Search

The goal of this document was to provide Canadian laboratories with a framework for consistent reporting and monitoring of multidrug resistant organisms (MDRO) and extensively drug resistant organisms (XDRO) for common gram-negative pathogens. This is the final edition of the interim recommendations, which were modified after one year of broad consultative review. This edition represents a consensus of peer-reviewed information and was co-authored by the Canadian Public Health Laboratory Network and the Canadian Association of Clinical Microbiology and Infectious Diseases. There are two main recommendations. The first recommendation provides standardized definitions for MDRO and XDRO for gram-negative organisms in clinical specimens. These definitions were limited to antibiotics that are commonly tested clinically and, to reduce ambiguity, resistance (rather than non-susceptibility) was used to calculate drug resistance status. The second recommendation identifies the use of standardized laboratory reporting of organisms identified as MDRO or XDRO. Through the broad consultation, which included public health and infection prevention and control colleagues, these definitions are ready to be applied for policy development. Both authoring organizations intend to review these recommendations regularly as antibiotic resistance testing evolves in Canada. [ABSTRACT FROM AUTHOR]

The article presents recommendations for the reporting of extensively drug resistant and pan-drug resistant isolates of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp. and Stenotrophomonas maltophilia. The recommendations provide Canadian laboratories with a framework for consistent reporting and monitoring of multi-drug resistant organisms (MDRO), extensively drug resistant organisms (XDRO), and pan-drug resistant organisms (PDRO).

Objectives: We report the use of IV dalbavancin in Canadian patients using data captured by the national CLEAR registry., Methods: The CLEAR registry uses the web-based data management program, REDCap™ (online survey https://rcsurvey.radyfhs.umanitoba.ca/surveys/?s=TPMWJX98HL) to facilitate clinicians entering details associated with their clinical experiences using IV dalbavancin., Results: Data were available for 40 patients. The most common infections treated were acute bacterial skin and skin structure infection (ABSSSI) (62.5% of patients), bone/joint infection (22.5%), bloodstream/vascular infection (7.5%) and endocarditis (5.0%). Dalbavancin was used as directed (75.0%) and empiric therapy (25.0%). MRSA was the most common identified pathogen (70.0%). Dalbavancin was used both in outpatient (e.g., emergency department) (65.0%), and inpatient treatment settings (e.g., hospital ward) (35.0%). Dalbavancin was used due to the convenience of a single dose treatment (77.5%) as well as to facilitate hospital discharge (7.5%). Dalbavancin was primarily used alone (90.0%), and most commonly using a single 1500 mg dose (77.5%). Microbiological success (pathogen eradicated or presumed eradicated) occurred in 88.2% of known cases, while clinical success (cure and/or improvement) occurred in 93.3% of known cases. No adverse events were reported., Conclusions: In Canada, IV dalbavancin is used as both directed and empiric therapy to treat ABSSSI as well as off-label (bone/joint, bacteremia/vascular, endocarditis, device-related) infections. It is used in both outpatient and inpatient settings due primarily to its convenience as a single-dose treatment regimen and to facilitate early hospital discharge. Dalbavancin use is associated with high microbiological and clinical cure rates along with an excellent safety profile., Competing Interests: Conflict of interests GZ has received research funding from Paladin Labs., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: We report the final results of the clinical usage of ceftobiprole in patients in Canada from data in the national CLEAR (Canadian Le adership on Antimicrobial Real-Life Usage) registry., Research Design and Methods: The authors review the final data using the national ethics approved CLEAR study. Thereafter, the literature is surveyed regarding the usage of ceftobiprole to treat patients with infectious diseases via PubMed (up to March 2024)., Results: In Canada, ceftobiprole is primarily used as directed therapy to treat a variety of severe infections caused by MRSA. It is primarily used in patients failing previous antimicrobials, is frequently added to daptomycin and/or vancomycin with high microbiological and clinical cure rates, along with an excellent safety profile. Several reports attest to the microbiological/clinical efficacy and safety of ceftobiprole. Ceftobiprole is also reported to be used empirically in select patients with community-acquired bacterial pneumonia (CABP), as well as hospital-acquired bacterial pneumonia (HABP)., Conclusions: In Canada, ceftobiprole is used mostly as directed therapy to treat a variety of severe infections caused by MRSA, in patients failing previous antimicrobials. It is frequently added to, and thus used in combination with daptomycin and/or vancomycin with high microbiological/clinical cure rates, and an excellent safety profile.

