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Biomedical subjects

A Patel

Publications and source records attributed to A Patel.

At least 397 records · Page 22Linked to original sources

Expression of a single dopamine transporter cDNA can confer two cocaine binding sites.

Radiolabeled cocaine analogs can bind to low and high affinity sites on striatal dopamine transporters (DAT). Recently, a cDNA encoding a rat brain dopamine transporter pDAT1 has been cloned. COS cells transfected with the pDAT1 in a eukaryotic expression vector express both a high (KD = 3.4 nM) and low affinity (KD = 163.6 nM) cocaine binding sites, suggesting that both sites are provided by a single gene product.

Animals↗

Endometriosis of the ureter.

Five patients with ureteric endometriosis are described. Extensive pre-operative investigation failed to reveal the aetiology of the unilateral upper urinary tract obstruction seen in all of these patients. Due to the dense fibrosis that invariably accompanies ureteric endometriosis, early surgical excision of the ureteric stricture permits effective resolution of upper tract dilatation and improved renal salvage.

Adult↗

Insulin resistance, secretion, and metabolism in users of oral contraceptives.

Studies of insulin employing the oral glucose tolerance test demonstrate marked differences between the effects of different oral contraceptives, but provide little insight into the underlying disturbances. We investigated the metabolic basis of these disturbances by computer modelling of iv glucose tolerance test glucose, insulin, and C-peptide concentration profiles. Insulin resistance, secretion, and metabolism were evaluated in 296 oral contraceptive users and 95 nonusers. Four estrogen/progestin combinations, with similar estrogen but differing progestin contents, and 1 progestin-only formulation were studied. Effects on iv glucose tolerance test glucose, insulin, and C-peptide concentrations varied according to progestin content, with levonorgestrel-containing combinations having the greatest effect, followed by desogestrel and norethindrone. However, these formulations increased insulin resistance to a similar extent. The progestin-only formulation did not affect insulin resistance. Levonorgestrel combinations increased second phase pancreatic insulin secretion by 60-90%, but did not affect the insulin half-life. The desogestrel combination increased the insulin half-life by 28%, but did not affect insulin secretion. The effects of different combined oral contraceptives on glucose tolerance test glucose, insulin, and C-peptide concentration profiles appears to be due to a combination of estrogen-induced insulin resistance and progestin-associated changes in insulin half-life.

Adolescent↗

Endometrioid carcinoma of the prostate: a misnomer?

The origin of this unusual variant of carcinoma of the prostate has provoked discussion ever since its first description in 1967. This is of both embryological interest and therapeutic importance. Four cases have been reviewed, and all have demonstrated immunohistochemical features consistent with an origin from prostatic tissue. In addition, three had evidence of disseminated disease which responded well to androgen ablation. It is concluded that the term endometrioid carcinoma is of descriptive value only, and these tumours are a variant of primary duct prostatic carcinoma. Patients should be treated by androgen ablation when metastases are present.

Adenocarcinoma↗

Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA.

A rat dopamine (DA) transporter complementary DNA has been isolated with combined complementary DNA homology and expression approaches. The DA transporter is a 619-amino acid protein with 12 hydrophobic putative membrane-spanning domains and homology to the norepinephrine and gamma-aminobutyric acid transporters. The expressed complementary DNA confers transport of [3H]DA in Xenopus oocytes and in COS cells. Binding of the cocaine analog [3H]CFT ([3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane) to transfected COS cell membranes yields a pharmacological profile similar to that in striatal membranes.

Amino Acid Sequence↗

Double-blind placebo-controlled comparison of the analgesic effects of single doses of lornoxicam and aspirin in patients with postoperative dental pain.

The pain experienced after third molar surgery was used as a model to evaluate the analgesic efficacy of a new non-steroidal anti-inflammatory drug, lornoxicam, in a Phase II study. One hundred and fifty fit, young adults participated in this randomised, single dose, double-blind, parallel group clinical study. Three doses of lornoxicam (2 mg, 4 mg, and 8 mg) were compared with aspirin 650 mg and placebo. Patients suffering from moderate to severe pain following surgery were monitored for up to 8 hours. All indices of efficacy showed similar results, all active treatments being associated with highly significant (P less than 0.0001) reductions in pain during the study period. Lornoxicam 8 mg demonstrated significant analgesic efficacy as compared with placebo. The two lower doses of lornoxicam and aspirin all showed apparent degrees of efficacy intermediate between that of placebo and lornoxicam 8 mg, although the trial proved to have inadequate power to show significant differences between these three treatments. Lornoxicam was very well tolerated at all three doses studied, with no adverse events definitely attributable to its administration.

