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Biomedical subjects

M McIntyre

Publications and source records attributed to M McIntyre.

At least 55 records · Page 3Linked to original sources
PubMed1998

Vascular smooth muscle cell polyploidy and cardiomyocyte hypertrophy due to chronic NOS inhibition in vivo.

To assess the vascular and cardiac response to NO (nitric oxide) synthase (NOS) blockade in vivo, Wistar-Kyoto rats (WKY) were treated for 3 wk with NG-nitro-L-arginine methyl ester (L-NAME; 10 mg.kg-1.day-1). L-NAME treatment induced hypertension that was associated with increased plasma renin activity. Flow cytometry cell cycle DNA analysis showed that aortic vascular smooth muscle cells (VSMC) from L-NAME-treated WKY had a significantly higher polyploid population compared with WKY controls. Using organ bath experiments, we have shown that aortic rings from L-NAME-treated WKY have an increased contractile response to phenylephrine and impaired relaxation to carbachol compared with control rings. NOS blockade in vivo caused a significant increase in cardiac and left ventricular hypertrophy. Northern mRNA analysis of the myocardium showed that L-NAME treatment caused reexpression of the fetal skeletal alpha-actin isoform without alterations in collagen type I expression, a pattern indicating true hypertrophy of the cardiomyocytes. These studies provide further insight to confirm that NO deficiency in vivo results in the development of vascular and cardiac hypertrophy.

Actins↗
PubMed1998

Issues in the implementation of cancer staging in Canada.

All sectors of the cancer control community in Canada agree that cancer staging is useful, and that stage should be assigned to every new case. At present, however, staging is not always recorded in the patient's records and treatment patterns and outcomes are rarely reported in terms of stage. This paper discusses what needs to be done to promote the use of staging in Canada. It is concluded that multifaceted programs of interventional continuing education (CE), tailored to meet the needs of the particular institution, offer the best prospect of success but the necessary organizational structure and information systems have to be put into place in advance. Implementation programs should be based on a thorough evaluation of the particular needs of the institution or community, and should be evaluated carefully in a few institutions before an attempt is made to disseminate them more widely. We recommend a phased approach to implementation which will first target institutions that already have the necessary infrastructure, i.e., provincial cancer centres. Demonstration of the feasibility and value of staging in that setting is seen as a means of promoting the adoption of staging in other institutions.

Academies and Institutes↗
PubMed1997

Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm.

The association of abnormal spermatogenesis in men with Y chromosome deletions suggests that genes important for spermatogenesis have been removed from these individuals. Recently, genes encoding two putative RNA-binding proteins (RBM and DAZ/SPGY) have been mapped to two different regions of the human Y chromosome. Both of these genes encode proteins that contain a single RNA recognition motif and a (different) internally repeating sequence. Y-linked RBM homologues are found in all mammalian species. We have raised an antiserum to RBM and used it to show that RBM is a nuclear protein expressed in fetal, prepubertal, and adult male germ cells. The distribution of RBM protein in the adult correlates with the pattern of transcriptional activity in spermatogenesis, suggesting that RBM is involved in the nuclear metabolism of newly synthesized RNA. RBM sequences are found on both arms of the Y chromosome making genotype-phenotype correlations difficult for this gene family. To address the location of the functional genes and the consequences of their deletion, we examined a panel of men with Y chromosome deletions and known testicular pathologies using this antiserum. This approach enabled us to map a region of the Y chromosome essential for RBM expression. In the absence of detectable RBM expression we see stages of germ cell development up to early meiosis, but not past this point into the haploid phase of spermatogenesis.

Adult↗
PubMed1997

Losartan, an orally active angiotensin (AT1) receptor antagonist: a review of its efficacy and safety in essential hypertension.

Losartan potassium, an angiotensin II receptor antagonist, is the first of a new class of agents to be introduced for the treatment of hypertension. In this review, we describe the clinical pharmacology of losartan, including its pharmacokinetics in healthy, male volunteers and special patient groups, such as the elderly, patients with liver disease and patients with renal impairment. We also review its pharmacodynamics, including safety and tolerability; specificity of action; and the effect of salt depletion. We then review the studies examining clinical efficacy and safety in hypertension.

Age Factors↗
PubMed1997

Diagnostic use of endoscopic mucosal resection.

