[General principles in interpreting diagnostic tests].
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Diagnosis, Differential↗
Biomedical subjects
A F Junod
Publications and source records attributed to A F Junod.
[Decision analysis: application of a diagnostic and therapeutic strategy in cases of bronchial carcinoma].
Faced with a constant development of new methods of treatment and diagnosis, the clinician does not always have an easy task: the multiplicity of options available makes it difficult to take decisions guaranteeing both maximum safety of diagnosis with a reasonable number of examinations. In relation to this problem the respective places of CT scanning, mediastinoscopy and exploratory thoracotomy in the search for metastatic mediastinal adenopathy in the course of the local and regional assessment of a bronchial carcinoma are considered. In this situation the general principles of decision analysis can be contemplated: the characteristics of the test (sensibility and specificity), the prevalence of the disease and Bayes theorem and the concept of utility. The consequences flowing from this approach are analysed.
Carcinoma, Bronchogenic↗
[Characteristics of respiratory functional involvement in MacLeod's syndrome (or Swyer-James syndrome)].
MacLeod's syndrome (Swyer-James' syndrome in the child) is a radiologic entity: hyperlucency of one or several lobes, or even of one lung, scarce hilar shadow on the same side as the abnormal transradiency, and barely visible arterial network on the abnormal side of the thorax. Distal bronchiectases (bronchography) and abnormal distal bronchi (necropsy) suggest that this disease may be due to bronchiolitis in childhood. An obstructive pulmonary disorder, assessed by pulmonary function tests, has been described in this syndrome. However, neither the prevalence nor the severity or evolution of the obstructive defect are known. We have studied two such patients for 5 and 12 years respectively: during this long follow-up period the obstructive disorder, albeit severe, remained stable. We have also analysed the 75 cases in the literature in which pulmonary function tests are available and comparable. We have been able to show that (1) an obstructive disorder is frequent in MacLeod's syndrome, (2) the severity of this disorder differs markedly between patients, and (3) this airflow limitation is probably stable on a long-term basis. These findings are compatible with the pathogenetic hypothesis at present accepted, ie bronchiolitis during childhood, and suggest that the inflammatory bronchial disease may have been generalized in many such patients.
Adult↗
[Case finding in bronchial carcinoma: cost-effectiveness].
The data in the study sponsored by the National Cancer Institute make it possible to calculate the cost of early detection of bronchial carcinoma by radiologic and/or cytologic examination. For the initial series of tests (prevalence study), the cost of one case of screening-related survival amounts to: 417 chest roentgenograms + 417 sputum cytological examinations + 33 investigations to clarify abnormal chest roentgenograms. If cytological investigation alone is performed 2500 examinations are needed for one case of screening-related survival. If these examinations are repeated on a yearly basis, the benefit related to this screening effort is less than 1 case of survival/1000 subjects/year.
Aged↗
Comparative study on the selenium- and N-acetylcysteine-related effects on the toxic action of hyperoxia, paraquat and the enzyme reaction hypoxanthine-xanthine oxidase in cultured endothelial cells.
The potential protective effect of N-acetylcysteine against various types of oxidative stress (exposure to hyperoxia, treatment with paraquat, incubation in the presence of the hypoxanthine-xanthine oxidase system) was tested in primary cultures of porcine aortic endothelial cells. It was compared to that of selenomethionine (Se-Met), known to increase glutathione peroxidase activity, when given either alone or in combination with N-acetylcysteine. LDH release, 3H-thymidine (TdR) incorporation into DNA and DNA content were measured to assess the cytotoxic effect of the conditions tested. Total and oxidized glutathione content was also determined. Whereas Se-Met had a partial protective effect on all the conditions but paraquat treatment, N-acetylcysteine administration had no effect on the hyperoxia induced changes and significantly worsened the cytotoxic action of paraquat. On the other hand, LDH release following an incubation in the presence of the hypoxanthine-xanthine oxidase was significantly reduced after N-acetylcysteine treatment. No major change in total nor in oxidized glutathione followed N-acetylcysteine treatment in control and experimental conditions. A dose-dependent protective effect of N-acetylcysteine was obtained when this agent was given concomitantly with the xanthine oxidase system. These data suggest that in cultured endothelial cells a N-acetylcysteine-related protective effect, if present, is most likely to result from the direct scavenging action of N-acetylcysteine.
