High dose ascorbate supplementation fails to affect plasma homocyst(e)ine levels in patients with coronary heart disease.

Pharmacologic doses of folate, in the absence of clinical folate deficiency, can reduce plasma levels of the putatively atherothrombotic amino acid, homocysteine (H(e)). Data suggesting that H(e) may accumulate in experimental scurvy prompted us to explore the efficacy of high dose ascorbate supplementation as a H(e)-lowering treatment, in the absence of clinical ascorbate deficiency. A randomized, placebo-controlled trial of 12 weeks of high dose (4.5 g/day) ascorbate supplementation was completed by 44 patients with established coronary heart disease. No significant change in mean fasting total plasma H(e) levels was demonstrable despite a marked increase in mean fasting plasma ascorbate levels amongst those patients randomized to active treatment. Ascorbate supplementation to prevent the development of fasting hyperhomocysteinemia may only be relevant at scorbutic levels of plasma ascorbate.

Pharmacologic treatment of diabetes in long-term care.

The majority of patients with diabetes are elderly, but little is known about their disease management. This study evaluates the prevalence and correlates of treatment of elderly diabetics residing in long-term care. We performed a retrospective, cross-sectional study of 75,829 elderly diabetics residing in nursing homes from 1992 to 1996. Nearly half (47%) of the residents received no antidiabetic medications. Independent predictors not receiving antidiabetic medications included age, race, impaired physical ability, and impaired cognitive function. Although the absence of resident's blood glucose or glycosylated hemoglobin (HbA1c) values prevents us from passing judgment about the adequacy of diabetic care, further research is needed to understand why some residents do not receive antidiabetic medications in the long-term care setting.

Evoked potentials in suspected multiple sclerosis: diagnostic value and prediction of clinical course.

Pattern visual, somatosensory and brainstem auditory evoked potentials (EPs) of 14 patients with definite multiple sclerosis, 222 patients suspected of having multiple sclerosis, 26 patients with isolated optic neuritis and 40 patients with a chronic not diagnosed neurologic disorder, were compared with their clinical diagnoses on 2 1/2-year follow-up. In the MS suspects, an EP abnormality demonstrating a clinically silent lesion in any modality (65 patients) was associated with a 71% chance of clinical deterioration (48% chance of definite MS within the follow-up period). Normal EPs (121 patients) were associated with a 16% chance of deterioration (4% chance of definite MS). EPs in patients in whom the only abnormalities confirmed known lesions (36 patients) did not predict follow-up status. Visual EPs demonstrated clinically silent lesions more frequently than somatosensory and auditory EPs (22%, 12% and 5% of patients). Only one of the patients with optic neuritis and 3 of the chronic not diagnosed group had EPs demonstrating clinically silent lesions. CSF and NMR studies also correlated with follow-up in subseries of the patients.

Angiotensin-converting enzyme inhibitor-induced cough.

A 65-year-old woman started taking enalapril 2.5 mg daily for hypertension. Twelve days later she complained of a persistent, dry cough. Due to the coughing and a preexisting cystocele, she developed stress incontinence and a marked decline in her functional status. The coughing and incontinence resolved with the discontinuation of enalapril. During a subsequent hospitalization the patient received captopril 6.25 mg twice daily for congestive heart failure. Within 24 hours the dry cough recurred. It resolved with the discontinuation of the drug. Cough is a symptom that is generally not recognized as a drug side effect. However, increasing numbers of case reports document angiotensin-converting enzyme inhibitor-induced cough. Although the actual frequency and mechanism are currently unknown, the dry cough typically begins early in the course of therapy. It may be specific to this pharmacologic class rather than to one individual agent. Age and sex may be contributing factors. While cough has been considered a minor side effect, unnecessary hospitalizations and inappropriate treatments may easily result. Even minor adverse reactions may have an impact on a patient's quality of life.

Correlates of oral contraceptive use in two New England communities: 1981-1993.

