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Biomedical subjects

C Contini

Publications and source records attributed to C Contini.

At least 37 records · Page 2Linked to original sources

Production of plasminogen activator and plasminogen activator inhibitors by alveolar macrophages in control subjects and AIDS patients.

OBJECTIVE: To reveal a possible impairment of the plasminogen activator system in the pulmonary infections of AIDS patients. DESIGN: To test the plasminogen activator system functionality in alveolar macrophages and bronchoalveolar lavage fluid (BALF) in control subjects and AIDS patients. Procedures were designed to detect the presence of imbalance in plasminogen activator activity and to ascertain if this imbalance is due to a direct effect of the HIV virus on macrophages or to superimposed opportunistic infection. METHODS: Alveolar macrophages obtained by bronchoalveolar lavage (BAL) were either lysed with Triton X-100 or cultured for 24 h. Plasminogen activators and plasminogen activator inhibitors (PAI) were measured by chromogenic substrate assay and binding to 125I-urokinase followed by 10% sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE), respectively. RESULTS: Plasminogen activator activity in BALF and in alveolar macrophages from AIDS patients was decreased. This reduction was independent of the presence of an infectious pulmonary process. In contrast, free PAI was increased in AIDS patients with Pneumocystis carinii infection. This increase is possibly caused by a different glycosylated form of PAI-2. CONCLUSIONS: Our data support the view that the pulmonary fibrogenic response is in part secondary to an imbalance within the plasminogen activator system and provide the basis for clarifying the role of these alterations in the pathophysiology of AIDS-related pulmonary infections.

Acquired Immunodeficiency Syndrome↗

Cytomegalovirus in bronchoalveolar lavage specimens from patients with AIDS: comparison with antigenaemia and viraemia.

Pulmonary infection with cytomegalovirus (CMV) is a well recognised complication of AIDS. It is often possible to detect CMV-infected cells in bronchoalveolar lavage (BAL) specimens with monoclonal antibodies, but the clinical significance of their presence remains unclear. To investigate this, 24 AIDS patients were tested for CMV antigenaemia and viraemia, in addition to CMV detection in BAL. CMV was detected in the BAL of nine patients (38%), five with clinical and laboratory evidence of pulmonary infection and four without pulmonary involvement. Blood samples positive for CMV antigen were observed in two patients with CMV-positive BAL specimens and, in both cases, antigenaemia resolved without therapy. No case of viraemia was detected. Pneumocystis carinii was detected concomitantly with CMV in the BAL of four of the patients with pulmonary involvement and in one without signs of pulmonary infection. These data suggest that CMV-positive BAL results are of limited significance in the diagnosis of CMV pneumonia in AIDS patients, unless associated with high levels of antigenaemia or viraemia and compatible clinical symptoms.

AIDS-Related Opportunistic Infections↗

Employment of terbinafine against Pneumocystis carinii infection in rat models.

The anti-Pneumocystis carinii response of terbinafine together with that of three other compounds, trimethoprim sulphamethoxazole (TMP-SMX), atovaquone (ATQ) and albendazole (ALB), has been investigated in immunosuppressed Sprague-Dawley rats with established pneumocystosis. Drugs were administered orally (terbinafine in dosages of 40 and 80 mg/kg per day, TMP 12.5 mg/kg per day plus SMX 62.5 mg/kg per day, ATQ 100 mg/kg per day and ALB 600 mg/kg per day) to six rat groups except one which served as a control. P. carinii pneumonia (PCP) was identified post-mortem in nine (90%) of the control rats which exhibited a marked P. carinii burden, and mean lung weights were higher with respect to the other treatment groups. During treatment, five rats in the control group died, whereas between 11 and 13 rats in all treatment groups survived. In the terbinafine groups (40 mg and 80 mg/kg per day), a mild P. carinii infection developed in three and two rats (27.2 and 18%), respectively, and almost the same infectivity score was obtained for those treated with 40 mg and 80 mg/kg per day. Histological changes in the lungs in animals receiving terbinafine treatment were minimal. Among the remaining compounds the rate of infection was seven (58.3%) for the ALB treatment group and five (45.4%) for the ATQ group (mean score 19.4 +/- 7.1 and 23 +/- 2.1, respectively). In the TMP-SMX treatment group, there were 13 surviving rats and P. carinii organisms were found in two (15.3%, mean infection score 8 +/- 1.1).

Administration, Oral↗

Diagnosis of Toxoplasma gondii infection in AIDS patients by a tissue-culture technique.

