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Biomedical subjects

I Yust

Publications and source records attributed to I Yust.

At least 19 recordsLinked to original sources
PubMed2004

Retinal and extraocular cytomegalovirus end-organ disease in HIV-infected patients in Europe: a EuroSIDA study, 1994-2001.

This multicentre prospective cohort study by the EuroSIDA study group was designed to determine the factors affecting the incidence of cytomegalovirus (CMV) end-organ disease (CMVD) and the rate of survival after diagnosis in patients with AIDS during the years 1994-2001. This period includes two eras, the pre-HAART era and the HAART era, because HAART affects the natural history of HIV infection, especially with respect to opportunistic infections, including CMV infection. Clinical and laboratory data were collected from the charts of 8,556 patients in 63 AIDS clinics in Europe. A total of 707 patients had CMVD at recruitment and at follow-up: 449 with retinitis (CMVR), 190 with extraocular CMV disease (EOCMVD), and 58 with both. Of the cases of EOCMVD, 66% involved the gastrointestinal tract and 17% the central nervous system. Of patients with a CD4+ count of < or =200 mm(-3) initially, 1.8% on HAART developed CMVD within a 24-month period, as compared to 11.1% on dual therapy and 14.3% without treatment (P<0.0001). There were highly significant differences in survival according to the calendar year (P<0.0001), with mortality declining from 79% during the years 1994-1995 to 42% in 2000-2001. The incidence of death after any CMVD was 28.4 per 100 patient-years of follow-up. Median survival of CMVR patients and EOCMVD patients was 11 and 7 months, respectively, the prognosis being better among patients with gastrointestinal rather than neurological CMVD. The initiation of HAART was associated with a 37% decrease in mortality (P<0.05). Eighteen percent of all deaths were caused by EOCMVD itself. This study describes a decline in the incidence and mortality of CMVR and EOCMVD during the HAART era of the HIV epidemic. It furthermore serves as a reminder of the importance of EOCMVD as a cause of morbidity and mortality in AIDS in the pre-HAART era.

AIDS-Related Opportunistic Infections↗
PubMed2004

Lung cancer in patients with HIV infection: is it AIDS-related?

HIV-infected individuals have an increased risk of malignancy, especially non-Hodgkin's lymphoma and Kaposi's sarcoma. Recently, several workers have noted a raised prevalence of lung cancer in HIV-positive subjects. We describe the diagnosis and clinical course for four HIV-seropositive patients who presented with lung cancer. All of the patients were young and were heavy smokers. They were all on highly active antiretroviral therapy (HAART), although the adherence varied from poor to excellent. The CD4 cell counts of these patients ranged from 200 to 686 cells/microL and their viral loads ranged from undetectable to 29,000 HIV-1 RNA copies/mL. After initial diagnosis of HIV infection between 5 and 13 years previously, they all presented with advanced lung cancer, with a very short clinical course, and all four died within 2-9 months of diagnosis. A comparison of the incidence of lung cancer in patients with HIV infection at our centre with that in the general population suggests that there is an increased prevalence in the HIV-infected patients. We review the literature and discuss whether lung cancer in HIV infection is coincidental or related to the primary disease.

Adult↗
PubMed2003

Induced sputum for diagnosing Pneumocystis carinii pneumonia in HIV patients: new data, new issues.

