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Biomedical subjects

C Graham

Publications and source records attributed to C Graham.

At least 37 records · Page 2Linked to original sources
PubMed2003

Characterization of Escherichia coli strains causing urinary tract infections in patients with transposed intestinal segments.

PURPOSE: Transposition of intestinal segments into the urinary tract predisposes to urinary tract infections. We characterized bacterial infections in these patients and examined the virulence genotype and persistence of Escherichia coli isolates. MATERIALS AND METHODS: We followed 26 patients who underwent bladder reconstructive surgery using transposed intestinal segments. E. coli strains isolated from the urine of these patients were genotyped for established virulence determinants and the frequency of carriage was compared with E. coli strains isolated from community acquired urinary infections and the fecal flora of anonymous volunteers. A longitudinal study of E. coli strains in 9 patients was also done using pulsed field gel electrophoresis. RESULTS: E. coli was the most frequently isolated organism, responsible for 59% (62 of 105) of monobacterial infections. Other bacteria isolated included Klebsiella species, Proteus species and Enterococcus faecalis. Community acquired E. coli strains were more likely to carry multiple determinants for particular adhesins (P and S fimbriae) and toxins (alpha-hemolysin and cytotoxic necrotizing factor) than fecal strains. Carriage frequency for bladder reconstruction strains was intermediary and not significantly different. The key finding was that E. coli strains persisted for prolonged periods, including 2 years in certain patients, often despite various antimicrobial treatments. CONCLUSIONS: This study highlights that further steps must be taken to prevent and treat urinary tract infections in this susceptible group. Particular attention should be given to the treatment of persistent infections.

Adult↗
PubMed2002

Characterization of a type IIb sodium-phosphate cotransporter from zebrafish (Danio rerio) kidney.

Zebrafish (Danio rerio) express two isoforms of the type IIb Na-dependent P(i) cotransporter (NaPi). Type NaPi-IIb1 has previously been cloned and characterized. Here, we report the cloning of the NaPi-IIb2 transcript from zebrafish kidney, its localization, and its functional characterization. RT-PCR with renal RNA and degenerate NaPi-IIb-specific primers resulted in a specific fragment. 3'-Rapid amplification of cDNA ends yielded a product that contained typical NaPi-IIb characteristics such as a cysteine-rich COOH terminus and a PDZ (PSD95- Dlg-zona occludens-1) binding motif. Several approaches were unsuccessful at cloning the 5' end of the transcript; products lacked an in-frame start codon. The missing information was obtained from an EST (GenBank accession number ). The combined clone displayed a high degree of homology with published type IIb cotransporter sequences. Specific antibodies were raised against a COOH-terminal epitope of both NaPi-IIb1 and NaPi-IIb2 isoforms. Immunohistochemical mapping revealed apical expression of both isoforms in zebrafish renal and intestinal epithelia, as well as in bile ducts. The novel clone was expressed in oocytes, and function was assayed by the two-electrode voltage-clamp technique. The function of the new NaPi-IIb2 clone was found to be significantly different from NaPi-IIb1 despite strong structural similarities. NaPi-IIb2 was found to be strongly voltage sensitive, with higher affinities for both sodium and phosphate than NaPi-IIb1. Also, NaPi-IIb2 was significantly less sensitive to external pH than NaPi-IIb1. The strong structural similarity but divergent function makes these zebrafish transporters ideal models for the molecular mapping of functionally important regions in the type II NaPi-cotransporter family.

Amino Acid Sequence↗
PubMed2002

Repeatability of long and short echo-time in vivo proton chemical-shift imaging.

We carried out long (145 ms) and short (25 ms) echo time spectroscopic imaging of the brain (chemical-shift imaging, CSI) on two occasions 1 week apart on 15 healthy individuals. We found coefficients of variation (CVs) generally in the range 10-25% for long and 15-30% for short echo-time measurements. The CVs of metabolite ratios were higher by about 5-10%. Limits of agreement (defined as mean+/-2 SD of the week 1-week 2 differences) were wider at the shorter echo time. The modest repeatability may be due in part to the difficulty of repositioning spectroscopic voxels at a scale of 1 mm. The generally higher CVs and wider limits of agreement at TE25 ms suggest that the increased spectral complexity more than offsets the theoretical advantage of increased signal at short echo-times. Analysis of variance general linear modelling of metabolites and metabolite ratios showed that, in general, the subject, region of the brain and hemisphere were more important than the occasion in explaining the variability of results. Unless information on short-T2 metabolites is specifically required, better results can probably be achieved with longer echo-times. The magnitude of the CVs needs to be taken into account in the calculation of sample size for cross-sectional or linear studies.

