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Biomedical subjects

J Dobkin

Publications and source records attributed to J Dobkin.

At least 19 recordsLinked to original sources

Validation of advanced ECG diagnostic software for the detection of prior myocardial infarction by using nuclear cardiac imaging.

The investigators report the diagnostic performance of the latest version (Version 2.5) of the recently developed Cardiovise algorithm for detecting prior myocardial infarction (MI). The Cardiovise 2.5 prior MI algorithm, a component of Cardiovise Cardiac Diagnostic System (Inovise Medical, Inc, Newberg, OR), uses scalar QRS, scalar T wave, and vectorcardiographic QRS criteria for detecting, sizing, and localizing prior MI. In this study only the detection part of the algorithm's performance was evaluated, using 105 patients with and 98 patients without prior MI as indicated by the results of cardiac imaging with Sestamibi. The specificity, and sensitivity of Cardiovise 2.5 for detecting prior MI in this population of patients are 97% and 79%, respectively. The sensitivity and overall diagnostic performance of Cardiovise 2.5 was significantly better than those of a total of 6 human readers (3 cardiologists and 3 primary care physicians) and to 2 commercially available ECG diagnostic algorithms.

Algorithms↗

Modulation of the multidrug resistance P-glycoprotein: detection with technetium-99m-sestamibi in vivo.

UNLABELLED: Overexpression of the multidrug resistance (MDR1) P-glycoprotein (Pgp) has been documented in nearly all forms of human cancers and increased levels of Pgp in some tumors correlate with poor response to treatment. Technetium-99m-sestamibi has recently been validated as a Pgp transport substrate. Pgp is also normally expressed along the biliary canalicular surface of hepatocytes and the luminal side of proximal tubule cells in the kidney, while not expressed in heart. METHODS: Focused on these organs with known Pgp status, we present the findings on 99mTc-sestamibi scintigraphy of three patients with refractory cancer who were imaged before and after administration of SDZ PSC 833, a second-generation, high-potency modulator of Pgp. RESULTS: Before treatment with SDZ PSC 833, scintigraphy using 99mTc-sestamibi showed normal, prompt clearance of the radiotracer from the liver and kidneys relative to the heart. After administration of the Pgp modulator, 99mTc-sestamibi was selectively retained in the liver and kidneys. CONCLUSION: Hepatobiliary and renal clearance of 99mTc-sestamibi are Pgp-mediated, and inhibition of Pgp transport in these organs can be successfully imaged using 99mTc-sestamibi in patients. Similar results might be expected with this and related radiopharmaceuticals for functional imaging of Pgp transport and modulation in tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Independent origin of mono-rifampin-resistant Mycobacterium tuberculosis in patients with AIDS.

Historically, infections caused by Mycobacterium tuberculosis have been treated simultaneously with isoniazid and rifampin. As a consequence of this combined therapy, strains resistant only to rifampin were rarely recovered. However, recently there has been an increasing number of reports describing HIV-positive patients infected with mono-rifampin-resistant M. tuberculosis strains. Organisms cultured from seven patients (including six with AIDS) with infections caused by mono-rifampin-resistant M. tuberculosis, and seen at one New York City hospital, were analyzed by molecular techniques to test the hypothesis that dissemination of a single clone had occurred. IS6110 DNA fingerprinting and automated DNA sequencing of a region of the RNA polymerase beta subunit structural gene (rpoB) containing mutations that confer rifampin resistance showed that all organisms independently acquired the mono-rifampin-resistant phenotype. Molecular analysis of mono-rifampin-resistant organisms cultured from 13 additional patients in New York City confirmed independent strain origin. The data rule out the possibility of person-to-person strain transmission among these patients, and they suggest that host factors such as poor compliance with antituberculosis medications or decreased absorption of rifampin have been a driving force in the origin of these strains.

AIDS-Related Opportunistic Infections↗

Peptide T in the treatment of painful distal neuropathy associated with AIDS: results of a placebo-controlled trial. The Peptide T Neuropathy Study Group.