The complexity of bronchoalveolar lavage (BAL) has motivated the search for noninvasive methodology to retrieve specimens for detecting the presence of various pulmonary diseases. Induced sputum (IS) has been shown to be a reliable tool in terms of sensitivity and specificity comparable to BAL. Investigators from institutions worldwide have published several reports providing evidence in support of one or the other or a combination of both approaches. Among them are studies demonstrating the sensitivity and specificity of IS in diagnosing Pneumocystis carinii pneumonia (PCP) in patients with acquired immunodeficiency syndrome (AIDS). In 1996, highly active antiretroviral therapy was introduced for routine use and the morbidity from opportunistic infections decreased sharply. An earlier study showed that cost-effectiveness depends on the prevalence of a given condition in the population. More recent studies have confirmed that prophylaxis against PCP can be stopped after increasing the CD4 cell count, thus reducing the attractiveness of IS as a preferred method for monitoring the course of disease. This review presents a brief description of the evolution of the bronchoalveolar lavage versus induced sputum controversy and reconsiders the strengths and weaknesses of the earlier arguments in light of newer data that have emerged with regard to Pneumocystis carinii pneumonia in acquired immunodeficiency syndrome.

Antiretroviral Therapy, Highly Active↗
PubMed2002

Anti-heart antibodies in postpericardiotomy syndrome: cause or epiphenomenon? A prospective, longitudinal pilot study.

OBJECTIVES: To assess the role of anti-heart antibodies (AHA) in postpericardiotomy syndrome (PPS) and the timing of their appearance in relation to the initial manifestations of PPS. DESIGN AND SUBJECTS: Twenty patients who were scheduled to undergo elective coronary artery bypass grafting (CABG) were enrolled in a prospective, longitudinal pilot study. METHODS: Serum was sampled for AHA on the day prior to surgery and at regular intervalsfollowing surgery in all patients. In those who developed PPS, the serum AHA was determined on the day that typical clinical manifestations of PPS appeared and at regular intervals following the onset of PPS. RESULTS: All patients were negative for AHA on the day precedingsurgery. Three(15%) patients developed PPS. Their sera were negative for AHA on the day they were diagnosed as sufferingfrom PPS and the sera became positive for AHA within 14 days from the time of diagnosis. The intensity of immunofluorescence decreased markedly 30 days afterwards and AHA had disappeared within 90days after diagnosis of PPS. The other 17 (85%) patients were negative for AHA prior to surgery and remained so during the six-month postoperative follow-up period. CONCLUSION: The findings of this study suggest that serum AHA may not play a causal role inthe pathogenesis of PPS, but may rather be an epiphenomenon, reflecting an immune response to pericardial and/or myocardial injury.

Adult↗
PubMed2001

Thromboagglutination by anticardiolipin antibody complex in the antiphospholipid syndrome: a possible mechanism of immune-mediated thrombosis.

The tendency for patients with antiphospholipid syndrome (APLS) to thromboembolism and the criteria for its detection are well established, whereas the mechanism of this thrombophilic syndrome is still obscure. Using immunofluorescent techniques and a microscopic spontaneous platelet aggregation test (mSPAT), we have previously demonstrated platelet binding by antibody followed by aggregation in patients with lupus anticoagulant. In the present study, we investigated 18 anticardiolipin antibody-positive (ACLA pos.) patients, comprised of 12 primary APLS and 6 secondary APLS lupus patients. We demonstrated direct platelet microaggregate formation in 16/18 cases, whereas this finding was not present in 20 ACLA-negative (ACLA neg.) subjects (P<.001). Indirect testing revealed 10/12 cases of platelet microaggregation and none in the ACLA neg. subjects. In addition, immunofluorescent studies showed that platelet antibody complex binding occurred in 8/12 cases tested directly and in 11/12 cases in indirect testing, as compared to 1 out of 20 binding in ACLA neg. subjects (P<.001). Antibody complex binding was inhibited in two cases by prior extraction of phospholipids. Platelet aggregation could be demonstrated in two ACLA neg. individuals by the addition of exogenous ACLA to platelets in EDTA-plasma. We therefore propose a mechanism for immune-mediated thrombosis in APLS in which calcium-independent platelet aggregation, or thromboagglutination, is initiated by an ACLA-phospholipid complex present in the patients' plasma. Following the antibody complex-induced platelet agglutination, thrombosis proceeds by release, recruitment, and fibrin formation. The mechanism should have important implications in the diagnosis, management, and monitoring of APLS.