Toxoplasma gondii infection was investigated in 14 AIDS patients with neurological involvement who showed clinical and computer tomographic scan signs suggestive of toxoplasmic encephalitis or extraneuronal localization suggestive of toxoplasmic infection. Blood, lung secretion (bronchoalveolar lavage and/or induced sputum sample) and cerebral spinal fluid (CSF) samples were cultured, and the results compared with the results of direct examination by Giemsa and by immunofluorescence of lung secretions and CSF. Toxoplasma gondii were observed directly in only four patients by immunofluorescence in bronchoalveolar lavage, induced sputum and CSF samples, and in three of these patients by Giemsa staining of bronchoalveolar lavage and CSF smears. In contrast, parasites were detected after 48 h in blood cultures from 11 of the 14 AIDS patients, in CSF cultures from eight of them and also in cultures of bronchoalveolar lavage and induced sputum from the six patients with respiratory and radiological features indicative of lung tissue damage. The findings indicate the value of tissue culture for diagnosis of toxoplasmosis as well as for monitoring the effects of treatment and also indicate that culture of induced sputum could be a powerful tool in establishing the incidence of pulmonary toxoplasmosis in AIDS patients.

AIDS-Related Opportunistic Infections↗

Evidence of Pneumocystis carinii in cell line cultures infected with peripheral blood mononuclear cells isolated from AIDS patients with P. carinii pneumonia.

The detection of Pneumocystis carinii was investigated in an in-vitro system consisting of a human lung epithelial cell line (A-549) inoculated with infected peripheral blood mononuclear cells (PMBC) from HIV-infected patients with proven or suspected P. carinii pneumonia (PCP), and from HIV-negative patients with other lung infections. Supernates from cultures were sampled daily and evaluated for the presence of P. carinii by Giemsa and immunofluorescence staining. P. carinii was isolated from 98 (95.1%) of 103 culture supernate samples from patients with proven pneumocystosis and 45 (66.1%) of 68 from patients with suspected PCP 40 or 72 h after PBMC inoculation. This system has been shown to support the growth of P. carinii but did not seem to be adequate for the production of large numbers of organisms, although long-term survival in vitro for up to 3 weeks was observed. Recovery of P. carinii from infected PBMC strongly supports previous observations about its ability to disseminate haematogenously and could represent a further advance in understanding the pathogenesis and diagnosis of PCP.

AIDS-Related Opportunistic Infections↗

Pneumocystis carinii pneumonia in preterm infants: report of two cases successfully diagnosed by non-bronchoscopic bronchoalveolar lavage.

We present two cases of Pneumocystis carinii pneumonia in apparently immunocompetent preterm infants presenting with unexplained respiratory distress associated with a predominantly interstitial process on the chest radiograph. Definite diagnosis was promptly established on the detection of cyst forms in the lung fluid obtained by non-bronchoscopic bronchoalveolar lavage, and a favourable outcome was achieved.

Bronchoalveolar Lavage↗

Activity of terbinafine against Pneumocystis carinii in vitro and its efficacy in the treatment of experimental pneumonia.

The antiprotozoan and antifungal agent, the terbinafine, was investigated for its potential activity against Pneumocystis carinii infection of the A549 cell line culture and on immunosuppressed Sprague Dawley rats in comparison with trimethoprim-sulphamethoxazole and pentamidine isethionate. Terbinafine suppressed P. carinii growth at doses up to 3 g/L within 24 h and it was able to inhibit cyst forms at 60 h post inoculation. With respect to trimethoprim-sulphamethoxazole and pentamidine isethionate P. carinii organisms decreased at the same time interval but cyst form elimination was less apparent than with terbinafine. The results of the in-vitro culture were consistent with the in-vivo observations. Of the 3 groups of rats tested, the occurrence of P. carinii pneumonia was documented in 18 (60%) of the control rats (group 3) which showed a high degree of P. carinii burden and a marked weight loss with respect to the beginning of the experiment. Among terbinafine treated rats (group 1), P. carinii pneumonia was present in one rat (3.3%), while no P. carinii infection occurred in the pentamidine isethionate and in trimethoprim-sulphamethoxazole treatment rat groups (group 2). All the agents investigated showed no particular signs of toxicity. These preliminary results suggest further explorations of the terbinafine in clinical trials for treatment and prophylaxis of P. carinii pneumonia.

Animals↗

Histologic evidence of myocardial damage in apparently healthy subjects with ventricular arrhythmias and myocardial dysfunction.

