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M Patel

Publications and source records attributed to M Patel.

At least 289 records · Page 16Linked to original sources
PubMed1995

Comparison of effects of platelet-derived growth factor isoforms on signaling and DNA synthesis of human cultured saphenous vein cells.

We examined the effect of platelet-derived growth factor (PDGF)-AA, PDGF-AB, and PDGF-BB isoforms on DNA synthesis, Ca2+ mobilization, and tyrosine phosphorylation in cultured human saphenous vein cells cultured by an explant technique; confluent cells derived from passage 3 were used for all studies. DNA synthesis was measured by [methyl3H]thymidine uptake, intracellular [Ca2+] ([Ca2+]i) was measured with the Ca(2+)-sensitive indicator fura-2, and tyrosine phosphorylation was measured by Western blotting techniques. All three isoforms of PDGF stimulated [methyl3H]thymidine uptake concentration dependently, with similar potency. PDGF-AB induced significantly greater [methyl3H]-thymidine uptake than PDGF-BB, and PDGF-AA was much less effective than either PDGF-AB or PDGF-BB. The effects of all three isoforms were inhibited by tyrphostin-23, a selective inhibitor of tyrosine kinases PDGF-AB and PDGF-BB increased [Ca2+]i, although the maximum response to PDGF-AB was significantly less than that to PDGF-BB. Both isoforms increased [Ca2+]i by stimulating influx and intracellular release of Ca2+. PDGF-AA had no measurable effect on [Ca2+]i. All three isoforms increased tyrosine phosphorylation of a 170-kDa protein detected by Western blotting. Quantitative densitometry indicated that PDGF-BB induced greater tyrosine phosphorylation than PDGF-AB and both PDGF-BB and PDGF-AB induced markedly more tyrosine phosphorylation than PDGF-AA. PDGF isoforms have differing efficacies in terms of DNA synthesis, Ca2+ mobilization, and tyrosine phosphorylation by human saphenous vein cells.

Blotting, Western↗
PubMed1995

(S)oxazepam glucuronidation is inhibited by ketoprofen and other substrates of UGT2B7.

1,4-Benzodiazepine anxiolytics such as diazepam and halazepam are converted in vivo to oxazepam, an active metabolite with a hydroxyl group at the asymmetric C3 position. D-glucuronic acid couples with the C3 hydroxyl group of oxazepam to form pharmacologically inactive diastereomeric glucuronide conjugates. Conjugation with glucuronic acid is catalysed by the microsomal UDP-glucuronosyltransferase (UGT) enzyme system, which includes an undetermined number of isozymes. Although 1,4-benzodiazepines are ultimately cleared as oxazepam glucuronide, little is known about the particular UGT isozyme(s) responsible for the conjugation at the C3 position of these molecules. Microsomal preparations from three human livers were used to study the glucuronidation of (R,S)oxazepam in vitro. The predominant formation of the S- over the R-glucuronide was reflected by the kinetic parameters: For (S)oxazepam glucuronide, the constants were Km = 0.18 +/- 0.02 mM and Vmax = 202.6 +/- 25.0 nmol min-1 per mg protein; for (R)oxazepam glucuronide, they were Km = 0.22 +/- 0.02 mM, Vmax = 55.4 +/- 9.5 nmol min-1 per mg protein. Inhibition studies suggest that the two diastereomeric glucuronidations are catalysed by different UGT isozymes. That is, there was competitive inhibition of (S)oxazepam glucuronidation by non-steroidal anti-inflammatory drugs (NSAIDs), including ketoprofen while (R)oxazepam glucuronidation was not equally inhibited by these compounds. The order of potency of inhibitors of (S)oxazepam glucuronidation in this study was the same as the rank order of substrates conjugated by UGT2B7; hyodeoxycholic acid, estriol, (S)naproxen, ketoprofen, ibuprofen, fenoprofen, clofibric acid, and morphine (in descending order). The inhibition profile of (S)oxazepam glucuronidation suggests that UGT2B7 is the catalysing enzyme.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Interindividual variability in the glucuronidation of (S) oxazepam contrasted with that of (R) oxazepam.