Adolescent↗
PubMed2001

Dissection of the humoral immune response toward an immunodominant epitope of HIV: a model for the analysis of antibody diversity in HIV+ individuals.

Understanding the dynamics of the humoral immune response to HIV epitopes in the presence of genetic drift and antigenic variation of the virus may reveal critical elements of protective immunity against HIV. Analysis of antibody maturation and diversity is difficult to study at the molecular level in humans. We used a combinatorial phage display peptide library to elucidate antibody diversity in HIV-infected individuals to a single immunodominant epitope in gp41. A serum sample derived from an HIV+ individual was used to screen a phage display a 12 mer cysteine-constrained loop peptide library. In doing so, we isolated mimotope-presenting phages corresponding to the immunodominant gp41 epitope CSGKLIC (residues 603-609). The mimotopes and control phages expressing epitope variants were reacted with a panel of 30 HIV+ sera. The patients showed distinct and variable recognition patterns compared with one another. Subfractions of the polyclonal sera were affinity purified and analyzed for epitope specificities. These analyses illustrated that epitope variants can be used to decipher antibody diversity. Elucidation of the plasticity of the humoral response and its polyclonality toward discrete epitopes contributes to our understanding of the antibody maturation process in individuals infected with viruses such as HIV.

Amino Acid Sequence↗
PubMed2000

The central nervous system-specific myelin oligodendrocytic basic protein (MOBP) is encephalitogenic and a potential target antigen in multiple sclerosis (MS).

Uncovering primary target antigens in multiple sclerosis (MS) is of major significance for understanding the etiology and pathophysiology of the disease, and for designing immunospecific therapy. In this study, a synthetic peptide representing a predicted T cell epitope on myelin oligodendrocytic basic protein (MOBP) was found to be encephalitogenic in C3H.SW mice, inducing experimental autoimmune encephalomyelitis with an abrupt onset. Two separate preliminary studies with MOBP peptides indicated that autoreactivity to MOBP occurs in MS. These data strongly suggest that MOBP is a highly relevant target in MS and further point to the complexity of antigen specificities in MS.

Amino Acid Sequence↗
PubMed1999

Immunologic responses of HIV-1-infected study subjects to immunization with a mixture of peptide protein derivative-V3 loop peptide conjugates.

V3 loop peptide sequences from several HIV-1 strains were covalently linked to purified protein derivative (PPD) of Mycobacterium tuberculosis. A mixture of PPD conjugates of V3 loop peptides from six different strains of HIV-1 induced a stronger antibody response than a single V3 peptide-conjugate administered to guinea pigs and humans. Sera from animals immunized with a PPD-six peptide-PPD conjugate neutralized multiple primary-isolate strains of HIV-1. Potent immune responses were noted only when animals were primed with bacillus Calmette-Guerin (BCG), PPD was covalently bound to the peptides, and PPD was used as the carrier protein. Based on these animal studies, an immunogen consisting of PPD-conjugated V3 loop peptides from five HIV-1 strains was tested in 7 HIV-1 seropositive PPD skin test positive study subjects. Vaccinees exhibited over time a uniform increase in neutralizing antibodies for both laboratory adapted and primary isolates of HIV-1, including strains from multiple clades. In 3 patients with baseline viral loads between 8000 and 12,000 RNA copies/ml, the viral load declined in 2 patients to <400 copies/ml and in 1 patient to 1200 copies/ml without concurrent administration of highly active antiretroviral therapy (HAART).

AIDS Vaccines↗
PubMed1999

Increased intracellular accumulation of macrophage inflammatory protein 1beta and its decreased secretion correlate with advanced HIV disease.

