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Biomedical subjects

J Gray

Publications and source records attributed to J Gray.

At least 163 records · Page 9Linked to original sources
PubMed1998

HLA typing in the United Kingdom multiple sclerosis genome screen.

The United Kingdom multiple sclerosis genome screen demonstrated a peak maximum lod score of 2.8 in the HLA region, together with statistically significant excess transmission of the 121-base pair (bp) allele of the tumour necrosis factor-a marker. In order to determine whether this association is independent of the established HLA association, or simply a consequence of the 121-bp allele being part of the same haplotype, we HLA-DR and -DQ typed the 227 sibling-pair families used in the original screen. The expected associations of multiple sclerosis with the DR15 (p=8.7E-18), DQ6 (p=2.0E-09) and DR51 (p=2.8E-16) phenotypes were confirmed, and excess transmission of the DRB1*1501 and DQB1*0602 alleles was demonstrated. Combining HLA typing with the original microsatellite data demonstrated extensive linkage disequilibrium between the 121-bp allele and the 1501-0602 haplotype. Outside this extended haplotype (121-1501-0602), none of the alleles demonstrated significant transmission distortion. Having established the importance of this extended haplotype, we reanalysed the entire genome screen data after excluding those sibling pairs sharing the extended haplotype (n=27). Conditioning the full genome screen data on the basis of identity by state sharing showed that some potential linkage regions identified in the original screen clustered in families, in which the extended haplotype was shared (1p, 2p and 17q), whereas others grouped with those in which it was not (5cen, 7p and Xq). This suggests complexity in the genetics of multiple sclerosis.

Genetic Markers↗
PubMed1998

Pharmacodynamics and pharmacokinetics of DMP 728, a platelet GPIIb/IIIa antagonist, in healthy subjects.

DMP 728 showed a dose-dependent inhibition of platelet aggregation at doses of 0.05 to 0.9 mg per subject, with a maximal inhibition (> 90%) of platelet aggregation at doses of 0.9 mg per subject and higher. Minimal changes in bleeding time from baseline were observed at doses up to 0.6 mg per subject. At the 0.9 mg/subject dose level, bleeding time was prolonged by approximately twofold to threefold above the baseline. At higher doses (1.5 mg/subject to 3.9 mg/subject), bleeding time prolongation was > 30 minutes during the infusion. In all dose groups, bleeding times returned to the control value within 8 hours after cessation of the infusion. Maximum plasma concentration and area under the curve of DMP 728 increased linearly and proportionally to the dose. No clinical changes in vital signs, 12-lead electrocardiograms, physical examinations, coagulation tests, or stool hemoccult tests were observed at any of the doses. In conclusion, DMP 728 is a potent antiplatelet agent and well tolerated at doses ranging from 0.05 to 3.0 mg/subject.

Adult↗
PubMed1998

Optimisation of the polymerase chain reaction and dot-blot hybridisation for detecting cytomegalovirus DNA in urine: comparison with detection of early antigen fluorescent foci and culture.

Rapid, sensitive and specific assays are required for the diagnosis of CMV infection following transplantation. We describe our experience in developing assays for detecting CMV in urine. Conventional preparation of probes cloned after amplification in E. coli led to contamination with E. coli nucleic acids; these hybridised to E. coli DNA present in urine and produced false positive results. Two CMV probes (Hind III and gL) hybridised to human DNA despite high stringency; these probes were thus unsuitable for detecting viral nucleic acids in clinical samples. A PCR derived probe from the immediate early gene of CMV detected dot-blotted CMV DNA specifically. Optimal preparation of urine for detection of CMV DNA was as follows; four freeze/thaw cycles and ultracentrifugation before in vitro proteinase K/SDS treatment, phenol:chloroform extraction, heat denaturation and direct application onto a nylon membrane. However, dot-blot hybridisation was a poor test for CMV in urine; it had low sensitivity and specificity compared with virus isolation and DEAFF. Single round PCR of a 293 bp region of CMV DNA was sensitive and specific to CMV targets. However, undiluted urine contained PCR inhibitors that could only be partly removed by using PEG precipitation. PCR of CMV DNA from urine was specific but was insensitive compared to conventional culture and DEAFF. A significant proportion of urine samples were toxic in conventional culture and DEAFF tests but, PCR of CMV DNA from urine is insensitive and despite its specificity is unlikely to be advantageous in clinical practice even when DEAFF or culture prove unreliable.

Antigens, Viral↗
PubMed1998

Cohorting of infants with respiratory syncytial virus.

