Evaluating networked drug checking services in Toronto, Ontario: study protocol and rationale.

BACKGROUND: The increasing incidence of fatal opioid overdose is a public health crisis in Canada. Given growing consensus that this crisis is related to the presence of highly potent opioid adulterants (e.g., fentanyl) in the unregulated drug supply, drug checking services (DCS) have emerged as part of a comprehensive approach to overdose prevention. In Canada's largest city, Toronto, a network of DCS launched in 2019 to prevent overdose and overdose-related risk behaviors. This network employs mass spectrometry technologies, with intake sites co-located with supervised consumption services (SCS) at three frontline harm reduction agencies. The protocol and rationale for assessing the impact of this multi-site DCS network in Toronto is described herein. The aims of this study are to (1) evaluate the impact of DCS access on changes in and factors influencing overdose and related risk behaviors, (2) investigate the perceived capacity of DCS to prevent overdose, and (3) identify composition (qualitative and quantitative) trends in Toronto's unregulated drug supply. METHODS: We will use a parallel-mixed-methods design with complementary data sources (including data from chemical analysis of drug samples, quantitative intake and post-test surveys, SCS, coroners, paramedic services, and qualitative interviews), followed by a meta-inference process wherein results from analyses are synthesized. RESULTS: Whereas most DCS globally target "recreational drug users," in Toronto, this networked DCS will primarily target marginalized people who use drugs accessing frontline services, many of whom use drugs regularly and by injection. This evolution in the application of DCS poses important questions that have not yet been explored, including optimal service delivery models and technologies, as well as unique barriers for this population. Increasing information on the unregulated drug supply may modify the risk environment for this population of people who use drugs. CONCLUSIONS: This study addresses evidence gaps on the emerging continuum of overdose prevention responses and will generate critical evidence on a novel approach to reducing the ongoing high incidence of drug-related morbidity and mortality in Canada and elsewhere.

Villoglandular adenocarcinoma of the cervix: clarity is needed on the histological definition for this difficult diagnosis.

BACKGROUND: Villoglandular adenocarcinoma (VGA) of the cervix is reported as a variant of a cervical adenocarcinoma with a good prognosis. CASES: We present two cases histologically reported as a villoglandular adenocarcinoma of the cervix that have recurred and progressed rapidly since initial treatment. External histopathological review suggested both had a prominent villoglandular pattern but with an associated underlying well-differentiated adenocarcinoma. CONCLUSION: The diagnosis of VGA is difficult. Current literature is not entirely consistent in the presented definition, and further clarity is needed. Because of the rarity of VGA and the difficulty but importance of the diagnosis, we would feel that a central review of all cases of VGA is warranted. This would assist in diagnosis and also in obtaining accurate follow-up data.

Performance and error analysis of automated external defibrillator use in the out-of-hospital setting.

STUDY OBJECTIVE: We determined whether automated external defibrillators (AEDs) can meet the American Heart Association performance criteria to detect and shock unstable cardiac rhythms (ventricular fibrillation [VF], ventricular tachycardia [VT]) in the setting of an out-of-hospital cardiac arrest. METHODS: AED performance was reviewed for cardiac arrests occurring between January 1, 1995, and December 31, 1997. After every cardiac arrest, data regarding each rhythm analyzed and subsequent response (shock or no shock) were downloaded from the AED memory module. The study paramedic and study physician independently reviewed each case and interpreted cardiac rhythms from downloaded AED data. The emergency medical services medical director resolved all discrepancies in a blinded manner. All cases of out-of-hospital cardiac arrest in which an AED was turned on and a rhythm analyzed were included. The primary objective was the correct identification and defibrillation of VF or VT. Sensitivity, specificity, and predictive values with 95% confidence intervals (CIs) were calculated. Sources of error in AED rhythm management are also described. RESULTS: A total of 3,448 AED rhythms were available for interpretation. Sensitivity and specificity for appropriate AED management of a shockable (VF or VT) rhythm were 81.0% (95% CI 77.9% to 83.8%) and 99.9% (95% CI 99.7% to 100%), respectively. Positive and negative predictive values were 99.6% (95% CI 98.7% to 99.9%) and 95.5% (95% CI 94.7% to 96.2%), respectively. There were 132 errors associated with AED management. Two errors resulted in delivery of an inappropriate shock. In the remaining 130 errors, a shockable rhythm was not shocked. Fifty-five (42.3%) errors were AED dependent, 70 (53.9%) were operator dependent, and 5 (3.9%) were unclassified. CONCLUSION: The AED had high specificity and moderately high sensitivity in detecting and shocking unstable cardiac rhythms in the out-of-hospital setting. Few cardiac rhythms were mismanaged by the AED. Elimination of operator-dependent errors could increase AED sensitivity.