Background and Objectives: An increasing number of research studies point toward the importance and prevalence of long-term neurocognitive symptoms following infection with COVID-19. Our objectives were to capture the prevalence of cognitive impairments from 1 to 16 months post-COVID-19 infection, assess the changes in neuropsychological functions over time, and identify factors that can predict long-term deficits in cognition., Methodology: A cross-sectional research design was adopted to compare four sub-samples recruited over a 16-month timeframe (1-4, 5-8, 9-12, and 13-16 months). Phone interviews were conducted at least 6 weeks after being infected by COVID-19. Sociodemographic and clinical questionnaires were administered followed by standardized neurocognitive and psychological tests and health questionnaires screening cognitive symptoms, anxiety, depression, fatigue, and autonomy., Results: Regarding general health questionnaires, 55.2% of the 134 participants had symptoms of psychiatric illness, while 21.6% of patients had moderate-to-severe anxiety or depression. Cognitive efficiency was diminished in 19.4% of our population. Executive dysfunction was screened in 56% of patients, and an impairment of cognitive flexibility and inhibition was revealed in 38.8%. Depression, hospital or intensive care unit (ICU) admission, and the duration of hospital or ICU stay were associated with an inhibition deficit. The duration elapsed from the initial infection, and the neurocognitive assessment was not associated with a decrease in inhibition deficit. The prevalence of cognitive impairments, other than inhibition deficit, tended to decrease during the study period., Discussion: This study supports the extensive literature on the cognitive and neuropsychiatric sequelae of COVID-19 and highlights long-lasting inhibition deficits, while other cognitive functions seemed to improve over time. The severity of infection could interact as a catalyst in the complex interplay between depression and executive functions. The absence of a relation between inhibition deficits and sociodemographic or medical factors reinforces the need for cognitive screening in all COVID-19 patients. Future research should focus on inhibition deficits longitudinally to assess the progression of this impairment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Saucier, Jose, Beroual, Al-Qadi, Chartrand, Libert, Losier, Cooling, Girouard, Jbilou and Chamard-Witkowski.)

