[Current methods of anti-infectious prophylaxis in patients with HIV infection].
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Biomedical subjects
Publications and source records attributed to C Mayaud.
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Blood monocytes from tuberculosis patients release high amounts of tumour necrosis factor-alpha (TNF-alpha). Because the biological efficiency of TNF-alpha would depend on the expression of TNF-alpha receptors on target cells, we thought to analyse the capacity of blood monocytes from a group of patients with pulmonary tuberculosis to bind 125I-TNF-alpha. We report a slight but not significant enhancement in specific binding of 125I-TNF-alpha on monocytes of 15 consecutively studied patients compared with 10 controls. Per cent cell surface bound and internalized 125I-TNF-alpha was identical in the two groups. To evaluate the receptor occupancy by endogenously generated TNF-alpha, similar experiments were performed after cell exposure to low-pH glycine buffer. Under these conditions, specific binding of 125I-TNF-alpha was significantly higher on tuberculosis monocytes compared with control monocytes. Moreover, the occupancy of TNF-alpha receptors by endogenously generated TNF-alpha that was found to be significantly higher on tuberculosis monocytes than on control monocytes, was directly related to the enhanced capacity of mononuclear cells to generate TNF-alpha in vitro. It normalized after 3 months of antituberculous therapy. Scatchard analysis of the binding data revealed that tuberculosis infection caused a significant increase in high affinity 125I-TNF-alpha binding to monocytes without any significant change in the dissociation constant. Collectively, these results indicate an up-regulation of TNF-alpha generation and binding to blood monocytes in patients with pulmonary tuberculosis. They provide support to the hypothesis that TNF-alpha is of critical importance in the pathogenesis of this infection.
The mortality rate among patients with human immunodeficiency virus (HIV) requiring mechanical ventilation (MV) for acute respiratory failure (ARF) secondary to Pneumocystis carinii pneumonia (PCP) is still a matter of discussion. For some authors, it is in the 50 percent range, while for others the prognosis is grim, with virtually no survivors. The aim of this retrospective study conducted between January 1987 and January 1992 was to analyze the outcome of such patients. We studied 33 patients, 29 men and 4 women (38.6 +/- 9.9 years, 21 homosexuals, 8 intravenous drug users, 3 transfusion related, 1 heterosexual) infected by HIV for at least 19.7 +/- 21.6 months. It was the first PCP episode in all but 2 patients and the diagnosis was made by bronchoalveolar lavage (n = 32) or lung biopsy specimen (n = 1). Only three patients were receiving primary prophylaxis for PCP (trimethoprim-sulfamethoxazole [TMP-SMZ], n = 2; pentamidine, n = 1). Pneumocystis carinii pneumonia was the first manifestation of AIDS in nine patients. The duration of symptoms prior to treatment was 19.6 +/- 11.3 days. At the time of hospital admission, laboratory findings were as follows: PaO2 = 40.7 +/- 7.8 mm Hg on room air; serum LDH = 1,172 +/- 792 IU/L; T4 cell count = 60.2 +/- 67/mm3. Mechanical ventilation was always required for ARF, which was never induced by bronchoscopy. The interval between treatment and MV was 8.1 +/- 6.5 days and the duration of MV was 11.4 +/- 9.9 days. The patients were classified into 3 groups on the basis of the duration and type of treatment before MV, as follows: group 1, n = 10: TMP-SMZ (20-100 mg/kg) IV and methylprednisolone (MP) < 5 days before MV; group 2, n = 4: TMP-SMZ > or = 5 days and MP < 5 days; group 3, n = 19: TMP-SMZ and MP > or = 5 days before MV. (The MP dose was as follows: 240 mg/d once a day from day 1 to day 3; 120 mg/d from day 4 to day 6; and 60 mg/d from day 7 to day 9.) Despite MV, TMP-SMZ, and MP, death secondary to PCP-related ARF occurred in 81.9 percent of patients, 20 +/- 4.8 days after the beginning of treatment and 11.4 +/- 9.9 days after the beginning of MV. Six patients survived, five in group 1 and one in group 3.(ABSTRACT TRUNCATED AT 400 WORDS)
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Drug-induced acute lung diseases constitute a chapter of pneumology and intensive care that is now in full mutation. In practice, these diseases are still inadequately indexed and little known, the only exception being those caused by cytotoxic drugs observed in onco-haematology. They create for clinicians difficult diagnostic and therapeutic problems. From the cases reported in the literature, recent review papers and 10 personal cases, the authors ask five successive questions concerning hypoxic pneumopathies: 1) which patients?; 2) which clinical features?; 3) which initial diagnostic discussion?; 4) which are the elements likely to support the drug-induced hypothesis?; 5) which outcome?
We report a case of pulmonary and cerebral nocardiosis in a patient infected with HIV. On the basis of this observation, the authors review the frequency of nocardiosis during the course of an HIV infection and the diagnostic problems proposed, and finally the therapeutic difficulties encountered.