This study compared the sociodemographic and cardiovascular correlates of oral contraceptive users and nonusers between 1981 and 1993. We also sought to determine changes in the prevalence of oral contraceptive use among older premenopausal women. Using data from six biennial cross-sectional household surveys in a population-based sample of two New England communities, 5239 women between ages 18 and 45 years were identified. Women using oral contraceptives were 5 years younger and better educated than nonusers, and users more frequently reported a per capita income above the median for the survey population than nonusers. Users were more likely to report smoking and have a lower body mass index than nonusers. Little use of oral contraceptives was detected among women ages 40-45 years despite changes in FDA recommendations about their use and increasing evidence of their noncontraceptive benefits in healthy older nonsmoking women.

Predictors of future antihypertensive use in patients with mildly elevated blood pressure.

We prospectively identified predictors of future antihypertensive use in untreated persons age 18-65 years who had elevated diastolic blood pressures of 90-104 mm Hg or systolic blood pressures of at least 140 mm Hg. Data were derived from two independent cohorts completing household surveys conducted in 1981-1984 and 8 years later, as part of the Pawtucket Heart Health Program. Demographics, self-reported health behaviors and beliefs, and physiologic measurements were obtained. Drug use was determined through structured interviews. Analysis of covariance and logistic regression were performed. In the 492 subjects, independent baseline predictors of future antihypertensive use (p < 0.05) included female gender, older age, diastolic blood pressure elevation, self-perceived high blood pressure, and self-reported salt limitation. Antihypertensive use for previously untreated mild hypertension is diverse. Older women with diastolic elevations who are health conscious are most likely to be treated.

Drug therapy and prevalence of erectile dysfunction in the Massachusetts Male Aging Study cohort.

STUDY OBJECTIVE: To examine the association of commonly used drugs with erectile dysfunction (ED) at two time points. DESIGN: Population-based, cross-sectional, survey analysis. PARTICIPANTS: Randomly selected cohort of men in the Massachusetts Male Aging Study (MMAS) that included 1476 men for the baseline (1987-1989) and 922 for the follow-up (1995-1997) analyses. INTERVENTION: Crude associations between specific drug categories were examined with chi2 statistics. Logistic regression analysis was used to separate the effect of drugs from the influence of heart disease, hypertension, untreated diabetes, or depressive symptoms. MEASUREMENTS AND MAIN RESULTS: In the MMAS, medical history, current drug use, and erectile function status were ascertained with in-home interviews. In unadjusted analyses, thiazide and nonthiazide diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, benzodiazepines, digitalis, nitrates, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, and histamine2 receptor antagonists were associated with prevalent ED. Adjustment for comorbidities and health behaviors attenuated these associations, with only nonthiazide diuretics and benzodiazepines remaining statistically significant. CONCLUSION: Several common drugs may increase prevalence of ED; however, additional data from larger populations are needed to determine whether these associations are independent of underlying health conditions and to explore the effects of dosage and duration of use.

The drug data base of the Pawtucket Heart Health Program: development and description.

Pharmacoepidemiology has become an important tool for identifying patterns of drug use and adverse drug reactions in the general population. Drug data bases derived from population-based samples have been particularly useful in addressing questions such as adherence to national guidelines for the treatment of chronic diseases. As part of the Pawtucket Heart Health Program, a continuing community-based research and demonstration project, detailed information regarding the use of drugs among the general population of two southeastern New England cities was collected using cross-sectional and longitudinal methodologies.

Is antidepressant use changing? Prevalence and clinical correlates in two New England communities.

We attempted to determine whether the prevalence of antidepressant use had increased in population-based samples between 1981 and 1993, and compared the characteristics of antidepressant users and nonusers. Data were derived from six biennial, random sample, cross-sectional household surveys conducted between 1981 and 1993 in two southeastern New England communities. For each survey, point prevalence estimates were determined for the major antidepressant categories. Antidepressant users were most likely to be women, slightly older, and less likely to be employed than nonusers (p < 0.0001). Comorbid conditions and concurrent drug therapy were present more frequently among users. The overall prevalence of antidepressant use per 1000 population increased from 7.8 (95% confidence interval 4.3, 11.3) in 1981-1982 to 31.4 (95% CI 23.9, 38.9) in 1992-1993, especially among women and respondents between ages 40 and 59 years.

