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Biomedical subjects

P Ernst

Publications and source records attributed to P Ernst.

At least 19 recordsLinked to original sources
PubMed1992

Effect of negative pressure ventilation in severe chronic obstructive pulmonary disease.

The hypothesis that patients with chronic obstructive pulmonary disease (COPD) have chronic inspiratory muscle fatigue was tested in an effectiveness trial in which negative pressure ventilation (NPV) was used to produce inspiratory muscle rest. In a double-blind study 184 patients with severe COPD were randomly allocated active or sham NPV treatment for a 12-week period of home use. The distance walked in a 6 min walk test was the primary outcome variable. Secondary outcome measures were cycle exercise endurance time, severity of dyspnoea, quality of life, arterial blood gas tensions, and respiratory muscle strength. The percentage reduction in amplitude of the diaphragmatic electromyographic signal multiplied by hours of NPV was used to reflect the dose of NPV so we could examine dose-response relations. Analysis was based on intention to treat. We found no evidence of a clinically or statistically significant difference in any outcome measure between active and sham groups. No dose-response relation was observed. Moreover, the intervention was poorly accepted despite substantial clinical support. We conclude that NPV as used in this study is difficult to apply and ineffective when used with the aim of resting the respiratory muscles in patients with stable COPD.

Aged↗
PubMed1992

The use of beta-agonists and the risk of death and near death from asthma.

BACKGROUND: Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of beta 2-agonist bronchodilators. METHODS: Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case-control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987. We matched 129 case patients who had fatal or near-fatal asthma with 655 controls (who had received medications for asthma but had not had fatal or near-fatal events) with respect to region of residence, age, receipt of social assistance, and previous hospitalization for asthma. RESULTS: The use of beta-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma (odds ratio, 2.6 per canister per month; 95 percent confidence interval, 1.7 to 3.9) and of death or near death from asthma, considered together (odds ratio, 1.9; 95 percent confidence interval, 1.6 to 2.4). For death from asthma, use of the beta-agonist fenoterol was associated with an odds ratio of 5.4 per canister, as compared with 2.4 for the beta-agonist albuterol. On a microgram-equivalent basis, the odds ratio for this outcome with fenoterol was 2.3, as compared with 2.4 with albuterol. CONCLUSIONS: An increased risk of death or near death from asthma was associated with the regular use of inhaled beta 2-agonist bronchodilators, especially fenoterol. Regardless of whether beta-agonists are directly responsible for these adverse effects or are simply a marker for more severe asthma, heavy use of these agents should alert clinicians that it is necessary to reevaluate the patient's condition.

Administration, Inhalation↗
PubMed1992

Role of T lymphocytes in intestinal mucosal injury. Inflammatory changes in athymic nude rats.

To determine the role of T cells versus mast cells in mucosal injury, we documented structural and functional changes in the intestine of congenitally athymic nude rats during infection with the enteric parasite, Nippostrongylus brasiliensis. Studies were conducted at days 4, 7, 10, and 21 postinfection; controls were uninfected. Villus damage was indicated by morphological abnormalities at days 7, 10, and 21 and reduced activities of disaccharidase enzymes at days 10 and 21. The activity of the proliferative enzyme, thymidine kinase, was increased only at day 21, at which time the crypts were elongated. Epithelial permeability increased significantly: 5-hr recovery (in urine and blood) of the probe molecule, [51Cr]EDTA, following injection into ligated jejunal segments, was elevated at days 7 and 10. Uptake of a protein antigen, ovalbumin, from lumen to blood followed a similar pattern. No evidence of functional T cells was demonstrated. However, mucosal mast-cell activation was indicated by elevated serum levels of rat mast-cell protease II at days 7 and 10. We conclude that the absence of thymus-derived T cells does not preclude mucosal damage involving impaired barrier and digestive function. Mucosal mast cells may be involved in causing the injury in this model.