Background: Insufficient data on the rate and distribution of SARS-CoV-2 infection in Canada has presented a substantial challenge to the public health response to the COVID-19 pandemic. Our objective was to assess SARS-CoV-2 seroprevalence in a representative sample of pregnant people throughout Canada, across multiple time points over 2 years of the pandemic, to describe the seroprevalence and show the ability of this process to provide prevalence estimates., Methods: This Canadian retrospective serological surveillance study used existing serological prenatal samples across 10 provinces over multiple time periods: Feb. 3-21, 2020; Aug. 24-Sept. 11, 2020; Nov. 16-Dec. 4, 2020; Nov. 15-Dec. 3, 2021; and results from the province of British Columbia during a period in which the SARS-CoV-2 B.1.1.529 (Omicron) variant was predominant, from Nov. 15, 2021, to June 11, 2022. Age and postal code administrative data allowed for comparison with concurrent polymerase chain reactivity (PCR)-positive results collected by Statistics Canada and the Canadian Surveillance of COVID-19 in Pregnancy (CANCOVID-Preg) project., Results: Seropositivity in antenatal serum as early as February 2020 indicates SARS-CoV-2 transmission before the World Health Organization's declaration of the pandemic. Seroprevalence in our sample of pregnant people was 1.84 to 8.90 times higher than the recorded concurrent PCR-positive prevalence recorded among females aged 20-49 years in November-December 2020. Overall seropositivity in our sample of pregnant people was low at the end of 2020, increasing to 15% in 1 province by the end of 2021. Seroprevalence among pregnant people in BC during the Omicron period increased from 5.8% to 43% from November 2021 to June 2022., Interpretation: These results indicate widespread vulnerability to SARS-CoV-2 infection before vaccine availability in Canada. During the time periods sampled, public health tracking systems were under-reporting infections, and seroprevalence results during the Omicron period indicate extensive community spread of SARS-CoV-2 infection., Competing Interests: Competing interests: Lori Beach reports receiving funding from the Public Health Agency of Canada (PHAC) and from the Canadian Diagnostic Executive Forum, Toronto, for support for travel to speak at a meeting. Dr. Beach is also division head of Public Outreach and Communications for the Canadian Society of Clinical Chemists. Shelly Bolotin reports receiving support for the present manuscript from COVID-19 Immunity Task Force and Public Health Ontario. Dr. Bolotin is co-investigator on several COVID-19 grants funded by the Canadian Institutes of Health Research (CIHR), the Canadian Immunity Taskforce, the Canadian Immunization Research Network and PHAC. Dr. Bolotin is associate professor at the University of Toronto and, as part of that role, is director of the centre for Vaccine Preventable Diseases at the university. The centre is supported by the Dalla Lana School of Public Health (DLSPH), which receives funding from government, philanthropic, not-for-profit and private-sector organizations. Private-sector funding sources include vaccine manufacturers, specifically Merck, Sanofi and Pfizer. A set of governance processes are in place at the DLSPH to ensure independent operation of the centre. Isabelle Boucoiran reports receiving grants or contracts from Altona, the National Institutes of Health, CIHR and the Québec Ministère de la Santé et des Services Sociaux, and consulting fees from Pfizer. Dr. Boucoiran has also received equipment, materials, drugs, medical writing, gifts or other services from Altona. Mel Krajden reports receiving reagent support from Siemens to assess SARS-CoV-2 serology and had a contract with Hologic to support respiratory virus testing. Vanessa Poliquin reports receiving grants or contracts from GSK as the site principal investigator for a respiratory syncytial virus vaccine study. Dr. Poloquin has received an honorarium from Sanofi Pasteur for teaching at a continuing medical education event and payment for expert testimony from the Department of Justice Canada. George Zahariadis reports receiving support for the current manuscript from the Public Health Agency of Canada, as well as grants or contracts from Genome Atlantic and CIHR. Dr. Zahariadis also reports receiving unrestricted educational funding from Roche and Abbott to the Eastern Health Regional Health Authority to attend virtual meetings and in specific restricted circumstances, travel to educational, technical and research meetings. Dr. Zahariadis is the past president of the National Molecular Users Group. Jason Robinson reports receiving a Roche Ideas Grant including in-kind reagents for previous work on salivary antibody detection. Vanessa Tran reports receiving grants from CIHR, the COVID-19 Immunity Task Force, Canadian Immunization Research Network and PHAC, outside the submitted work. Dr. Tran is also a member of Canadian Immunization Research Network Management Committee and the COVID-19 Immunity Task Force Leadership Group. Deborah Money reports receiving support for the present manuscript from PHAC, paid to the institution on behalf of the COVID-19 Immunity Task Force. Dr. Money has also received past funding for unrelated work from Merck, GSK, Sanofi and Novartis, paid to the institution. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Obesity is a major risk factor for cancer. Conventional thought suggests that elevated adiposity predisposes to heightened inflammatory stress and potentiates tumor growth, yet underlying mechanisms remain ill-defined. Here, we show that tumors from patients with a body mass index >35 carry a high burden of senescent cells. In mouse syngeneic tumor models, we correlated a pronounced accretion of senescent cancer cells with poorly immunogenic tumors when mice were subjected to diet-induced obesity (DIO). Highly immunogenic tumors showed lesser senescence burden suggesting immune-mediated elimination of senescent cancer cells, likely targeted as a consequence of their senescence-associated secretory phenotype. Treatment with the senolytic BH3 mimetic small molecule inhibitor ABT-263 selectively stalled tumor growth in mice with DIO to rates comparable to regular diet-fed mice. Thus, consideration of body adiposity in the selection of cancer therapy may be a critical determinant for disease outcome in poorly immunogenic malignancies.

