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Biomedical subjects

E Goldstein

Publications and source records attributed to E Goldstein.

At least 37 records · Page 2Linked to original sources

Reactivities of human sera with human herpesvirus-8-infected BCBL-1 cells and identification of HHV-8-specific proteins and glycoproteins and the encoding cDNAs.

The reactivates of human sera with uninduced and phorbol ester (TPA)-induced human herpesvirus-8 (HHV-8)-infected BCBL-1 cells were examined by immunofluorescence assay (IFA) and by radioimmunoprecipitation reactions (RIP). The seroprevalence of HHV-8 infections is low in the United States general population and only low levels of HHV-8 antibodies were detected in the seropositive sera. In contrast, high levels of antibodies against HHV-8 lytic and latent antigens were detected by IFA in the sera from HIV+ Kaposi's sarcoma (KS)-positive individuals. These sera recognized several proteins and glycoproteins from BCBL-1 cells in RIP reactions. Two types of antibody responses were detected in the sera from HIV+ KS- homosexual men. In majority of the sera with and without detectable HHV-8 DNA in the peripheral blood mononuclear cells (PBMC), significantly low levels of HHV-8 antibodies were detected by IFA. These sera recognized only a subset of HHV-8 proteins and glycoproteins in RIP reactions. In contrast, in a subgroup of sera from HIV+ KS- homosexual men, higher levels of IFA antibodies against HHV-8 lytic and latent antigens were detected. These sera also recognized several viral proteins and glycoproteins in RIP reactions. These results suggest that antibody response profiles to HHV-8 infection vary significantly and serologic assays to detect antibody responses to a panel of both lytic and latent antibodies may be required for maximum sensitivity. Screening of a cDNA library from TPA-induced BCBL-1 cells with an HIV+ KS+ serum identified cDNAs encoding 12 HHV-8 proteins. Further characterization of these HHV-8 proteins would define the HHV-8 antigens useful for seroepidemiological studies and in discriminating lytic, latent, past, and/or reactivation infections.

Acquired Immunodeficiency Syndrome↗

Use of retinal biopsy to diagnose Bartonella (formerly Rochalimaea) henselae retinitis in an HIV-infected patient.

A patient with the acquired immunodeficiency syndrome developed bilateral retinitis due to a Bartonella (formerly Rochalimaea) henselae infection. A retinal biopsy was performed when severe and progressive retinal infection failed to respond to empirical treatment for cytomegalovirus and Toxoplasma gondii. The biopsy specimen was stained with routine histopathological stains and the Steiner silver stain. Ribosomal DNA was extracted from formalinfixed, paraffin-embedded retinal tissue and amplified with the polymerase chain reaction assay, using Bartonella-specific primers. The amplified DNA fragment was cloned and sequenced. Staining with hematoxylin-eosin revealed tufts of proliferating vascular endothelium with numerous fusiformappearing cells, consistent with a diagnosis of bacillary angiomatosis. A Steiner silver stain revealed numerous small bacilli in the biopsy specimen. Amplification of DNA extracted from the tissue produced a fragment of 16S ribosomal DNA of the expected size; sequencing of the DNA fragment revealed that the infection was caused by B henselae. The retinal infection was treated with minocycline, doxycycline, and ciprofloxacin with improvement in visual acuity in the ensuing 12 weeks. To our knowledge, this is the first human immunodeficiency virus-infected patient with retinitis due to B henselae who was diagnosed by the identification of silver-staining bacilli and amplification and sequencing of B henselae with a polymerase chain reaction assay using a biopsy specimen of retinal tissue. Retinal biopsy is indicated, despite its potential for serious complications, in patients with acquired immunodeficiency syndrome who have a progressive, sight-threatening retinitis that is undiagnosed and unresponsive to therapy.

AIDS-Related Opportunistic Infections↗

Sources of information for HIV prevention program managers: a national survey.

