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Biomedical subjects

K Mead

Publications and source records attributed to K Mead.

10 recordsLinked to original sources

The inner dynein arms I2 interact with a "dynein regulatory complex" in Chlamydomonas flagella.

We provide indirect evidence that six axonemal proteins here referred to as "dynein regulatory complex" (drc) are located in close proximity with the inner dynein arms I2 and I3. Subsets of drc subunits are missing from five second-site suppressors, pf2, pf3, suppf3, suppf4, and suppf5, that restore flagellar motility but not radial spoke structure of radial spoke mutants. The absence of drc components is correlated with a deficiency of all four heavy chains of inner arms I2 and I3 from axonemes of suppressors pf2, pf3, suppf3, and suppf5. Similarly, inner arm subunits actin, p28, and caltractin/centrin, or subsets of them, are deficient in pf2, pf3, and suppf5. Recombinant strains carrying one of the mutations pf2, pf3, or suppf5 and the inner arm mutation ida4 are more defective for I2 inner arm heavy chains than the parent strains. This evidence indicates that at least one subunit of the drc affects the assembly of and interacts with the inner arms I2.

Actins

Effects of dosing intervals on the development of tolerance to high dose transdermal nitroglycerin.

To investigate the antiischemic efficacy and development of tolerance to transdermal nitroglycerin, 14 patients with chronic, stable angina pectoris were studied using continuous ambulatory electrocardiographic monitoring. Patients demonstrated initial hemodynamic responsiveness to sublingual nitroglycerin and were titrated to a maximally tolerated dose of 30 to 60 mg/24 hours (52 +/- 5 mg). Two crossover phases were use in a randomized, double-blind, placebo-controlled manner: continuous nitroglycerin therapy (patches containing active drug worn for 24 hours) and intermittent nitroglycerin therapy (12-hour active drug followed by a 12-hour nitrate-free period). There were no differences in frequency or duration of ischemic episodes between the placebo days of each phase. A significant effect in frequency of episodes was observed between placebo and treatment days of continuous therapy (p less than 0.05). Nonsignificant reductions in frequency and duration of ischemic episodes also occurred during intermittent therapy. The major antiischemic effect of transdermal nitroglycerin therapy occurred during the first day of treatment but was lost by 48 hours. Reductions in frequency and duration of ischemic episodes (p less than 0.05) were present on day 1 of continuous therapy but ischemic episodes returned to placebo levels by day 2, suggesting the development of tolerance. Intermittent therapy did not prevent the development of tolerance on day 2 of treatment. The results demonstrate that the use of high doses of transdermal nitroglycerin in patients with chronic, stable coronary artery disease produced a beneficial reduction in the frequency and duration of ischemia. However, the antiischemic benefit was lost between 24 nd 48 hours after the onset of continuous and intermittent therapy, presumably due to tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous

Effect of smoking on the activity of ischemic heart disease.

Cigarette smoking has been causally linked to coronary heart disease. To investigate the effect of smoking on the activity of ischemic heart disease, 65 patients with chronic stable manifestations of coronary disease and a positive exercise tolerance test underwent continuous ambulatory monitoring to quantify the amount of ischemic ST segment depression during daily life. Twenty-four smokers were compared with 41 nonsmokers for frequency and duration of electrocardiographic signs of ischemia during 24 hours. A total of 4,968 hours of ambulatory monitoring were analyzed. The frequency of episodes was three times as often (median) and the duration of ischemia was 12 times longer (median duration, 24 vs 2 min/24 h) in smokers than nonsmokers. This finding remained statistically significant when a number of potentially confounding factors were controlled by means of logistic regression. This study shows that patients with coronary artery disease who smoke have significantly and substantially more active myocardial ischemia during daily life than patients who do not.

Activities of Daily Living

Frequency of ST-segment depression produced by mental stress in stable angina pectoris from coronary artery disease.

Physical exertion is a well-documented trigger of transient myocardial ischemia in patients with coronary disease. More recently, studies have shown that mental stress may also be a cause of myocardial ischemia. The purpose of this study was to examine the relationship of physical activities and perceived mental states to myocardial ischemia while patients were going about their normal daily activities. Twenty-eight patients with documented coronary artery disease underwent ambulatory monitoring of the electrocardiogram. Physical activity and perceived mental status were recorded by patients in a diary which was then graded according to intensity of the activity. Analyses of the continuous electrocardiographic recordings were done separately from the analysis of the diaries. The time of each episode of ischemia, the duration of each episode in minutes and the number of episodes in each 24-hour period were calculated. A total of 372 episodes of ST-segment depression occurred in 912 hours of monitoring. Ischemic events occurring during usual physical and usual mental activities were most frequent (36%). Twenty-six percent of ischemic episodes occurred during increased physical activity, but usual mental activities. Interestingly, 22% of the ischemic events occurred at high levels of mental stress, but low physical activity. Ten percent of episodes occurred during sleep. Although the majority of events occurred during usual daily activities, when duration of ischemia was normalized for time spent in each category, increasing physical or mental activity was associated with an increasing duration of ischemia per unit (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living

Variability of transient myocardial ischemia in ambulatory patients with coronary artery disease.

