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Biomedical subjects

L D Fisher

Publications and source records attributed to L D Fisher.

At least 19 recordsLinked to original sources
PubMed1992

Ursodeoxycholic acid treatment of refractory chronic graft-versus-host disease of the liver.

OBJECTIVE: To determine the safety and efficacy of ursodeoxycholic acid treatment in patients with chronic graft-versus-host disease (GVHD) of the liver. DESIGN: Open-label study in which each patient served as his or her own control. SETTING: Private practice and a university bone marrow transplant center. PATIENTS: Twelve patients with refractory chronic GVHD of the liver were studied after allogeneic bone marrow transplantation. INTERVENTIONS: After baseline data collection, patients were given ursodeoxycholic acid (UDCA, 10 to 15 mg/kg body weight per day) for 6 weeks. After discontinuation of the drug, patients were followed for an additional 6 weeks. Doses of immunosuppressive drugs were unchanged for these 12 weeks. MEASUREMENTS: Signs, symptoms, Karnofsky performance scores, hematocrit, total leukocyte count, absolute neutrophil count, platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyltransferase (GGT), total serum bilirubin, prothrombin time, serum creatinine, and blood urea nitrogen were assessed. RESULTS: Serum tests of cholestatic liver injury measured at 2, 4, and 6 weeks showed improvement compared with baseline. At 6 weeks, the percent decrease from baseline in total serum bilirubin was 33% (P less than 0.005); in alkaline phosphatase the decrease was 32% (P less than 0.038); and in AST the decrease was 37% (P less than 0.007). After discontinuation of UDCA therapy, 11 patients were followed for 6 additional weeks. All showed significant worsening in liver function test results. Symptom scores were unchanged throughout the study. One patient with pruritus improved while receiving therapy with UDCA. No adverse effects were observed. CONCLUSION: Therapy with UDCA was safe, well-tolerated, and efficacious in the short-term treatment of refractory chronic GVHD of the liver. Further investigation is needed to evaluate the long-term effects of UDCA therapy.

Bilirubin↗
PubMed1992

Effects of smoking on survival and morbidity in patients randomized to medical or surgical therapy in the Coronary Artery Surgery Study (CASS): 10-year follow-up. CASS Investigators.

OBJECTIVES: The goal of this study was to ascertain how continued cigarette smoking or smoking cessation related to long-term survival and morbidity in patients with established coronary artery disease managed with medical therapy or coronary bypass surgery. BACKGROUND: Although the association of cigarette smoking with coronary artery disease is well established, the morbidity and mortality associated with smoking behavior in patients with such disease receiving medical or surgical therapy are less well established. METHODS: The 780 patients randomized to medical therapy or coronary bypass surgery in the Coronary Artery Surgery Study (CASS) were subgrouped according to smoking behavior during a mean 11.2-year follow-up interval. Comparisons between smokers and nonsmokers were accomplished by univariate and Cox time-dependent multivariate analyses. RESULTS: Survival at 10 years after entry into the study was 82% among 468 patients who reported no smoking during follow-up (nonsmokers) compared with 77% among the 312 smokers (p = 0.025). Survival was 80% among those who smoked at entry but stopped (quitters) versus 69% among those who continued smoking (p = 0.025). For patients who smoked at baseline and were randomized to bypass surgery, survival at 10 years was 84% among quitters and 68% among nonquitters (p = 0.018); the difference in survival between quitters (75%) and nonquitters (71%) was less among those randomized to medical therapy (p = NS). Among those who smoked at baseline, continued smoking increased the relative risk of death by 1.73. After 10 years, smokers, in comparison with nonsmokers, were less likely to be angina free and more likely to be unemployed and had more activity limitation and more hospital admissions (primarily for chest pain, heart attack, cardiac catheterization, peripheral vascular surgery and stroke). CONCLUSIONS: Thus, among patients with documented coronary artery disease, continued cigarette smoking may result in decreased survival--especially among those undergoing bypass surgery. Moreover, smokers have more angina, more unemployment, a greater limitation of physical activity and more hospital admissions.

Coronary Artery Bypass↗
PubMed1992

MMPI scale 3 as a predictor of back injury report: what does it tell us?

