Biomedical subjects
Publications and source records attributed to D Kaufman.
Three patients with intracranial Ewing's sarcoma had neuro-ophthalmologic manifestations. In one patient, the primary tumor was in the skull and in two, it involved the long bones. Two patients complained of intermittent headache associated with bilateral, transient visual symptoms suggestive of migraine, which prompted imaging that showed occipital metastases. The third patient had an orbital syndrome.
Opioidergic neurotransmission and, specifically, the mu opioid receptor have been implicated in the reinforcing effects of a variety of drugs of abuse. Consequently, the present study examined the association of a polymorphic (CA)n repeat at the OPRM1 locus (the gene coding for the mu opioid receptor) to alcohol or drug dependence in 320 Caucasian and 108 African-American substance-dependent or control subjects. Among Caucasians, suggestion of a modest association, which could be interpreted as statistically significant (p = 0.03), was observed between OPRM1 alleles and substance (alcohol, cocaine, or opioid) dependence. Analysis by specific substance showed only a trend level association to alcohol dependence. Comparisons among African Americans yielded no evidence for association. Further studies of the association between alleles of the OPRM1 gene and substance dependence appear warranted, particularly if they use a family-based approach to control for population stratification. Phenotypes other than a broad diagnostic categorization, such as opioid antagonist effects on drinking behavior in alcoholics, may provide more consistent evidence of a role for OPRM1 in behavioral variability.
Pyrogenic reactions are potentially life-threatening complications caused by bacterial endotoxin. After two cardiac catheterization patients developed rigors the same day, the procedures were halted and a case control study was conducted. To identify case patients (persons with rigors < or = 3 hr after catheterization during September 25-November 9, 1995), we reviewed medical records of all cardiac catheterization patients who had a blood culture or received intravenous meperidine. Twelve case patients and 40 randomly selected control patients were identified. No specific catheter was associated with case patients, but exposure to intracoronary-nitroglycerin (NTG) was (odds ratio = 12.0; 95% confidence interval 2.2, 75.6). NTG or indocyanine green dye was poured into glass medicine cups previously washed in an enzyme cleaner and then sterilized. The cleaner, used for an entire day, had elevated levels of gram-negative bacteria (> 10(4) colony forming units/mL) and endotoxin (434 endotoxin units [EU]/mL]); the reprocessed cups had no live bacteria but had elevated endotoxin levels (median 2,250 EU). Exposure to contaminated glass medicine cups probably resulted in pyrogenic reactions and contributed to death in two critically ill patients.
Aplastic anemia is more common in the Orient than in western countries, with an incidence in Thailand that is 2- to 3-fold higher than in Europe. Aplastic anemia after hepatitis is a well characterized clinical entity, and clinical hepatitis is also prevalent in the Far East. We performed a prospective case-control study to determine risk factors for aplastic anemia in Bangkok and two rural regions during 1989 to 1994. A total of 375 cases were identified, along with 1,174 hospital controls matched for age and sex. Historical data were collected by trained interviewers. Sera from a subset of cases (N = 177) and controls (N = 183) were tested for antibodies to hepatitis viruses A, B, and C and hepatitis B surface antigen. There was no evidence of association of aplastic anemia with hepatitis B or hepatitis C. Previous exposure to hepatitis A, as determined by immunoglobulin G (IgG) seropositivity, was significantly associated with aplastic anemia: the relative risk adjusted for confounding was 2.9 (95% confidence interval 1.2-6.7). The same association also existed for persons under age 25 years, in whom the prevalence of hepatitis A IgG was lower than in the total population. However, no patients showed evidence of recent infection with hepatitis A (immunoglobulin M [IgM] seropositivity). These results indicate that exposure to a hepatitis virus is a risk indicator for aplastic anemia in Thailand, and while itself unlikely to be etiologic, hepatitis A may be a surrogate marker for another enteric microbial agent.