Acetylcysteine↗
Thymidine kinase, thymidylate synthase, and endothelial cell growth under hyperoxia.
To determine the respective role of thymidine kinase and thymidylate synthase activities in the hyperoxia-induced decrease in DNA synthesis and their relationship with cell replication, we measured these two enzyme activities in primary cultures of porcine aortic endothelial cells under different O2 concentrations for various durations. In confluent cells, exposure to 95% O2 for 5 days reduced thymidine kinase activity to 15% of control values; thymidylate synthase activity was unaffected. In preconfluent cells exposed to 95% O2 for 2 days, similar results were obtained, together with evidence for arrest in cell proliferation. Thymidylate synthase activity could therefore not be related to decreased cell proliferation under hyperoxia. [3H]thymidine incorporation into DNA, thymidine kinase activity, and cell proliferation were all similarly affected under exposure to graded O2 concentration for 2 days. Thymidine kinase appears to be a key enzyme in the modulation of DNA synthesis from thymidine and in its replication in endothelial cells.
Animals↗
Protein synthesis in hyperoxic endothelial cells: evidence for translational defect.
To study the effects of hyperoxia on protein synthesis in primary cultures of porcine aortic endothelial cells, we exposed confluent cells to different O2 concentrations for various durations. Exposure to 95% O2 for 5 days resulted in a 71% inhibition of [3H]phenylalanine incorporation into total proteins. When compared with control cells, we observed no changes in 1) the pool size of free cytoplasmic phenylalanine and of phenylalanine attached to transfer RNA (tRNA), 2) the rate of protein degradation, and 3) the rate of charging of tRNA with phenylalanine. We found that under hyperoxic conditions 1) the incorporation of [3H]-uridine into total and polyadenylated RNA was increased, 2) the efficiency of extracted messenger RNA to direct protein synthesis in a reticulocyte lysate was maintained, 3) the proportion of polymeric to monomeric ribosomes was slightly increased, and 4) the rate of elongation, as measured by the ribosomal transit time, was decreased. Thus the reduction in protein synthesis in hyperoxic cells appears to result primarily from defects at the translational level in polypeptide chain elongation.
Animals↗
Effects of oxygen intermediates on cellular functions.
This brief illustration of the effects of O2 metabolites and of hyperoxia on some of the main functions of the cells, DNA and protein synthesis, indicates that major changes can occur in cells exposed to oxidative stresses such as those occurring in an inflammatory reaction. The relative sensitivity of the various cell populations may favor the emergence of some cells and the disappearance of others. Depending on the sensitivity of different enzymes to oxidative injury, the response of cells in terms of both mediator production and of response to the action of the mediators themselves may be affected.
Animals↗
[Pulmonary toxicity of drugs].
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Anti-Bacterial Agents↗
Rapidly progressive interstitial lung disease in a hard metal coating worker undergoing hemodialysis.
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Acute Disease↗
[Aspergillosis with obstruction of the central airways].
Two cases are reported of obstruction of central airways by plugs containing Aspergillus fumigatus. In one case the obstruction was located in the right stem bronchus and, despite treatment with amphotericin B, the immunocompromised patient died from invasive disseminated aspergillosis. In the other case the obstruction was in the trachea and, since the immune function of the patient was normal, she responded favorably to treatment by amphotericin B.
Adolescent↗
[The role of broncho-alveolar lavage in clinical pneumology and research].
Bronchoalveolar lavage is a recently developed technique which serves to sample the cells free in the alveolar spaces. It has thus been found that many pulmonary interstitial disorders are characterized by increased cellularity involving lymphocytes and/or polymorphonuclears, neutrophils or eosinophils. Bronchoalveolar lavage is rarely of diagnostic use but may provide interesting information on the inflammatory activity of many pulmonary diseases. Bronchoalveolar lavage appears to be a promising tool for study of the pathogenesis of these diseases.
Bronchi↗
Exercise induced asthma and endogenous opioids.
Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV1 was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV1; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, beta endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma.
