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Biomedical subjects

L D Fisher

Publications and source records attributed to L D Fisher.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1991

Oral protein intake and the risk of acute graft-versus-host disease after allogeneic marrow transplantation.

The possibility that antigenically active protein macromolecules affect the risk of developing acute graft-versus-host disease (aGVHD) was investigated in a cohort of patients who underwent allogeneic marrow transplantation for hematologic malignancy (n = 575). Daily records of food intake from transplant through discharge or death were evaluated for grams of total protein and summed over consecutive 4-day intervals. The day of onset of aGVHD was partitioned into 4-day time intervals such that assessments of food intake preceded onset of aGVHD by 3-6 days. Acute GVHD developed in 308 (54%) patients. The cumulative incidence of aGVHD among patients eating any amount of protein was lower (4-13%) than that of patients not eating protein (8-19%) for each of the time intervals through day 21 post-transplant; the relative risk associated with protein intake, adjusted for patient and transplant characteristics that are correlated with the occurrence of aGVHD, ranged from 0.23 (95% confidence interval (CI) 0.09, 0.63) to 0.83 (CI 0.46, 1.51). A proportional hazards regression analysis, using protein intake as a time-dependent covariate, confirmed these results. The findings of this study provide no support for the hypothesis that intake of protein-containing foods during the first 3 weeks after marrow transplantation increases the risk of aGVHD.

Administration, Oral↗
PubMed1991

Busulfan and cyclophosphamide as a preparative regimen for bone marrow transplantation in patients with prior chest radiotherapy.

In a previous study, we reported that patients with hematologic malignancies who had received prior chest radiotherapy had a 32% risk of developing fatal interstitial pneumonia (IP) when prepared for bone marrow transplantation (BMT) with a regimen containing total body irradiation (TBI). To determine if avoidance of TBI would lessen the incidence of fatal IP, 37 patients who had received prior chest radiotherapy in excess of 2000 cGy were prepared with busulfan (BU, 4 mg/kg x 4 days) and cyclophosphamide (CY, 60 mg/kg x 2 days) followed by autologous (n = 15) or allogeneic (n = 22) BMT. Thirty-five of these patients had recurrent or refractory hematologic malignancies and most were heavily pretreated. Results were compared with the group of similar patients (n = 25) previously treated at our institution with a CY/TBI conditioning regimen. Among those treated with BU/CY, two patients (5%) developed fatal interstitial pneumonia, 12 (32%) died of other transplant related toxicities and 13 (35%) died of relapse. Seven (19%) patients remain alive and well. Among those treated with CY/TBI, eight (32%) died of pneumonia, six (24%) died of relapse, nine (36%) died of other causes and two (8%) remain alive and well. The 5% incidence of fatal interstitial pneumonitis in the chemotherapy conditioned group was significantly less than the 32% incidence in the previously treated CY/TBI group (p = 0.005). However, long-term survival and relapse probabilities were not significantly better than seen previously with CY/TBI, although a trend towards improved survival was observed in the BU/CY group. Avoidance of TBI appeared to lower the incidence of fatal pneumonitis in patients with prior chest radiotherapy.

Adolescent↗
PubMed1990

Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B.

BACKGROUND AND METHODS: The effect of intensive lipid-lowering therapy on coronary atherosclerosis among men at high risk for cardiovascular events was assessed by quantitative arteriography. Of 146 men no more than 62 years of age who had apolipoprotein B levels greater than or equal to 125 mg per deciliter, documented coronary artery disease, and a family history of vascular disease, 120 completed the 2 1/2-year double-blind study, which included arteriography at base line and after treatment. Patients were given dietary counseling and were randomly assigned to one of three treatments: lovastatin (20 mg twice a day) and colestipol (10 g three times a day); niacin (1 g four times a day) and colestipol (10 g three times a day); or conventional therapy with placebo (or colestipol if the low-density lipoprotein [LDL] cholesterol level was elevated). RESULTS: The levels of LDL and high-density lipoprotein (HDL) cholesterol changed only slightly in the conventional-therapy group (mean changes, -7 and +5 percent, respectively), but more substantially among patients treated with lovastatin and colestipol (-46 and +15 percent) or niacin and colestipol (-32 and +43 percent). In the conventional-therapy group, 46 percent of the patients had definite lesion progression (and no regression) in at least one of nine proximal coronary segments; regression was the only change in 11 percent. By comparison, progression (as the only change) was less frequent among patients who received lovastatin and colestipol (21 percent) and those who received niacin and colestipol (25 percent), and regression was more frequent (lovastatin and colestipol, 32 percent; niacin and colestipol, 39 percent; P less than 0.005). Multivariate analysis indicated that a reduction in the level of apolipoprotein B (or LDL cholesterol) and in systolic blood pressure, and an increase in HDL cholesterol correlated independently with regression of coronary lesions. Clinical events (death, myocardial infarction, or revascularization for worsening symptoms) occurred in 10 of 52 patients assigned to conventional therapy, as compared with 3 of 46 assigned to receive lovastatin and colestipol and 2 of 48 assigned to receive niacin and colestipol (relative risk of an event during intensive treatment, 0.27; 95 percent confidence interval, 0.10 to 0.77). CONCLUSIONS: In men with coronary artery disease who were at high risk for cardiovascular events, intensive lipid-lowering therapy reduced the frequency of progression of coronary lesions, increased the frequency of regression, and reduced the incidence of cardiovascular events.

