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J Gray

Publications and source records attributed to J Gray.

At least 91 records · Page 5Linked to original sources
PubMed2001

Three-year survey of bacteremia and fungemia in a pediatric intensive care unit.

BACKGROUND: Knowledge of the pattern of blood stream infection (BSI) in patients in intensive care units (ICUs) can help determine antibiotic prescribing policy and infection control procedures. However, there have been few pediatric-based studies. METHODS: Surveillance of BSI in a pediatric ICU for 3 years, amounting to 131 episodes of significant bacteremia and fungemia. RESULTS: The incidence of BSI was 39.0 per 1,000 admissions (10.6 per 1,000 bed days). Eighty-four (64.1%) episodes were ICU-acquired, and 27 (20.6%) were community-acquired. Gram-positive, Gram-negative and anaerobic bacteria accounted for 62.2, 30.8 and 1.4%, respectively, of the 143 microorganisms isolated, 5.6% were yeasts. Neisseria meningitidis was the most common species in community-acquired infections, and staphylococci predominated in hospital-acquired episodes. Eighty-seven percent of patients had significant underlying disease, including 60.3% with congenitally acquired conditions. Intravascular devices were the most common source of infection, accounting for 41.2% of all episodes. The crude mortality in children with BSI was 26.5%, compared with 8.1% in those without BSI. CONCLUSIONS: The pattern of BSI in ICUs is partly determined by the type of patient treated. However, some observations are generally applicable, notably the increasing importance of antibiotic-resistant bacteria that are often of low virulence and device-associated. Our experience suggests that universal use of broad spectrum empiric antibiotics to cover these pathogens (which risks further promoting antibiotic resistance) may not improve patient outcome. Our study provides a basis for other pediatric ICUs to evaluate their rates and outcomes of BSI.

Adolescent↗
PubMed2001

Amino acid substitution within the VP7 protein of G2 rotavirus strains associated with failure to serotype.

Rotavirus strains collected in the United Kingdom during the 1995-1996 season and genotyped as G2 by reverse transcription-PCR failed to serotype in enzyme-linked immunosorbent assays using three different G2-specific monoclonal antibodies. The deduced amino acid sequences of the antigenic regions A (amino acids 87 to 101), B (amino acids 142 to 152), and C (amino acids 208 to 221) of VP7 revealed that a substitution at position 96 (Asp-->Asn) correlated with the change in ability to serotype these G2 strains.

Amino Acid Sequence↗
PubMed2001

Reassortment in vivo: driving force for diversity of human rotavirus strains isolated in the United Kingdom between 1995 and 1999.

The G and P genotypes of 3,601 rotavirus strains collected in the United Kingdom between 1995 and 1999 were determined (M. Iturriza-Gómara et al., J. Clin. Microbiol. 38:4394-4401, 2000). In 95.4% of the strains the most common G and P combinations, G1P[8], G2P[4], G3P[8], and G4P[8], were found. A small but significant number (2%) of isolates from the remaining strains were reassortants of the most common cocirculating strains, e.g., G1P[4] and G2P[8]. Rotavirus G9P[6] and G9P[8] strains, which constituted 2.7% of all viruses, were genetically closely related in their G components, but the P components of the G9P[8] strains were very closely related to those of cocirculating strains of the more common G types (G1, G3, and G4). In conclusion, genetic interaction by reassortment among cocirculating rotaviruses is not a rare event and contributes significantly to their overall diversity.

DNA, Viral↗
PubMed2001

Selective inactivation of p53 facilitates mouse epithelial tumor progression without chromosomal instability.

