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Biomedical subjects

S Bonora

Publications and source records attributed to S Bonora.

At least 37 records · Page 2Linked to original sources

Recovery of long-term natural protection against reactivation of CMV retinitis in AIDS patients responding to highly active antiretroviral therapy.

OBJECTIVES: To see whether in severely immunosuppressed AIDS patients (with prior Cytomegalovirus retinal disease) who have significant increases in CD4+ lymphocytes following the initiation of highly active antiretroviral therapy (HAART) anti-Cytomegalovirus (CMV) maintenance therapy can be withdrawn with no subsequent progression of CMV retinitis. METHODS: Eight patients with AIDS and one or more previous episodes of CMV retinitis interrupted anti-CMV maintenance therapy following the successful beginning of HAART. CD4 cell counts and HIV-RNA were monitored monthly while measurement of CMV antigenemia and ophthalmoscopy were carried every 2 weeks thereafter. RESULTS: The HAART recipients in whom anti-CMV maintenance therapy had been interrupted had measureable increases of CD4+ T lymphocytes, substantial control of both HIV-RNA and CMV viraemia and did not show recurrence of retinitis during a mean follow-up of 98.4 weeks (range 78-120, SD 15.2). CONCLUSIONS: Anti-CMV maintenance therapy can be interrupted with no subsequent progression of retinal damage over a long time in patients with AIDS who successfully respond to HAART with a significant increase in CD4 cell count.

AIDS-Related Opportunistic Infections↗

Rapid absorption and clinical effectiveness of intragastric mefloquine in the treatment of cerebral malaria in African children.

To obviate the lack of injectable quinine in a hospital in rural Burundi, mefloquine, only available as an oral formulation, was administered (25 mg/kg bodyweight) as a single dose by nasogastric tube to four small children with cerebral malaria. All patients recovered uneventfully after a mean coma duration of 20.5 h. Mefloquine was rapidly absorbed and therapeutic serum concentrations were achieved within a few hours in all subjects, with parasite reduction ratios after 48 h within the expected range for drug-sensitive parasites. These findings suggest that intragastric mefloquine deserves consideration whenever parenteral drugs are not available for the treatment of cerebral malaria.

Absorption↗

Comparative evaluation of ligation-mediated PCR and spoligotyping as screening methods for genotyping of Mycobacterium tuberculosis strains.

Spoligotyping has been suggested as a screening test in multistep genotyping of Mycobacterium tuberculosis strains. Relying on restriction fragment length polymorphism (RFLP) analysis with IS6110 (IS6110 RFLP analysis) as a "gold standard," we performed a comparative evaluation of spoligotyping and ligation-mediated PCR (LMPCR), a recently described PCR-based typing method, as rapid screening tests for fingerprinting of 158 M. tuberculosis strains collected in Verona, Italy. LMPCR seemed to be comparable to spoligotyping in terms both of feasibility with rapidly extracted DNA and of generation of software-analyzable images. Moreover, LMPCR grouped considerably fewer strains than spoligotyping (38 versus 67%) and was found to reduce the cluster overestimation rate (26.3 versus 58%) and to give a better discriminatory index (0.992 versus 0.970) compared to spoligotyping. In our geographical region, where there was no evidence of clustered strains carrying fewer than six IS6110 copies, LMPCR was found to be more discriminatory than spoligotyping. We also evaluated two models of three-step typing strategies, involving the use of spoligotyping and LMPCR as screening methods and IS6110 RFLP analysis as a further supporting test. LMPCR proved to be a more effective first-step test than spoligotyping, significantly reducing the need for subtyping. LMPCR should be considered an alternative to spoligotyping as a rapid screening method for M. tuberculosis fingerprinting, particularly in areas with a low prevalence of M. tuberculosis strains carrying few copies of IS6110.

DNA Transposable Elements↗

Response of uncomplicated falciparum malaria to oral chloroquine and quinine in Burundi highlands.

The in vivo response of falciparum malaria to oral chloroquine and quinine was evaluated in two identical hospital-based, comparative open trials carried out 2 years apart in the same seasonal period at a hospital located in the highlands of Northern Burundi. Children aged 0-14 with uncomplicated falciparum malaria were administered either chloroquine, at 25 mg/kg over 3 days, or quinine, at 10 mg/kg per 8 hourly for 5 days (alternate allocation) and treatment response was evaluated by the WHO 7-day test. In the first study (1992/1993) 472 patients qualified for analyses (211 in the chloroquine and 261 in the quinine group), as compared to 249 subjects in the second study (1994/1995). In each study, the response to quinine was significantly higher than that to chloroquine (P = 0.004 and < 0.001, respectively). While the response to quinine showed insignificant changes over time (95.8 vs. 92.9%), chloroquine was found to be significantly less effective in the second study as compared to the first (77.8 vs. 63.1%; OR (95% CI) 2.04 (1.21-3.43)). Such decline in chloroquine efficacy was attributable to the age group < 5 years of age, where response to chloroquine decreased from 72.9% in 1992/93 to 56% in 1994/1995. Uncontrolled chloroquine use, which spread after the onset in late 1993 of the still ongoing ethnic fighting, appears to be the most likely reason for such a decrease in chloroquine efficacy. Chloroquine resistance has long been known to be present in the hyperendemic lowlands of Burundi, but no data have so far been reported on the response to antimalarials in the highlands of the country. These findings should be considered when deciding on drug policies for the treatment of falciparum malaria in Burundi.

Administration, Oral↗

Fatal primary multidrug-resistant tuberculosis in a heart transplant recipient.

The incidence of tuberculosis (TB) worldwide is currently on the rise, not only in the general population but also quite notably among immunosuppressed patients. Its incidence among patients undergoing antirejection therapy is considerably higher than in the general population, and heart transplant recipients have been found to carry the highest risk of TB. There are no reported data, however, on primary TB caused by multidrug-resistant (MDR) Mycobacterium tuberculosis (M. tuberculosis) in heart transplant recipients. We describe the case of a patient who developed active primary MDR TB following the reactivation of a latent tuberculous infection 6 months after transplantation. The patient was most likely infected by M. tuberculosis during a period of time he spent in prison 10 years before undergoing transplantation, but he never developed active tuberculosis, nor did he ever receive antituberculous medication prior to transplantation. Because of the atypical clinical presentation, establishment of the diagnosis was postponed, and the resistance pattern of the isolate grown from bronchoalveolar lavage (BAL) specimens (resistant to isoniazid and rifampicin) led to treatment failure and a fatal outcome. The adoption of the most rapid diagnostic tools for the identification of M. tuberculosis and for a quick screening of drug-resistant isolates is urgently needed in those centers where organ transplantation is carried out.

Fatal Outcome↗

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↗

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↗

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↗