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Biomedical subjects

A B Miller

Publications and source records attributed to A B Miller.

At least 199 records · Page 11Linked to original sources
PubMed1991

Double-blind, dose-response, placebo-controlled multicenter study of nisoldipine. A new second-generation calcium channel blocker in angina pectoris.

BACKGROUND: Nisoldipine is a potent 1:4 dihydropyridine calcium channel antagonist, and doses of 5 or 10 mg administered either once or twice daily have been claimed to exert antianginal effects. There is, however, little information regarding the dose-response relation and whether the drug exerts any consistent effects throughout the dosing interval. In this placebo-controlled, parallel-design study, the dose-response relation of monotherapy with nisoldipine administered twice daily was studied in patients with stable angina pectoris. METHODS AND RESULTS: Two hundred thirty-one patients received single-blind placebo for 2 weeks; of these, 185 patients who reproducibly stopped treadmill exercise because of angina of moderate severity and had greater than or equal to 1 mm ST segment depression during exercise and experienced an average of three episodes of anginal attacks per week were randomized in a double-blind manner to one of the four treatment groups: placebo (n = 48), nisoldipine 2.5 mg (n = 47), nisoldipine 5 mg (n = 44), or nisoldipine 10 mg (n = 46). Nisoldipine or placebo was administered twice daily for 4 weeks and symptom-limited exercise tests were repeated at 2 and 10-14 hours after the double-blind medication. One hundred sixty-eight patients completed the study and 181 patients were valid for efficacy analysis. Compared with double-blind placebo, there were marginally significant trends toward increases for time to onset of angina for the 10-mg-b.i.d. group (83 versus 108 seconds, p = 0.08), time to 1 mm ST segment depression for the 5-mg-b.i.d. group (54 versus 83 seconds, p = 0.08), and total exercise time for the 5- (30 versus 50 seconds, p = 0.10) and 10-mg-b.i.d. (30 versus 58 seconds, p = 0.06) groups at 2 hours after the dose (peak effect) after 4 weeks of therapy. At 10-14 hours after the dose (trough effect), no differences between placebo and any of the nisoldipine doses on any of the exercise parameters were found after 4 weeks of therapy. A subset analysis of patients who stopped exercise within 10 minutes because of angina of moderate severity during single-blind placebo therapy (n = 123) revealed significant increase in total exercise duration and time to 1 mm ST segment depression at 2 hours after the dose in the 5- and 10-mg-b.i.d. dose groups compared with double-blind placebo (p less than 0.04). No significant trough effects, however, were observed even in this subgroup after any of the doses of nisoldipine. The frequency of anginal attacks decreased by 44%, 41%, 30%, and 41% after twice-daily therapy with 2.5 mg, 5 mg, 10 mg nisoldipine, and placebo groups, respectively (p = NS, nisoldipine versus placebo). The incidence of adverse events (minor and major) was 43.8% in the placebo group and 42.6%, 45.5%, and 56.5% in the nisoldipine 2.5-, 5-, and 10-mg-b.i.d. groups, respectively (p = NS compared with placebo). However, four patients developed unstable angina while on nisoldipine therapy (two in the 2.5-mg, one in the 5-mg, and one in the 10-mg-b.i.d. group) and two patients died suddenly in the nisoldipine 10-mg-b.i.d. group. CONCLUSIONS: Monotherapy with 2.5, 5, and 10 mg nisoldipine twice a day was not superior to placebo therapy in treating patients with angina pectoris, and the 10-mg-b.i.d. therapy resulted in a statistically insignificant but clinically important increase in the incidence of serious adverse events.

Adult↗
PubMed1991

Cancer patterns in the Inuit population of Canada 1970-1984.

