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Biomedical subjects

M Patel

Publications and source records attributed to M Patel.

At least 361 records · Page 20Linked to original sources

Inhibitory action of orotate, 2-thioorotate and isoorotate on nucleotide metabolism and nucleic acid synthesis in hepatoma cells.

1. The specificity of the action of orotate on hepatoma cells was investigated. 2. Orotic acid and its methyl ester had similar inhibitory effects on the incorporation of [3H]thymidine into DNA of hepatoma cells. 3. In contrast to previous studies in vivo, incubation of rat kidney cells with orotate caused an increase in the ratio of UTP/ATP concentrations that was similar to effects on hepatic cells. 4. Inhibitory effects of 2-thioorotate and isoorotate on metabolism were found to be less selective and required higher concentrations than with orotate.

Animals↗

The impact of automated blood pressure devices on the efficiency of clinical trials.

By reducing measurement error, automated blood pressure (BP) devices should enhance the precision of BP estimation and thereby decrease sample size requirements in clinical trials of BP-lowering therapy. Enhanced precision would be particularly relevant to clinical trials assessing the efficacy of nonpharmacological therapies. In the present investigation, resting (clinic) BPs by the Dinamap 8100 (a stationary device) and the Accutracker II (an ambulatory device) were as precise as manual BPs given an equal number of observations by each method. However, both the Dinamap and Accutracker devices underestimated resting diastolic BP in comparison to the manual observers. Estimates of average daytime and 24-hour ambulatory BP, based on large numbers of observations over an extended period of time, were extremely precise. These findings suggest that the use of automated devices to measure resting BP may not reduce samples sizes, whereas use of ambulatory BP devices should reduce samples sizes considerably.

Bias↗

A simplified technique to resect abnormal bony radiolocalizations using a gamma counter.

A simplified technique for localizing and verifying the correct biopsy site of lesions identified on a bone scan has been utilized. A hand-held gamma counter was used for localization of incision placement, determination of extent of bone to be resected, and verification that appropriate tissue was resected. This technique was used to guide biopsy of bony lesions in five patients and to guide resection of a pubic ramus chondrosarcoma. We conclude that intraoperative use of a gamma counter to guide biopsy of bony lesions minimizes surgery time, increases the confidence of obtaining correct tissue, and makes a frequently frustrating procedure very simple. In addition, the probe may assist with determining adequate margins at definitive resection of tumours which accumulate technetium-99m MDP.

Adult↗

Variability of acetaminophen metabolism in Caucasians and Orientals.

Acetaminophen (paracetamol) is extensively conjugated with glucuronic acid and sulfate prior to renal excretion. A minor metabolic route involves microsomal oxidation of acetaminophen to a hepatotoxic reactive intermediate, which subsequently undergoes glutathione (GSH) conjugation, yielding cysteine and mercapturate conjugates, both of which are excreted in the urine (Slattery et al., 1987). Data collected by de Morais et al. (1989) indicated that in comparison with normal subjects, glucuronidation of acetaminophen was impaired in subjects with Gilbert's syndrome, a genetically-based impairment of bilirubin glucuronidation. Thus, inter-subject and ethnic differences in acetaminophen disposition have pharmacogenetic and toxicological implications. This study was conceived to explore these differences. Urinary excretion of acetaminophen and its metabolites was observed in 125 Caucasian and 33 Oriental subjects. No appreciable difference was noted in the mean fraction of drug excreted as glucuronide between the two groups (51.5% in Caucasians vs 51.8% in Orientals). However, the data strongly indicated that the excretion of acetaminophen glucuronide was not normally distributed. Bimodality was apparent in both groups, with 20% of Caucasian and 33% of Oriental subjects displaying relatively extensive glucuronidation. In addition, glucuronidation displayed a strong negative correlation with sulfation (r = -0.97), suggesting the existence of a compensatory mechanism between the two metabolic pathways. The mean fractional excretions of cysteine and mercapturate conjugates did show significant differences between Caucasians and Orientals (p < 0.005). In addition, the ratio of mercapturate to total GSH-derived conjugates recovered appeared to be bimodal, indicating possible heterogeneity in the conversion of the cysteine conjugate to mercapturate via N-acetylation.

Acetaminophen↗

Functional comparisons of gastrin/cholecystokinin receptors in isolated preparations of gastric mucosa and ileum.