Although conjugation with glucuronic acid is a major process for converting many xenobiotics into hydrophilic, excretable metabolites, relatively little has been reported concerning interindividual variability of glucuronidation in human populations. Oxazepam, a therapeutically active metabolite of diazepam, is one of a number of C3-hydroxylated benzodiazepines for which glucuronide conjugation is the predominant pathway of biotransformation. The drug is normally formulated as a racemic mixture of inactive (R) and active (S) enantiomers. In the present study we have investigated the use of oxazepam as a potential probe drug for studying the variability of glucuronide conjugation, and for demonstrating the extent to which genetic factors may be responsible. In preliminary studies we determined oxazepam pharmacokinetics metabolite profiles after administration of racemic (R,S) oxazepam to eleven human volunteers. The (S) glucuronide was preferentially formed and excreted in nine of the eleven subjects. The ratios of (S) to (R) glucuronide metabolites (S/R ratios) were 3.87 +/- 0.79 (mean +/- SD) and 3.52 +/- 0.60 in urine and plasma, respectively. However, both ratios were significantly lower in two subjects (p < 0.01). In these two atypical subjects, the half-life of (R,S) oxazepam was also markedly longer (14.7 and 15.9 h) than in the other subjects (8.1 +/- 3.2 h). A good correlation (rs = 0.90) between the S/R-glucuronide ratio in urine and the plasma clearance of (R,S) oxazepam suggested that a low S/R ratio may be a marker of poor elimination of oxazepam. In further investigations, the drug was administered to 66 additional subjects. The S/R-glucuronide ratio in 8 h pooled urine was bimodally distributed, with 10% of all subjects possessing ratios below an apparent antimode of 1.9. A survey of the in vitro formation of oxazepam glucuronides by microsomes from 37 human livers also showed that 10% of the livers displayed an abnormally high apparent Michaelis constant (Km) for the formation of the (S) glucuronide, but not of the (R) glucuronide. These results suggest that the glucuronidation of the pharmacologically active (S) enantiomer of oxazepam is decreased in a significant percentage (10%) of Caucasian individuals. The observed in vitro differences in apparent kinetics of the S-glucuronidation reaction may reflect defects at the genetic level, leading to structural changes in the isozyme(s) of UDP-glucuronyltransferase that catalyse this reaction.

Adult↗
PubMed1995

Stroke in young black patients. Risk factors, subtypes, and prognosis.

BACKGROUND AND PURPOSE: Stroke subtypes and prognosis differ among older black patients compared with whites; however, few data are available regarding stroke among young black patients. METHODS: To determine the risk factors for stroke, stroke subtype, and prognosis among young black patients, we retrospectively reviewed the medical records of all 15- to 44-year-old patients admitted with stroke to a university-affiliated public hospital from January 1990 through June 1994. RESULTS: Of the 248 eligible patients admitted with stroke, 219 were blacks. Hypertension was more frequently associated with stroke in young black than in non-black patients (55% versus 24%, P = .003). Cocaine abuse was frequent among both black and non-black patients (27% versus 38%, P = NS). Hypertensive intracerebral hemorrhage (64%) was the most common subtype of intracerebral hemorrhage (n = 67), and lacunar infarction (21%) was the most common subtype of cerebral infarction (n = 112) in young black patients. Outcome in black patients with stroke at discharge was 69% independent, 8% dependent, and 23% dead. CONCLUSIONS: The high frequency of hypertension, hypertensive intracerebral hemorrhage, and lacunar infarction among young black patients with stroke suggests accelerated hypertensive arteriolar damage, possibly due to poor control of hypertension.

Adolescent↗
PubMed1995

The effect of aspirin desensitization on urinary leukotriene E4 concentrations in aspirin-sensitive asthma.

Patients with aspirin sensitive asthma (ASA) can be desensitized to aspirin but the mechanisms by which this happens are unknown. To test the hypothesis that there may be a reduction in aspirin-induced leukotriene release following aspirin desensitization, we studied nine patients with ASA, 37 +/- 2.3 yr of age (mean +/- SEM) with a baseline FEV1 of 94 +/- 3.5%. Urinary leukotriene E4 (LTE4) and FEV1 were measured before and after ingestion of a threshold dose of aspirin leading to a 15% decrease in FEV1, and then at intervals following desensitization, when a maintenance dose of 600 mg aspirin was ingested. Prior to desensitization, the maximum decrease in FEV1 following ingestion of a threshold dose of aspirin was 15.3 +/- 3.9%, and urinary LTE4 rose from a baseline value of 235 +/- 79.4 pg/mg creatinine to 1,714 +/- 783 pg/mg creatinine at 3 h. Immediately after acute desensitization, which was performed over several days, 600 mg aspirin provoked a maximum decrease in FEV1 of only 3.3 +/- 2.4%, and urinary LTE4 increased from a baseline of 645 +/- 223 pg/mg creatinine to 1,256 +/- 456 pg/mg creatinine. Following ingestion of 600 mg aspirin for 9 +/- 3.2 mo (n = 5; chronic desensitization), urinary LTE4 rose from a basal level of 432 +/- 127 pg/mg creatinine to 749 +/- 257 pg/mg creatinine at 3 h after 600 mg aspirin, and this was accompanied by a maximum decrease in FEV1 of 7.4 +/- 4.5%. Although there was significantly less aspirin-induced LTE4 excretion after acute desensitization, substantial amounts of LTE4 were still produced without any significant change in lung function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Breast irradiation postlumpectomy: development and evaluation of a decision instrument.

