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Biomedical subjects

A Cazzadori

Publications and source records attributed to A Cazzadori.

At least 19 recordsLinked to original sources

CD4(+) T cell clones producing both interferon-gamma and interleukin-10 predominate in bronchoalveolar lavages of active pulmonary tuberculosis patients.

The pattern of cytokine production in T cell clones derived from bronchoalveolar lavages (BAL) of active pulmonary tuberculosis (TB) patients was analyzed in clones obtained by limiting dilution procedures which expand with high efficiency either total T lymphocytes, independently of their antigen-recognition specificity, or Mycobacterium tuberculosis-specific T cells. BAL-derived clones, representative of CD4(+) cells from five patients with active TB, produced significantly higher amounts of IFN-gamma than BAL-derived CD4(+) clones from three inactive TB donors or four controls (with unrelated, noninfectious pathology). Average IL-4 and IL-10 production did not differ significantly in the three groups. Although these data suggest a predominant Th1 response to M. tuberculosis infection in the lungs, the majority of BAL-derived CD4(+) clones produced both IFN-gamma and IL-10 and the percentage of clones with this pattern of cytokine production was significantly higher in clones derived from BAL of active TB patients than from controls. Only rare clones derived from peripheral blood (PB)-derived CD45RO(+) CD4(+) T cells of both patients (nine cases) and controls (four cases) produced both IFN-gamma and IL-10; instead, the IL-10-producing clones derived from PB T cells most often also produced IL-4, displaying a typical Th2 phenotype. Higher average amounts of IFN-gamma and IL-10 were produced by BAL-derived CD8(+) clones of four active TB patients than of four controls, although the frequency of CD8(+) clones producing both IFN-gamma and IL-10 was lower than that of CD4(+) clones. The M. tuberculosis-specific BAL-derived T cell clones from three active TB patients were almost exclusively CD4(+) and produced consistently high levels of IFN-gamma often in association with IL-10, but very rarely with IL-4. Unlike the BAL-derived clones, the M. tuberculosis-specific clones derived from PB CD45RO(+) CD4(+) T cells of three different active TB patients and two healthy donors showed large individual variability in cytokine production as well as in the proportion of CD4(+), CD8(+), or TCR gamma/delta(+) clones. These results indicate the predominance of CD4(+) T cells producing both the proinflammatory cytokine IFN-gamma and the anti-inflammatory cytokine IL-10 in BAL of patients with active TB.

Antigens, Bacterial↗

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↗

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↗

Penetration of dapsone into pulmonary lining fluid of human immunodeficiency virus type 1-infected patients.

We studied the penetration of dapsone into the epithelial lining fluid (ELF) of sixteen human immunodeficiency virus type 1-infected patients who had received the drug at a dose of 100 mg twice weekly as primary prophylaxis for Pneumocystis carinii pneumonia. Bronchoscopy, bronchoalveolar lavage (BAL), and venipuncture were performed for each patient at a specific time after administration of the last dose of dapsone. Dapsone concentrations in plasma and BAL were determined by high-performance liquid chromatography. The apparent volume of ELF recovered by BAL was determined by using urea as an endogenous marker. The mean concentrations of dapsone in ELF at 2 h (five patients), 4 h (three patients), 12 h (two patients), 24 h (three patients), and 48 h (three patients) were 0.95, 0.70, 1.55, 0.23, and 0.45 mg/liter, respectively, while concentrations in plasma were 1.23, 0.79, 1.31, 0.83, and 0.18 mg/liter, respectively. Dapsone concentrations in ELF were 76, 79, 115, 65, and 291% of those observed in plasma at the same times, respectively. These data show that dapsone is well distributed into ELF and that a twice-weekly 100-mg prophylactic regimen results in sustained concentrations in this compartment.

Adult↗

Pharmacokinetics of antimicrobial agents in the respiratory tract.

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.

Animals↗

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↗

Invasive pulmonary aspergillosis complicating allergic bronchopulmonary aspergillosis.

Invasive pulmonary aspergillosis is a frequent complication in immunocompromised patients. The role of the prolonged use of steroids in predisposing to invasive aspergillosis has been recognized, but exceptionally described in asthmatic patients. We report the case of a 59-year-old woman with bronchial asthma treated with steroid therapy for a long time, who developed an invasive pulmonary aspergillosis with an unusual combination of invasive and allergic disease. It seems reasonable to think that allergic disease due to allergic bronchopulmonary aspergillosis (ABPA) preceded the terminal invasive process. Adjunctive therapy with antifungal agents in patients with ABPA is considered, since there is the risk of an invasive pulmonary aspergillosis.

Aspergillosis↗

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↗

[Tracheal sleeve lobectomy in the radical surgery for lung cancer].

Tracheal sleeve lobectomy is right upper lobectomy extended to include resection of the main bronchus, the carina and a segment of the trachea with end-to-end anastomosi of the trachea and end-to-side anstomosis of the intermediate bronchus on the main left bronchus, or the upper lobe on the trachea. This operation is possible with the aid of high frequency jet ventilation. The surgical indication of this operation is bronchoscopic and functional and guarantees a good oncological radicality in the presence of N0.

Anastomosis, Surgical↗