Israel Yust

Fatal necrotizing esophagitis due toPenicillium chrysogenum in a patient with acquired immunodeficiency syndrome

Although blue-green molds of the genusPenicillium are ubiquitous in the human environment, invasive penicilliosis is uncommon and primarily encountered among immunosuppressed patients. A patient with HIV infection who died of severe necrotizing esophagitis caused byPenicillium chrysogenum is reported and the relevant English language literature on human penicilliosis is reviewed. Although infectious esophagitis is commonly associated with AIDS,Penicillium esophagitis has not been described in such patients.

Prevalence and clinical features of dementia associated with the antiphospholipid syndrome and circulating anticoagulants.

The increasing prevalence with age of antiphospholipid antibodies (aPL), of dementia and of stroke complicates the study of a causal relationship between antiphospholipid syndrome (APS) and dementia. Prolonged aPTT due to circulating anticoagulants (CAC) may serve as a more specific laboratory marker of APS. In a hospital-based study, we examined all patients with CAC and included 23 who fulfilled standard criteria for primary APS. These patients were assessed for dementia, vascular brain disease, autoimmune disease activity and dementia risk factors. Among CAC-positive APS patients, 13 of the 23 (56%) were demented and these were significantly older (mean age+/-S.E., 68+/-3 years) than the nondemented APS group (n=10, 51+/-4 years; p<0.01, Students t-test). The demented patients had significantly more pathology on computerized brain tomography (CT) and electroencephalography (EEG) studies but six of them had no clinical or CT evidence of vascular brain disease. Erythrocyte sedimentation rate was significantly lower in the dementia group, in which there was also a significant negative correlation between levels of aPL and age. CAC-positive APS patients seem to be at risk for developing dementia with age, suggesting a pathogenic role for prolonged exposure to elevated aPL.

Demonstration of antispermatozoal antibodies in varicocele-related infertility with an enzyme-linked immunosorbent assay (ELISA)

To assess the existence of a possible immunologic factor in varicocele-associated infertility, we searched for antispermatozoal antibodies in serum, seminal plasma, and bound to spermatozoa in 32 infertile men with varicocele and 22 infertile patients without palpable varicocele, with the use of an enzyme-linked immunosorbent assay. In addition, we performed morphologic and microbiologic analyses of the semen and urethral smears for isolation of Chlamydia trachomatis. Twenty-nine men from the varicocele group (90.6%) demonstrated antispermatozoal antibodies, compared with only 9 men (40.9%) in the control group. The antibodies in both groups, when present, were mainly serum and seminal plasma immunoglobulins IgA and IgM. A significant quantitative difference between the varicocele and control groups was also observed for serum IgA, seminal plasma IgA and IgM, and sperm-bound IgG, IgA, and IgM. Oligozoospermia and asthenozoospermia were significantly more prevalent in the varicocele men. An asymptomatic genital tract infection with C. trachomatis, Ureaplasma urealyticum, and Escherichia coli was traced in 40.6% of the varicocele men and in 45.5% of the control group. No interaction could be demonstrated between the infection and antispermatozoal antibody formation. These data suggest that an immunologic factor may play a role in varicocele-associated infertility; however, its impact on reproduction has yet to be assessed.

Evaluation of a Benchtop HIV Ultradeep Pyrosequencing Drug Resistance Assay in the Clinical Laboratory

ABSTRACT Detection of low-abundance drug resistance mutations (DRMs) of HIV-1 is an evolving approach in clinical practice. Ultradeep pyrosequencing has shown to be effective in detecting such mutations. The lack of a standardized commercially based assay limits the wide use of this method in clinical settings. 454 Life Sciences (Roche) is developing an HIV ultradeep pyrosequencing assay for their benchtop sequencer. We assessed the prototype plate in the clinical laboratory. Plasma samples genotyped by the standardized TruGene kit were retrospectively tested by this assay. Drug-treated subjects failing therapy and drug-naive patients were included. DRM analysis was based on the International AIDS Society USA DRM list and the Stanford algorithm. The prototype assay detected all of the DRMs detected by TruGene and additional 50 low-abundance DRMs. Several patients had low-abundance D67N, K70R, and M184V reverse transcriptase inhibitor mutations that persisted long after discontinuation of the drug that elicited these mutations. Additional patient harbored low-abundance V32I major protease inhibitor mutation, which under darunavir selection evolved later to be detected by TruGene. Stanford analysis suggested that some of the low-abundance DRMs were likely to affect the resistance burden in these subjects. The prototype assay performs at least as well as TruGene and has the advantage of detecting low-abundance drug resistance mutations undetected by TruGene. Its ease of use and lab-scale platform will likely facilitate its use in the clinical laboratory. The extent to which the detection of low-abundance DRMs will affect patient management is still unknown, but it is hoped that use of such an assay in clinical practice will help resolve this important question.

Long-Term Treatment of the Syndrome of Inappropriate Antidiuretic Hormone Secretion with Phenytoin

A 68-year-old patient with the syndrome of inappropriate antidiuretic hormone secretion secondary to basilary skull fracture was treated successfully with demeclocycline and phenytoin. Phenytoin, which was considered in the past only as a useful diagnostic tool, was given to the patient on a long-term basis. The drug reversed the patients symptoms and abnormal laboratory values to normal limits without adverse reactions during a treatment period of 8 months.

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

HIV‐infected individuals have an increased risk of malignancy, especially non‐Hodgkins lymphoma and Kaposis 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/μL 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.

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.

Platelet antibody binding and spontaneous aggregation in 21 lupus anticoagulant patients

In order to ascertain the role of the antiphospolipid antibody in the pathogenesis of thrombotic disorders, a study of 21 lupus anticoagulant‐positive patients was done by a number of serologic and functional platelet tests. In immunofluorescent studies, we found that 80% showed a mitochondrial pattern on HEp cells and all patients gave an ubiquitously intense staining of donor platelets. By a microscopic spontaneous aggregation test, all lupus anticoagulant‐positive patients showed accelerated platelet aggregation which was calcium‐independent. The results show that the plasma of lupus anticoagulant‐positive patients contains a platelet‐binding antibody and causes spontaneous agglutination of platelets. These properties may play a role in the thrombogenesis common to the antiphospholipid syndrome.

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.

Autoimmune and inflammatory responses may have an additive effect in postpercutaneous transluminal coronary angioplasty restenosis

Patients who had an increase in their serum amyloid type A level of > 100% in the first 24 hours after percutaneous transluminal coronary angioplasty (PTCA) and also developed a positive antibody result (antinuclear factor or anticardiolipin), had a relative risk of 10.6 for developing restenosis in the first year after PTCA.