OBJECTIVE: To assess the safety and efficacy of Peptide T in the treatment of painful distal symmetrical polyneuropathy (DSP) associated with human immunodeficiency virus (HIV) infection. BACKGROUND: Painful DSP is a frequent complication of HIV infection, although its etiology and optimal treatment are unknown. Peptide T (D-(alpha 1)-Peptide T-amide) has been found in phase I trials and anecdotal reports to relieve neuropathic pain in AIDS patients. DESIGN/METHODS: In this multicentered, double-blind, randomized study, subjects received intranasal Peptide T 6 mg/day or placebo for 12 weeks. The primary outcome measure was change in the modified Gracely pain score. Secondary efficacy variables were results of neurologic examination, neuropsychological and electrophysiologic studies, global evaluation, and CD4 lymphocyte counts. RESULTS: Of 81 evaluable subjects, 40 received Peptide T and 41 received placebo. The change in pain scores was not significantly different (p = 0.32) in the Peptide T group (-0.24) as compared to placebo (-0.39). Group comparisons were not significantly different for change in any clinical examination or neuropsychologic measure, sural nerve amplitude or conduction velocity, or CD4 lymphocyte count. No significant drug-related adverse effects occurred in either group. CONCLUSION: Intranasal Peptide T is safe but ineffective in the treatment of painful DSP associated with AIDS.

Acquired Immunodeficiency Syndrome↗

TAT-mediated transcellular activation of HIV-1 long terminal repeat directed gene expression by HIV-1-infected peripheral blood mononuclear cells.

We have previously shown evidence of Tat-mediated transcellular activation of the HIV-1 long terminal repeat (LTR) in vitro by using a laboratory-adapted strain of HIV-1. To examine the biologic significance of this observation, we asked whether primary PBMCs from HIV-1-infected individuals will transactivate the HIV-1 LTR transcellularly in suitable indicator cells. In cultures of PBMCs isolated from HIV-1-infected patients at various clinical stages, with either HIV-1 LTR-transfected Jurkat T cells or nonfusigenic HIV-1 LTR-transfected murine fibroblasts, transcellular activation was readily detected. Transactivation of the LTR in cocultured cells with HIV-1-infected PBMCs is detectable 1 to 2 wk before the onset of significant virus production and at ratios as low as 1 infected cell to 10(6) surrounding cells. Addition of the Tat inhibitor RO5-3335 substantially decreases transcellular activation, even at low concentrations (0.01 microM) that do not affect virus levels. In contrast, addition of the antiretroviral agent zidovudine has no effect on transcellular activation. These data suggest that Tat-mediated transcellular activation of the HIV-1 LTR occurs independently of cellular infection, and provides a mechanism that can promote the spread of HIV-1 in susceptible cell populations.

Cells, Cultured↗

HIV-1 seroprevalence and risk behaviors in an urban African-American community cohort.

OBJECTIVES: Previous attempts at obtaining population estimates of human immunodeficiency virus type 1 (HIV-1) seroprevalence have been beset by problems of cooperation bias. As part of the fourth round of study with an urban African-American community cohort, the following investigation was aimed at assessing HIV-1 prevalence and the relative importance of sex and drug injection as risk factors in infection. METHODS: Personal interviews were conducted in the home with 364 respondents, followed by voluntary blood sample collection from 287 of these individuals. RESULTS: Blood assays showed a point prevalence of 8.4% HIV-1 seropositivity in this community cross section, with a higher female-to-male ratio than appears among acquired immunodeficiency syndrome (AIDS) case reports. Most infected persons were unaware and unsuspecting of their infection. CONCLUSIONS: First, findings underscore the need to focus on risk behaviors rather than on risk groups. Second, the smaller than 2:1 ratio of infected men to women suggests that current AIDS case reports seriously underestimate HIV-1 infection among certain cohorts of African-American women. Finally, widespread ignorance of own infected status and inaccurate risk assessment signal the substantial task for community health educators in reaching inner-city African-American men and women at risk.