PURPOSE: To develop an instrument to help clinicians inform patients about the benefits and risks of breast irradiation following lumpectomy and to help an informed patient decide whether she prefers this treatment. METHODS: A Decision Board consisting of written material and visual aids was developed. It provides the patient with detailed information about her choices (breast irradiation or not), outcomes (breast recurrence and survival), probability of those outcomes, and quality of life associated with treatment and outcome. We studied the decision-making process in 82 consecutive node-negative lumpectomy patients who were seen in consultation by a radiation oncologist and oncology nurse. The Decision Board was used in the last 30 patients in the cohort. RESULTS: Patient comprehension following the consultation without the Decision Board was greater than 65% for all questions addressed, except for poor understanding of the lack of survival benefit associated with breast irradiation (12% of patients answered correctly) and that it could not be repeated (15% of patients answered correctly). Comprehension following the consultation with the Decision Board was similar, but understanding regarding the repetition of radiation (83%) was improved. Only 70% of patients in the no-Decision Board group felt they were offered a choice. This was increased to 97% in the Decision-Board group. Overall, 95% of patients chose breast irradiation, and this did not differ between groups. Patients reported several reasons for choosing breast irradiation, all of equal importance. CONCLUSION: The Decision Board facilitated shared decision making in node-negative lumpectomy patients who chose breast irradiation, but it did not affect a patient's choice to select breast irradiation.

Analysis of Variance↗
PubMed1995

Evidence for the hormonal function of a CRF-related diuretic peptide (Locusta-DP) in Locusta migratoria

Locusta-DP is a corticotropin-releasing factor (CRF)-related diuretic peptide isolated from the migratory locust Locusta migratoria. At nanomolar concentrations, synthetic Locusta-DP stimulated fluid secretion and cyclic AMP production by Malpighian tubules isolated in vitro and increased the rate of amaranth clearance in starved locusts to levels comparable with those observed during post-feeding diuresis. The peptide also caused a marked (approximately 10 %), but short-lived, reduction in the haemolymph volume of starved locusts. A polyclonal antiserum raised against Locusta-DP(29-46) was shown to block peptidergic signal transfer in vitro and in vivo. Pre-treatment of Locusta-DP (5 nmol l-1) with antiserum diluted 1:100 resulted in a rapid reduction in the free peptide concentration to less than 1 nmol l-1, the threshold for a measurable effect on cyclic AMP production by isolated tubules. In intact insects, passive immunization with Locusta-DP antiserum blocked increases in the rate of amaranth clearance in response to exogenous diuretic peptide or in response to feeding. The latter was due specifically to the binding of Locusta-DP, because when the relevant antibodies were preadsorbed with Locusta-DP(29-46), the antiserum had no effect on amaranth clearance by recently fed insects. This provides unequivocal evidence of a hormonal function for Locusta-DP in the control of primary urine production.

Journal Article↗
PubMed1995

Evaluation of the circle of Willis with three-dimensional CT angiography in patients with suspected intracranial aneurysms.

PURPOSE: To determine the usefulness of CT angiography in the setting of suspected acute subarachnoid hemorrhage or intracranial aneurysm. METHODS: We prospectively studied 68 patients suspected of having subarachnoid hemorrhage or an intracranial aneurysm with noncontrast CT of the head followed immediately by contrast-enhanced helical CT of the circle of Willis with three-dimensional reconstruction. Twenty-seven patients with CT findings positive for subarachnoid hemorrhage or intracranial aneurysm were evaluated with digital subtraction angiography or MR angiography within 12 hours of CT angiography. Patients with negative CT/CT angiography findings were followed up with lumbar puncture. RESULTS: CT angiography showed 23 of 24 aneurysms and 2 of 2 arteriovenous malformations (sensitivity, 96%; specificity, 100%). Aneurysm size ranged from 2 to 40 mm (mean, 7.9 mm). Interobserver variability was 10%. In the 23 cases of subarachnoid hemorrhage, cisternal blood did not limit the three-dimensional reconstruction. Two patients with aneurysms on CT angiography had normal noncontrast scans. CONCLUSIONS: CT angiography of the circle of Willis is a useful technique for evaluation of suspected acute subarachnoid hemorrhage and intracranial aneurysm. It provides anatomic display of intracranial aneurysms, allowing for planning of conventional angiography and surgical approach. In selected cases, CT angiography may eliminate the need for preoperative conventional angiography.