We report two cases of gastric carcinoma where repeated, multiple conventional endoscopic biopsies were falsely negative. Endoscopic mucosal resection gave a positive diagnosis in both these patients. New equipment for aspiration mucosectomy makes the technique easier to perform, and a larger, deeper biopsy is obtained.

Adenocarcinoma↗
PubMed1997

Effects of elevated dissolved CO2 levels on batch and continuous cultures of Aspergillus niger A60: an evaluation of experimental methods.

The effects of elevated levels of dissolved carbon dioxide (dCO2), produced by gassing with CO2-enriched gas mixtures, upon an industrial strain of Aspergillus niger (strain A60) producing citrate and gluconate were quantitatively assessed. Particular attention was paid to the reliability and accuracy of the steam-sterilizable dCO2 probe, especially in the presence of high concentrations of potentially interfering acidic species. The response of the organism to elevated dCO2 levels was assessed by using both batch and chemostat cultures, and the sensitivity of the organism in different growth phases (lag, exponential, and stationary) was examined. Chemostat cultures showed markedly less inhibition (in terms of biomass and organic acid synthesis) than did batch cultures. Studies in batch culture indicated that lag-phase cultures were especially sensitive to elevated dCO2 levels. Overall, the results of this study indicate that previous experimental methods used to examine dCO2 effects in submerged cultures (continuous CO2-enriched gassing of batch cultures from time zero) have been inappropriate and have led to systematic overestimation of the inhibitory effects of dCO2 on mycelial organisms.

Aspergillus niger↗
PubMed1997

Nitric oxide and cardiovascular disease.

Endothelium-derived nitric oxide is an important regulatory molecule in cardiovascular function. Reduced availability of nitric oxide has been implicated in the pathogenesis of hypertension and atherosclerosis.

Arteriosclerosis↗
PubMed1997

Sex differences in the abundance of endothelial nitric oxide in a model of genetic hypertension.

A deficiency of nitric oxide may be responsible for the increased vascular resistance associated with human essential hypertension and that seen in animal models of hypertension. Premenopausal females are relatively protected from hypertension and cardiovascular complications. Levels of superoxide can influence the availability of nitric oxide. We hypothesize that there are differences in nitric oxide availability between stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) and that superoxide may be responsible for at least some of these differences. We studied vascular reactivity in endothelium-intact aortic rings from WKY and SHRSP. We measured nitric oxide synthase activity in endothelial cells removed from aortas and also measured circulating nitrite/nitrate levels. We found the response to N(G)-nitro-L-arginine methyl ester to be significantly greater in WKY compared with SHRSP (95% CI: 20 to 174; P=.015) and in females compared with males in WKY (95% CI: 143 to 333; P=.00004) and SHRSP (95% CI: 70 to 224; P=.0006). Endothelial nitric oxide synthase activity was significantly greater in SHRSP compared with WKY (95% CI: 2.3 to 17.6; P=.016). The EC50 for relaxation to carbachol was significantly greater in male rats compared with female rats (95% CI: -1.1 to -0.2; P=.003) within the SHRSP strain. The maximum relaxation to carbachol was significantly attenuated in stroke prone spontaneously hypertensive compared with Wistar-Kyoto rats (95% CI: 1.7 to 14.4; P=.015). Diethyldithiocarbamate had a significantly greater effect on the stroke prone spontaneously hypertensive rats' carbachol response than that of Wistar-Kyoto rats (95% CI: 14.3 to 47.0; P=.0008). We conclude that superoxide may be responsible for strain differences in vascular reactivity, whereas nitric oxide availability may be responsible for sex differences independently of endothelial nitric oxide synthase activity and superoxide.

Animals↗
PubMed1996

The incidence of Cyclospora cayetanensis in stool samples submitted to a district general hospital.

Cyclospora cayetanensis is the cause of a prolonged diarrhoeal syndrome. In the UK most cases are seen in travellers who have returned from countries in which the organism is endemic. The purpose of this investigation was to determine the incidence of C. cayetanensis in stool samples submitted to a district general hospital. A total of 6151 stools from 5374 different patients were screened for the presence of C. cayetanensis over a 1-year period using the modified Ziehl-Neelsen technique. Oocysts of C. cayetanensis were found in 7 stools (0.1%) from 4 patients (0.07%). All four patients were adult travellers who had visited countries in which C. cayetanensis is known to be endemic. In the population of this study, C. cayetanensis was found to be a rare cause of diarrhoea. Although C. cayetanensis infection should be considered in individuals of all ages who have lived in, or have travelled to endemic areas, there is no need to screen stool samples for the organism in those without such a travel history.

