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S Swindells

Publications and source records attributed to S Swindells.

34 records · Page 2Linked to original sources
PubMed1996

Regulation and characterization of the interferon-alpha present in patients with advanced human immunodeficiency virus type 1 disease.

To examine a possible association between plasma viremia and interferon-alpha (IFN-alpha) in patients with the acquired immunodeficiency syndrome (AIDS), we performed IFN plasma immunoadsorption by apheresis (IFN-alpha apheresis) in four volunteers with AIDS who had sustained levels of endogenous plasma IFN-alpha. IFN-alpha apheresis with two plasma volume exchanges was performed daily for 5 days. Clinical signs and symptoms and hematologic, virologic, and immunologic parameters were monitored. Two subjects developed anemia from phlebotomy, and one had a catheter++-associated bacteremia. The IFN-alpha apheresis was effective only in transiently removing IFN-alpha: depletion of IFN-alpha led only to its rapid reconstitution. Cell-associated HIV-1 was unchanged, but three of four subjects had a modest decrease in culturable plasma virus burden following the procedures. The recovery of in vivo HIV-1-related IFN-alpha by apheresis allowed its biologic and biochemical characterization. The HIV-1 IFN-alpha showed characteristics on ELISA, western blot, and biologic assays similar to two subspecies of the natural protein. The natural, recombinant, and HIV-1-induced IFN-alpha s demonstrated nearly identical antiviral activities. The HIV-1 IFN-alpha eluted from the column was not acid labile. The inability of large amounts of plasma IFN-alpha found in some patients with AIDS to affect viral burden likely reflects properties of the virus or of host factors independent of IFN-alpha.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Increased plasma human immunodeficiency virus type 1 burden following antigenic challenge with pneumococcal vaccine.

Primary factors that influence virus burden during human immunodeficiency virus type 1 (HIV-1) disease progression remain a fundamental issue in pathogenesis. Because pneumococcal vaccine is routinely given to HIV-1-infected patients and replication of HIV-1 within CD4 T cells is dependent on the activation state of the cell, it was investigated whether the T cell activation that enhances the immune response to vaccines may also enhance HIV-1 replication. Vaccination of asymptomatic HIV-1-infected patients led to rapid and significant increases in virus burden in some patients. The magnitude of these increases correlated significantly with the extent of the antibody response to the vaccination. Thus, antigenic stimulation by vaccines designed to prevent secondary infections may promote HIV-1 replication in certain patients. These findings provide a window for examining HIV-1 pathogenesis and for determining the appropriate preventive measures against other diseases in HIV-1-infected persons.

Adult↗
PubMed1996

AIDS-associated non-Hodgkin's lymphomas as primary and secondary AIDS diagnoses in hemophiliacs. Hemophilia Malignancy Study Group.

We studied the characteristics and temporal trends of AIDS- associated non-Hodgkin's lymphoma (AIDS-NHL) in individuals with hemophilia. Prospective data were collected on 33 HIV-positive hemophiliacs with AIDS-NHL enrolled in the Hemophilia Malignancy Study (HMS), of whom 21 had primary and 12 had secondary or subsequent AIDS-defining illnesses, and analyzed for frequency and temporal trends. As compared with primary AIDS- NHL, secondary AIDS-NHL occurred at an older mean age, 37 versus 29 years (p = 0.12); at a lower mean CD4 count, 46 versus 154 (p = 0.07); after a longer period of immunosuppression (CD4 < 200/microl), 41 versus 16 months (p = 0.03); and with shorter median survival, 2 versus 7 months (p = 0.09). The presence of EBV in tumor tissue was associated with shorter survival, 1 versus 7 months (p = 0.17). Between 1981 and 1988 and 1989 and 1994, the proportion of primary AIDS diagnoses that were AIDS-NHL changed minimally, 4.6 versus 6.1%, whereas there were significant decreases in Pneumocystis carinii pneumonia (PCP, p = 0.02) and wasting (p = 0.07), and an increase in Candida (p = 0.004). These findings confirm that an increasing proportion of AIDS-NHL in hemophiliacs are occurring as secondary or later AIDS diagnoses, and they are associated with prolonged duration of immunosuppression.

AIDS-Related Opportunistic Infections↗
PubMed1995

Molecular basis of cell cycle dependent HIV-1 replication. Implications for control of virus burden.

Research is beginning to yield insight into determinants which govern cell cycle dependence of provirus establishment by the onco-retroviruses. In the case of HIV-1, nucleophilic components associated with the viral preintegration complex facilitate mitosis independent nuclear localization of viral DNA and provirus establishment. Differences in the metabolic activity between G0 T cells and macrophages, the two primary targets for HIV-1 infection, lead to significantly different outcomes with regards to provirus establishment following infection of these cells. Thus, macrophages appear fully permissive to productive HIV-1 replication while non-dividing (G0 T cells) restrict virus replication at a step which proceeds nuclear import of viral DNA. The requirement for T cell activation in productive HIV-1 replication has important implications for the relationship between immune activation and virus burden. It remains to be determined whether modulating the immune activation status of the infected individual may provide an opportunity for modulating virus burden and influencing disease course.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Utility of cerebral proton magnetic resonance spectroscopy in differential diagnosis of HIV-related dementia.

