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Biomedical subjects

B Housset

Publications and source records attributed to B Housset.

At least 55 records · Page 3Linked to original sources

[Diagnostic strategies of pulmonary pneumocystis infection in patients with HIV infection. Decision analysis and medico-economic consequences].

P. carinii pneumonia is one of the most frequent opportunistic infections in HIV-infected patients. Clinical and radiological manifestations are non-specific and reference diagnostic procedure remains broncho-alveolar lavage which is costly and invasive. Alternative diagnostic strategies have been proposed. We report here our experience as well as literature date in this field with the purpose to show the usefulness of decision analysis techniques in choosing an optimal cost-effective strategy.

AIDS-Related Opportunistic Infections↗

[Clinical aspects and outcome of COPD].

Chronic obstructive pulmonary disease (COPD) is a frequent disease which is too often diagnosed when already severe. Major known risk factors are tobacco smoking, occupational exposure, and severe respiratory infections during childhood. Diagnostic should be evoked on functional non specific symptoms: chronic cough and sputum, progressive dyspnea. Some physical signs, correlated with the degree of airway obstruction, may be more specific but their diagnostic value remains to be assessed. These signs reflect distension of the chest as well as airway obstruction: pursed lips breathing, increased expiration duration, Hoover and Campbell signs, inspiratory contraction of scalen muscles. COPD results over years in chronic respiratory insufficiency and evolution is associated with episodes of bronchial and parenchymal infections as well as pulmonary emboli which are particularly frequent in these patients.

Adult↗

Direct toxic effect of bleomycin on alveolar type 2 cells.

We studied the in vitro toxicity of bleomycin (BLM) on primary cultures of rat alveolar type 2 cells (T2 cells). It was shown that BLM was directly toxic for T2 cells in a dose- and time-dependent manner. Lung fibroblasts (LF) appear to be more resistant than T2 cells. Modulation of intracellular glutathione concentration was associated with changes in cytotoxicity. Furthermore, the addition of O-phenanthroline to the cellular medium reduced significantly BLM toxicity, suggesting the involvement of intra-cellular ferric ion. We also found that BLM toxicity was associated with a decreased release of phosphatidylcholine by T2 cells, the main component of surfactant. Protective effect of O-phenanthroline and the involvement of glutathione may be an alternative approach to the protection of BLM-induced damage.

Animals↗

Use of the polymerase chain reaction technique on induced-sputum samples for the diagnosis of Pneumocystis carinii pneumonia in HIV-infected patients. A clinical and cost-analysis study.

The purpose of this study was to assess the sensitivity and specificity of the polymerase chain reaction (PCR) on induced sputum (IS) for the diagnosis of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients, as well as its diagnostic value and cost as a routine clinical tool. Forty-nine patients with suspected PCP who had IS were studied and if negative, followed by bronchoalveolar lavage (BAL). Pneumocystis carinii was detected in these samples using standard staining techniques. Polymerase chain reaction was used with IS samples in a blinded fashion. The patients with negative BAL samples were closely monitored for 1 month. In the absence of any clinical or radiologic features of PCP during this period, they were considered as being free of PCP. The cost analysis considered only the direct costs of the various tests in three diagnostic strategies: routine BAL (BAL); IS with standard staining, if negative, followed by BAL (IS); and IS with standard staining followed, if negative, by PCR on IS samples (PCR-IS). Using standard staining P carinii was found in 13 cases (6 IS and 7 BAL). None of the 36 patients with negative BAL developed further signs of PCP. Thus, the prevalence of PCP was 26.5% and the sensitivity and specificity of BAL were 100%. Standard staining of IS had a specificity of 100% and a sensitivity of 46.5%. The sensitivity and specificity of PCR-IS were each 100%. The costs of strategies BAL, IS, and PCR-IS were $14,010, $18,300, and $18,040, respectively. The costs of the BAL strategy depended only on the cost of the relevant tests, whereas the costs of strategies IS and PCR-IS depended on the costs of the tests, the sensitivity of IS with standard staining, and the prevalence of PCP in the test population. The routine clinical use of PCR-IS is currently limited by the time required to obtain the results.

AIDS-Related Opportunistic Infections↗

[Oxidants and antioxidants. Biological effects and therapeutic perspectives].