Adolescent↗

Contamination of adenosine deaminase by superoxide dismutase. Stabilization of endothelium-derived relaxing factor.

We have measured cyclic GMP accumulation in co-cultures of bovine aortic endothelial cells and rat smooth muscle cells as an index of endothelium-derived relaxing factor (EDRF) production. Adenosine deaminase (EC 3.5.4.4, Sigma type VI) produced a 5- to 10-fold increase in the basal and bradykinin-stimulated cyclic GMP content of co-cultures but had no effect on smooth muscle cells alone. Cyclic GMP accumulation in response to adenosine deaminase was not blocked by adenosine deaminase inhibitors or affected by adenosine, the products of adenosine deamination (inosine and ammonia), or adenosine receptor antagonists. Since superoxide anion is known to destroy EDRF and nitric oxide (NO) (which is similar or identical to EDRF in composition), we tested for superoxide dismutase (SOD, EC 1.15.1.1) in single lots of eight commercial sources of adenosine deaminase by measuring inhibition of the superoxide-mediated reduction of cytochrome c. SOD activity was found in all sources of adenosine deaminase, but varied widely. One lot of Sigma type VI enzyme contained 0.08 units SOD/unit adenosine deaminase. The EC50 values of purified SOD (0.23 units/mL) and Sigma type VI adenosine deaminase (2.1 units/mL) needed to increase the cyclic GMP content of co-cultures differed by a similar factor, 0.11. Thus, the SOD activity in adenosine deaminase is sufficient to account for its effect on cyclic GMP accumulation. One lot of Boehringer Mannheim adenosine deaminase contained much less SOD contamination (0.006 units SOD/unit adenosine deaminase) and produced much less accumulation of cyclic GMP in co-cultures. Cyclic GMP accumulations in response to adenosine deaminase and SOD were both abolished by the NO synthetase inhibitor NG-monomethyl-L-arginine (0.1 mM), consistent with the idea that these enzymes act by stabilizing EDRF. Adenosine deaminase and the SOD activity contaminating it were found to have similar molecular masses of 33-34 kD as assessed by gel permeation chromatography. When run under reducing conditions to dissociate homodimeric SOD into monomers, a 16.6 kD peptide which co-migrates with purified cupro-zinc SOD was visible in silver-stained sodium dodecyl sulfate-polyacrylamide gels of the Sigma type VI but not the Boehringer Mannheim adenosine deaminase. We conclude that commercial sources of adenosine deaminase are variably contaminated by SOD. Since EDRF is synthesized by many tissues, the use of adenosine deaminase contaminated with SOD may produce numerous effects not attributable to the deamination of adenosine.

Adenosine↗

Improved diagnosis and characterization of postinfarction left ventricular pseudoaneurysm by cardiac magnetic resonance imaging.

A patient with a ruptured left ventricular pseudoaneurysm complicating an acute posteroinferior myocardial infarction is described. Left ventricular pseudoaneurysms are a rare complication of acute myocardial infarction, usually occurring with inferior and/or posterior infarction. In contrast to true aneurysms, pseudoaneurysms are much more likely to rupture, regardless of size, causing hemopericardium and death. Therefore, once the diagnosis has been confirmed, prompt surgical resection is the current accepted treatment. The most accurate noninvasive diagnostic method has been echocardiography, with recent reports suggesting improved diagnosis with color flow Doppler echocardiography. Ventriculography confirms the diagnosis with more accurate anatomic detail, but is an invasive procedure. In our patient, two-dimensional and color Doppler echocardiography could not demonstrate the suspected pseudoaneurysm, which was demonstrated by ventriculography. However, magnetic resonance imaging (MRI) demonstrated the pseudoaneurysm, showing detailed anatomy not obvious on ventriculography. Before surgery could be performed, the patient died and was autopsied. Heart sections corresponding to MRI planes confirmed the MRI findings. A review of the literature has revealed no similar reports using MRI in the diagnosis of postinfarction pseudoaneurysms. Major advantages of MRI are generation of three-dimensional soft tissue images noninvasively, and generation of tissue contrast by rapid imaging sequences, obviating the need for contrast injection. Major disadvantages of MRI are the high cost of instrumentation, nonportability, and a requirement for patient immobility during the study. In cases of suspected pseudoaneurysm with equivocal echocardiography findings, MRI could provide early diagnosis, leading to early surgical intervention and increased patient survival.

Aged↗

Calcitonin gene-related peptide and substance P decrease in the rabbit colon during colitis. A time study.