This study's objective was to find out if HIV prevention program planners seek out science in designing interventions, and if not, where they turn for prevention information. Researchers conducted a survey of 284 program managers of AIDS prevention programs across the United States. Respondents' three most important sources of information were peers and colleagues, departments of public health (DPH) and the centers for Disease Control (CDC). The four least important sources included scientific publications and government reports. We find that most program managers do not turn to research, nor do they perceive it as an important source of information. They turn to each other, their DPH, and the CDC. The authors have made suggestions for researchers, community-based organizations, state DPHs, and the CDC to close the gap between HIV prevention science and prevention practice. We must ensure that our efforts will not be wasted, and we can make a difference in the fight against HIV.

Community Health Services↗

Detection of human herpesvirus 8 DNA in Kaposi's sarcoma lesions and peripheral blood of human immunodeficiency virus-positive patients and correlation with serologic measurements.

Polymerase chain reaction (PCR) was used to examine human herpesvirus 8 (HHV-8) DNA from Kaposi's sarcoma (KS) lesions, normal skin, and peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients who did or did not have KS. Of 9 KS biopsies, 8 were positive for five HHV-8 open-reading frames and ranged from 1 viral genome per 2.5-12.7 cells. Two putative replicative gene RNAs were detected by reverse transcription-PCR at low levels in 1 KS lesion. HHV-8 DNA was detected in 4 of 8 PBMC samples from patients with KS and in 2 of 18 PBMC samples from patients without KS. Sera were tested for reactivity with BCBL-1 cells (HHV-8 positive): High immunofluorescence antibody titers against HHV-8 lytic and latent antigens were detected in samples from KS-positive patients, and >20 polypeptides from induced BCBL-1 cells were recognized. Sera from 6 of 18 patients without KS showed low levels of antibodies against HHV-8 lytic and latent antigens.

Adolescent↗

Health status during the transition in Central and Eastern Europe: development in reverse?

This paper reports on a study of the cross-national trends in health status during the economic transition and associated health sector reforms in Central and Eastern Europe (CEE). The central premise is that before long-run gains in health status are realized, the transition towards a market economy and adoption of democratic forms of government should lead to short-run deterioration as a result of: (i) reduction in real income and widening income disparities; (ii) stress and stress-related behaviour; (iii) lax regulation of environmental and occupational risks; and (iv) breakdown in basic health services. Analysis focused on three broad indicators of health status: life expectancy at birth, infant mortality rate and the probability of dying between the ages of 15 and 65 years, shown by the notation '50q15'. The study revealed significant new information about health status and the health sector which could not have been obtained without a proper cross-national study. Infant mortality rates in former socialist economies (FSE) follow the global trend, declining as per capita income rises. However, rates are lower than would be predicted given their income levels. Despite declining infant mortality, life expectancy at birth in the former socialist economies decreases as per capita income rises, in marked contrast to global trends. This is because rising income level is associated with greater probability of death between the ages of 15 and 65: the wealthier the society, the less healthy is its population, particularly for its males. Causes of death in the FSE follow global trends: higher death rates due to infectious and parasitic diseases in poorer countries, and higher death rates due to chronic diseases in wealthier countries. However, age-standardized death rates for chronic diseases generally associated with unhealthy lifestyles and environmental risk factors are very high when compared with wealthier established market economies (EME). Policies and procedures which alter the effectiveness of health services have had a demonstrable but mixed impact on health status during the early phase of transition. Effective preventive health strategies must be formulated and implemented to reverse the adverse trends observed in Central and Eastern Europe.

Adolescent↗

Frequency and effect of negative comments ("badmouthing") on medical students' career choices.

