[Present and future of the antiretroviral therapy].
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Biomedical subjects
Publications and source records attributed to J M Martinez-Vazquez.
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In this double-blind, placebo-controlled trial of HIV-infected asymptomatic haemophiliacs, the efficacy of 2-year zidovudine therapy (1000 mg daily in two divided doses) in preventing progress of HIV infection was prospectively evaluated. Drug tolerance was also studied. 143 haemophiliacs from five European countries and Australia with p24 antigenaemia and/or CD4 cell counts of 0.1-0.4 x 10(9)/l were enrolled. The main measures of outcome were progression to AIDS, CDC group IV disease, symptomatic HIV-related disease, and a decrease in CD4+ T-lymphocyte count to fewer than 0.2 x 10(9)/l. There were no significant treatment differences in the proportion of patients progressing to AIDS, CDC group IV or symptomatic disease. Analysis of time to CD4+ counts less than 0.2 x 10(9)/l showed a non-significant trend in favour of zidovudine. Haemoglobin concentrations were less than 8 g/dl in 4% of zidovudine recipients; neutropenia was less than 0.75 x 10(9) cells/l in 5% of zidovudine recipients; alanine aminotransferase levels were greater than 10 times the upper normal limit in 3% of zidovudine recipients, but also in 4% of placebo recipients. Hence there was a very low prevalence of side-effects in haemophiliacs, despite the use of a higher zidovudine dosage than is currently widely used.
Three patients with bronchiolitis obliterans organizing pneumonia are described. Chest X-ray films showed peripheral densities and pulmonary function tests a restrictive pattern. In all three cases transbronchial biopsy was not useful for diagnosis and we point out the importance of an open lung biopsy in order to make the differential diagnosis with other infiltrative lung disease with a different prognosis and therapy.
A prospective study on 386 consecutive patients affected of ischemic stroke (IS) has been analysed in relation to etiologies, comparing them with a control group of 100 people. The atherotrombotic etiology subgroups are associated with family history of stroke, risk factors, atheromatosis, occlusive peripheral arteriopathy, previous of stroke, high levels of hematocrit and hemoglobin, impaired lipid fractions and high levels of uric acid. The cardiac embolism etiology subgroups are associated with the presence of personal history of stroke, just as the mitral valva prolapse (MVP) patients group. The migraine group is significantly related with the intake of oral contraceptives.
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T-lymphocytes previously sensitized by an antigen undergo blastic transformation and produce IFN tau when stimulated by the same antigen. We studied the lymphoblastic response to PPD and IFN tau production in pleural fluid and peripheral blood of 41 patients (15 with tuberculous pleural effusion, 13 with nontuberculous pleurisy and positive tuberculin skin test, and 13 with tuberculin-negative nontuberculous pleurisy). In tuberculous pleuritis, pleural lymphocyte blastic response and IFN tau production were higher than those of peripheral lymphocytes, whereas in tuberculin-positive nontuberculous patients, peripheral lymphocyte response and IFN tau production were higher than those of pleural lymphocytes. Tuberculous pleural fluid lymphocytes underwent greater blastic transformation and produced more IFN tau than pleural lymphocytes of tuberculin-positive nontuberculous patients, whereas the opposite occurred in peripheral lymphocytes. In tuberculin-negative nontuberculous patients, there was no lymphoblastic response in either the pleural fluid or peripheral blood. These results concur with the concept of immunologic compartmentalization. In tuberculous pleuritis, there would be clonal expansion of PPD-responding T-lymphocytes in the pleural compartment. This expansion of PPD-specific lymphocytes would not occur in nontuberculous pleuritis, but lymphocytes sensitized to other antigens would accumulate in the pleural compartment.
An ischemic stroke (IS) group including 386 patients under 50 years old is analysed taking into account different etiological subgroups and comparing risk factors against a control group of 100 people. The series points out the presence of 66.1% patients included in the inconclusive-atherothrombosis group, of which 22.7% had defined criteria of atheromatosis, while 11.6% were diagnosed of lacunar infarct. 13.5% of cases were considered as cardiac origin embolisms, and 14.1% were affected of mitral valve prolapse. The migraine group includes 4.9% of the patients while 17.6% belong to the miscellaneous group. The comparison of each of these groups with the control group showed significant differences for family history of stroke, personal history of peripheral arteriopathy, tobacco, arterial hypertension and previous IS.
