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Biomedical subjects

S Slagle

Publications and source records attributed to S Slagle.

17 recordsLinked to original sources

A titrated morphine analgesic regimen comparing substance users and non-users with AIDS-related pain.

To compare morphine dosage and effectiveness in AIDS patients with/without prior substance use and pain, a prospective, open-label case series lasting 3-18 days was conducted in both outpatients and inpatients at major pain service teaching programs. Forty-four patients, 13 with prior drug use history, who had pain associated with HIV infection or its treatment were administered sustained-release morphine (SRM) every 12 hours. The dose was titrated to pain relief for a period of > or =3 consecutive days (associated with < or =2 immediate-release morphine tablets per 24 hours), or until the patient discontinued from the study or completed 18 study days. Forty-four patients were enrolled (13 with a prior drug use history). Forty were evaluable for an intent-to-treat analgesia, including 11 with a drug use history. Twenty-four (6 users) completed this study. Former users and non-users were similar in demographics, baseline pain intensities, causes of pain, discontinuation, quality of life, and acceptability of therapy. Pain intensity decreased by > or =50% in both groups (P < or = 0.0001). To identify a stable dose, the dose of SRM more than doubled in former users and rose by 31% in non-users (mean final dose 177.4 mg and 84.9 mg, respectively) (P = 0.0018). Immediate-release morphine decreased in both; former users required more (P = 0.0006). These data suggest the utility of morphine for AIDS-related pain. Patients with a prior drug use history benefited but required substantially more morphine.

Acquired Immunodeficiency Syndrome↗

Sustained-release morphine sulfate in the management of pain associated with acquired immune deficiency syndrome.

Sustained-release morphine (SRM) was studied in patients with acquired immune deficiency syndrome (AIDS)-related chronic pain. Outpatients and inpatients with AIDS-related pain were studied for 3-18 days in an open-label prospective survey. Patients were stratified according to prior opioid analgesic use for the purposes of initiating and titrating SRM, which was administered at a 12-hr interval. Immediate-release morphine (IRM) was offered every 2 hr as needed for supplemental analgesia at one-quarter to one-third of the 12-hourly SRM dose. Pain intensity (PI), quality of life (QL), acceptability of therapy (AT), side effects, safety, and morphine usage were evaluated. Of 44 patients enrolled, 40 (91%) were evaluable for intent-to-treat analysis, and 24 (55%) completed the study. PI decreased by 50% (from severe to mild-moderate) in the intent-to-treat patients and by 65% (from severe to mild) in the completed patients. QL was fair to good in 80% and poor in 20% of both groups. AT was good to excellent in 78% of the intent-to-treat and in 96% of the completed patients. Of 61 adverse events reported, 61% required intervention, and 92% were resolved. Total morphine dose remained stable while IRM dosage and frequency of use significantly decreased with escalation of the SRM dose. A significant reduction in PI was achievable with SRM in a variety of painful conditions experienced by AIDS patients, with limited or manageable side effects in most. This study supports the usefulness of opioid analgesia for severe pain in AIDS.

Acquired Immunodeficiency Syndrome↗

A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis.

We found Cop 1 to be effective and relatively safe in a previous (exacerbating-remitting) clinical trial. This current trial involves 106 chronic-progressive patients. The major end point, confirmed progression of 1.0 or 1.5 units (depending on baseline disability) on the Kurtzke Expanded Disability Status Scale, was observed in nine (17.6%) treated and 14 (25.5%) control patients. The differences between the overall survival curves were not significant. Progression rates at 12 and 24 months were higher for the placebo group (p = 0.088) with 2-year probabilities of progressing of 20.4% for Cop 1 and 29.5% for placebo. We found a significant difference at 24 months between placebo and Cop 1 at one but not the other center. Two-year progression rates for two secondary end points, unconfirmed progression, and progression of 0.5 EDSS units, (p = 0.03) are significant.

Chronic Disease↗

The clinical use of nuclear exercise tests.

In the mid-1970s, after decades of clinical use, the utility of electrocardiographic exercise testing for the evaluation of patients with suspected ischemic heart disease was critically examined and questioned. Concurrent with this critique, two sophisticated, more expensive and powerful "nuclear" exercise tests were introduced sequentially for clinical use: myocardial perfusion imaging with thallium-201 and radionuclide ventriculography with technetium 99m. The published indications for the two tests are similar, and both have been shown to offer advantages over ECG stress testing in selected populations. However, few data are available regarding the comparative utility of thallium versus ventriculographic imaging. As part of a prospective study to assess the efficacy of cardiovascular nuclear medicine studies, we undertook the present analysis to assess the clinical evolution of these tests and to elucidate factors responsible for clinicians' choice for the often competing examinations. The study examined 213 consecutive patient referrals for thallium scintigraphy and 183 referrals for ventriculography, ranging from patients with no symptoms or highly non-specific chest pain syndromes (21% of referrals) to patients with proven coronary disease (28% of the referrals). Twenty-one percent of patients were referred to confirm the clinical impression that the patient did not have coronary disease, 40% to confirm its presence, and 37% to determine its severity. Analyses were undertaken to determine the factors that dictated a preference for thallium scintigraphy rather than ventriculography; only the physician's intent in testing and level of training were significant predictors for a particular nuclear test.