Adolescent↗
PubMed1995

Antitumor effect of keto-diepoxides isolated from the fungus Nattrassia mangiferae.

A novel keto-diepoxide Sch 49209 and its derivative Sch 50672, produced by the fungus Nattrassia mangiferae, inhibited tumor cell invasion through an artificial basement membrane. These compounds, at nontoxic concentrations, inhibited invasion of HT-1080 cells in a dose-dependent manner. The IC50 values for Sch 49209 and Sch 50672 were 0.75 and 8 microM, respectively, when cells were incubated with drugs for 5 h. Sch 49209 inhibited both tumor cell invasion and cell motility to the same extent under conditions that did not cause any apparent cytotoxicity. Sch 4209 and Sch 50672, however, inhibited the growth of ras-transformed cells in a semisolid medium in a 5-day culture with IC50 values of 0.6 and 2.4 microM, respectively. They also inhibited the anchorage-dependent growth of pT24 cells in vitro with IC50 values of 0.5 and 0.9 microM for Sch 40209 and Sch 50672, respectively. Using the murine lung epidermoid carcinoma M27 cells implanted SC in mice as a model, we found both Sch 49209 and Sch 50672 inhibited the growth of this tumor at doses ranging from 2 to 10 mg/kg. These compounds also decreased the formation of spontaneous lung metastasis in this model. Sch 50672 inhibited the growth of human tumor xenografts, SW620 and A431, in athymic mode mice. Our data suggest that keto-diepoxides inhibit tumor growth and metastasis and that this activity may be due, in part, to anti-invasive activity.

Animals↗
PubMed1995

Fenestration of the internal carotid artery: a rare mass of the hypotympanum associated with persistence of the stapedial artery.

A 61-year-old woman was examined because of unilateral nonpulsatile tinnitus involving the right ear. CT scanning showed a soft-tissue mass in the hypotypanum. Angiographically, the mass was identified as a fenestrated or duplicated internal carotid artery associated with persistence of the stapedial artery. Embryologic considerations are discussed.

Arteries↗
PubMed1995

The value of brain imaging in children with headaches.

OBJECTIVE: To determine the value of performing computed tomography (CT) on magnetic resonance imaging (MRI) studies in children with chronic headaches. BACKGROUND: Headache is a common complaint in children. With the proliferation of brain imaging centers and the increasing patient demand for CT or MRI studies, brain imaging has become widely used to evaluate headaches. METHODS: A retrospective chart review was conducted of all children referred to the pediatric neurology clinic for evaluation of headaches over a 2-year period. Charts were reviewed for headache characteristics, clinical indications for performing CT and MRI studies, and imaging results. Particular attention was paid to evidence of brain tumors, vascular anomalies, or hydrocephalus. RESULTS: A total of 133 records were studied. Subjects ranged in age from 3 to 18 years. Most patients were diagnosed as having either vascular migrainous headaches (52%) or chronic tension headaches (21%). Other headache diagnoses were mixed tension-migraine, psychogenic, and post-traumatic. Headaches were unclassified in 25 patients (19%). Seventy-eight patients (59%) had brain imaging: 45 had MRI, 27 had CT, and 6 patients had both. In most cases, brain imaging studies were performed in patients with atypical headache pattern, presence of neurologic abnormalities during the headache, general symptoms (ie, weight loss or fatigue), or because of parents' or doctors' concerns about brain tumors. Cerebral abnormalities were found on brain imaging in four patients, but none indicated the presence of a treatable disease and all were deemed unrelated to the presenting complaint. Our findings of no relevant abnormalities in a series of 78 brain imaging studies indicate that the maximal rate at which such abnormalities might appear in this population is 3.8%. CONCLUSIONS: These results indicate that brain imaging studies have very limited value in evaluating headaches in pediatric patients without clinical evidence of an underlying structural lesion.

Adolescent↗
PubMed1994

The Nd:YAG laser in caries removal.

This paper shows how a laser can be used in the various stages of caries removal prior to the placement of a glass-ionomer restoration. In the future the laser may prove to be a valuable tool in enabling the dentist to perform surgical procedures with maximum comfort to the patient.