It has been observed that T-lymphocytes of patients with tuberculosis produce interferon gamma (IFN gamma) in vitro. Based on this idea, we studied IFN gamma in pleural fluid and serum. We studied 80 patients with pleural effusion; 30 patients with tuberculous pleurisy had high IFN gamma concentrations in pleural fluid. Patients with malignant pleural effusions, nonspecific pleural effusion, parapneumonic effusions and pleural transudates had low levels. The IFN gamma levels were higher in those with massive tuberculous effusion and apparent pulmonary lesion on x-ray film. We found that the T4/T8 lymphocyte ratio was higher in pleural fluid than in peripheral blood. Numbers of T3 and T4 lymphocytes were higher in tuberculous pleural effusions compared with those in other patients. There is no correlation between IFN gamma levels and lymphocyte subsets in pleural effusion. Perhaps pleural T-lymphocytes produce IFN gamma after stimulation by mycobacterial antigens and this lymphokine activates macrophages, increasing their bactericidal activity against Mycobacterium tuberculosis.
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We studied the activity of adenosine deaminase in the cerebrospinal fluid of 40 normal controls and 205 patients who were grouped according to disease (tuberculous, viral, and purulent meningitis; neoplasms; stroke; and miscellaneous). The mean enzyme value was clearly higher for the patients with tuberculous meningitis (15.7 +/- 4.3 U/liter) than for the other patients (1.4 +/- 1.5 U/liter). The sensitivity of the test for diagnosing tuberculous meningitis was 1 and specificity, 0.99. The enzyme activity, as well as progression of the disease, was studied in 32 patients with tuberculous meningitis. A significant rise in levels of enzyme was observed during the first 10 days of therapy, was followed by a gradual decline, and reached normal values after three to four months of treatment. Two patients showed substantial increases that coincided with the development of complications. The test proved to be a simple and reliable method for early diagnosis and follow-up of tuberculous meningitis.
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We studied the activity of adenosine deaminase in 74 lymphocytic pleural effusions which were divided into four groups according to the aetiology: tuberculous (38 cases), neoplastic (17), lymphomatous (7) and miscellaneous (12). The mean enzyme value was significantly higher in the tuberculous cases (93.81 +/- 29.56 U/I) than for the other three groups and significantly higher in pleural effusions of lymphomatous origin than in the neoplastic and miscellaneous groups. Based on the lowest value of enzyme activity found in the tuberculous group (50 U/I), the test had a sensitivity of 1 and a specificity of 0.97.
Radioimmunoassay-determined myelin basic protein (MBP) shed to CSF during active demyelination, has been found to be a useful but non-specific test for MS. CSF creatin kinase BB (CK-BB), as measured by radioimmunoassay, is increased in a variety of neurological diseases, and has been considered a useful indication of brain damage but not of demyelinating diseases. Taking into account that the mean concentration of CSF CK-BB should not be increased in patients during the acute phase of MS, we suggest that the CSF MBP/CK-BB ratio could be a more specific index to demyelination than CSF-MBP alone. We also defined a laboratory demyelination pattern (CSF MBP greater than mean control MBP + 2 S.D. and CK-BB less than MBP). CSF levels of MBP and CSF levels of CK-BB were determined by radioimmunoassay in 232 patients with several neurological disorders and 33 control subjects. Patients diagnosed as having MS with clinical exacerbation had significantly higher values of CSF-MBP/CSF-BB ratio than control subjects. Our study showed a significant presence of demyelination pattern in CSF of patients with MS. We conclude that the CSF MBP/CK-BB ratio and the CSF demyelination pattern may be new and reliable tests for the diagnosis of MS.
We studied the activity of adenosine deaminase in the peritoneal fluid of 66 patients who were divided into five groups according to causes of ascites as follows: tuberculous peritonitis (group I), septic peritonitis (group II), secondary to malignant tumours (group III), miscellaneous conditions (group IV), and control subjects of transudates (group V). In patients with tuberculous peritonitis the enzyme activity was significantly higher than for the rest of the groups (p less than 0.001), and enzyme concentrations in all patients were well above the upper non-tuberculous value. Adenosine deaminase activity in the peritoneal fluid has proved to be a simple and reliable method for early diagnosis of tuberculous peritonitis.
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