Considering that the chemokine macrophage inflammatory protein 1beta (MIP1beta) may serve as a competitive inhibitor for HIV entry, the objective of this study was to compare intracellular and extracellular levels of MIP1beta, in untreated HIV-infected individuals. HIV patients and healthy controls were tested by two-color flow cytometry for intracellular MIP1beta, in freshly explanted CD4 and CD8 lymphocytes, and in monocytes. Sera and plasma collected on the same day were tested, respectively, by enzyme-linked immunosorbent assay (ELISA) for MIP1beta concentration and for number of HIV-RNA copies, using nucleic acid sequence-based amplification procedure (NASBA) methodology. Results demonstrate that a high intracellular level of MIP1beta appears to be linked to a deterioration in the immune status of HIV patients (i.e., low CD4 counts) and to a high viral load. Moreover, an inverse relationship exists between the intracellular and the "secreted" form of MIP1beta, thus leading to the hypothesis that the regulation of cellular accumulation and secretion of MIP1beta and of other chemokines may be disrupted during AIDS development.

Case-Control Studies↗
PubMed1999

Pulmonary adiaspiromycosis in a patient with acquired immunodeficiency syndrome.

Adiaspiromycosis is a noninfectious, nonarthropod-transmitted fungal infection that occurs worldwide in lower vertebrates, especially rodents. However, humans may become accidental hosts. Reported here is a case of adiaspiromycosis of the lung in an HIV-positive, 40-year-old, bisexual man who first presented with cough and dyspnea. Cultures of a bronchoalveolar lavage and protected brush specimen revealed the presence of fungal elements that were identified as Emmonsia parva var. parva. The patient was successfully treated with amphotericin B and thereafter with fluconazole. This organism should be added to the list of pathogens that cause pulmonary infection in AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed1999

Anti-HIV indeterminate western blot in dialysis patients: a long-term follow-up.

In a group of 520 patients undergoing chronic hemodialysis, 23 (4. 4%) were enzyme immunoassay (EIA) positive for human immunodeficiency virus (HIV) and indeterminate by Western blot (IWB) analysis. The antibodies were mostly directed against p24 and p55 antigens. A comparison between hemodialysis patients with and without IWB showed significant differences between the two groups with respect to number of units of blood transfused, history of renal transplant rejection, and Rh status. No significant differences were observed with respect to ethnic group, nature of renal disease, duration of hemodialysis, associated diseases, and ABO blood group. The HIV IWB phenomenon may represent abnormal immune reactivity as a result of transplantation antigens and/or autoantibody formation. Five-year follow-up of the HIV EIA-positive IWB patients showed that none had seroconverted to HIV-positive status.

Blood Donors↗
PubMed1998

Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group.

BACKGROUND: The introduction of combination antiretroviral therapy and protease inhibitors has led to reports of falling mortality rates among people infected with HIV-1. We examined the change in these mortality rates of HIV-1-infected patients across Europe during 1994-98, and assessed the extent to which changes can be explained by the use of new therapeutic regimens. METHODS: We analysed data from EuroSIDA, which is a prospective, observational, European, multicentre cohort of 4270 HIV-1-infected patients. We compared death rates in each 6 month period from September, 1994, to March, 1998. FINDINGS: By March, 1998, 1215 patients had died. The mortality rate from March to September, 1995, was 23.3 deaths per 100 person-years of follow-up (95% CI 20.6-26.0), and fell to 4.1 per 100 person-years of follow-up (2.3-5.9) between September, 1997, and March, 1998. From March to September, 1997, the death rate was 65.4 per 100 person-years of follow-up for those on no treatment, 7.5 per 100 person-years of follow-up for patients on dual therapy, and 3.4 per 100 person-years of follow-up for patients on triple-combination therapy. Compared with patients who were followed up from September, 1994, to March, 1995, patients seen between September, 1997, and March, 1998, had a relative hazard of death of 0.16 (0.08-0.32), which rose to 0.90 (0.50-1.64) after adjustment for treatment. INTERPRETATION: Death rates across Europe among patients infected with HIV-1 have been falling since September, 1995, and at the beginning of 1998 were less than a fifth of their previous level. A large proportion of the reduction in mortality could be explained by new treatments or combinations of treatments.

