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Biomedical subjects

R Patel

Publications and source records attributed to R Patel.

At least 163 records · Page 9Linked to original sources
PubMed1999

Regulation of cytosolic COX-2 and prostaglandin E2 production by nitric oxide in activated murine macrophages.

Murine macrophages (RAW 264.7) when stimulated with LPS show 90% distribution of cyclooxygenase-2 (COX-2) in the nuclear fraction and approximately 10% in the cytosolic fraction. Further analysis of this cytosolic fraction at 100,000 x g indicates that the COX-2 is distributed both in the 100,000 x g soluble fraction and membrane fraction. Stimulation of RAW 264.7 cells with LPS in the presence of inducible nitric oxide synthase inhibitor L-NMMA at concentrations that inhibit nitrite accumulation by </=80% is inadequate to augment PGE2 production. However, inhibition of nitrite accumulation by >/=85% with higher concentrations of L-NMMA shows 1) up-regulation of PGE2 production, 2) accumulation of COX-2 protein in the 100,000 x g soluble and membrane fractions of the cytosolic fraction, and 3) with no significant effects on the accumulation of COX-2 mRNA. These experiments suggest that low concentrations of nitric oxide (10-15% of the total) attenuate PGE2 production in response to LPS in RAW 264.7 cells. This inhibition is, in part, due to decreased expression of cytosolic COX-2 protein.

3T3 Cells↗
PubMed1999

Calcium/calmodulin-dependent phosphorylation and activation of human Cdc25-C at the G2/M phase transition in HeLa cells.

The human tyrosine phosphatase (p54(cdc25-c)) is activated by phosphorylation at mitosis entry. The phosphorylated p54(cdc25-c) in turn activates the p34-cyclin B protein kinase and triggers mitosis. Although the active p34-cyclin B protein kinase can itself phosphorylate and activate p54(cdc25-c), we have investigated the possibility that other kinases may initially trigger the phosphorylation and activation of p54(cdc25-c). We have examined the effects of the calcium/calmodulin-dependent protein kinase (CaM kinase II) on p54(cdc25-c). Our in vitro experiments show that CaM kinase II can phosphorylate p54(cdc25-c) and increase its phosphatase activity by 2.5-3-fold. Treatment of a synchronous population of HeLa cells with KN-93 (a water-soluble inhibitor of CaM kinase II) or the microinjection of AC3-I (a specific peptide inhibitor of CaM kinase II) results in a cell cycle block in G2 phase. In the KN-93-arrested cells, p54(cdc25-c) is not phosphorylated, p34(cdc2) remains tyrosine phosphorylated, and there is no increase in histone H1 kinase activity. Our data suggest that a calcium-calmodulin-dependent step may be involved in the initial activation of p54(cdc25-c).

Benzylamines↗
PubMed1999

Addition of angiotensin II receptor blockade to maximal angiotensin-converting enzyme inhibition improves exercise capacity in patients with severe congestive heart failure.

BACKGROUND: Incomplete suppression of the renin-angiotensin system during long-term ACE inhibition may contribute to symptomatic deterioration in patients with severe congestive heart failure (CHF). Combined angiotensin II type I (AT1) receptor blockade and ACE inhibition more completely suppresses the activated renin-angiotensin system than either intervention alone in sodium-depleted normal individuals. Whether AT1 receptor blockade with losartan improves exercise capacity in patients with severe CHF already treated with ACE inhibitors is unknown. METHODS AND RESULTS: Thirty-three patients with severe CHF despite treatment with maximally recommended or tolerated doses of ACE inhibitors were randomized 1:1 to receive 50 mg/d losartan or placebo for 6 months in addition to standard therapy in a multicenter, double-blind trial. Peak aerobic capacity (V(O2)) during symptom-limited treadmill exercise and NYHA functional class were determined at baseline and after 3 and 6 months of double-blind therapy. Peak V(O2) at baseline and after 3 and 6 months were 13.5+/-0.6, 15.1+/-1.0, and 15.7+/-1.1 mL. kg-1. min-1, respectively, in patients receiving losartan and 14.1+/-0.6, 14.3+/-0.9, and 13.6+/-1.1 mL. kg-1. min-1, respectively, in patients receiving placebo (P<0.02 for treatment group-by-time interaction). Functional class improved by at least one NYHA class in 9 of 16 patients receiving losartan and 1 of 17 patients receiving placebo. CONCLUSIONS: Losartan enhances peak exercise capacity and alleviates symptoms in patients with CHF who are severely symptomatic despite treatment with maximally recommended or tolerated doses of ACE inhibitors.