We examined the selective pressure for, and the impact of, p53 inactivation during epithelial tumor evolution in a transgenic brain tumor model. In TgT(121) mice, cell-specific inactivation of the pRb pathway in brain choroid plexus epithelium initiates tumorigenesis and induces p53-dependent apoptosis. We previously showed that p53 deficiency accelerates tumor growth due to diminished apoptosis. Here we show that in a p53(+/-) background, slow-growing dysplastic tissue undergoes clonal progression to solid angiogenic tumors in all animals. p53 is inactivated in all progressed tumors, with loss of the wild-type allele occurring in 90% of tumors. Moreover, similar progression occurs in 38% of TgT(121)p53(+/+) mice, also with loss of at least one p53 allele and inactivation of p53. Thus, the selective pressure for p53 inactivation, likely based on its apoptotic function, is high. Yet, in all cases, p53 inactivation correlates with progression beyond apoptosis reduction, from dysplasia to solid vascularized tumors. Hence, p53 suppresses tumor progression in this tissue by multiple mechanisms. Previous studies of fibroblasts and hematopoietic cells show that p53 deficiency can be associated with chromosomal instability, a mechanism that may drive tumor progression. To determine whether genomic gains or losses are present in tumors that progress in the absence of p53, we performed comparative genomic hybridization analysis. Surprisingly, the only detectable chromosomal imbalance was partial or complete loss of chromosome 11, which harbors the p53 gene and is thus the selected event. Flow cytometry confirmed that the majority of tumor cells were diploid. These studies indicate that loss of p53 function is frequent under natural selective pressures and furthermore that p53 loss can facilitate epithelial tumor progression by a mechanism in addition to apoptosis reduction and distinct from chromosomal instability.

Animals↗
PubMed2001

Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery.

OBJECTIVES: To determine whether continued methotrexate treatment increases the risk of postoperative infections or of surgical complications in patients with rheumatoid arthritis (RA) within one year of elective orthopaedic surgery. DESIGN: A prospective randomised study of postoperative infection or surgical complications occurring within one year of surgery in patients with RA who underwent elective orthopaedic surgery. SUBJECTS: 388 patients with RA who were to undergo elective orthopaedic surgery. Patients who were receiving methotrexate were randomly allocated to groups who either continued methotrexate (group A) or who discontinued methotrexate from two weeks before surgery until two weeks after surgery (group B). Their complication rates were compared with complications occurring in 228 patients with RA (group C) who were not receiving methotrexate and who also underwent elective orthopaedic surgery. MAIN OUTCOME MEASURES: Signs of postoperative infection were recorded, including rubor, discharge, systemic infection, and frequency of wound dehiscence as well as the incidence of any surgical complication requiring a secondary revision procedure that occurred within one year of surgery. The frequencies of flare up activity of RA at six weeks and six months after surgery were also recorded. A flare of rheumatoid disease was defined as an increase in joint pain in two or more joints notified by the patient as well as by an increase in articular index of at least 25% after surgery. RESULTS: Signs of infection or surgical complications occurred in two of 88 procedures in group A (2%), 11 of 72 procedures in group B (15%), and 24 of 228 (10.5%) procedures in group C. The surgical complication or infection frequency in group A was less than that in either group B (p<0.003) or group C (p=0.026). At six weeks after surgery there were no flares in group A, six flares in group B (8%), and six flares in group C (2.6%). Logistic regression analysis of the overall surgical complication rate in all the patients with RA studied showed that methotrexate, whether continued or discontinued before surgery, did not increase the early complication rate in the patients with RA who underwent elective orthopaedic surgery. Other drugs-penicillamine, indometacin, cyclosporin, hydroxychloroquine, chloroquine, and prednisolone-all did significantly increase the risk of infection or surgical complication after elective orthopaedic surgery. The risk of surgery was also increased in the presence of intercurrent chronic diseases-diabetes, hypertension, bronchiectasis, psoriasis, asthma, and ischaemic heart disease. CONCLUSION: Continuation of methotrexate treatment does not increase the risk of either infections or of surgical complications occurring in patients with RA within one year of elective orthopaedic surgery. Thus methotrexate treatment should not be stopped in patients whose disease is controlled by the drug before elective orthopaedic surgery.

Adult↗
PubMed2001

No association between multiple sclerosis and the Notch3 gene responsible for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

The clinical and radiological overlap between multiple sclerosis and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL; MIM 125310) raises the possibility of diagnostic confusion and suggests that pleiotropic effects of the Notch3 gene might include influencing susceptibility to multiple sclerosis. To investigate these possibilities three microsatellites markers closely flanking the Notch 3 gene in 745 simplex families with multiple sclerosis were genotyped and exon 3 and exon 4 of the gene were directly sequenced in a subset of the index members from these families (n=93). No evidence for association was found in any of the three markers and none of the commoner mutations causing CADASIL were found in the sequenced patients.

Adult↗
PubMed2001

Ecological relationships between the prevalence of cattle shedding Escherichia coli O157:H7 and characteristics of the cattle or conditions of the feedlot pen.

