Prevalence of HIV and sexually transmitted and blood-borne infections,and related preventive and risk behaviours,among gay,bisexual and other men who have sex with men in Montreal,Toronto and Vancouver: results from the Engage Study

ObjectivesThe last Canadian biobehavioural surveillance study of HIV and other sexually transmitted and blood-borne infections (STBBI) among gay, bisexual and other men who have sex with men (GBM) was conducted in 2010. We designed a study to measure STBBI prevalence among GBM in metropolitan Montreal, Toronto and Vancouver and to document related preventive and risk behaviours.MethodsThe Engage Cohort Study used respondent-driven sampling (RDS) to recruit GBM who reported sex with another man in the past 6 months. At baseline, we examined recruitment characteristics of the samples, and the RDS-II-adjusted distributions of socio-demographics, laboratory-confirmed HIV and other STBBI prevalence, and related behaviours, with a focus on univariate differences among cities.ResultsA total of 2449 GBM were recruited from February 2017 to August 2019. HIV prevalence was lower in Montreal (14.2%) than in Toronto (22.2%) or Vancouver (20.4%). History of syphilis infection was similar across cities (14–16%). Vancouver had more HIV-negative/unknown participants who reported never being HIV tested (18.6%) than Toronto (12.9%) or Montreal (11.5%). Both Montreal (74.9%) and Vancouver (78.8%) had higher proportions of men who tested for another STBBI in the past 6 months than Toronto (67.4%). Vancouver had a higher proportion of men who used pre-exposure prophylaxis (PrEP) in the past 6 months (18.9%) than Toronto (11.1%) or Montreal (9.6%).ConclusionThe three largest cities of Canada differed in HIV prevalence, STBBI testing and PrEP use among GBM. Our findings also suggest the need for scale-up of both PrEP and STI testing among GBM in Canada.     

Epicoccum allergy: skin reaction patterns and spore/mycelium disparities recognized by IgG and IgE ELISA inhibition

Comparable degrees of skin reactivity were observed towards spore and mycelium extracts from two isolates of Epicoccum and to one preparation of Alternaria in 35 rural and 120 university patients. The best experimental extracts detected Epicoccum sensitivity in 70% of the group tested while the commercial extract detected sensitivity in only 6%. Skin reaction correlations were greatest within isolates (eg, spore-A/mycelium-A), then for specific fungus parts (eg, spore-A/spore-B), then between isolates and parts (spore-A/mycelium-B). High correlations were found between individual IgG and IgE ELISA values for all antigens using serum from Epicoccum skin-reactive patients. ELISA inhibition results suggested that significant cross-reactivity exists between Epicoccum and Alternaria antigens recognized by IgG but not by IgE. ELISA inhibition cross-reaction patterns among Epicoccum antigens were comparable to skin reactions while IgG patterns showed little variability. Further characterization of spore/mycelium and interstrain recognition patterns among different immunoglobulin isotypes will be necessary before complete standardization of extracts from different parts of fungi will be possible. The use of spore material for skin testing and treatment of Epicoccum sensitivity appears to be both premature and unnecessary at this time.     

Immunization with cholinergic cell bodies induces histopathological changes in rat brains

We have previously shown that sera from patients with Alzheimer’s disease (AD) contain antibodies to the cell bodies (perikarya; PK) of purely cholinergicTorpedo neurons, and that repeated immunization of rats with this neuronal preparation for over a year induces learning and memory impairments. In the present study, we examined the brain morphology of cholinergic PK immunized rats relative to controls. Immunohistochemical studies of the brains of these rats revealed the accumulation of IgG in specific areas, such as, the hippocampus. Parallel histochemical studies demonstrated significant changes in the hippocampus, and in white matter areas. They included large vacuoles and necrotic nuclei in the granular layer of the dentate gyrus, tangle-like appearance in some pyramidal neurons of the hippocampus, and vacuolar degeneration accompanied by oligodendroglia hypertrophy in white matter tracts, such as, the corpus callosum and fimbria. In contrast, immunization withTorpedo cholinergic nerve terminals, that has no cognitive effects on the rat, also did not induce brain morphological changes. These findings suggest that the learning and memory deficits induced by immunizing rats with cholinergic PK are related to the observed brain morphological changes, and support the hypothesis that the antibodies to cholinergic neurons found in the sera of AD patients may play a role in neuronal degeneration in this disease.     