OBJECTIVES: Androgen ablation with luteinizing hormone-releasing hormone (LHRH) agonists, orchiectomy, or oral estrogens has significant untoward sexual side effects. We evaluated a combination of finasteride and flutamide as potency-sparing androgen ablative therapy (AAT) for advanced adenocarcinoma of the prostate. In addition, we evaluated whether finasteride provided additional intraprostatic androgen blockade to flutamide. METHODS: Twenty men with advanced prostate cancer were given flutamide, 250 mg orally three times daily. Serum prostate-specific antigen (PSA) values were measured weekly. At a nadir PSA value, finasteride, 5 mg orally every day, was added. PSA values were then measured weekly until a second nadir PSA value was achieved. Sexual function was evaluated at baseline, at the second nadir PSA value, and every 3 months thereafter. Testosterone, dihydrotestosterone (DHT), and dehydroepiandrostenedione (DHEA) levels were measured at baseline and at the first and second nadir PSA values. RESULTS: The median follow-up period was 16.9 months. Therapy failed in 1 patient with Stage D2 disease at 12 months, but an additional response to subsequent LHRH agonist therapy was observed. One patient developed National Cancer Institute grade 3 diarrhea and was withdrawn from the study. Seven of 20 men developed mild gynecomastia, and 3 of 20 developed mild transient liver function test elevations. Mean PSA levels were 94.6 +/- 38.2 ng/mL at baseline and 7.8 +/- 2.7 and 4.7 +/- 2.2 ng/mL at the first and second PSA nadir values, respectively (P = 0.034). Mean percent decline in PSA value from baseline was 87.0 +/- 3.1% with flutamide alone and 94.0 +/- 1.9% with both flutamide and finasteride (P = 0.001). Eleven of 20 men were potent at baseline. At the second nadir PSA value, 9 (82%) of 11 were potent, whereas 2 (18%) of 11 were impotent. With longer follow-up (median 16.4 months), 6 (55%) of 11 men were potent, 2 (18%) of 11 were partially potent, and 3 (27%) of 11 were impotent. With flutamide alone, testosterone rose a mean of 77 +/- 14.7% of baseline (P = 0.0001), DHEA fell a mean of 32.4 +/- 4.6% (P = 0.0001), and DHT was unchanged. With the addition of finasteride, testosterone rose another 14 +/- 6% (P = 0.06, not significant), DHEA was unchanged, and DHT fell a mean of 34.8 +/- 4.7% (P = 0.0009). CONCLUSIONS: Finasteride and flutamide were safe and well tolerated as AAT for advanced prostate cancer. Finasteride provided additional intraprostatic androgen blockade to flutamide, as measured by additional PSA suppression. Sexual potency was preserved initially in most patients, although there was a reduction in potency and libido in some patients on longer follow-up. Further evaluation of this therapy is needed.
Fresh intact human teeth were cut and treated with 3 commonly used gutta-percha solvents: chloroform, xylene, and Endosolv-E. Treatment consisted of embedding the specimens of each group for 15 or 30 min in the test solution. After each time interval, the specimens were rinsed, dried, and prepared for surface energy dispersive spectrometric analysis. The calcium and phosphorus levels in each specimen were recorded and the differences between the test groups were statistically analyzed. The changes in the calcium and phosphorus levels following treatment with the gutta-percha solvents were minimal and statistically nonsignificant.
Flecainide toxicity can impair cardiac function and precipitate circulatory collapse, which in turn depresses clearance and redistribution of flecainide. Treatment directed at improving cardiac function is often ineffective in the presence of persistently increased flecainide levels. We report a novel approach to severe flecainide overdose using peripheral cardiopulmonary bypass support (CBS) to maintain perfusion of the liver, thereby allowing clearance of the drug. CBS was initiated to resuscitate a young woman who had ingested flecainide in a suicide attempt. The patient had an agonal rhythm, no effective blood pressure, and a flecainide level of 5.4 micrograms/mL (therapeutic range, .2 to 1.0 microgram/mL). During 10 hours of CBS, the flecainide level decreased to 1.4 micrograms/mL, a half-life of 6 hours. Effective cardiac rhythm and blood pressure returned. CBS successfully supported this patient until the flecainide level decreased as a result of redistribution and normal clearance mechanisms. Unfortunately, because of severe neurologic damage sustained at the time of overdose, the patient died 4 days after admission.
The first case of the use of a tissue expander in revision total knee surgery is reported. A 76-year-old woman presented with extremely adherent scare tissue on the anterior proximal tibia that was the result of multiple debridements and skin grafting for an infected primary total knee arthroplasty. The tissue expander was placed prior to subsequent revision total knee arthroplasty to permit complete excision of the scar and to provide tension-free closure with normal skin at the time of revision. Three years after the surgery, the patient is doing well.
Tardive dystonia is a form of tardive dyskinesia for which there is little satisfactory treatment. We reviewed our experience at four movement disorder centers in the treatment of tardive dystonia with botulinum toxin A (BTX-A). Thirty-four patients with relatively localized tardive dystonia unresponsive to oral medications were treated with injections of BTX-A into dystonia muscles. Cervical dystonia was the most frequent manifestation of tardive dystonia in this group of patients. There was marked or moderate improvement in 29 of 34 patients. Eighteen of 24 patients with cervical dystonia showed either marked or moderate improvement. In this retrospective review, BTX-A provided useful symptomatic treatment for localized dystonia in patients with tardive dystonia unresponsive to other treatment. A controlled, prospective trial of BTX-A in tardive dystonia is warranted.
