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Biomedical subjects

A B Miller

Publications and source records attributed to A B Miller.

At least 145 records · Page 8Linked to original sources
PubMed1994

Conversion from immediate-release to extended-release diltiazem in angina pectoris.

This multicenter, open-label, single crossover study examined 195 patients taking an immediate-release diltiazem tablet as chronic stable angina therapy to determine if apparently logical methods of converting them to an extended-release, once-daily formulation were effective. Patients were converted from the immediate-release (Phase I) to an extended-release (Phase II) formulation of diltiazem on a mg-for-mg basis or, when a similar dose was not available, to the next higher 120 mg dose. Weekly angina occurrences and nitroglycerin use, exercise testing at the end of each phase, and ambulatory electrocardiographic monitoring (AEM) during the week prior to the exercise study were evaluated. There was a statistically significant decrease in angina frequency and nitroglycerin consumption during Phase II. In the exercise studies, there was an insignificant increase in time to 1 mm ST-segment depression and total exercise time associated with a statistically significantly lower end-exercise blood pressure and heart rate in Phase II. In those patients who had ischemia during either phase on AEM, total ischemic duration and ischemic episodes were insignificantly lower in Phase II. All observations were similar in the subgroup of patients who were converted mg-for-mg. Adverse reactions were equal. Thus, in converting patients from an immediate- to an extended-release diltiazem formulation for the treatment of symptomatic coronary artery disease, it is reasonable to convert directly to the same or, if not available, the next higher available dose of the extended-release preparation.

Aged↗
PubMed1994

Mammography screening guidelines for women 40 to 49 and over 65 years old.

Many organizations in the United States recommend mammography screening at 1- to 2-year intervals for those 40 to 49 years old. In most areas of Canada and Europe, screening mammography is not recommended for women 40 to 49 years old. These differences have arisen over interpretation of data from the Health Insurance Plan (HIP) study and the Breast Cancer Detection Demonstration Project (BCDDP). The apparent benefit in the HIP study is probably attributable to poor survival of control subjects with stage 1 cancers. In the BCDDP, although high cancer detection rates by mammography and improved survival of patients with screen-detected cancer were seen, the latter was probably largely due to lead time bias. The screening studies in Canada and Europe show no evidence of effectiveness of mammography screening in women 40 to 49 years old, at least in the first 10 years after screening is initiated. For women over 65 there are few data, but screening to age 74 is probably appropriate.

Adult↗
PubMed1994

Canadian contributions to cancer control.

Cancer control comprises prevention, screening, treatment, rehabilitation and palliative care. Preventive approaches need to be congruent with those adopted for other chronic diseases, with a major impact to be expected from smoking control and dietary modification. Canadian studies have contributed substantially to knowledge in both areas. Increasing interest is now being paid to other environmental causes of cancer, and to gene-environment interactions. Canadian studies have shown that screening for cancer of the cervix is effective, but improved organization of services is required to make it realize its full potential. The National Breast Screening Study has reminded us that a prerequisite for effective screening is effective therapy for the detected abnormalities, yet as therapy improves, so the contribution of screening may fall. Treatment has improved dramatically in recent decades for childhood cancer, where it is the mainstay of control. For adults, Canadian studies have contributed to improved therapy for some solid and hematogenous tumors, but important breakthroughs from molecular biology are still awaited. Finally, Canadians have been at the forefront of palliative care, as well as recognizing the need for improvement in the organization of cancer control.

Canada↗
PubMed1994

Mammography screening controversies.

Some organizations in the U.S. recommend mammography screening at 1- to 2-year intervals for those aged 40 to 49 and annually from the age of 50. In Canada and Europe, screening mammography is not recommended for women aged 40 to 49, and mammography every 2 to 3 years for women aged 50 to 69. The screening studies in Europe show no evidence of effectiveness of mammography screening in women aged 40 to 49 in the first 8 to 10 years after initiation of screening. Although at 12 years the recent Swedish overview analysis shows a 13% reduction, this is nonsignificant and the confidence intervals are wide. In the National Breast Screening Study (NBSS) in Canada, annual two-view mammography and physical examinations by carefully trained health professionals were given. In women aged 40 to 49 the ratio of proportions of deaths was 1.36 (95% CI 0.84, 2.21). For women aged 50 to 59, the NBSS evaluated the contribution of mammography over and above physical examination. In spite of detecting many more cancers, mammography did not result in a reduction in breast cancer mortality at 7 years (OR 0.97; 95% CI 0.62, 1.52). Although these results suggest the benefit from screening may be less than assumed, for women over 50, biennial screening to age 74 is probably appropriate in population programs, although careful monitoring will be necessary to ensure that the anticipated effect is achieved.