Attenuating pathological angiogenesis in diseases characterized by neovascularization such as diabetic retinopathy has transformed standards of care. Yet little is known about the molecular signatures discriminating physiological blood vessels from their diseased counterparts, leading to off-target effects of therapy. We demonstrate that in contrast to healthy blood vessels, pathological vessels engage pathways of cellular senescence. Senescent (p16 INK4A -expressing) cells accumulate in retinas of patients with diabetic retinopathy and during peak destructive neovascularization in a mouse model of retinopathy. Using either genetic approaches that clear p16 INK4A -expressing cells or small molecule inhibitors of the anti-apoptotic protein BCL-xL, we show that senolysis suppresses pathological angiogenesis. Single-cell analysis revealed that subsets of endothelial cells with senescence signatures and expressing Col1a1 are no longer detected in BCL-xL-inhibitor-treated retinas, yielding a retina conducive to physiological vascular repair. These findings provide mechanistic evidence supporting the development of BCL-xL inhibitors as potential treatments for neovascular retinal disease., Competing Interests: Declaration of interests At the time of this work, P.R.T., R.D.R., S.Y.C., T.D., S.R.R., R.O., S.A., C.B.Y., D.M., and P.J.B. were employees of UNITY Biotechnology. P.S. is a consultant for UNITY Biotechnology. The rest of the authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The preferred ambulatory IV therapy for cellulitis is often once-daily cefazolin combined with once-daily oral probenecid (C+P). However, due to a national probenecid drug shortage in 2011, our centre developed a replacement protocol for the administration of cefazolin continuous infusion (CCI) using elastomeric infusers. Our goal was to compare treatment efficacy, duration of IV therapy, and recurrence associated with CCI and C+P using retrospective data from our centre., Methods: We conducted a non-inferiority single-centre retrospective cohort study of emergency department medical records. Patients received either C+P (cefazolin 2 g IV once daily plus probenecid 1 g PO once daily) or CCI (cefazolin 2 g IV loading dose, followed by cefazolin 6 g IV via continuous infusion over 24 hours, via an elastomeric infuser). We compared treatment efficacy, duration of IV therapy, and recurrence rates., Results:  total of 203 patients were analyzed, with 107 included in the CCI arm and 96 in the C+P arm. Overall, CCI users and C+P users were comparable in their sociodemographic and clinical variables measured at admission. We observed increased odds of achieving successful treatment among the CCI group, however it did not reach statistical significance (odds ratio [OR] 2.25; 95% CI 0.84 to 6.07). Recurrence rates were similar between both groups (OR 1.91; 95% CI 0.32 to 11.31). The average duration of IV therapy was similar between groups ( p = 0.6)., Conclusions: ith results suggesting that CCI was non-inferior to C+P, and that both approaches required similar treatment durations, CCI could represent an acceptable alternative to C+P for the ambulatory IV treatment of cellulitis., Competing Interests: DLL reports funding to cover travel expenses from Baxter outside the submitted work. LPJ reports travel grants from Baxter Canada outside the submitted work. SE, GG, JC, and MB have nothing to disclose, (Copyright © 2019, Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada).)

During the 2014-15 influenza season, 13/168 respiratory samples from students with influenza-like illness (ILI) at a college in New York, USA, were positive for human adenovirus (HAdV); 4/13 samples were positive for HAdV-B14p1. During influenza season, HAdV should be included in the differential diagnostic panel used to determine the etiology of ILI.