This study was designed to describe the percentage of cattle shedding Escherichia coli O157:H7 in Midwestern U.S. feedlots and to discover relationships between the point prevalence of cattle shedding the organism and the characteristics of those cattle or the conditions of their pens. Cattle from 29 pens of five Midwestern feedlots were each sampled once between June and September 1999. Feces were collected from the rectum of each animal in each pen. Concurrently, samples of water were collected from the water tank, and partially consumed feed was collected from the feedbunk of each pen. Characteristics of the cattle and conditions of each pen that might have affected the prevalence of cattle shedding E. coli O157:H7 were recorded. These factors included the number of cattle; the number of days on feed; and the average body weight, class, and sex of the cattle. In addition, the temperature and pH of the tank water were determined, and the cleanliness of the tank water and the condition of the pen floor were subjectively assessed. The samples of feces, feed, and water were tested for the presence of E. coli O157:H7. E. coli O157:H7 was isolated from the feces of 719 of 3,162 cattle tested (23%), including at least one animal from each of the 29 pens. The percentage of cattle in a pen shedding E. coli O157:H7 did not differ between feedyards, but it did vary widely within feedyards. A higher prevalence of cattle shed E. coli O157:H7 from muddy pen conditions than cattle from pens in normal condition. The results of this study suggest that E. coli O157:H7 should be considered common to groups of feedlot cattle housed together in pens and that the condition of the pen floor may influence the prevalence of cattle shedding the organism.

Animal Feed↗
PubMed2001

Development of a protocol for evaluation of mammographic surveillance services in women under 50 with a family history of breast cancer.

BACKGROUND: Preliminary retrospective data suggest it is possible to identify impalpable breast cancer in women presenting with a family history of breast cancer under the age of 50, by using regular mammography. In consequence, this service is offered in a number of centres in the UK. The effectiveness of such a service, however, has not been fully evaluated. METHODS: We propose to perform such an evaluation in a cohort of 20000 women under the age of 50 with a significant family history of breast cancer, given regular mammographic surveillance over 5 years. Comparison of surgical and pathological data with completed and ongoing population screening trials using analysis techniques of varying complexity will be performed to obtain an accurate prediction of future breast-cancer mortality reduction. The formal aims are: i) to estimate the difference in breast-cancer mortality in women under the age of 50 with a significant family history of breast cancer having regular mammography, compared with those not being screened; ii) to estimate the cost-effectiveness of regular mammography in this group of women, compared with no screening. The increase in health service resource use attributable to such a policy will be compared with no screening, and costed. Incremental cost-effectiveness ratios of implementing the standardised mammography strategy compared with no screening will be presented in terms of the additional cost per cancer detected, per life saved and per life-year saved.

Adult↗
PubMed2000

Identifying patients with ischaemic heart disease in general practice: cross sectional study of paper and computerised medical records.

OBJECTIVES: To identify patients with ischaemic heart disease by using a practice computer and to estimate the work required to do so. DESIGN: Cross sectional study. Data from the notes and from the computer records of 1680 patients were used to build a database. This was used to compare different methods of identifying patients with ischaemic heart disease. SETTING: 11 general practices in the Battersea primary care group in south London. SUBJECTS: 1 in 40 random sample of patients aged 45 or older. MAIN OUTCOME MEASURES: Numbers of patients identified with ischaemic heart disease. RESULTS: The combination of the Read code for ischaemic heart disease (G3) and a prescription for a nitrate had a 73% sensitivity and a yield (100/positive predictive value) of one case of ischaemic heart disease for every 1.2 sets of notes reviewed. By searching the records of patients also receiving aspirin, atenolol, digoxin, or a statin, the sensitivity was increased to 96% but the yield fell to one in three. CONCLUSION: Although commonly used to identify cases, a computer search for G3 code or nitrate missed almost 30% of patients with ischaemic heart disease. A substantially higher percentage of patients can be identified by adding other drugs to the search strategy.

Aged↗
PubMed2000

Randomized trial of a specialist genetic assessment service for familial breast cancer.