Items and selected subscales of Scale 3 (Hysteria) of the MMPI were examined to pinpoint personality or emotional factors predictive of back injury reports in an industrial setting. Data were derived from a previous prospective-design study of back pain in volunteer hourly wage employees of an aircraft manufacturing company. After physical examination and completion of questionnaires pertaining to demographic, psychosocial (including the MMPI), and workplace factors, workers were followed for an average of 3 years. Those who subsequently reported back injury were compared with those who did not. In that study three variables predicted report of back injury, one of which was Scale 3 of the MMPI. Individual items, Ornduff et al. subscales of Psychological Denial and Body Concern, and the five Harris-Lingoes (1955) subscales of Scale 3 were analyzed. Three Harris-Lingoes subscales showed significant relationships to the criterion. Hy-3: Lassitude/Malaise; Hy-1: Denial of Social Anxiety; and, marginally, Hy-2: Need for Affection, significantly contributed to prediction effectiveness. Results and implications for the understanding of factors predicting back injury reports and for the medical evaluation of pain and the concept of pain are discussed.

Back Injuries↗
PubMed1992

A prospective evaluation of preemployment screening methods for acute industrial back pain.

Preemployment screening methods have been ineffective in predicting those at risk, and in curbing the impact of back problems in industry. Such methods have centered on individual physical factors (capacities and clinical examination). This study evaluates commonly used physical examination measures and simple historical data for its ability to predict individuals at risk for future back injury reporting in the aircraft industry. In this study, once simple historical information about previous pain treatment was known, information gained from physical factors added no significant predictive value.

Adult↗
PubMed1992

Effect of completeness of revascularization on long-term outcome of patients with three-vessel disease undergoing coronary artery bypass surgery. A report from the Coronary Artery Surgery Study (CASS) Registry.

BACKGROUND: Complete revascularization after coronary artery bypass surgery is a logical goal and improves symptomatic outcome and survival. However, the impact of complete revascularization in patients with three-vessel coronary disease with varying severities of angina and left ventricular dysfunction has not been clearly defined. METHODS AND RESULTS: The study was performed as a retrospective analysis of 3,372 nonrandomized surgical patients from the Coronary Artery Surgery Study (CASS) Registry who had three-vessel coronary disease. Group 1 (894 patients) had class I or II angina (Canadian Cardiovascular Society criteria) and group 2 (2,478 patients) had class III or IV angina. In group 1, adjusted cumulative 4-year survivals according to the number of vessels bypassed were 85% (one vessel), 94% (two vessels), 96% (three vessels), and 96% (more than three vessels) (log rank, p = 0.022). Adjusted event-free survival (death, myocardial infarction, definite angina, or reoperation) was not influenced by the number of vessels bypassed, nor was the anginal status among patients remaining alive after 5 years. In group 2, adjusted cumulative 5-year survivals were 78% (one vessel), 85% (two vessels), 90% (three vessels), and 87% (more than three vessels) (log rank, p = 0.074). Adjusted event-free survivals after 6 years were 23% (one vessel), 23% (two vessels), 29% (three vessels), and 31% (more than three vessels) (p = 0.025); at 5 years, those with more complete revascularization were more likely to be asymptomatic or free of severe angina. Among group 2 patients with ejection fractions less than 0.35, 6-year survival was 69% for those with grafts to three or more vessels versus 45% for those with grafts to two vessels (p = 0.04). Placing grafts to three or more vessels was independently associated with improved survival and event-free survival in group 2 but not group 1 patients. The case-fatality rates among 529 patients experiencing a myocardial infarction during follow-up was significantly higher for patients with less complete revascularization. CONCLUSIONS: Complete revascularization (grafts to three or more vessels) in patients with three-vessel coronary disease appears to most benefit those with severe angina and left ventricular dysfunction.

Angina Pectoris↗
PubMed1992

A longitudinal, prospective study of industrial back injury reporting.

The authors prospectively evaluated 3020 volunteers of the Boeing-Everett plant to assess risk factors that predispose workers to file industrial back injury claims. During four years of follow-up observation, more than 279 subjects reported acute back problems. The effect of the only predictive physical variable was explainable by a history of medical treatment. The most predictive individual factors were (1) job task dissatisfaction and (2) distress as reported on Scale 3 of the Minnesota Multiphasic Personality Inventory (MMPI). This data perhaps explains why the focus on purely physical and injury-related factors has met with little success in dealing with what has become the most expensive orthopedic problem. Clinically, nonphysical factors that significantly impact the reporting of back injuries may also affect patients' responses to medical treatment.

Accidents, Occupational↗
PubMed1991

Significance of silent myocardial ischemia during exercise testing in patients with diabetes mellitus: a report from the Coronary Artery Surgery Study (CASS) Registry.