The majority of studies on lethal radiobiological damage have focused on double-strand breaks (DSBs), a type of clustered DNA damage and the evaluation of their toxicity, while other types of clustered DNA damage have received much less attention. The main purpose of this study is to evaluate the contribution of different lesions induced by ionizing radiation to the loss of plasmid DNA functionality. We employed a simple model system comprising E. coli transformed with an irradiated plasmid [pGEM-3Zf (-)] to determine the effect of DSBs and other lesions including base damage and clustered lesions on the functionality ("viability") of the plasmid. The yields of γ-radiation-induced single-strand breaks (SSBs) and DSBs were measured by gel electrophoresis. We found that the transformation efficiency decreases with radiation dose, but this decrease cannot be explained by the formation of DSBs. For example, at doses of 500 and 700 Gy, the relative transformation efficiency falls from 100% to 53% and 26%, respectively, while only 5.7% and 9.1% of the plasmids contain a DSB. In addition, it is also unlikely that randomly distributed base lesions could explain the loss of functionality of the plasmid, since cells can repair them efficiently. However, clustered lesions other than DSBs, which are difficult to repair and result in the loss of information on both DNA strands, have the potential to induce the loss of plasmid functionality. We therefore measured the yields of γ-radiation-induced base lesions and cluster damage, which are respectively converted into SSBs and DSBs by the base excision repair enzymes endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg). Our data demonstrate that the yield of cluster damage (i.e., lesions that yield DSBs following digestion) is 31 times higher than that of frank DSBs. This finding suggests that frank DSBs make a relatively minor contribution to the loss of DNA functionality induced by ionizing radiation, while other toxic lesions formed at a much higher frequencies than DSBs must be responsible for the loss of plasmid functionality. These lesions may be clustered lesions/locally multiply damaged sites (LMDS), including base damage, SSBs and/or intrastrand and interstrand crosslinks, leading to the loss of vital information in the DNA. Using a mathematical model, we estimate that at least three toxic lesions are required for the inactivation of plasmid functionality, in part because even these complex lesions can be repaired.

We describe 3 culture-proven cases of adenovirus serotype 14 infection in New Brunswick, Canada, during the summer of 2011. Strains isolated from severely ill patients were closely related to strains of a genomic variant, adenovirus 14p1, circulating in the United States and Ireland. Physicians in Canada should be aware of this emerging adenovirus.

Introduction: Little is known about the role of herpes simplex virus (HSV) type 1 (HSV1) in the epidemiology of genital herpes in Canada. Data on herpes viral cultures for two consecutive years obtained from L'Hôpital Dr GL Dumont, which performs all the viral culture testing in New Brunswick, were reviewed. It was hypothesized that HSV1 was the main cause of genital herpes in New Brunswick., Methods: Samples of genital origin sent to the laboratory for HSV culture testing between July 2006 and June 2008 were analyzed. Samples from an unspecified or a nongenital source were excluded from analysis. Multiple positive samples collected from the same patient were pooled into a single sample., Results: HSV was isolated from 764 different patients. HSV1 was isolated in 62.6% of patients (male, 55%; female, 63.8%). HSV1 was isolated in 73.2% of patients 10 to 39 years of age and in 32% of patients ≥40 years of age. The difference in rates of HSV1 infection between the 10 to 39 years of age group and the ≥40 years of age group was statistically significant (P<0.001 [χ(2)]). In a similar Canadian study performed in Nova Scotia, HSV1 was recovered in 53.7% of positive cultures (male, 36.7%; female, 58.1%). The rates of HSV1 infection reported by this study and the present study were significantly different (P<0.001 [χ(2)] for male, P=0.012 for female)., Conclusion: In New Brunswick, HSV1 is the dominant type of HSV isolated in samples collected from a genital site. Significant rate differences were demonstrated between the groups 10 to 39 years of age and ≥40 years of age., Introduction: Little is known about the role of herpes simplex virus (HSV) type 1 (HSV1) in the epidemiology of genital herpes in Canada. Data on herpes viral cultures for two consecutive years obtained from L’Hôpital Dr GL Dumont, which performs all the viral culture testing in New Brunswick, were reviewed. It was hypothesized that HSV1 was the main cause of genital herpes in New Brunswick., Methods: Samples of genital origin sent to the laboratory for HSV culture testing between July 2006 and June 2008 were analyzed. Samples from an unspecified or a nongenital source were excluded from analysis. Multiple positive samples collected from the same patient were pooled into a single sample., Results: HSV was isolated from 764 different patients. HSV1 was isolated in 62.6% of patients (male, 55%; female, 63.8%). HSV1 was isolated in 73.2% of patients 10 to 39 years of age and in 32% of patients ≥40 years of age. The difference in rates of HSV1 infection between the 10 to 39 years of age group and the ≥40 years of age group was statistically significant (P<0.001 [χ 2 ]). In a similar Canadian study performed in Nova Scotia, HSV1 was recovered in 53.7% of positive cultures (male, 36.7%; female, 58.1%). The rates of HSV1 infection reported by this study and the present study were significantly different (P<0.001 [χ 2 ] for male, P=0.012 for female)., Conclusion: In New Brunswick, HSV1 is the dominant type of HSV isolated in samples collected from a genital site. Significant rate differences were demonstrated between the groups 10 to 39 years of age and ≥40 years of age.