Challenges of leadership in an era of health care reform

Health care leadership has never been more difficult than in the past decade--and the next ten years promise to be even more demanding. As a new era for health care emerges, organizational leaders will be required to manage increased levels of risk, uncertainty, and rapid change. Successful chief executives will be those who recognize and nurture intangible leadership qualities including knowledge of self, commitment to service, and depth and breadth of vision. With the continued shift away from hospital inpatient care, health care leaders will be called on to develop multipurpose delivery systems that move from a market-based to a community-based focus and deliver high quality services in a cost-effective manner. Several leadership themes will unfold in the midst of health care reform, including: exploiting change for the good of the organization and community; serving as educator, communicator, and comforter to divergent constituencies; and reestablishing a balance between short-term goals and long-term vision.     

Low-dose sufentanil and lidocaine supplementation of general anaesthesia

This randomized double-blind study compared the effects of: (1) saline infusion (C); (2) sufentanil alone (1.0 micrograms.kg-1) (S); and (3) low-dose sufentanil (0.5 micrograms.kg-1) in combination with lidocaine (1.5 mg.kg-1) (LS): on the cardiovascular responses to tracheal intubation and on postoperative ventilation as monitored by respiratory inductive plethysmography in day-care surgical procedures of approximately 60 min duration. Thirty healthy, unpremedicated patients were studied. Thiopentone requirements were reduced by 40 and 28 per cent in the S and LS groups respectively compared with control (P less than 0.001). Both treatments suppressed HR and BP responses (P less than 0.005) to intubation. Postoperatively, PaCO2 was elevated (P less than 0.05) in group S. Dose-related respiratory depression was observed. The incidence of postoperative apnoea was significantly higher in both S and LS groups than compared with control (P less than 0.05). However, only patients in group S showed higher apnoea index and mean apnoea duration over the initial 10-20 min after surgery compared with control (P less than 0.005). In addition, group S showed slower respiratory frequency and prolonged expiratory time (P less than 0.005). In conclusion, an induction dose of sufentanil (1 microgram.kg-1) used in balanced anaesthesia of less than 70 min duration was associated with significant respiratory depression, particularly during the initial 10-20 min after surgery, whereas low-dose sufentanil (0.5 micrograms.kg-1) with lidocaine (1.5 mg.kg-1) had minimal postoperative respiratory depression and comparable attenuation of pressor responses to intubation.     

Metabolism and elimination of rhodamine 123 in the rat

Summary Little is known of the pharmacology of rhodamine 123 (RH-123), an agent reported to have carcinoma-selective experimental antitumor activity. Accordingly, using a high-performance liquid chromatographic assay system with fluorescence detection, we examined the plasma decay and the biliary and urinary elimination of parent drug and metabolites in female Sprague-Dawley rats receiving RH-123 at an intravenous dose (5 mg/kg) equivalent to the therapeutic dose used in murine tumor models. Following drug administration to unconscious animals, plasma levels of drug-associated fluorescence fell in a triphasic manner (t_1/2, 15 min; t_1/2, 1 h; t_1/2, 4.7 h). In plasma, unchanged drug predominated but lower levels of the deacylated metabolite rhodamine 110 (RH-110) and two unknowns were also detectable throughout the study. Drug fluorescence was recovered extensively in both urine and bile. In unconscious animals with ureteral cannulae, urinary excretion (11.4% of the dose in 6 h) occurred predominantly as unchanged RH-123 (97% of the total), with low levels of RH-110 (2.4%) and two unknowns (<0.6% combined) also being present. Similarly dosed conscious animals (without surgical intervention) housed in metabolic cages showed a comparable pattern of urinary excretion, with 11.9% of the drug dose being recovered in 6 h and 21.9%, by 48 h. Biliary drug elimination accounted for 8% of the delivered dose in 6 h in unconscious animals and for 11% by 36 h in conscious animals fitted with biliary cannulae. In contrast to urinary excretion, in which unchanged drug predominated, only 50% of the fluorescence recovered in bile was attributable to RH-123. The remainder was due to a number of products that were detectable throughout the study. Of these, one present at significant levels was identified as a glucuronide conjugate of RH-123, based on the liberation of parent drug when the purified metabolite was incubated with -glucuronidase or hydrolyzed with 1 N hydrochloric acid. Further studies with a radiolabeled form of RH-123 are necessary to establish the identity of the remaining unknowns disclosed in this work.This work was supported in part by research grants CA 44890 (T.W.S.) and CA 37082 (M.I.) from the National Cancer Institute, National Institutes of Health, United States Public Health Service     

Mesoaccumbens dopamine-opiate interactions in the control over behaviour by a conditioned reinforcer