To evaluate the significance of ischemic ST depression without anginal chest pain during exercise testing among patients with diabetes mellitus, the data on 45 such patients from the Coronary Artery Surgery Study registry were analyzed. These patients (group 1, silent ischemia) were compared with 37 diabetic patients with both ischemic ST depression and chest pain (group 2, symptomatic ischemia), with 31 diabetic patients without ischemic ST depression or chest pain (group 3, no ischemia), and with 429 patients without diabetes who had silent ischemia during exercise testing. All patients had documented coronary artery disease (CAD) (greater than 70% diameter narrowing). The 6-year survival among patients with silent ischemia was worse in diabetic than nondiabetic patients (59 vs 82%, respectively, p less than 0.001). By contrast, the 6-year survival among patients without ischemia was similar among diabetic and nondiabetic patients (93 vs 85%, respectively, p = 0.476). Among diabetic patients, survival at 6 years with medical treatment was 59% for group 1, 66% for group 2 and 93% for group 3 (p = 0.008). Survival among subsets of patients with diabetes and silent ischemia (group 1) based on the extent of CAD and left ventricular function ranged from 100 to 32% (p = 0.093). The survival of the 45 patients with diabetes mellitus and silent ischemia (group 1) treated medically was compared with that of 28 patients receiving coronary artery graft bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Bypass↗
PubMed1991

Allogeneic marrow transplantation in patients with chronic myeloid leukemia in the chronic phase: a randomized trial of two irradiation regimens.

A randomized trial was performed to compare two regimens of total body irradiation in patients with chronic myeloid leukemia treated by allogeneic marrow transplantation while in the chronic phase. All patients received cyclophosphamide 120 mg/kg followed by total body irradiation and marrow from HLA-identical siblings. Cyclosporine and methotrexate were used for prophylaxis against acute graft-versus-host disease. Fifty-seven patients were randomized to receive 2.0 Gy fractions of irradiation daily for 6 days and 59 were randomized to receive 2.25 Gy fractions daily for 7 days. The probabilities of relapse at 4 years were 0.25 for the 12.0 Gy group and 0.00 for the 15.75 Gy group (P = .008). The actuarial probabilities of survival and relapse-free survival at 4 years were 0.60 and 0.58 among the patients who received 12.0 Gy compared with 0.66 and 0.66 for those who received 15.75 Gy. The 4-year probabilities of transplant-related mortality were 0.24 and 0.34 respectively (P = .13) while the probability of moderate to severe acute graft-versus-host disease was 0.33 for the 12.0 Gy group and 0.44 for the 15.75 Gy group (P = .15). The lower relapse probability in the patients receiving the higher dose of total body irradiation did not result in improved survival because mortality from causes other than relapse was increased.

Adult↗
PubMed1991

Once-daily verapamil in the treatment of mild-to-moderate hypertension: a double-blind placebo-controlled dose-ranging study.

Supine office blood pressures (SOBP) and 24-hour automated ambulatory blood pressure monitorings (AABPM) showed blood pressure reductions from a stable baseline to active treatment with 120-, 240-, and 480-mg doses of a new verapamil QD capsule (solid-spheroidal-oral once-daily drug-absorption system: (SODAS) in patients with mild-to-moderately severe (diastolic blood pressures 95-119 mm Hg) essential hypertension. Reductions were documented at 24 hours, hourly, and by the 24 hour average, using SOBP and AABPM, after the once-daily verapamil administration. Both SOBP and the 24-hour average by AABPM were significantly reduced from baseline by active verapamil treatment of 120-, 240-, and 480-mg doses. In comparison to verapamil QD (0 mg), blood pressure reductions from baseline to active treatment were significant at the 240- and 480-mg doses but not at the 120-mg dose. There was a significant linear dose response. This verapamil formulation (SODAS) was effective throughout the 24-hour period after once-daily dosing.

Blood Pressure↗
PubMed1991

Prevalence and prognostic significance of silent and symptomatic ischemia after coronary bypass surgery: a report from the Coronary Artery Surgery Study (CASS) randomized population.

The prevalence and prognostic significance of postoperative myocardial ischemia, as detected by exercise testing, were prospectively assessed in 174 patients from the Coronary Artery Surgery Study (CASS) randomized surgical population who had exercise testing before and 6 months after coronary artery bypass graft surgery. Whereas the prevalence of symptomatic ischemia significantly decreased postoperatively (52% vs. 6%, p less than 0.001), the frequency of silent myocardial ischemia did not change (30% vs. 29%). Survival at 12 years after bypass surgery based on the 6-month postoperative exercise test results was significantly better for the 112 patients with no ischemia (80%) than for the 51 patients with silent ischemia (68%) or the 11 patients with symptomatic ischemia (45%). These data show that coronary artery bypass graft surgery diminishes the overall prevalence of symptomatic but not silent ischemia and that both silent and symptomatic ischemia adversely affect the postoperative prognosis of these patients.

