Biomedical subjects

M Pettinger

Publications and source records attributed to M Pettinger.

11 recordsLinked to original sources

PubMed1992

Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate.

Previous studies of risk factors for acute graft-versus-host disease (GVHD) involved patients receiving predominantly single-agent prophylaxis. Therefore, a retrospective analysis was performed on 446 patients, from a single institution, who received transplants of marrow from HLA-identical siblings and the combination of cyclosporine (CSP) and methotrexate (MTX) to determine risk factors for acute GVHD associated with this more effective form of GVHD prophylaxis. The incidences of Grades II-IV and Grades III-IV (severe) acute GVHD were 35% and 16%, respectively. Increased clinical grades of acute GVHD in patients without advanced malignant disease were associated with a decreased survival. In a multivariate Cox regression analysis, risk factors associated with the onset of Grades II-IV acute GVHD were sex mismatch and donor parity (P = .001), increased dose of total body irradiation (TBI) (P = .001), and reduction to less than 80% of the scheduled dose of MTX (P = .02) or CSP (P = .02). The multivariate analysis indicated a relative risk of 1.37 for acute GVHD in a group defined as having advanced malignant disease at transplant; however, this difference failed to reach conventional levels of statistical significance (P = .07). Reduction of MTX and CSP occurred in up to 36% and 44% of patients, respectively, primarily because of renal or hepatic dysfunction. The periods of increased risk for the onset of acute GVHD were up to 1 week after a reduction of MTX and 2 weeks after a reduction in CSP. When only patients who developed Grades II-IV acute GVHD were considered, the more severe acute GVHD of Grades III-IV was associated with increased patient age of 40 years or greater (P = .05) and dose reductions of CSP (P = .008). Serologic status of patient and donor for cytomegalovirus (CMV), HLA antigens in the A and B loci, and isolation in a laminar air flow room during marrow transplantation, all previously identified as risk factors for acute GVHD, were not confirmed as risk factors in this study population. The toxicity of MTX and CSP and the development of acute GVHD from inadequate immunosuppression because of dose reduction warrants further trials with potentially less toxic immunosuppressive agents. Risk factors for acute GVHD should be considered in clinical management and in the design of clinical trials.

Adult↗

PubMed1992

Cytomegalovirus antigen detection in peripheral blood leukocytes after allogeneic marrow transplantation.

Detection of cytomegalovirus (CMV) antigenemia was compared with shell vial centrifugation cultures for rapid detection of CMV infection. In a prospective study, 59 CMV seropositive patients were monitored weekly during the first 100 days after allogeneic marrow transplantation for virus excretion from urine, throat, and blood and for antigenemia by direct staining of peripheral leukocytes using an antibody pool directed against pp 65. Antigenemia was present in 21 of 22 patients with culture-proven CMV infection and in 3 of 37 without culture-proven CMV infection (sensitivity 95%, specificity 91%). The median time of onset of antigenemia and shell vial cultures was day 47 and 55 after transplant, respectively (P = .0006). Among patients who developed CMV disease without preceding cultures, antigenemia was detected in all patients with CMV pneumonia (N = 6) and in two of three patients with gastrointestinal disease by a median of 10 and 7 days, respectively, before the onset of disease (P = .0002). Levels of antigenemia were significantly higher in patients with disease or viremia than in patients with excretion from urine or throat (P less than .05). Whether the antigenemia assay is more sensitive than rapid culture methods to focus antiviral prophylaxis in marrow transplant patients must be determined in controlled studies.

Antigens, Viral↗

PubMed1990

Ten-year follow-up of survival and myocardial infarction in the randomized Coronary Artery Surgery Study.

The Coronary Artery Surgery Study (CASS) randomized 780 patients to an initial strategy of coronary surgery or medical therapy. Of medically randomized patients, 6% had surgery within 6 months and a total of 40% had surgery by 10 years. At 10 years, there was no difference in cumulative survival (medical, 79% vs. surgical, 82%; NS) and no difference in percentage free of death and nonfatal myocardial infarction (medical, 69% vs. surgical, 66%; NS). Patients with an ejection fraction of less than 0.50 exhibited a better survival with initial surgery treatment (medical, 61% vs. surgical, 79%; p = 0.01). Conversely, patients with an ejection fraction greater than or equal to 0.50 exhibited a higher proportion free of death and myocardial infarction with initial medical therapy (medical, 75% vs. surgical, 68%; p = 0.04) although long-term survival remained unaffected (medical, 84% vs. surgical, 83%; p = 0.75). There were no significant differences either in survival and freedom from nonfatal myocardial infarction, whether stratified on presence of heart failure, age, hypertension, or number of vessels diseased. Thus, 10-year follow-up results confirm earlier reports from CASS that patients with left ventricular dysfunction exhibit long-term benefit from an initial strategy of surgical treatment. Patients with mild stable angina and normal left ventricular function randomized to initial medical treatment (with an option for later surgery if symptoms progress) have survival equivalent to those patients randomized to initial surgery.

Coronary Artery Bypass↗

PubMed1989

Comparison of coronary angioplasty with medical treatment for single- and double-vessel coronary disease with left anterior descending coronary involvement: long-term outcome based on an Emory-CASS registry study.

