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The purpose of this study (the third in a series of similar studies) is to evaluate the prevalence of Staphylococcus aureus (SA), methicillin-resistant SA (MRSA) and mupirocin-resistant SA (MuRSA) carriers in a peritoneal dialysis centre where patients have been instructed to use prophylactic mupirocin ointment at the catheter exit site over the last 7 years.

Background: Citizenship and Immigration Canada (CIC) screens immigrants for TB and permits those with inactive pulmonary TB to enter Canada conditionally, subject to medical surveillance; we studied this program in Ontario. Method: This was an administrative database study with linkage of national and provincial data. Results: In 1994–95, 1,341 cases of foreign-born active TB were diagnosed and a CIC record was found for 1,095. 149 (14%) were classified for surveillance and 142 were included in the analysis. A significant proportion (39/142: 27%) were diagnosed either before or as a result of immigration screening in Canada. These persons had arrived as visitors or refugees and were excluded from further analysis. Only 21 of the remaining 103 persons (20%) with immigration screening before the diagnosis of TB adhered to surveillance. Only 1 of 16 (6%) eligible persons was given therapy to prevent future episodes of active TB. Most presented with symptoms (82/103: 82%) suggesting potential for TB transmission in Ontario. Interpretation: The current TB surveillance system for high-risk immigrants to Ontario is not effective in identifying and treating latent infection, and thus not effective in preventing future cases. Contexte: Le ministère de la Citoyenneté et de l’Immigration (CIC) prévoit un dépistage de la tuberculose chez les immigrants et autorise les personnes atteintes de tuberculose pulmonaire latente à entrer au Canada à condition qu’elles se soumettent à une surveillance médicale. Nous avons étudié ce programme en Ontario. Méthode: Nous avons recoupé les données nationales et provinciales d’une base de données de gestion. Résultats: En 1994–1995, on a diagnostiqué 1 341 cas de tuberculose active dans la population née à l’étranger, et 1 095 de ces cas étaient répertoriés par CIC. Notre analyse a porté sur 142 des 149 personnes (14 %) placées sous surveillance médicale par CIC. Une proportion significative de ces personnes (39/142: 27 %) avaient été diagnostiquées avant ou durant le dépistage exigé par l’immigration. Elles étaient entrées au Canada en qualité de visiteurs ou de réfugiés. Seules 21 des 103 personnes restantes (20 %) ayant fait l’objet d’un dépistage de l’immigration avant leur diagnostic de tuberculose respectaient l’obligation de se soumettre à une surveillance médicale. La plupart (82/103: 82 %) présentaient des symptômes, mais 1 seule des 16 personnes admissibles (6 %) était traitée pour une tuberculose latente, ce qui suggère que la tuberculose a pu se propager en Ontario. Interprétation: Le système de surveillance de la tuberculose en vigueur en Ontario pour les immigrants très vulnérables ne parvient pas à détecter et à traiter les infections latentes, ni donc à prévenir les cas futurs.

Escherichia coli verotoxin, also known as Shiga-like toxin, binds to eukaryotic cell membranes via the glycolipid Gb(3) receptors which present the P(k) trisaccharide Galalpha(1-4)Galbeta(1-4)Glcbeta. Crystallographic studies have identified three P(k) trisaccharide (P(k)-glycoside) binding sites per verotoxin 1B subunit (VT1B) monomer while NMR studies have identified binding of P(k)-glycoside only at site 2. To understand the basis for this difference, we studied binding of wild type VT1B and VT1B mutants, defective at one or more of the three sites, to P(k)-glycoside and pentavalent P(k) trisaccharide (pentaSTARFISH) in solution and Gb(3) presented on liposomal membranes using surface plasmon resonance. Site 2 was the key site in terms of free trisaccharide binding since mutants altered at sites 1 and 3 bound this ligand with wild type affinity. However, effective binding of the pentaSTARFISH molecule also required a functional site 3, suggesting that site 3 promotes pentavalent binding of linked trisaccharides at site 1 and site 2. Optimal binding to membrane-associated Gb(3) involved all three sites. Binding of all single site mutants to liposomal Gb(3) was weaker than wild type VT1B binding. Site 3 mutants behaved as if they had reduced ability to enter into high avidity interactions with Gb(3) in the membrane context. Double mutants at site 1/site 3 and site 2/site 3 were completely inactive in terms of binding to liposomal Gb(3,) even though the site 1/site 3 mutant bound trisaccharide with almost wild type affinity. Thus site 2 alone is not sufficient to confer high avidity binding to membrane-localized Gb(3). Cytotoxic activity paralleled membrane glycolipid binding. Our data show that the interaction of verotoxin with the Gb(3) trisaccharide is highly context dependent and that a membrane environment is required for biologically relevant studies of the interaction.

