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Biomedical subjects

P Bossi

Publications and source records attributed to P Bossi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Polymorphism of the human immunodeficiency virus type 1 (HIV-1) protease gene and response of HIV-1-infected patients to a protease inhibitor.

In order to analyze the impact of protease gene polymorphism on response to regimens containing a protease inhibitor, the entire protease coding domain from 58 human immunodeficiency virus type 1 (HIV-1)-infected patients who were protease inhibitor naive was sequenced before therapy was started. Plasma HIV-1 RNA levels were measured at baseline and at month 3 and month 6 after treatment. All patients were treated with a combination of two reverse transcriptase inhibitors and a protease inhibitor (saquinavir EOF [n = 28], ritonavir [n = 16], or indinavir [n = 14]). Before treatment, 30 different positions whose codons differed from the subtype B consensus sequence were observed. Major mutations associated with protease inhibitor resistance were not observed. No statistical correlation between the number of amino acid differences and the treatment efficacy at month 3 (-2.4 log) or month 6 (-2.7 log) was observed. At baseline, genotypic analysis of the HIV-1 protease gene of patients who have never received a protease inhibitor does not allow prediction of the efficacy of regimens containing a protease inhibitor.

Acquired Immunodeficiency Syndrome↗
PubMed1999

[Polymorphism of protease genes in patients infected with HIV-1 and response to therapy including a protease inhibitor].

Protease inhibitors (PIs) are recently introduced drugs that have improved the survival of HIV-infected patients when given in combination with two reverse transcriptase inhibitors. The HIV-1 protease gene is naturally highly polymorphic. Selection pressure due to IP use can result in major or minor resistance-associated mutations (RAMs). This study investigated whether presence before IP therapy of minor RAMs on the protease gene predicts the virological response. Of the 58 PI-naive patients included in the study, 12 had received two nucleoside reverse transcriptor inhibitors, 14 had received indinavir, 16 ritonavir, and 28 saquinavir-SGC. Viral load was measured on D0 (prior to PI initiation) and at M3 and M6 (Roche Monitor 1.5 with 200 and 20 copies/ml as the thresholds). The protease gene was fully sequenced on D0 using the ABI 377 automatic sequencer after RNA amplification by nested RT-PCR. None of the viral strains exhibited major mutations, but 57 of 58 (98%) had at least one minor mutation (median number of substitutions, 4), 60% had 1 to 4 substitutions, and 40% had 5 to 9 substitutions. Substitutions seen with a prevalence > 20% were located at codons 15, 35, 37, 41, 63, and 77. Numbers of substitutions at M3 and M6 were not correlated with viral load or the nature of the PI used, and neither were they significantly different between patients with more or fewer than 20 copies/ml. These data suggest that the protease genotype at PI initiation does not predict the efficacy of a regimen including a PI and is of no assistance in deciding whether or not to include a PI in a triple combination regimen.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Fractal and spectral dimension analysis of liver fibrosis in needle biopsy specimens.

OBJECTIVE: To evaluate the usefulness of a reliable and reproducible mathematical scoring system based on fractal geometry for quantifying the irregular pattern in fibrosis commonly seen in liver biopsy specimens from chronic liver diseases. STUDY DESIGN: The study used 26 standard liver biopsy specimens obtained from patients with chronic hepatitis C virus-related liver disease. The degree of fibrosis in each specimen was estimated using a quantitative scoring system based on the computer-assisted evaluation of both the fractal and spectral dimensions of deposited collagen. The fractal dimension was then compared with the percent area of collagen measured using an image analysis system. RESULTS: The fractional dimension of its irregular shape defines fibrosis as a natural fractal structure. The complex distribution of its collagenous components (unmeasurable by means of the usual morphometric parameters) can be optimally quantified using a single numerical score that seems to be a better alternative to the semiquantitative methods adopted so far. The proposed method is reproducible, rapid and inexpensive; furthermore, supported by specific software, its mathematical approach excludes subjectivity and eliminates the external factors capable of influencing staging and classification. CONCLUSION: This study demonstrated that it is possible to quantify the irregularity of the structures of the liver in an objective manner and that the box-counting fractal dimension does not depend on the amount of collagen deposited on the slide. Furthermore, as has been found in other fields of investigation, study of the fractal properties of the liver is likely to reveal more about its structure and the pathogenesis of liver diseases.

