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Biomedical subjects

K Gunn

Publications and source records attributed to K Gunn.

14 recordsLinked to original sources
PubMed2006

An outbreak of Escherichia coli O157 gastroenteritis in a care home for the elderly.

In the summer of 2001 an outbreak of Escherichia coli O157 gastroenteritis affected staff and residents of a care home for the elderly in the West Midlands, UK. E. coli O157 phage type 2 was isolated from faeces in eight patients and 12 staff members. Thirty-five staff and 40 residents met the case definition for clinical gastrointestinal infection. Serological testing identified a further 14 possible cases of infection amongst asymptomatic staff and residents. The outbreak was atypical, as the disease seemed to be milder than has been observed in past outbreaks in similar settings. The index case, a member of staff, developed bloody diarrhoea and haemolytic-uraemic syndrome (HUS), but only one resident developed bloody diarrhoea and required hospitalization. No deaths occurred, despite the high-risk nature of the affected population. The source of the outbreak could not be identified. The prolonged nature of the outbreak and observed lapses in infection control practices indicated that person-to-person spread was the likely route of transmission. This outbreak illustrates the importance of observing appropriate infection control measures in the institutions providing residential and nursing care to the elderly.

Aged↗
PubMed2005

Urinary catheterization in care homes for older people: self-reported questionnaire audit of catheter management by care home staff.

A self-administered questionnaire was used to determine care home staff's reported knowledge of the urinary catheter care standards published by the National Institute for Clinical Excellence (NICE) and the Association of Continence Care, and to see whether this differed in homes with higher catheterization rates. Seven hundred and fifty out of 1438 (52%) nursing and care staff from 37 randomly selected care homes with high, medium and low catheterization rates responded. There was no difference in reported practice in care homes in the three health districts sampled or those with differing catheterization rates. Eighty-three percent of the nursing staff and 40% of the other care staff received formal catheter care training. However, at least 10% of all staff reported not washing their hands before handling a catheter, and delaying emptying a urine bag until it was full, rather than three-quarters full. Only 45% of nursing staff and 40% of other care staff encouraged residents to empty their own catheter bags. Routine use of catheter maintenance solutions or bladder washouts was reported by 50% of all staff. Nursing staff (29%) and other care staff (54%) took urine specimens from the catheter bag tap. Compliance with standards has improved greatly since an audit in 1998. However, some non-compliance remains. There is a need for ongoing local audit and formal training in urinary catheter care, particularly for non-qualified care staff. Education is needed to ensure local implementation of NICE guidance.

Aged↗
PubMed2003

Prevalence of urinary catheterization in UK nursing homes.

A postal questionnaire survey was undertaken in registered nursing homes in three different health districts in England: Gloucestershire, North Staffordshire and Leeds. Nursing homes may be registered as general nursing or mental health homes. If homes also have provision for residential beds these are defined as dual registered homes. Overall, 9% (438/4900) of residents, with an equal male:female split, had urinary catheters. There was no significant difference in the overall urinary catheterization rate in the three districts (P=0.9). There was a wide range of urinary catheterization prevalence between homes, with some homes of all three categories having no catheterized residents and several with a prevalence of over 40%. The wide range of prevalence may be due to differences in residents' underlying medical conditions or to differences in attitudes towards urinary catheterization by nursing home staff. Almost all homes (114/124, 92%) stated they had an infection control policy, but 31% (38/124) did not have a written policy on urinary catheter care. In view of the potential for morbidity, infection control policies should include a section on the care of urinary catheters and this should form part of the continuing training of nursing home staff.

Aged↗
PubMed2002

The impact of sporadic campylobacter and salmonella infection on health and health related behaviour: a case control study.

The aim of the work was to explore the impact on general and psychological health of those with a proven bacterial gastrointestinal infection and to compare this with controls from whom no bacterial pathogen was identified. A case control study was conducted using an interviewer-administered questionnaire. Thirty-nine cases from whose faeces salmonella or campylobacter had been cultured were compared with matched controls. Reported gastrointestinal symptoms, general health and self-reported hygiene practices were compared. At the time of acute illness the General Household Questionnaire suggested similar levels of morbidity, though by follow up the controls were substantially more likely to be distressed. Cases were more likely to have changed their food preparation practices, to avoid certain eating places and to have been given advice about food preparation. In this small study a positive diagnosis of salmonella or campylobacter seems to have had a reassuring effect when compared with those for whom no diagnosis was made.