The association of ventricular arrhythmias and myocardial dysfunction could be considered an early step toward cardiomyopathy; therefore, we studied 28 patients in NYHA class I and II, characterized by complex ventricular arrhythmias (VA) on 24-h Holter monitoring and volumetric and/or contractile abnormalities on a standard two-dimensional echocardiogram (2-D echo). All patients underwent radioisotopic angiography, 20 patients complete hemodynamic study, and 15 patients endomyocardial biopsy. Ambulatory ECG monitoring showed the presence of frequent premature ventricular contractions in 14 patients (50%) and episodes of ventricular tachycardia in 16 patients (57%). 2-D echo showed mono- or biventricular enlargement and dyssynergies in 25 patients (89%) (left ventricle in 6, right ventricle in 11, both in 8). Two patients showed only left ventricle enlargement and one patient isolated left ventricular dyssynergies. Radioisotopic angiography showed mono- or biventricular ejection fraction reduction in 24 patients (85%) and regional dyssynergies in 24 patients (85%) in accordance with 2-D echo. Hemodynamic study showed in all patients normal coronary arteries, and right and left angiography confirmed enlargement and/or regional dyssynergies. Endomyocardial biopsy was abnormal in 11 of 15 patients: various degrees of hypertrophy, parcellar fibrosis, and adipogenic infiltration were found. Our preliminary data suggest that the simultaneous occurrence of ventricular arrhythmias and ventricular dyssynergies and/or enlargement in patients without apparent clinical heart disease may represent an early stage of dilated cardiomyopathy.

Adolescent↗

Evidence for the existence of ganglioside molecules on Pneumocystis carinii from human lungs.

This study was undertaken to assess whether glycolipid antigens (particularly gangliosides) are associated with Pneumocystis carinii obtained from human lungs. Gangliosides were extracted, purified in high performance thin-layer chromatography and stained with resorcinol. Two resorcinol-positive bands, co-migrating with GM1 and GD1a were demonstrated, suggesting the existence of ganglioside molecules on P. carinii. No resorcinol-positive bands were revealed in the pulmonary control tissue. In addition, an antiserum obtained from rabbits immunized with P. carinii antigen reacted with gangliosides GM1 and GD1a, as revealed by a dot immunobinding assay. This reactivity was inhibited by first incubating the antiserum with ganglioside micelles. Furthermore, anti-glycosphingolipid antibodies (aGM1) reacted with the bands of 200 and 55 kDa of P. carinii antigen. These results suggest that ganglioside antigens expressed on P. carinii can trigger specific immune responses.

Acquired Immunodeficiency Syndrome↗

[Endoscopic palliative treatment of malignant bile duct obstruction by endoprosthesis].

Endoscopic positioning of a large biliary endoprosthesis has become a well codified procedure for palliative treatment of primary or metastatic malignant bile duct obstruction. Authors' experience, regarding 47 patients treated by this technique from February 1992, is reported. Furthermore, either absolute or site-related per cent rate of successful positioning of endoprosthesis, efficacy of procedure, early and late complications and mean survival are reported. Results confirm the effectiveness of the procedure in reducing jaundice resulting from malignant bile duct obstruction and low complication rate; early detection and treatment of prosthetic obstruction with subsequent cholangitis, that is the most important factor responsible for death, depend upon close collaboration between physician and endoscopist.

Aged↗

Production and characterization of monoclonal antibodies to human Pneumocystis carinii for the diagnosis of P. carinii pneumonia.

OBJECTIVES: Monoclonal antibodies against human Pneumocystis carinii were produced by fusion of myeloma cells (X63-AG8.653) with splenocytes from Biozzi mice that had been immunized against P. carinii cysts isolated from infected human lung. The aim of this study was to evaluate the usefulness of these monoclonal antibodies for the diagnosis of P. carinii pneumonia by indirect immunofluorescence in comparison with a modified silver stain method and commercial kits. METHODS: One hundred fifty-seven specimens from 87 patients, infected or non-infected with human immunodeficiency virus, were examined for the presence of P. carinii. Specimens were either induced sputum samples or bronchoalveolar lavage fluids. Indirect immunofluorescence was performed with six stable clones obtained by limiting dilution. Four of the monoclonal antibodies were IgG1 isotypes, one was an IgG3 and one was an IgM. Their isoelectric points varied from 6.5 to 8.3. Tests were also performed with silver methenamine staining and with two commercially available monoclonal antibodies (Monofluo kit from Diagnostics Pasteur and MAb from Dako). RESULTS: The 6 antibodies all recognized P. carinii cysts in indirect immunofluorescence. No cross reactivity was observed with yeast or host cells. P. carinii antigens could not be identified with western immunoblotting suggesting that the monoclonal antibodies recognized native antigens. This result was confirmed by dot blot analysis. Spots were observed with native but not with denatured antigens. Inhibition studies showed that these 6 antibodies recognized the same or overlapping sites. The sensitivities of detection of P. carinii in sputum were 87% by silver stain and from 93.5 to 96.7% by immunofluorescence. The sensitivities of detection in bronchoalveolar lavage were 67.3% by silver stain and from 75.7% to 76.8% by immunofluorescence. CONCLUSION: Immunofluorescence was more sensitive than silver staining and the best results were obtained with E5-8 and A8-13 monoclonal antibodies and with Monofluo kit.

Animals↗