AbstractObjective:To compare three laboratory screening protocols for the detection of methicillin-resistant Staphylococcus aureus(MRSA) from surveillance specimens (mannitol-salt agar containing 2 μg/mL of oxacillin [MSA-2], mannitol-salt agar containing 4 μg/mL of oxacillin [MSA-4], and a broth-containing protocol as recommended by the American Society for Microbiology [M-ASM]).Design:Blinded comparative laboratory study and cost analysis.Setting:University-affiliated microbiology laboratory.Methods:Outcome measurements included rate of detection of MRSA-positive specimens and patients, turnaround time, and media and technologist costs. All MRSA culture swabs obtained from any patient site from November 1998 to April 1999 were included.Results:The M-ASM protocol detected between 19.1% and 32.0% more MRSA-positive specimens and between 13.3% and 23.3% more MRSA-positive patients per surveillance event than the MSA-4 and MSA-2 protocols, respectively. There was no difference in positive-culture reporting time between the M-ASM and MSA-4 protocols. The broth-containing protocol was 2- to 2.5-fold more expensive than the simpler protocols, taking into account media and laboratory personnel costs.Conclusions:It remains to be determined whether it is cost beneficial for a hospital to adopt the M-ASM, as the potential cost of MRSA transmission from unidentified MRSA-colonized patients is unknown. A broth-containing protocol should be considered the gold standard in future studies examining newer MRSA screening protocols.

ABSTRACTThe crystal structure of the verotoxin 1 (VT1) B subunit complexed with a globotriaosylceramide (Gb3) analogue showed the presence of three receptor binding sites per monomer. We wished to study the effects of altering the three sites, singly or in combination, on animal toxicity and cytokine induction in vitro. We found that while the site 1 and 2 mutants were modestly (two- to sevenfold) reduced in their ability to cause disease in BALB/c mice, the site 3 mutant, W34A, was as toxic as VT1. However, all the double-mutant proteins, irrespective of which two sites were mutated, exhibited approximately a 100-fold reduction in their 50% lethal doses for mice. These results suggest that multivalent receptor binding is important in vivo and that all three binding sites make a similar contribution to the latter process. The triple-mutant holotoxin, F30A G62T W34A, administered intraperitoneally without adjuvant, stimulated a strong antibody response in BALB/c mice, and the immune sera neutralized the activity of VT1 in vitro. Induction of tumor neurosis factor alpha release from differentiated human monocytes (THP-1 cells) was relatively impaired for site 1 and site 2 but not site 3 mutants, suggesting an auxiliary role for the latter site in mediation of cytokine release in vitro. Cytotoxicity assays on undifferentiated THP-1 cells have also demonstrated the importance of sites 1 and 2 and the relatively small role played by site 3 in causing cell death. These data suggest an association between the cytotoxicity of the protein and its ability to induce cytokine release.

