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It is well established that extreme prematurity can be associated with cerebellar lesions potentially affecting the neurologic prognosis. One of the commonly observed lesions in these cases is pontocerebellar hypoplasia resulting from prematurity, which can pose challenges in distinguishing it from genetically caused pontocerebellar hypoplasia. This confusion leads to unacceptable and prolonged diagnostic ambiguity for families as well as difficulties in genetic counseling. Therefore, it is crucial to identify the clinical and neuroradiologic features allowing to differentiate between acquired and genetic forms of pontocerebellar hypoplasia in order to guide clinical practices and improve patient care. In this regard, we report in the present manuscript the clinical, developmental, and radiologic characteristics of 19 very premature children (gestational age <28 weeks, now aged 3-14 years) with cerebellar lesions and discuss the causal mechanisms. Our findings support the notion that a combination of specific clinical and radiologic criteria is essential in distinguishing between acquired and genetic forms of pontocerebellar hypoplasia., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Pediatric spinal low-grade glioma (LGG) and glioneuronal tumours are rare, accounting for less 2.8-5.2% of pediatric LGG. New tumour types frequently found in spinal location such as diffuse leptomeningeal glioneuronal tumours (DLGNT) have been added to the World Health Organization (WHO) classification of tumours of the central nervous system since 2016, but their distinction from others gliomas and particularly from pilocytic astrocytoma (PA) are poorly defined. Most large studies on this subject were published before the era of the molecular diagnosis and did not address the differential diagnosis between PAs and DLGNTs in this peculiar location. Our study retrospectively examined a cohort of 28 children with LGGs and glioneuronal intramedullary tumours using detailed radiological, clinico-pathological and molecular analysis. 25% of spinal PAs were reclassified as DLGNTs. PA and DLGNT are nearly indistinguishable in histopathology or neuroradiology. 83% of spinal DLGNTs presented first without leptomeningeal contrast enhancement. Unsupervised t-distributed stochastic neighbor embedding (t-SNE) analysis of DNA methylation profiles showed that spinal PAs formed a unique methylation cluster distinct from reference midline and posterior fossa PAs, whereas spinal DLGNTs clustered with reference DLGNT cohort. FGFR1 alterations were found in 36% of spinal tumours and were restricted to PAs. Spinal PAs affected significantly younger patients (median age 2 years old) than DLGNTs (median age 8.2 years old). Progression-free survival was similar among the two groups. In this location, histopathology and radiology are of limited interest, but molecular data (methyloma, 1p and FGFR1 status) represent important tools differentiating these two mitogen-activated protein kinase (MAPK) altered tumour types, PA and DLGNT. Thus, these molecular alterations should systematically be explored in this type of tumour in a spinal location., (© 2022. The Author(s).)

Background: Myhre syndrome (MS) is a rare genetic disease characterized by skeletal disorders, facial features and joint limitation, caused by a gain of function mutation in SMAD4 gene. The natural history of MS remains incompletely understood., Methods: We recruited in a longitudinal retrospective study patients with molecular confirmed MS from the French reference center for rare skeletal dysplasia. We described natural history by chaining data from medical reports, clinical data warehouse, medical imaging and photographies., Results: We included 12 patients. The median age was 22 years old (y/o). Intrauterine and postnatal growth retardation were consistently reported. In preschool age, neurodevelopment disorders were reported in 80% of children. Specifics facial and skeletal features, thickened skin and joint limitation occured mainly in school age children. The adolescence was marked by the occurrence of pulmonary arterial hypertension (PAH) and vascular stenosis. We reported for the first time recurrent strokes from the age of 26 y/o, caused by a moyamoya syndrome in one patient. Two patients died at late adolescence and in their 20 s respectively from PAH crises and mesenteric ischemia., Conclusion: Myhre syndrome is a progressive disease with severe multisystemic impairement and life-threathning complication requiring multidisciplinary monitoring., (© 2022. The Author(s).)