The sensory neuropeptides, substance P and calcitonin gene-related peptide, have been implicated in inflammatory reactions in several tissues. An immune-complex model of colitis was used in rabbits to determine the colonic content (nmol/g protein) of immunoreactive substance P and calcitonin gene-related peptide at various times after induction of inflammation to assess changes in these neuropeptides during the inflammatory response. Calcitonin gene-related peptide content was decreased by 66% 4 hours after induction of inflammation and reached a maximum of 80% at 48 hours. The substance P content was decreased at 8 hours, with a maximum decrease of 64% at 48 hours. Substance P decrease was detected in the muscle layer. The amounts of substance P in the mucosal/submucosal layer extracts were too low to allow accurate measurements. Calcitonin gene-related peptide decreased both in the muscle and the mucosal-submucosal layers. Immunohistochemical analysis showed that calcitonin gene-related peptide and substance P innervation patterns were comparable in normal and inflamed colon, even though there appeared to be a decrease in density and intensity of the staining, particularly for calcitonin gene-related peptide at 48 hours. The early decrease of calcitonin gene-related peptide and substance P during the time course of colitis might be due to release from nerve terminals of the gut during the inflammatory response. The profound changes in colonic calcitonin gene-related peptide and substance P content during colitis may have important implications during inflammation and subsequent tissue repair and may also lead to disturbances in gut motility.

Animals↗

Case report: isolated right coronary artery obstruction presenting as acute anterior myocardial infarction.

A patient presented with chest pain and S-T segment elevation in the anterior chest leads diagnostic of acute anterior myocardial infarction (MI). The non-invasive imaging studies showed no evidence of left ventricular anterior MI but showed a right ventricular MI. Coronary angiography showed an isolated right coronary artery obstruction. Occasionally, the ECG in acute right ventricular myocardial infarction may resemble an anterior MI. The differentiation is important from a therapeutic viewpoint.

Adult↗

Polycystic ovarian syndrome: safety and effectiveness of stepwise and low-dose administration of purified follicle-stimulating hormone.

OBJECTIVE: An attempt to induce ovulation with a single dominant follicle in polycystic ovarian syndrome (PCOS) patients. DESIGN: Comparing ultrasound and estradiol (E2) measurements during treatment with a low-dose protocol (using purified follicle-stimulating hormone, starting with 75 IU/d and increasing every 7 days by 37.5 IU/d) with those obtained following treatment with a conventional protocol using the same drug. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS PARTICIPANTS: Eight PCOS patients of whom six had failed to respond adequately to the conventional protocol. MAIN OUTCOME MEASURE: Rate of cancellation of cycles, number of leading follicles, and serum E2 concentration at the time of ovulation. RESULTS: Treatment with the low-dose protocol resulted in a significant reduction in the number of leading follicles (P less than 0.04), serum E2 concentrations (P less than 0.0002), and a higher rate of ovulation. As a result, five patients conceived compared with none in the conventional protocol. CONCLUSION: Using the low-dose protocol permitted induction of ovulation safely and successfully in a selected group of PCOS patients who were previously difficult to treat with the conventional ovulation induction protocol.

Adult↗

Is it possible to run a successful ovulation induction program based solely on ultrasound monitoring? The importance of endometrial measurements.

OBJECTIVE: To attempt the monitoring of ovulation induction solely with ultrasound (US). DESIGN: Using serial US measurements to monitor ovulation induction using human menopausal gonadotropin and human chorionic gonadotropin (hCG), in comparison with estradiol (E2) concentrations that became available at the end of each cycle. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Twenty hypogonadotropic and 29 ultrasonically diagnosed polycystic ovary patients. MAIN OUTCOME MEASURE: Follicular growth, uterine measurements, endometrial thickness, and serum E2 concentrations. RESULTS: Follicular growth, uterine measurements, and endometrial thickness correlated strongly with E2 concentrations (P less than 0.0001). The endometrium on the day of hCG administration was significantly thicker (P less than 0.01) in the conception (n = 27) compared with the nonconception cycles (n = 87), whereas no significant difference were observed in serum E2 concentrations. No pregnancy was observed when hCG had been administered when the endometrial thickness was less than or equal to 7 mm. Midluteal endometrial thickness of greater than or equal to 11 mm was found to be a good prognostic factor for detecting early pregnancy (P less than 0.008). CONCLUSIONS: Serial US examinations used alone have proven to be safe and highly efficient. It also has a unique ability to detect pregnancy in the midluteal phase.

Adult↗