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Biomedical subjects

M McIntyre

Publications and source records attributed to M McIntyre.

At least 73 records · Page 4Linked to original sources
PubMed1995

Comparison of the oral angiotensin II receptor antagonist UP 269-6 or enalapril 20 mg on blood pressure and neurohormonal effects in salt-deplete man.

We compared the response of the oral angiotensin II (Ang II) receptor antagonist (ARA) UP 269-6 with an angiotensin converting enzyme inhibitor (ACEI) enalapril 20 mg or placebo, during salt depletion in normal men. We also evaluated safety and tolerability. Sixteen healthy, normotensive male volunteers followed a standardised salt-depletion regimen for 3 days before each study day. Seven different doses of UP 269-6 (5, 10, 20, 40, 80, 120 and 180 mg) were administered double blind in a four-panel dose escalation, with enalapril and placebo randomised within each panel. Supine and erect blood pressure (BP) and heart rate (HR); serum and urinary electrolytes; plasma active renin (PAR), aldosterone, and Ang II were measured at intervals. Urinary electrolytes and aldosterone were measured for the 24 h before dosing and for 24 h after dosing. Dizziness and light-headedness on standing were reported after UP 269-6 at higher doses. Enalapril caused one episode of symptomatic postural hypotension. No other drug-related adverse events (AE) were noted. There was a dose-related decrease in supine and erect systolic and diastolic BP (SBP, DBP) with UP 269-6 at > or = 40 mg, with no change in HR. Based on the maximal decrease in mean arterial pressure (MAP), UP 269-6 at 180 mg had an effect largely comparable to that of enalapril 20 mg. There was a dose-related increase in PAR with UP 269-6. Although this was greater with UP 269-6 180 mg than with enalapril, serum and 24-h urinary aldosterone suppression was greater with enalapril than with any dose of UP 269-6.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Interleukin-6 production by bladder tumors is upregulated by BCG immunotherapy.

PURPOSE: To determine whether BCG therapy could upregulate interleukin-6 (IL-6) production in human transitional cell carcinomas (TCC). MATERIALS AND METHODS: Immunohistochemistry of tumor biopsies and urinary cytospins and ELISA studies of urine from bladder cancer patients and TCC cell-line supernatants, before and after exposure to BCG, were performed. RESULTS: Constitutive staining for IL-6 was found in the majority of bladder tumors. Interleukin-6 was detected in the urine of all 13 patients with carcinoma in situ and increased 5-fold during BCG therapy. Levels were variable but were greater in nonresponders (p < 0.01). During therapy both detached bladder urothelial cells and polymorphonuclear leukocytes stained for IL-6. Production of IL-6 increased in only 3 cell lines after exposure to BCG, but all 7 cell lines showed increases after exposure to interferon-gamma (p = 0.015). Grade 3 cell lines showed much greater upregulation than grade 1 and 2 cell lines. CONCLUSIONS: The increase in IL-6 during BCG therapy may be caused by urothelial cells as well as leukocytes. The higher levels seen in nonresponders may be due to either higher grade or persisting tumor.

BCG Vaccine↗
PubMed1995

"The focus of the discipline of nursing": a critique and extension.

Influential writings in nursing tend to align with views held and privileged in the scientific community. By taking this stance nurses resist changes that would advance the discipline and give voice and visibility to marginalized people in society who seek the socially relevant service that nursing purports to offer. The difficulty stems not only from the failure to question the dominance of particular approaches for knowledge generation over others, but also from the failure to recognize that our questions are constructed to support rather than to challenge existing knowledge. Revisioning a pivotal article--"The focus of the discipline of nursing"--enhances its usefulness for nursing curricula.

Curriculum↗
PubMed1994

Induction of ICAM 1 expression on bladder tumours by BCG immunotherapy.

AIMS: To determine the expression of intercellular adhesion molecule 1 and 2 (ICAM 1 and 2) in transitional cell carcinoma cells before and after immunotherapy with Calmette-Guérin bacillus (BCG). METHODS: Frozen sections from 22 untreated bladder carcinomas were immunohistochemically examined with monoclonal antibodies to ICAM 1 and 2. Urinary cytospin slides were made for six patients for each of the six clinical instillations which constitute a therapeutic course. These slides were also stained for ICAM 1 and for leucocyte function associated antigen 1 (LFA 1). RESULTS: Bladder cancer cells did not essentially express either ICAM 1 or 2, but cells in the stromal areas surrounding tumour expressed both these antigens. After repeated instillations of BCG organisms ICAM 1 positive normal and neoplastic epithelial cells were observed in the urine. Cells obtained from the first three instillations expressed lower densities of ICAM 1 than those from the later instillations. Many neutrophils expressing LFA-1 and some lymphocytes were also noted in the cytospin slides and some of these were conjugated to tumour cells expressing ICAM 1. Six months after treatment a single maintenance dose of BCG induced ICAM 1 expression. CONCLUSION: Untreated superficial bladder carcinoma cells do not express ICAM 1 or 2, but these important immunological molecules were expressed in the stromal areas of tissue. Importantly, neoplastic cells in the urine expressed ICAM 1 after immunotherapy. This molecule can render bladder tumour cells vulnerable to non-antigen specific cytotoxicity mediated by activated lymphocytes.