Adult↗
PubMed1999

Regulation of nitric oxide and prostaglandin E2 production by CSAIDS (SB203580) in murine macrophages and bovine chondrocytes stimulated with LPS.

OBJECTIVE AND DESIGN: To compare two anti-inflammatory drugs: CSAIDS (SB203580) and hydrocortisone on iNOS and COX-2 expression. MATERIAL OR SUBJECTS: Murine macrophages and bovine chondrocytes stimulated with LPS and human OA-affected cartilage were used in this study. TREATMENT: The macrophages and chondrocytes were preincubated (30 min) with 0.1-1.0 microM CSAIDS or 10 microM of hydrocortisone before stimulating them with 1-100 microg/ml LPS. METHODS: The end products of iNOS and COX-2: nitric oxide (NO) and PGE2 were estimated by Greiss method and RIA, respectively. RESULTS: CSAIDS (1 microM) inhibited the production of NO and PGE2 (p< or =0.01) in bovine chondrocytes, but not in murine macrophages (RAW 264.7) (p< or =0.1). In fact, CSAIDS (in murine macrophages) marginally augmented nitrite accumulation (approximately 20%) at 14-24 h of LPS stimulation. Western blot analysis of COX-2 in bovine chondrocytes show decrease in COX-2 expression by hydrocortisone but not CSAIDS, although hydrocortisone and CSAIDS inhibit PGE2 accumulation. Hydrocortisone inhibited both PGE2 and NO production significantly (p< or =0.01) in murine macrophages. Furthermore, hydrocortisone significantly inhibited (p< or =0.01) PGE2 but marginally (p< or =0.05) NO in bovine chondrocytes. CONCLUSION: These experiments demonstrate differential action of CSAIDS and hydrocortisone on NO and PGE2 production in bovine chondrocytes and RAW 264.7 cells.

Animals↗
PubMed1999

An unexpected change in DXA calibration not detected by routine quality control checks.

Since its commercial introduction a decade ago, the technique of dual-energy X-ray absorptiometry (DXA) has been widely recognized as a useful and sensitive method of measuring changes in bone mineral density (BMD) at selected sites in the skeleton such as the spine and proximal femur. Because of their high precision and stable calibration, DXA scanners are frequently used in clinical trials to evaluate new treatments for osteoporosis. Quality assurance procedures based on regular scanning of phantoms are widely adopted in such trials, and continuity of the phantom BMD measurements is generally believed to ensure continuity in the in-vivo calibration. We report a change in calibration of a DXA scanner that occurred during a clinical trial where the calibration shift was different for the spine and femur sites and was not predicted or explained by the standard quality control procedures using phantoms. However, we show that provided patients enrolled in studies are thoroughly randomized and the statistical analysis is confined to the differences between the treated and control groups, then the effects of such calibration shifts on conclusions regarding the efficacy of treatment are considerably smaller than the random statistical errors.

Absorptiometry, Photon↗
PubMed1999

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

We report the activity of the new oxazolidinone antimicrobial agent linezolid 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 20 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci were inhibited by < or = 4 ug/ml of linezolid. All isolates of methicillin-resistant S. aureus were inhibited by < or = 8 ug/ml of linezolid. All isolates of penicillin-resistant S. pneumoniae were inhibited by < or = 2 ug/ml of linezolid. Linezolid inhibits strains of multidrug resistant Gram-positive cocci in vitro at concentrations < or = 8 ug/ml.

Acetamides↗
PubMed1999

Radiation dose to the patient and operator from a peripheral dual X-ray absorptiometry system.

