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Biomedical subjects

A G Saimot

Publications and source records attributed to A G Saimot.

At least 37 records · Page 2Linked to original sources
PubMed1993

Dapsone-pyrimethamine compared with aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia and toxoplasmosis in HIV infection. The PRIO Study Group.

BACKGROUND: Pneumocystis carinii pneumonia and toxoplasmic encephalitis are frequent life-threatening opportunistic infections in patients with human immunodeficiency virus (HIV) infection. Primary prophylaxis against P. carinii pneumonia is now common, but there are few data on regimens for primary prophylaxis against toxoplasmosis. METHODS: We conducted a randomized trial that compared two prophylactic regimens: dapsone (50 mg per day) plus pyrimethamine (50 mg per week) was compared with aerosolized pentamidine (300 mg per month). The patients had symptomatic HIV infection, no history of P. carinii pneumonia or symptomatic toxoplasmosis, and CD4+ counts below 200 per cubic millimeter (0.2 x 10(9) per liter). RESULTS: In an intention-to-treat analysis, after a median follow-up of 539 days P. carinii pneumonia developed in 10 patients in each group, whereas toxoplasmosis developed in 32 of 176 patients in the pentamidine group and 19 of 173 patients in the dapsone-pyrimethamine group. Those assigned to pentamidine had a risk of P. carinii pneumonia that was similar to the risk in those assigned to dapsone-pyrimethamine (adjusted relative risk, 1.13; 95 percent confidence interval, 0.44 to 2.92; P = 0.79), but a higher risk of toxoplasmosis (adjusted relative risk, 1.81; 95 percent confidence interval, 1.12 to 2.94; P = 0.02). Among the 262 patients with serologic evidence of past exposure to Toxoplasma gondii, the relative risk of symptomatic toxoplasmosis was 2.37 times higher in those assigned to pentamidine (95 percent confidence interval, 1.3 to 4.4; P = 0.006). More patients discontinued dapsone-pyrimethamine than pentamidine because of toxicity (42 vs. 3; P < 0.001). Survival was similar in the two groups. CONCLUSIONS: For primary prevention of P. carinii pneumonia, dapsone-pyrimethamine is as effective, though not as well tolerated, as aerosolized pentamidine. Dapsone-pyrimethamine also prevents first episodes of toxoplasmosis.

AIDS-Related Complex↗
PubMed1993

Detection of Toxoplasma gondii in venous blood from AIDS patients by polymerase chain reaction.

Detection of Toxoplasma gondii in blood by means of the polymerase chain reaction (PCR) may facilitate the diagnosis and follow-up of cerebral toxoplasmosis in patients with AIDS. We evaluated this approach with seven patients with tissue culture-proven parasitemia, 14 patients with presumptive cerebral toxoplasmosis, and 17 healthy human immunodeficiency virus-positive controls. Each sample of blood was assayed on three different occasions by a PCR assay based on detection of the gene encoding the P30 surface protein. A positive PCR diagnosis required positivity in at least two of the three PCR tests. None of the controls had a positive PCR diagnosis, but six of the seven patients with parasitemia did. Cerebral toxoplasmosis was confirmed in 13 of the 14 patients with a presumptive diagnosis; diagnosis by PCR was positive before treatment for 9 of these 13 patients, whereas tissue culture was positive for only 1 patient. During treatment, blood samples were taken from 14 patients at regular intervals until day 12. PCR diagnosis became negative on ethidium-stained gels, but persistent signals were observed after hybridization, in some cases, for up to 12 days after initiation of therapy. PCR on venous blood could thus be a sensitive and noninvasive method for the diagnosis of cerebral and disseminated toxoplasmosis in AIDS patients and could be a potential tool for monitoring the effects of treatment.

AIDS-Related Opportunistic Infections↗
PubMed1993

[Renal parenchymatous involvements in African and Caribbean patients with human immunodeficiency virus infection. Apropos of 10 cases].

Between 1989 and 1990, 10 HIV-infected patients with renal involvement (proteinuria and/or renal failure) were followed. The 5 men and 5 women black (4 Haitians, 3 Zairians, 2 Congolese and 1 Angolan). Their mean age was 31.7 +/- 4 years. No known risk factor was identified and transmission was probably heterosexual. When renal disease was diagnosed, 4 patients had AIDS, 5 had ARC and 1 was asymptomatic. Kidney biopsies were performed in 7 patients: 4 HIV-associated nephropathies (HIV AN) with segmental and focal hyalinizations, 1 thrombotic angiopathy, and 2 interstitial nephropathies, 1 with proliferative glomerulonephritis. The clinical, biological and radiographic patterns of 2 of the remaining 3 patients were suggestive of HIV AN. Four of the 6 patients with HIV AN developed end-stage renal disease within 5 +/- 2.5 months; renal function in the other 2 remained stable for 25 and 41 months, respectively, while they were receiving zidovudine, but deteriorated rapidly within weeks of withdrawing this drug. Zidovudine may have delayed the evolution of the nephropathies in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1992

[Prophylaxis and maintenance treatments of opportunistic infections in adults].