These experiments examined the role of dopamine-opiate interactions in the ventral tegmental area (VTA) and nucleus accumbens in the mediation of reinforcement-related behaviour. It has been shown previously that opiates induce a dopamine-dependent increase in locomotor activity in rats when infused into the VTA, and a dopamine-independent hyperactivity when infused into the nucleus accumbens. The present study investigated the generality and significance of these two findings, by examining dopamine-opiate interactions in the control over behaviour exerted by a conditioned reinforcer (CR), an arbitrary stimulus which gains control by association with primary reinforcement. Rats were trained to associate a light/noise stimulus with sucrose reinforcement, and the efficacy of the CR in controlling behaviour was assessed by measuring its ability to support a new lever pressing response. Responding on one lever (CR lever) produced the CR, responding on the other lever had no programmed consequences. In experiment 1, intra-accumbens infusions ofd-amphetamine (10 µg), the D₁ dopamine receptor agonist SKF-38393 (0.1 µg), the D₂ dopamine receptor agonist LY-171555 (quinpirole; 0.1 µg) or the opiate receptor agonist [d-Ala²]-methionine enkephalinamide (DALA; 1 µg) selectively increased responding on the CR lever. Infusion with DALA intra-VTA had no effect. However, pretreatment with DALA intra-VTA (10 × 1 µg/day) subsequently reduced the selectivity of the response to infusions intra-accumbens withd-amphetamine or SKF-38393, and blocked the response to LY-171555 or DALA. Pretreatment also shifted to the right the dose-response function for DALA intra-accumbens. In experiment 2, intra-accumbens infusions ofd-amphetamine, SKF-38393, LY-171555 or DALA again increased responding on the CR lever only. Pretreatment with intra-accumbensd-amphetamine (5 × 1 µg/day) reduced the selectivity of the response subsequently tod-amphetamine, and blocked the response to SKF-38393, LY-171555 or DALA. In experiment 3, intra-accumbens infusions of the -opiate receptor agonist [d-Ala²,N-Me-Phe⁴,Gly⁵-ol]-enkephalin (0.003–0.1 µg), or the -opiate receptor agonist [d-Pen^2, 5]-enkephalin (0.03–1 µg) enhanced selectively responding on the CR lever. Thus, the dopamine-dependent locomotor-stimulant properties of intra-VTA infusions of opiates are associated with impaired conditioned reinforcer efficacy. Finally, repeated stimulation of the mesoaccumbens dopamine pathway may compromise the dopamine-independence of the opiate system within the nucleus accumbens.     

Epidural anesthesia in anin vitro fertilization and embryo transfer program

Objectives To investigate the potential advantages of epidural anesthesia in an in vitro fertilization and embryo transfer program.Study Design Between January 1991 and December 1992, 148 infertile patients underwent transvaginal ultrasound guided oocyte retrieval. A total of 44 patients (group A) had 50 retrievals under epidural anesthesia, and 104 patients (group B, control group) 112 retrievals under intravenous sedation (propofol) with mask-assisted ventilation (nitrous oxide).Results In group A satisfactory anesthesia was achieved in 49 of the 50 cases (98%); one patient required additional intravenous administration of propofol owing to extreme anxiety. No complications were observed. Adversely, in group B nausea was observed in 16 cases (14%) and nausea and vomiting in 7 cases (6%). In group A the fertilization, cleavage and pregnancy rates were 67.2%, 92% and 20% respectively, while in group B the rates were 69.3%, 93% and 19.6% respectively; the differences are not statistically significant.Conclusions Epidural anesthesia is an effective method for transvaginal oocyte retrieval but does not improve the treatment outcome as compared to an intravenous sedation with mask-assisted ventilation using propofol and nitrous oxide.     

The effect of a chemical phosphatase on single calcium channels and the inactivation of whole-cell calcium current from isolated guinea-pig ventricular myocytes

A chemical phosphatase, butanedione monoxime (BDM, at 12–20 mM), reduced open probability (P ₀) of single cardiac L-type Ca²⁺ channels in cellattached patches from guinea-pig ventricular myocytes, without effect on the amplitude of single-channel current, the mean open time or the mean shorter closed time, but it increased mean longer closed time and caused a fall in channel availability. A decrease in the mean time between first channel opening and last closing within a trace was principally due to an inhibition of the longer periods of activity. As a result, the time course of the mean currents, which resolved into an exponentially declining and a sustained component, was changed by an increase in the rate of the exponential phase and a profound reduction of the sustained current. Essentially similar results were obtained when studying whole-cell Ba²⁺ currents. The inactivation of the whole-cell Ca²⁺ currents was composed of two exponentially declining components with the slower showing a significantly greater sensitivity to BDM, an effect that was much more pronounced in myocytes exposed to isoprenaline with adenosine 5-O-(3-thiotriphosphate) (ATP[S]) in the pipette solution. The actions of BDM, which are the opposite of those produced by isoprenaline, suggest that the level of phosphorylation affects processes involved in the slow regulation of channel activity under basal conditions and that several sites (and probably several kinases) are involved. Channels with an inherently slow inactivation would seem to be converted into channels with a rapid inactivation by a dephosphorylation process.