Background:Shiga-like toxins (SLTs) are produced by the pathogenic strains of Escherichia colithat cause hemorrhagic colitis and hemolytic uremic syndrome. These diseases in humans are generally associated with group II family members (SLT-II and SLT-IIc), whereas SLT-IIe (pig edema toxin) is central to edema disease of swine. The pentameric B-subunit component of the majority of family members binds to the cell-surface glycolipid globotriaosyl ceramide (Gb3), but globotetraosyl ceramide (Gb4) is the preferred receptor for SLT-IIe. A double-mutant of the SLT-IIe B subunit that reverses two sequence differences from SLT-II (GT3; Gln65→Glu, Lys67→Gln, SLT-I numbering) has been shown to bind more strongly to Gb3than to Gb4.

The reproductions shown here are of p. 49 and Fig. XVI (which refers) from A sure guide to buildersby Batty Langley, published in 1729 and dedicated to Thomas Scawen Esq., of Carshalton. The reference is to the construction“of oval-like figures” and the implication, towards the bottom of the page, is clearly that something very close to “an ellipsis” is what Mr. Langley had in mind. The poor plate engraver was hard put to it to draw an ellipse from the instructions in the text and a careful examination of his effort reveals that his final solution was to draw, very faintly, an ellipse and try to fit tangents to it from the divisions along the sides.

• The beneficial effects of delayed closure of contaminated wounds are recognized, but not well defined. Rats with abdominal incisions were infected with Staphylococcus aureus or Escherichia coli and then subgrouped for primary or secondary healing. Noninfected rats served as controls. Between seven and 119 days later, the wounds were subjected to breaking-strength determination, hydroxyproline analysis, and light and scanning electron microscopy. In the controls, secondary closure gave stronger wounds than primary closure. In those infected with S aureus the wounds were stronger than in the primary-closure control group, regardless of the closure method. Of the E coli–infected wounds, those primarily closed were weaker than those secondarily closed. Secondary closure gave infected wounds fewer complications. Biochemical and microscopic examination did not explain these findings.(Arch Surg 1982;117:1189-1193)

Three of 19 strains of Haemophilus ducreyi, isolated during a recent outbreak of chancroid, were found to produce β-lactamase and to harbor a 6.0 × 106-dalton plasmid. Escherichia colitransformed with this plasmid acquired β-lactamase-mediated resistance to ampicillin. The guanine-plus-cytosine content of the plasmid was found to be 41 mol%. Restriction endonuclease digestion studies suggest that a relatively large portion of the Tn1translocon is carried by this plasmid. Whereas this plasmid could not be transferred to H. influenzaeby mating on membrane filters, a strain of H. ducreyiwas able to receive and donate a 30 × 106-dalton ampicillin resistance plasmid from H. influenzae. The ability of H. ducreyito receive and donate conjugative plasmids may result in the appearance of multiply resistant strains.

Background: A multi-organ donor seronegative for hepatitis C virus (HCV) by 1st generation enzyme immunoassay (EIA) supplied 5 solid organs and 2 corneas to 7 recipients. This donor was retrospectively shown to be 2nd generation HCV EIA-positive and polymerase chain reaction (PCR)-positive. All 5 solid organ recipients but none of the corneal recipients developed HCV infection. Objectives: To demonstrate the discordance between serological and PCR-based HCV detection in solid organ transplant recipients and the lack of transmission of HCV to the two corneal transplant recipients. Study design: All 5 solid organ recipients were retrospectively shown to be HCV PCR-negative and -seronegative pre-transplant and HCV PCR-positive post-transplant. Serial serum samples on 3 recipients were evaluated by 2nd generation EIA, a prototypic structural and non-structural dual bead assay (EIA-SA, Abbott), the Chiron Recombinant Immunoblot Assay, 2nd generation (RIBA-2), and the Chiron RIBA HCV Test System Strip Immunoblot Assay 3.0 (RIBA-3, Chiron). Results: The dual bead EIA-SA and RIBA-3 were able to detect HCV seroconversion approximately 6 months earlier than the 2nd generation EIA in 2 recipients, and in 1 recipient only PCR detected infection within the first 10 months. There was no evidence of HCV transmission to the corneal recipients. Conclusions: Although third generation assays such as the RIBA-3 and EIA-SA narrowed the window of HCV seronegativity in transplant recipients compared with the 2nd generation EIA, PCR was the most sensitive method of detecting acute HCV infection. Despite transmission of HCV to all of the solid organ recipients HCV was not transmitted to the corneal transplant recipients.