Ischemia and reperfusion cause coronary vascular and myocardial injury, which may be due to leukocyte-mediated processes. Antileukocyte measures have reduced injury after brief reperfusion periods of 1-3 h, but there has been little information on whether benefits are apparent after longer periods of reperfusion. We examined the effect of pretreatment with a monoclonal antibody (R15.7) to the CD18 family of leukocyte adhesion molecules (beta2-integrins) in dogs exposed to regional coronary ischemia for 1 h of left anterior descending coronary artery ligation and then reperfused for 48 h. Coronary microvascular permeability was assessed in vivo by measurement of protein leak index (PLI), using a double-isotope technique with autologous radiolabeled transferrin and erythrocytes. Vasorelaxation was measured in vitro with preconstricted epicardial coronary artery rings subjected to increasing concentrations of the endothelium-dependent vasodilators bradykinin (BK) and ADP and the endothelium-independent vasodilator nitroprusside. At 48 h of reperfusion in untreated dogs there were substantial increases in PLI in the previously ischemic regions, indicative of increased extravascular transferrin. These abnormalities were decreased, but not abolished, in the dogs treated with R15.7. Relaxation of rings from the ischemic/reperfused artery to BK and ADP were blunted in the untreated dogs. R15.7 resulted in improvement in some, but not all, indexes of relaxation in response to BK and ADP. Relaxation to nitroprusside was normal in ischemic/reperfused coronary rings from both treated and untreated dogs. Therefore, after 1 h of regional coronary ischemia and 48 h of reperfusion, coronary endothelial injury, which was manifested by increased coronary microvascular permeability and abnormalities in coronary endothelium-dependent relaxation, was reduced by pretreatment with the anti-CD18 integrin antibody R15.7.
A total of 149 college students, 48 men and 101 women, completed the Irrational Beliefs and the Need for Cognition scales to assess irrationality and the tendency to engage in effortful cognitive activity. Although substantial overlap between the constructs was found (r = -.29, p < .001), the relationship was not linear. Need for Cognition appears to be a process variable, while irrational belief appears to be a content variable. Results suggest that the Need for Cognition must achieve a minimum threshold before spontaneous critical self-examination can occur.
Tamoxifen is a substituted triphenylethylene antiestrogen used in the adjuvant therapy and chemoprevention of breast cancer. The antiestrogenic activity of the compound has been attributed to its metabolism to an active 4-hydroxy derivative and the avid binding of the active metabolite to the estrogen receptor. Receptor binding of the antiestrogen alters the transcriptional activity normally attributed to the estradiol-bound estrogen receptor. Tamoxifen is both an antagonist and an agonist of the estrogen receptor. However, a molecular explanation exists for this apparent paradox. The dual action is a function of the estrogen receptor complex present in a particular cell or tissue. If a cell type requires activating factors 1 and 2 of the estrogen receptor to be functioning concurrently, tamoxifen is antagonistic. However, if a cell or tissue requires only activating factor 1 to interact with transcription factors at the promoter, tamoxifen is agonistic. The implication is that the investigators must understand the fundamental biology of the estrogen receptor complex in a tissue context before one can predict tissue activity of tamoxifen.
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The effects of cystamine on the human immunodeficiency virus (HIV-1) expression in cord blood monocytes-derived macrophages (CBMDM) and lymphocytes were investigated. Cystamine suppressed HIV-1 expression in CBMDM and lymphocytes in a concentration-dependent fashion as determined by HIV-1 reverse transcriptase (RT) activity. This inhibitory effect of cystamine occurred with all five HIV-1 strains (both laboratory adopted and fresh isolates) tested in the study. The addition of cystamine to cultures of HIV-1 chronically infected CBMDM also suppressed 80% to 90% of RT activity in comparison with untreated controls. Cystamine also decreased HIV-1 protein expression in CBMDM as determined by indirect immunofluorescence assay. The inhibitory effects of cystamine on HIV-1 did not appear to be caused by toxicity to CBMDM or lymphocytes because there was no change in cell viability or cellular DNA synthesis as evaluated by trypan blue dye exclusion and [3H]-thymidine incorporation at doses of cystamine that inhibit the virus. HIV-1 infected CBMDM or lymphocyte cultures (without cystamine treatment) demonstrated giant syncytium formation or cytopathic effect (CPE), respectively, whereas cystamine-treated cultures lacked the giant syncytia or CPE induced by HIV-1 infection. Thus, these observations indicate that cystamine may have the potential to limit HIV-1 replication in monocytes/macrophages and lymphocytes in vivo and may represent a potentially useful compound in the treatment of pediatric HIV-1 infection and acquired immunodeficiency syndrome.