Coronary Artery Bypass↗
PubMed1991

The use of one-sided tests in drug trials: an FDA advisory committee member's perspective.

The use of one-sided or two-sided tests in drug trials to evaluate new compounds is considered. For drugs that may be tested against placebos, with two positive trials required (as in the United States), it is argued that from both a regulatory and pharmaceutical industry perspective, one-sided tests at the 0.05 significance level are appropriate. In situations where only one trial against placebo may be done (for example, survival trials), one-sided tests at the 0.025 level are appropriate in many cases. For active control trials it is argued that two-sided tests are usually appropriate.

Clinical Trials as Topic↗
PubMed1991

Cytomegalovirus (CMV)-specific intravenous immunoglobulin for the prevention of primary CMV infection and disease after marrow transplant.

Cytomegalovirus (CMV)-specific immunoglobulin (IVIG) was evaluated in a randomized controlled trial in CMV-seronegative marrow transplant patients with seropositive marrow donors for the prevention of primary CMV infection during the first 100 days after transplant. Patients received 200 mg/kg CMV IVIG on days 8 and 6 before transplant, the day after transplant, weekly for the first month, and then every 2 weeks to complete 10 doses. Patients were followed with weekly CMV cultures and serologic studies and for clinical and histologic evidence of CMV disease. Sixty patients were evaluable in each group. There was significantly less CMV excretion (P = .04) and viremia (P = .01) in the treatment group. However, the incidence of CMV disease including CMV pneumonia, CMV enteritis, and CMV syndrome (fever, leukopenia, hepatitis) was not statistically different. There was also no difference in median time of onset of CMV infection or disease, median number of hospital days, or survival between the two groups.

Adolescent↗
PubMed1991

Clinical features and analysis of risk factors for invasive candidal infection after marrow transplantation.

Of 1506 marrow transplant patients from 1980 through 1986 reviewed for risk factors for invasive candidal infection defined by positive blood cultures, biopsy, or histologic evidence of tissue invasion, 171 (11.4%) had invasive infection, with a significantly higher incidence in the more recent years of review; 40% (69 patients) had evidence of tissue-invasive disease without fungemia. Of 102 patients with fungemia, 45% had candidemia alone with a mortality of 39%. Mortality in patients with tissue involvement was 90% with or without fungemia. Factors that increased infection were age, acute graft-versus-host disease, and donor mismatch. Factors that decreased infection included conditioning with 12 Gy of fractionated irradiation and cyclophosphamide, transplantation for aplastic anemia, and more rapid engraftment. Among fungemic patients, the number of days of fungemia was a risk factor for tissue invasion while more rapid engraftment was protective.

Adolescent↗
PubMed1991

Air jet noise exposure rapidly increases blood pressure in young borderline hypertensive rats.

The present study tested the hypothesis that air jet noise exposure elicits sympathetically-mediated increases in the blood pressure of weaning-aged borderline hypertensive rats (BHR). BHR were the F1 offspring of spontaneously hypertensive female rats and male Wistar-Kyoto rats. Beginning at weaning (4 weeks of age), restrained BHR were exposed to air jet noise (30-120 s pulses of 120 dB) for 2 h/day, 5 days per week. Controls were restrained but did not receive air jet noise exposure. After only 1 week of air jet exposure, the systolic blood pressure (SBP) levels of the noise-exposed rats were increased significantly above those of restrained controls. Measures of mean arterial pressure (MAP) made in the home cage after 2 weeks of noise exposure confirmed the increased SBP. Ten weeks of air jet noise exposure increased MAP compared with restrained controls (144 +/- 4 versus 128 +/- 4 mmHg), with both SBP and diastolic blood pressure (DBP) being significantly increased. Baroreceptor sensitivity, assessed by bradycardic responses to graded doses of phenylephrine (0.5, 1, 2 and 4 micrograms/kg, intravenously), did not differ from restrained controls after 10 weeks of noise exposure. Autonomic (largely sympathetic) influence on home-cage blood pressure, inferred from ganglion blockade with chlorisondamine, also did not differ between groups after 10 weeks of stress. After maximal vasodilation with hydralazine, the DBP of air jet noise-exposed rats was somewhat higher than restrained controls (62 +/- 5 versus 49 +/- 3 mmHg; P = 0.08), suggesting that structural changes may have contributed to the increased MAP in air jet noise-exposed rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

A prospective study of work perceptions and psychosocial factors affecting the report of back injury.