ABSTRACTShiga toxin-producing Escherichia coli(STEC) O157:H7 is an attaching and effacing pathogen that causes hemorrhagic colitis and the hemolytic-uremic syndrome. Although this organism causes adhesion pedestals, the cellular signals responsible for the formation of these lesions have not been clearly defined. We have shown previously that STEC O157:H7 does not induce detectable tyrosine phosphorylation of host cell proteins upon binding to eukaryotic cells and is not internalized into nonphagocytic epithelial cells. In the present study, tyrosine-phosphorylated proteins were detected under adherent STEC O157:H7 when coincubated with the non-intimately adhering, intimin-deficient, enteropathogenic E. coli(EPEC) strain CVD206. The ability to be internalized into epithelial cells was also conferred on STEC O157:H7 when coincubated with CVD206 ([158 ± 21] % of control). Neither the ability to rearrange phosphotyrosine proteins nor that to be internalized into epithelial cells was evident following coincubation with another STEC O157:H7 strain or with the nonsignaling espBmutant of EPEC.E. coliJM101(pMH34/pSSS1C), which overproduces surface-localized O157 intimin, also rearranged tyrosine-phosphorylated and cytoskeletal proteins when coincubated with CVD206. In contrast, JM101(pMH34/pSSS1C) demonstrated rearrangement of cytoskeletal proteins, but not tyrosine-phosphorylated proteins, when coincubated with intimin-deficient STEC (strains CL8KO1 and CL15). These findings indicate that STEC O157:H7 forms adhesion pedestals by mechanisms that are distinct from those in attaching and effacing EPEC. Taken together, these findings point to diverging signal transduction responses to infection with attaching and effacing bacterial enteropathogens.

The simplest overhand knot, if tied in a strip of paper and carefully pressed flat, forms a regular pentagon (Fig. 1). All higher order polygons can be produced in this way with the single exception of the regular hexagon which requires two strips. The reason for this exception is interesting.

Backache is one of the common symptoms complained of by many patients seeking advice concerning their disabilities. In some instances it assumes the paramount infirmity, particularly in men. In women, this complaint is borne with greater fortitude; they apparently consider that the dull aching variety of backache is a necessary evil, to which they must submit throughout life and the presence of which is admitted only after interrogation.In the recent literature the gynecologists have considered the question of backache from the point of view of that specialty. Sturmdorf1 described gynecopathic myospastic backache in women, and that associated with retroversion. Ward,2 quoting statistical data in his series, stated that 85 per cent of the cases were due to pelvic disease and 15 per cent to orthopedic or nonsurgical conditions. Bullard3 admitted that in fifteen of every hundred patients operated on, the backache persisted after otherwise successful correction

If inhaled irritants lead to airway obstruction, the distribution of ventilation will be altered so that the inspired gas is diverted principally through unobstructed airways. Continued exposure to the irritant will thus establish a vicious cycle in which the irritant will principally be distributed to the healthy airways. In addition, radial diffusion of inspired gas wherever the velocity profile at the front between inspired and alveolar gas is other than blunt will enrich the fast-moving central core with the particulates so that alveolar penetration is deeper than would otherwise be the case.

This article reports on a qualitative study which explored online student engagement experiences in a higher education institution. There are very few studies providing in-depth perspectives on the engagement experiences of online students. The project adopted a case study approach, following 24 online students over one academic year. The setting for the study was an undergraduate online Humanities programme at Dublin City University. The research question for the study was: What themes are central to online student engagement experiences?Data was collected from participant-generated learning portfolios and semi-structured interviews and analysed following a data-led thematic approach. The five central themes that make up the study’s findings highlight key issues of students’ sense of community, their support networks, balancing study with life, confidence, and their learning approaches. The findings of this study indicate that successful online student engagement was influenced by a number of psychosocial factors such as peer community, an engaging online teacher, and confidence and by structural factors such as lifeload and course design. One limitation of the study is that it is a relatively small, qualitative study, its findings provide insights into how online degrees can support online students to achieve successful and engaging learning experiences.

