Biomedical subjects
Publications and source records attributed to E Concia.
In a retrospective study, 42 (7.7%) of 545 patients with AIDS from a single area of Italy had non-Hodgkin's lymphoma (28 systemic and 14 primary central nervous system lymphomas). The improved outcome and survival of treated patients outlines the clinical benefit of antineoplastic treatment in selected cases.
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Patients undergoing mechanical ventilation (MV) after an isolated closed head injury (ICHI) have often been found to develop hospital-acquired pneumonia (HAP) well before subjects who require MV for different reasons. In a prospective study of patients receiving MV after an ICHI. 38 subjects (out of 65 with clinically suspected HAP) had a bacteriological diagnosis established on the basis of correspondence between cultures made from bronchoalveolar lavage and protected specimen brush (with quantitative thresholds of 10(4) and 10(3) cfu ml-1, respectively). Patients were separated according to the time of onset of HAP, with 20 subjects who developed HAP within 4 days of the start of MV (early onset pneumonia, EOP) and 18 subjects who developed HAP after the fourth day (late onset pneumonia, LOP). In those who had LOP, an expected spectrum of organisms was found, with Gram-negatives (especially Pseudomonas sp.) accounting for the majority of isolates. However, in EOP cases, Gram-positive bacteria (especially Staphylococcus sp. and Streptococcus pneumoniae) were found to largely predominate (P = 0.0000026). This confirms the high incidence of staphylococcal pneumonia in neurosurgery patients, and also provides evidence that the vast majority of such staphylococcal pneumonia are EOP. Unlike most previous reports, the microbiological findings from the present study suggest that a cut-off point of 4 days successfully distinguishes between EOP and LOP. Since these two clinical entities differ significantly in terms of pathogenesis and aetiology, preventive measures and therapeutical protocols have to be tailored accordingly.
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In this multicenter study (ISS 902), 554 previously untreated patients with <500 CD4 cells/mm3 and mildly symptomatic human immunodeficiency virus disease were randomized to receive zidovudine or didanosine (ddI). After a mean follow-up of 20 months, 80 patients (40 zidovudine, 40 ddI) had died and 146 had at least one AIDS-defining event (73 zidovudine, 73 ddI). Overall, no difference was found between treatments with respect to progression to AIDS or death. The analysis of relative risk (RR) of progression over time, however, showed an initially minor risk for zidovudine patients and an inversion in the zidovudine-ddI RR in the second and third years of follow-up. Didanosine showed a greater effect on CD4 cell count response. The two drugs confirmed the toxicity patterns already reported in other trials, with a low occurrence of pancreatitis (ddI 1.3%, zidovudine 0.4%). The overall results suggest that, in this population, zidovudine and ddI monotherapies have comparable long-term clinical efficacy and that more powerful regimens should be preferred.
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OBJECTIVE: To evaluate prospectively the diagnostic efficacy and safety of stereotactic brain biopsy and its impact on treatment, outcome, and survival in human immunodeficiency virus-infected patients with focal brain lesions. METHODS: Computed tomography-guided stereotactic brain biopsy was performed in 26 patients, of whom 17 failed to respond to a 2- to 3-week anti- Toxoplasma regimen. Exclusion criteria for biopsy were overt acquired immunodeficiency syndrome for 2 years or longer, Karnofsky score less than 50, and severe coagulopathies. RESULTS: A definitive diagnosis was obtained in 24 patients (92%), of whom 12 (46%) had primary brain lymphoma, six (23%) had progressive multifocal leukoencephalopathy, and four (15%) had Toxoplasma encephalitis. Two thirds of contrast-enhancing lesions on computed tomography were lymphoma and three fourths of contrast-negative lesions were leukoencephalopathy. Three patients had biopsy-related cerebral hemorrhages (morbidity, 11.5%). Median follow-up and survival for the entire group were 24 weeks (range, 6 to 135 weeks). Twenty patients (77%) received specific therapy and 13 (50%) responded to treatment. Of 11 patients with lymphoma undergoing irradiation treatment (whole-brain radiotherapy in seven and gamma-knife treatment in four), nine (82%) had clinical and radiologic response, with a median survival of 34 weeks (range, 13 to 57 weeks). CONCLUSIONS: Stereotactic brain biopsy has high diagnostic efficacy and clinical benefit in carefully selected human immunodeficiency virus-infected patients. The procedure should be performed essentially in patients with contrast-enhancing lesions on computed tomography who have a high frequency of treatable cerebral diseases.
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BACKGROUND: Fulminant hepatitis on withdrawal of chemotherapy has been described in chronic hepatitis B virus infection, but not in hepatitis C virus (HCV) infection. The relation between HCV and immune response to this virus, and disease severity, has not been examined. We present two patients with HCV who developed fulminant liver failure after chemotherapy was stopped. PATIENTS AND FINDINGS: Two patients with chronic HCV infection and malignant lymphoma received chemotherapy (cyclophosphamide, adriamycin, vincristine, bleomycin, etoposide, and prednisolone in patient 1; doxorubicin, bleomycin, vinblastine, and dacarbazine in patient 2), on withdrawal of which both developed fulminant hepatitis. Alanine aminotransferase (ALT) concentrations were greatly raised (6030 and 3870 IU/L in patients 1 and 2, respectively), and serum HCV-RNA was low in both patients when severe disease developed (10(2) genome equivalents per mL). Patient 1 died, and necropsy showed massive liver necrosis. INTERPRETATION: The findings suggest an immune-mediated mechanism for hepatocyte damage in HCV infection. Careful monitoring of ALT concentrations is necessary in such patients during and after chemotherapy.
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The ability of antibiotics to penetrate into the respiratory tract has been investigated at several sites, namely, sputum and bronchial secretions, tissue homogenates, pleural fluid and, more recently, epithelial lining fluid and alveolar macrophages. The major reason for such investigations is that these data may be helpful to a more thorough understanding of drug distribution in the lung tissue and fluids and to a more accurate prediction of clinical outcome. However, the study of drug concentration at each of these sites presents problems in terms of methodology and data interpretation. The advantages and disadvantages of each of these methods are considered, and the data on penetration of betalactams, aminoglycosides, macrolides, fluoroquinolones and other antimicrobial agents (including antifungal and antiprotozoan drugs) are reviewed.
SETTING: Clinical features of human immunodeficiency virus (HIV)-associated tuberculosis depend upon the patients' residual immunity. An immune-dependent presentation has also been described at the histopathological level in many extra-pulmonary sites, but no descriptions have so far been made on the histopathology of HIV-associated pulmonary tuberculosis. OBJECTIVE: To compare the histopathological features of pulmonary tuberculosis in HIV-infected subjects and seronegative patients. DESIGN: We carried out a retrospective comparative study on 16 HIV-infected subjects and 16 seronegative patients with culture-proven pulmonary tuberculosis who underwent transbronchial biopsy. We evaluated the bacillary burden and the parenchymal inflammatory reaction by means of a four-graded scoring system giving an approximate quantitative measure of the two parameters. RESULTS: HIV-associated pulmonary tuberculosis was found to differ significantly from disease forms seen in seronegative patients, with a significant tendency to develop highly bacillary and poorly reactive histopathological pictures along with the downgrading evolution of immune function. CONCLUSION: Pathologic features of pulmonary tuberculosis in HIV-infected subjects differ from those encountered in seronegative patients depending upon the individual immunity of the former. HIV-associated progressive depletion of CD4+ lymphocytes leads to substantial changes in pulmonary reactivity to Mycobacterium tuberculosis; multibacillary pictures in a background of loose inflammatory reactions are quite common findings at the extreme phase of HIV-related immune deterioration.