Adult↗
PubMed1990

Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens.

A randomized trial of 12.0 Gy versus 15.75 Gy of total body irradiation (TBI) was performed in patients with acute myeloid leukemia undergoing allogeneic marrow transplantation while in first complete remission. All patients received 120 mg/kg cyclophosphamide followed by TBI and marrow from HLA-identical siblings. Cyclosporine and methotrexate were used for prophylaxis against acute graft-versus-host disease (GVHD). Thirty-four patients received 2.0-Gy fractions of irradiation daily for 6 days and 37 received 2.25-Gy fractions daily for 7 days. The 3-year actuarial probabilities for relapse-free survival were 0.58 for the patients who received 12.0 Gy and 0.59 for those who received 15.75 Gy. The 3-year probabilities of relapse were 0.35 for the 12.0 Gy group and 0.12 for the 15.75 Gy group (P = .06). The 3-year probabilities of transplant-related mortality were 0.12 and 0.32, respectively (P = .04). The probability of moderate to severe acute GVHD was 0.21 for the 12.0 Gy group and 0.48 for the 15.75 Gy group (P = .02). Patients exposed to the higher irradiation dose received less immunoprophylaxis against, and had a higher incidence of, acute GVHD. The increased dose of TBI significantly reduced the probability of relapse but did not improve survival because of increased mortality from causes other than relapse.

Adolescent↗
PubMed1990

Cytomegalovirus infection after autologous bone marrow transplantation: occurrence of cytomegalovirus disease and effect on engraftment.

Epidemiologic and clinical characteristics of cytomegalovirus (CMV) infection and disease were analyzed retrospectively in 159 autologous marrow transplant recipients. The probability of CMV infection by day 100 after transplant was 22.5% in patients seronegative to CMV before transplant versus 61.1% in seropositive patients (P less than .0001 by logrank test). Multivariate analysis identified positive pretransplant CMV serology as the only definable risk factor for CMV infection (relative risk 1.4, P less than .0001). CMV pneumonia developed in 11 patients at a median time of 100 days after transplant and was fatal in nine cases. CMV pneumonia was associated with significantly decreased probability of survival by day 100 after transplant (relative risk of death of 16.7, P less than .0001). In contrast to earlier reports, CMV infection had no significant effect on the rapidity of platelet or neutrophil recovery after transplant as assessed by time-dependent multivariate analysis. Because the incidence of severe CMV disease is not negligible after autologous marrow transplantation, preventive measures against CMV infection are warranted, as in allogeneic marrow transplantation.

Adult↗
PubMed1990

Bone marrow transplantation for patients with myelodysplasia. Pretreatment variables and outcome.

STUDY OBJECTIVE: To determine the efficacy of allogeneic bone marrow transplantation for severe myelodysplasia, and to identify variables predictive of outcome. DESIGN: Case series study. SETTING: A referral-based bone marrow transplant center. PATIENTS: Consecutive series of 59 patients with myelodysplasia or closely related disorders and either life-threatening cytopenia or a progressive increase in marrow blast percentage. INTERVENTION: Patients were treated with high-dose cyclophosphamide and total body irradiation followed by allogeneic bone marrow transplantation from either an HLA-identical (n = 45) or HLA-partially matched (n = 14) donor. MEASUREMENTS AND MAIN RESULTS: The product-limit estimate for disease-free survival 3 years after transplant is 45% (95% CI, 32% to 59%). The commonest causes of death after transplant were disease recurrence, interstitial pneumonia, and graft-versus-host disease, accounting for eight deaths each. In a univariate analysis, younger patients, those with shorter disease duration, and those whose disease was characterized by an abnormal cytogenetic karyotype had better survival and disease-free survival than the group as a whole. In a multivariate analysis, younger age and abnormal karyotype were independent predictors of improved disease-free survival and overall survival. Patients who received transplants when they had fewer blasts in their bone marrow had a decreased chance for disease recurrence when compared with patients with excess blasts. CONCLUSIONS: Bone marrow transplantation offers a potential cure for many patients with myelodysplasia. Best results can be expected in younger patients who receive transplants relatively early in their disease course.

Adolescent↗
PubMed1990

Clinical predictors of completed suicide and repeated self-poisoning in 8895 self-poisoning patients.

The diagnoses of 8895 patients who were admitted for intentional self-poisoning with psycho-active drugs were studied in order to find predictors for subsequent completed suicide and repeated self-poisoning. Automated record linkage by means of the Swedish personal identification numbers was performed between the Stockholm County inpatient registry and the cause-of-death registry. With Cox regression models, several diagnostic predictors were identified although they were generally unspecific and insensitive. This may be due both to the low base rate of suicides, and to the omission of other more powerful non-clinical predictors, such as personality traits, hopelessness and social disruption. It is concluded that secondary psychiatric prevention may still be justified, although it will be applied to large numbers of patients who will not eventually commit suicide or repeat self-poisoning.

