Biomedical subjects

L D Fisher

Publications and source records attributed to L D Fisher.

At least 55 records · Page 3Linked to original sources

PubMed1993

Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome.

We treated 93 patients with myelodysplastic syndrome using cyclophosphamide and either total body irradiation (n = 88) or busulfan (n = 5) followed by marrow transplantation. Sixty-five marrow donors were genotypically HLA-identical siblings and 28 were other family members or unrelated donors. Before transplantation all patients had either severe neutropenia or thrombocytopenia or had greater than 5% blasts in the marrow or peripheral blood. The probabilities of disease-free survival, relapse, and non-relapse mortality at 4 years were 41%, 28%, and 43%, respectively. Multivariate analysis revealed that younger age and shorter disease duration were significantly associated with improved disease-free survival and decreased non-relapse mortality. Relapse was seen only in patients with excess blasts at the time of transplantation (51% at 4 years). Patients younger than age 40 and without excess blasts had a 4-year disease-free survival of 62%. This study confirms that allogeneic marrow transplantation can cure some patients with myelodysplasia. Because of the favorable outcome in younger patients without excess blasts, we recommend that transplantation be considered early for patients younger than age 40, before disease progression or development of life-threatening cytopenias. For older patients and those with excess blasts, changes in the transplant procedure will be necessary to improve outcome.

Adolescent↗

PubMed1993

Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients.

OBJECTIVE: To determine the incidence and clinical course of veno-occlusive disease of the liver (VOD) after bone marrow transplantation and to analyze risk factors for severe VOD. DESIGN: Cohort study of 355 consecutive patients. SETTING: A bone marrow transplantation center. MEASUREMENTS: Each patient was prospectively evaluated for VOD, and many risk factors for severe VOD were analyzed using logistic regression models. The relation of VOD to renal and cardiopulmonary failure was analyzed using time-dependent proportional hazards models. RESULTS: Veno-occlusive disease developed in 190 of 355 patients (54%; 95% CI, 48% to 59%): Fifty-four patients had severe VOD and 136 had mild or moderate VOD. Independent variables derived from a multivariate model for predicting severe VOD included elevated transaminase values before transplantation (relative risk, 4.6; P < 0.0001); vancomycin therapy during cytoreductive therapy (relative risk, 2.9; P = 0.003); cytoreductive therapy with a high-dose regimen (relative risk, 2.8; P = 0.01); acyclovir therapy before transplantation (relative risk, 4.8; P = 0.02); mismatched or unrelated donor marrow (relative risk, 2.4; P = 0.02); and previous radiation therapy to the abdomen (relative risk, 2.2; P = 0.04). Vancomycin therapy was a marker for persistent fever. Multiorgan failure was more frequent among patients with VOD and usually followed the onset of liver disease. CONCLUSIONS: Veno-occlusive disease, which developed in 54% of bone marrow transplant recipients, is frequently associated with renal and cardiopulmonary failure. Pretransplant transaminase elevations, use of high-dose cytoreductive therapy, and persistent fever during cytoreductive therapy are independent predictors of severe VOD.

Acyclovir↗

PubMed1993

Five-year angiographic follow-up of factors associated with progression of coronary artery disease in the Coronary Artery Surgery Study (CASS). CASS Participating Investigators and Staff.

OBJECTIVES: The Coronary Artery Surgery Study (CASS) required participants to undergo follow-up angiography at 5 years to identify clinical and angiographic features associated with progression of coronary artery disease. BACKGROUND: The CASS randomized 780 patients at 11 participating clinical centers between an initial strategy of medical therapy versus bypass surgery. Five clinical sites accomplished follow-up angiography in > 50% of their randomized subjects within a 42- to 66-month period after the entry arteriogram (n = 314). METHODS: Qualified clinical site angiographers, using side by side film review, evaluated an average of 13 segments/patient on both arteriograms for initial stenosis severity, morphologic features, lesion location and occurrence of disease progression or occlusion. Progression was defined as further definite narrowing by > or = 15% and occlusion as lesion progression to > or = 98%. Lesions were subcategorized as to whether they were univariate and had or had not been treated with bypass surgery. Multivariate logistic regression analyses were performed. RESULTS: For nonbypassed segments, right coronary artery and left anterior descending artery proximal and midlocations were associated with disease progression. For stenosis-containing segments, the initial severity, a non-left anterior descending artery location and increased treadmill duration predicted progression. Segment occlusion was associated with initial lesion severity, right coronary artery location and subsequent interval myocardial infarction. There were few predictors of progression or occlusion in bypassed arteries, other than initial lesion severity. CONCLUSIONS: Univariate and multivariate associations with lesion progression and occlusion included diabetes, lesion location, elevated cholesterol level, interval infarction and lesion morphology. These angiographic results, collected in a prospective trial, are consistent with known risk factors.

Coronary Angiography↗

PubMed1993

Axillofemoral bypass with externally supported, knitted Dacron grafts: a follow-up through twelve years.

