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Biomedical subjects

P R Chadwick

Publications and source records attributed to P R Chadwick.

At least 19 recordsLinked to original sources
PubMed2003

Glutamine deprivation facilitates tumour necrosis factor induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate.

BACKGROUND AND AIMS: Factors that induce luminal bacteria to cross the intestinal epithelium following injury remain poorly defined. The aim of this study was to investigate the interaction between glutamine metabolism, energy supply, and inflammatory mediators in determining the translocation of non-pathogenic bacteria across cultured enterocytes. METHODS: The effect of tumour necrosis factor alpha (TNF-alpha) on translocation of Escherichia coli C25 across Caco-2 epithelial monolayers was studied in the presence of products and inhibitors of glutamine metabolism. Simultaneous measurements of transepithelial electrical resistance (TEER) and flux of lucifer yellow were used to assess effects on the paracellular pathway. Lactate dehydrogenase release was used to monitor enterocyte integrity. Imaging of monolayers in these experimental conditions was undertaken with transmission electron microscopy. RESULTS: Exposure to basolateral TNF-alpha (20 ng/ml) for six hours induced translocation of E coli across Caco-2 but only if accompanied by simultaneous glutamine depletion (p<0.01). Translocation was inhibited by addition of glutamine for two hours (p<0.01) but not by an isonitrogenous mixture of non-glutamine containing amino acids. Inhibition of glutamine conversion to alpha-ketoglutarate, but not blockade of glutathione or polyamine synthesis, also induced translocation in the presence of TNF-alpha. Manipulations that induced bacterial translocation were associated with a marked reduction in enterocyte ATP levels. No effect of these treatments on paracellular permeability or lactate dehydrogenase release was observed. Conditions in which translocation occurred were associated with the presence of bacteria within enterocyte vacuoles but not the paracellular space. CONCLUSIONS: In inflammatory conditions, the availability of glutamine as an enterocyte fuel substrate is essential for the preservation of a functional barrier to microorganisms. In conditions of acute glutamine depletion, cytokine mediated bacterial translocation appears to be primarily a transcellular process.

Adenosine Triphosphate↗
PubMed2002

Increased stool sampling during a waterborne outbreak of cryptosporidiosis does not increase the detection of other faecal pathogens.

AIMS: To ascertain the effect of enhanced surveillance following an outbreak of waterborne cryptosporidiosis on the number of faecal specimens submitted to the local microbiology laboratory and the number positive for common enteric pathogens. The outbreak provided an opportunity to estimate the extent of routine under ascertainment of common enteric pathogens. METHOD: Retrospective search of the computerised microbiology system database for details of faecal examination requests for the period 26 April to 6 June in 1998 and 1999 (period of outbreak). RESULTS: Specimens were received from 378 community patients during the six week period 26 April to 6 June 1999. This was double that for the same period in 1998 (a non-outbreak year). Oocysts of Cryptosporidium parvum were detected in 59 patients, an eightfold increase compared with the same period in 1998. Despite the greater number of patients tested, the detection of other pathogens in patients with gastroenteritis was not altered when compared with the same period in the previous year. CONCLUSION: This study found no evidence of under ascertainment of gastrointestinal infection (common bacterial pathogens and rotavirus) by local general practitioners.

Adolescent↗
PubMed2000

Preventing pancreatic infection in acute pancreatitis.

In acute pancreatitis, pancreatic inflammation may be complicated by the development of pancreatic infection with a high associated mortality. Pancreatic infection is related to the extent of pancreatic inflammation and necrosis and typically occurs in the second or third week of severe disease. It may be associated with a wide range of Gram-positive and Gram-negative bacteria, notably enterobacteria and also with Candida spp. Current surgical practice in the UK is to use prophylactic antimicrobial therapy in patients with severe disease, with the aim of preventing secondary pancreatic infection. Experimental evidence demonstrates that prophylactic antibacterial therapy prevents pancreatic infection and reduces mortality. Furthermore, studies of antibacterial prophylaxis in patients with acute pancreatitis suggest that prophylactic antibacterial therapy is associated with a reduction in mortality, particularly in those with severe disease. In general, broad-spectrum antibiotics have been used in animal and human studies. However, current evidence does not allow comparisons to be made between different antimicrobial agents. Nutritional strategies may also be important in the prevention of pancreatic infection. Enteral, rather than parenteral, nutrition has been associated with an improved clinical outcome in severe pancreatitis.

Acute Disease↗
PubMed2000

Management of hospital outbreaks of gastro-enteritis due to small roundstructured viruses.