Acute dapsone intoxication: a pediatric case report.

INTRODUCTION: There are many case reports of dapsone overdose in adults but only a few reports of dapsone-induced methemoglobinemia in children. We report a case of a three-year-old boy who developed prolonged recurrent methemoglobinemia following an ingestion of dapsone. METHODS: Case report. ETHICS: Not applicable. STATISTICS: Not applicable. RESULTS: This child developed significant symptoms of methemoglobinemia approximately two hours after ingesting dapsone 37.5 mg/kg. The initial methemoglobin level measured 2.5 hours after ingestion was 44%. The patient was treated with multiple doses of activated charcoal and methylene blue. Three doses of methylene blue reduced the methemoglobin level to 6% by approximately 16 hours after the overdose but the level rebounded to nearly 15% at 64 hours postingestion. DISCUSSION: Dapsone is a drug that is being used for a wide variety of clinical conditions. The primary clinical manifestation of dapsone overdose is methemoglobinemia. An important aspect of dapsone poisoning is its ability to produce methemoglobinemia, which is long lasting and which may recur following methylene blue therapy. Because of this, dapsone-poisoned children need to be monitored for two to three days.

Age-related changes in the secretion of growth hormone in vivo and in vitro in infantile and prepubertal Holstein bull calves.

The average concentration of GH in blood is high at birth and declines during the period of sexual maturation in bulls. The objectives of these studies were (1) to define age-related changes in vivo in the pulsatile secretion of GH from birth to puberty, (2) to determine whether pituitary cell content of GH and characteristics of the secretion of GH in vitro reflect age-related changes in vivo, and (3) to examine whether responsiveness to GH-releasing hormone (GHRH) and somatostatin (SRIF) in vitro changed with age in Holstein bull calves. In experiment 1, calves were bled every 15 min for 12 h at < 1, 12 and 42 weeks of age (n = 5/group), these being representative of infantile, juvenile and pubertal stages of development. Calves were killed 3 to 5 days later and the pars distalis of the anterior pituitary gland was enzymatically dispersed into a suspension of single cells. Aliquots of cells were extracted with 0.01 mol NaHCO3/l to determine the content of GH and cultured for 18 and 72 h. As expected, the average concentration of GH in plasma decreased with age (P < 0.001). The initial decrease in GH was caused by a reduction in the baseline concentration between birth and 12 weeks of age. There was a marked decrease in GH pulse amplitude between 12 and 42 weeks of age and a further reduction in the baseline concentration. In contrast, the pulse frequency of GH increased (P < 0.05) from < 1 week to 12-weeks of age and remained constant thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Testicular development in bulls treated with recombinant bovine somatotropin.