Animals↗
PubMed1992

Double-lung transplantation for cystic fibrosis. The Cystic Fibrosis Transplant Study Group.

One hundred twenty cystic fibrosis patients were accepted for transplantation. Twenty-five patients underwent double-lung transplantation. Twenty-five patients died awaiting transplantation (20.6%). There were 13 female and 12 male patients. Their mean age was 28 years (range, 7 to 34 years), and mean percentage ideal body weight was 76% (range, 58.5% to 91.9%). Most patients were hypoxic and hypercarbic. Two patients underwent tracheal anastomosis, 15 had en bloc bronchial anastomoses, and 8 had sequential single-lung transplants. Operative mortality was 16%; all deaths were related to bleeding from extensive adhesions. Actuarial survival at 1 year was 64%. Rejection and infection were frequent during the first month and decreased thereafter. Airway complications occurred in 5 patients but were amenable to laser therapy and stenting. We conclude that double-lung transplantation is an acceptable modality for the treatment of cystic fibrosis patients with end-stage lung disease. It may be a better alternative to heart-lung transplantation considering the paucity of thoracic organ donors.

Adolescent↗
PubMed1992

Morphologic immunophenotypic and cytogenetic patterns of adult acute myeloid leukemia in Saudi Arabia.

During a 6-year period we received bone marrow (BM) and peripheral blood (PB) samples from 178 patients with acute myeloid leukemia (AML). All patient BM, and occasionally, PB samples were characterized according to FAB criteria, and by immunophenotyping (IP) and cytogenetics (CG). This report summarizes the findings in the 125 patients who were older than 15 years. Their mean and median ages were 39.4 and 37.0 years. There were 8 (6.4%) M1, 27 (21.6%) M2, 15 (12.0%) M3, 49 (39.2%) M4, 14 (11.2%) M5A, 9 (7.2%) M5B and 2 (1.6%) M6. IP showed that HLA-DR was most strongly and frequently expressed by M1 blasts (53.5%, 86%) and least strongly and frequently expressed by M3 blasts (4.5%, 0%). HLA-DR was also relatively strongly expressed by M4, M5A, M5B (21.5%, 43%; 34.9%, 69%; and 19.2%, 56%, respectively). CD11b was uniformly weakly expressed by all FAB subgroups. CD13 was most strongly and frequently expressed by M4 (20%, 43%), and was relatively weakly and infrequently expressed by the other FAB subtypes (9.5%, 9.2%, 16.4%, 8.4%, 16.3%). CD14 was moderately expressed by M4 (15.2%, 25%) and M5B (14.0%, 22%) and M1 (7.0%, 40%). CD33 was most strongly expressed by M3 blasts (26.3% and 61%), and was most weakly expressed by M5B (10.6% and 22%). Fourteen (11.2%) patients had blasts that showed lymphoid antigens (5 T, 5 B, 5 CALLA) in addition to myeloid characteristics. Fifty-four (51.9%) of 104 patients tested had one or more karyotypic abnormalities, the most frequent of which was 8+. Only the t(15:17) was specific, and was seen in M3. Four patients with anomalous IP had trisomy 21, one of whom also had 11q-. We conclude that Saudi Arabian AML shows FAB patterns similar to patients in the West, and that M3 patients have a characteristic IP and cytogenetic pattern. Apart from this the MIC classification failed to reveal characteristic modes.

Adolescent↗
PubMed1992

Double-blind randomized study of the effect of infusion rates on toxicity of amphotericin B.