1. The gastrin cholecystokinin (CCK) receptors mediating stimulation of acid secretion in rat isolated gastric mucosa (RGM) and contraction in guinea-pig isolated ileum longitudinal muscle-myenteric plexus (GPI) have been characterized by use of peptide agonists and the non-peptide antagonists, lorglumide, devazepide and L-365,260. 2. In RGM, gastrin peptides (sulphated gastrin heptadecapeptide (G-17), non-sulphated (ns) G-17 and pentagastrin) were potent agonists of acid secretion (EC50 values of 4.3, 16 and 27 nM respectively). Sulphated CCK octapeptide (CCK-8) was also a potent agonist, (EC50 = 0.9 nM), but was less efficacious, producing a lower maximal response. In contrast, in GPI, CCK-8 was a potent full agonist (EC50 = 1.4 nM) and was more than 1000 times more potent than the gastrin peptides in producing a sustained contractile response. 3. In GPI, CCK-8 (0.1 to 100 nM) produced sustained contractile responses, whilst CCK-4 (3 to 1000 nM) produced transient responses. These responses had different sensitivities to atropine (1 microM), suggesting that more than one receptor may mediate contraction in this tissue. 4. In RGM, L-365,260 was the most potent antagonist of pentagastrin-stimulated acid secretion (pA2 = 7.6). This functional affinity estimate was similar to that for L-365,260 as an antagonist of excitatory responses in rat ventromedial hypothalamic slices (Kemp et al., 1989) but differed from binding affinity estimates in guinea-pig cortex and gastric glands (Freidinger, 1989). 5. In GPI, devazepide, L-365,260 and lorglumide yielded different affinity estimates when compared against CCK-8 and CCK-4 or pentagastrin respectively.These studies were consistent with the view that the sustained response produced by CCK-8 was mediated by CCKA receptors and the transient response produced by CCK-4 and pentagastrin was mediated by CCKB receptors.6. Affinity estimates for L-365,260 and lorglumide against CCK-4 or pentagastrin in GPI were significantly different from corresponding estimates against pentagastrin in RGM. These studies are consistent with the view that gastrin/CCKB receptors in GPI may differ from those in RGM.

Animals↗

Clinical-radiographic correlations within the first five hours of cerebral infarction.

Fifty patients, ages 54-79, with ischemic hemispheric strokes productive of hemiparesis, at a minimum, underwent standardized neurological evaluations, computed tomographic scanning and cerebral angiography (N = 38) or carotid ultrasound (N = 12) within 5 h of onset. A second scan was performed at 5-7 days. Clinical scores were not associated with a history of, or the presence of: hypertension, smoking or cardiac disease, including atrial fibrillation, nor with severe internal carotid artery stenosis or occlusion. Clinical scores were adversely affected by early scan abnormalities (especially mass effect), lesion size, intracranial arterial occlusions, elevated serum glucose levels and the subsequent development of hemorrhagic infarction. Glucose levels correlated with infarct size and the development of hemorrhagic infarction. Delayed intracranial arterial filling and collateral flow were associated with reduced infarct size but did not confer clinical protection. We believe that combining the initial glucose level and scan results has prognostic significance, and early angiography is valuable in characterizing infarct etiology and assessing clinical severity.

Aged↗

Outbreak of ceftazidime resistance due to a novel extended-spectrum beta-lactamase in isolates from cancer patients.

Ceftazidime is widely used in the therapy of infectious complications in neutropenic patients. We studied an outbreak of ceftazidime-resistant gram-negative bacillary infections in pediatric cancer patients receiving empirical ceftazidime therapy for neutropenic fever. Fourteen isolates (12 Klebsiella pneumoniae and 2 Escherichia coli) from 13 patients were studied. Specimens were obtained from multiple clinical sites including blood, urine, throat, and lung. The organisms were resistant to ceftazidime, aztreonam, and penicillins but remained susceptible to cephamycins and imipenem. All resistant isolates produced a novel beta-lactamase (TEM-26) with a pI of approximately 5.58, which was transferred by transformation to E. coli on a 7.9-kb nonconjugative plasmid which cotransferred resistance to trimethoprim-sulfamethoxazole. This enzyme readily hydrolyzed ceftazidime, aztreonam, and penicillins in a spectrophotometric assay. DNA sequencing data suggest that TEM-26 is derived from TEM-1.

Bacteria↗

Susceptibility testing of clinical isolates of Enterococcus faecium and Enterococcus faecalis.

We collected 103 clinical Enterococcus faecium isolates from across Canada, performed standard broth microdilution susceptibility testing, and compared these results with results from the MicroScan Pos MIC Type 6 panel (Baxter Health Care Corp., West Sacramento, Calif.) and the AMS-Vitek Gram-Positive Susceptibility card (Vitek Inc., St. Louis, Mo.). High-level aminoglycoside resistance to gentamicin and streptomycin was detected by a single-concentration agar method with 1,000 micrograms of each aminoglycoside per ml. In addition, we tested the effect of the lower calcium content in broth media as recommended in National Committee for Clinical Laboratory Standards (NCCLS) guideline M7-A2 on the activity of the highly calcium-dependent agent daptomycin. Of the 103 E. faecium isolates, there were 4 and 30 isolates with high-level gentamicin resistance (HLGR) and high-level streptomycin resistance (HLSR), respectively. An additional 39 (37 with HLGR and 36 with HLSR) E. faecium isolates were tested by both the MicroScan and the AMS-Vitek systems. The AMS-Vitek card demonstrated sensitivities of 95 and 82% for detecting HLGR strains and HLSR strains, respectively. The MicroScan panel demonstrated improved sensitivities for detecting HLGR (42 to 97%) and HLSR (64 to 84%) when readings were performed manually instead of being generated automatically. Ampicillin resistance (MIC, greater than or equal to 16 micrograms/ml) was detected in 23 of the 103 E. faecium isolates. Only 14 and 20 of these were detected by the MicroScan panels and AMS-Vitek cards, respectively. beta-Lactamase activity was not detected in any isolates. The lower calcium content in broth media recommended by NCCLS guideline M7-A2 markedly reduced the in vitro activity of daptomycin against Enterococcus spp.