The main oxidizing free radicals (FR) are oxygen-derived metabolites (superoxide anion O2-, hydrogen peroxide H2O2, hydroxyl radical OH (zero)), hypochloric acid, chloramines, nitrogen dioxide, ozone and lipid peroxides. They are produced continually by living organisms, either in the intracellular compartment by the mitochondrial respiratory chain and mixed function oxidase system, or in the extracellular compartment, especially by phagocytes. The body possesses complex protective antioxidant systems against this potentially toxic production, such as dismutase superoxides, catalase, the glutathione enzyme system, metallic ion sequestration, enzymes degrading proteins injured by FR, metabolising hydroperoxides, and repairing DNA, and vitamins E, C, P, and betacarotene. A physiological steady-state is established under normal conditions between the production of oxidants and their neutralization by antioxidants. Oxidative lesions result from a disturbance of the oxidant-antioxidant balance. Oxygen-derived metabolites act on polyunsaturated cell membrane lipids, induce genetic alterations, and oxidize sulfhydryl groups of proteins, thereby modifying their functions. FR are involved in major physiological mechanisms such as phagocytosis, the inflammatory reaction, and the reperfusion ischaemia phenomenon observed during organ storage. The therapeutic use of enzymatic (SOD, catalase, GSH) and nonenzymatic antioxidants (vitamins E, N-acetylcysteine, allopurinol and oxypurinol) has yet to be evaluated. The current state of our knowledge indicates the extreme complexity of these systems and calls for caution in the therapeutic use of antioxidant substances.

Antidotes↗

Cost-analysis of four diagnostic strategies for Pneumocystis carinii pneumonia in HIV-infected subjects.

The aim of this study was to analyse the cost-effectiveness ratio of four diagnostic strategies for Pneumocystis carinii pneumonia (PCP) in patients infected with human immunodeficiency virus (HIV). Two hundred and ten HIV-infected patients with suspected PCP underwent induced-sputum (IS) followed, if negative, by bronchoalveolar lavage (BAL); 85 of these patients were able to undergo an exercise test (ET), prior to induced sputum and BAL. The following strategies were analysed: BAL strategy (BAL whenever PCP is suspected); IS strategy (induced sputum followed by BAL if negative); exercise test (ET) strategy, (ET followed by BAL if the results are abnormal); and the ES (exercise sputum) strategy (i.e. BAL only after abnormal ET and negative IS). The cost of each strategy was calculated by taking into account only direct costs; the conditions in which two given strategies would be cost-equivalent were also evaluated. The prevalence of PCP in this population was 31%; IS had 100% specificity and 71% sensitivity, whilst ET had 100% sensitivity and 77% specificity. The costs of BAL, IS, ET and ES strategies were 210,000, 191,940, 140,700 and 112,700 FF, respectively. The ES strategy is, thus, most suitable for our unit. The most economic strategy depends not only on the cost and characteristics of the procedures, but also on the prevalence of PCP in the test population. In conclusion, we developed a model for use by diagnostic centres in choosing the most suitable strategy, on the basis of the local prevalence of PCP.

AIDS-Related Opportunistic Infections↗

Analysis of emergency department interpretation of electrocardiograms.

The objective of the study was to determine the concordance of emergency physicians' and cardiologists' interpretations of emergency department (ED) electrocardiograms (ECG), to evaluate the impact of ECG misinterpretation on patient management, and to determine error rates as a function of the level of physician training and the specific ECG diagnoses. ECG interpretations were registered prospectively using a programmed-response data sheet. A second blinded interpretation by a staff cardiologist was assumed to be correct. Only ECG discrepancies with potential or probable clinical importance were considered as errors. The ED management of patients with ECG misinterpretations was reviewed by the investigators. The study was performed at an urban university hospital using 300 consecutive ED ECGs. The analysis found 154 errors of interpretation of which nine had probable clinical significance, and 56 had indeterminant significance. The concordance was weak at 0.69 (Kappa = 0.32, weighted Kappa = 0.30) with a significant discordance (McNemar Chi 2:P < 0.05). Error rates did not differ significantly between the diverse categories of physicians. In two cases, interpretation errors impacted patient management decisions but not patient outcomes. The most frequent errors involved repolarization abnormalities, ventricular hypertrophy and hemi-blocks. While discordance was significant, errors in ECG interpretation rarely impacted patient management. Prospective evaluation of ECG interpretation may be a useful means of gauging physician skills. It can also serve to focus educational activities on problem areas in electrocardiography.

Adult↗

Histamine H2 receptors and histidine decarboxylase in normal and leukemic human monocytes and macrophages.