The article discusses the risk factors that could trigger heart disease when getting older. The author explains that the risk factors include cigarette smoking which increases blood pressure, decreases exercise tolerance and increases the tendency for blood to clot, stress caused by upsetting emotional events, high-pressure work or uncontrolled anger, alcohol which could damage heart muscle leading to heart failure, and sleep apnea triggered by obesity, and taking sleeping tablets.

BACKGROUND: Current literature reports that outpatient parenteral antimicrobial therapy (OPAT) programs improve cure rates, and reduce length of hospitalization and costs. OPAT programs are still relatively new in Canada.OBJECTIVE: To evaluate the benefits of an OPAT program initiated at a multispecialty tertiary care facility in Toronto, Ontario, compared with the previous standard of care.METHODS: The present retrospective observational study was conducted using data from a group of surgical patients who were treated for active infections. Between February 1, 2010 and November 30, 2010, a total of 108 surgical patients were enrolled in the OPAT program. Patients were matched 1:1 with historical controls discharged between January 1, 2001 and January 1, 2010 according to age, sex, type of surgery, infection and comorbidities (Charlson Comorbidity Index). Cure rate, 30-day rehospitalization and length of stay were evaluated as primary end points.RESULTS: Of 108 eligible OPAT patients, 21 were matched to the control group using the prespecified criteria. For this cohort, the OPAT program was associated with improved cure rates (OPAT 61.7% versus control 57.1%; P>0.10), reduction in rehospitalization rate (14.3% versus 28.6%; P>0.10) and reduced length of stay (10.7 versus 13.9 days, P>0.10) compared with the control group.CONCLUSIONS: For this cohort of surgery patients, the OPAT program demonstrated a trend toward improved outcomes but did not achieve statistical significance. Due to the lack of statistical power, further evaluation is required to determine the full benefit of OPAT to patients and the health care system.

BACKGROUND: West Nile virus (WNV) is a rapidly spreading infectious disease in North America. Critical care issues related to WNV are not well described.OBJECTIVES: Three cases of severe WNV meningoencephalitis with flaccid paralysis are reported and relevant critical care issues are highlighted.METHODS: Case series and a review of the literature.RESULTS: Three patients with WNV meningoencephalitis and flaccid paralysis were admitted to the authors' academic, tertiary-care intensive care unit (ICU) in the late summer of 2002. All three patients were middle-aged or elderly and presented with a febrile illness that preceded or coincided with their neurological symptoms. Confirmation of WNV infection was problematic because each patient had at least one initial negative serum serology test. Radiological testing yielded nonspecific results. Serial electroencephalograms were consistent with severe toxic metabolic encephalopathy in all cases. All patients had a severe, diffuse axonal polyneuropathy demonstrated by nerve conduction studies and electromyography. Prolonged mechanical ventilation resulted in ICU lengths of stay of 44 to 118 days. At one point, 21% of the ICU beds were dedicated for these patients. All three patients died in hospital -- two following the withdrawal of life support. One patient demonstrated resolving encephalitis and was discharged from the ICU after a 118-day ICU stay, but later died in a step-down unit.CONCLUSIONS: The management of WNV-related critical illness creates challenges in making a timely and accurate diagnosis, and predicting patient morbidity and mortality. As a consequence, end-of-life discussions with families are especially difficult. The prolonged ICU length of stay and growing incidence of this disease may challenge limited critical care resources.

Helicobacter cinaedi (formerly Campylobacter cinaedi) has been associated with enteric disease in homosexual men. The authors report two cases of H cinaedi bacteremia occurring in patients with human immunodeficiency virus (HIV) infection. These cases illustrate that H cinaedi may act as an opportunistic pathogen in patients with HN infection or the acquired immune deficiency syndrome.