During two winter periods (1994-1995 and 1995-1996), nasopharyngeal aspirates were obtained from infants and young children with an acute respiratory illness, after initial assessment in an area with six cubicles which serves as an admissions unit. Aspirates were sent for rapid diagnostic testing. Respiratory syncytial virus (RSV) positive patients were cohorted into two six-bedded bays on the paediatric wards. Over the two successive winter periods studied, 347 RSV positive patients were assigned to the cohort. No nosocomial infections were identified during the first winter; in the second, two were identified. Cohorting at admission eased clinical management, with one area used for high-dependency care and cubicles being freed for children with other infectious diseases. Nosocomial infection was minimized.

Child, Preschool↗
PubMed1998

Plasma aspartate aminotransferase and creatine kinase activities in thoroughbred racehorses in relation to age, sex, exercise and training.

In order to investigate the effect of age, sex and month on the response of plasma aspartate aminotransferase (AST) and creatine kinase (CK) to exercise, blood samples were collected once a month between March and September from a group of 40 2- and 3-year-old (2yo and 3yo) thoroughbred racehorses (kept under the same managemental regimen) at rest before exercise (PRE) and at 2 (2H) and 24 h (24H) post-exercise. The absolute change in activities between the 2H and PRE samples (2H delta) and the 24H and PRE samples (24H delta) was also calculated. Age had a significant effect on all measured and calculated parameters for colts (C), apart from 24H delta CK but showed no effect in the fillies (F). Sex only had a significant effect in the 3yo in the 2H delta CK. In the 2yo, significant effects of sex were found for both CK and AST in the PRE, 2H and 24H samples. The effect of month varied according to the classification group with only the 2yoC not showing any significant effect on any parameter. Fillies were, in general, more likely than colts to show greater than a twofold increase in CK activity at 2H post-exercise and the number of animals showing such an increase decreased as the season progressed. Very little change in AST activities occurred with exercise.

Age Factors↗
PubMed1998

BRCA1 and BRCA2 in breast cancer families from Wales: moderate mutation frequency and two recurrent mutations in BRCA1.

Mutations in the BRCA1/BRCA2 genes account for varying proportions of breast cancer families studied, and demonstrate considerable variation in mutational spectra coincident with ethnic and geographical diversity. We have screened for mutations in 17 families from Wales with two or more cases of breast cancer under age 50 and/or ovarian cancer. Eight out of 17 (47%) families had demonstrable mutations. Six out of 17 (35%) carried BRCA1 mutations and 2 out of 17 (12%) carried BRCA2 mutations. Two recurrent mutations in BRCA1 were identified, which appear to represent founder mutations in this population. These data support the existence of additional breast and ovarian cancer susceptibility genes.

Adult↗
PubMed1998

Discharges of krypton from Sellafield, 1951-1997, and the resultant doses to members of the public.

The radionulide 85Kr, which has a half-life of 10.72 years, is produced, almost exclusively, by reprocessing operations during which the fission product is released from irradiated nuclear fuel by chemical dissolution. Reprocessing plants at Sellafield, in Cumbria, have released the noble gas to atmosphere since operations commenced in 1952. Historically, krypton discharges were classified for security reasons, although these have been monitored and published by BNFL for each year since 1977. This paper reviews discharges of 85Kr from Sellafield, and consequent radiation doses, since its earliest operations. Over the past three years, discharges of 85Kr have increased due to the operation of the Thermal Oxide Fuel Reprocessing Plant (Thorp). Nonetheless, the associated annual committed effective dose to individuals remains low, peaking around 1.5 microSv a-1 to the identified critical groups, which compares with typical annual committed effective doses from natural sources of radiation of 2200 microSv. Maximum collective doses predicted from any single year of operations are 0.6 man Sv, 2 man Sv and 42 man Sv to the UK, Europe and the world respectively. Comparison may be made to natural background committed effective doses, which are of the order of 130,000 man Sva-1, 750,000 man Sva-1 and 13,000,000 man Sva-1 to the UK, EU and world populations respectively.

England↗
PubMed1998

The genetics of multiple sclerosis: principles, background and updated results of the United Kingdom systematic genome screen.