Changing trends in antihypertensive therapy in two New England communities during the 1980s.

The prevalence rates and correlates of antihypertensive drug use among individuals with hypertension were determined using data derived from five biennial population-based surveys conducted between 1981 and 1990 in two New England communities. Point prevalence estimates were determined for nine categories of antihypertensive agents at five time points, and were analyzed by age and sex using multiple logistic regression. In the first cross-sectional survey, the prevalence of use per 1000 individuals with hypertension was 235.4 for diuretics, 57.1 for beta-blockers, 65.5 for combination products, 29.2 for central alpha-agonists, 2.8 for peripheral alpha-antagonists, and 8.4 each for adrenergic blockers and direct vasodilators. The prevalence rates for calcium channel blockers and angiotensin-converting enzyme inhibitors increased sharply between the third and fourth survey cycles. Significant age- and sex-related differences in antihypertensive use were detected.

The effect of high-dose ascorbate supplementation on plasma lipoprotein(a) levels in patients with premature coronary heart disease.

STUDY OBJECTIVE: To determine the efficacy of high-dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinic. PATIENTS: Forty-four patients with documented premature CHD, defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years. INTERVENTIONS: Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks. MEASUREMENTS AND MAIN RESULTS: High-dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p < 0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p = 0.39) in a model that included treatment group assignment, and baseline Lp(a) levels. CONCLUSIONS: Our findings do not support a clinically important lowering effect of high-dose ascorbate on plasma Lp(a) in patients with premature CHD.

Measurement of central somatosensory conduction time in patients undergoing cardiopulmonary bypass: an index of neurologic function.

It is feasible to monitor somatosensory evoked potentials and central somatosensory conduction times during open heart surgery and cardiopulmonary bypass with moderate or profound hypothermia. Central conduction times are reproducible, have acceptably low interpatient and intrapatient variability, and are not significantly affected by fentanyl-induced anesthesia. There is a predictable logarithmic relationship between central conduction times and temperature with the central conduction time increasing by 6.6 percent for a 1 degree C decrease in temperature. These data indicate that somatosensory conduction times may be a useful index of central nervous system integrity during open heart surgery that utilizes cardiopulmonary bypass and hypothermia.

Bias functions and operating characteristics of rats discriminating auditory stimuli.

Rats were trained to discriminate between two bursts of random noise that differed in intensity. In a two-lever, discrete-trial procedure, correct responses were reinforced with brain stimulation, and incorrect responses produced timeout. Responding was studied as a function of the decibel difference between the stimuli, the probabilities of presenting the stimuli, the relative duration of timeout consequent upon the two types of incorrect responses, and the absolute duration of timeout consequent upon incorrect responses. The results showed that the distribution of responses between the two levers depended upon the stimulus probabilities, but were independent of either the absolute or relative durations of timeout. When the stimulus probabilities were varied, the response probabilities did not match the stimulus probabilities; when the relative durations of timeout were varied, the animals did not obtain the maximum rate of reinforcement per unit time. Instead, the animals distributed their responses so as to obtain the maximum number of reinforcements at each level of discrimination. In addition, the level of discrimination increased as a function of the decibel difference between the stimuli.

Cerebral monitoring by compressed spectral array.

Application of a frequency analysis technique, the compressed spectral array (CSA), permits the display of cerebral activity recorded by the electroencephalogram (EEG) over long periods of time in a succinct, graphic manner. This report is a description of a system which is being developed to investigate long-term monitoring of the EEGs of critically ill patients. The computer-based methodology which has been used to implement this system is described, with illustrations of CSA-transformed EEGs.