Results of a double-blind randomized non-crossover study of rapid (45 min) versus slow (4 h) infusion of amphotericin B administered to 20 patients with proven or suspected fungal infection are reported. Toxicity was higher in the rapid infusion group than it was in the slow infusion group (mean total 7-day chill score, 173 +/- 276 versus 20 +/- 30 [P less than 0.01]; mean total 7-day dosage of meperidine required to abate rigors, 180 +/- 133 versus 58 +/- 78 mg [P less than 0.05]; and mean maximum total 7-day pulse rise, 225 +/- 64 versus 135 +/- 56 beats per min [P less than 0.02], respectively). When analyzed on a daily basis, the mean chill score, meperidine dosage, and pulse rise were also higher; and in addition, nausea and vomiting (5 of 11 patients who received a rapid infusion versus 0 of 9 patients who received a slow infusion [P less than 0.01]) appeared to be more common in those who received amphotericin B rapidly. The daily analysis approach proved that tolerance to these side effects developed with each subsequent infusion day, and by day 7 the incidence and severity were the same. This development of tolerance was significant for the mean chill score in the rapid infusion group (P less than 0.05) and for the proportion of patients with chills (P less than 0.005 for the slow infusion group; P less than 0.05 for the rapid infusion group). A decrease in creatinine clearance to greater than 51% of the baseline value was seen in two patients in each group. There were five deaths (four in the rapid infusion group, 1 in the slow infusion group) within 1 month, but none was clearly related to the amphotericin B infusion. The mean time to defervescence was similar for each group (10.8 +/- 4.1 days in the slow infusion group versus 9.9 +/- 5 days in the rapid infusion group). A rapid infusion regimen for amphotericin B cannot be recommended, at least during the first 5 to 7 days of treatment.

Adolescent↗
PubMed1992

Spirometric lung function. Distribution and determinants of test failure in a young adult population.

Spirometric test failure has been defined as failure by a subject to meet the acceptability and/or reproducibility criteria laid down by the American Thoracic Society for measurements derived from forced expiratory maneuvers. The prevalence and determinants of spirometric test failure were examined in 416 men and women aged 20 to 45 yr working in an office environment. In this study population, 11.5% (28 men and 20 women) exhibited test failure for forced expiratory volume in one second (FEV1). The main determinant of test failure in men was bronchial hyperresponsiveness to methacholine challenge (odds ratio 6.7; confidence interval 1.7, 27.1) and in women being a current smoker (odds ratio 4.02; confidence interval 1.13, 14.33). There was also a relationship to eczema in both men and women, but not at a statistically significant level. When FEV1 variability was defined as the difference (in milliliters) between the two best FEV1 values and the results of men and women combined for analysis, significant predictors were a history of eczema, recurrent chest illness in the past 3 yr, and level of bronchial responsiveness to inhaled methacholine. These findings contribute to the gathering evidence that test failure may be of itself an indicator of impaired respiratory health, and its association with bronchial hyperresponsiveness to methacholine in men suggests that in them test failure is related to airway lability, but in women the relationship to smoking suggests an irritative mechanism.

Adolescent↗
PubMed1992

Autologous versus allogeneic bone marrow transplantation for non-Hodgkin's lymphoma: a case-controlled analysis of the European Bone Marrow Transplant Group Registry data.

PURPOSE: A case-controlled study of patients who reported to the European Bone Marrow Transplant Group (EBMTG) was performed to investigate the relative roles and efficacy of allogeneic (alloBMT) and autologous bone marrow transplantation (ABMT) in non-Hodgkin's lymphoma. PATIENTS AND METHODS: Of 1,060 patients who reported to the lymphoma registry, 938 patients underwent ABMT and 122 patients underwent alloBMT. A case-controlled study was performed by matching 101 alloBMT patients with 101 ABMT patients. The case matching was performed after the selection of the main prognostic factors for progression-free survival by a multivariate analysis. RESULTS: The progression-free survival was similar in both types of transplants (49% alloBMT v 46% ABMT). The overall relapse and progression rate for the alloBMT patients was 23% compared with 38% in the ABMT patients. This difference was not significant statistically. In the lymphoblastic lymphoma subgroup, alloBMT was associated with a lower relapse rate than ABMT (24% alloBMT v 48% ABMT; P = .035). The progression-free survival, however, was not significantly different because patients with lymphoblastic lymphoma who underwent alloBMT had a higher procedure-related mortality (24% alloBMT v 10% ABMT; P = .06). A significantly lower relapse/progression rate was also observed in patients with chronic graft-versus-host disease (cGVHD) compared with those patients without (0% cGVHD v 35% no cGVHD; P = .02). Fourteen of 18 patients who had cGVHD also had lymphoblastic lymphoma. CONCLUSION: This study suggests that ABMT and alloBMT for non-Hodgkin's lymphoma are comparable, with the exception of lymphoblastic lymphoma in which a graft-versus-lymphoma effect may account for the lower relapse rate for patients who underwent alloBMT.