BACKGROUND: Some call it "medical bigotry," and others describe it as the "hidden curriculum," but, by any name, the superficial and demeaning comments that students hear about particular career choices are thought to play a major role in discouraging the selection of primary care careers. This paper explores the frequency and effect of "badmouthing" on career choice with the hypothesis that it is more frequently heard about primary care disciplines but has relatively little influence on actual career choice. METHOD: In 1993, 129 (79%) of the 163 University of Washington School of Medicine graduates responded to a two-page questionnaire about badmouthing. This information was used to refine the questionnaire. In 1994, 1,447 graduating students from nine medical schools were surveyed with the revised questionnaire. The schools were chosen to represent schools that had high, medium, and low proportions of students going into primary care careers. RESULTS: A total of 1,114 questionnaires were returned, for a response rate of 77%. Badmouthing was heard frequently (76% of the responding students) and often occurred as early as the first and second years of medical school. The students heard badmouthing about their career choices most frequently when they selected surgery (91%) and family medicine (87%) and least frequently when they chose pediatrics (57%), p < .001. The students reported that the influence on career choice was low in general, but 186 students (17% of all respondents) did report altering their choices based on badmouthing. CONCLUSION: Primary care fields and non-primary care fields were equally affected by career changes due to badmouthing. This study indicates that badmouthing, while pervasive across all disciplines and an unattractive aspect of the educational experience, cannot alone account for the low proportion of graduates choosing primary care careers.

Attitude↗

Evaluation of cerebrospinal fluid in Southeast Asian refugees with reactive serologic tests for syphilis.

To determine the prevalence of cerebrospinal fluid abnormalities in Southeast Asian refugees with reactive serologic tests for syphilis, we evaluated 65 patients, 36 prospectively and 29 retrospectively, in a primary care clinic. Information was collected on history of treponemal infections, neurologic symptoms and signs, and total protein concentration, leukocyte count, and the VDRL test in the cerebrospinal fluid. Neurologic symptoms were reported by all patients for whom data were available. Abnormal neurologic signs were found or noted in medical records in 15 (42%) prospectively evaluated patients and 9 (64%) of 14 retrospectively evaluated patients for whom data were available. No patient had evidence of congenital or non-neurologic sequelae such as cutaneous or cardiovascular manifestations of syphilis. No patient had a positive cerebrospinal fluid VDRL test, 1 had more than 5 x 10(6) leukocytes per liter (5 leukocytes per mm3), and 6 (9%) had elevated total protein levels in the cerebrospinal fluid. Previous therapy for syphilis was not associated with lower serum VDRL reactions, neurologic symptoms and signs, or cerebrospinal fluid findings. In the absence of other indications, routine examination of the cerebrospinal fluid in seropositive Southeast Asian refugees who have nonspecific neurologic symptoms has a low yield, perhaps because of the high prevalence of yaws in this population, and may not be warranted.

Adolescent↗

"Strong medicine": Cambodian views of medicine and medical compliance.

OBJECTIVE: To identify important determinants of noncompliance among Cambodian refugees. DESIGN: Open-ended interviews. SETTING: University-affiliated ambulatory care clinic in an inner-city hospital. PARTICIPANTS: Thirty adult Cambodian refugees (15 men and 15 women) who were regular utilizers of a refugee clinic. MEASUREMENTS AND MAIN RESULTS: Sixty-seven percent of the participants described being noncompliant with at least one of their medications. Four common causes of noncompliance were identified: 1) misunderstanding the intent of the medication; 2) side effects; 3) concern about the effect of medication on "internal strength"; and 4) Cambodian ideas about pharmacokinetics. CONCLUSIONS: Noncompliance was commonly reported by the Cambodian respondents. Noncompliance was both intentional and unintentional; the unintended noncompliance derived from patients' attempting to comply with therapy according to Cambodian ideas about the body and Western medication. This article suggests clinical approaches to enhance compliance with prescribed regimens among recent Cambodian immigrants and refugees.

Adult↗

Are serum levels of vancomycin useful in the first week of therapy?