Acute Disease↗
PubMed2001

Liver resections in Auckland 1998-2001: mortality, morbidity and blood product use.

AIMS: There has been a marked increase in the number of liver resections undertaken at Auckland Hospital since 1998. Low central venous pressure anaesthesia was routinely used for liver resection during this period. The aim of this study was to review this experience, with particular emphasis on the peri-operative outcomes of morbidity, mortality and blood product use. METHODS: All patients undergoing liver resection from January 1998 to May 2001 were included in the review. Standardised data were collated retrospectively from hospital records and transferred to an electronic database for analysis. RESULTS: Of 123 patients undergoing liver resection, 113 were elctive and ten were urgent operations. 65% had major resections and 10% had synchronous extrahepatic surgery. There were three post-operative deaths (mortality 2.4%) due to liver failure and sepsis. One or more complications occurred in 68 patients (morbidity 55%). 72% did not receive a blood transfusion during their hospital stay. Only two of 113 elective patients required a massive blood transfusion (ten or more units). CONCLUSIONS: Mortality in the study period was low but morbidity remains significant. Blood product use was low in elective patients. These results compare well with those of specialised hepatobiliary units internationally.

Adolescent↗
PubMed1999

Safety and efficacy of target controlled infusion (Diprifusor) vs manually controlled infusion of propofol for anaesthesia.

In this multi-centre, randomized trial, we compared the safety and efficacy of Diprifusor TCI with manually controlled infusion (MCI) of propofol for anaesthesia. With approval, 123 adult male and female patients were studied. Firstly, each investigator anaesthetized five patients to familiarize themselves with Diprifusor TCI. In Stage 2, 98 patients were randomized to receive propofol-based anaesthesia via TCI or MCI. Adjuvant drugs, airway management and monitoring were managed at the discretion of the anaesthetist. Results are presented as mean (SD). Induction times were significantly longer [67 (32) vs 54 (17)s] and induction doses were significantly lower [14 (5) vs 16 (4) ml] in the TCI vs the MCI group. Recovery times and total doses were not significantly different. There were statistically but not clinically significant differences in mean arterial blood pressure and heart rate. Quality of anaesthesia and ease of control of anaesthesia were similar. We conclude that Diprifusor TCI and MCI are similar in terms of safety and efficacy.

Anesthesia, General↗
PubMed1998

Structure and functional relationships in human pur H.

1. The human pur H (ATIC) gene encoding a bifunctional protein, hPurH, which carries the penultimate and final enzymatic activities of the purine nucleotide synthesis pathway, AICARFT & IMPCH, has been cloned and sequenced. The gene product, hPurH has been overexpressed in E. coli, purified to homogeneity and crystallized. 2. The human pur H gene lies on chromosome 2, between band q34 and q35. There is at least one intron of 278 bp near the 5' end. 3. Truncation mutant studies demonstrate two non-overlapping functional domains in the protein arranged as indicated in Figure 5. The existence of a linker or interaction region between the catalytic domains remains to be established. 4. Cleland-type kinetic inhibition experiments indicate that the AICARFT reaction is of the ordered, sequential type with the reduced folate cofactor binding first. 5. The reaction has a broad pH optimum in the alkaline range, with a maximum at about pH 8.2. 6. Preliminary transient phase kinetic studies show the presence of a "burst" indicating that a late step in the reaction sequence is rate limiting. 7. A PurH crystal structure is that of a dimer, with a putative single binding site for the reduced folate cofactor formed using elements from each of the monomer subunits. Probable binding sites for AICAR and FAICAR can be identified on each monomer. 8. Equilibrium sedimentation studies show hPurH apoprotein to be a monomer:dimer equilibrium mixture with a kD of 0.55 uM. 9. The crystal structure has permitted identification of a number of candidate amino acid residues likely to be involved in catalysis and/or substrate binding. Among these, we have thus far completed studies on two, Lysine 265 and Histidine 266. These appear to be critically involved in the AICARFT reaction, although whether their role(s) are in catalysis or binding remains to be determined.