Although peripheral dual X-ray absorptiometry (pDXA) scanners for measuring bone mineral density (BMD) in the forearm are known to produce an exceptionally low radiation dose to the patient, quantitative assessment of patient dose from pDXA procedures is important for reassuring patients about their safety. We have estimated the effective dose of radiation (ICRP-60) to the patient and also the scattered dose to the operator from a forearm BMD examination performed on a DTX-200 pDXA system (Osteometer Meditech, Hoersholm, Denmark). Measurements were performed using thermoluminescent dosimeters (TLD's) attached to the forearm phantom supplied by the manufacturer. The effective dose to a patient was estimated to be 0.1 microSv. At a distance of 1 m from the center of the forearm, the time-averaged scattered dose to the operator assuming scanning five patients per hour was measured to be <0.1 microSv/h. The dose rate over the outside surface of the DTX-200 in line with the primary X-ray beam was measured to be 1.4 microSv/h. These figures compare with a natural background radiation in the United Kingdom of 7 microSv/d. In conclusion the radiation doses from forearm pDXA to both patients and operator were found to be truly trivial.

Absorptiometry, Photon↗
PubMed1999

Large-scale synthesis of hematoregulatory nonapeptide SK&F 107647 by fragment coupling.

Linear and convergent routes for the large-scale preparation of the hematoregulatory nonapeptide (Glp-Glu-Asp)2-DAS-(Lys)2 (2, SK&F 107647) were investigated. A convergent approach ('3 + 2'-route employing Boc-and benzyl ester protecting groups) was selected for the preparation of multihundred-gram quantities of 2. Key steps were the preparation and the coupling of tripeptide hydrochloride (HCl.H)2-DAS-(Lys(Z)-OBn)2 (6, DAS-2,7-L,L-diaminosuberic acid) and tripeptide Glp-Glu(OBn)-Asp(OBn)-OH (26). Several coupling reagents were investigated in order to reduce the amount of epimerization of this fragment coupling. TDBTU [O-(3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-yl-1,1,3,3-tetrameth yluronium tetrafluoroborate] was identified as the condensation reagent of choice. Using this synthetic route > 97% pure final product in an overall yield of 35% calculated on di-Boc protected 2,7-L,L-diaminosuberic acid was prepared.

Indicators and Reagents↗
PubMed1999

A review of the management of 323 consecutive patients seen in a specific learning difficulties clinic.

Visual correlates of specific learning difficulties (SpLD) include: binocular instability, low amplitude of accommodation, and Meares-Irlen Syndrome. Meares-Irlen Syndrome describes asthenopia and perceptual distortions which are alleviated by using individually prescribed coloured filters. Data from 323 consecutive patients seen over a 15 month period in an optometric clinic specialising in SpLD are reviewed. Visual symptoms and headaches were common. 48% of patients were given a conventional optometric intervention (spectacles, orthoptic exercises) and 50% were issued with coloured filters, usually for a trial period. 40% of those who were given orthoptic exercises were later issued with coloured overlays. 32% of those who were issued with coloured overlays were ultimately prescribed Precision Tinted lenses. Approximately half the sample were telephoned more than a year after the last clinical appointment. More than 70% of those who were prescribed Precision Tints were still wearing them daily, and results for this intervention compared favourably with data for non-tinted spectacles. The data suggest that many people with SpLD need optometric care and that the optometrist needs to be skilled in orthoptic techniques and cognisant of recent research on coloured filters.

Accommodation, Ocular↗
PubMed1999

Cortical representation of swallowing in normal adults: functional implications.

OBJECTIVE: Dysphagia of neurogenic or postsurgical origin presents management and therapeutic challenges to the otolaryngologist. Improvements in management and therapeutic approaches may be facilitated by understanding how the central nervous system controls swallowing. The purpose of this investigation was to utilize functional magnetic resonance imaging to determine patterns of cortical activity during swallowing in normal, healthy adult subjects. STUDY DESIGN: Functional magnetic resonance imaging (fMRI) was performed on eight healthy adult subjects using conventional BOLD (blood oxygenation level dependent) techniques. METHODS: Subjects performed three different swallowing tasks including dry and bolus swallows, and performed a control finger movement task. Statistical maps of cortical activation were generated using a cross-correlation analysis. One-way and two-way ANOVA statistical analyses were performed to compare activated areas among the different tasks and to determine the effects of task sequence. RESULTS: Activation during the three swallowing tasks occurred in the primary motor cortex, primary somatosensory cortex, and other cortical and subcortical sites. Cortical representation of swallowing and finger movement followed somatotopic maps. Differential distribution of cortical activation was observed for the different swallowing tasks. CONCLUSIONS: Activation of the primary motor and somatosensory cortices, as well as other sensory-motor areas, occurs with swallowing in normal adults. Differential distribution of cortical activity with different swallowing tasks suggests differential functional organization for different swallowing tasks. Understanding these mechanisms may facilitate improved management and therapeutic intervention for neurogenic and postsurgical dysphagia.