Adult↗
PubMed1990

Cytomegalovirus excretion as a predictor of cytomegalovirus disease after marrow transplantation: importance of cytomegalovirus viremia.

Cytomegalovirus (CMV) viremia and excretion from the oropharynx and urine were examined for their utility in predicting the development of CMV disease, including pneumonia and gastrointestinal disease, among 617 marrow allograft recipients. CMV viremia had a 60% and excretion from oropharynx or urine or viremia a 44% positive predictive value for the development of CMV disease. Viremia or excretion preceded disease onset by a median of 15 days among those in whom excretion occurred first. In stepwise time-dependent proportional hazards regression analyses, CMV viremia and positive serology before transplant were predictive for both CMV pneumonia and gastrointestinal disease. Oropharyngeal excretion was independently predictive for gastrointestinal disease but not pneumonia. Urinary excretion was not independently predictive. Acute graft-versus-host disease was predictive for pneumonia but not gastrointestinal disease. Thus use of CMV excretion, particularly viremia, as a marker to determine the initiation of antiviral chemotherapy could be effective in preventing progression of infection to serious disease. However, with standard virologic techniques this strategy would not be effective in patients (32% in this study) without CMV excretion detected before the onset of pneumonia or gastrointestinal disease.

Adolescent↗
PubMed1990

Ten-year follow-up of quality of life in patients randomized to receive medical therapy or coronary artery bypass graft surgery. The Coronary Artery Surgery Study (CASS)

Quality of life indexes were assessed in 780 patients 10 years after randomization to medical therapy (n = 390) or coronary artery bypass graft surgery (n = 390) in the Coronary Artery Surgery Study. At 10 years, mortality was 21.8% in the medical group and 19.2% in the surgical group (p = NS), and 144 (37%) of the medical group had undergone surgery because of increasing chest pain. At study entry, 22% of medical and surgical patients were angina free; at 1 and 5 years after entry, the frequency of asymptomatic patients was 66% and 63% in the surgical group and 30% and 38% in the medical group. However, by 10 years after entry, the proportion of patients free of angina had fallen to 47% in the surgical group and to 42% in the medical group. Activity limitation and use of beta-blockers and long-acting nitrates were less in the surgical than the medical group at 1 and 5 years after entry but little different from the medical group at 10 years after entry. Throughout follow-up, recreational status, employment status, frequency of heart failure, use of other medications, and hospitalization frequency were similar between the two groups. Thus, indexes of quality of life such as angina relief, increased activity, and reduction in use of antianginal medications initially appear superior in patients with stable manifestations of ischemic heart disease assigned to surgery, but by 10 years after entry, these advantages are much less apparent. Although the observed similarities of the medically and surgically assigned groups at 10 years reflect return of symptoms in the surgical group to some extent, a more important explanation is the performance of late surgery in a large proportion of the medically assigned patients, rendering them asymptomatic.

Activities of Daily Living↗
PubMed1990

Autologous marrow transplantation for malignant lymphoma: a report of 101 cases from Seattle.

Between October 1979 and January 1988, 101 patients with malignant lymphoma who failed initial induction treatment or relapsed received high-dose combination chemotherapy or chemoradiotherapy followed by infusion of autologous bone marrow. Twenty-eight of the 101 patients survive, 18 of whom are disease-free for a median of 26 (range, 12 to 66) months. The 5-year actuarial probabilities of survival, event-free survival (EFS), and relapse from transplantation were 20%, 11%, and 84%, respectively. Multivariate analysis showed that the likelihood of EFS was decreased among patients transplanted with a Karnofsky score of less than 80%. Recurrent lymphoma after transplant was the most important cause of treatment failure with 36 of 62 relapses occurring within 100 days from marrow infusion. Early, but not late relapse, was more frequent in patients transplanted for advanced lymphoma, and both early and late relapses were increased among patients with impaired pretransplant clinical performance or high-grade histology of lymphoma. Ten patients who relapsed post-transplant are alive, seven in remission. Further improvement of these results will require earlier transplantation, improved preparative regimens, or early posttransplant therapy.

Adolescent↗
PubMed1990

The role of spinal flexibility in back pain complaints within industry. A prospective study.

Commonly used clinical measurements of spinal flexibility in the sagittal and frontal planes were examined as predictors of future back pain reports within industry. The study sample consisted of 3,020 aircraft manufacturing employees who were examined and tracked for more than 4 years for reports of back pain. Modified Schober, sit-and-reach, and lateral bending measurements were not significantly associated with risk of future back pain reporting, nor were any trends present. There was a statistically significant relationship between decreased flexibility and reports of current or previous back problems. However, the differences in flexibility between subjects with and without a history of back problems were too small to be of practical significance.

Adult↗