1. Rates for lung cancer in Canadian Inuit are high and increasing for both men and women; in fact they are the highest reported rates for lung cancer among any Inuit population. 2. Cervical cancer in Canadian Inuit are high but rates appear to be stable, unlike the rapidly increasing trend reported in both Alaska and Greenland. 3. Rates for traditional Inuit cancers such as those of the nasopharynx and salivary gland do not appear to be declining in Canadian Inuit. 4. Rates for colorectal cancer in Canadian Inuit are similar to those expected for the Canadian population as a whole and do not appear to be increasing. 5. Finally, cancers traditionally reported to be rare in Inuit are still rare in the Canadian Inuit population; these include breast, prostate, bladder, and endometrial cancer. Cancer is a disease which can be controlled through prevention, early detection or treatment. The following future directions arising from this work reflect this paradigm. First, the Inuit cancer registry developed for this analysis will be used as a base for further research into environmental and genetic factors influencing cancer rates in the Inuit. Second, given that at least 40% of cancers in Canadian Inuit are cancers of the lung and cervix, health promotion programs should be developed to encourage tobacco-free environments to halt the epidemic of lung cancer, and also to make available Pap smear programs for early detection of cervical cancer. Third, health care services and programs, including diagnosis and treatment, should be culturally accessible to the Inuit population (6).(ABSTRACT TRUNCATED AT 250 WORDS)

Canada↗
PubMed1991

Role of early diagnosis and screening; biomarkers.

Currently there is evidence to support the inclusion of screening for breast and cervix cancer in programs for cancer control. Breast cancer programs have an important impact in women over the age of 50, but increasingly there are suggestions that, at least in the early years, there are no benefits for women age 40 to 49, and even that mortality from breast cancer may be increased. Cervix cancer programs can have a major impact if appropriately organized. There is no justification at present to recommend screening for colorectal cancer. Screening can be expected to have only a minor influence on reduction in cancer mortality by the year 2000. Biomarkers may be of value as indicators of risk or indicators of disease. Some have been proposed for the former, such as mammographic parenchymal patterns and breast cancer risk. There are good theoretical reasons for not incorporating them in screening programs, as the program sensitivity will decrease, even if the program specificity increases. Biomarkers as indicators of disease may be valuable when the marker is linked to the etiologic agent for the disease, providing that valid screening tests can be developed for the marker, or could be a biological indicator of the presence of disease, such as a monoclonal antibody, specific to the cancer. Examples include markers for hepatitis B virus (HBV) infection and liver cancer screening, and potentially in the future, markers for human papillomavirus (HPV) infection and cervix cancer screening. Specific monoclonal antibodies to cancer utilizable in screening are being sought, but are not yet available for use. One example under evaluation is the CA 125 monoclonal for ovarian cancer.

Biomarkers, Tumor↗
PubMed1990

Rome women's screening study: knowledge, attitudes and practices of women regarding screening for breast and cervical cancer.

A survey on knowledge, attitudes, and practice regarding breast and cervical cancer screening was conducted in Rome on a sample of women aged 18-64 years. Of the 793 interviewees, 31.9% had undergone at least one breast imaging examination; examinations were more frequent in women over 35 and in those familiar with breast self-examination and female pathophysiology. Seventy percent of the women had had at least one Pap smear. Women were classified as Pap smear underusers (26.0%), appropriate users (28.8%), and overusers (45.2%) as compared to standard screening recommendations, according to their age and their lifetime number of smears. Age over 35 was associated with both underuse and overuse. Such inappropriate screening patterns could be related in part to the fact that the women reported that their physicians recommendations for Pap smear frequency were once a year or more in 62%, and once every two or three years in only 2%.

Adult↗
PubMed1990

Echocardiographic assessment of the left ventricle of endurance athletes just before and after exercise.

Fourteen normal subjects and 10 marathon runners were studied using postexercise echocardiography to assess left ventricular (LV) wall thickness, afterload and systolic performance. Cuff systolic blood pressures and M-mode echocardiographic recordings were obtained in the supine position before and within 2 minutes of termination of maximal treadmill exercise. Both groups had increased LV dimensional shortening (% fractional shortening) and stroke volume after exercise, although runners had larger increases compared to untrained normal subjects (p less than 0.05). Preload, as estimated by LV end-diastolic dimension, was greater in runners compared to normal subjects at rest (52 vs 48 mm, p less than 0.05). However, preload did not change after exercise in either group. Afterload, estimated by LV end-systolic wall stress, decreased after exercise in both groups; however, runners had lower afterload at rest and immediately after exercise compared to normal subjects (p less than 0.05). The runners' greater LV end-systolic wall thickness appears to account for their lower afterload. Data indicate that marathon runners have lower afterload at rest and greater decrease in afterload after maximal exercise, compared to untrained normal subjects.