Biopsy, Needle↗
PubMed1998

Prevalence of human herpesvirus 8 infection measured by antibodies to a latent nuclear antigen in patients with various dermatologic diseases.

BACKGROUND: Human herpesvirus 8 (HHV-8) has been detected in all epidemiological forms of Kaposi sarcoma (KS). The role of HHV-8 in dermatologic diseases other than KS is controversial. Some studies based on polymerase chain reaction findings suggest an association between HHV-8 and epithelial tumors of the skin, lymphoproliferative disorders, or pemphigus. OBJECTIVE: To assess the prevalence of antibodies against a latent nuclear antigen of HHV-8 in patients with various dermatologic diseases. DESIGN: An indirect immunofluorescence assay was used to search for HHV-8 antibodies. SETTING: Ambulatory or hospitalized patients from a university hospital associated with a research laboratory. PATIENTS: Eighty-three patients with various non-KS dermatologic diseases and 16 patients with KS who were seronegative for the human immunodeficiency virus. Controls were 100 healthy subjects living in the same area. RESULTS: Antibodies to HHV-8 were found in 100% (16/16) of the patients with KS and 3.6% (3/83) of the patients with non-KS dermatologic diseases: 1 patient with pemphigus vulgaris, 1 with discoid lupus erythematosus, and 1 with bullous pemphigoid. The prevalence of antibodies to HHV-8 in controls was 2% (2/100) and was not significantly different than the prevalence in patients with dermatologic diseases other than KS (P =.28). CONCLUSIONS: Our serologic study confirms the higher prevalence of HHV-8 antibodies in patients with KS and demonstrates that contrary to other human herpesviruses, HHV-8 is not a ubiquitous virus in France. We could not determine any causal association between HHV-8 and pemphigus or lymphoproliferative disorders of the skin.

Adult↗
PubMed1998

Acquired hemophilia due to factor VIII inhibitors in 34 patients.

BACKGROUND: Acquired hemophilia is a rare disease caused by the development of auto-antibodies against factor VIII. SUBJECTS AND METHODS: We studied the characteristics and outcomes of 34 patients (19 women and 15 men) with acquired hemophilia from 1980 to 1997. RESULTS: The mean age of the patients was 61 years (range, 22-93 years). An underlying disease was observed in 18 (53%) patients: 5 patients had cancer, 4 an autoimmune disorder, 2 a dermatologic disorder, 3 asthma, 3 were postpartum, and 1 had an adverse reaction to ampicillin. Factor VIII level was <5% in 30 (90%) patients; factor VIII antibodies were elevated (>10 Bethesda units) in 23 (69%) patients. Bleeding requiring transfusions was reported in 25 (75%) patients. Human factor VIII was given to 14 patients and porcine factor VIII to 5. Six patients received prothrombin complex concentrates and one desmopressin. Several immunosuppressive treatments were used, mainly corticosteroids, cyclophosphamide, and intravenous immunoglobulin. Bleeding stopped in all but one patient within 2 weeks. Most patients achieved complete remission, although two relapses were observed subsequently. CONCLUSION: This large study helps to clarify the presentation and clinical course of acquired hemophilia. Prospective studies are needed to determine the efficacy of treatment.

Adult↗
PubMed1998

[Epidemiologic characteristics of cerebral toxoplasmosis in 399 HIV-infected patients followed between 1983 and 1994].