Background: The Public Health Agency of Canada's integrated bio-behavioural surveillance system-Tracks surveys-assesses the burden of HIV, hepatitis C and associated risks in key populations in Canada. From 2018-2020, Tracks surveys were successfully implemented by First Nations Health Services Organizations in Alberta and Saskatchewan., Methods: First Nations-led survey teams invited community members who identified as First Nations, Inuit or Métis to participate in Tracks surveys and testing for HIV, hepatitis C and syphilis. Information was collected on social determinants of health, use of prevention services, substance use, sexual behaviours and care for HIV and hepatitis C. Descriptive statistics are presented., Results: Of the 1,828 survey participants, 97.4% self-identified as First Nations and 91.4% lived in an on-reserve community. Over half (52.2%) were cisgender female, average age was 36.3 years, 82.5% lived in stable housing, 82% had access to primary healthcare and 73.8% reported having good to excellent mental health. Most participants (97%) had a family member who had experienced residential school. High proportions experienced stigma and discrimination (65.6%), financial strain (64.3%) and abuse in childhood (65.1%). Testing for HIV (62.8%) and hepatitis C (55.3%) was relatively high. Prevalence of HIV was 1.6% (of whom 64% knew their infection status). Hepatitis C ribonucleic acid prevalence was 5% (44.9% of whom knew their current infection status)., Conclusion: Historical and ongoing experiences of trauma, and higher prevalence of hepatitis C were identified, reaffirming evidence of the ongoing legacies of colonialism, Indian Residential Schools and systemic racism. High participation in sexually transmitted blood-borne infection testing and prevention reflect the importance of First Nations-led culturally sensitive, safe and responsive healthcare services and programs to effect improved outcomes for First Nations peoples., Competing Interests: Competing interests: None.

Foreign body ingestion is a frequent issue in paediatrician's practice. Foreign bodies often pass the gastro-intestinal tract spontaneously but can sometimes generate complications (1% of the cases). The migration of ingested foreign bodies is rare, but their spontaneous extrusion through the skin is even rarer and was previously described only in the neck. We report an unusual case of a spontaneous extrusion of an ingested foreign body through the skin of the lower abdomen. Observation: A 2 year-old boy, presented with a 2cm inflammatory swelling of the hypogastric region. Laboratory analysis showed hyperleukocytosis (16 7770 /mm3) and high C reactive protein level at 12mg/L. Ultrasonography and computed tomography allowed us to diagnose a parietal foreign body extruding through the skin and to eliminate associated complication (perforation, vascular fistula…). The foreign body was extracted by a surgical incision. This observation is very rare but it is also uncommon because of the nature of the ingested foreign body which was a wooden piece. Its ingestion was explained by a paediatric mental disorder.

Background: The correlation between vedolizumab trough levels during induction therapy and mucosal healing remains unknown., Aim: To compare early vedolizumab trough levels in patients with and without mucosal healing within the first year after treatment initiation., Methods: We prospectively collected vedolizumab trough levels in all inflammatory bowel disease patients at weeks 2, 6 and 14 of vedolizumab treatment in three French referral centres between 1 June 2014 and 31 March 2017. Results of every patient that underwent mucosal assessment by magnetic resonance imaging and/or endoscopy in the first year after treatment initiation were analysed., Results: Median vedolizumab trough levels in the overall population (n = 82) were 27 μg/mL (interquartile range, IQR 21.2-33.8 μg/mL) at week 2, 23 μg/mL (IQR 15-34.5 μg/mL) at week 6 and 10.7 μg/mL (IQR 4.6-20.4 μg/mL) at week 14. Only median vedolizumab trough levels at week 6 differed between patients with and without mucosal healing within the first year after treatment initiation (26.8 vs 15.1 μg/mL, P = 0.035). A cut-off trough level of 18 μg/mL at week 6 predicted mucosal healing within the first year after the start of vedolizumab with an area under the receiver operating curve of 0.735 (95% confidence interval 0.531-0.939). A vedolizumab trough level above 18 μg/mL at week 6 was the only independent variable associated with mucosal healing within the first year of treatment (odds ratio 15.7, 95% confidence interval 2.4-173.0, P = 0.01)., Conclusion: Early therapeutic drug monitoring might improve timely detection of vedolizumab-treated patients in need for an intensified dosing regimen., (© 2018 John Wiley & Sons Ltd.)