Aminoimidazole Carboxamide↗
PubMed1996

Regulation of membrane and subunit interactions by N-myristoylation of a G protein alpha subunit in yeast.

Initiation of the mating process in yeast Saccharomyces cerevisiae requires the action of secreted pheromones and G protein-coupled receptors. As in other eukaryotes, the yeast G protein alpha subunit undergoes N-myristoylation (GPA1 gene product, Gpa1p). This modification appears to be essential for function, since a myristoylation site mutation exhibits the null phenotype in vivo (gpa1(G2A)). Here we examine how myristoylation affects Gpa1p activity in vitro. We show that the G2A mutant of Gpa1p, when fused with glutathione S-transferase, can still form a complex with the G protein betagamma subunits. The complex is stabilized by GDP and is dissociated upon treatment with guanosine 5'-O-(thiotriphosphate). In addition, there is no apparent difference in the relative binding affinity of Gbetagamma for mutant and wild-type Gpa1p. Using sucrose density gradient fractionation of cell membranes, Gpa1p associates normally with the plasma membrane whereas Gpa1pG2A is mislocalized to a microsomal membrane fraction. A portion of Gbetagamma is also mislocalized in these cells, as it is in a gpa1Delta strain. In contrast, wild-type Gpa1p reaches the plasma membrane in cells that do not express Gbetagamma or cell surface receptors. These findings indicate that mislocalization of Gpa1pG2A is not caused by a redistribution of Gbetagamma, nor is it the result of any difference in Gbetagamma binding affinity. These data suggest that myristoylation is required for specific targeting of Gpa1p to the plasma membrane, where it is needed to interact with the receptor and to regulate the release of Gbetagamma.

Base Sequence↗
PubMed1996

Comparison of methods for analysis of clinical [11C]raclopride studies.

Five different methods for the estimation of the binding potential, a measure of Bmax/Kd, of [11C]raclopride in human striatum were compared using data from a dose ranging study of the neuroleptic CP-88,059-01. Binding potential was estimated indirectly, from distribution volumes in striatum and cerebellum, using both single- and two-tissue compartment models with a metabolite-corrected plasma curve as input function. The two-tissue compartment model was also used for a direct estimate of the binding potential. In addition, a direct estimate was obtained from the reference tissue compartment model using the cerebellum as indirect input function. Finally, an estimate of binding potential was calculated from the ratio of striatum over cerebellum counts at late times after injection. The estimates of striatum binding potential from all methods, except the direct determination using a two-tissue compartment model with metabolite-corrected plasma input function, correlated with each other. Use of an average metabolite correction resulted in only a small reduction in accuracy in this series of normal subjects. The reference tissue model provided estimates of the binding potential with the same sensitivity for detecting changes as those methods that required a metabolite-corrected plasma input function. This indicates that for routine analysis of clinical [11C]raclopride studies, no arterial cannulation is required. The range of normal values was significantly less variable with the reference tissue method than when simple striatum-to-cerebellum ratios were used.

Adult↗
PubMed1995

Clinical sevoflurane metabolism and disposition. II. The role of cytochrome P450 2E1 in fluoride and hexafluoroisopropanol formation.