Adult↗
PubMed1994

Mammography in women under 50.

In this article, the evidence relating to the evaluation of effectiveness of early detection of breast cancer in women age 40 to 49 is reviewed, in light of the considerable controversy that has arisen over whether women in this age group should be given routine mammography screening. Of necessity, evidence is also provided on its effectiveness in older women, to facilitate comparison.

Age Factors↗
PubMed1993

2-(Quinuclidin-3-yl)pyrido[4,3-b]indol-1-ones and isoquinolin-1-ones. Potent conformationally restricted 5-HT3 receptor antagonists.

Several series of N-(quinuclidin-3-yl)aryl and heteroaryl-fused pyridones were synthesized and evaluated for 5-HT3 receptor affinity. In the heteroaryl series, 2-(quinuclidin-3-yl)tetrahydropyrido-[4,3-b]indol-1-one (8a) and the 4,5-alkano-bridged analogues (14 and 15) displayed high 5-HT3 receptor affinity with pKi values > 9. The (3S)-quinuclidinyl isomers had > 10 fold higher affinity than the (3R)-isomers. In a series of 2-quinuclidin-3-yl)isoquinolin-1-ones, derivatives substituted with small lipophilic groups (25b-e) and with 4,5-alkano-bridges (34-36) also displayed high affinity. In particular, the hexahydro-1H-benz[de]isoquinolinone (S,S)-37 was the highest affinity 5-HT3 receptor ligand prepared (pKi 10.4). A number of the high affinity ligands were shown to be potent 5-HT3 receptor antagonists in vivo as determined by inhibition of the B-J reflex in the anesthetized rat. Again, (S,S)-37 was the most active agent tested (ID50 0.02 microgram/kg i.v.), and this compound was also potent in blocking cisplatin-induced emesis in both the ferret and the dog. Computer modeling studies were performed, and previously reported 5-HT3 receptor antagonist pharmacophore models were refined to include a key lipophilic binding domain.

Animals↗
PubMed1993

Are female smokers at higher risk for lung cancer than male smokers? A case-control analysis by histologic type.

A case-control study of male-female differences in cigarette smoking and lung cancer was conducted during 1981-1985 in Toronto, St. Catharine's, and Niagara Falls, Ontario, Canada. In total, 442 female and 403 male histologically verified cancer cases were individually matched by age and area of residence to each other and to 410 female and 362 male randomly selected population controls. Subjects were interviewed concerning their exposures to various life-style factors, and in particular, they received detailed questioning regarding their lifelong histories of usage of tobacco products. It was found that, for both sexes, a greatly elevated risk of developing lung cancer was associated with cigarette consumption, increasing with pack-years of cigarettes smoked and declining with duration of time since quitting smoking. Furthermore, the association was significantly (p = 0.010) and appreciably stronger for females than for males. At a history of 40 pack-years relative to lifelong nonsmoking, the odds ratio for women was 27.9 (95% confidence interval (CI) 14.9-52.0) and that for men was 9.60 (95% CI 5.64-16.3). Higher odds ratios for females were also seen within each of the major histologic groupings. Thus, the higher elevated risk of lung cancer currently observed in other studies for female ever smokers compared with male ever smokers, while possibly attributable in part to greater smoking cessation among males, may be due to higher susceptibility among females.

Adenocarcinoma↗
PubMed1993

A cohort study of alcohol consumption and risk of breast cancer.

The association between alcohol consumption and breast cancer risk was examined in 519 newly incident, histologically confirmed cases of breast cancer diagnosed between 1982 and 1987 within a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study. These women had completed a self-administered food frequency questionnaire including alcohol consumption at enrollment into the study prior to their breast cancer diagnosis. For the total cohort, only a weak association between total alcohol consumption and breast cancer risk is observed, the adjusted relative risk for those drinking 30 or more g/day being 1.22 (95% confidence interval (CI) 0.78-1.90) compared with nondrinkers. There is some evidence for a positive association in women who were premenopausal at the time of enrollment for whom there was a monotonic increase in risk with increasing alcohol intake. Compared with nondrinkers, the adjusted relative risk for alcohol consumption of between 0 and < 10 g of alcohol daily was 1.11 (95% CI 0.71-1.71), between 10 and < 20 g was 1.37 (95% CI 0.79-2.36), between 20 and < 30 g was 1.51 (95% CI 0.80-2.86), and > or = 30 g was 1.86 (95% CI 0.96-3.66; p (trend) = 0.07). These findings contrasted with the results for postmenopausal women where there appeared to be no evidence of any relation. The association in premenopausal women is generally reasonably consistent with that of other studies that have found positive associations with alcohol intake.