Spontaneous and all-trans-retinoic acid (RA)-induced differentiation of normal human monocytes and of leukemic THP-1 monocytes into macrophages resulted in a progressive loss of adenosine 3',5'-cyclic monophosphate production induced by histamine via typical H2 receptors (H2R). In THP-1 cells and in HL-60 human acute myelocytic leukemia cells, RA treatment increased the abundance of the 4.5-kb messenger RNA of the H2R gene fourfold, suggesting transcriptional control by a RA response element. Scatchard plots of [3H]tiotidine binding indicated the expression of H2R with similar affinity and binding capacity in THP-1 monocytes and macrophages, while the conversion of normal monocytes into macrophages decreased H2R density from 91.8 to 43.1 fmol/mg protein, with no change in affinity (Kd = 9.9 to 11.2 nM). In THP-1 macrophages, histamine inhibited 4 beta-phorbol 12-myristate 13-acetate (PMA)-induced H2O2 formation via the activation of H2 receptors. Expression of the H2R gene, histamine accumulation, and histidine decarboxylase activity were also demonstrated in normal human monocytes/macrophages and peripheral lymphocytes. Histamine and H2R may therefore affect, via intracrine, autocrine, and paracrine pathways, various immune and inflammatory responses of the lymphoid and myeloid progenitors and lineages in the bone marrow and peripheral tissues.

Adenylyl Cyclases↗

Novel Pseudomonas product stimulates interleukin-8 production in airway epithelial cells in vitro.

Because high concentrations of IL-8 are found in the sputum of cystic fibrosis patients, we hypothesized that Pseudomonas aeruginosa (PA) induces the production of IL-8 in airway epithelial cells and in monocytes. Therefore, we incubated the supernatant from PA culture with human transformed bronchial epithelial cells (16-HBE) or with monocytes. The culture medium of 16-HBE cells that had been incubated with PA supernatant for 6 h had chemotactic activity that was inhibited by an antibody to human IL-8. The PA supernatant induced IL-8 production by primary bronchial epithelial cells, by 16-HBE cells, and by monocytes. After incubation with PA supernatant, 16-HBE cells showed a marked increase in the levels of IL-8 gene expression. The PA product responsible for IL-8 production resisted freezing, boiling, and proteolysis. This product was not lipid extractable and was present in a 1-kD filtrate. We conclude that a small molecular mass product of PA stimulates IL-8 production by 16-HBE cells and by monocytes, and that the chemotactic activity produced by 16-HBE cells after exposure to PA is due principally to IL-8.

Blotting, Northern↗

[Free radicals and respiratory pathology].

The lung is particularly exposed to various inhaled toxic products whose toxicity can be at least partly mediated by the generation of free radicals. Oxidants burden can also result from lung metabolism of xenobiotics or from activation of phagocytes. Free radicals are mainly derived from an univalent sequential reduction of molecular oxygen. Mitochondria is the main location of intracellular production which may also result from auto-oxidation of small molecules or function of some enzymes. To prevent the deleterious effects of free radicals produced by normal metabolism, cells are equipped with an antioxidant system composed of enzymes (superoxide dismutase, catalase, glutathione peroxidase) and non enzymatic substances such as glutathione, iron chelators, vitamin E and C, ceruleoplsamin). Targets of free radicals toxicity are phospholipids by initiation of lipid peroxidation, proteins which may be activated or inactivated via oxidation of sulfhydryl residues. Another target is DNA with possible strand breaks or mutation. Transcription activities can be also altered and it has been recently reported that some transcription factors such as NF-kB can be activated by oxidants. Under these circumstances free radicals may be considered as second messengers. Lung oxygen toxicity has been largely studied. Oxygen-induced lung lesions are non specific. It is possible to induce a resistance to 100% O2 by the pre-exposure of animals to 85% O2. This tolerance phenomenon is associated with an increased lung content in antioxidant substances. The mechanisms of gene regulation of antioxidant enzymes are still poorly understood in eukaryotes. Overproduction of free radicals in the lung is also involved in various clinical settings such as ischemia-reperfusion, exposure to ozone or NO2, acute respiratory distress syndrome, drug induced lung toxicity, pathogenesis of COPD, asthma, cancer and ageing. The precise role of free radicals among other mechanisms of lung injury is still unclear. A better knowledge of free radicals mechanisms of toxicity and of antioxidant regulation is needed to develop antioxidant therapeutic strategies.

Animals↗

Arterial blood gases in elderly persons with chronic obstructive pulmonary disease (COPD).