Opportunistic infections often coexist with human immunodeficiency virus (HIV) infection in brain. Making the correct diagnosis is often difficult despite recent advances in neuroimaging techniques. 1H magnetic resonance spectroscopy (1H MRS) is an emerging non-invasive examination for diagnosis and monitoring of brain disorders. 1H MRS measures a variety of organic compounds using magnetism and radio waves. Biochemical aberrations in brain, not shown by conventional tests, may be demonstrated by 1H MRS testing. A patient coinfected with HIV and hepatitis B (HBV) presented with progressive dementia. Clinical, neuroradiological and cerebrospinal fluid (CSF) examinations failed to provide a diagnosis in support of either HIV-1-associated cognitive/motor complex or HBV-induced hepatic encephalopathy (HE), 1H MRS was used in an attempt to discriminate between these diagnoses. Spectroscopy demonstrated increased glutamine and normal N-acetyl aspartate (NAA) levels, metabolic changes consistent with HE. These findings were later confirmed pathologically. Proton magnetic resonance spectroscopy is a non-invasive test with utility for the differential diagnosis of HIV-associated dementia.

AIDS Dementia Complex↗
PubMed1994

Primary care physicians and the cost of drugs: a study of prescribing practices based on recognition and information sources.

Rapidly inflating health care costs limit patient care, and prescription drug costs constitute a major component of this expenditure. This study examines attitudes toward and knowledge of prescription drug costs of primary care physicians. Access to information about drug costs and implications for medical education are also explored. A questionnaire survey was sent to 137 internists, family, and general practitioners, randomly selected from a list provided by the Ohio State Medical Board. The questionnaire elicited information on demographic characteristics of respondents, influence of drug costs on prescribing habits, actual knowledge of prices of the 20 most commonly used drugs, attitudes toward generic drug use, sources of information on costs, and desire for emphasis on drug costs in medical education. Responding physicians indicated consideration of drug costs in therapeutic decisions, but lacked information and often made inaccurate assumptions about costs of drugs prescribed. Most felt they could provide better service and reduce costs if information about drug prices was readily available. Most agreed medical education should address drug costs. Drug cost estimates varied widely; correct responses ranged from 9% to 53%. No statistically significant pattern emerged regarding demographics of respondents or information sources used. Primary care physicians consider drug costs important and realize that cost-effective prescribing may lower health care costs. However, because physician knowledge of drug costs is inadequate and costs are not readily accessible, implications for better physician education and improved abscess are substantial.

Drug Costs↗
PubMed1994

Oral histoplasmosis in a patient infected with HIV. A case report.

Histoplasmosis is a frequent complication of HIV infection and is usually the result of reactivation. In the immunocompromised host, histoplasmosis may cause a chronic pulmonary infection or disseminated disease. In the setting of disseminated disease, oral lesions are present in 30% to 50% of patients and may occur in almost every part of the oral mucosa. The most common sites are the tongue, palate, and buccal mucosa. In some cases, oral lesions appear to be the primary or only manifestation of disease. We have been able to find only five case reports in the literature of histoplasmosis in HIV infection with oral lesions. In two of the cases, histoplasmosis was apparently localized to the oral cavity, whereas two cases also had evidence of disseminated disease, the fifth was undetermined. We report one such case of apparently localized oral histoplasmosis in a patient with HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1994

Prospective utility of cerebral proton magnetic resonance spectroscopy in monitoring HIV infection and its associated neurological impairment.

Neurological manifestations of HIV disease occur in most adults and children with AIDS. Many of those affected will inevitably suffer clinical neurological deficits involving mental function, movement, and sensation. Surprisingly, there are not as yet adequate monitoring systems to predict the onset and/or progression of HIV infection of the CNS. Neurological, neuropsychological, CSF, and magnetic resonance imaging (MRI) analyses cannot accurately detect mental deterioration during advancing HIV disease. Reports suggest that in vivo proton MR spectroscopy (1H MRS) of the brain could be a predictor of virus-induced neurological deterioration. H MRS can measure N-acetylaspartate (NAA), a metabolite present only in neurons. Decreased NAA reflects neuronal loss seen during HIV infection of brain. To uncover possible associations between NAA levels and HIV-induced neurological disease we performed serial 1H MRS brain tests in HIV-infected patients with or at risk for encephalopathy. Serial testing, for 1 year, of 10 patients showed that brain NAA levels decreased in all HIV-infected subjects. The most severe NAA reductions were associated with progressive neurological impairment. These findings suggest that NAA can be used as a noninvasive measure of neuronal loss in patients with HIV disease. Most important, the results suggest that 1H MRS could be used to monitor therapeutics directed against HIV infection within the CNS.

AIDS Dementia Complex↗
PubMed1994

Platelet-activating factor: a candidate human immunodeficiency virus type 1-induced neurotoxin.