Adult↗

Miliary tuberculosis in pregnancy.

Although miliary tuberculosis is uncommon in pregnancy, it is difficult to diagnose when present and is often associated with a maternal history of intravenous drug abuse, malignancy, alcoholism, or human immunodeficiency virus infection. This article reports two antepartum cases of miliary tuberculosis without any of these risk factors. Bronchial washings for Pneumocystis carinii and HIV screening were negative for both patients. Acid-fast bacilli stains of the bronchial washing and ascitic fluid were also negative. Several weeks were required for ascitic fluid and bronchial biopsy Mycobacterium cultures to be positive. In contrast, acid-fast bacilli were seen within 24 hours in multiple sections of the delivered placentas. Confirming the diagnosis of miliary tuberculosis is an arduous process requiring a high index of suspicion. During pregnancy, pathologic examination of tissue obtained by placental biopsy may facilitate making an early diagnosis of extrapulmonary tuberculosis.

Adult↗

Detection of complications after liver transplantation by technetium-99m mebrofenin hepatobiliary scintigraphy.

Fifty-five hepatobiliary scintigraphic studies using 99mTc-Mebrofenin were performed in 52 orthotopic liver transplant patients to evaluate suspected biliary complications, namely biliary extravasation and extrahepatic obstruction. Final diagnosis was made by analysis of the clinical course and other procedures. Three out of three studies of biliary leak and four out of five studies of biliary obstruction were detected. There were no false positives in either complication. The sensitivity, specificity and accuracy were 100, 100, 100% for ectravasation and 80, 100, 98% for obstruction, respectively. Hepatobiliary scintigraphy appears to be an accurate means of detecting biliary leak and obstruction associated with the transplanted liver.

Adolescent↗

Resurgent tuberculosis in New York City. Human immunodeficiency virus, homelessness, and the decline of tuberculosis control programs.

The resurgence of tuberculosis in New York City has been largely attributed to the acquired immune deficiency syndrome (AIDS) epidemic. However, historical events predating the advent of AIDS and worsening economic and social conditions, including a rise in homelessness, have contributed significantly to the increase. We prospectively studied 224 consecutive patients with tuberculosis admitted to a large public hospital in New York over the first 9 months of 1988. Initial assessment included medical status, human immunodeficiency virus (HIV) risk factors, and detailed social information, including substance abuse history and housing status. All patients were tracked after discharge to determine compliance and cure rates. Tuberculosis patients were predominantly male (79%), with high rates of alcohol use (53%), intravenous drug and/or "crack" cocaine use (64%), and homelessness or unstable housing (68%). Half the patients had AIDS or AIDS-related complex (ARC) or were HIV antibody positive. A total of 178 patients were discharged on tuberculosis treatment, but 89% of these were lost to follow-up and failed to complete therapy. Of the 178 discharged patients, 48(27%) were readmitted within 12 months with confirmed active tuberculosis. Of these patients, 40 were discharged on treatment and at least 35 were again lost to follow-up. In a multivariate regression model noncompliance was significantly associated with the absence of AIDS or ARC (p less than 0.001), homelessness (p less than 0.005), and alcoholism (p less than 0.05). Because HIV infection and tuberculosis converge in a subpopulation with high rates of substance abuse and homelessness, the problem of ensuring treatment compliance may grow considerably in the future.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗

A tale of two cities: tuberculosis control in Nicaragua and New York City.

The tuberculosis (TB) control programs in Managua, Nicaragua, and New York City are compared, including their methods of case finding, treatment, follow-up, data collection, and cure rate. In all areas, Managua's program has proven more successful than New York City's, despite the enormously greater resources available in the latter. Nicaragua's TB program concentrated on active cases, had immediately available diagnosis with a microscope in each clinic, had nearly 100% directly observed therapy during at least the first 2 months, and sent its workers into the field immediately after a patient broke an appointment. New York City's program has fewer than 2% of its patients under directly observed therapy, operates a laboratory and clinic system in which obtaining sputum smear results requires 10 to 20 days, and has delays of weeks to months in returning patients to supervision after a broken appointment. The numbers speak for themselves: the Nicaraguan TB program cured nearly 80% of the patients enrolled in the mid-to late 1980s, whereas New York City's program rarely cured 50% and in some areas cured less than 15%.