Small round structured viruses (SRSVs, Norwalk-like viruses, NLVs) are the most common cause of outbreaks of gastro-enteritis in hospitals and also cause outbreaks in other settings such as schools, hotels, nursing homes and cruise ships. Hospital outbreaks often lead to ward closure and major disruption in hospital activity. Outbreaks usually affect both patients and staff, sometimes with attack rates in excess of 50%. For this reason, staff shortages can be severe, particularly if several wards are involved at the same time. SRSVs may be spread by several routes: faecal-oral; vomiting/aerosols; food and water. Viruses may be introduced into the ward environment by any of these routes and then propagated by person-to-person spread. In an outbreak setting, the diagnosis can usually be made rapidly and confidently on clinical and epidemiological grounds, particularly if vomiting is a prominent symptom. By the time an SRSV outbreak has been recognized at ward level, most susceptible individuals will have been exposed to the virus and infection control efforts must prioritize the prevention of spread of infection to other clinical areas bycontainment of infected/exposed individuals (especially the prevention of patient and staff movements to other areas), hand-hygiene and effective environmental decontamination. This report of the Public Health Laboratory Service Viral Gastro-enteritis Working Group reviews the epidemiology of outbreaks of infection due to SRSVs and makes recommendations for their management in the hospital setting. The basic principles which underpin these recommendations will also be applicable to the management of some community-based institutional outbreaks.

Caliciviridae Infections↗
PubMed1999

Detection of glycopeptide-resistant enterococci in routine diagnostic faeces specimens.

Faeces received in a diagnostic laboratory were screened for glycopeptide-resistant enterococci (GRE) on modified Lewisham medium, with and without enrichment in Enterococcosel broth. Colonization by GRE was detected in 102/838 patients (12.2%). In 74 (73%) of colonized patients GRE were detected by both methods and in 28 (27%) they were detected only after enrichment. The carriage rate in hospitalized patients was 32% (93/289) compared with 2.3% (11/425) in the community (GP patients and food-handlers). Carriage of GRE increased with age. Clostridium difficile isolation was associated with GRE colonization, odds ratio 6.76 (P<0.001). Fifty-nine percent (60/102) of the GRE had the VanA phenotype and 41% (42/102) had the VanB phenotype. In the community VanA predominated (91%), whereas 64% (57/89) of the isolates from hospitalised patients were of the VanB phenotype.

Adolescent↗
PubMed1999

A study of infection in elderly nursing/residential home and community-based residents.

It is commonly believed that patients admitted to hospital from nursing homes/residential homes (NHRH) with infections are less likely to respond to treatment and have a higher fatality rate than counterparts admitted from their own homes ('the Community'). It is also believed that NHRH's harbour a reservoir of unusual and resistant organisms. These preconceptions may influence how these patients are managed. A database of 10593 sequential admissions to a Geriatric Medical unit over a three-year period was used to identify NHRH and community populations with a principal diagnosis of infection. They were investigated using the Department of Microbiology's database. The admission rate in the NHRH group was twice that of the community group. There were no significant differences in length of stay (LOS) [16 +/- 2 vs 17 +/- 2 days (s.e.m.)], or mean survival time (ST)(61 days (37-84) vs 48 days (25-72): 95% confidence intervals) between the two groups. Subgroups of the NHRH group did have significantly different survival times. Fatality rate was not significantly different between the NHRH (40%) or Community (35%) groups. Both the NHRH and community group underwent very similar levels of investigation (189 vs 200 investigations performed). The types and frequencies of pathogen seen in the two groups were very similar.

Aged↗
PubMed1997

Molecular epidemiology of glycopeptide-resistant Enterococcus faecium on a renal unit.

The clinical and molecular epidemiology of glycopeptide-resistant Enterococcus faecium was investigated during an outbreak on a renal unit. Forty-nine patients were colonized or infected during a 15-month period. Sites of colonization included faeces, urine, intravenous (IV) catheter tips and wound swabs. Ten patients had infections, which included five bacteraemias and three episodes of peritonitis. Pulsed-field gel electrophoresis of 43 patient isolates of glycopeptide-resistant E. faecium identified seven strains during the first 7 months of the outbreak. Three of these strains affected five or more patients. One strain accounted for 17/43 isolates. Isolates that were possibly related to another renal unit strain were cultured from patients at two other Manchester hospitals. These isolates were epidemiologically-related, and may represent a single Manchester epidemic strain. Of five patients who had multiple isolates of glycopeptide-resistant E. faecium, three had isolates representing a single strain and two were colonized or infected by more than one strain.

Adult↗
PubMed1997

Strains of glycopeptide-resistant Enterococcus faecium can alter their van genotypes during an outbreak.

Two isolates of Enterococcus faecium with VanA glycopeptide resistance were isolated during a hospital outbreak of E. faecium with plasmid-mediated VanB resistance. Both were found to be identical to the VanB outbreak strain by pulsed-field gel electrophoresis. The genotype of this strain changed from vanB to vanA through an intermediate isolate that contained both the vanA and vanB gene clusters on distinct plasmids.

Anti-Bacterial Agents↗