Antigens, CD↗
PubMed1993

Audit and its impact in the management of advanced prostatic cancer.

From a prospective database of 614 consecutive men with newly diagnosed prostatic cancer an audit of outcome was studied in 169 men who presented with bone metastases and subsequently received hormonal manipulation in the form of monotherapy. The cohort was divided into 2 groups according to serum alkaline and acid phosphatase enzyme levels. Men with normal alkaline phosphatase levels (41.5%) had a better prognosis (median survival 38 months) than those with elevated levels at presentation (58.5%) (median survival 19 months). This difference was highly significant. A similar stratification on prostatic acid phosphatase levels did not yield any prognostic significance. With regard to cause-specific survival, serum alkaline phosphatase was an even more powerful prognosticator, with a median survival of 45 and 21 months for patients with normal and elevated levels respectively. Thus monotherapy is recommended for metastatic prostate cancer patients with normal serum alkaline phosphatase, but for those with elevated alkaline phosphatase the alternative avenues of treatment must be explored.

Acid Phosphatase↗
PubMed1993

Frequency of changing enteral alimentation bags and tubing, and adverse clinical outcomes in patients in a long term care facility.

Enteral alimentation, given via nasogastric or gastrostomy tubes, is a well established practice to provide nutrition for patients with significant neurological injury. The frequency with which enteral feeding bags and tubes require change and potential adverse effects associated with bacterial contamination of tube feeds remain controversial. The authors studied different times between enteral feeding bag and tube changes, and the effect on adverse clinical outcomes in residents of a long term care facility. In the first study, residents were randomized to 24 h (n = 2), 48 h (n = 3) or 72 h (n = 6) tube feeding and bag changes with clinical status monitored in a standardized fashion for six months. In the second study, patients were randomized to 24 h (n = 6) or 72 h (n = 6) changes. Patient-days of follow-up were 382, 574 and 1000 for the three arms of the first study period and 556 and 496 for the two arms of the second study. No differences in potential clinical adverse events--including fever, gastrointestinal symptoms or pneumonia--were observed with different durations of tubing change. This study suggests it is appropriate to change alimentation tube and feeding bags every 72 h (rather than every 24 h). The less frequent changes will decrease supply costs and free nursing time for other activities.

Aged↗
PubMed1992

Microencapsulated islet grafts in the BB/E rat: a possible role for cytokines in graft failure.

Alginate-polylysine microencapsulation has been proposed as a method of protecting transplanted pancreatic islets against immunological attack. Using this technique, prolonged graft survival has been reported in some diabetic animals. However, in the spontaneously diabetic insulin-dependent BB/E rat we found that intraperitoneal implantation of microencapsulated islets had only a short-lived effect on hyperglycaemia. Recovered microcapsules (both those implanted empty and containing islets) were surrounded by a foreign body type cellular overgrowth and, although many capsules remained intact, encapsulated islets were observed to be disintegrating. Loss of Beta cells was confirmed by immunohistology. Various polymer materials used in artificial membranes have been shown to activate macrophages involved in foreign body reactions and induce synthesis of interleukin-1 beta, a known Beta-cell toxin. Reduced secretion of insulin and progressive islet damage (indicated by a significant reduction in residual islet insulin and DNA content) were demonstrated when microencapsulated islets were incubated with interleukin-1 beta in vitro for 9 days. Similar effects were seen following exposure to a combination of gamma interferon and alpha tumour necrosis factor. Successful use of microencapsulation in islet transplantation depends upon the development of biocompatible membranes. The exclusion of smaller molecules, such as cytokines, which may be involved in foreign body mediated damage and microencapsulated islet graft rejection, could also be important.

Alginates↗
PubMed1992

Asymptomatic bacteriuria, urinary antibody, and survival in the institutionalized elderly.

OBJECTIVE: To compare clinical status of elderly institutionalized subjects with asymptomatic bacteriuria and normal urinary antibody to those with elevated urinary antibody to the major outer membrane of Escherichia coli. DESIGN: Retrospective review. SETTING: Long term facility for the elderly. PARTICIPANTS: Convenience sample of 63 elderly subjects, 26% of those resident in the institution, aged 78.8 +/- 8.4 years with urine specimens collected and stored in 1987. MAIN OUTCOME MEASURES: Differences in clinical or functional status, demographic features, and outcome during 3-years follow-up between bacteriuric subjects with normal and elevated urine antibody. RESULTS: Thirteen subjects had no bacteriuria, and 12 had infrequent, intermittent bacteriuria; 38 (60%) had persistent bacteriuria, including four with frequent, intermittent infections. In the persistently bacteriuric group, 18 (47%) had persistently elevated urine antibody. There was no significant differences between bacteriuric residents with normal vs elevated urine antibody in clinical or functional status, age, duration of residence, or infecting organisms. However, 11 of 20 in the cohort with normal urine antibody were alive at 3 years compared to 3 of 18 with elevated urine antibody (P = 0.014). CONCLUSIONS: Elderly institutionalized subjects with persistent bacteriuria and elevated urine antibody have decreased survival compared to those with normal urine antibody. No differences in underlying illness or clinical course to explain this survival difference were identified.