The pathogenesis of central nervous system disease during human immunodeficiency virus type 1 (HIV-1) infection revolves around productive viral infection of brain macrophages and microglia. Neuronal losses in the cortex and subcortical gray matter accompany macrophage infection. The question of how viral infection of brain macrophages ultimately leads to central nervous system (CNS) pathology remains unanswered. Our previous work demonstrated high-level production of tumor necrosis factor alpha, interleukin 1 beta, arachidonic acid metabolites, and platelet-activating factor (PAF) from HIV-infected monocytes and astroglia (H. E. Gendelman, P. Genis, M. Jett, and H. S. L. M. Nottet, in E. Major, ed., Technical Advances in AIDS Research in the Nervous System, in press; P. Genis, M. Jett, E. W. Bernton, H. A. Gelbard, K. Dzenko, R. Keane, L. Resnick, D. J. Volsky, L. G. Epstein, and H. E. Gendelman, J. Exp. Med. 176:1703-1718, 1992). These factors, together, were neurotoxic. The relative role(s) of each of these candidate neurotoxins in HIV-1-related CNS dysfunction was not unraveled by these initial experiments. We now report that PAF is produced during HIV-1-infected monocyte-astroglia interactions. PAF was detected at high levels in CSF of HIV-1-infected patients with immunosuppression and signs of CNS dysfunction. The biologic significance of the results for neurological disease was determined by addition of PAF to cultures of primary human fetal cortical or rat postnatal retinal ganglion neurons. Here, PAF at concentrations of > or = 300 pg/ml produced neuronal death. The N-methyl-D-aspartate receptor antagonist MK-801 or memantine partially blocked the neurotoxic effects of PAF. The identification of PAF as an HIV-1-induced neurotoxin provides new insights into how HIV-1 causes neurological impairment and how it may ultimately be ameliorated.

AIDS Dementia Complex↗
PubMed1993

Fluconazole-resistant Candida albicans.

Mucocutaneous candidiasis caused by Candida albicans is a common complication of human immunodeficiency virus (HIV) infection. Recent reports of isolation of resistant strains of C. albicans raise the specter of more widespread resistance, but limited series are available to analyze situations in which the likelihood of resistance is greatest. We present our experience with fluconazole-resistant candidiasis in patients with HIV infection obtained from retrospective chart review and by testing strains of C. albicans isolated during relapse for susceptibility to antifungal agents. The possible reasons for failure of antifungal therapy are discussed, as well the correlation between in vivo and in vitro data. Resistant candidiasis in patients with HIV disease is an emerging problem of considerable concern that merits further study.

AIDS-Related Opportunistic Infections↗
PubMed1989

Changes in intracranial pressure during haemofiltration in oliguric patients with grade IV hepatic encephalopathy.

Seven consecutive patients with grade IV hepatic encephalopathy, due to fulminant hepatic failure complicated by oliguric renal failure were allocated at random to treatment with daily machine haemofiltration (MHF) or continuous arteriovenous haemofiltration (CAVHF). Intracranial pressure (ICP) was continuously monitored using a subdural catheter. Four patients received 17 treatments by MHF, and ICP increased from 8.4 +/- 1.5 mm Hg (mean + SEM) prior to treatment to 12.6 +/- 1.8 mm Hg on completion (p less than 0.05). Active intervention was required on twenty occasions to treat sustained increases in ICP (greater than 25 mm Hg maintained for 5 min or longer). A total of 12 haemofilters were used in the treatment of 3 patients by CAVHF. The ICP showed greater stability during CAVHF therapy, the mean pressure prior to treatment was 15.6 +/- 5.2 mm Hg and fell to 11.7 +/- 2.3 mm Hg at 4 h. Sustained increases in ICP occurred in only 1 patient as a preterminal event. These findings suggest that CAVHF is the preferred method of treatment in patients with fulminant hepatic failure complicated by oliguric renal failure who are at risk of developing cerebral oedema.

Acute Kidney Injury↗
PubMed1989

Changes in intracranial pressure during machine and continuous haemofiltration.

Nine consecutive patients with both fulminant hepatic failure and acute oliguric renal failure were treated either by daily machine haemofiltration (MHF), or by continuous arterio-venous haemofiltration (CAVHF). Six patients received a total of twenty treatments by MHF and four CAVHF, mean duration of treatment 56 hours, range 24-160. Intracranial pressure (ICP) was measured using a subdural catheter. During treatment with MHF, the mean ICP increased from 8.9 +/- 1.4 mmHg at the start of filtration to 14.8 +/- 2.1 mmHg at the end of treatment (p less than 0.05), whereas there was no corresponding increase during the same period of time with CAVHF treatment, the mean ICP fell, but not significantly from 19.4 +/- 4.8 mmHg to 11.2 +/- 2.3 mmHg. The mean ICP increased to greater than 25 mmHg on eleven occasions during treatment with MHF, requiring treatment with bolus mannitol or propofol, during the same period of treatment with CAVHF no such surges in ICP were recorded. This suggests that continuous haemofiltration is to be preferred to intermittent machine haemofiltration in the management of patients with acute hepatorenal failure.

Adult↗