OBJECTIVE: To describe the epidemiological characteristics of toxoplasmic encephalitis in HIV-infected patients with a more than 12-year follow-up. METHODS: From a data base of 1,628 AIDS subjects hospitalized from 1983 to 1994, we studied the epidemiological characteristics of 399 patients with toxoplasmic encephalitis. Diagnosis of toxoplasmic encephalitis was based on the association of central neurological disorders, typical lesions on CT scan or MRI, and favorable outcome under appropriate toxoplasmosis therapy. RESULTS: Four hundred sixty-four cases of toxoplasmic encephalitis were reported in 399 patients (24.5% of the patients with AIDS). The overall incidence was 20.5 per 100 patients-year. Toxoplasmic encephalitis was the first AIDS defining event in 51% of the cases and revealed HIV infection in 13% of the cases. In the remaining 49%, the mean delay from AIDS diagnosis to toxoplasmic encephalitis was 13 months (range: 1-71 months). At the time of diagnosis, mean CD4 count was 44/mm3 (range: 0-408/mm3). Antibodies to Toxoplasma gondii were found in 97% of the cases. Before the first episode of toxoplasmic encephalitis, 58% of the patients were given antiretroviral therapy (mean: 17.8 months; range: 1-64 months). Of the 399 patients with toxoplasmic encephalitis, 366 (92%) did not receive any primary toxoplasmosis prophylaxis. Among them, 205 (56%) did not receive any drug prophylaxis, and 161 (44%) had Pneumocystis carinii pneumonia prophylaxis alone (aerosolized pentamidine). Thirty-three failures were observed (8%) with cotrimoxazole: 14 cases (3%) were considered to have irregular compliance. Sixty-five relapses were observed in 52 patients. At the end of the study 334 patients had died (84%). The median survival was 11.4 months (95% confidence interval, range: 10.4-12.4 months). CONCLUSIONS: Toxoplasmic encephalitis incidence has decreased since the introduction of appropriate drug prophylaxis.

AIDS-Related Opportunistic Infections↗
PubMed1998

The level of human immunodeficiency virus (HIV) type 1 RNA in cerebrospinal fluid as a marker of HIV encephalitis.

We prospectively evaluated the level of human immunodeficiency virus (HIV) type 1 RNA in cerebrospinal fluid (CSF) as a marker of HIV encephalitis. Fifty-two HIV-1-infected patients (41 males and 11 females; mean age, 39 years) were tested for the presence of HIV-1 RNA in plasma and CSF. Samples of CSF were obtained by lumbar puncture to evaluate cognitive deficits, seizures, or fever among these patients. HIV encephalitis was diagnosed in 11 patients (21%), other CNS diseases were diagnosed in 12 (23%), and fever without CNS disease was diagnosed in 29 (56%). HIV-1 RNA was detectable in 92% of the plasma specimens and 75% of the CSF specimens. No significant difference was observed in CSF levels of HIV-1 RNA between patients with or without HIV encephalitis. CSF levels of HIV-1 RNA correlated with plasma levels of HIV-1 RNA (Spearman's rank correlation, +0.31; P = .02) and CSF white blood cell counts (Spearman's rank correlation, +0.4; P < .01). The absence of any significant difference between patients with or without HIV encephalitis suggests that the CSF HIV-1 RNA level is not a good marker for the diagnosis of HIV encephalitis.

AIDS Dementia Complex↗
PubMed1998

Toxoplasma gondii-associated Guillain-Barré syndrome in an immunocompetent patient.

We report a case of Guillain-Barré syndrome associated with an acute, disseminated toxoplasmosis due to a new and unknown zymodeme (zymodeme 12) in an immunocompetent patient. The patient's condition improved with pyrimethamine and sulfadiazine. Only the standard treatment for toxoplasmosis was effective, whereas intravenous immunoglobulins were ineffective.

Adult↗
PubMed1998

Cell cycle-related gene abnormalities and product expression in esophageal carcinoma.