Primary prophylaxis against opportunistic infections is a capital advance in the management of HIV-infected patients. In cases with pneumocystosis prophylaxis is recommended when the number of T4 cells reaches 200/mm3 or 15 to 20% and constitutes a major incitation to apply for detection of seropositivity. It can be predicted that other prophylaxis of this type will be available for other main opportunistic infections whose proportion is increasing due to extension of the patient's life expectation (e.g. toxoplasmosis). Research in this field relies on new drugs, on the use of older drugs, and above all on experimental models providing a good preclinical evaluation. The development of combined prophylactic treatments against several opportunistic infections is a priority target. Maintenance treatments are systematically given after a first opportunistic infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Recombinant interferon-alpha for chronic hepatitis C in patients positive for antibody to human immunodeficiency virus. Comité des Anti-Viraux.

To assess the response to and tolerance of recombinant interferon-alpha administration in patients with chronic hepatitis C and human immunodeficiency virus (HIV) infection, 12 patients with chronic hepatitis C and HIV infection were given interferon-alpha, 1, 3, or 5 million units thrice weekly, for 4 or 6 months. Four patients had a complete response (normal serum alanine aminotransferase activity [ALT]), 3 had a near-complete response (serum ALT less than one-and-one-half times the upper limit of normal), and 5 had no response at the end of administration. Histologic examination of liver showed an improvement in 1 patient with complete response and no improvement in another patient with no response. In patients with chronic hepatitis C with HIV infection, the response to and tolerance of recombinant interferon-alpha were not different from those usually observed in patients with chronic hepatitis C infection without HIV infection.

Adult↗
PubMed1992

Qualitative and quantitative analysis of human cytotoxic T-lymphocyte responses to HIV-1 proteins.

OBJECTIVE: To study the degree of immunogenicity of each HIV-1 protein. DESIGN: In most viral systems, antiviral cytotoxic T-lymphocytes (CTL) from a given donor preferentially recognize only one or a small number of viral proteins. METHODS: Anti-HIV CTL were generated by in vitro stimulation of peripheral blood mononuclear cells from seropositive donors and tested against multiple HIV-1 proteins or groups of proteins encoded by seven genes (env, gag, pol, nef, rev, tat and vif). Using autologous target cells infected with recombinant vaccinia viruses expressing one of the HIV-1LAI proteins, we compared the cytolytic activities obtained from bulk culture with those found in limiting dilution analysis (LDA). RESULTS: Our results were noteworthy for the following reasons. (1) Each responding donor reacted simultaneously to multiple proteins; this is very unusual in other viral systems. Anti-Gag CTL were detected in most, and anti-Pol in approximately three-quarters, of the patients, together with very high amounts of the corresponding CTL precursors in LDA. CTL against Env and Nef were found in two-thirds of the patients, while Vif- and Rev-specific CTL were less frequent. Finally, Tat was seldom recognized by CTL, but its antigenicity was revealed in LDA. (2) All responding cells revealed in bulk cultures as well as in LDA were CD8+ T-cells, and their in vitro differentiation did not require the help of CD4+ T-cells. (3) Proteins from the HIV-1LAI isolate were recognized with high frequency by CTL from seropositive donors, most certainly being infected by other isolates, which suggests that relatively conserved epitopes are predominant targets of CTL. CONCLUSION: Taken together, these results are encouraging for vaccine purposes, since anti-HIV-1 CTL stimulation is thought to be a requirement for such a vaccine.

AIDS Vaccines↗
PubMed1991

Six epitopes reacting with human cytotoxic CD8+ T cells in the central region of the HIV-1 NEF protein.

In order to identify the target epitopes recognized by specific CTL in the NEF protein of HIV-1, 33 peptides derived from the HIV-BRU sequence were tested with NEF-specific CTL generated from HIV-seropositive donors. Six different epitopes were identified and several points were remarkable: 1) They were all located in two regions of the central part of the NEF protein corresponding to residues 73 to 94 and 113 to 147, respectively. 2) The CTL issued from a single donor could recognize several peptides of the NEF protein. 3) Some of these peptides could be recognized in association with at least two or three different HLA class I molecules. 4) Two different overlapping epitopes were present in a relatively short sequence of 15 amino acids. These results suggest that multiple epitopes corresponding to different HLA restrictions could coexist in a relatively small region of the NEF protein. The implications of these results in vaccine strategies using synthetic peptides bearing CTL epitopes are discussed.

Amino Acid Sequence↗
PubMed1991

[Pneumocystis carinii pneumonia in HIV infection. Diagnosis, prognostic factors and curative treatment].

The diagnosis of Pneumocystis carinii pneumonia (PCP) rests on the isolation of this micro-organism in patients whose latest blood count, less than 2 months old, shows less than 250 CD4 lymphocytes per cubic mm and who present with signs of impaired lung function. Bronchoalveolar lavage (BAL) is the reference diagnostic method, but induced expectoration may be the initial examination, in which case BAL is performed only when the latter fails or gives negative results. Prognostic factors are those of any interstitial pneumonia plus those specific to PCP and those associated with HIV infection. It is only when no initial severity factor is present that cure can be contemplated, provided the effectiveness of treatment is evaluated daily. Cotrimoxazole is the reference drug for comparisons with all new treatments; the indications of corticosteroid therapy and the necessity of intensive care techniques are now better determined. The frequency of PCP and its mortality rate should be reduced, and one may look forward to a time when this disease will be rare and atypical, thereby raising other diagnostic and therapeutic problems.

