Seroprevalence of and risk factors for HIV-1 infection in injection drug users in Montreal and Toronto: a collaborative study.

OBJECTIVE: To determine the prevalence of antibodies to HIV-1 and risk factors for HIV-1 infection among injection drug users. DESIGN: Questionnaire survey. A venous blood sample was taken for HIV-1 antibody testing. SETTING: Montreal and Toronto. PARTICIPANTS: A total of 810 subjects who had used injection drugs in the previous 6 months recruited mainly from treatment centres and from the street in Montreal (425 subjects) and from treatment centres in Toronto (385 subjects) between September 1988 and September 1990. The overall participation rate was 82%. OUTCOME MEASURES: HIV-1 seropositivity, sociodemographic and behavioural risk factors for HIV-1 infection. RESULTS: The overall seroprevalence rate of HIV-1 infection was 4.8% (95% confidence limits [CL] 3.5 and 6.5). In Montreal the rate was 8.2% (95% CL 6.0 and 11.2), and in Toronto 1.0% (95% CL 0.4 and 2.6) (p < 0.001). Seropositive subjects were significantly older (p = 0.041) and were more likely to have a history of imprisonment (p = 0.006) than seronegative subjects. In univariate analysis seropositivity was associated with the following behaviours: more frequent cocaine use (p < 0.001), injecting drugs in "shooting galleries" (p = 0.002), sharing equipment with a person known to be HIV-1 seropositive (p = 0.006), "booting" fresh blood (p = 0.004), homosexual or bisexual orientation (p = 0.006), engaging in prostitution (p < 0.001) and, for men, number of male sexual partners in the previous 6 months (p = 0.007). In multivariate analysis the determinants of HIV-1 seropositivity were Montreal as the city of recruitment (odds ratio [OR] 6.7, 95% CL 2.32 and 19.42), engaging in prostitution (OR 2.13, 95% CL 1.01 and 4.75), a history of imprisonment (OR 3.51, 95% CL 1.33 and 9.29) and sharing equipment with a person known to be HIV-1 seropositive (OR 4.43, 95% CL 1.43 and 13.74). CONCLUSIONS: Our findings show that HIV-1 is circulating among injection drug users in Montreal and Toronto and that both drug use and sexual behaviours are implicated in the transmission of infection in the populations studied. Adapted preventive programs should be developed to prevent further spread of HIV-1 infection in this population.     

Preventing alcohol problems: survey of Canadian medical schools.

In preparation for a national conference on medical education in the prevention of alcohol problems, a survey of conference participants was conducted. Participants were undergraduate and postgraduate representatives from each Canadian medical school and representatives from 11 provincial and territorial alcohol and other drug agencies. There was agreement that physicians and medical schools have important roles in prevention and treatment of alcohol problems, with "traditional" medical roles seen as the most important. Current training is variable and was seen as inadequate, with more time devoted to treatment than prevention. To correct this situation, renewed priorities and faculty leadership are needed. Respondents felt that there should be uniform standards for assessing undergraduate students' skills in dealing with alcohol problems. Provincial alcohol and other drug agencies are underused in medical education in the prevention and treatment of alcohol problems.     

ANEURYSM OF SINUS OF VALSALVA DISSECTING INTO THE INTERVENTRICULAR SEPTUM – ECHOCARDIOGRAPHIC DIAGNOSIS (A Case Report)

Aneurysm of sinus of Valsalva dissecting into interventricular septum is a rare entity. We report one such case who was incidentally diagnosed by echocardiography to have this abnormality during evaluation of a clinically suspected isolated aortic regurgitation.KEY WORDS: Aneurysm – dissecting – sinus of Valsalva, Echocardiography     