This study was conducted to test the hypothesis that administering recombinant bovine somatotropin (rbST) would affect testicular development in Holstein bulls. From 4 until 32 wk of age, bulls received a daily injection of either placebo (C) or rbST (.2 mg/kg BW.75, i.m.; n = 10/group). At 14-d intervals, blood was obtained and assayed for testosterone (T); BW, shoulder height (SH), and testis length (TL) were recorded. At 7, 12, and 24 wk of age, bulls were bled at 10-min intervals for 6 h to determine the secretory patterns of LH, growth hormone (GH), and IGF-I. All bulls were killed at 40 wk of age. One testis was used for determination of daily sperm production (DSP), and the number of spermatids per gram of parenchyma (SP/G); the remaining testis was perfused and fixed for histological analysis of numbers of Sertoli cell nuclei (SCN/ST) and spermatids per seminiferous tubule cross-section (SP/ST). Epididymal spermatozoa were collected to test effects of rbST on the integrity of spermatozoal chromatin structure. Administration of rbST increased (P < .0001) concentrations of GH (nanograms/milliliter) in plasma at all ages (C vs rbST; wk 7, 8.9 +/- 1.0 vs 51.9 +/- 6.8; wk 12, 12.8 +/- 1.4 vs 59.2 +/- 6.4; and wk 24, 5.2 +/- 1.5 vs 42.6 +/- 12.2). There was an age x treatment interaction (P < .0183) for concentrations of IGF-I (nanograms/milliliter) in plasma (C vs rbST; wk 7, 149.7 +/- 6.1 vs 148.6 +/- 8.6; wk 12, 184.1 +/- 12.8 vs 216.6 +/- 15.9; and wk 24, 392.8 +/- 24.8 vs 484.7 +/- 19.9).(ABSTRACT TRUNCATED AT 250 WORDS)

Prepubertal changes in plasma FSH and inhibin in Holstein bull calves: responses to castration and(or) estradiol.

The objectives of two studies were to determine 1) whether plasma concentrations of inhibin (INH) changed with age in prepubertal bulls and whether these changes were related to changes in FSH, testosterone or testis length; and 2) whether castration and(or) estradiol implants affected plasma concentrations of INH and FSH. In Exp. 1, plasma INH remained constant from 4 until 8 wk of age then increased from 120 pM to 202 pM between 8 and 12 wk. Thereafter, INH decreased to 90 pM by 36 wk. Between 4 and 10 wk, plasma FSH increased from .32 to .43 ng/ml, apparently increasing before the initial rise in plasma INH. Between 10 and 12 wk, FSH declined from .43 to .33 ng/ml. After 12 wk, FSH increased as INH decreased. Initial increases in testis length and concentrations of plasma testosterone occurred at 14 wk coincident with the second rise in FSH. In Exp. 2, bull calves were either left intact, castrated, castrated and implanted with estradiol, or left intact and implanted with estradiol at 7.5 wk of age. Castration decreased concentrations of INH and increased concentrations of FSH. Castrated calves implanted with estradiol had decreased concentrations of both INH and FSH. Intact bulls implanted with estradiol had decreased concentrations of FSH relative to intact unimplanted bulls; however, concentrations of INH did not display the age-related changes observed in intact, unimplanted bulls. In summary, age-related changes in plasma INH and FSH occur in bulls. Furthermore, plasma concentrations of INH and FSH increased before changes in gonadal size were detected. The bovine testis may be a major source of circulating INH because castration decreased concentrations of plasma INH.

Effect of naloxone on the secretion of LH in infantile and prepubertal Holstein bull calves.

Administration of naloxone (100 mg i.v.; approximately 1.21 mg/kg body weight0.75) to 10 intact calves (24 weeks of age) caused an acute release of LH that was similar in amplitude and duration to spontaneous discharges of LH that occur at the same age. The naloxone-induced release of LH was abolished in 9/10 calves (intact and castrated) treated with oestradiol-17 beta. To determine the ontogeny of opioid control of secretion of LH, 12 calves were randomly assigned to receive saline or naloxone (1.21 mg/kg body weight0.75, i.v.) at 3, 5, 7, 9, 11, 13, 17 and 21 weeks of age. At each age, blood was collected at 10-min intervals for 4 h and saline or naloxone was administered (i.v.) after collection of the 120-min sample. Before administration of naloxone, plasma LH values increased with age (P less than 0.01) but did not differ between the control and naloxone groups (age x treatment, P greater than 0.05). Administration of naloxone caused concentrations of plasma LH to increase at 3, 11, 13, 17 and 21 weeks of age (treatment x time, P less than 0.001). Concentrations of LH (saline vs naloxone, ng/ml) reached a maximum within 20 min after treatment at Weeks 3 (0.3 vs 1.2), 11 (0.6 vs 2.6), 13 (0.6 vs 3.7), 17 (1.1 vs 2.6), and within 40 min after treatment at Week 21 (1.0 vs 3.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Herpes zoster ophthalmicus with delayed cerebral infarction and meningoencephalitis.