PURPOSE: The purpose of this study was to review our experience with externally supported, knitted Dacron grafts used for axillofemoral bypass. METHODS: Retrospective analysis was performed on records of 79 consecutive axillofemoral bypass graft operations performed on 77 patients from January 1978 to April 1990. RESULTS: The mortality rate within 30 days of operation was 5% (four of 79); 36 patients died in the follow-up period; none died of graft causes. During this 12-year period (mean follow-up 42 months) three patients were unavailable for follow-up. The primary patency rate was 78% at 5 years and 73% at 7 years, with no change thereafter. Neither the graft configuration (i.e., axillounifemoral [n = 50] vs axillobifemoral [n = 29]) nor patency of the superficial femoral artery had an impact on the primary patency rate. Patients who underwent surgery for disabling claudication (n = 30 grafts) had a primary patency rate of 80% at 6 years compared with 65% at 6 years for those who required surgery for limb salvage (n = 49 grafts); the difference was not significant (p = 0.37). Actuarial survival of patients with axillofemoral grafts was 23% at 10 years compared with 72% in a concurrent population of patients with aortofemoral bypass (p < 0.001). CONCLUSION: These findings indicate that axillofemoral bypass grafts may be appropriate for high-risk patients with severe aortoiliac disease who require revascularization for either limb salvage or incapacitating claudication.

Adult↗

PubMed1993

Platelet aggregometry can accurately predict failure of externally supported knitted Dacron femoropopliteal bypass grafts.

PURPOSE: Our purpose was to evaluate whether a method for quantification of platelet aggregability will predict failure of knitted Dacron femoropopliteal bypass grafts. METHODS: A numerically derived platelet aggregation (PA) score, based on the aggregation pattern and platelet count, was determined in the 40 patients available for platelet analysis who underwent 53 femoropopliteal bypass grafts with preclotted, 6 mm, externally supported knitted Dacron grafts from 1981 to 1991 (mean follow-up 50 months). The preoperative score was found to remain stable after surgery, enabling the use of postoperative values when preoperative values were not available. The PA score was available in 19 patients (23 grafts) before surgery and 23 patients (30 grafts) after surgery. The following factors were analyzed for predicting graft failure by the Cox proportional hazards regression model: PA score, age, gender, history of smoking, coronary artery disease, hypertension, hyperlipidemia, cerebrovascular disease, diabetes, claudication versus limb salvage, site of the distal anastomosis, previous ipsilateral bypass, and state of the runoff as determined by preoperative angiography. RESULTS: Of the studied risk factors, the value of the PA score was the most significant predictor of graft closure (p < 0.0001). An increase of 10 units was associated with an increased relative risk of 2.02. Throughout the follow-up period, 15 of 16 grafts remained patent in patients with a PA score of 15 or less, but only 2 grafts out of 17 remained patent in patients with a PA score of 30 or greater. CONCLUSIONS: These data suggest that the PA score is a potential risk factor for failure of femoropopliteal bypass with externally supported knitted Dacron grafts.

Adenosine Diphosphate↗

PubMed1993

Summarizing data on survival, relapse, and chronic graft-versus-host disease after bone marrow transplantation: motivation for and description of new methods.

Kaplan-Meier curves are frequently used to summarize survival, relapse, and chronic graft-versus-host disease (GVHD) data in the bone marrow transplant setting. Some fundamental problems with the use of Kaplan-Meier curves for the summary of relapse and GVHD are described. Alternatively, the use of simple probability and conditional probability curves for summarizing relapse incidence and transplant-related mortality is illustrated with previously published data from a randomized clinical trial. Prevalence curves provide an appropriate alternative for the summary of a transient condition such as chronic GVHD. When combined with Kaplan-Meier curves for survival and/or relapse-free survival, these methods provide a more accurate and comprehensive summary of the various marrow transplant outcomes. These methods of display are also applicable to other settings where more than one type of treatment failure can occur and where follow-up time may be variable.

Bone Marrow Transplantation↗

PubMed1993

Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease: the 21-year Seattle experience.

PURPOSE: To analyze results of 127 patients undergoing myeloablative therapy followed by marrow transplantation for relapsed or refractory Hodgkin's disease. PATIENTS AND METHODS: Twenty-three patients had primary refractory disease, 34 were in early first relapse or second complete remission (CR), and 70 had refractory first relapse or disease beyond second CR. Preparative regimens included total-body irradiation (TBI) and chemotherapy (n = 61) or chemotherapy only (n = 66). Sixty-eight patients received autologous marrow, six syngeneic marrow, and 53 allogeneic marrow. RESULTS: The 5-year actuarial probabilities of survival, event-free survival (EFS), relapse, and nonrelapse mortality for the entire group were 21%, 18%, 65%, and 49%, respectively. HLA-identical allogeneic marrow recipients had a statistically lower relapse rate compared with recipients of autologous marrow, but survival, EFS, and nonrelapse mortality rates were not significantly different. In the multivariate analysis, higher performance status and absence of bulky disease predicted for improved EFS and lower relapse rates, while fewer prior treatment regimens predicted for improved EFS and lower nonrelapse mortality rates. Additionally, the univariate analysis showed that patients who underwent transplantation with disease refractory to chemotherapy or beyond second CR had a worse outcome compared with those who had less advanced disease. CONCLUSION: Outcome with transplantation for patients with Hodgkin's disease is improved if transplantation is performed early after relapse when disease burden is less, tumor chemosensitivity is greater, and the patient is likely to have a better performance status. The use of HLA-matched sibling marrow results in a lower relapse rate and, thus, for some individuals, may be preferable to the use of autologous marrow.

Actuarial Analysis↗

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↗