Coronary Disease↗

Clinical experience with COP-1 in multiple sclerosis.

COP-1 is one of a series of polypeptide preparations developed to stimulate myelin basic protein (MBP), a natural component of the myelin sheath. MBP in Freund's complete adjuvant induces experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). In saline, MBP suppresses EAE. This is the rationale for the use of COP-1 in MS.

Adult↗

A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis.

Cop 1 is a random polymer (molecular weight, 14,000 to 23,000) simulating myelin basic protein. It is synthesized by polymerizing L-alanine, L-glutamic acid, L-lysine, and L-tyrosine. It suppresses but does not induce experimental allergic encephalomyelitis, an animal model of multiple sclerosis. It is not toxic in animals. In a double-blind, randomized, placebo-controlled pilot trial, we studied 50 patients with the exacerbating-remitting form of multiple sclerosis, who self-injected either 20 mg of Cop 1 dissolved in 1 ml of saline or saline alone daily for two years. Six of 23 patients in the placebo group (26 percent) and 14 of 25 patients in the Cop 1 group (56 percent) had no exacerbations (P = 0.045). There were 62 exacerbations in the placebo group and 16 in the Cop 1 group, yielding two-year averages of 2.7 and 0.6 per patient, respectively. Among patients who were less disabled on entry (Kurtzke disability score, 0 to 2), there were 2.7 exacerbations in the placebo group and 0.3 in the Cop 1 group over two years. Among patients who were more affected (Kurtzke disability score, 3 to 6), there was an average of 2.7 exacerbations in the placebo group and 1.0 in the Cop 1 group. Over two years, less disabled patients taking Cop 1 improved an average of 0.5 Kurtzke units; those taking placebo worsened an average of 1.2 Kurtzke units. More disabled patients worsened by 0.3 (Cop 1 group) and 0.4 (placebo group) unit. Irritation at injection sites and rare, transient vasomotor responses were observed as side effects. These results suggest that Cop 1 may be beneficial in patients with the exacerbating-remitting form of multiple sclerosis, but we emphasize that the study is a preliminary one and our data require confirmation by a more extensive clinical trial.

Adult↗

Nuclear scans: a clinical decision making tool that reduces the need for cardiac catheterization.

We have assessed the impact of cardiovascular nuclear medicine studies (CVNMS) on physicians' decisions to send patients with suspected ischemic heart disease (N = 439) on to cardiac catheterization at three Bronx hospitals. A change in management plans with respect to catheterization was observed in 31% of cases. Catheterization rates were reduced by 25% among patients referred for resting studies and by 49% for exercise studies (thallium perfusion or exercise wall motion studies). Results of CVNMS had little impact on catheterization decisions for resting study patients (N = 192). Among exercise study patients (N = 247), those with normal results had a relative reduction in catheterization post-CVNMS of 82% vs 27% for patients with abnormal results (p less than 0.001). However, impact of exercise CVNMS test results on post-CVNMS catheterization rates obtained for men only; women with abnormal exercise study results were much less likely to undergo subsequent catheterization (7.7%) than men with abnormal results (41.9%), p less than 0.005, independent of age. The apparent discrepancy in referral for catheterization based on sex needs to be investigated further.

Adolescent↗

Chemoprevention of cervix cancer: Phase I-II: A feasibility study involving the topical vaginal administration of retinyl acetate gel.

A Phase I-II clinical trial has been conducted with a retinyl acetate (RA) gel applied cervicovaginally in women having a histopathologic lesion diagnosed as mild or moderate dysplasia. With informed consent, volunteer subjects were observed and followed with Pap smears and colposcopy in a standardized protocol involving a self-administered 7-day treatment course for three successive menstrual cycles. Varying dosages of RA including placebo, 3, 6, 9, and 18 mg per 6 g of an inert vehicle were employed. A total of 50 subjects were monitored for local and systemic side effects. No intolerable side effects or disturbing toxicity was reported or detected at any of these doses. With the 18-mg dosage, significant discomfort was reported by all women. Despite associated side effects and a considerable patient effort involved in carrying out the self-administration of the gel, a high level of compliance was achieved in this trial. It has been established that women will voluntarily participate in an intervention clinical trial to determine whether retinyl acetate is an alternative method of therapy of presumed precancerous lesions of the cervix. The analysis of the side effects of the gel at the various dosage concentrations favors the selection of the 9-mg dosage for a multicenter Phase III clinical trial to determine efficacy.