Anesthesia, Dental↗
PubMed1994

Accidental displacement of impacted maxillary third molars.

Displacement of an impacted maxillary third molar into the infratemporal fossa is frequently mentioned but rarely reported. Imaging and retrieval of such a displaced tooth is difficult and requires urgent referral and hospitalisation for removal under general anaesthetic. The use of image intensification equipment in theatre allows removal of such a displaced tooth with minimal morbidity and is recommended. Prevention of displacement with the use of a distal retractor is strongly recommended when surgically removing impacted maxillary third molars.

Adult↗
PubMed1994

Osmotic regulation of taurine transport via system beta and novel processes in mouse preimplantation conceptuses.

Taurine was shown recently to increase the frequency at which 2-cell mouse conceptuses develop into blastocysts in vitro. For this reason and because taurine helps cells adapt to external stresses, we studied transport of this and related amino acids by preimplantation mouse conceptuses. The most conspicuous component of taurine transport in conceptuses at the 1-cell through blastocyst stages of development was both Na(+)- and Cl(-)-dependent. This Na(+)- and Cl(-)-dependent transport system interacted relatively strongly with beta- but not alpha-amino acids. By these criteria, transport system beta is responsible for Na(+)-dependent taurine transport in preimplantation mouse conceptuses. Moreover, detection of mRNA encoding the taurine transport protein (TAUT) in early conceptuses supports the theory that TAUT is a major component of system beta. Transport of taurine by system beta in 1-cell conceptuses was slower in hypotonic than in hypertonic media, whereas the reverse was true for system beta in blastocysts. In contrast, hypotonically stimulated Na(+)-independent taurine transport was, of course, more rapid in hypotonic than in hypertonic media in both 1-cell conceptuses and blastocysts. Transport via this hypotonically stimulated process also showed no sign of saturation by up to 10 mM taurine. Hypotonically stimulated taurine transport appeared transiently in 1-cell conceptuses under hypotonic conditions until they had recovered their initial volumes. Hence, we suggest that a decrease in taurine uptake via system beta and an increase in taurine exodus via the Na(+)-independent, nonsaturable transport process could contribute to the regulatory volume decrease in 1-cell conceptuses in hypotonic medium. Since taurine uptake by system beta in blastocysts is, however, higher in hypotonic than in hypertonic media, taurine uptake by system beta in blastocysts might intensify a tendency to increase cell volume in hypotonic medium. Such an increase in taurine uptake could further favor anabolic changes associated with cell swelling. In addition to contributing to regulation of cellular volume and perhaps metabolism, the hypotonically stimulated Na(+)-independent transport processes in early embryos have novel characteristics. Hypotonically stimulated Na(+)-independent taurine transport was inhibited by niflumate, N-ethylmaleimide and NaN3 but not by furosemide, iodoacetate, KCN, ouabain or alpha- or beta-amino acids. Furthermore, 4,4'-diisothiocyanostilbene-2,2'-disulfonate inhibited this transport in 1-cell conceptuses but not in blastocysts. Hence, different hypotonically stimulated Na(+)-independent taurine transport processes appear to be present in 1-cell conceptuses vs. blastocysts. The functions of these and other instances of developmental regulation of expression of transport processes in preimplantation conceptuses remain largely to be elucidated.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1994

A new strategy for spectroscopic imaging.

This paper describes a new approach for reducing ringing artifacts in spectroscopic imaging (or chemical-shift imaging). The new method is aimed at reducing the signal contamination in areas of interest, due to ringing, that often arises from adjacent areas with high intensity, such as subcutaneous fat in the case of 1H spectroscopy and skeletal muscle in case of the 31P spectroscopy. The method is based on the fact that the high-intensity signals which are the major source of contamination can be captured with one or few acquisitions and the metabolite resonances in areas of interest require considerably more averaging in the data acquisition due to low signal-to-noise ratio. In order to reduce ringing and maintain adequate SNR for the metabolites, the data points in high k space are measured with one or few excitations while those in the low k space are sampled with many excitations. By virtue of this sampling scheme, the data contain more noise in the high-spatial-frequency region and direct Fourier transformation reconstruction generates a very noisy image. Therefore, a new reconstruction technique is developed for the reconstruction. This approach has been studied by simulations and its practical utility is demonstrated by an in vivo proton CSI experiment. Technical details and simulation and experimental results are presented. From these results, it is concluded that the technique is robust and can be used for in vivo applications.

Artifacts↗