Herpes zoster ophthalmicus can be complicated by a delayed ipsilateral cerebral angiitis which may cause infarction and a smoldering meningoencephalitis. We describe such a case treated successfully with steroids and acyclovir. It is important to consider the diagnosis of this disorder early since therapeutic intervention may prevent an otherwise high morbidity and mortality. Steroids may have to be continued for some time after clinical resolution, using the ESR as a guideline for decreasing dosages.

Luteinizing hormone response to pulsatile luteinizing hormone-releasing hormone in prepubertal heifers.

The effects of 12 hourly 5-micrograms injections of luteinizing hormone-releasing hormone on luteinizing hormone release, were examined in 18 prepubertal Holstein heifers at 4, 7, or 10 mo of age. During a 6-h pretreatment period, mean serum luteinizing hormone concentrations and mean number of endogenous luteinizing hormone episodes per hour were not influenced by age. The 12-h treatment regimen induced a pulsatile release of luteinizing hormone in all heifers. The magnitude, pattern, and total amount of luteinizing hormone released were not influenced by age. However, in the 4 and 10-mo-old age groups, magnitude of luteinizing hormone response to the 3rd hourly injection of luteinizing hormone-releasing hormone was greater than the response to the second injection. Magnitudes of luteinizing hormone responses decreased with time after the 4th hourly injection through the 12th injection and patterns of decline appeared similar among the three age groups. The pituitary of the prepubertal dairy heifer is able to respond to an hourly pulsatile administration of luteinizing hormone-releasing hormone and this treatment regimen appears to produce a self-priming effect on luteinizing hormone release.

Three new strains of infectious pancreatic necrosis virus isolated in Canada.

Three new samples of infectious pancreatic necrosis virus (IPNV) isolated in Canada were compared with known serotypes by phenotypic properties, immunofluorescence, and protein and RNA molecular weights. The three new isolates were each found to be unique by these parameters. The most convincing physical difference used to distinguish the new isolates from known serotypes was their RNA molecular weights. Thus, the new CB, NASRC, and Char isolates of IPNV represent three new strains of the virus.

Evidence that infectious pancreatic necrosis virus has a genome-linked protein.

The double-stranded RNA segments of infectious pancreatic necrosis virus were extracted from virions by a method which avoids proteinase. In contrast to proteinase-treated RNA, such segments (i) exhibited a lower electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels and agarose gels, (ii) had a slightly lower buoyant density, and (iii) demonstrated a marked tendency toward aggregation as observed by electron microscopy. A small amount of protein tightly bound to the RNA could account for the above properties, and a 110,000-dalton protein was liberated from purified virion RNA by sequential digestion with RNase III and RNase A. The amount of radioactivity associated with RNA from virions labeled in vivo with [35S]methionine suggested that an average of 1.4 molecules was bound per RNA segment. Interactions between RNA segments seen in electron micrographs appeared to occur only among the ends of the segments, suggesting these were the exclusive sites of protein attachment.

Persistent infection with infectious pancreatic necrosis virus mediated by defective-interfering (DI) virus particles in a cell line showing strong interference but little DI replication.

The characteristics of chinook salmon embryo cells persistently infected with infectious pancreatic necrosis virus were consistent with defective-interfering (DI) particle-mediated persistence. All the cells were infected and were slowly releasing virus, but they could be cured of virus in the presence of antiserum. Immunofluorescence showed that the amount of virus antigen in persistently infected cells was low. This fact, coupled with the observation that few DI particles were released by these cells, indicated that DI particles were not replicated to excess in this cell line.

Immunofluorescent detection of double-stranded RNA in cells infected with reovirus, infectious pancreatic necrosis virus, and infectious bursal disease virus.

Urea treatment of ethanol-fixed virus-infected cells exposed nucleic acid antigens for immunofluorescence. Three double-stranded (ds) RNA-containing viruses showed bright fluorescence using antibodies against dsRNA. Three single-stranded RNA-containing viruses showed less intense fluorescence with anti-dsRNA. Four out of five cell lines persistently infected with various RNA-containing viruses showed no dsRNA detectable by immunofluorescence.