Calcium↗

Evaluation of commercial and standard methodology for determination of oxacillin susceptibility in Staphylococcus aureus.

Agar dilution with and without 4% NaCl, broth microdilution with 2% NaCl, the dried MicroScan Rapid Positive MIC 1 panel (Baxter Health Care Corp., West Sacramento, Calif.), the Vitek GPS-SA card (Vitek Systems, Hazelwood, Mo.), and the oxacillin agar screen plate were compared with a DNA probe encoding the mec gene for their abilities to detect oxacillin resistance in 506 clinical isolates of Staphylococcus aureus. The results of testing for the mec gene showed that there were 254 oxacillin-resistant and 252 oxacillin-susceptible isolates of S. aureus. There were 14.2% very major errors with Vitek (a resistant isolate was interpreted as susceptible) and 6.7% very major errors with MicroScan. Fewer major errors were seen: 0.8% with MicroScan (a susceptible isolate was interpreted as resistant) and 0.4% with Vitek. No very major errors but 2.4% major errors occurred by agar dilution with 4% NaCl supplementation, whereas there were 0.8% very major and 0.4% major errors without 4% NaCl supplementation. By broth microdilution there were 2.0% very major and 0.8% major errors. The results of the oxacillin agar screen plate method were 100% concordant with those of the mec gene probe method.

DNA Probes↗

Sch 42137, a novel antifungal antibiotic from an Actinoplanes sp. Fermentation, isolation, structure and biological properties.

A novel polycyclic xanthone, Sch 42137, related to the albofungin family of compounds was isolated from culture broth. Its structure was determined by detailed spectroscopic studies and comparison of circular dichroic studies to related compounds albofungin and simaomicin. Sch 42137 exhibited MIC values less than 0.125 micrograms/ml against yeasts and dermatophytes. Details are presented herein.

Actinomyces↗

Macrolactams: a novel class of antifungal antibiotics produced by Actinomadura spp. SCC 1776 and SCC 1777.

Three novel antifungal antibiotics, Sch 38518, Sch 39185 and Sch 38516 were isolated from the fermentation broths of two actinomycetes identified by chemical, morphological and physiological analysis as a new species of Actinomadura. The compounds were isolated from broth by solvent extraction and purified by silica gel chromatography. Physico-chemical properties, mass spectral analysis, IR and UV suggested the compounds were similar. Sch 38518 and Sch 39185 have a molecular formula of C25H48N2O5. 1H NMR, 13C NMR and hydrolysis indicated the aglycones were identical, however the compounds differed in containing isomeric sugar moieties. Sch 38518 contains mycosamine while Sch 39185 contains 3,6-dideoxy-3-amino-L-talopyranose. Sch 38516 has a molecular formula of C24H46N2O5 and is a lower homolog of Sch 39185. The three compounds, Sch 38518 (1), Sch 39185 (2), and Sch 38516 (3) exhibit similar activity against Candida spp. with geometric mean MICs of 1.81, 2.00 and 0.91 micrograms/ml, respectively.

Actinomycetales↗

Macrolactams: two novel homologous series of compounds produced by Actinomadura sp. SCC 1778.

Eight antifungal compounds were identified from the fermentation of Actinomadura sp. SCC 1778. This culture produces four homologous compounds (C22H42N2O5 approximately C25H48N2O5) containing the sugar, mycosamine, and four homologous compounds (C22H42N2O5 approximately C25H48N2O5) containing the sugar, 3,6-dideoxy-3-amino-L-talopyranose. Five of the compounds identified were novel macrolactams. All these compounds exhibit antifungal activity against Candida spp. with geometric mean MICs ranging from approximately 1.0 micrograms/ml for the higher homologs to 30 micrograms/ml for the lower homologs.

Actinomycetales↗

Scaphoid enchondroma.

Enchondromas are rarely found in carpal bones. This paper reports a case with scaphoid enchondroma and reviews three cases from previous literature. Three of the patients with scaphoid enchondromas presented with pathologic fractures after traumatic events. Each enchondroma had characteristic histopathologic findings. It is important to realize that although enchondroma is usually a painless lesion, it weakens the cortex of the involved bone, facilitating fracture. Thus, when cystic scaphoid fractures are encountered, enchondroma must be part of the differential diagnosis.

Adult↗