Background: Tuberculosis continues to disproportionately affect many Indigenous populations in the USA, Canada, and Greenland. We aimed to investigate whether population-based tuberculosis-specific interventions or changes in general health and socioeconomic indicators, or a combination of these factors, were associated with changes in tuberculosis incidence in these Indigenous populations., Methods: For this population-based study we examined annual tuberculosis notification rates between 1960 and 2014 in six Indigenous populations of the USA, Canada, and Greenland (Inuit [Greenland], American Indian and Alaska Native [Alaska, USA], First Nations [Alberta, Canada], Cree of Eeyou Istchee [Quebec, Canada], Inuit of Nunavik [Quebec, Canada], and Inuit of Nunavut [Canada]), as well as the general population of Canada. We used mixed-model linear regression to estimate the association of these rates with population-wide interventions of bacillus Calmette-Guérin (BCG) vaccination of infants, radiographic screening, or testing and treatment for latent tuberculosis infection (LTBI), and with other health and socioeconomic indicators including life expectancy, infant mortality, diabetes, obesity, smoking, alcohol use, crowded housing, employment, education, and health expenditures., Findings: Tuberculosis notification rates declined rapidly in all six Indigenous populations between 1960 and 1980, with continued decline in Indigenous populations in Alberta, Alaska, and Eeyou Istchee thereafter but recrudescence in Inuit populations of Nunavut, Nunavik, and Greenland. Annual percentage reductions in tuberculosis incidence were significantly associated with two tuberculosis control interventions, relative to no intervention, and after adjustment for infant mortality and smoking: BCG vaccination (-11%, 95% CI -6 to -17) and LTBI screening and treatment (-10%, -3 to -18). Adjusted associations were not significant for chest radiographic screening (-1%, 95% CI -7 to 5). Declining tuberculosis notification rates were significantly associated with increased life expectancy (-37·8 [95% CI -41·7 to -33·9] fewer cases per 100 000 for each 1-year increase) and decreased infant mortality (-9·0 [-9·5 to -8·6] fewer cases per 100 000 for each death averted per 1000 livebirths) in all six Indigenous populations, but no significant associations were observed for other health and socioeconomic indicators examined., Interpretation: Population-based BCG vaccination of infants and LTBI screening and treatment were associated with significant decreases in tuberculosis notification rates in these Indigenous populations. These interventions should be reinforced in populations still affected by tuberculosis, while also addressing the persistent health and socioeconomic disparities., Funding: Public Health Department of the Cree Board of Health and Social Services of James Bay., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Contact investigations are a critical component of tuberculosis control in high-income countries. However, the relative success of conventional methods by population group and place of residence is unknown. This study compares outcomes of contact investigations of Canadian-born Indigenous tuberculosis cases living on- and off-reserve with other Canadian-born cases., Methods: In a retrospective analysis, Canadian-born adult culture-positive pulmonary TB cases (2001-2010) were identified. Characteristics of source cases and their contacts were compared by population group. Outcomes of contact investigations, including completion of recommended investigations and preventive therapy, were compared in multivariable analysis., Results: Of 171 cases of tuberculosis identified, 49 (29%) were Indigenous on-reserve, 62 (36%) Indigenous off-reserve, and 60 (35%) non-Indigenous or Canadian-born, "other". Indigenous people had more contacts identified per case compared to non-Indigenous patients. Case population group and smear status were the main predictors of the success of contact investigations. Of those recommended preventive therapy, close contacts of Indigenous cases on-reserve had the highest rate of completion, at 54%, vs. 41% and 37% for close contacts of Indigenous living off-reserve and Canadian-born "other" respectively (p = 0.02). Contacts of Indigenous cases living off-reserve had the greatest delay in assessment and the lowest rates of completion of assessment and preventive therapy. In multivariable analysis, population group, smear status of source case and proximity of contact were predictors of preventive therapy acceptance and/or completion., Conclusions: Significant differences in outcomes of contact investigations were observed between population groups. The higher priority of contacts of smear-positive cases appears to influence efficiency of service delivery, regardless of population group. Jurisdictional differences in program delivery, resource availability and perceived risk of transmission likely influence outcomes of contact investigations.

Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most significant pathogens affecting global public health and health care systems. In Canada and the United States, the spread of MRSA is primarily attributed to a single dominant epidemic clone: CMRSA10/USA300. Despite this, the CMRSA7/USA400 epidemic clone has been reported to be the predominate epidemic clone in several Canadian provinces and some parts of the United States. This study examined the epidemiology of CMRSA7/USA400 MRSA in Alberta, Canada, from June 2005 to December 2012. Molecular characterization of CMRSA7/USA400 isolates was done using spa, SCCmec, PVL, and PFGE typing and identified two predominant spa types in Alberta: t128 and t1787. Although closely related, these spa types have distinct geographic distributions. From 2010 to 2012, the number of t128 infections has remained stable while there has been a nearly 3-fold increase in the number of provincial t1787 infections, accompanied by 10-fold increases in t1787 infection rates in some communities. Most t128 and t1787 patients were First Nations or Inuit people, and isolates were usually from skin and soft tissue infections in outpatients. t128 patients were significantly older than t1787 patients. Antimicrobial susceptibility testing showed higher mupirocin resistance in t1787 than in t128 MRSA. Improved strategies to reduce or stabilize t1787 infections in Alberta are needed., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Purpose: Severe Combined Immune Deficiency (SCID) is universally fatal unless treated with hematopoietic stem cell transplantation (HSCT). Following the identification of disseminated Bacille Calmette-Guérin (BCG) infections in Canadian First Nations, Métis and Inuit (FNMI) children with unrecognized primary immune deficiencies, a national surveillance study was initiated in order to determine the incidence, diagnosis, treatment and outcome of children with SCID in Canada., Methods: Canadian pediatricians were asked to complete a monthly reporting form if they had seen a suspected SCID case, from 2004 to 2010, through the Canadian Paediatric Surveillance Program (CPSP). If the case met CPSP SCID criteria, more detailed data, including demographics and clinical information about investigations, treatment and outcome was collected., Results: A total of 40 cases of SCID were confirmed for an estimated incidence of SCID in non-FNMI Canadian children of 1.4 per 100,000 live births (95 % CI 1 to 1.9/100,000). The proportion of SCID cases that were FNMI (17.5 %) was almost three times higher than was expected on the basis of proportion of the pediatric population estimated to be FNMI (6.3 %) resulting in an estimated incidence of 4.4 per 100,000 live births (95 % CI 2.1 to 9.2/100,000) in FNMI Canadian children. The mean age at diagnosis for all SCID cases was 4.2 months (range 1–583 days). There were 12 deaths (30 %; 95 % CI 18–46 %); seven died of confirmed or suspected infections before they could receive an HSCT., Conclusions: The frequency of SCID cases in FNMI children is higher than in the general Canadian pediatric population. The high mortality rate, due primarily to infection, suggests that early diagnosis by newborn screening followed by HSCT could significantly benefit children with SCID.

Background: The tuberculin skin test (TST) is often used to screen for latent tuberculosis infection (LTBI) in school children, many of whom were bacille Calmette-Guérin (BCG)-vaccinated in infancy. The reliability of the TST in such children is unknown., Methods: TSTs performed in low-risk BCG-vaccinated and -nonvaccinated grade 1 and grade 6 First Nations (North American Indian) school children in the province of Alberta, Canada, were evaluated retrospectively. To further assess the specificity of the TST, BCG-vaccinated children with a positive TST (≥10 mm of induration) and no treatment of LTBI were administered a QuantiFERON-TB Gold In-Tube test (QFT-GIT, Cellestis International)., Results: A total of 3996 children, 2063 (51.6%) BCG-vaccinated and 1933 (48.4%) BCG-nonvaccinated, were screened for LTBI. Vaccinated children were more likely than nonvaccinated children to be TST positive (5.7% vs. 0.2%, P < 0.001). Vaccinated children with a positive TST were more likely to have a recent past TST as compared with those with a negative TST (6.8% versus 2.8%, P = 0.01). Among 65 BCG-vaccinated TST-positive children who underwent a QFT-GIT, only 5 (7.7%; 95% CI: 2.5%, 17.0%) were QFT-GIT positive. A TST of ≥15 mm was more likely to be associated with a positive QFT-GIT than a TST of 10 to 14 mm, 16.0% (95% CI: 4.5%, 36.1%) versus 2.5% (95% CI: 0.1%, 13.2%), P = 0.047., Conclusion: The TST is unreliable in school children, BCG-vaccinated in infancy, and who are at low risk of infection. The QFT-GIT is a useful confirmatory test for LTBI in BCG-vaccinated TST-positive school children.