Adult↗
PubMed2002

Linkage disequilibrium analysis of chromosome 12q14-15 in multiple sclerosis: delineation of a 118-kb interval around interferon-gamma (IFNG) that is involved in male versus female differential susceptibility.

We have recently reported the association of a polymorphic intronic CA-repeat in the interferon-gamma gene (IFNG) with gender bias in susceptibility to multiple sclerosis (MS) in a Sardinian population. This association could refer to a functional polymorphism within IFNG or could be due to linkage disequilibrium between the IFNG marker and a neighbouring susceptibility locus. Within the average reach of linkage disequilibrium, various other candidate genes are located. Among these the most striking ones are the genes coding for the cytokines interleukin-22 (IL-22) and interleukin-26 (IL-26) that constitute together with IFNG a cytokine cluster on chromosome 12q14. To determine more precisely the location of this gender-associated susceptibility locus, we have now performed a more extensive linkage disequilibrium screen of this region using nine additional microsatellite markers. This locus appeared to be confined to a 118-kb interval that is bordered by the markers D12S313 and D12S2511, in which IFNG itself remains the main candidate gene. Haplotype analysis confirmed that this MS-associated locus protects males from developing MS according to a recessive or allele-dosage model. Our results indicate that the well-documented gender differences in susceptibility to MS are at least partially caused by genetic factors in the region surrounding IFNG.

Adolescent↗
PubMed2002

Series of incidents of Listeria monocytogenes non-invasive febrile gastroenteritis involving ready-to-eat meats.

AIMS: A series of cases and outbreaks of febrile noninvasive gastrointestinal disease involving 31 identified cases was investigated in terms of the numbers and types of Listeria monocytogenes present in the suspect foods (ready-to-eat meats) and clinical samples from cases. METHODS AND RESULTS: Foods and faecal samples involved in the incidents were tested for the presence and number of L. monocytogenes. Isolates were typed by macrorestriction analysis using pulsed-field gel electrophoresis. The foods contained high levels of L. monocytogenes, in one case 1.8 x 10(7) g-1. Faecal samples contained L. monocytogenes for up to 15 d after the contaminated food was consumed. All isolates from the food and faecal samples were of serotype 1/2 and were indistinguishable from one another by macrorestriction typing. CONCLUSIONS: It is likely that the meats were contaminated either during their manufacture after they had been cooked or by underprocessing. The long shelf lives on these products would have allowed the contaminating L. monocytogenes to grow to the high numbers measured in this study, causing food poisoning as described. SIGNIFICANCE AND IMPACT OF THE STUDY: Outbreaks of febrile noninvasive listeriosis are relatively rare. This report adds ready-to-eat meats to the range of foods that have acted as vehicles for such outbreaks.

Bacterial Typing Techniques↗
PubMed2002

The social functioning of older adults with schizophrenia.

A cross-sectional survey of the social functioning of community dwelling older adults was undertaken. Older adults with no psychiatric morbidity, depressed older adults and older adults with schizophrenia were surveyed to see if there were differences in the level of social functioning of the three groups. The setting was two old age psychiatric services, one in an urban area of London and the other in a semi-rural area of Leicestershire. Participants consisted of depressed (n = 81) or normal (n = 101) older persons identified as part of a general practice over 75 years check and clients over 65 years with schizophrenia (n = 30) known to mental health teams for older adults. All participants were interviewed by one of two trained researchers and completed the Mini-Mental State Examination questionnaire, the 15-item Geriatric Depression Scale, a social functioning questionnaire, and the Schedules for Clinical Assessment in Neuropsychiatry or the Brief Psychiatric Rating Scale. In our sample population, community dwelling older persons without any psychiatric diagnosis were the least isolated from their local community, reported more private leisure activities, and had the least contact with professional community services. Clients with schizophrenia reported more isolation from their local community and fewer private leisure activities than clients with a diagnosis of depression.

Aged↗
PubMed2002

An evaluation of the performance of XLD, DCA, MLCB, and ABC agars as direct plating media for the isolation of Salmonella enterica from faeces.