Colposcopy↗

Radionuclide ventriculographic responses to graded supine and upright exercise: critical role of the Frank-Starling mechanism at submaximal exercise.

To assess the influence of work load and posture on the response to exercise, 25 patients with coronary artery disease (CAD) and 17 normal subjects underwent graded supine and upright exercise radionuclide ventriculography. In both groups, end-diastolic counts increased with supine exercise (p less than 0.001). The ejection fraction and peak systolic pressure-end-systolic volume relation increased in normal subjects (p less than 0.02), but not in patients with CAD. At upright rest, end-diastolic counts decreased in both groups (p less than 0.001) and then increased with exercise (p less than 0.001). The increase in end-diastolic counts was most pronounced on the transition from upright rest to the 150-kpm work load and resulted in a significant increase in stroke counts (p less than 0.05) for both patients with CAD and normal subjects, without a measurable change in the ejection fraction or the peak systolic pressure-end-systolic volume relation. Later in exercise, end-diastolic counts plateaued, and the ejection fraction and the peak systolic pressure, end-systolic volume relation increased only among normal subjects. Thus, low-level upright exercise is highly dependent on the Starling mechanism in both normal subjects and patients with CAD, with enhanced contractility apparent only during more vigorous exercise in normal subjects.

Blood Pressure↗

Separation and quantitation of subclasses of human plasma high density lipoproteins by a simple precipitation procedure.

Studies in recent years have suggested that measurement of high density lipoprotein (HDL) subclasses may provide significant information beyond that provided by measurement of total HDL. However, conventional methodology for separation of HDL subclasses involves various types of ultracentrifugation that are time-consuming, costly, and not suitable for many clinical or epidemiological studies. We have developed a simple precipitation method for the separation of HDL subclasses in human plasma. After precipitation of apoB-containing lipoproteins with heparin-Mn2+, HDL2 is precipitated by addition of dextran sulfate (mol wt 15,000). HDL2 cholesterol is calculated as the difference between total HDL cholesterol (heparin-Mn2+ supernatant) and HDL3 cholesterol (dextran sulfate supernatant). HDL2 determined by this method correlated well with results obtained by preparative ultracentrifugation (n = 295, r = 0.91) and analytical ultracentrifugation (n = 17, r = 0.92). In the original method final concentration of dextran sulfate was 0.09 g/dl; however further studies indicated that 0.13 g/dl is a more suitable concentration. The chemical compositions of HDL2 and HDL3 isolated by the precipitation method were very similar to those of HDL2 and HDL3 isolated by preparative ultracentrifugation. The concentration of HDL2 cholesterol was 40% higher in normal women than in normal men. In men with coronary heart disease, total HDL was decreased by 28%, HDL2 was decreased by 44%, while HDL3 was 19% lower. A similar pattern of change was found in women with coronary heart disease. In other conditions where total HDL either increased or decreased, the change in HDL2 was always proportionately greater than the change in total HDL. HDL3 showed relatively less change, and in some instances its concentration was unchanged. Thus HDL2 is the more variable component and may be a more meaningful index of altered HDL metabolism.

Chemical Phenomena↗

Dietary vitamin C and uterine cervical dysplasia.

A case-control study of women with cervical abnormalities identified through Pap smears, was conducted in the Bronx, New York, to explore the relationship between nutritional intake and cervical dysplasia. Nutrient intake was estimated from computer analysis of three-day food records and 24-hour recall for 169 study participants (87 cases, 82 controls), including a subset of 49 pairs matched for age, race and parity. Mean vitamin C intake per day from three-day food record for controls was 107 mg, compared to 80 mg for cases (p less than 0.01). Analysis of matched pairs showed similar results; 29% of cases compared to 3% of controls in matched subset had vitamin C intake less than 50% of the recommended daily allowance, yielding a ten-fold increase in risk of cervical dysplasia as estimated by odds ratio (p less than 0.05). Younger age, greater frequency of sexual intercourse and younger age at first intercourse were associated with higher risk of cervical dysplasia. Multiple logistic analyses indicated that low vitamin C intake is an independent contributor to risk of severe cervical dysplasia when age and sexual activity variables are controlled. Approximately 35% of US women in their reproductive years have daily vitamin C intake below 30 mg, and 68% have vitamin C intake below 88 mg. If other studies confirm these findings, it may be important to explore a possible protective role of supplementary vitamin C for women at high risk of cervical cancer.

Adolescent↗