Hypothesis: Local wound management using a simple wound-probing protocol (WPP) reduces surgical site infection (SSI) in contaminated wounds, with less postoperative pain, shorter hospital stay, and improved patient satisfaction., Design: Prospective randomized clinical trial., Setting: Academic medical center., Patients: Adult patients undergoing open appendectomy for perforated appendicitis were enrolled from January 1, 2007, through December 31, 2009., Interventions: Study patients were randomized to the control arm (loose wound closure with staples every 2 cm) or the WPP arm (loosely stapled closure with daily probing between staples with a cotton-tipped applicator until the wound is impenetrable). Intravenous antibiotic therapy was initiated preoperatively and continued until resolution of fever and normalization of the white blood cell count. Follow-up was at 2 weeks and at 3 months., Outcome Measures: Wound pain, SSI, length of hospital stay, other complications, and patient satisfaction., Results: Seventy-six patients were enrolled (38 in the WPP arm and 38 in the control arm), and 49 (64%) completed the 3-month follow-up. The patients in the WPP arm had a significantly lower SSI rate (3% vs 19%; P = .03) and shorter hospital stays (5 vs 7 days; P = .049) with no increase in pain (P = .63). Other complications were similar (P = .63). On regression analysis, only WPP significantly affected SSI rates (P = .02). Age, wound length, body mass index, abdominal circumference, and diabetes mellitus had no effect on SSI. Patient satisfaction at 3 months was similar (P = .69)., Conclusions: Surgical site infection in contaminated wounds can be dramatically reduced by a simple daily WPP. This technique is not painful and can shorten the hospital stay. Its positive effect is independent of age, diabetes, body mass index, abdominal girth, and wound length. We recommend wound probing for management of contaminated abdominal wounds.

Objective: To determine colorectal and overall cancer incidence as part of a three-pronged investigation in response to the concerns of a First Nations community in Alberta, Canada, located close to sulfur-rich natural gas installations, and to determine whether the incidence of cancers observed in this reserve was higher than expected., Methods: A population dataset with information identifying First Nations status and band affiliation was linked to the Alberta Cancer Registry to determine cancer incidence cases between 1995 and 2006 for on- and off-reserve study populations. Using indirect standardized incidence ratios, observed cancer incidence cases for the study populations were compared with cases expected based on three separate reference populations., Results: Observed colorectal and overall cancer incidence cases within the First Nations community were not higher than expected. Cervical cancer incidence cases, however, were higher than expected for on- and off-reserve populations; public health measures designed to address this risk have been implemented and on-going surveillance of cancer incidence in the community will be maintained.

In May 2005, a cluster of four hantavirus pulmonary syndrome (HPS) cases was confirmed in Alberta, Canada. The cluster is unusual given that three cases were from a single family and involved a 7-year-old child. This is the first family cluster reported in Canada and includes one of the youngest cases of HPS reported in North America.

Background: On April 1, 2004, BCG (bacille Calmette-Guérin), a tuberculosis (TB) control vaccine, was discontinued in all but four high-risk communities in Alberta. To confirm the safety of vaccine withdrawal, and for future planning, the annual risk of infection (ARI) was determined in preschool First Nations children., Methods: First Nations children born into reserve communities in Alberta between April 1, 1998 and March 31, 2004, and still living on reserve in 2004-2005, were identified. Health centre TB histories were validated by cross-referencing the birth cohort with the provincial TB Registry. Children that were not BCG vaccinated and not known to be tuberculin skin test (TST) positive underwent a TST. Birth cohort children were grouped as follows: (i) BCG vaccinated; (ii) BCG non-vaccinated, no TST; (iii) BCG non-vaccinated, TST; (iv) BCG vaccination status unknown. The ARI was calculated and the age and community characteristics of the groups were compared., Results: There were 8447 children in the 6-year birth cohort, 4699 (55.6%) vaccinated, 2696 (31.9%) non-vaccinated, and 1052 (12.5%) whose vaccination status was unknown. Of the non-vaccinated children, 1921 (71.3%) were tested and only 2 were TST positive. No other TST positive, BCG non-vaccinated children were identified in the TB Registry cross-match. The prevalence of infection in 2004-2005 was 0.1% and the ARI was 0.03%. The community risk of TB exposure was comparable in tuberculin-tested and non-tested BCG non-vaccinated children., Conclusion: In low BCG-uptake First Nations communities in Alberta, the ARI is low and it is safe to withdraw BCG.