BACKGROUND: Because of the growing demand for genetic assessment, there is an urgent need for information about what services are appropriate for women with a family history of breast cancer. Our purpose was to compare the psychologic impact and costs of a multidisciplinary genetic and surgical assessment service with those of current service provisions. METHODS: We carried out a prospective randomized trial of surgical consultation with (the trial group) and without (the control group) genetic assessment in 1000 women with a family history of breast cancer. All P: values are from two-sided tests. RESULTS: Although statistically significantly greater improvement in knowledge about breast cancer was found in the trial group (P: =.05), differences between groups in other psychologic outcomes were not statistically significant. Women in both groups experienced statistically significant reductions in anxiety and found attending the clinics to be highly satisfying. An initial specialist genetic assessment cost pound 14.27 (U.S. $22.55) more than a consultation with a breast surgeon. Counseling and genetic testing of affected relatives, plus subsequent testing of family members of affected relatives identified as mutation carriers, raised the total extra direct and indirect costs per woman in the trial group to pound 60.98 (U.S. $96.35) over costs for the control subjects. CONCLUSIONS: There may be little benefit in providing specialist genetics services to all women with a family history of breast cancer. Further investigation of factors that may mediate the impact of genetic assessment is in progress and may reveal subgroups of women who would benefit from specialist genetics services.

Adult↗
PubMed2000

The microfossil record of early land plants.

Dispersed microfossils (spores and phytodebris) provide the earliest evidence for land plants. They are first reported from the Llanvirn (Mid-Ordovician). More or less identical assemblages occur from the Llanvirn (Mid-Ordovician) to the late Llandovery (Early Silurian), suggesting a period of relative stasis some 40 Myr in duration. Various lines of evidence suggest that these early dispersed microfossils derive from parent plants that were bryophyte-like if not in fact bryophytes. In the late Llandovery (late Early Silurian) there was a major change in the nature of dispersed spore assemblages as the separated products of dyads (hilate monads) and tetrads (trilete spores) became relatively abundant. The inception of trilete spores probably represents the appearance of vascular plants or their immediate progenitors. A little later in time, in the Wenlock (early Late Silurian), the earliest unequivocal land plant megafossils occur. They are represented by rhyniophytoids. It is only from the Late Silurian onwards that the microfossil/ megafossil record can be integrated and utilized in interpretation of the flora. Dispersed microfossils are preserved in vast numbers, in a variety of environments, and have a reasonable spatial and temporal fossil record. The fossil record of plant megafossils by comparison is poor and biased, with only a dozen or so known pre-Devonian assemblages. In this paper, the early land plant microfossil record, and its interpretation, are reviewed. New discoveries, novel techniques and fresh lines of inquiry are outlined and discussed.

Biological Evolution↗
PubMed2000

Interleukin 1 receptor antagonist (IL-1ra) in multiple sclerosis.

The autoimmune nature of multiple sclerosis introduces cytokine genes as logical candidates for the loci determining susceptibility to the disease, and/or influencing disease progression. Working on this principle, several groups have investigated the relevance of polymorphism in the interleukin 1 receptor antagonist gene (IL1RN) but with conflicting results. In an effort to clarify this situation, we typed the functionally significant variable number of tandem repeat (VNTR) polymorphism from intron 2 of IL1RN in 536 simplex families with multiple sclerosis. In order to improve the information extracted from these families, we also typed a closely mapped single nucleotide polymorphism (SNP) from the promoter of IL1B (the gene for IL-1beta). Disease associations were assessed by transmission disequilibrium testing (TDT), alone and after haplotype construction. There was highly significant (P</=2.48.10(-16)) linkage disequilibrium (LD) between the two polymorphisms studied, illustrating that LD adjacent to an SNP can be considerably more extensive than has recently been suggested. None of the alleles from the VNTR, the SNP or their haplotype showed statistically significant evidence for association. We stratified patients for current disability status but using this manoeuvre found no evidence that either of the polymorphisms influences disease severity. Combining the available data on the IL1RN VNTR suggests that any effect of this gene on susceptibility to multiple sclerosis, or its progression is, at best, small.

Adult↗
PubMed2000

Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.

The vanilloid receptor-1 (VR1) is a ligand-gated, non-selective cation channel expressed predominantly by sensory neurons. VR1 responds to noxious stimuli including capsaicin, the pungent component of chilli peppers, heat and extracellular acidification, and it is able to integrate simultaneous exposure to these stimuli. These findings and research linking capsaicin with nociceptive behaviours (that is, responses to painful stimuli in animals have led to VR1 being considered as important for pain sensation. Here we have disrupted the mouse VR1 gene using standard gene targeting techniques. Small diameter dorsal root ganglion neurons isolated from VR1-null mice lacked many of the capsaicin-, acid- and heat-gated responses that have been previously well characterized in small diameter dorsal root ganglion neurons from various species. Furthermore, although the VR1-null mice appeared normal in a wide range of behavioural tests, including responses to acute noxious thermal stimuli, their ability to develop carrageenan-induced thermal hyperalgesia was completely absent. We conclude that VR1 is required for inflammatory sensitization to noxious thermal stimuli but also that alternative mechanisms are sufficient for normal sensation of noxious heat.