Ambulatory electrocardiographic (ECG) monitoring of patients with chronic stable angina has demonstrated frequent and prolonged episodes of ischemic ST segment depression, but its clinical use requires an understanding of the components and extent of variability. Therefore, variations in the frequency and duration of episodes of ST segment depression were evaluated with ambulatory ECG recording at daily, weekly, and monthly intervals in 42 patients with chronic stable angina and known coronary artery disease. Data were analyzed with a nested analysis of variance design that yields estimates of variance components. From the estimates of variance components, power calculations and minimum significant percent reductions in frequency and duration of ischemia were derived. During 4,656 hours of ambulatory ECG monitoring, 1,262 episodes of ischemic ST segment depression were detected. The frequency of episodes was 6.3 +/- 0.45/24 hr (mean +/- SEM), and the duration of episodes was 18.3 +/- 2.8/24 hr. Because of variability over time, the ability to detect significant changes was dependent upon the number of subjects, length of monitoring period, and intervals between monitoring periods. In a clinical trial, for example, a sample size of 25 patients monitored for 48 hours with 1 week between control and test conditions would require a 65% reduction in frequency, whereas a sample size of 50 patients monitored under similar conditions would require a 46% reduction in frequency, to attribute the change with 90% power to a therapeutic intervention rather than to a spontaneous variation. When monitoring a single patient for 48 hours with 1 week or 1 month between control and repeat monitoring sessions, episodes of ischemic ST depression must be eliminated to detect significant therapeutic changes in ischemic activity at the 95% confidence level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Prognostic importance of myocardial ischemia detected by ambulatory monitoring in patients with stable coronary artery disease.

To assess the relations of electrocardiographic measures of ischemia with the development of adverse coronary events, 86 patients with stable coronary artery disease and positive exercise tests for myocardial ischemia underwent ambulatory monitoring of the electrocardiogram. Monitoring was performed after withdrawal of antianginal medications, and prospective follow-up was obtained on routine medical care as prescribed by physicians who were unaware of monitor results. Forty-nine patients (57%) had a total of 426 episodes of ST segment depression; only 60 episodes (14%) were associated with symptoms of angina or an equivalent. During a mean follow-up of 12.5 +/- 7.5 months, there were two cardiac deaths, four myocardial infarctions, four hospitalizations for unstable angina, and 11 revascularization procedures required for new or worsening symptoms in 15 patients. All but one of these events (a hospitalization for unstable angina) occurred in the group of patients with ST segment depression on monitoring (p = 0.003). In multivariate analysis controlling for age, sex, and clinical descriptions of angina, the presence of ischemia on ambulatory monitoring was a significant predictor of outcome, while exercise test characteristics were not. Therefore, ischemia detected by ambulatory monitoring was common in patients with stable symptoms of coronary artery disease, and its presence identified a high-risk group for the development of subsequent unfavorable outcomes while on routine medical therapies.

Adult

Ambulatory monitoring of the digitized electrocardiogram for detection and early warning of transient myocardial ischemia in angina pectoris.

Patients with coronary artery disease have frequent asymptomatic episodes of ischemic ST-segment depression. A new solid-state recorder that analyzes the digitized electrocardiogram (ECG) in real time has been tested for accuracy in detection and quantitation of these events by comparison with a direct ECG during exercise testing and a frequency-modulated recorder during ambulatory monitoring. The device can also be programmed to produce a tone at the onset of ischemic ST-segment depression, and this tone is used to initiate self-administration of nitroglycerin in an attempt to control myocardial ischemic events. The solid-state recorder demonstrated adequate sensitivity and specificity during exercise (100% and 92%, respectively) for detection and quantitation of episodes of ischemic ST-segment depression. In addition, Monitor One accurately measured the duration of ischemic events during exercise testing (r = 0.95, p = 0.001) and the number (r = 0.92, p = 0.001) and duration (r = 0.97, p = 0.001) of ischemic events during ambulatory monitoring. When the audible tone was used to initiate use of nitroglycerin, the duration of episodes of ischemic ST-segment depression was reduced from 105 +/- 74 min/24 hours to 58 +/- 49 min/24 hours (p = 0.02). Thus, a solid-state ECG recorder capable of long-term monitoring appears to accurately detect and quantify episodes of ischemic ST-segment depression in patients with coronary artery disease. Also, patients can interact with an audible tone to key self-administration of therapy in an attempt to control asymptomatic episodes of transient myocardial ischemia.

Adult

Tetanus and diphtheria immunity in urban Minnesota adults.

Tetanus and diphtheria antitoxin levels were measured in 183 urban adults, using a hemagglutination technique. Protective levels (greater than 0.01 unit/mL) of tetanus antitoxin were present in more than 85% of sera from all subjects under 40 years of age and from men between 40 and 59 years old. A minority of women (36%) between 40 and 59 years of age, and of men (41%) and women (29%) over 60 years of age, were protected. Less than one quarter of the study group had protective levels (greater than 0.01 unit/mL) of diphtheria antitoxin. The results of the study suggest that a minority of middle-aged women and older adults have been appropriately immunized against diphtheria and tetanus.

Adolescent

An outbreak of infections caused by strains of Staphylococcus aureus resistant to methicillin and aminoglycosides. I. Clinical studies.

In a 22-month period, strains of Staphylococcus aureus resistant to methicillin and multiple aminoglycosides, (designated MARS) were recovered from 108 inpatients with nosocomial infections at a hospital in the midwestern United States. Sixty-six of these patients were staying in a burn unit, and 42 were on other hospital wards. Among the patients with burns, MARS were recovered from the burn wounds of 64%; 32% of the patients with burns had MARS bacteremia. The patients without burns were age-matched with patients with nosocomial infections caused by antibiotic-susceptible strains of S. aureus. Patients from whom MARS were isolated had a longer mean hospital stay (79.6 days vs. 36.9 days; P less than 0.01), developed infection later (26.5 days vs. 13.5 days after admission; P less than 0.01), and had received antibiotic therapy before infection more often (81% vs. 38% of patients; P less than 0.01) than patients in the comparative population. Types of infection and incidences of death and bacteremia were similar in the two groups. Antibiotic-resistant strains of S. aureus may cause serious infections and significant mortality.

Aminoglycosides