With the increasing number of elderly people in developed countries, physicians are often confronted with patients whose arterial oxygen tension, PaO2, is lower than that of normal young adults. The normal values predicted in the literature for very old individuals are generally extrapolated from younger subjects. The purpose of the present study was to obtain PaO2 values from a large population of elderly subjects with normal and obstructive ventilatory function. We measured arterial blood gases in 274 subjects, aged 65-100 yrs (mean 82 yrs), with chronic bronchitis and moderate airways obstruction (mean forced expiratory volume in one second (FEV1), 53% pred). Mean PaO2 was 10.0 +/- 1.4 kPa (75.2 +/- 10.8 mmHg) and mean arterial carbon dioxide tension (PaCO2) was 5.4 +/- 0.8 kPa (40.5 +/- 6.1 mmHg). Both PaO2 and PaCO2 were independent of age. Blood gas abnormalities were associated with airways obstruction: PaO2 was positively correlated to FEV1 and PaCo2 was negatively correlated to FEV1. PaO2 was 10.8 +/- 1.4 kPa (81.5 +/- 10.7 mmHg) in the patients with FEV1 > or = 90% predicted versus 9.5 +/- 1.3 kPa (71.5 +/- 10.1 mmHg) in those with FEV1 < or = 35% pred. These findings suggest that the predicted PaO2 extrapolated from younger normal values are often erroneously underestimated. It is probably more accurate to accept as normal a PaO2 of 10.6-11.3 kPa (80-85 mmHg) for all subjects over 65 yrs, irrespective of their age.

Aged↗

[Consequences of specific prevention on the diagnosis of Pneumocystis carinii pneumonia in patients with HIV infection. Comité SIDA de l'Hôpital Saint-Antoine].

In a prospective study the authors compared the clinical, radiological, biochemical and diagnostic features of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients who were or were not receiving a specific prophylactic treatment. The study included 386 patients with suspected PCP, 201 of whom were under specific prophylactic therapy. Induced expectoration and/or bronchoalveolar lavage provided a diagnosis of PCP in 89 patients, 21 of whom were under specific prophylaxis. Apart from a number of circulating CD4 lymphocytes that was significantly lower in the patients under prophylaxis, there was no significant difference between the two groups. Thus, being under specific prophylaxis should have no effect on the diagnosis of PCP in HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Cost effectiveness of noninvasive oxygen saturation measurement during exercise for the diagnosis of Pneumocystis carinii pneumonia.

We assessed (1) the sensitivity and specificity of exercise oxygen saturation measurement (EOS) for the diagnosis of Pneumocystis carinii pneumonia (PCP); and (2) the cost of introducing this indirect diagnostic test compared with that of standard diagnostic strategies for PCP. In a prospective study, 85 HIV-infected patients with suspected PCP underwent EOS, followed by induced sputum (IS) and bronchoalveolar lavage (BAL) if IS was negative for P. carinii. The prevalence of PCP was 0.22, the sensitivity of IS was 0.6, and its specificity was perfect. The cost ratios of IS to BAL and EOS to BAL were 0.1 and 0.2, respectively. A desaturation of three points was the best cutoff point, giving perfect sensitivity and a specificity of 0.77. The cost analysis showed that the introduction of EOS into diagnostic strategies for PCP is highly justified when the local prevalence is low. Exercise oxygen saturation measurement is simple and safe, and the results are available rapidly; its sensitivity is perfect and its specificity good. Its economic utility depends on its cost and the local prevalence of PCP in the test population.

AIDS-Related Opportunistic Infections↗

Mechanisms of impaired arterial oxygenation in patients with liver cirrhosis and severe respiratory insufficiency. Effects of indomethacin.

The mechanisms of impaired arterial oxygenation that occur in certain patients with chronic liver cirrhosis are still debated. In the present study, we investigated nine cirrhotic patients with severe respiratory disability (mean PaO2, 64 +/- 5 mm Hg), using the inert gas elimination technique to assess the distribution of ventilation-perfusion (VA/Q) ratios. We also determined shunt fraction during pure oxygen breathing, both in supine and sitting positions. To test the hypothesis that vasodilating prostaglandins could contribute to alter gas exchange in such patients with cirrhosis, we examined the hemodynamic and gasometric responses to indomethacin, 50 mg IV, in six of them. During baseline conditions, patients had high cardiac index (CI, 4.9 +/- 0.2 L/min/m2), and low pulmonary (PVR, 1.78 +/- 0.37 mm Hg/L/min/m2) or systemic (SVR, 17.7 +/- 1.15 mm Hg/L/min/m2) vascular resistances. Large intrapulmonary shunt fraction was documented in each patient with a mean value of 19.6 +/- 2.7 percent. Small perfusion in low VA/Q areas was associated with shunt in only three patients (2.5 to 5.3 percent of blood flow). Arterial PO2 was negatively related to shunt (p < 0.01) and to the dispersion of blood flow distribution (p < 0.02). There was no difference between measured and predicted PaO2. Shunt estimates from the inert gas and the 100 percent O2 breathing techniques were, respectively, 19.6 +/- 2.7 percent and 21.7 +/- 3.0 percent. During 100 percent oxygen breathing, changing from supine to sitting position decreased PaO2 from 401 +/- 50 to 333 +/- 64 mm Hg (p < 0.02), while O2 shunt remained unchanged, arteriovenous difference widened, and mixed venous PO2 decreased, from 61 +/- 3 to 47 +/- 4 mm Hg (p < 0.001). Indomethacin did not improve gas exchange or VA/Q distribution and did not affect systemic or pulmonary hemodynamics. The results show that in cirrhotic patients with severe respiratory disability, intrapulmonary shunting is the main determinant of impaired gas exchange, with no evidence of a defect in oxygen diffusion or an extrapulmonary shunt. Vasodilating prostaglandins do not appear to contribute to these alterations.