Adult↗
PubMed1999

Adrenal dysfunction in hemodynamically unstable patients in the emergency department.

OBJECTIVE: Adrenal failure, a treatable condition, can have catastrophic consequences if unrecognized in critically ill ED patients. The authors' objective was to prospectively study adrenal function in a case series of hemodynamically unstable (high-risk) patients from a large, urban ED over a 12-month period. METHODS: In a prospective manner, critically ill adult patients presenting to the ED were enrolled when presenting with a mean arterial blood pressure < or =60 mm Hg requiring vasopressor therapy for more than one hour after receiving fluid resuscitation (central venous pressure of 12-15 mm Hg or a minimum of 40 mL/kg of crystalloid). Patients were excluded if presenting with hemorrhage, trauma, or AIDS, or if steroids were used within the previous six months. An adrenocorticotropic hormone (ACTH) stimulation test was performed and serum cortisol was measured. Treatment for adrenal insufficiency was not instituted. RESULTS: A total of 57 consecutive patients were studied. Of these, eight (14%) had baseline serum cortisol concentrations of <20 microg/dL (<552 nmol/L), which was considered adrenal insufficiency (AI). Three additional patients (5%) had subnormal 60-minute post-ACTH-stimulation cortisol responses (<30 microg/dL) and a delta cortisol < or =9 microg/dL, which is the difference between the baseline and 60-minute levels. This is functional hypoadrenalism (FH). There were no laboratory abnormalities that distinguished patients with AI or FH from those with preserved adrenal function (PAF). Rates of survival to discharge did not differ between the AI group (7 of 8) and PAF patients (21 of 46; p = 0.052). CONCLUSIONS: Adrenal dysfunction is common in high-risk ED patients. Overall, it has a frequency of 19% among a homogeneous population of hemodynamically unstable vasopressor-dependent patients. The effect of physiologic glucocorticoid replacement in this setting remains to be determined.

Adrenal Insufficiency↗
PubMed1999

Ketolide treatment of Haemophilus influenzae experimental pneumonia.

The MICs of HMR 3004 and HMR 3647 at which 90% of beta-lactamase-producing Haemophilus influenzae isolates were inhibited were 4 and 2 micrograms/ml, respectively. Both HMR 3004 and HMR 3647 were active against beta-lactamase-producing H. influenzae in a murine model of experimental pneumonia. As assessed by pulmonary clearance of H. influenzae, HMR 3004 was more effective (P < 0.05) than was azithromycin, ciprofloxacin, clarithromycin, erythromycin A, pristinamycin, or HMR 3647 in this model.

Animals↗
PubMed1999

Impact of suppressive antiviral therapy on the health related quality of life of patients with recurrent genital herpes infection.

OBJECTIVE: To investigate whether suppressive antiviral therapy improves health related quality of life in patients with recurrent genital herpes. METHODS: Health related quality of life was measured using the disease specific recurrent genital herpes quality of life questionnaire (RGHQoL) as part of a randomized, double blind, 52 week, placebo controlled, dose ranging study of once and twice daily valaciclovir or aciclovir for the suppression of recurrent genital herpes in patients with six or more recurrences per year. RESULTS: Of 1479 participants, 1349 patients completed the baseline questionnaire. There were no significant baseline differences in RGHQoL score between any of the treatment groups. After 3 months there were significantly greater improvements in mean RGHQoL scores for all active treatment groups compared with placebo (p < 0.05). Mean RGHQoL score improvements from baseline remained significantly higher in the active treatment groups than in the placebo group after 6 and 12 months, indicating that the improved health related quality of life in patients receiving suppressive antiviral therapy was sustained over a prolonged period of time. CONCLUSION: Suppressive antiviral therapy is an effective strategy for improving the quality of life of patients with recurrent genital herpes. These improvements in quality of life are sustained over time, thus enhancing the clinical benefit in the long term management of this condition.

Acyclovir↗