Adult↗
PubMed1990

Dietary factors and risk of pancreatic cancer: results of a Canadian population-based case-control study.

Dietary information from a case-control study of pancreatic cancer conducted in Metropolitan Toronto between 1983 and 1986 is reported. A total of 249 cases and 505 population-based controls completed quantitative diet histories from which total caloric intake and the intake of a number of nutrients were estimated. A positive association with total caloric intake was observed with a relative risk of 2.39, 95% confidence interval 1.18-4.83 (highest versus lowest quartile), due primarily to the intake of carbohydrates. Inverse associations were seen with fibre from fruit, vegetable and cereal sources, with a relative of risk of 0.42, 0.22-0.78 (highest versus lowest quartile), for total fibre intake.

Age Factors↗
PubMed1990

Dietary factors and risk of lung cancer: results from a case-control study, Toronto, 1981-1985.

Associations between dietary factors and risk of lung cancer are reported from a study of 839 cases and 772 population-based controls interviewed in metropolitan Toronto between 1981 and 1985. Increased consumption of vegetables is associated with a decreased relative risk of 0.60 (95% confidence limits = 0.40 to 0.88) for those in the highest compared with the lowest quartile. Cholesterol intake is associated with increased risk, but this is restricted to those in the highest quartile for whom the relative risk is 1.58 (95% confidence limits = 1.05 to 2.38) compared with those in the lowest quartile. The results of this study suggest that dietary factors may affect the risk of lung cancer, but identification of the specific constituents involved will require further research.

Adult↗
PubMed1990

The role of the reference radiologist. Estimates of inter-observer agreement and potential delay in cancer detection in the national breast screening study.

The Canadian National Breast Screening Study (NBSS) is a randomized controlled trial to assess the effect of screening on breast cancer mortality. The NBSS designated a single reference radiologist who blindly reviewed over the course of the study 5200 randomly selected two-view mammographic examinations of women not known to have breast cancer. He also reviewed 575 screening-detected breast cancer (SBC) cases and 102 interval breast cancer (IBC) cases. All cancers were histologically proven. As a result of the reviews, comments on inter-observer agreement, interpretation, and technical quality were conveyed on an ongoing basis to radiologists appointed to 15 NBSS screening centers. Agreement of the reference radiologist with center radiologists was better for breast cancer cases (kappa = 0.511, P less than .002) than for those not known to have breast cancer (kappa = 0.307, P less than .002). Observer error and technical problems led to delayed detection in 22% of SBCs and 35% of IBCs. Another 11% of SBCs and 58% of IBCs were probably mammographically occult. No similarly comprehensive review of mammography during a screening program has been published. Suggestions arising from the NBSS review were sometimes resisted by center radiologists. Measures are suggested which might facilitate acceptance of recommendations arising from audit mechanisms in mammography screening programs, thereby enhancing opportunities for mammographic excellence.

Breast Neoplasms↗
PubMed1990

Psychopathology among cocaine abusers entering treatment.

A number of different indicators of psychopathology were assessed in this study of 76 cocaine and crack abusers who entered outpatient treatment in New York City between June and December 1987. The majority (75%) had used cocaine for 4 years or more, and the majority (62%) spent over one thousand dollars a month on cocaine in the 6 months before entry into treatment. Forty-seven percent of the sample were found to be clinically depressed. Phobic disorders were the only other axis I diagnoses found in addition to depression, and all persons who were found to have phobic disorders also were diagnosed as having some form of depressive disorder. The four most common axis II diagnoses were antisocial personality (21%), passive-aggressive (21%), borderline (18%) and self-defeating (18%). Subjects were classified as falling into one of the following three categories of a newly developed "psychopathology classification": a) no diagnosed psychopathology except substance abuse or dependency; b) one or more axis II diagnoses, but no axis I diagnoses except for substance abuse or dependency; c) at least one axis I diagnosis in addition to drug disorders whether or not accompanied by an axis II diagnosis. Mean scores on subscales and total score on the SCL-90, as well as total score on the Beck Depression Inventory, were ordered by category of the classification scheme, with those having no diagnosed psychopathology except substance abuse having the lowest score and persons in the third category having the highest score.(ABSTRACT TRUNCATED AT 250 WORDS)

Cocaine↗
PubMed1990

Canadian National Breast Screening Study: assessment of technical quality by external review.