In esophageal carcinoma, individual genetic alterations of cyclins, cyclin-dependent kinase inhibitors, and final effectors of the G1-to-S transition have been documented. Our aim was to design a comprehensive analysis of the role and clinical significance of some critical genes, namely cyclin D1, MTS1, and Rb. To this end, cyclin D1 gene amplification and protein accumulation, Rb gene allelic loss and protein expression, and MTS1 gene mutation and DNA methylation were investigated in a series of 74 esophageal carcinomas. Cyclin D1 amplification was documented in 17 of 55 (31 %) cases, being a feature of squamous cell type (14 of 17 amplified cases). Cyclin D1 accumulation significantly correlated with lymph node metastasis (p < 0.02), advanced tumor stage (p < 0.05), and a reduced overall survival rate (p < 0.03). Rb gene loss of heterozygosity occurred in 14 of 39 (36%) informative cases and was associated with an unfavorable survival rate (p < 0.01). MTS1 gene mutations were detected in 2 adenocarcinomas only; gene methylation was observed in 17 of 72 cases (24%) without any correlations with the variables investigated. A direct association between cyclin D1 and Rb gene accumulation (p < 0.0005) and an inverse one between RB loss of heterozygosity and MTS1 abnormalities (p < 0.05) emerged from this study. These results have important clinical implications because both cyclin D1 and Rb gene deregulation are significantly related to an unfavorable survival rate. In addition, cyclin D1 amplification is associated with esophageal carcinoma of squamous cell type, being totally absent in adenocarcinomas (p < 0.01). The combined evaluation of these genes also demonstrates that molecular abnormalities of genes belonging to the same pathway are mutually exclusive and unnecessary for the neoplastic transformation and tumor progression.

Carcinoma↗
PubMed1998

[Clinical importance of the quantification of HIV-1 RNA in cerebrospinal fluid for the diagnosis of HIV encephalitis].

We evaluated prospectively the HIV-1 RNA level in CSF as a marker of HIV encephalitis diagnosis. 110 HIV-1 infected patients (mean age: 39 years; sex-ratio M/F: 94/16) were tested for HIV-1 RNA in plasma and CSF. Lumbar punctures were performed to explore cognitive deficit, seizure or fever. HIV encephalitis was diagnosed in 15 patients (14%), other CNS disease in 34 (31%), and fever without CNS disease in 61 (55%). HIV-1 RNA was detectable in 93% of the plasma and in 62% of the CSF. No significant difference was observed in CSF HIV-1 RNA between patients with or without HIV encephalitis. CSF HIV-1 RNA was correlated with plasma HIV-1 RNA (p < 0.01), CSF protein (p < 0.01) and CSF white cell counts (p < 0.01). The absence of any significant difference between patients with or without HIV encephalitis, suggests that the CSF HIV-1 RNA level is not a good marker for its diagnosis.

AIDS Dementia Complex↗
PubMed1998

[HHV-8 related diseases].

KAPOSI'S DISEASE: HHV-8 sequences have been found in all the epidemiological forms of Kaposi's disease. There is a direct relationship between HHV-8 infection and PBMC and later development of Kaposi's disease. The HHV-8 sequences can be found in spindle cells or endothelial cells in Kaposi lesions. OTHER DISEASES: HHV-8 is also associated with certain lymphomas including body-cavity-based lymphomas and Castleman's disease. It has also been put forward that there is a relationship between HHV-8 and multiple myeloma, epithelial tumors in kidney transplant recipients, angiosarcoma, and angiolymphoid hyperplasia.

Herpesvirus 8, Human↗
PubMed1998

[Resistance to antiretroviral agents: mechanism and study methods].

FREQUENT MUTATIONS: Associated with the high turnover rate of the HIV, frequent inverse transcriptase errors lead to a wide range of possible mutations. Certain mutations can modify the response to antiretroviral agents. The development of resistant strains is mediated by the selection pressure of antiretroviral agents and occurs at a very variable rate depending on the antiretroviral agent used. TO LOWER THE RISK OF RESISTANCE: Persistent replication, whatever the cause, favors the emergence of resistant mutants. Thus the antiretroviral treatment must be initiated early and with the most powerful protocol possible in order to reduce viral replication as quickly as possible. CONTRIBUTION OF VIROLOGY TESTS: It is not always possible to predict the efficacy of antiviral agents from phenotyping and genotyping results. Their use is currently limited to cases of treatment failure. Their contribution in everyday clinical practice remains to be defined.