Controversy exists regarding the need to monitor serum concentrations of vancomycin with some investigators recommending measurement of peak and trough concentrations in the first week of therapy and regularly thereafter, whereas others contend that empiric dosing produces safe and effective drug concentrations so that testing is unnecessary. Since vancomycin concentrations are measured, routinely in our hospital in the first week of therapy, we conducted a 12 month study to assess their clinical value in patients who were treated when gram positive cocci were detected in blood culture smears. One-hundred-five patients had gram positive cocci on blood culture smears. These bacteria were pathogens in 15 patients with Staphylococcus aureus and in 18 with coagulase negative staphylococci based on microbiologic criteria and a chart review confirming their clinical significance. Ten patients with S. aureus and 8 patients with coagulase negative staphylococci that were pathogens and 10 patients with coagulase negative staphylococci that were contaminants were treated with vancomycin. Serum peak and trough concentrations of vancomycin obtained within the first 5 days of therapy in these 28 patients were 14 to 40 micrograms/ml and 4.8 to 20 micrograms/ml. These concentrations were much above the MIC's of the microorganisms (< 4 micrograms/ml). Five patients had increases of serum creatinine of more than 0.6 mg% and in each patient the increases were attributable to other causes-shock, heart failure, and preexisting renal failure. Fifty five peak and trough concentrations 19 of which were drawn in patients with contaminated cultures were measured at a cost of $2,475.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteremia↗

Anandamide (arachidonylethanolamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acrosome reaction.

Anandamide (arachidonylethanolamide) is an endogenous cannabinoid receptor agonist in mammalian brain. Sea urchin sperm contain a high-affinity cannabinoid receptor similar to the cannabinoid receptor in mammalian brain. (-)-delta 9-Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in marihuana, reduces the fertilizing capacity of sea urchin sperm by blocking the acrosome reaction that normally is stimulated by a specific ligand in the egg's jelly coat. We now report that anandamide produces effects similar to those previously obtained with THC in Strongylocentrotus purpuratus in reducing sperm fertilizing capacity and inhibiting the egg jelly-stimulated acrosome reaction. Arachidonic acid does not inhibit the acrosome reaction under similar conditions. The adverse effects of anandamide on sperm fertilizing capacity and the acrosome reaction are reversible. The receptivity of unfertilized eggs to sperm and sperm motility are not impaired by anandamide. Under conditions where anandamide completely blocks the egg jelly-stimulated acrosome reaction, it does not inhibit the acrosome reaction artificially initiated by ionomycin, which promotes Ca2+ influx, and nigericin, which activates K+ channels in sperm. These findings provide additional evidence that the cannabinoid receptor in sperm plays a role in blocking the acrosome reaction, indicate that anandamide or a related molecule may be the natural ligand for the cannabinoid receptor in sea urchin sperm, and suggest that binding of anandamide to the cannabinoid receptor modulates stimulus-secretion-coupling in sperm by affecting an event prior to ion channel opening.

Acrosome↗

Effect of newer quinolones on the extra- and intra-cellular chemiluminescence response of human polymorphonuclear leucocytes.

The direct effect of four quinolones on the intracellular production and extracellular release of reactive oxygen species was investigated in vitro using a chemiluminescence (CL) assay. Polymorphonuclear leucocytes (PMNs) were obtained from healthy volunteers and exposed for 10 min at 37 degrees C to 1.6, 6.25 and 25 mg/L ofloxacin, ciprofloxacin, sparfloxacin and temafloxacin. The luminol-dependent CL response of the PMNs was then measured for 30 min following stimulation with nonopsonized zymosan or phorbol myristate acetate (PMA). The intracellular CL response was also measured for 30 min during phagocytosis of lumispheres. The integrated CL was calculated and compared for cells which were incubated with the antibiotic and unincubated controls. Preincubation with ofloxacin resulted in increased zymosan and PMA-induced, luminol-dependent CL. Similar increases were observed for ciprofloxacin except that 25 mg/L decreased the PMA-induced, luminol dependent CL. Preexposure to ofloxacin and ciprofloxacin did not affect lumisphere-induced CL significantly, although there was a tendency for this to decrease after exposure to ciprofloxacin. In contrast sparfloxacin and temafloxacin caused progressive decreases in zymosan and PMA-induced, luminol-dependent PMN CL which reached statistical significance at the higher concentrations. The same pattern was observed in the experiments using lumispheres. These findings indicate that these quinolones modulate the oxygen metabolism of PMNs and that this effect varies with the individual drug.