Adult↗
PubMed1998

Increased intracellular macrophage inflammatory protein-1beta correlates with advanced HIV disease.

The objective of this study was to correlate between macrophage inflammatory protein-1beta (MIP1beta) and viral loads in untreated, HIV-infected individuals. For that purpose, HIV-positive patients were tested for number of copies of HIV-RNA in plasma and for intracellular MIP1beta in freshly explanted CD8 and CD4 lymphocytes and monocytes. Results demonstrate that the levels of MIP1beta in the various cell populations were significantly higher in the HIV group than in age-matched healthy individuals. Moreover, patients with low CD4 cell counts (<500/microl) and relatively high viral loads exhibited much higher levels of intracellular MIP1beta than patients with lower viral loads and CD4 counts >500/microl. We conclude therefore that although MIP1beta is induced in the various cell populations as a result of HIV infection in vivo, a high intracellular level of MIP1beta appears to be linked to a deterioration in the immune status of the patients.

CD4 Lymphocyte Count↗
PubMed1998

Serum amyloid type A may be a predictor of restenosis.

BACKGROUND: Elevation of acute phase proteins [C-reactive protein (CRP) and serum amyloid type A (SAA)] has been demonstrated in unstable angina with an adverse clinical prognosis. HYPOTHESIS: The study was undertaken to determine the effect of angioplasty on the levels of SAA and the correlation with postangioplasty restenosis. METHODS: In a university-affiliated tertiary medical center, a prospective case study was undertaken in 55 patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) of a single coronary lesion for angina pectoris. Three groups of patients were clinically characterized according to Braunwald's classification of anginal syndrome: Group A: class III; Group B: class I; Group C: stable angina. Serum amyloid type A was measured by an ELISA method before PTCA and after 24 h, 1, and 3 months. Patients were followed clinically for 12 months. A thallium stress perfusion scan was performed 3 months after PTCA and coronary angiography was repeated in patients with an abnormal thallium perfusion scan. RESULTS: Serum amyloid type A levels > 100 micrograms/ml could identify Group A patients with a high sensitivity and specificity (r = 0.85 and 0.86, respectively). Of the patients studied, 75% increased their SAA level 24 h after angioplasty. An increase of SAA by > 100% was associated with an increased risk of restenosis, with a relative risk of 6.4 (p < 0.05). CONCLUSION: Increased levels of SAA characterize patients with unstable angina pectoris with a high specificity and sensitivity. Levels of SAA that increase > 100% 24 h after angioplasty may serve as a marker of restenosis.

Adult↗
PubMed1997

Molecular epidemiology of HIV in Israel.

The aim of this study was to identify the HIV types and subtypes prevalent in Israel among different populations in terms of risk or geographic origin of the HIV infection. A total of 149 blood samples were collected from HIV-positive persons from different risk groups for HIV infection who were living in Israel. HIV subtyping was performed by a V3-based peptide enzyme immunoassay, supplemented by direct sequencing of polymerase chain reaction products from the V3 region. Multiple HIV-1 subtypes were shown to circulate in Israel; whereas most of the infections among Israelis and Palestinians were of subtype B, infections among the large Ethiopian population in Israel were caused by HIV-1 subtype C. Occasionally, we found HIV-1 subtypes A and D and a putative B/C recombinant. No HIV-2 infection was identified. Sequence comparisons and phylogenetic tree analyses point at multiple introductions of HIV into the country. The presence of mainly two different HIV-1 subtypes, B and C, in two separated populations in Israel may result in two distinct epidemiologic patterns among HIV-infected individuals in Israel. Subtype C infection among the Ethiopians in Israel opens new research avenues toward better understanding the natural history of infection with HIV-1 subtype C in Ethiopians living in a Western society compared with those living in Ethiopia.

Amino Acid Sequence↗