Our proprietary preparation obtained by extraction of Chlorella pyrenoidosa cells, ONC-107 (Respondin), was recently found to selectively boost antibody response to the influenza vaccine in a human clinical trial. Respondin is a potent stimulator of mouse B cell proliferation and an activator of macrophages. Bioactivity-guided resolution concluded that Respondin is composed of a mixture of immunostimulatory principles of different chemical nature. A combination of size exclusion, anion exchange and hydrophobic interaction chromatography revealed that the bulk of the immunostimulatory activity resides in polysaccharide/protein complexes with molecular masses larger than 100 kDa that are composed primarily of galactose, rhamnose and arabinose.

Niemann-Pick type II disease is an autosomal recessive disorder characterized by a defect in intracellular trafficking of sterols. We have determined the intron/exon boundaries of eight exons from the conserved 3' portion of NPC1, the gene associated with most cases of the disease. SSCP analyses were designed for these exons and were used to identify the majority of mutations in 13 apparently unrelated families. Thirteen mutations were found, accounting for 19 of the 26 alleles. These mutations included eight different missense mutations (including one reported by Greer et al. [1998]), one 4-bp and two 2-bp deletions that generate premature stop codons, and two intronic mutations that are predicted to alter splicing. Two of the missense mutations were present in predicted transmembrane (TM) domains. Clustering of these and other reported NPC1 mutations in the carboxy-terminal third of the protein indicates that screening of these exons, by means of the SSCP analyses reported here, will detect most mutations. The carboxy-terminal half of the Npc1 protein shares amino acid similarity with the TM domains of the morphogen receptor Patched, with the largest stretch of unrelated sequence lying between two putative TM spans. Alignment of this portion of the human Npc1 protein sequence with Npc1-related sequences from mouse, yeast, nematode, and a plant, Arabidopsis, revealed conserved cysteine residues that may coordinate the structure of this domain. That 7 of a total of 13 NPC1 missense mutations are concentrated in this single Npc1-specific domain suggests that integrity of this region is particularly critical for normal functioning of the protein.

Niemann-Pick type D (NPD) disease is a progressive neurodegenerative disorder characterized by the accumulation of tissue cholesterol and sphingomyelin. This disorder is relatively common in southwestern Nova Scotia, because of a founder effect. Our previous studies, using classic linkage analysis of this large extended kindred, defined the critical gene region to a 13-cM chromosome segment between D18S40 and D18S66. A recently isolated gene from this region, NPC1, is mutated in the majority of patients with Niemann-Pick type C disease. We have identified a point mutation within this gene (G3097-->T; Gly992-->Trp) that shows complete linkage disequilibrium with NPD, confirming that NPD is an allelic variant of NPC1.