Mammograms from the Canadian National Breast Screening Study (NBSS) were reviewed by three external experts to provide an objective evaluation of their technical quality, to establish a model for auditing mammograms in a screening program, and to assess whether NBSS mammograms improved over time. The sample reviewed included 10 randomly chosen mammograms from each of 15 screening centers for each calendar year of their operation between 1980 and 1987. All 830 mammograms were reviewed on two consecutive days in randomized sequence by each reader, and rated 0-3 for each of four criteria including positioning and image quality, with a total possible score of 0-12. Although the mammograms were not in temporal sequence when reviewed, the scores assigned by each reader were significantly higher for mammograms dating from later years. Subjects' ages at entry (40-49 vs 50-59 years) did not affect the score. The largest increase in scores was associated with a 1985 protocol change in which mediolateral oblique positioning replaced straight mediolateral positioning. This study reinforces the importance of monitoring technical quality in screening programs and establishes that the NBSS benefited from technical improvements during its operation. A retrospective review of NBSS mammography by three external reviewers confirmed that technical quality improved from 1980 to 1987. This improvement was associated with improved technology (film, processing, and units) and with the quality assurance programs operating during the NBSS, which identified problems and offered remedies.

Adult↗
PubMed1990

Diet and cancer. A review.

Diet is one of the major causes of cancer. The epidemiologic data on which this conclusion is based has been derived from analytic epidemiologic studies, buttressed by descriptive (ecologic) epidemiology and studies in experimental animals. Although the evidence is not entirely consistent, high dietary fat intake appears to be a major cause of breast cancer, and more consistently, of colorectal cancer, and probably prostate cancer as well. Obesity is an important cause of endometrial cancer, and increases the risk of breast cancer in postmenopausal women, though increasingly there is evidence that suggests that obesity is protective for breast cancer in premenopausal women. There is inconsistent evidence that dietary fibre is protective for colorectal cancer, though good evidence that vegetable consumption is protective. Several studies have pointed to a protective effect of betacarotene for lung cancer, but betacarotene may be acting as an indicator of other protective factors in diet. Recommendations for dietary modification, congruent with recommendations for the prevention of cardiovascular and other chronic diseases, are now appropriate.

Alcohol Drinking↗
PubMed1989

Mortality from breast cancer after irradiation during fluoroscopic examinations in patients being treated for tuberculosis.

The increasing use of mammography to screen asymptomatic women makes it important to know the risk of breast cancer associated with exposure to low levels of ionizing radiation. We examined the mortality from breast cancer in a cohort of 31,710 women who had been treated for tuberculosis at Canadian sanatoriums between 1930 and 1952. A substantial proportion (26.4 percent) had received radiation doses to the breast of 10 cGy or more from repeated fluoroscopic examinations during therapeutic pneumothoraxes. Women exposed to greater than or equal to 10 cGy of radiation had a relative risk of death from breast cancer of 1.36, as compared with those exposed to less than 10 cGy (95 percent confidence interval, 1.11 to 1.67; P = 0.001). The data were most consistent with a linear dose-response relation. The risk was greatest among women who had been exposed to radiation when they were between 10 and 14 years of age; they had a relative risk of 4.5 per gray, and an additive risk of 6.1 per 10(4) person-years per gray. With increasing age at first exposure, there was substantially less excess risk, and the radiation effect appeared to peak approximately 25 to 34 years after the first exposure. Our additive model for lifetime risk predicts that exposure to 1 cGy at the age of 40 increases the number of deaths from breast cancer by 42 per million women. We conclude that the risk of breast cancer associated with radiation decreases sharply with increasing age at exposure and that even a small benefit to women of screening mammography would outweigh any possible risk of radiation-induced breast cancer.

Adolescent↗