Applying quality of life data in practice. Considerations for antihypertensive therapy.

Quality of life issues have become increasingly important in tailoring antihypertensive therapy to individual patients. The application of quality of life data to the practice setting is frequently difficult, however. The effective use of this information requires an understanding of its definition and measurement, as well as of study methods. Quality of life findings may be specific to particular disease states, patient populations, and pharmacologic agents. The addition of hydrochlorothiazide to concurrent methyldopa, propranolol, or captopril therapy has been reported to reduce patients' overall sense of well-being. beta-Adrenergic blockers may exert either positive or negative effects on quality of life. Angiotensin-converting enzyme (ACE) inhibitors may have positive effects on quality of life; however, the cost of therapy is an important consideration. Information on calcium antagonists is limited. The findings of the Treatment of Mild Hypertension Study (TOMHS) may eventually provide comparative quality of life data on the four first-line antihypertensive therapies.

Clinical pharmacists in family practice residency programs.

A project was undertaken to determine the number, specific activities, and demographics of clinical pharmacists directly involved with residency programs in family practice. A survey was mailed to the directors of all 381 family practice residencies, with a request either to forward it to the participating pharmacist or to return the survey if a pharmacist did not directly participate in the teaching program. With two mailings, responses were received from 85.3% of the residencies, with 80 pharmacists completing surveys. While the involvement of pharmacists in family practice residencies was similar to that reported in a survey 9 years ago, academic appointments and funding, in whole or in part by a college of medicine, had increased. This increased involvement may represent an acknowledgment by medical educators in family practice of the value of pharmacists participating in residency programs.

Oral contraceptives in the immediate postpartum period.

PIP: Although there is a critical need for effective contraception in the immediate postpartum period for women who are not breastfeeding, this need must be balanced against the inherent risks. The most effective form of contraceptive protection--oral contraceptives (OCs)--can present an increased risk of thromboembolism in the period after delivery. The thrombotic changes associated with pregnancy, and the statistics and vascular damage following a delivery, can combine to create greater potential for thromboembolism after delivery than during pregnancy. Reported here is the case of a 21-year-old woman who, 4 weeks postpartum, developed pain and swelling in the right lower calf and mottled discoloration extending from the proximal thigh to the toes. A diagnosis of deep venous thrombosis was made and heparin was administered. In the hospital, the patient experienced pleuritic chest pain and diaphoresis. A ventilation-perfusion scan indicated a pulmonary embolism. 1 week after delivery, the patient had initiated use of Triphasil. Although this woman had other risk factors (obesity, light cigarette smoking, and a sedentary life-style), OC use in the immediate postpartum period may have been the final factor precipitating the thromboembolic event. It is recommended that OC use should be delayed until at least 2 weeks postpartum in women without other risk factors for thromboembolism and until 4-6 weeks postpartum in those with such factors.^ieng

Prevalence of hypertension, dyslipidemia, and dyslipidemic hypertension.

BACKGROUND: It has been proposed that dyslipidemic hypertension is part of a distinct metabolic syndrome related to insulin resistance. This paper describes the prevalence and cross-sectional relations of dyslipidemic hypertension in a population-based sample of men and women. METHODS: In two southeastern New England communities, 11,199 randomly selected participants were evaluated as part of a cross-sectional surveillance program of coronary heart disease risk factors between 1981 and 1990. RESULTS: The frequency of dyslipidemia was 38% and of hypertension was 26.5%; the conjoint frequency (dyslipidemic hypertension) was 15.0%, which is 1.49 times the expected value if the two diseases were independent P < .05). Using a discrete multivariate model, dyslipidemia and hypertension were associated with sex, obesity, and diabetes mellitus. The excess association of dyslipidemic hypertension, compared with individual effects of dyslipidemia and hypertension, was not related to these factors. CONCLUSIONS: This study suggests that dyslipidemic hypertension is common but may not be a unique entity associated with a distinct metabolic syndrome.