BACKGROUND: Sevoflurane is metabolized to free fluoride and hexafluoroisopropanol (HFIP). Cytochrome P450 2E1 is the major isoform responsible for sevoflurane metabolism by human liver microsomes in vitro. This investigation tested the hypothesis that P450 2E1 is predominantly responsible for sevoflurane metabolism in vivo. Disulfiram, which is converted in vivo to a selective inhibitor of P450 2E1, was used as a metabolic probe for P450 2E1. METHODS: Twenty-one patients within 30% of ideal body weight, who provided institutional review board-approved informed consent and were randomized to receive disulfiram (500 mg oral, n = 11) or nothing (control, n = 10) the night before surgery, were evaluated. All patients received sevoflurane (2.7% end-tidal, 1.3 MAC) in oxygen for 3 h after propofol induction. Thereafter, sevoflurane was discontinued, and anesthesia was maintained with propofol, fentanyl, and nitrous oxide. Blood sevoflurane concentrations during anesthesia and for 8 h thereafter were measured by gas chromatography. Plasma and urine fluoride and total (unconjugated plus glucuronidated) HFIP concentrations were measured by an ion-selective electrode and by gas chromatography, respectively, during anesthesia and for 96 h postoperatively. RESULTS: Patient groups were similar with respect to age, weight, sex, case duration, and intraoperative blood loss. The total sevoflurane dose, measured by cumulative end-tidal sevoflurane concentrations (3.7 +/- 0.1 MAC-h; mean +/- SE), total pulmonary uptake, and blood sevoflurane concentrations, was similar in both groups. In control patients, plasma fluoride and HFIP concentrations were increased compared to baseline values intraoperatively and postoperatively for the first 48 and 60 h, respectively. Disulfiram treatment significantly diminished this increase. Plasma fluoride concentrations increased from 2.1 +/- 0.3 microM (baseline) to 36.2 +/- 3.9 microM (peak) in control patients, but only from 1.7 +/- 0.2 to 17.0 +/- 1.6 microM in disulfiram-treated patients (P < 0.05 compared with control patients). Peak plasma HFIP concentrations were 39.8 +/- 2.6 and 14.4 +/- 1.1 microM in control and disulfiram-treated patients (P < 0.05), respectively. Areas under the plasma fluoride- and HFIP-time curves also were diminished significantly to 22% and 20% of control patients, respectively, by disulfiram treatment. Urinary excretion of fluoride and HFIP was similarly significantly diminished in disulfiram-treated patients. Cumulative 96-h fluoride and HFIP excretion in disulfiram-treated patient was 1,080 +/- 210 and 960 +/- 240 mumol, respectively, compared to 3,950 +/- 560 and 4,300 +/- 540 mumol in control patients (P < 0.05). CONCLUSIONS: Disulfiram, an effective P450 2E1 inhibitor, substantially decreased fluoride ion and HFIP production during and after sevoflurane anesthesia. These results suggest that P450 2E1 is a predominant P450 isoform responsible for human sevoflurane metabolism in vivo.

1-Propanol↗
PubMed1993

Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and 11C-raclopride.

Positron emission tomography (PET) and 11C-raclopride were used to measure the occupancy of central dopamine D2 receptors by a new neuroleptic, CP-88,059-1. In a double blind dose escalation study, seven healthy male subjects received a predose of between 2 mg and 60 mg CP-88,059-1, 5 h before PET scanning. One additional subject was assigned to placebo predose. Receptor occupancy was defined as the percentage reduction in binding potential compared with that seen in the subject predosed with placebo and with that seen in seven unmedicated normal volunteers previously studied. Binding of 11C-raclopride decreased in a dose dependent manner, and 85% dopamine D2 receptor occupancy was achieved with the highest dose of CP-88,059-1. The findings confirm that brain dopamine D2 receptors are blocked by CP-88,059-1 and suggest that an effective antipsychotic dose will be between 20 mg and 40 mg. The study high-lights the potential of positron emission tomography in the preclinical evaluation of new drugs.

Adult↗
PubMedDate not supplied

Premature ejaculation: definition and prevalence.

Premature ejaculation (PE) is likely the most common sexual dysfunction in men, with a worldwide prevalence of approximately 30%. To date, the lack of a universally acknowledged definition of PE has complicated the examination and analysis of PE in clinical and research-related settings. The impact of PE on men and their partners also needs to be clearly defined. Clearly, a better understanding of the epidemiology of this disorder, especially with regard to prevalence and risk factors, is necessary. The prevalence of PE appears to vary across socio-cultural and geographic populations. The elucidation of the etiology of PE and risk factors associated with PE has been difficult. However, several risk factors for PE exist that have strong support in the literature. Clearly, an improved and universal definition and understanding of PE and its epidemiology will improve the clinical management of PE and the success of future epidemiologic studies and clinical trials.

Clinical Trials as Topic↗