Adolescent↗
PubMed1992

No advantage for patients who receive splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia: results of a prospective randomized study.

A total of 239 patients with chronic myeloid leukaemia (CML) in chronic phase awaiting bone marrow transplantation (BMT) from an HLA-identical sibling donor were randomized to receive, as part of their conditioning, splenic irradiation (SI+) or no splenic irradiation (SI-). There was no difference between the SI+ and SI- groups regarding the distribution of age, sex, donor/recipient sex combination and blood counts at diagnosis and at BMT. Survival, leukaemia-free survival (LFS), incidence of transplant-related mortality, incidence of rejection and probability of relapse do not differ between the 117 SI+ and the 118 SI- patients at a median follow-up time of 2.5 years (minimum 0.5 years). LFS at 30 months is 56% (SE 5%) for the SI+ and 51% (SE 6%) for the SI- group (p = 0.65). LFS is better for younger patients (less than 25 years), for patients without T cell depletion and for those with a low white blood cell count at diagnosis (less than 30 x 10(9)/l) (p less than 0.05). It is worst for male recipients of a female marrow (p less than 0.05). The incidence of graft-versus-host disease grade greater than or equal to II was higher in the SI+ group, though not significantly. We conclude that routine splenic irradiation prior to BMT for patients with CML is of no benefit and should not be used as a routine procedure.

Adolescent↗
PubMed1991

Fissural thickening and exposure to asbestos: occurrence, determinants, and functional impact.

The occurrence and determinants of thickened interlobar fissures were assessed in 147 insulators, in order to test the hypothesis that radiographic abnormalities in minor (FMN) and/or major (FMJ) interlobar fissures are associated with restrictive respiratory impairment, which may reflect early parenchymal lung fibrosis. According to the diagnostic criteria developed, definite interlobar thickening was found in 33 (FMN) and in 73 (FMJ) men, and was frequently associated with the presence of classical asbestos pleural disease, though not parenchymal abnormality. Multivariate analyses did not demonstrate any association between either FMN or FMJ and lung function. Such an association, however, was found in the case of the usual asbestos-related pleural change. These findings suggest that fissural thickening seen on chest radiography represents a component of asbestos pleural disease and not asbestosis.

Adolescent↗
PubMed1991

Simplified determination of antipyrine clearance by liquid chromatography of a microsample of saliva or plasma.

We describe a simplified and rapid liquid chromatographic determination of antipyrine clearance (CLAP) calculated from peak height ratios of drug/internal standard. Saliva or plasma was collected 24 hr after the oral administration of 1 g of antipyrine to the subject. A 25-microliter aliquot of the sample is deproteinized with acetonitrile containing 3-nitrophenol (internal standard) and injected into a radial compression module equipped with a 10-micron, 8 mm x 10-cm C18 cartridge, using a 0.025 M aqueous solution of sodium acetate and acetonitrile (88.5:11.5). The minimum measurable concentration was 0.2 microgram/ml. The obtained CLAP values in five healthy subjects and five patients with chronic liver disease coincided well (r greater than 0.9994) with those generated by the use of an established method. The antipyrine clearance in the healthy subjects ranged from 2.203 to 5.721 liters/hr, while in patients with chronic liver disease it was significantly (P less than 0.0027) less (range, 0.544 to 1.103 liter/hr). We also determined antipyrine clearance in two of these subjects given lower doses of this drug and found that the dose has no significant impact on this parameter.