The 3 to 5-year clinical outcomes of 627 consecutive patients selected for treatment with percutaneous transluminal coronary angioplasty (PTCA) at Emory University Hospital for one- or two-vessel coronary artery disease with involvement of the left anterior descending coronary artery, between July 1981 and June 1983, and 865 patients in the Coronary Artery Surgery Study with similar coronary artery disease involvement selected for medical therapy between 1975 and 1979 were compared. Cox analyses and stratified life table analyses were used to adjust for differences in 13 variables including concurrent medical therapy. Complete follow-up was obtained in 97% of PTCA patients and 99% of medically treated patients. After correction for baseline differences in significantly predictive variables, there was no difference between the relative risk of death after PTCA vs medical therapy (RR = 0.7; p = 0.36). However, results of analysis of prospectively defined subsets showed a potential survival benefit after PTCA for patients with an ejection fraction less than 50% (RR = 0.2; p = 0.02) and also for patients with two-vessel disease (RR = 0.2; p = 0.04). For the groups as a whole there was no difference in risk of infarction after PTCA and medical therapy (RR = 0.8; p = 0.58). However, for patients with 90% to 99% LAD stenosis there was a trend toward lessened risk of infarction after PTCA (RR = 0.6; p = 0.15). No patient subset had a higher risk of death or infarction with PTCA (p less than or equal to 0.15). The likelihood of later surgery was increased after PTCA (RR = 1.5; p = 0.002). Angina, employment, and activity levels were improved after PTCA. Thus PTCA compared to medical therapy was associated with improved functional status and may decrease the risk of death and infarction in certain patient subsets. However, bypass surgery was more often performed in patients initially treated with PTCA. These data should be interpreted in light of their nonrandomized study origin and generation from different clinical sites.

Activities of Daily Living↗

PubMed1988

The prevalence of steal-prone coronary anatomy in patients with coronary artery disease: an analysis of the Coronary Artery Surgery Study Registry.

Coronary steal requires a specific anatomic arrangement of coronary occlusion, collateral vessels, and stenosis of the artery supplying the collaterals. The prevalence of this anatomic variant, steal-prone coronary anatomy, was investigated in 16,249 patients with coronary artery disease whose angiograms were carefully recorded as part of the Coronary Artery Surgery Study (CASS). Almost half of the angiograms had one or more total occlusions, and, of these, about 80% had angiographically visible collateral supply to the area distal to the occlusion. Of subjects with an occlusion and collaterals, about 60% had a hemodynamically significant stenosis of the artery supplying the collateral vessels. In summary, 23% of the patients in the CASS Registry demonstrated steal-prone coronary anatomy. Thus, coronary steal could possibly affect almost a quarter of the patients with coronary artery disease having anesthesia. Studies that seek clinical evidence of harm from coronary steal must be done in that subset of patients with coronary artery disease with steal-prone anatomy.

Angiography↗

PubMed1988

Clinical implications of internal mammary artery bypass grafts: the Coronary Artery Surgery Study experience.

From the Coronary Artery Surgery Study Registry, all patients undergoing initial bypass surgery procedures with independent vein grafts were identified. The 950 patients receiving an internal mammary artery bypass graft were compared with the 6027 patients receiving vein graft alone. Improved survival rates with internal mammary artery grafts were noted at hospitals in which these grafts were performed infrequently as well as those in which the internal mammary artery graft was used frequently. The improved survival was noted in patients with normal (p = .004) as well as impaired (p = .004) ventricular function, in men (p = .0001) as well as women (p = .005), in patients over age 65 (p = .01) as well as younger patients (p less than .0001), and in those with (p = .05) or without (p less than .0001) critical stenosis of the left main coronary artery. The internal mammary artery bypass graft was an independent predictor of survival (p = .0004) and reduced the risk of dying by a factor of 0.64. It was concluded that the internal mammary artery graft is the bypass vessel of choice and should not be denied any subgroup.

Blood Vessel Prosthesis↗

PubMed1988

ST segment elevation with exercise: a marker for poor ventricular function and poor prognosis. Coronary Artery Surgery Study (CASS) confirmation of Seattle Heart Watch results.

The functional and prognostic significance of exercise-induced ST elevation (by computer averaging) in ambulatory patients with coronary heart disease was recently reported for 181 patients in the Seattle Heart Watch (SHW). To further evaluate this, 3050 approximately similar patients enrolled in CASS were analyzed with respect to initial findings, survival, and incidence of secondary coronary events over the next 6 years. The ST elevation responses in CASS patients were classified by visual interpretation of 1 mm or more, whereas the SHW patients were identified by voltage greater than 0 mV. Accordingly, prevalence of exercise-induced ST elevation was lower in CASS patients, but they had greater frequencies of prior myocardial infarction and left ventricular enlargement and dysfunction. The poor survival was similar in the subgroup with ST elevation during exercise and recovery in CASS and SHW. Although not an independent predictor when invasive variables are known, ST elevation emerges as a useful predictor when exercise testing is performed before diagnostic invasive studies.