Adult↗
PubMed1996

Percutaneous feeding tube changes in long-term-care facility patients.

OBJECTIVE: To compare patient outcomes when percutaneous feeding tubes were changed routinely each month or only when necessary (prn). DESIGN: Prospective, randomized, nonblinded crossover study of 6 months of routine monthly changes compared with 6 months of prn changes. SETTING: 416-bed long-term-care facility. PATIENTS: 26 permanent residents with nutrition managed through percutaneous gastrostomy or jejunostomy feeding tubes. The median age was 61.5 years; 8 (31%) also had tracheostomies, and 3 (12%) had indwelling urinary catheters. RESULTS: The frequency of feeding tube changes was 40 per 1,000 patient-days during the 6 months of routine tube changes and 14 per 1,000 when tubes were changed prn (P < .001). There were no differences between the two study periods in frequency of stoma site infections, fever, episodes of emesis, and total antibiotic courses. The median duration in situ of feeding tubes with prn changes was 104 days. For both periods, feeding tubes were significantly more likely to fall out and require replacement with-in 24 hours of previous tube replacement. CONCLUSION: There were no observed differences in clinical outcomes in long-term-care facility patients when feeding tubes were changed only as necessary as compared to routine monthly changes.

Adult↗
PubMed1996

Dose-ranging study of the angiotensin II receptor antagonist irbesartan (SR 47436/BMS-186295) on blood pressure and neurohormonal effects in salt-deplete men.

We characterised the blood pressure (BP) and hormonal responses to the oral angiotensin II (Ang II) receptor antagonist irbesartan (SR47436/BMS-186295) or placebo in normal men with an activated renin-angiotensin system (RAS) during salt depletion. We also evaluated safety and tolerability. Twelve healthy, normotensive male volunteers followed a standardised salt-depletion regimen for 3 days before each study day. Six different single oral doses of irbesartan (1, 5, 10, 25, 50, and 100 mg) were administered double-blind in a three-panel, dose escalation with placebo randomised in each panel. Supine and erect BP and heart rate (HR), serum and urinary electrolytes: plasma renin activity (PRA), and Ang II were measured at intervals. Urinary electrolytes were measured for the 24-h period before dosing (to confirm salt depletion) and for 24 h afterward. No drug-related side effects were noted. There was a dose-related decrease in supine and erect systolic and diastolic BP (SBP, DBP) with irbesartan from 10 mg and beyond, with no change in HR. Supine mean arterial pressure (MAP) decreased by 18.8 mm Hg. There was a dose-related reactive increase in PRA (to 35 ng/ml/h) and Ang II (to 450 pg/ml) with irbesartan. Irbesartan is an orally active AT1 receptor antagonist. In salt-deplete normal men, it has a dose-related haemodynamic, hormonal, and electrolyte profile characteristic of AT1 antagonists. The dose range studied did not show a plateau or maximum effect.

Adult↗
PubMed1996

Modified detergent Ziehl-Neelsen technique for the staining of Cyclospora cayetanensis.

Cyclospora cayetanensis is a cause of prolonged diarrhoea, mainly in travellers. Laboratory diagnosis may be achieved by a number of methods such as the staining of faecal smears by the modified Ziehl-Neelsen (ZN) technique. Safer methods using this technique have been described for the staining of acid fast bacilli and cryptosporidia by replacing the phenol content of the carbol fuschin stain with various concentrated detergents. In this report the technique was modified slightly using a non-concentrated detergent and applied to the staining of oocysts of C cayetanensis. It was found that oocysts of C cayetanensis do not stain using the modified detergent ZN method when compared with similar preparations containing oocysts of Cryptosporidium spp.

Animals↗
PubMed1996

Typing of proteus from patients with bacteriuria.

Forty-five strains of Proteus mirabilis isolated from hospital in-patients, out-patients and community patients with significant bacteriuria, were investigated to determine whether a predominant type was present using the Dienes test. Antimicrobial susceptibility patterns of the 45 strains of Proteus mirabilis were also determined. There were 38 different Dienes types which shows that there is no predominant type of Proteus amongst the isolates examined in this study. This suggests that there is no predominant type of Proteus mirabilis in the community and hospital acquired bacteriuria. The antimicrobial susceptibility pattern of an isolate was not a useful marker for typing because susceptibility patterns between different Dienes types were so similar.

Adolescent↗