Previous reports concerning the location of D18S44 with respect to the centromere have been ambiguous. Also, it has not been possible, based on formerly reported markers, to show that contigs WC18.0 and WC18.1 overlap. However, the data presented here definitively show, using FISH technology, that D18S44 (located on WC18.0) maps to proximal 18q. Furthermore, inter-Alu fingerprinting shows a clear overlap between WC18.0 and WC18.1, thereby establishing a complete contig between D18S44 and markers from WC18.1.

Niemann-Pick type II disease is a severe disorder characterized by accumulation of tissue cholesterol and sphingomyelin and by progressive degeneration of the nervous system. This disease has two clinically similar subtypes, type C (NPC) and type D (NPD). NPC is clinically variable and has been identified in many ethnic groups. NPD, on the other hand, has been reported only in descendants of an Acadian couple who lived in Nova Scotia in the early 18th century and has a more homogeneous expression resembling that of less severely affected NPC patients. Despite biochemical differences, it has not been established whether NPC and NPD are allelic variants of the same disease. We report here that NPD is tightly linked (recombination fraction .00; maximum LOD score 4.50) to a microsatellite marker, D18S480, from the centromeric region of chromosome 18q. Carstea et al. have reported that the NPC gene maps to this same site; therefore we suggest that NPC and NPD likely result from mutations in the same gene.

The catalytic activity of the adenovirus cysteine peptidase is increased by a specific 11-amino-acid peptide adduct (GVQSLKRRRCF, referred to as pVIc). To identify additional peptides which might bind and alter the activity of the protease, a cysteine-constrained random peptide phage library was screened. Of 29 different phages which were isolated, 7 contained the consensus sequence VEGGS. Despite a superficial similarity to the substrate cleavage site of the protease, the peptide was not digested by the enzyme. VEGGS and pVIc altered protease activity similarly without sharing sequence similarity. To similar degrees, pVIc and VEGGS (a) stimulated the activity of the recombinant protease, (b) had no effect on viral protease, (c) increased the fluorescence emission of tryptophan residues in the protease, suggesting a conformational change, and (d) inhibited wt virus infection, but rescued ts1 infection at the nonpermissive temperature. The experiments also suggest that once the protease has been stimulated by one peptide, the other peptide has no further activity on the recombinant adenovirus cysteine protease, suggesting that the two peptides bring about the same change on the protease via different binding sites.

We describe four children with severe supraglottic infections caused by group A beta-hemolytic streptococci. In each case the clinical presentation suggested Hemophilus influenzae epiglottitis. In only one patient was there significant involvement of the epiglottis, whereas all had striking inflammation of the aryepiglottic folds. Group A beta-hemolytic streptococcus was isolated in blood cultures in two patients and from the supraglottic area and trachea in two others. Fever persisted for 6 to 22 days, and tracheal intubation was necessary for 2 to 16 days, despite appropriate antibiotic therapy. The evolution of streptococcal supraglottitis may be protracted, and it must be managed accordingly.

The incidence of nausea and vomiting after strabismus surgery was studied in 64 children aged one to six years. Incidence was determined in the post-anaesthesia recovery room (PARR), in the same day surgery (SDS) unit, and at home on days one and two after the operation. After induction of anaesthesia, the children received an intravenous injection of droperidol (50 micrograms . kg-1) or saline in a double-blind randomized fashion, and an intravenous injection of glycopyrrolate (7.5 micrograms . kg-1) or atropine (10 micrograms . kg-1) in an open randomized fashion. The incidence of emetic symptoms was highest in the SDS unit and at home on day one. Droperidol slightly but significantly delayed awakening and was not, at least in this particular age group, associated with any difference in postoperative sickness. Despite theoretical advantages, glycopyrrolate offered no significant benefit over atropine as far as postoperative emesis was concerned.