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Biomedical subjects

P Ernst

Publications and source records attributed to P Ernst.

At least 145 records · Page 8Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Descriptive study of prognostic factors influencing survival of compensated silicotic patients.

The objective of this study was to assess survival and the prognostic influencing survival of compensated silicotic patients. All workers compensated for silicosis in the Province of Quebec from 1938 to 1985 (n = 1,165) were included. Clinical data were those collected during the exam that led to a compensation decision. Due to missing data, a subcohort of 961 patients was used for multivariate analysis of clinical prognostic factors with the Cox proportional hazards model. The following factors made an independent contribution to survival: age at compensation, smoking, dyspnea, expectoration, abnormal breath sounds, radiographic appearance, and vital capacity. On the basis of the model, patients with small opacities alone on their chest radiograph and who did not have dyspnea, expectoration, or abnormal breath sounds had a survival similar to the average Quebec man; other patients had a poorer survival. We conclude that it is possible to identify at the time of compensation, silicotic patients who are likely to have a life expectancy similar to that of the general population. Symptoms and physical signs as well as radiographic and lung function abnormalities appear to be useful prognostic indicators in compensated silicotic patients.

Dyspnea↗

Clinical complexity and epidemiologic uncertainty in case-control research. Fenoterol and asthma management.

Two recent epidemiologic case-control studies suggested that fenoterol, a selective beta-adrenergic agonist, was associated with an increase in the risk of asthma death. The results of these studies were criticized because of methodologic problems in the choice and selection of control subjects; the different methods used to gather exposure data in cases and control subjects; and because of inadequate classification and adjustment for asthma severity. In response to this controversy, a new study is underway, the Saskatchewan Asthma Epidemiology Project. The SAEP includes two complementary studies, an historic cohort and a case-control analysis, that employ the computerized databases of the Saskatchewan Health Department. A unique aspect of the SAEP is the attempt to incorporate knowledge of asthma physiology and management into the design of the studies. Specifically, the study design recognized the role of antiinflammatory drugs in asthma treatment; the distinction between asthma death and near-fatal asthma; the severity of asthma; patterns of drug use; and the distinction between inadequate clinical care and disease severity. The strategies we employed in the SAEP may prove helpful to investigators whenever clinical and biologic processes create sources of potential bias requiring special procedures for the design and analysis of epidemiologic studies.

Adolescent↗

Ventilatory lung function in young cigarette smokers: a study of susceptibility.

The objective of this study was to estimate the effect of cigarette smoking on ventilatory lung function among young adults with special emphasis on the recognition of susceptible subgroups. In a cross-sectional study of 1,044 adults aged 15-40 yrs, a statistically significant linear relationship between quantity of smoking in cigarette-years and level of forced expiratory volume in one second (FEV1) was found. Among current cigarette smokers, FEV1 level was on average 35 ml lower for each 100 cigarette-years of exposure (corresponding to smoking of ten cigarettes per day for 10 yrs) compared to lifelong nonsmokers in a linear regression adjusted for confounding. Potentially susceptible subgroups were studied by introducing interaction terms between quantitative smoking and gender, wheezing, atopy, asthma, childhood respiratory illness and exposure to environmental tobacco smoke during the growth period, to the additive linear regression model explaining the FEV1 level. Wheezing was found to modify the effect of smoking significantly: the FEV1 level was on average 68 ml lower for each 100 cigarette-years due to interaction between smoking and wheezing. An introduction of the interaction term eliminated the independent effect of smoking. The results suggest that the detrimental effect of smoking on FEV1 in young adults may be limited to individuals with wheezing. Thus, the presence of wheezing among smokers indicates a higher risk for low level of ventilatory lung function compared to smokers who do not wheeze.

Adolescent↗

Dry electrolyte-balanced heparinized syringes evaluated for determining ionized calcium and other electrolytes in whole blood.

By analyzing whole blood containing no anticoagulants (uncoagulated whole blood) immediately after collection, we evaluated the relative changes in the concentrations of ionized calcium and other electrolytes in whole blood collected in dry heparinized syringes and in serum prepared from blood collected in evacuated blood-collection tubes. Using these dry heparinized syringes, we collected and analyzed whole blood that contained either 33 or 13 int. units of lithium heparin or 40 int. units of electrolyte-balanced heparin per milliliter of blood. We evaluated the effects both of these heparins at different concentrations of ionized calcium and of the incomplete filling of the syringes. We conclude that: (a) when analyzed within 2-3 min after collection, uncoagulated whole blood provides ionized calcium results unaffected by anticoagulants or cellular metabolism; (b) the preparation of serum unpredictably changes ionized calcium; (c) the use of dry electrolyte-balanced heparin virtually eliminates the interference in ionized calcium concentrations between 0.9 and 1.6 mmol/L; and (d) incomplete filling of electrolyte-balanced heparinized syringes produces no effect in syringes two-thirds full (60 int. units/mL heparin concentration) and a small effect in syringes one-third full (120 int. units/mL heparin).

Adult↗