Antipyrine↗
PubMed1991

Comparison of French and English versions of the American Thoracic Society respiratory questionnaire in a bilingual working population.

Standardized French and English versions of the American Thoracic Society (ATS) respiratory disease questionnaire were administered to 204 English-speaking and 406 French-speaking male blue-collar aviation workers unexposed to occupational respiratory hazards. After adjusting for smoking status, age, years of education, foreign birth and maternal language other than French or English, no significant differences between the two questionnaires were found for response rates to usual cough, usual phlegm, mild or moderate dyspnoea, and chronic bronchitis. French-speaking workers reported significantly less wheeze with colds (OR = 0.60, p less than 0.02) and wheeze apart from colds (OR = 0.55, p less than 0.05) than the English-speaking group, but, the occurrence of wheeze on most days or nights was similar for both groups (OR = 1.02, NS). For 66 bilingual workers who completed both French and English questionnaires at a time interval of approximately two months, highly consistent results were found for sociodemographic data, smoking habits, cough, phlegm, breathlessness and chronic bronchitis, but not for wheeze with or apart from colds (agreement less than 90%; Kappa less than 0.50). These results reflect the difficulties in translating the concept of 'wheeze' from English to French. We conclude that most symptoms elicited by the French questionnaire may be generalized to English-speaking populations, but that questions pertaining to wheeze on most days or nights may be preferable to other questions concerning wheeze.

Data Collection↗
PubMed1991

Effect of cigarette smoking on evolution of ventilatory lung function in young adults: an eight year longitudinal study.

BACKGROUND: There are few data on the quantitative effects of cigarette smoking on lung function in young adults. These effects are important in the understanding of the early stages of chronic airflow obstruction. METHODS: A longitudinal study over eight years was carried out to estimate quantitatively the effect of cigarette smoking on ventilatory lung function in young adults and to examine the possibility that the effect is modified by other factors. The study population were 15 to 40 years of age at initial examination, when they underwent spirometry and completed an interviewer administered questionnaire on respiratory health. Eight years later 391 of the subjects were re-examined (38% response rate). The quantitative effect of cigarette smoking during the study period on the average change of forced expiratory volume in one second (FEV1) over time (delta FEV1) was estimated in two linear regression models that included potential confounders and other determinants of outcome. RESULTS: The first model showed a significant dose-response relation between the average rate of smoking during the study period and delta FEV1, giving an estimate of annual change in FEV1 of -0.42 ml for each cigarette smoked per day (-8.4 ml for each pack) (p = 0.04). In the second model, which took smoking before the study period as a potential confounder, the effect of smoking during the study period was slightly smaller (-0.33 ml/year for each cigarette smoked per day). This indicated that smoking before the study period had a marginal latent effect on delta FEV1 during the study. However, neither the effect of smoking before the study nor that of smoking during the study was significant, presumably because of collinearity. Interactions between cigarette smoking and gender, wheezing, atopy, and exposure to environmental tobacco smoke during the growth period were not significant with respect to their effect on the relation between cigarette smoking and delta FEV1. CONCLUSION: Cigarette smoking has a dose related adverse effect on the evolution of ventilatory lung function in young adulthood.

Adolescent↗
PubMed1991

Successful treatment of steroid-resistant double-lung allograft rejection with Orthoclone OKT3.

An 18-yr-old woman with cystic fibrosis who received a double-lung transplant developed a severe episode of acute lung rejection. Bronchoalveolar lavage and transbronchial biopsy were used to establish the diagnosis. The rejection was refractory to administration of high-dose pulse steroids. OKT3 therapy was successfully used to reverse this episode. This is the first case report of a steroid-resistant double-lung allograft rejection successfully treated with OKT3.

Adolescent↗