Objectives: Sexual partnerships can be viewed as networks in order to study disease transmission. We examined the transmission of Neisseria gonorrhoeae in a localised outbreak in Alberta, Canada, using measures of network centrality to determine the association between risk of infection of network members and their position within the sexual network. We also compared risk in smaller disconnected components with a large network centred on a social venue., Methods: During the investigation of the outbreak, epidemiological data were collected on gonorrhoea cases and their sexual contacts from STI surveillance records. In addition to traditional contact tracing information, subjects were interviewed about social venues they attended in the past year where casual sexual partnering may have occurred. Sexual networks were constructed by linking together named partners. Univariate comparisons of individual network member characteristics and algebraic measures of network centrality were completed., Results: The sexual networks consisted of 182 individuals, of whom 107 were index cases with laboratory confirmed gonorrhoea and 75 partners of index cases. People who had significantly higher information centrality within each of their local networks were found to have patronised a popular motel bar in the main town in the region (p = 0.05). When the social interaction through the bar was considered, a large network of 89 individuals was constructed that joined all eight of the largest local networks. Moreover, several networks from different communities were linked by individuals who served as bridge populations as a result of their sexual partnering., Conclusion: Asking clients about particular social venues emphasised the importance of location in disease transmission. Network measures of centrality, particularly information centrality, allowed the identification of key individuals through whom infection could be channelled into local networks. Such individuals would be ideal targets for increased interventions.

Background: The tuberculosis control strategy of vaccinating First Nations newborns with BCG (bacille Calmette-Guerin) is currently undergoing re-evaluation in Canada. Review of recent pediatric tuberculosis morbidity could inform this re-evaluation., Methods: Potential source cases and pediatric cases of tuberculosis from Alberta First Nations were identified over the 10 years 1991-2000. The distribution of pediatric disease was described. The effect of BCG on tuberculosis morbidity in two large outbreaks was determined., Results: A total of 57 potential source cases and 41 pediatric cases of tuberculosis were reported from 17 (41.5%) and 8 (19.5%) of the 41 on-reserve First Nation Community Health Centres, respectively. Three outbreaks traceable to three source cases accounted for 34 (18, 3, and 13, respectively) of the 41 (82.9%) pediatric cases. Each outbreak was spatially and temporally separate from the other. Each outbreak strain of Mycobacterium tuberculosis had a unique DNA fingerprint. In the largest outbreaks, disease-to-infection ratios (secondary case rates) were higher in newly infected unvaccinated versus vaccinated close pediatric contacts (12/13 [92.3%] versus 7/15 [46.7%], p=0.02), but the infection rate was almost certainly falsely high in the BCG vaccinated. One unvaccinated child had a brain tuberculoma in addition to primary pulmonary tuberculosis., Conclusion: For most Alberta First Nations communities, the spatial and temporal distribution of disease, and the meager impact on morbidity, challenge the rationale for continued use of BCG.

Background: In January 2001 we investigated an outbreak of Neisseria gonorrhoeae in a northern region of Alberta, Canada, and here we report on the epidemiology of the outbreak., Goal: The goal was to examine the outbreak etiology and make recommendations for strengthening regional STD programs., Study Design: Provincial STD notification forms were reviewed to identify cases, and a case-control study was undertaken to identify risk factors for infection., Results: Gonorrhea was reported among 81 individuals, aged 15 to 60 years, between January 1999 and March 2001 in 8 neighboring communities. Attendance at a public bar in one community was associated with infection (P < 0.01). Cases were predominantly Aboriginal (96.3%) and aged less than 30 years (77.6%), and at least 39% of cases reported multiple sex partners. Casual partnering and extended sexual networks are believed to have influenced the spread of infection., Conclusion: This study emphasizes the importance of site-specific health interventions to effectively target at-risk individuals at high-risk locations, with preventive measures aimed at members of high-risk sexual networks. Effective interventions must ensure the availability of and access to appropriate health services for all residents of northern regions in Alberta.

While injuries due to a hypoxic state commonly appear later in both intestinal crypts and basal portion of the villi than in the apical portion, a nonhomogeneous distribution of blood flow in the intestinal mucosa may be supposed. The presence of two different microvascular plexuses inside the mucosa, corresponding to the cryptal plexus and the villous plexus, supports the above hypothesis. This work studies the intestinal microvasculature in shocked versus normal rats. Forty-five rats were divided into four groups to study the histological damage and the microvascular bed by ink injection, fluorescent microsphere infusion, and resin injection for scanning electron microscopy (SEM) of vascular corrosion cast (VCC) observations. An infusion pressure of 100 +/- 5 mm Hg was used in control animals, while 30 +/- 5 mm Hg infusion pressure was adopted for controls as well as for shocked animals to simulate physiological or shock conditions. Hemorrhagic shock was induced by removing blood and maintaining a mean arterial pressure of 30 +/- 5 mm Hg for 45-120 mins. A close connection among the patterns of microvasculature obtained with VCC and ink injection technique can be appreciated. In normal rats the whole microvasculature was visualized, but in both normal and shocked animals injected at low pressure different patterns could be found, generally showing a highly incomplete visualization of the vascular network. A significant decrease of visualization of both the entire microvasculature and the villous plexus is present in shocked animals when compared to unshocked controls, while no difference in the cryptal plexus visualization was observed. These observations suggest that the cryptal plexus is perfused preferentially during hemorrhagic shock, as a consequence of its peculiar microvascular organization. This may explain the relative resistance of the crypts, compared to villi, to hypoxic injuries in order to sustain endocrine function and the regenerative capability of the mucosa after prolonged hypoperfusion conditions that can lead to villous damage and temporary loss of the intestinal barrier function.