AIMS: To compare the performance of four media, singly and in combination, as direct plating media for the isolation of Salmonella enterica from human faeces. METHODS: Two thousand four hundred and nine routine, faecal samples received by four laboratories were inoculated on to xylose lysine desoxycholate (XLD), desoxycholate citrate (DCA), mannitol lysine crystal violet brilliant green (MLCB), and alpha-beta chromogenic (ABC) agars using standardised protocols, reagents, and data collection. Isolates of presumptive salmonellae were identified using standard laboratory techniques and the results were analysed statistically. RESULTS: Direct plating recovered 46 of the 60 possible isolates of Salmonella spp recovered via enrichment broth. No isolates were recovered from direct plating that were not recovered via selenite enrichment. MLCB gave the highest isolation rate individually (84.8%) and amounts of competing flora (CF) did not affect the recognition of colonies. ABC proved highly specific, but insensitive, and isolation rates were adversely affected by any amount of CF. Isolation rates from XLD and DCA were only affected when the CF load was heavy. DCA was least specific, with only 9.01% of picks positive and greatest number of confirmatory tests. XLD and MLCB, in combination, gave the highest isolation rate. CONCLUSIONS: Where the earlier results of direct plating may be advantageous, XLD and MLCB provide the optimal combination. For non-typhi salmonellae, MLCB is the best, single direct plating medium. For routine diagnostic work, XLD is most effective.

Bacteriological Techniques↗
PubMed2002

A national study of clinical and laboratory factors affecting the survival of patients with multiple drug resistant tuberculosis in the UK.

BACKGROUND: This study aimed to describe the clinical, microbiological, molecular epidemiology and treatment of multidrug resistant tuberculosis (MDRTB) cases in the UK and to determine factors associated with survival. METHODS: Ninety MDRTB cases were identified from 1 January 1996 to 30 June 1997; 69 were DNA fingerprinted. Date of diagnosis was determined and data were collated on key demographic factors, clinical, radiological and treatment details. Variables associated with survival were included in a Cox proportional hazards model. RESULTS: Most of the patients (72.4%) were male, born outside the UK (57.1%), were sputum smear positive (82.2%), and had entered the UK more than 5 years previously (61.9%). Thirty eight of 78 cases (48.7%) had prior TB. Sufficient data on 82 patients were available for survival analysis; 20/27 (74.1%) known to be dead at the end of the observation period had died of tuberculosis. Median survival time overall was 1379 days (95% CI 1336 to 2515) or 3.78 (95% CI 3.66 to 6.89) years (858 days (95% CI 530 to 2515) in immunocompromised individuals (n=32) and 1554 (95% CI 1336 to 2066) days in immunocompetent cases (n=48)). Median survival in patients treated with three drugs to which the bacterium was susceptible on in vitro testing (n=62) was 2066 days (95% CI 1336 to 2515) or 5.66 years, whereas in those not so treated (n=13) survival was 599 days (95% CI 190 to 969) or 1.64 years. CONCLUSIONS: Immunocompromised status, failure to culture the bacterium in 30 days or to apply appropriate three drug treatment, and age were significant factors in mortality. An immunocompromised patient was nearly nine times more likely to die, while application of appropriate treatment reduced the risk (risk ratio 0.06). Increasing age was associated with increasing risk of death (risk ratio 2.079; 95% CI 1.269 to 3.402)-that is, for every 10 year increase in age the risk almost doubled. Overall survival was lower than that reported in previous studies.

Adolescent↗
PubMed2001

Cloning and characterization of 13 novel transcripts and the human RGS8 gene from the 1q25 region encompassing the hereditary prostate cancer (HPC1) locus.

The aim of this study was to develop a saturated transcript map of the region encompassing the HPC1 locus to identify the susceptibility genes involved in hereditary prostate cancer (OMIM 176807) and hyperparathyroidism-jaw tumor syndrome (OMIM 145001). We previously reported the generation of a 6-Mb BAC/PAC contig of the candidate region and employed various strategies, such as database searching, exon-trapping, direct cDNA hybridization, and sample sequencing of BACs, to identify all potential transcripts. These efforts led to the identification and precise localization on the BAC contig of 59 transcripts representing 22 known genes and 37 potential transcripts represented by ESTs and exon traps. Here we report the detailed characterization of these ESTs into full-length transcript sequences, their expression pattern in various tissues, their genomic organization, and their homology to known genes. We have also identified an Alu insertion polymorphism in the intron of one of the transcripts. Overall, data on 13 novel transcripts and the human RGS8 gene (homologue of the rat RGS8 gene) are presented in this paper. Ten of the 13 novel transcripts are expressed in prostate tissue and represent positional candidates for HPC1.