Adult↗

Neurologic disease in human immunodeficiency virus-infected drug abusers.

Previous studies of human immuno-deficiency virus-related neurologic disease have been either retrospective or have included mostly homosexual patients. We sought to determine (1) the true prevalence of neurologic abnormalities in patients with acquired immunodeficiency syndrome or lymphadenopathy acquired immunodeficiency-related complex, and (2) whether differences in prevalence or type of neurological abnormality exist between parenteral drug abusers and non-parenteral drug abusers. We prospectively evaluated 190 adult inpatients with either acquired immunodeficiency syndrome (129) or lymphadenopathy acquired immunodeficiency-related complex (61); 151 (80%) were parenteral drug abusers, and 172 patients (91%) had neurologic symptoms or signs. There was no significant difference in prevalence of neurologic disease between parenteral drug abusers and non-parenteral drug abusers, or between patients with acquired immunodeficiency syndrome and those with lymphadenopathy acquired immunodeficiency-related complex. The prevalence of neurologic symptoms in these patients with lymphadenopathy acquired immunodeficiency-related complex and acquired immunodeficiency syndrome is the highest reported to date and appears to reflect the prospective nature of the study.

AIDS-Related Complex↗

Occult polymicrobial endocarditis with Haemophilus parainfluenzae in intravenous drug abusers.

PURPOSE AND PATIENTS AND METHODS: Fewer than 8 percent of intravenous drug abusers are found to have polymicrobial endocarditis. We report on cases of occult polymicrobial infective endocarditis with Haemophilus parainfluenzae in 10 intravenous drug abusers. Clinical and laboratory data on all 10 patients were obtained from hospital charts, and information on illicit drug use methods was given by five patients. Blood cultures were performed, as well as susceptibility testing to antibiotics. Subsequent molecular epidemiologic studies were performed on selected Staphylococcus aureus and H. parainfluenzae strains. Phage typing of S. aureus and biotyping of H. parainfluenzae strains were also done. RESULTS: Results of the initial blood cultures were positive on the second to fifth days (mean, 2.6 days), demonstrating a gram-positive pathogen in nine patients and Bacteroides asaccharolyticus in one. Significantly, in each case, H. parainfluenzae alone was subsequently identified from additional blood cultures, with a mean delay of 20.4 days (range, five to 57 days) to the isolation of this organism. Epidemiologic data indicated that our cases did not represent a point-source outbreak. Antibiotic therapy uniformly failed until an agent active against H. parainfluenzae was added. The constellation of clinical, microbiologic, and epidemiologic findings was similar, and permitted prospective diagnosis and therapy in three patients. Despite the absence of S. aureus bacteremia in four, all 10 patients had right-sided endocarditis with septic pulmonary emboli. Five patients had initial blood cultures that were positive for two facultative gram-positive cocci (S. aureus and commensal oral streptococcal species). CONCLUSION: Our findings suggest that polymicrobial endocarditis with H. parainfluenzae in intravenous drug abusers is a distinct clinical syndrome, and should be considered in all patients if the response to appropriate antibiotics is atypical or if pulmonary emboli continue with therapy.

Adult↗

Pulmonary embolism: diagnosis and treatment.

Pulmonary embolism is a condition with a potentially high mortality that often goes unrecognized. Prompt diagnosis and treatment effectively reduce the mortality rate. Clinical judgment alone is insufficient for diagnosis; objective testing is needed. Once the diagnosis is made, effective treatment should be instituted. Treatments differ, based on several factors including disease severity, contraindications to treatment and pre-existing diseases. The major thrust of training should be to teach medical care workers how to prevent deep vein thrombosis and its most serious complication, pulmonary embolism.

Anticoagulants↗