A preliminary examination of cryotherapy and secondary injury in skeletal muscle

PURPOSE: The purpose of this study was to document the presence of secondary injury in skeletal muscle, to quantify it, and to determine whether it is altered by acute cryotherapy. METHODS: Crush injuries to the triceps surae of 19 adult male Sprague-Dawley rats were either treated continuously with ice for 5 h (N = 10) or received no ice treatment (N = 9). After treatment, tissues were assayed for the reduction of triphenyltetrazolium chloride (TTC) to triphenylformazan (formazan red). TTC reduction is indicative of oxidative function and serves as an indicator of cellular damage. RESULTS: A significantly lower TTC reduction rate was seen in both cold-treated injured tissue (6.59 +/- 1.01 microg x mg(-1) x h(-1)) and nontreated injured tissue (4.48 +/- 0.79 microg x mg(-1) x h(-1)) compared with uninjured controls (ice group = 7.94 +/- 1.49 microg x mg(-1) x h(-1), no-ice group = 6.62 +/- 0.75 microg x mg(-1) x h(-1)). These data indicate that crushing of muscle tissue produces injury measurable with the TTC reduction assay. Additionally, in crush-injured tissues, a significantly lower TTC reduction rate was seen in untreated tissues (4.48 +/- 0.79 microg x mg(-1) x h(-1)) compared with ice treated tissues (6.59 +/- 1.01 microg x mg(-1) x h(-1)), indicating that cryotherapy reduces the magnitude of secondary injury. CONCLUSIONS: From these data, it can be concluded that secondary injury occurs after primary crush injury and that secondary injury is retarded by acute treatment with 5 h of continuous cryotherapy.     

Interferon-β inhibits proliferation and progression through S phase of the cell cycle in five glioma cell lines

Summary The growth inhibitory effect of IFN- was evaluated in 5 human glioma cell lines (AO2V4, GJC, GJR, NN and NNR) and in normal astrocyte cultures (SC and TM). All 5 glioma cell lines showed an anti-proliferative response to IFN- whereas normal glial cells were non-responsive. IFN- at 10, 100 and 500 U/ml lead to a 30%,70% and 80% relative decrease in cell number after 12 days, respectively in AO2V4 cells. GJC and GJR cell lines also responded significantly to the lowest concentration of IFN- tested and at 500 U/ml the relative cell number decreased 55%. The NN and NNR cells were the least responsive to IFN- with maximum growth inhibition of 30% at 500 U IFN-/ml. Following treatment with IFN-, AO2V4, GJC, GJR and normal astrocytes all expressed mRNA encoding the anti-viral protein, 2-5A synthetase demonstrating that IFN- bound to receptors on all four cell lines and activated signal transduction pathways required for induction of an anti-viral protein. A determination of the relative number of viable cells showed that none of these cells exhibited a significant decrease in cell viability. Since the antiproliferative response to IFN- was not primarily due to cell death, the effect of IFN- on cell cycle progression was evaluated by flow cytometry. All treated glioma cell lines showed a relative increase in proportion of cells in S phase. AO2V4 cells had a 50%–80% increase in the percentage of cells in S phase, whereas GJC, GJR and NNR had percentage increases of 20%–40%. IFN- treatment of normal astrocytes did not significantly alter their cell cycle profile. These data suggest that IFN- exerts its antiproliferative effect on glioma cells by arresting the ordered progression through S phase or decreasing entry into G₂/M phase of the cell cycle.     

Dementing Illnesses in Rural Populations: The Need for Research and Challenges Confronting Investigators

Expansion of the world's elderly populations has increased concerns about aging-related medical disorders like Alzheimer's disease and other dementias. In the United States, one fourth of those older than age 65 and at greatest risk for developing dementia live in rural environments that may influence its manifestation. The objectives of this study were to determine the need for and potential benefits of further epidemiological research concerning dementia and similar disorders in rural U.S. populations and to identify pertinent methodological issues related to rural dementia research. This study employed a National Library of Medicine (MEDLINE) document search based on the key words "cognitive disorders," "dementia," "Alzheimer's disease," and "rural," followed by recovery of literature resources references in the bibliographies of selected articles. Nineteen studies focusing on dementia or related disorders in rural settings have been reported from around the world. While four of these were conducted in the United States, only one rural dementia prevalence study has been undertaken in this country. Because of methodological variability, comparisons of prevalence estimates between these rural studies, as well as with those from urban investigations, is difficult. Nonetheless, there is reason to believe that certain potentially dementing illnesses are more common in rural populations. There is also evidence to suggest that the screening instruments commonly used in such studies tend to misclassify rural elders as "false positive" dementia cases. Information regarding dementing disorders, particularly Alzheimer's disease, in rural populations is scarce. Preliminary observations that dementia may be more common in rural settings and that rural families are more likely to maintain their dementing elders in the community imply that further rural dementia research could yield important insights into the risk factors for these illnesses, the variables influencing their course, and the methods by which they can be more effectively managed. A determination of the reliability and validity of commonly used dementia screening instruments in rural populations would represent an important advancement in this area of research.     

Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group.

PURPOSE: This phase III randomized trial compared two chemotherapy regimens, gemcitabine plus carboplatin and mitomycin, ifosfamide, and cisplatin, in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). The regimens were compared with regard to effects on survival, response rates, toxicity, and quality of life. PATIENTS AND METHODS: Eligible patients had previously untreated stage IIIB or IV NSCLC suitable for cisplatin-based chemotherapy. Randomly assigned patients were to receive four cycles, each at 3-week intervals, of carboplatin area under the curve of 5 on day 1 plus gemcitabine 1,200 mg/m(2) on days 1 and 8 (GCa) or mitomycin 6 mg/m(2), ifosfamide 3g/m(2), and cisplatin 50 mg/m(2) on day 1 (MIC). RESULTS: Between February 1999 and August 2001, 422 patients (GCa, n = 212; MIC, n = 210) were randomly assigned in the United Kingdom. The majority of patients received the intended four cycles (GCa, 64%; MIC, 61%). There was a significant survival advantage for GCa compared with MIC (hazard ratio, 0.76; 95% CI, 0.61 to 0. 93; P = .008). Median survival was 10 months with GCa and 7.6 months with MIC (difference, 2.4 months; 95% CI, 1.0 to 4.0), and 1-year survival was 40% with GCa and 30% with MIC (difference, 10%; 95% CI, 3% to 18%). Overall response rates were similar (42% for GCa v 41% for MIC; P = .84). More thrombocytopenia occurred with GCa (P = .03), but this was not associated with increased hospital admission or fatality. GCa caused less nausea, vomiting, constipation, and alopecia and was associated with fewer admissions for administration and better quality of life. CONCLUSION: In patients with advanced NSCLC, GCa chemotherapy was shown to be a better-tolerated treatment that conferred a survival advantage over MIC.     

Immunogenicity, including vitiligo, and feasibility of vaccination with autologous GM-CSF-transduced tumor cells in metastatic melanoma patients.

PURPOSE: To determine the feasibility, toxicity, and immunologic effects of vaccination with autologous tumor cells retrovirally transduced with the GM-CSF gene, we performed a phase I/II vaccination study in stage IV metastatic melanoma patients. PATIENTS AND METHODS: Sixty-four patients were randomly assigned to receive three vaccinations of high-dose or low-dose tumor cells at 3-week intervals. Tumor cell vaccine preparation succeeded for 56 patients (88%), but because of progressive disease, the well-tolerated vaccination was completed in only 28 patients. We analyzed the priming of T cells against melanoma antigens, MART-1, tyrosinase, gp100, MAGE-A1, and MAGE-A3 using human leukocyte antigen/peptide tetramers and functional assays. RESULTS: The high-dose vaccination induced the infiltration of T cells into the tumor tissue. Three of 14 patients receiving the high-dose vaccine showed an increase in MART-1- or gp100-specific T cells in the peripheral blood during vaccination. Six patients experienced disease-free survival for more than 5 years, and two of these patients developed vitiligo at multiple sites after vaccination. MART-1- and gp100-specific T cells were found infiltrating in vitiligo skin. Upon vaccination, the T cells acquired an effector phenotype and produced interferon-gamma on specific antigenic stimulation. CONCLUSION: We conclude that vaccination with GM-CSF-transduced autologous tumor cells has limited toxicity and can enhance T-cell activation against melanocyte differentiation antigens, which can lead to vitiligo. Whether the induction of autoimmune vitiligo may prolong disease-free survival of metastatic melanoma patients who are surgically rendered as having no evidence of disease before vaccination is worthy of further investigation.