Amino Acid Sequence↗
PubMed2001

Melatonin and 6-OHMS in high-intensity magnetic fields.

We determined if all-night exposure to 60 Hz magnetic fields at an intensity well within the upper range of occupational exposures (resultant intensity = 127.3 microTesla [muT]) resulted in suppression of melatonin or its major metabolite 6-hydroxymelatonin-sulfate (6-OHMS) in the first-void morning urine of 24 healthy male volunteers. Measures collected after continuous and intermittent magnetic field exposure test conditions were compared to similar measures collected after an equivalent no-exposure control condition. Urinary concentrations of melatonin and 6-OHMS did not differ as a function of type of magnetic field exposure, nor did they differ between field exposure and control conditions. These results demonstrate that the nocturnal secretion and metabolism of melatonin are not altered in humans by field exposure at an intensity over 600 times higher than that typically encountered in the home.

Adult↗
PubMed2001

All-night exposure to EMF does not alter urinary melatonin, 6-OHMS or immune measures in older men and women.

Healthy men (n = 22) and women (n = 24), 40-60 years of age, were exposed all-night (23:00-07:00 hr) to 60-Hz magnetic fields at an intensity (resultant flux density = 28.3 microTesla [microT]) well within the occupational-exposure range, or sham exposed under equivalent, counter-balanced, no-exposure ( < or = 0.2 microT) control conditions. Concentrations of melatonin, and the major metabolite of melatonin, 6-hydroxymelatonin-sulfate (6-OHMS), in first-void morning urine were not altered in either gender by exposure to the magnetic field, compared to control conditions. Statistical analysis also failed to reveal any evidence for exposure-related alterations in blood concentrations of multiple hematologic and immune system parameters (CD3, CD4, CD8, natural killer [NK] cells). The present results replicate and extend earlier negative findings based on the exposure of young men to power-frequency magnetic fields.

Adult↗
PubMed2001

Tuberculosis at the end of the 20th century in England and Wales: results of a national survey in 1998.

BACKGROUND: A national survey of tuberculosis was conducted in England and Wales in 1998 to obtain detailed information on the occurrence of the disease and recent trends. This survey also piloted the methodology for enhanced tuberculosis surveillance in England and Wales and investigated the prevalence of HIV infection in adults with tuberculosis. METHODS: Clinical and demographic data for all cases diagnosed during 1998 were obtained, together with microbiological data where available. Annual incidence rates in the population were estimated by age, sex, ethnic group, and geographical region using denominators from the 1998 Labour Force Survey. Incidence rates in different subgroups of the population were compared with the rates observed in previous surveys. The tuberculosis survey database for 1998 was matched against the Communicable Disease Surveillance Centre HIV/AIDS database to estimate the prevalence of HIV co-infection in adult patients with tuberculosis. RESULTS: A total of 5658 patients with tuberculosis were included in the survey in England and Wales (94% of all formally notified cases during the same period), giving an annual rate of 10.93 per 100 000 population (95% CI 10.87 to 10.99). This represented an increase of 11% in the number of cases since the survey in 1993 and 21% since 1988. In many regions case numbers have remained little changed since 1988, but in London an increase of 71% was observed. The number of children with tuberculosis has decreased by 10% since 1993. Annual rates of tuberculosis per 100 000 population have continued to decline among the white population (4.38) and those from the Indian subcontinent, although the rate for the latter has remained high at 121 per 100 000. Annual rates per 100 000 have increased in all other ethnic groups, especially among those of black African (210) and Chinese (77.3) origin. Over 50% of all patients were born outside the UK. Recent entrants to the UK had higher rates of the disease than those who had been in the country for more than 5 years or who had been born in the UK. An estimated 3.3% of all adults with tuberculosis were co-infected with HIV. CONCLUSIONS: The epidemiology of tuberculosis continues to change in England and Wales and the annual number of cases is rising. More than one third of cases now occur in young adults and rates are particularly high in those recently arrived from high prevalence areas of the world. The geographical distribution is uneven with urban centres having the highest rates. The increase in the number of cases in London is particularly large. Tuberculosis in patients co-infected with HIV makes a small but important contribution to the overall increase, particularly in London. To be most effective and to make the most efficient use of resources, tuberculosis prevention and control measures must be based on accurate and timely information on the occurrence of disease. A new system of continuous enhanced tuberculosis surveillance was introduced in 1999, based on the methodology developed in this national survey.

AIDS-Related Opportunistic Infections↗
PubMed2001

Examination of the melatonin hypothesis in women exposed at night to EMF or bright light.