Adenosine Triphosphate↗
PubMed2000

Characterisation of rotavirus G9 strains isolated in the UK between 1995 and 1998.

G9P[6] and G9P[8] rotavirus strains were identified during 1995/96 through the molecular epidemiological surveillance of rotavirus strains circulating in the UK between 1995 and 1998. An increase in the incidence and spread of sporadic infections with rotavirus genotype G9P[8] across the UK was detected in the two following seasons. Partial sequencing of the VP7 gene showed that all the UK strains shared a high degree of homology and were related very closely to G9 strains from the US and from symptomatic infections in India (> or =96% homology). The UK strains were related more distantly to the apathogenic Indian strain 116E (85-87.8% homology). Phylogenetic analysis revealed clustering of the UK strains into 3 different lineages (I to III) and into two sub-lineages within lineage I. There were correlations between VP7 sequence clustering, the P type and the geographical origin of the G9 strains. Partial sequencing of the VP4 gene showed high degree of homology (>98%) among all the P[6] strains, and the sequences obtained from the P[8] strains clustered into 2 of the 3 global lineages described for P[8] strains associated with other G types. These data suggest that G9 strains may be a recent importation into the UK, and that G9P[8] strains may have emerged through reassortment in humans between G9P[6] strains introduced recently and the more prevalent cocirculating G1, G3 and G4 strains that normally carry VP4 genes of P[8] type.

Aged↗
PubMed2000

Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11 (CZP3) and a novel mutation in connexin 46 (GJA3).

We describe a four-generation family with fully penetrant, autosomal dominant, congenital cataracts (ADCC), presenting with morphologically homogeneous "zonular pulverulent" cataracts (CZP) and typical early-onset phenotype. Linkage analysis was performed with a panel of polymorphic markers mapped to all genomic regions of ADCC susceptibility. Contiguous significant two-point lod scores were generated at autosomal region 13q11-q13 and further linkage and haplotype studies confined the disease locus to 13q11, supporting a previous linkage of CZP (specifically CZP3) to 13q11. Mutations in a gap-junction protein, connexin 46 (alphaa3 subunit or GJA3), have recently been reported as being linked to the 13q11 region. Mutational analysis of connexin 46 in our family revealed a C-->T at position 560 (P187L) of the cDNA sequence creating a novel MnlI restriction site that segregated with affected members of the pedigree. This family represents a second report of CZP3 linkage to 13q and is associated with a novel mutation in the connexin 46 (GJA3) gene.

Base Sequence↗
PubMed2000

Academic progress of children who attended a preschool for abused children: a follow-up of the keepsafe project.

OBJECTIVE: This study was undertaken to assess academic progress of children 1 to 5 years after graduating from the C. Henry Kempe Center's Therapeutic Preschool Day Treatment Program. METHOD: Information was gathered through chart review; telephone surveys of care providers, relatives, and social service workers; as well questionnaires on all children who attended the therapeutic preschool day treatment program between 1984 and 1989, including the 24 children reported on by Oates, Gray, Schweitzer, Kempe, and Harmon, 1995. RESULTS: Classroom placement was determined for 27 of the 44 graduates (61.4%), 14 of whom (51.9%) were in a regular classroom, 10 (37.0%) in special education, two (7.4%) in residential treatment, and one (3.7%) was receiving home schooling. Twenty-two of the 27 children (81.5%) improved or remained in the same grade and type of classroom as they had been staffed into at the time of their graduation from the preschool day treatment program. Factors thought to affect stability of classroom placement were studied, of which frequency of family moves was the only significant variable. Its significance was in the direction opposite to that expected. The most effective method of locating families was to contact the Department of Social Services who provided information used to find 60% of them. CONCLUSIONS: Intervention in a therapeutic preschool day treatment program was found to be beneficial, as it enabled most of the children to progress appropriately in public school.

Achievement↗