Coronary Disease↗

PubMed1986

Should airline pilots be eligible to resume active flight status after coronary bypass surgery?: a CASS registry study.

Medical certification to return to work after coronary bypass surgery in occupations that carry a risk to public safety is controversial, particularly for airline pilots. To address this issue, 10,312 patients from the CASS registry who underwent coronary bypass surgery were studied and 2,326 men with clinical and postoperative characteristics similar to those of the average airline pilot who might apply to renew his license after surgery were selected. The 5 year probability of remaining free of an acute cardiac event, defined as acute coronary insufficiency, myocardial infarction or sudden death, was 0.92 +/- 0.01 (mean +/- SE) for the 1,207 men without previous myocardial infarction and 0.98 +/- 0.01 for the 122 men who never smoked and did not have a history of hypertension. Among the 1,119 men with a previous myocardial infarction, the probability of remaining free of acute cardiac events was 0.91 +/- 0.02 and 0.92 +/- 0.02 when left ventricular contraction score was 5 to 9 and 10 or greater, respectively. In this patient subgroup, mortality rate was similar to that of the age-matched U.S. male population when the left ventricular contraction score was 5 to 9 (4.0% versus 4.3%; p = NS) but significantly worse when the left ventricular contraction score was 10 or greater (7% versus 4.2%; p = 0.05). The data from this CASS registry study are pertinent to the question of operationally unlimited first-class medical certification of carefully selected airline pilots after coronary bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

The effect of medical and surgical treatment on subsequent sudden cardiac death in patients with coronary artery disease: a report from the Coronary Artery Surgery Study.

The effect of medical and surgical treatment on subsequent sudden cardiac death was assessed in 13,476 patients in the Coronary Artery Surgery Study registry who had significant coronary artery disease, operable vessels, and no significant valvular disease. (Patients were assigned to medical or surgical therapy on the basis of clinical judgment and not according to a randomization scheme; therefore, biases associated with unknown variables could not be evaluated.) Sudden cardiac death occurred in 452 patients (3.4%) during a mean follow-up of 4.6 years. Five year survival free of sudden death for medically treated patients was 94 +/- 0.3%, and that for surgically treated patients was 98 +/- 0.2% (p less than .0001). Twelve baseline clinical, electrocardiographic, and angiographic variables were significantly different between patients alive at the last follow-up and those suffering sudden death. Data on these variables were available for 11,508 patients. Sudden death occurred in 257 (4.9%) of 5258 medically treated and 101 (1.6%) of 6250 surgically treated patients. In a high-risk patient subset with three-vessel disease and history of congestive heart failure, 91% of surgically treated patients had not suffered sudden death compared with 69% of medically treated patients. After Cox survival analysis was used to correct for baseline variables, surgical treatment had an independent effect on sudden death (p less than .0001). This reduction was most pronounced in high-risk patients.

Coronary Artery Bypass↗

PubMed1985

A test of the National Death Index using the Coronary Artery Surgery Study (CASS).

The National Death Index (NDI) is a central, computerized index of death record information compiled from records submitted by the Vital Statistics Office of each state to the National Center for Health Statistics. A selection of 1180 cases, including 370 decedents, from the Coronary Artery Surgery Study was sent to the NDI to test the reliability of the index in identifying decedents. Five possible matching rules are considered: an NDI match with soundex included, an NDI match without soundex matches, an NDI match on social security number, an NDI match on personal data (first name, last name, sex, race, and month, day, and year of birth), and an NDI match on social security number or personal data. In determining death, the greatest positive predictive value was given by a match on social security number, while the greatest negative predictive value was given by an NDI match with soundex included. Further comparisons of sensitivity and specificity, and figures that relate predictive values to the population mortality rate, are given to assist potential users in determining an optimal matching rule.

Coronary Disease↗

PubMed1985

The effect of clinical characteristics on the comparison of medical and surgical therapy in the Coronary Artery Surgery Study (CASS) and the Veterans Administration Cooperative trial.

The CASS randomized trial was compared with the Veterans Administration (VA) randomized study of coronary bypass surgery with respect to the influence of clinical characteristics on the comparison of medical and surgical therapy. With regard to clinical baseline characteristics, the CASS population was overall at lower risk than the VA population. Average percent survival for years 1 through 6 were greater in the CASS than in the VA study for patients in both the medical and surgical groups. In the VA population, a multivariate risk index was developed with the use of presence or absence of New York Heart Association functional class III or IV, history of hypertension, history of myocardial infarction, and ST depression on the resting electrocardiogram. Low-, middle-, and high-risk terciles in the VA study population were determined based on this index. In the low-risk tercile, VA patients treated medically had a greater percent survival at 6 years than those treated surgically. In the high-risk tercile, VA patients treated surgically had markedly improved survival compared with those treated medically. These results were not replicated by the CASS study. In CASS, there were no significant differences between patients assigned to medical and surgical treatment within the terciles. Other noninvasive risk indexes were explored in CASS, but no subgroups defined solely by clinical features could be found wherein patients assigned to medical and surgical therapy were significantly different. Basic differences in the populations sampled are the most probable reason for the different results in the CASS and VA trials.

Clinical Trials as Topic↗