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Biomedical subjects

G Di Perri

Publications and source records attributed to G Di Perri.

At least 55 records · Page 3Linked to original sources

Failure of prophylaxis against PCP in patients with HIV infection.

Since the end of the 1980s, primary anti-Pneumocystis carinii pneumonia (PCP) prophylaxis has become a fundamental part of the global AIDS control strategy in industrialized countries. The widespread adoption of anti-PCP chemoprophylaxis has been a key element in prolonging the survival of patients with AIDS. There is general agreement on the need to begin chemoprophylaxis when individual CD4+ cell counts drop below the value of 200/microL. However, PCP still develops in up to 27% of susceptible HIV-infected patients despite regular prophylaxis intake. Failure of chemoprophylaxis may depend on different factors. The choice of the regimen and the patient's compliance to it have been the first variables to be identified, whereas the importance of the residual cellular immune function as complementary protective mechanism against PCP has emerged in subsequent clinical studies. Albeit of limited general concern, issues such as P. carinii drug resistance and defective drug absorption may play some role in prophylaxis failure in selected patients. Regarding the epidemiology of primary and recurrent episodes of PCP, recent studies based on genetic fingerprinting techniques revealed that interhuman transmission of the organism could be more relevant than so far expected, thus raising some concern of the possibility of nosocomial spread among susceptible individuals. The downgrading tendency of immune competence in HIV infection and the related increasing risk of developing PCP make it possible to envisage a two-step chemoprophylactic strategy, with the most effective compound, cotrimoxazole, to be reserved for the last and most risky disease stage, when immune response no longer provides any support for preventing the development of PCP.

AIDS-Related Opportunistic Infections↗

Association of tuberculosis risk with the degree of tuberculin reaction in HIV-infected patients. The Gruppo Italiano di Studio Tubercolosi e AIDS.

BACKGROUND: The risk of developing active tuberculosis associated with a different size of induration to purified protein derivative (PPD) has not been prospectively assessed among individuals infected with human immunodeficiency virus (HIV). The quantification of this risk is important to more appropriately identify candidates for preventive therapy for tuberculosis. METHODS: A prospective, multicenter, cohort study on tuberculosis in HIV-infected patients was conducted in 23 infectious disease units in public hospitals in Italy. Two thousand six hundred ninety-five HIV-infected patients were enrolled in the study. Of these, 1054 patients who were nonanergic at the time of entry were included in the present analysis. The median duration of follow-up was 102 weeks. The main outcome measure was a diagnosis of active tuberculosis confirmed by the isolation of Mycobacterium tuberculosis in culture. RESULTS: Among the 252 patients with PPD reactivity, patients with an induration to PPD of 2 to 4 mm had a median CD4+ lymphocyte count of 0.34 x 10(9)/L (interquartile [IQ] range, 0.14 x 10(9)-0.56 x 10(9)), those with a response of 5 to 9 mm had a median count of 0.38 x 10(9)/L (IQ range, 0.24 x 10(9)-0.56 x 10(9)), and those with a response of 10 mm or higher had a median count of 0.37 x 10(9)/L (IQ range, 0.23 x 10(9)-0.52 x 10(9)) (P = .38). Compared with the 802 nonanergic PPD-negative patients, hazard ratios of tuberculosis were 2.1 (95% confidence interval [CI], 0.2-18.3) among the 55 patients with a response to PPD of 2 to 4 mm, 5.7 (95% CI, 1.6-19.8) among the 128 patients with a response to PPD of 5 to 9 mm, and 23.1 (95% CI, 7.8-68.6) among the 69 patients with a response to PPD of 10 mm or higher. CONCLUSIONS: Among nonanergic HIV-infected patients, the degree of response to tuberculin does not appear to reflect the degree of immunosuppression and is strongly correlated with the subsequent incidence of tuberculosis. To identify HIV-infected patients who are at an increased risk of tuberculosis and may benefit from preventive therapy, a response to PPD of 5 mm appears to be an appropriate cutoff point.

AIDS-Related Opportunistic Infections↗

Aetiology of pneumonia following isolated closed head injury.

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.

Adolescent↗

Fulminant hepatitis on withdrawal of chemotherapy in carriers of hepatitis C virus.

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.

Adult↗

Comparative histopathological study of pulmonary tuberculosis in human immunodeficiency virus-infected and non-infected patients.

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.

AIDS-Related Opportunistic Infections↗

Epstein-Barr virus as a trigger for autoimmune hepatitis in susceptible individuals.

During follow-up of healthy relatives of 13 patients with autoimmune hepatitis, seven cases of infectious mononucleosis due to Epstein-Barr virus (EBV) occurred. In two of these seven, before EBV infection, there was a defect in suppressor-inducer T lymphocytes specifically controlling immune responses to the asialoglycoprotein receptor, an antigen expressed on the hepatocyte surface. In these two, antibodies to this autoantigen persisted and increased after infectious mononucleosis, and autoimmune hepatitis developed within 4 months. In susceptible individuals, EBV is a trigger for autoimmune hepatitis.

Adolescent↗

Pentoxifylline as a supportive agent in the treatment of cerebral malaria in children.

In an open, randomized, controlled therapeutic trial, 56 children with cerebral malaria (CM) were randomly assigned to receive standard quinine regimen with or without pentoxifylline (10 mg/kg/day by continuous intravenous infusion). Pentoxifylline exerted an inhibitory effect on the synthesis of tumor necrosis factor (TNF), a possible mediator of CM. The 26 children who received pentoxifylline had significantly shorter comas than controls (median, 6 vs. 46 h; P < .001) Pentoxifylline recipients showed a trend toward a lower mortality, with a borderline significant difference (P = .055). The better outcome in the pentoxifylline group was associated with a decline in TNF serum levels on the third day of treatment in a few subjects that was not seen in controls. While alternative or concurrent mechanisms of action may be of some relevance, larger double-blind trials are needed to determine whether pentoxifylline has a therapeutic role in CM.

Adolescent↗

Transbronchial biopsy in the diagnosis of pulmonary infiltrates in immunocompromised patients.

Bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) frequently are performed in the investigation of immunocompromised patients with lung disorders. The risk-benefit ratio of TBB currently is debated, since several authors have found that the less invasive BAL may provide as much information as TBB, with the avoidance of some biopsy-related side effects. We retrospectively evaluated 157 instances of bronchoscopy carried out on 142 immunocompromised patients, with both BAL and TBB performed in every case. Immunosuppressant conditions were HIV infection (79), hematologic malignancies (36), and antirejection therapy in renal transplant recipients (27). Transbronchial biopsy provided a diagnostic yield significantly higher than that obtained by BAL in all categories investigated; diagnostic rates were 77.3% for TBB and 47.6% for BAL (p < 0.001) in patients with HIV infection, 55 and 20% (p < 0.001) in patients with hematologic malignancies, and 57.5 and 27.2% (p < 0.001) in renal transplant recipients. Looking at the whole series, the diagnostic rates of TBB and BAL were 67.5 and 36.3%, respectively (p < 0.001), with a total additional yield of 33% provided by TBB, while in only 2% of cases BAL gave rise to diagnostic information not achieved by TBB. Considering that side effects followed TBB at a negligible rate (2.5%), we believe that TBB should be routinely carried out in these patients once the diagnostic strategy has been oriented to bronchoscopy.

Adolescent↗