Genetic susceptibility to multiple sclerosis is implicated on the basis of classical family studies and phenotype analyses. The only reproducible legacy from the candidate gene approach has been the discovery of population associations with alleles of the major histocompatibility complex. Systematic genome scanning has since been applied using a panel of anonymous markers to identify areas of linkage in co-affected siblings. Here, we describe the principles of genome screening and update the UK survey of multiple sclerosis. This identified 20 regions of potential interest, but in none was there unequivocal linkage. In theory, attempting to replicate these findings in a second set of sibling pair families is the most appropriate way to distinguish true from false positives, but unfortunately the number of families required to do this reliably is prohibitively large. We used three approaches to increase the definition achieved by the screen: (i) the number of sibling pairs typed in an identified region of potential linkage was extended; (ii) the information extraction was increased in an identified region; and (iii) a search was made for missed regions of potential linkage. Each of these approaches has considerable limitations. A chromosome-by-chromosome account is given to direct future searches. Although an additional marker placed distal to the 'hit' on chromosome 14q increased linkage in this area, and typing extra sibling pairs increased linkage on chromosomes 6p and 17q, evidence for linkage was more commonly reduced and no additional regions of interest were found. A further refinement of the genome screen was undertaken by conditioning for the presence of HLA-DR15. This produced a surprising degree of segregation among the regions of interest, which divided into two distinct groups depending on DR15 sharing: the DR15-sharing cohort comprised loci on chromosomal areas 1p, 17q and X; and the DR15-non-sharing cohort was made up of loci on 1cen, 3p, 7p, 14q and 22q. This result further highlights the genetic complexity of multiple sclerosis. What can now be inferred is that a gene of major effect is excluded from 95% of the genome and one with a moderate role from 65%, whereas genes which make a very small biological contribution cannot be discounted from any region. The available results suggest that multiple sclerosis depends on independent or epistatic effects of several genes each with small individual effects, rather than a very few genes of major biological importance.

Genetic Linkage↗
PubMed1998

Enterococcal bacteremia in children: a review of seventy-five episodes in a pediatric hospital.

BACKGROUND: Enterococcal bacteremia is being increasingly reported. Although there have been a number of recent studies of enterococcal bacteremia in adults, there are few studies involving children. We carried out a prospective study to determine the epidemiologic, clinical and laboratory characteristics of such bacteremia in children. METHODS: Clinical and microbiologic data were recorded prospectively for all episodes of enterococcal bacteremia occurring during a 3-year period between January 1, 1995, and December 31, 1997. RESULTS: Seventy-five episodes of enterococcal bacteremia occurring in children at our institution during a 3-year period were prospectively analyzed. Serious underlying disease was present in 67 (89.3%) episodes, and in 48 (64.%) episodes patients had received antibiotics during the 2 weeks preceding enterococcal bacteremia. Forty-seven (62.7%) episodes were nosocomial in origin and 26 (34.7%) were polymicrobial. Fifty (66.7%) episodes occurred in children 1 year old or less. A source of bacteremia was identified in 33 (44%) episodes, intravascular device being the most common identifiable source. Of the 73 isolates identified to species level, there were 36 Enterococcus faecium, 36 Enterococcus faecalis and one Enterococcus avium. In 60 (80%) episodes appropriate anti-enterococcal therapy was given. The overall mortality rate was 7.5%. Four clinical patterns of infection were identified: self-limited bacteremia, 16.0%; low grade sepsis with a favorable outcome after specific therapy, 65.3%; severe and prolonged infection associated with a high mortality rate, 14.7%; and fulminant neonatal sepsis in previously healthy babies, 4.0%. CONCLUSION: Enterococcal bacteremia in children comprises a heterogeneous group. Bacteremias that are mild and self-limited and respond promptly to antibiotic therapy appear to be more common in children.

Adolescent↗
PubMed1998

The role of betamethasone in the treatment of acute exudative pharyngitis.

OBJECTIVE: To compare betamethasone with placebo as an adjuvant to antibiotic therapy in the treatment of acute exudative pharyngitis. METHODS: The study was a randomized, doubled-blind, placebo-controlled, single-center, parallel, outpatient clinical trial. After consent was obtained, each patient was asked to rate his or her pain on a 10-cm numbered visual analog scale (VAS; 0-10). All of the patients received injectable benzathine penicillin. If allergic to penicillin, they were started on a 10-day course of polyenteric-coated erythromycin (PCE). Each patient was randomized to receive either i.m. betamethasone or i.m. placebo. All patients were contacted by telephone at 24 and 48 hours by one of the study investigators and asked to rate their pain based on another VAS. If their pain was not resolved by 48 hours, they were called again daily between the third and seventh days after the initial visit to determine the time of pain resolution. RESULTS: A total of 92 patients were enrolled in the study, with 46 randomized to receive placebo and 46 to receive betamethasone. Eight patients were excluded from the statistical analysis because of inability to obtain follow-up. Demographic comparison showed that gender distributions, ages, mean initial pain scores, mean times to the first and second follow-up calls, and treatment regimens were similar in the 2 groups. There were significantly better pain scores for the betamethasone group at first follow-up (p = 0.0005), at second follow-up (p = 0.004), and in number of hours until relief of pain (p = 0.004). When only those patients with a positive culture for a streptococcus species were analyzed, there also were significant reductions in pain score at the first (p = 0.006) and second (p = 0.02) follow-up visits. CONCLUSION: Pain relief was greater and more rapid in patients treated with betamethasone as an adjuvant therapy in acute exudative pharyngitis.