We have investigated the effects of SP on the constitutive and/or lipopolysaccharide (LPS)-induced expression of interleukin-10 (IL-10) and tumor necrosis factor (TNF-alpha) in both freshly isolated cord blood monocytes (FICBM) and cord blood monocyte-derived macrophages (CBMDM). The cells were treated with SP at various concentrations (10(-14) to 10(-6) M) in the presence or absence of LPS and culture supernatants were analyzed for IL-10 and TNF-alpha as measured by an enzyme immunosorbent assay (ELISA). FICBM and CBMDM treated with SP alone increased TNF-alpha secretion. The stimulatory effects of SP on TNF-alpha secretion are inhibited by a anti-SP polyclonal antibody and SP antagonists, spantide ([D-Arg-1-D-Trp-7-D-Trp-9-Leu-11]-SP) and CP-96,345 (a nonpeptide antagonist of the SP receptor). Although the treatment with SP alone did not enhance IL-10 secretion by both freshly isolated and cultured cord monocytes, treatment with SP in combination with LPS leads to a synergistic interaction in upregulation of IL-10 secretion. Fragments of SP (SP1-4 and SP5-11) in the presence or absence of LPS show little effects on IL-10 secretion by FICBM. SP reverses the inhibitory effect of IFN-gamma on LPS-induced IL-10 secretion by FICBM. In addition, the two SP antagonists and the anti-SP polyclonal antibody blocked the SP effect on IL-10 secretion by FICBM, indicating that these effects are specific and SP receptor mediated. Thus, SP is likely to play an important role in certain inflammatory conditions in the immune and nervous systems.
PURPOSE: To compare the learning opportunities for internal medicine residents in tertiary care and community hospital settings. METHOD: Two sites were studied: Victoria General Hospital, a teaching hospital affiliated with the Dalhousie University Faculty of Medicine, staffed by five general internists and serving Halifax County (population of 420,000); and South Shore Regional Hospital, serving the community of Bridgewater (with a catchment area of 50,000) and staffed by three general internists. All in- and outpatients seen in the two settings over a one-year period (1993) were described in accordance with the Canadian Institute for Health Information's major clinical categories, as well as a case mixture recommended as providing appropriate learning experiences for internal medicine clerks. Over a one-month period (August 1993), consecutive patients were interviewed, completing a health status questionnaire, the Medical Outcome Study Short Form 36 (SF-36). RESULTS: Data were collected from the records of 2,763 patients, and the SF-36 questionnaire was administered to 406 patients. The data indicate that the settings were relatively similar except that there was more case variety in the tertiary care setting, and that more patients with cardiovascular disease and no patient with acquired immune deficiency syndrome were seen in the regional setting. Quality-of-life scores showed similarities to norms in the United States and United Kingdom, except that the ambulatory patients in the regional setting had rather lower scores. CONCLUSION: Overall, the patients' problems in the regional and tertiary care settings offered similar learning opportunities.
OBJECTIVE: To evaluate the effect of neuromuscular paralysis on systemic and splanchnic oxygen utilization in patients in respiratory failure during controlled mechanical ventilation. SETTING: A university-affiliated teaching hospital. INTERVENTION: Mechanically ventilated patients, who were undergoing hemodynamics monitoring and who had a gastric intramucosal pH (pHi) of less than 7.35, were studied. Prior to paralysis, the patients were sedated with lorazepam and morphine to standard end points, and the cardiac output and oxygenation were optimized. The patients were then paralyzed with doxacurium and the ventilator rate adjusted to keep the PaCO2 at baseline value. The hemodynamic and oxygenation profile and pHi were determined prior to paralysis and repeated 2 to 2.5 h later. RESULTS: Eight patients were studied; their mean age was 63 +/- 8 years and acute physiology and chronic health evaluation II score was 22 +/- 4. The mean fraction of inspired oxygen, positive end-expiratory pressure, and venous admixture ratio prior to the study was 0.7 +/- 0.14, 11.8 +/- 2.4 cm H2O, and 26 +/- 9%, respectively. Prior to paralysis, the mean set assist controlled ventilation rate was 15 +/- 2 breaths/min and the patient rate was 23 +/- 5 breaths/min. With neuromuscular paralysis, the cardiac index fell from 4.6 +/- 2.2 to 4.3 +/- 2.4 L/min/m2 (p=0.1), the oxygen delivery fell from 537 +/- 129 to 471 +/- 95 mL/min/m2 (p=0.03), and the oxygen consumption and extraction ratio fell from 200 +/ 77 to 149 +/- 35 mL/min/m2 (p=0.03) and 36 +/- 5 to 31 +/- 10, respectively (p=0.2). The pHi increased from 7.21 +/- 0.16 to 7.29 +/- 0.1 (p=0.02). CONCLUSION: In critically ill patients in respiratory failure, neuromuscular paralysis decreased whole body oxygen consumption and increased pHi. Presumably, by eliminating the work of breathing, there is a redistribution of blood flow from the respiratory muscles to the splanchnic and other nonvital vascular beds.
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