Anti-HIV Agents↗
PubMed1997

[Tuberculous meningitis: clinical, biological and x-ray computed tomographic comparison between patients with or without HIV infection].

OBJECTIVES: Determine possible differences in clinical manifestations, laboratory findings and neuroimaging results in tuberculous meningitis patients with and without HIV infection. PATIENTS AND METHODS: We retrospectively reviewed data of 38 patients with positive cerebrospinal fluid cultures for Mycobacterium tuberculosis who were hospitalized in 3 university hospitals in Paris over the last 11 years. RESULTS: There were 24 HIV-infected patients and 14 without HIV infection. Mean CD4 lymphocyte count was 103 +/- 180/mm3 in the HIV group. Age (median age = 33 years for the HIV group vs. 53 for the non-HIV group), sex ratio (3 vs. 0.75), and prior history of tuberculosis (46% vs. 43%) were similar in both groups. Clinical presentation was similar for headache (83% in HIV group vs. 50% in non-HIV group; p = 0.02) and confusion (54% vs. 93% in non-HIV group p = 0.05). Serum natremia (mmol/l) (131 +/- 5 vs. 125 +/- 8; p = 0.024), white blood cell count (x 10(9)/l) (5.8 +/- 4.7 vs. 10.7 +/- 1.7; p = 0.37) and erythrocyte sedementation rate (mm/h) (68 +/- 34 vs. 31 +/- 35; p = 0.003) were significantly different in the 2 groups. Median cerebrospinal fluid findings were similar in the 2 groups: leukocytes (x 10(6)/l) (375 +/- 860 vs 218 +/- 250), glucose (mmol/l) (2.3 +/- 0.9 vs 2.7 +/- 1.9) and protein (g/l) (3.8 +/- 7.1 vs. 2.6 +/- 1.6). CT-scans of the brain were similar in the 2 groups. Mortality during hospitalization was similar (42% vs 36%; NS). CONCLUSION: HIV infection appears to have little impact on the presentation of tuberculous meningitis.

Adult↗
PubMed1997

p53 protein accumulation and p53 gene mutation in esophageal carcinoma. A molecular and immunohistochemical study with clinicopathologic correlations.

BACKGROUND: p53 gene mutation and p53 protein accumulation are common in human cancer. However, their clinical significance is controversial and p53 accumulation may not correlate with gene mutation. The current study investigates the occurrence of p53 alterations in esophageal carcinoma, the correlation between the analyses at the gene and protein level, and their prognostic significance. METHODS: A series of 74 esophageal carcinomas (46 squamous cell carcinomas, 21 Barrett's adenocarcinomas, and 7 undifferentiated carcinomas) was studied by single strand conformation polymorphism (SSCP) analysis and immunohistochemistry (IHC) to detect p53 mutation and accumulation, respectively. RESULTS: p53 mutations in exons 5-8 were detected in 53% of the carcinomas whereas p53 accumulation was observed in 57% of cases. Comparing SSCP and IHC, there were 27 discordant cases (38%). Overall, only 20 tumors (27%) did not display p53 mutation and/or p53 accumulation. No associations were found between p53 aberrations and clinicopathologic parameters, including patients age and gender tumor type, stage, and grade. p53 protein accumulation and p53 gene mutation were not related to patient survival by univariate or multivariate analysis in esophageal carcinomas. CONCLUSIONS: p53 aberrations are very common in esophageal carcinomas. However, p53 gene mutation and p53 protein accumulation have a significant discordance, suggesting that p53 function may be inactivated by mechanisms other than mutation. p53 aberrations do not independently predict prognosis in esophageal tumors.

Adenocarcinoma↗