In a regional oncology hospital using cotrimoxazole (trimethoprim-sulphamethoxazole) prophylaxis during chemotherapy-induced neutropenia, a single strain of Escherichia coli (indole negative) caused 15 of 27 episodes of Gram-negative rod bacteremia in 1987, and four of 32 such episodes in 1988. This biotype had not been recovered in 1986. Investigations during this ‘outbreak’ of bacteremias revealed enteric colonization with this strain of E coli in 37% of patients on leukemia or bone marrow transplant wards and in several staff members in July 1987. In 1988, 11 of 32 Gram-negative rod bacteremias were secondary to other strains of indole positive E coli of several different biotypes and plasmid profiles. Indole negative strains all exhibited low level trimethoprim resistance, whereas indole positive strains which subsequently appeared exhibited high level trimethoprim resistance. Failure of cotrimoxazole prophylaxis was initially due to the clonal dissemination of a single strain of E coli within the institution, with the subsequent appearance of multiple E coli strains with probable differing genetic bases for their resistance.

The eae gene has recently been shown to be necessary for the attaching and effacing (AE) activity of enteropathogenic Escherichia coli (EPEC) on intestinal epithelial cells. In this paper we report the cloning and nucleotide sequence of a similar gene from a strain of enterohemorrhagic E. coli (EHEC) serotype O157:H7. An EHEC eae sequence was identified which was 97% homologous to the EPEC eae gene for the first 2200 bp and 59% homologous over the last 800 bp. Both eae sequences show 50% homology to the central region of the Yersinia pseudotuberculosis inv gene. The receptor-binding domain of the inv gene product lies near the carboxyl terminus. This suggests that the predicted amino acid sequence divergence in the carboxyl termini of the eae gene products might result in different antigenic and receptor specificity of these putative adhesins.

A randomized, double-blind study was done to compare the efficacy and toxicity of daily single-dose therapy with intravenous ceftriaxone (2 g every 24 h) with daily multiple-dose therapy with cefotaxime (2 g every 6 h) for treatment of serious bacterial infections in nonneutropenic patients. Of the 325 patients who were evaluable for toxicity, 241 (74.2%) were evaluable for efficacy. Infection sites included lung (106), urinary tract (42), skin and soft tissue (43), bone and joint (23), bacteremia (21), and hepatobiliary (5). Definite infections were present in 173cases (71.8%) and possible infections in 68 (28.2%). Analysis of clinical and bacteriologic responses and adverse drug reactions showed no significant differences between the regimens. Values for 95% confidence limits on the differences between regimens for positive clinical and bacteriological outcomes in definite infections were −0.8% to 3.0% and −1.9% to 9.1%, respectively. Thus, daily single-dose therapy with ceftriaxone was comparable to daily multiple-dose therapy with cefotaxime in treating these bacterial infections.

From 1990 to 1993, an outbreak of respiratory Acinetobacter baumannii infection occurred in five intensive care units (lCUs) of a tertiary care center. A. baumannii was subsequently isolated fromdisinfected temperature probes and ventilator circuits. Pulsed-field gel electrophoresis suggested that a single strain accounted for 93% of patient isolates and 88% of environmental isolates. Univariate risk factors for A. baumannii acquisition were tracheostomy (P < .01), ventilation >3 days (P < .01), dialysis (P = .03), Stenotrophomonas maltophilia respiratory colonization (P = .02), parenteral nutrition (P = .05), and enteric feeding (P < .01). Logistic regression analysis showed duration of ventilation and enteric feeding to be independent risk factors. The outbreak strain was relatively antibiotic-susceptible, but the mortality attributable to respiratory A. baumannii acquisition was 23%. Only the APACHE II score was independently associated with increased mortality. Multifacetedcontrol measures, including gas sterilization of temperature probes, terminated the outbreak.