We describe four children who died of suffocation by rubber balloons in Canada between 1983 and 1988. In the United States, at least 121 children have died in a similar manner in the 15 years between 1973 and 1988 according to a report by the US Consumer Product Safety Commission. Although the highest mortality occurred among infants, 30 (25%) of the 121 deaths occurred in children 6 years of age or older. Balloons account for 43% of the approximately 15 childhood deaths related to children's products that are documented each year by the Consumer Product Safety Commission. Toy rubber balloons are thus the leading cause of pediatric choking deaths from children's products. Preventive efforts should be directed toward a ban on this type of balloon and the development of safer alternatives. Meanwhile, public information campaigns should alert parents, physicians, and policymakers to the dangers of toy rubber balloons.

A 42-year-old man with a 26-year history of duodenal ulcer volunteered for a 24-hour intragastric pH monitoring study, at which time his fasting gastrin concentration was found to be elevated. Secretin injection decreased the serum gastrin concentration. When not on treatment his total gastrin, gastrin-17 (G-17), and gastrin-34 (G-34) response to a protein-containing breakfast was marked. Immunocytochemical staining of antral biopsies showed hyperplasia of gastrin-containing cells, more pronounced for G-17 than for G-34. Cimetidine or cimetidine plus pirenzepine increased 24-hour intragastric pH, whereas pirenzepine alone rendered the gastric contents more acidic, particularly overnight. The total serum gastrin concentrations increased after meals and were unaffected by cimetidine or pirenzepine; enprostil, however, reduced the postprandial increase in total gastrin, G-34, and G-17. After six weeks of treatment with enprostil, the number of cells containing G-17 and G-34 was reduced. The findings show that G-cell hyperplasia may occur in the presence of a normal fasting serum gastrin concentration; fasting serum gastrin concentrations may fluctuate widely over time; the food-stimulated increase in G-17 was greater than that for G-34, and is associated with more pronounced antral hyperplasia for G-17 and G-34; and enprostil blunts the postprandial increase in G-17, G-34, and total gastrin. These observations suggest that enprostil may reduce G-cell hyperplasia and hypergastrinemia.

A 56-year-old woman newly diagnosed as having Zollinger-Ellison syndrome due to a metastatic gastrinoma underwent 24-hour intragastric pH monitoring, serum gastrin (total, G-17 and G-34) measurements, and immunoperoxidase staining of duodenal, antral, and gastric body biopsies for gastrin, somatostatin, and serotonin. Determinations were made while the patient was given different doses of ranitidine, enprostil (a synthetic orally administered prostaglandin E2), or ranitidine plus enprostil. Following are the findings from this single-patient study: Intragastric pH was persistently low but varied in response to food when the patient was given ranitidine. Immunocytochemical staining of antral biopsies obtained before the patient was treated revealed a reduced number of cells containing G-17 and G-34 but an increase in the antral somatostatin-containing D-cells. Treatment with 35 micrograms of enprostil BID plus 300 mg of ranitidine BID for two and 11 weeks was associated with an increased number of duodenal G-cells, a decrease in antral D-cells, and a decrease in the number of antral serotonin-containing cells. Enprostil in a dosage of 35 or 70 micrograms BID had no effect on intragastric pH, but when enprostil was given in combination with ranitidine, postprandial and nocturnal intragastric alkalinity was accentuated along with a return of duodenal and antral G-cells and a loss of the antral D-cell hyperplasia. Optimal pH control was achieved with 300 mg of ranitidine BID; more frequent dosing with ranitidine did not further increase intragastric pH. Both the total serum gastrin concentration and G-17 levels fluctuated in response to meals. The serum concentrations of total gastrin, G-17, and G-34 were reduced with enprostil and with ranitidine.