Adult↗
Differential effects of hyperoxia and hydrogen peroxide on thymidine kinase and adenosine kinase activities of cultured endothelial cells.
To compare the respective sensitivity of two nucleoside kinases, adenosine kinase and thymidine kinase, to oxidative stress, we measured these enzyme activities in cultured aortic endothelial cells exposed for 48 h to various O2 concentrations, and in cell extracts treated with H2O2 or the enzyme system hypoxanthine-xanthine oxidase. Adenosine kinase activity was not significantly influenced by the exposure to hyperoxia, nor by treatment with the enzyme system hypoxanthine-xanthine oxidase or with H2O2. On the other hand, there was a dose-dependent inhibitory effect on thymidine kinase activity resulting from exposure to various O2 concentrations or from treatment with various amounts of xanthine oxidase. Incubation of cell extracts in the presence of H2O2 also resulted in a significant reduction of thymidine kinase activity. These results indicate that thymidine kinase exhibits a selective sensitivity to the toxic effect of O2 concentrations and of O2 intermediates such as H2O2.
Adenosine Kinase↗
[Interauricular right-left shunt: a serious complication of primary pulmonary arterial hypertension].
Primary pulmonary hypertension is a rare and generally progressive disease in which mild hypoxemia at rest, with lower PaO2 during exercise, is consistently reported. Severe hypoxemia at rest suggests the occurrence of a right to left intracardiac shunt, most often due to patency of a foramen ovale. Two cases are reported of primary pulmonary hypertension which rapidly developed severe hypoxemia at rest with worsening of pulmonary hypertension, from which interatrial communication was identified. The prognostic and therapeutic implications of this situation are discussed.
Adult↗
Effects of LTB4 and Ca++ ionophore A23187 on the release by human alveolar macrophages of factors controlling fibroblast functions.
Cultured human alveolar macrophages from smokers with lung cancer produced spontaneously variable amounts of factors stimulating fibroblast proliferation and production of prostaglandin E2 and collagenase by fibroblasts. These biological activities belong to molecules similar or identical to interleukin 1. Exogenous leukotriene B4 added to alveolar macrophage cultures increased the production of these factors. The Ca++ ionophore A23187 was found to have similar effects. By the control of monokine production, leukotriene B4 locally released by inflammatory cells may modulate lung fibroblast functions.
Calcimycin↗
Cultured human alveolar macrophages from smokers with lung cancer: resolution of factors that stimulate fibroblast proliferation, production of collagenase, or prostaglandin E2.
Marked connective tissue remodelling involves both destruction and repair in inflammatory lung diseases. Throughout the remodelling event, it was reasoned that alveolar macrophages may release substances similar to those produced by blood monocyte-macrophages that affect fibroblast functions, ie, the interleukin 1 family of monokines (or cytokines). We have examined human alveolar macrophage cultures obtained after bronchoalveolar lavage of freshly excised lungs from heavy smokers with bronchial carcinoma. Crude culture media contained fibroblast proliferative activity and collagenase- and PGE2- production-stimulating activity. The main peak of these biological activities was located around approximately 18 kilodaltons (kD) on gel filtration chromatography. Resolution of this peak by high performance liquid chromatography showed the presence of three distinct peaks, with quantitative and qualitative differences in biological activities. This suggests the presence of heterogeneous factors.
Cell Division↗
Circulating endogenous opioids and ventilatory response to CO2 and hypoxia.
The role of endogenous opioids in the control of breathing is not yet well defined. Radioimmunoassays that measure beta-endorphin (BE) and met-enkephalin (MET) having recently become available, we decided to evaluate the possible relation between the blood levels of these two opioids and different hypercapnic and hypoxic ventilatory responses observed in a group of normal subjects. Ventilatory response to hypercapnia (n = 9) and to hypoxia (n = 7) were determined by classical rebreathing methods. A voluntary isocapnic normoxic hyperventilation test was used as a control. Basal levels of BE and MET did not correlate with the magnitude of the ventilatory response to either hypercapnia or hypoxia. Moreover, BE and MET levels measured repeatedly up to 30 min after each test did not change significantly. We conclude that circulating endogenous opioids do not play a role in the control of breathing in normal humans. These results do not rule out a possible role for these substances as locally released mediators.
Adult↗