It has been hypothesized that the increased incidence of breast cancer in industrial societies is related to greater exposure to power-frequency electric and magnetic fields (EMF) and/or the presence of high levels of light at night (LAN). EMF and LAN are said to reduce circulating levels of the hormone melatonin which, in turn, allows estrogen levels to rise and stimulate the turnover of breast epithelial stem cells and increase the risk for malignant transformation. Three laboratory-based studies, in which a total of 53 healthy young women were exposed at night to EMF or to LAN under controlled exposure conditions, were performed to determine whether such exposures reduce melatonin and are associated with further alterations in estrogen. All-night exposure to industrial-strength magnetic fields (60 Hz, 28.3 microT) had no effect on the blood levels of melatonin or estradiol. In contrast, nocturnal melatonin levels were profoundly suppressed, and the time of peak concentration was significantly delayed in women exposed to LAN, regardless of whether they were in the follicular or luteal phase of the menstrual cycle. These changes, however, were not associated with alterations in point-for-point matching measures of estradiol. Women who chronically secrete high or low amounts of melatonin each night (area-under-curve range: 86-1,296 pg/mL) also did not differ in their blood levels of estradiol. Taken together, these results are consistent with a growing body of evidence which generally suggests that environmental EMF exposure has little or no effect on the parameters measured in this report.

Adult↗
PubMed2001

Protein kinase C theta is expressed in mast cells and is functionally involved in Fcepsilon receptor I signaling.

We investigated possible expression and function in mast cells of protein kinase C (PKC) theta, a member of the PKC family with demonstrated function in a limited range of cell types. We found that PKC theta is expressed in bone marrow-derived mast cells and in the RBL-2H3 mast cell line. PKC theta underwent translocation to the membrane in response to Fcepsilon receptor I (FcepsilonR I) activation. Receptor activation induced phosphorylation of PKC theta. The tyrosine phosphorylation of PKC theta is delayed relative to PKC delta and coincides temporally with PKC theta association with c-src family members Lyn and SRC: Studies of RBL-2H3 cells transduced with PKC theta constructs indicated a role for PKC theta in receptor-induced activation of extracellular regulated kinases, interleukin-3 gene transcription, and degranulation in response to antigen stimulation. These studies extend the known functions of PKCtheta to another important immune cell type and indicate the concurrent participation of multiple PKCs in the FcepsilonR I-mediated response of mast cells.

Animals↗
PubMed2001

PHLS primary care consultation--infectious disease and primary care research and service development priorities.

In 1999 for the first time the PHLS undertook a questionnaire survey of general practitioners' views of the burden of infectious disease and the priorities for research and development of infectious disease services within the PHLS. Three hundred and seventy-one (38%) of 979 questionnaires mailed to chairs of primary care groups in England, and general practitioners in research networks, were returned. Service areas: computer transfer of laboratory results was considered of greatest priority. Guidance on antibiotic usage, guidance on infectious diseases and education for general practitioners were ranked two, three and four. Burden of infectious disease in primary care: upper respiratory tract infections, tonsillitis/pharyngitis, otitis media/externa and acute cough were placed one, three, four and seven respectively. Urinary tract infections were ranked second and dyspepsia/Helicobacter pylori fifth. Leg ulcers, diarrhoea, genital chlamydia infection and vaginal discharge were other diseases considered to cause a large burden of ill-health. Genital chlamydia, tuberculosis, Helicobacter pylori and meningococci were ranked one, two, three, and five in the NHS opportunity to affect the burden of ill-health. Priorities for improvements to diagnostic tests, evidence on which to base treatment and guidance: chronic fatigue/ME was ranked top in these areas. The other top ten syndromes ranked in order were genital chlamydia infections, antibiotic resistance surveillance, vaginal discharge, leg ulcers, sinusitis, otitis media/externa, dyspepsia/Helicobacter pylori, Creutzfeld Jacob Disease, and tonsillitis. This consultation exercise has highlighted broad areas for future PHLS involvement in primary care. In order to make progress, further consultation is needed with groups of GPs, and other relevant bodies. Particularly for the areas ranked in the top ten, the type of further PHLS involvement needs to be defined. For some syndromes (chronic fatigue and leg ulcers) this may be writing guidance and for others (respiratory tract infections) more treatment trials are required. The purposes and possible methods of communicable disease surveillance in general practice should be the subject of additional consultation.

Attitude of Health Personnel↗