Aged↗
PubMed1991

Rapid identification of Legionella pneumophila zinc metalloprotease using chromogenic detection.

Strains of Legionella spp. produce extracellular proteases than can be detected using synthetic chromogenic peptides. Chromogenic tri- and tetrapeptides show a high degree of sensitivity, specificity and reagent stability when linked to para-nitroaniline (pNA). For example, SucOMe-Arg-Pro-Tyr.pNa (S-2586) is specifically hydrolysed by proteases of Legionella pneumophila and some other Legionella species. A paper disc method to sample protease directly from agar plates has been used to evaluate chromogenic peptides as reagents for diagnostic purposes. Strains of Legionella spp., Pseudomonas spp. and Enterobacteriaceae were examined, together with a recombinant Escherichia coli strain containing the cloned 38 kDa zinc metalloprotease from L. pneumophila, S-2586 was hydrolysed by 282 out of 283 L. pneumophila strains, and by the recombinant E. coli. Two of the six strains representing other Legionella species, and 22 of the 50 strains from the Pseudomonas group were also positive. No reaction was seen with any of the Enterobacteriaceae strains. Although there was functional homology between proteases from several bacterial groups, the high prevalence of S 2586-hydrolysing proteases within L. pneumophila indicates a potential usefulness for phenotypic identification.

Bacterial Proteins↗
PubMed1991

Lung cancer in lifelong non-smokers. Edinburgh Lung Cancer Group.

The Edinburgh Lung Cancer Group registered 3070 new patients with lung cancer in the five years 1981-5 from a catchment population of 950,000. After review only 74 (2%) were classified as lifelong non-smokers. They differed significantly from the 2996 smokers with lung cancer in that far more were female (77% v 26%) and their mean age was higher (75.4 v 68.0 years). More were in the worst Karnofsky performance categories and fewer patients underwent surgery. The stages of disease were similarly distributed in the two groups and the five year survival was equally poor (5%). Histological cell type was determined in 59 of the 74 patients. All histological cell types were present. More non-smokers had adenocarcinoma than smokers (42% v 13%) and fewer had squamous cell carcinoma (32% v 49%) or small cell carcinoma (15% v 24%). Lung cancer in lifelong non-smokers is uncommon and the diagnosis should therefore always be questioned.

Adenocarcinoma↗
PubMed1990

Radiation-induced prostatic sarcoma: a case report.

A 64-year-old man had a prostatic sarcoma 8 years after transurethral prostatectomy and radical bilateral pelvic lymph node dissection with insertion of 125iodine implants for stage B1N carcinoma of the prostate. Therapy for the sarcoma consisted of isolated pelvic perfusion and then pelvic exenteration with creation of an ileal conduit and colostomy. The pathology report showed well encapsulated grade 2 spindle cell sarcoma of the prostate. Multiple small metallic particles were embedded in the tumor specimen.

Adenocarcinoma↗
PubMed1990

Legionella pneumophila serogroup 1 population in Italy by monoclonal subtyping.

The Oxford panel of monoclonal antibodies was used to subtype 83 strains of Legionella pneumophila serogroup 1 of human and environmental origin. The International panel was also used to subtype 50 of them. All the 18 patients' isolates were of the Pontiac subgroup, and 40/43 of the environmental strains of the Pontiac subgroup were associated with human infection. The remaining environmental strains were subgroups Olda (15 strains), Camperdown (5 strains), and Bellingham (2 strains). The Philadelphia subgroup was the commonest among the environmental strains tested with the international MABs panel. This study confirms previous findings that L. pneumophila serogroup 1 isolates with the Pontiac (Oxford panel) or MAB-2 (international panel) reacting antigen marker seem to be more virulent than the other subgroups.

Antibodies, Monoclonal↗
PubMed1990

Prevalance of antibodies to 15 antigens of Legionellaceae in patients with community-acquired pneumonia.

Sera from 252 patients with community-acquired pneumonia were examined for the presence of antibodies to 15 antigens of 7 Legionella spp. by indirect immunofluorescent antibody testing. The sera had been collected as part of the British Thoracic Society/Public Health Laboratory Service study of community-acquired pneumonia in adults. We also examined sera from 20 patients with gram-negative sepsis. Using a limited range of antigens of L. pneumophila, nine cases of legionellosis were diagnosed in the original study. However, using antigens to other Legionella spp., we identified two further cases, caused by L. micdadei and L. gormanii respectively. Twenty-six other patients had titres of 16 or 32 to one or more antigens, most commonly L. bozemanii serogroup 1, L. micdadei and L. dumoffi. None of the patients with non-legionella pneumonia, however, had significant changes in legionella antibody titres. All of the patients with Gram-negative sepsis had titres of less than 16.

Antibodies, Bacterial↗