A longitudinal, prospective study was conducted on 3,020 aircraft employees to identify risk factors for reporting acute back pain at work. The premorbid data included individual physical, psychosocial, and workplace factors. During slightly more than 4 years of follow-up, 279 subjects reported back problems. Other than a history of current or recent back problems, the factors found to be most predictive of subsequent reports in a multivariate model were work perceptions and certain psychosocial responses identified on the Minnesota Multiphasic Personality Inventory (MMPI). Subjects who stated that they "hardly ever" enjoyed their job tasks were 2.5 times more likely to report a back injury (P = 0.0001) than subjects who "almost always" enjoyed their job tasks. The quintile of subjects scoring highest on Scale-3 (Hy) of the MMPI were 2.0 times more likely to report a back injury (P = 0.0001) than subjects with the lowest scores. The multivariate model, including job task enjoyment, MMPI Scale-3, and history of back treatment, revealed that subjects in the highest risk group had 3.3 times the number of reports in the lowest risk group. These findings emphasize the importance of adopting a broader approach to the multifaceted problem of back complaints in industry and help explain why past prevention efforts focusing on purely physical factors have been unsuccessful.

Adult↗
PubMed1991

Evidence for entry of plasma insulin into cerebrospinal fluid through an intermediate compartment in dogs. Quantitative aspects and implications for transport.

To study the route by which plasma insulin enters cerebrospinal fluid (CSF), the kinetics of uptake from plasma into cisternal CSF of both insulin and [14C]inulin were analyzed during intravenous infusion in anesthetized dogs. Four different mathematical models were used: three based on a two-compartment system (transport directly across the blood-CSF barrier by nonsaturable, saturable, or a combination of both mechanisms) and a fourth based on three compartments (uptake via an intermediate compartment). The kinetics of CSF uptake of [14C]inulin infused according to an "impulse" protocol were accurately accounted for only by the nonsaturable two-compartment model (determination coefficient [R2] = 0.879 +/- 0.044; mean +/- SEM; n = 5), consistent with uptake via diffusion across the blood-CSF barrier. When the same infusion protocol and model were used to analyze the kinetics of insulin uptake, the data fit (R2 = 0.671 +/- 0.037; n = 10) was significantly worse than that obtained with [14C]inulin (P = 0.02). Addition of a saturable component of uptake to the two-compartment model improved this fit, but was clearly inadequate for a subset of insulin infusion studies. In contrast, the three-compartment model accurately accounted for CSF insulin uptake in each study, regardless of infusion protocol (impulse infusion R2 = 0.947 +/- 0.026; n = 10; P less than 0.0001 vs. each two-compartment model; sustained infusion R2 = 0.981 +/- 0.003; n = 5). Thus, a model in which insulin passes through an intermediate compartment en route from plasma to CSF, as a part of a specialized transport system for the delivery of insulin to the brain, best accounts for the dynamics of this uptake process. This intermediate compartment could reside within the blood-CSF barrier or it may represent brain interstitial fluid, if CNS insulin uptake occurs preferentially across the blood-brain barrier.

Animals↗
PubMed1991

Treatment of adult acute lymphoblastic leukemia with allogeneic bone marrow transplantation. Multivariate analysis of factors affecting acute graft-versus-host disease, relapse, and relapse-free survival.

Between February 1972 and December 1987, 192 adults (greater than or equal to 18 years old) with acute lymphoblastic leukemia were transplanted using genotypically HLA-identical marrow donors. Median patient age was 23 years. Eighty-nine patients were in marrow remission and 103 were in relapse. Conditioning regimens included chemotherapy alone (three patients) or in combination with 9.2-17.5 Gy total body irradiation (189 patients). Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate and/or cyclosporine. Seventy-nine patients developed grades II-IV acute GVHD and 28 of 122 patients who survived at least 100 days developed chronic GVHD. Relapse-free survival at 5 years was 21% for patients transplanted in first remission, 15% for those in greater than or equal to 2nd remission, and 12% for those transplanted in relapse. Patient and donor characteristics were evaluated in multivariate analyses for their effect on development of acute GVHD, survival, relapse, and relapse-free survival. An increased risk of developing acute GVHD was associated with increasing donor age. Variables significantly associated with both increased survival and relapse-free survival included transplantation in first remission, younger patient age, and not developing interstitial pneumonia. A decreased probability of relapse was associated with transplantation in first remission, male patient sex, and grades II-IV acute GVHD.

Acute Disease↗