Adult↗
PubMed1993

Mammography.

Explore the source record for details and available documents.

Breast Neoplasms↗
PubMed1993

Single site experience with high-speed coronary rotational atherectomy.

This report describes a single site experience as part of a multicenter clinical trial with high-speed rotational atherectomy in human coronary arteries. A total of 108 patients with 143 lesions had interventions, were grouped by success or failure, and were analyzed by patient, lesion, and procedural variables. Satisfactory results were achieved in 131 of 143 lesions (92%) and 99 of 108 (92%) patients. Neither patient-related variables (age, gender, diabetes, hypertension, cigarette use, restenosis, previous myocardial infarction, and left ventricular function) nor lesion characteristics (length, ostial or bifurcation location, calcification, lesion classification, and coronary location) were predictive of poor outcome. Tears, acute closure, percentage stenosis after rotational atherectomy and after adjunctive balloon angioplasty were the procedural variables that were statistically associated with outcome by univariate methods. Multivariate analysis isolated postintervention residual stenosis as the only variable that was statistically different between groups. Serious complications included one death in the catheterization laboratory, one Q-wave myocardial infarction, three non-Q myocardial infarctions, and three emergency coronary bypass operations for sustained vessel closure. One patient required emergency surgery for a pacing wire perforation not related to the use of the device. The potential benefits of high-speed rotational atherectomy include increased safety in complex lesions, the ability to address lesions not amenable to balloon techniques, and the possibility of reducing the incidence of restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1993

Computer-assisted molecular modeling: indispensable tools for molecular pharmacology.

Ball-and-stick mechanical models, typically associated with chemists, have been helpful in understanding structural problems and the relationship between structure and biologic activity. With progress in computer speed, graphics performance, and software innovation, molecules of biological interest can be subjected to rigorous calculations. Computational chemistry and biology are rooted in the belief that theoretical physics can be used to calculate accurate molecular structures. Although in its infancy, computer-assisted molecular modeling is gaining attention and acceptability as an increasing number of researchers turn their attention toward rational molecular design. The trend to use theoretical methods can be traced to the greater availability of computer graphics work-stations, decreasing computer costs, faster central processing units, more robust algorithms, and "user-friendly" software codes. Every major pharmaceutical company has invested in these resources to reduce the time it takes to design and develop pharmaceutical agents. Because of the vast financial and manpower investments needed to introduce a single drug, medicinal chemists and pharmacologists are interested in understanding and predicting drug action at the molecular level. Although drug action is still poorly understood, molecular modeling should reduce some of the labor in the development of pharmaceutical agents.

Computer Graphics↗
PubMed1993

Dietary fiber, vitamins A, C, and E, and risk of breast cancer: a cohort study.

Risk of breast cancer was examined in relation to intake of dietary fiber and vitamins A, C, and E, and food groups which are sources of these dietary constituents, in a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study. Between 1982 and 1987, 519 incident, histologically confirmed cases of breast cancer were identified among women who previously had completed self-administered dietary questionnaires. Their nutrient and food intake was compared with that of 1,182 women who had not developed breast cancer during the follow-up period. Women at the uppermost quintile level of dietary fiber intake had a 30 percent reduction in risk of breast cancer relative to that for women at the lowest quintile level (adjusted odds ratio = 0.68, 95 percent confidence interval = 0.46-1.00), and the reduction in risk persisted after adjustment (separately) for total vitamin A, beta-carotene, vitamin C, and alpha-tocopherol. Inverse associations of similar magnitude were observed in association with consumption of pasta, cereals (the trend for which was statistically significant), and vegetables rich in vitamins A and C. Smaller, statistically nonsignificant reductions in risk were observed with increasing intake of dietary retinol, beta-carotene, and vitamin C, but the magnitude of these associations was reduced after adjustment for other dietary factors. Vitamin E intake was not associated with altered risk of breast cancer.

Ascorbic Acid↗