Anti-Infective Agents↗

Comparative study of the effects of cefodizime and HBW 538 in potentiating the production of reactive oxygen species by human polymorphonuclear leukocytes.

The immunomodulatory activity of cefodizime (CDZM), an aminothiazolylcephalosporin, was compared to that of HBW 538, a derivative of the CDZM side chain at position 3 (the mercaptothiazolyl group) in respect to the production of reactive oxygen species (ROS) by human whole blood and polymorphonuclear leukocytes (PMN) in vitro. Ten-fold diluted whole blood and PMN from healthy individuals were incubated with CDZM or HBW 538 alone at the concentrations of 1, 10, or 100 micrograms/ml, or CDZM or HBW 538 at 100 micrograms/ml in combination with tumor necrosis factor-alpha (TNF-alpha) at 100 U/ml or lipopolysaccharide (LPS) at 1 microgram/ml. The production of ROS was measured by a chemiluminescence (CL) assay in which luminol was added to a mixture and after which the PMN or whole blood were stimulated with nonopsonized zymosan or phorbol myristate acetate. The following results were obtained: (1) The CL responses of whole blood and PMN were slightly but not significantly enhanced by CDZM at 100 micrograms/ml, whereas both CL responses were significantly enhanced by exposure to HBW 538 at 10 and 100 micrograms/ml. (2) The enhanced PMN CL response which followed priming with TNF-alpha or LPS was not augmented by CDZM but was significantly augmented by HBW 538. These results indicate that the ability of the HBW 538 molecule to enhance the production of ROS by stimulated PMN and to act agonistically with TNF-alpha or LPS is abrogated when HBW 538 is part of the CDZM molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefotaxime↗

Antidepressant-associated mania: a controlled comparison with spontaneous mania.

OBJECTIVE: Antidepressants have been associated with the induction of mania and rapid cycling. This study examined whether antidepressant-associated manic states differ in any way from spontaneous mania. METHOD: Forty-nine consecutive inpatients with antidepressant-associated manic states were compared with 49 matched inpatients with spontaneous mania in a blind, retrospective chart review. RESULTS: Across virtually every clinical measure examined, the patients with antidepressant-associated manic states experienced milder and more time-limited manic episodes than the patients with spontaneous mania. The patients with antidepressant-associated manic states were subject to frequent checking by nurses and hall restriction for a significantly shorter period of time than the patients with spontaneous mania. The patients with antidepressant-associated manic states also had significantly less severe levels of delusions, hallucinations, psychomotor agitation, and bizarre behavior, according to a standard rating instrument, than the patients with spontaneous mania. For further study the patients with antidepressant-associated mania were divided into subgroups taking four individual classes of antidepressant drugs: tricyclics (N = 19), fluoxetine (N = 13), monoamine oxidase inhibitors (MAOIs) (N = 8), and bupropion (N = 6); three patients taking combinations of drugs were not included in these analyses. The patients with MAOI- and bupropion-associated mania had a slightly lower overall rating of severity of psychopathology at admission than the subgroups with fluoxetine- and tricyclic-associated mania. CONCLUSIONS: Antidepressant-associated mania appears to be a milder and more time-limited syndrome than spontaneous mania and may represent a distinct clinical entity. MAOIs and bupropion may be associated with milder manic states than either tricyclic drugs or fluoxetine.

Adult↗