Aged↗

[Mercury pulmonary embolism after voluntary injection].

We describe a case of pulmonary emboli due to mercury in a female drug addict who was HIV positive and had voluntarily injected herself with mercury. The diagnosis was guided by the history and by the characteristics of the chest radiograph and was confirmed by blood and urine levels of mercury and the radiograph taken of the site of the intravenous injection. Three years after the injection the patient did not reveal any signs suggesting disturbance due to the chronic pulmonary exposure to mercury, but there was a reduced carbon monoxide transfer, whose interpretation was difficult due to the past respiratory history and to the drug addiction.

Adult↗

Endothelin-1 secretion by human gallbladder epithelial cells in primary culture.

BACKGROUND: The three isoforms of endothelin (ET), ET-1, ET-2, and ET-3 are potent contractile agonists for smooth muscle in a wide variety of tissues including the gallbladder. There is increasing evidence that endothelin acts in a paracrine fashion, however, its cell source in the gallbladder is unclear. EXPERIMENTAL DESIGN: To examine the production of ET by gallbladder and bile duct epithelium. RESULTS: We show that human gallbladder epithelial cells in primary culture secrete endothelin. ET release was time-dependent, and intracellular ET was negligible, indicating de novo synthesis. Secretion was increased by physiologic concentrations of cholecystokinin. Epithelial cells lining hepatic cysts in primary culture also released ET, suggesting that the intrahepatic, as well as the extrahepatic biliary epithelium is a source of this cytokine. High performance liquid chromatography separation of the conditioned medium from both cell types showed a single peak corresponding to that of ET-1. In vivo, ET-1 was present in hepatic cyst fluid, but was not detectable in gallbladder or choledochal bile. On tissue sections, both intrahepatic and extrahepatic bile duct epithelial cells were labeled with an anti-"big" ET-1 polyclonal antibody. CONCLUSIONS: These results suggest that ET-1 is locally produced in the biliary tract and by a paracrine route, could play a role in choledochal motility and gallbladder contraction.

Bile Ducts↗

Cost effectiveness of the induced sputum technique for the diagnosis of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients.

The purpose of this study was to assess: 1) the percentage of human immunodeficiency virus (HIV)-infected patients with suspected Pneumocystis carinii pneumonia (PCP) but unable to undergo the induced sputum procedure, together with the reasons involved; 2) the sensitivity and specificity of induced sputum procedure, using conventional stains and an immunofluorescence test; and 3) the cost of introducing induced sputum procedure for the diagnosis of PCP. One hundred and thirty eight HIV-infected patients with suspected PCP underwent induced sputum procedure and bronchoalveolar lavage (BAL). P. carinii was identified in induced sputum and BAL samples using conventional and immunofluorescence staining. The economic analysis took into account the direct costs of the two procedures. The induced sputum procedure was either not feasible or unsuccessful in 29% of the patients. The sensitivity of induced sputum, using conventional and immunofluorescence staining, was 0.27 and 0.56 respectively. The economic analysis showed that the two strategies (systematic BAL versus BAL only after negative induced sputum) are equivalent in cost terms when the induced sputum to BAL cost ratio is equal to the product of the prevalence of PCP by the sensitivity of induced sputum procedure. We conclude that the immunofluorescence test should be the reference technique for induced sputum samples, whilst conventional stains are more clinically relevant for BAL samples. The cost of introducing induced sputum should take into account the sensitivity of induced sputum and the prevalence of PCP in the suspected population.

AIDS-Related Opportunistic Infections↗