between the Force 40 and the Force 2 (P > 0.4), but a new computer-controlled constant power output generator (Force FX) did significantly improve tissue vaporization at an equivalent power setting (P < 0.005 and P < 0.01, respectively). Tissue removal was also dependent upon electrode configuration, with the VaporTrode-Grooved Bar removing significantly more tissue than either an ungrooved roller bar of equivalent size or 2-mm smooth roller ball, respectively, both after a single pass (P < 0.001 and P < 0.05) and after five repeated passes (P < 0.05 and P < 0.005). The histologic depth of tissue thermal effect was less than 1 mm, but it was 38% greater for the VaporTrode-Grooved Bar (0.68 mm) than for the standard cutting loop (0.5 mm, P < 0.01). CONCLUSIONS: Using a novel method to quantify tissue removal, we have demonstrated that electrode configuration, excursion rate, applied load, power setting, and generator performance are interdependent factors that influence the efficacy of the electrovaporization process in a fluid environment.

Animals↗
PubMed1997

A pilot study of energy utilization patterns during different transurethral electrosurgical treatments of the prostate.

OBJECTIVES: During a prospective randomized study of prostatic and periprostatic heating during transurethral electrosurgical treatment, energy utilization was studied with respect to electrode configuration and prostate size. METHODS: Patients were stratified for gland volume (transrectal ultrasound [TRUS] 50 cc or less and more than 50 cc) and randomized to treatment either with loop resection (transurethral resection of the prostate [TURP]) or electrovaporization (transurethral electrovaporization [TUEVAP]. VaporTrode-Grooved Bar, CIRCON ACMI). Power was provided by a radiofrequency unit (Force FX, Valleylab) initially set at 150 W. A passive feed-through system was connected to the patient circuit to record current and voltage at 10 Hz during each activation of the cut mode in real time. RESULTS: Patients (6 per group) were well matched for prostate volume (P < 0.57) and operating time (P < 0.33). Power settings were also similar (120 to 190 W). Both total energy utilization (P < 0.025) and energy used per minute of treatment (P < 0.004) were greater for TUEVAP than for TURP. The higher energy deposition per unit time for TUEVAP was not associated with undesirable periprostatic heating. For TURP, more energy was used per unit time for each gram resected in small prostates than in larger glands. Comparing energy consumption per minute per cubic centimeter of prostate, we found a 2:1 ratio between TUEVAP and TURP in large prostates, which increased to 3.4:1 (P < 0.049) in small glands. CONCLUSIONS: For the same panel power settings, more energy is deposited at the tissue interface during TUEVAP than during TURP. This extra energy provides better surface hemostasis without undesirable deep heating and can be explained by the larger contact surface and contact time (slower speed of excursion) of the VaporTrode than a regular loop. The novel observation that more energy is required for small prostates during both treatments suggests that these glands have different electrical properties and higher tissue impedance than larger glands.

Electrosurgery↗
PubMed1997

Lack of pineal beta-adrenergic receptor alterations in suicide victims with major depression.

Noradrenergic function may be altered in depressive illness and thereby contribute to decreased pineal production of melatonin levels, as previously described in some depressed subjects. In the present study, the hypothesis was tested that pineal beta-adrenergic binding would be increased in persons committing suicide with evidence of depressive disorders, reflecting diminished noradrenergic input. Initially, post-mortem human pineal glands were obtained at autopsy. Diagnostic and symptomatic information was then systematically collected from family members using standardized interview techniques. Seven subjects who committed suicide and suffered from major depression, and without exposure to treatment for depressive symptoms were age- and sex-matched with control subjects. Pineal beta-adrenergic binding was assessed by quantitative autoradiography employing four concentrations of [125I]pindolol. Because of possibly complex adrenergic regulation of the pineal, beta-adrenergic receptor binding were subtyped using the selective blocker ICI 89406. No differences in beta-adrenergic receptors were detected between subjects with major depression compared to the matched controls.

Adult↗
PubMed1997

Prevalence of capsular serotypes among Staphylococcus aureus isolates from cows with mastitis in the United States.

Development of an appropriate Staphylococcus aureus vaccine for bovine mastitis has eluded researchers for decades. The ability of S. aureus to form a protective exopolysaccharide capsule has posed a major obstacle because of the multiple serotypes and the poor immune response elicited by exopolysaccharides. This study characterized S. aureus serotypes isolated from cases of bovine mastitis obtained from veterinary diagnostic laboratories that service 44% of the dairy cattle in the United States. Major milk producing areas of the northeast, north central, Pacific coast and southwest were proportionately represented. Sub-samples of mastitic milk that contained S. aureus were frozen and sent to our laboratory for strain serotyping. The only other regional serotyping of S. aureus from bovine mastitis to date was done in France. The primary serotypes found were types 5 (51%) and 8 (18%) and 31% were non-typeable. In the current study, serotype 5 accounted for 18% of the isolates and serotype 8 for 23%. More importantly 59% of the isolates were not typeable with either type 5 or 8 antisera. These data indicate that S. aureus vaccines employing serotypes 5 and 8 would only be marginally effective in the United States. These data also suggest that development of a S. aureus vaccine for bovine mastitis should take into account regional variation in S. aureus serotypes.

Animals↗
PubMed1997

Radial scars: a review of 30 cases.

Radial Scars/Complex Sclerosing Lesions are benign breast lesions that are seen more frequently now with the advent of screening mammography. These lesions need to be excised surgically in the absence of classical diagnostic features.

Breast↗
PubMed1997

Expanding the horizons of SWL through adjunctive use of retrograde intrarenal surgery: new techniques and indications.

The recognition of high retreatment rates and lower success rates after SWL monotherapy in certain situations led us to explore a new endourologic strategy including retrograde intrarenal surgery (RIRS). Examples of situations in which RIRS + SWL is appropriate are coexistence of stones and coagulopathy, stones associated with intrarenal stenosis, concomitant renal and ureteral stones, renal anomalies, and failed SWL. Lithotripter-specific guidelines for the adjunctive use of RIRS may be appropriate.

Adolescent↗