Adrenal Cortex Hormones↗
PubMed1990

Immunohistochemical evidence for human immunodeficiency virus-1 infection of liver Kupffer cells.

To investigate the possibility of human immunodeficiency virus-(HIV) 1 infection of liver cells, liver samples from 17 patients with either acquired immunodeficiency syndrome (AIDS, 13), AIDS-related complex (ARC, 3), or lymphadenopathy syndrome (LAS, 1) were studied. A monoclonal antibody directed against the p24 gag HIV-1 protein was used in an immunoperoxidase assay and yielded positive results in seven out of 17 samples. Staining by anti-p24 antibody was of three types: diffuse in Kupffer cells of most samples, inside granuloma in cells that were probably histiocytes, and in some sinusoidal cells whose origin was difficult to ascertain. Attempts to locate the CD4 membrane antigen showed that it was mainly present on endothelial sinusoidal cells. These results indicate that liver cells, including Kupffer cells, might be infected by HIV-1, and that these cells might be involved in certain liver lesions observed during HIV-1 infection, particularly sinusoidal abnormalities.

AIDS-Related Complex↗
PubMed1990

[Hepatic involvement in AIDS. A retrospective clinical study in 71 patients].

In order to determine the extent of liver abnormalities occurring during acquired immunodeficiency syndrome, the available histological analyses of liver samples (32 biopsies, 52 autopsies) from 71 AIDS patients, for the period 1982-1986, were studied retrospectively. Hepatomegaly was the most common clinical symptom (23 patients, 32.4%), while jaundice was rare, being seen in only 5 cases (7%). Progressive anicteric cholestasis was the most frequently observed biological anomaly (29/52, 55.7%). Ten patients had liver infections: 2 Mycobacterium tuberculosis, 8 Mycobacterium avium intracellulare. Cytomegalovirus was present in 3 patients and 1 individual was infected with Cryptococcus neoformans. Granulomatous hepatitis was associated with these infectious agents in 11 patients, but remained unexplained in 11 others. Three patients had cholangitis (2 with CMV inclusions, 1 unexplained). Among the 32 biopsies, 5 elucidated the origin of unexplained fever. Kaposi's sarcoma of the liver was found in 10/52 autopsy samples (19%) and hepatic lymphoma in 2 cases. Non-specific histological lesions were common: inflammation of the portal spaces (48 cases, 67.6%), steatosis (32 patients, 45%), peliosis hepatis (9 cases, 12.6%) and sinusoidal dilations (39 cases, 54.9%).

Acquired Immunodeficiency Syndrome↗
PubMed1989

An antigenic peptide of the HIV-1 NEF protein recognized by cytotoxic T lymphocytes of seropositive individuals in association with different HLA-B molecules.

By using target cells that expressed only the regulatory NEF protein of the human immunodeficiency virus (HIV), we were able to identify specific cytolytic T cells (CTL) from most of the seropositive patients tested. This NEF-specific cytolytic activity was mediated by CD8+ lymphocytes. In two different donors, we identified a unique peptide in the NEF protein that could be recognized in association with two different HLA class I molecules. The definition of such a peptide should prove useful in evaluating vaccine strategies.

Amino Acid Sequence↗
PubMed1989

Intestinal infections in patients with acquired immunodeficiency syndrome. A prospective study in 132 patients.

We studied prospectively 132 patients with acquired immunodeficiency syndrome to define the spectrum of enteric pathogens during this disease, with special reference to the correlation between the lesions, the infections, and the symptoms. Forty-four percent of the patients harbored at least one enteric pathogen: the most frequently recovered were Cryptosporidium (28), cytomegalovirus (16), Entamoeba histolytica (13), Giardia lamblia (9), and Mycobacterium avium intracellulare (7). Patients harboring pathogens were more likely to be diarrheics (69%) than patients without a pathogen (38%; P = 0.01) and more likely to have endoscopic lesions (29%) than patients without a pathogen (4%; P less than 0.001). The most common pathogen associated with diarrhea was Cryptosporidium. Cytomegalovirus, Entamoeba histolytica, and Salmonella typhimurium were each significantly associated with endoscopic lesions. Patients with cytomegalovirus infection tended to have a greater incidence of ulcer than patients without cytomegalovirus infection. Stool analysis diagnosed 61% of the infections, while endoscopy diagnosed 44%. Seven percent were recognized by stool analysis and endoscopy. When considering the 24 patients in whom accurate diagnosis warranted endoscopic biopsies, stool examination alone would have given an incomplete diagnosis in 14 patients (due to the presence of polyinfection). The frequency of inaccurate diagnosis of infection by stool determination alone, plus the development of new antiviral agents that suppress cytomegalovirus, may favor the earlier application of endoscopic evaluation in these patients.

Acquired Immunodeficiency Syndrome↗