OBJECTIVE: To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. DESIGN: Case study. SETTING: Intensive care unit of a referral hospital. PATIENT: A 51-year-old man with chronic bronchitis who developed a hypersensitivity pneumonitis within 1 month after exposure to minocycline, amoxicillin, and erythromycin. INTERVENTION: Sequential bronchoalveolar lavages after reexposure to minocycline and amoxicillin. MEASUREMENTS: Immunologic analysis of the phenotype and function of alveolar lymphocytes. RESULTS: Reexposure to minocycline but not to amoxicillin was followed by an interstitial pneumonitis. Sequential bronchoalveolar lavages showed a transient rise of eosinophils and neutrophils and a persistent alveolar lymphocytosis. Alveolar lymphocytes consisted predominantly of CD8+ but also CD4+ cells. Two CD8+ lymphocyte subsets were identified: CD8+ D44+ cytotoxic T cells that increased rapidly after the drug was resumed and CD8+ CD57+ suppressor T cells that predominated 11 days after the drug's withdrawal. In-vitro assays showed the presence of a lymphocyte-mediated specific cytotoxicity against minocycline-bearing alveolar macrophages. CONCLUSION: These results support the hypothesis of a central role of T lymphocytes in the pathogenesis of drug-related hypersensitivity pneumonitis.
Cytotoxic T lymphocytes (CTL) specific for human immunodeficiency virus (HIV) proteins have been analyzed in lymphoid organs from seropositive patients. Indeed, an active HIV replication coexists with a major CD8+ lymphocytic infiltration in these organs. We have shown in a previous report that HIV-seropositive patients lungs were infiltrated by HIV specific CD8+ lymphocytes. In the present report, we show that HIV-specific CTL responses can also be detected in lymph nodes and spleens, and were mainly directed against the ENV, GAG, and NEF HIV-1 proteins. The primary NEF-specific CTL responses were further characterized by epitope mapping. Determination of epitope-specific CTL frequencies were performed by limiting dilution analysis. Our results indicated that, in addition to the central region of NEF (AA66-148), a new immunodominant region is recognized by CTL. This region corresponds to the carboxyl-terminal domain of NEF (amino acids 182-206). AA182-206 is recognized in association with at least two common human histocompatibility leukocyte antigen (HLA) molecules (HLA-A1 and B8), with clonal frequencies of one CTL per 10(-5) to 10(-6) splenic lymphocytes. Our data indicate that lymphoid organs may represent a major reservoir for in vivo activated HIV-specific CTL. Furthermore, the carboxyl-terminal domain of NEF was found to be conserved among several HIV strains. Therefore, our finding is of interest for further HIV vaccines development.
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Hyperinfestation with Strongyloides is a severe complication in immunodepressed patients. It may present with various clinical signs, notably acute respiratory failure. Diagnosis may be difficult, particularly when the strongyloidiasis is associated with septicaemia caused by Gram-negative organisms. We report a new case of hyperinfestation with Strongyloides in a patient treated for periarteritis nodosa. This case was remarkable on two scores: the diagnosis problem raised by the presence of intrapulmonary haemorrhages, and the favourable outcome of an acute and initially severe respiratory failure which had required assisted ventilation. The role played in the patient's cure by the doses of thiabendazole given and the duration of their administration is discussed.
Pneumonias occupy a prominent situation among lower respiratory tract infections where they are remarkable for their potential mortality and for our relative knowledge of the responsible micro-organisms. Analysis and synthesis of each series published must answer several questions, such as: what are the lung diseases considered? which investigations have been performed? which criteria of imputability have been used? in which patients has the study been carried out? in which place, which period and which structure? In spite of methodological lacunae and of the inhomogeneous answers to the questions asked, there is some concordance between the series found in the literature. Thus, more than 90% of community-acquired pneumonias with microbiological identification are caused by Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia psittaci (or pneumoniae), or Influenza A virus.
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We retrospectively compared the results of 67Ga chest scans and 99mTc-DTPA aerosol clearance measurements with those of fiberoptic bronchoscopy in 88 patients infected with the human immunodeficiency virus. Of 100 investigations, a pulmonary infection was diagnosed in 39, mainly Pneumocystis carinii pneumonia and a noninfectious disorder was found in 42, mainly Kaposi's sarcoma and lymphocytic alveolitis. Gallium scans and DTPA clearance were abnormal respectively in 74% and 92% of infectious complications, and in 12% and 60% of noninfectious disorders. In 10 cases, DTPA clearance was accelerated, while chest x-ray, arterial blood gases and even gallium scanning were normal. A value of DTPA clearance greater than 4.5%.min-1 was both sensitive and specific for the diagnosis of Pneumocystis carinii pneumonia. The gallium scan was always normal in bronchopulmonary Kaposi's sarcoma. We conclude that in symptomatic patients: (1) DTPA clearance measurements are useful for detecting lung disease when chest x-ray and/or PaO2 are normal and (2) a gallium scan is indicated to distinguish progressive Kaposi's sarcoma from a superimposed second process when radiological abnormalities of pulmonary Kaposi's sarcoma are present.