Acute Disease↗
PubMed1998

Experience of changing between signal and Bactec 9240 blood culture systems in a children's hospital.

AIM: To compare experience of positive blood cultures in successive years before and after changing from Signal (Unipath) to Bactec 9240 (Becton Dickinson) blood culture systems. METHODS: Analysis of data collected prospectively on 7967 Signal and 7062 Bactec blood culture sets. RESULTS: Significant growths occurred in 5.7% of Signal and 8.9% of Bactec cultures; 33.0% more significant isolates and 24.0% more episodes of bacteraemia were detected in the second year, following introduction of the Bactec system. Inpatient hospital activity increased by 8.2% between the first and second years, although the numbers of blood cultures received actually fell by 11.4%. There were striking increases in numbers of isolates of coagulase negative staphylococci (47.7%) and Enterobacteriaceae (56.8%) from Bactec cultures. Two anaerobic bacteraemias were detected in Signal blood cultures, whereas none was detected by the Bactec system, despite 12.1% of sets including an anaerobic bottle. Of significant positive cultures, 90.2% were detected within one day with the Bactec 9240, compared with only 50.0% of Signal cultures; 20.7% of significant positive Signal blood cultures were detected only on terminal subculture. Microorganisms that were not significant were isolated from 5.1% Signal and 3.8% Bactec cultures. CONCLUSIONS: Compared with the Signal system, the Bactec 9240 offers markedly more rapid and sensitive detection of bacteraemia, together with a lower rate of non-significant isolates. However, using a single PEDS PLUS/F bottle the few episodes of anaerobic bacteraemia that occur in children are likely to be missed.

Bacteremia↗
PubMed1998

Polydactyly and psychosis. Five cases of co-occurrence.

BACKGROUND: Abnormalities presumed to occur during foetal life have been associated with schizophrenia. Polydactyly is a developmental abnormality but no previous association has been reported between polydactyly and functional psychotic illness. METHOD: Individuals with both polydactyly and a functional psychosis were ascertained during a study of familial schizophrenia. RESULTS: Five such individuals were ascertained in the course of assessing 234 individuals with familial psychosis, giving a rate of polydactyly in the sample of around 10 times the general population rate. CONCLUSIONS: This study provides preliminary evidence that polydactyly is over-represented in individuals with familial schizophrenia and related psychotic illnesses.

Adult↗
PubMed1998

Liaison between gynaecologists, microbiologists and genitourinary medicine clinics in the management of patients with genital chlamydia and gonococcal infections.

Inadequate treatment and follow-up of women with genital infection with Chlamydia trachomatis and Neisseria gonorrhoeae can cause long-term morbidity. Inadequate contact tracing can predispose to re-infection. As some women with genital infections present to agencies other than genitourinary medicine (GUM) clinics, improved liaison between these and GUM departments are important in safeguarding proper follow-up and contact tracing.

Adolescent↗
PubMed1998

Harm reduction in the hills of northern Thailand.

The human immunodeficiency virus (HIV) pandemic has swept through injecting drug user (IDU) communities around the world. Once HIV is present in an IDU community, seroprevalence rates escalate rapidly unless immediate and comprehensive prevention methods are put in place. Such measures often include providing IDUs with sterile injecting equipment and dispensing methadone or other opiate substitution formulas. These measures fall under the rubric of harm reduction-an attempt to reduce the harm to drug users, their families, and communities, including preventing or limiting the transmission of HIV and other blood-borne viruses. In Thailand, HIV-1 spread rapidly among IDUs with seroprevalence rates jumping from 1 to 40% in the space of a year. Current incidence rates are estimated at 11 per 100 person years. This paper describes the establishment and implementation of needle and syringe exchanges among injecting drug users in nine Hilltribe communities in Northern Thailand. The exchanges have been operating for between 1 and 3 years and have been effective in limiting the transmission of HIV within these small communities. The needle and syringe exchanges are run by indigenous staff with the cooperation of the community and provide a good example of the feasibility of establishing locally-run, community-based harm reduction programs.

Feasibility Studies↗
PubMed1998

Telematics in the neonatal ICU and beyond: improving care, communication and information sharing.

In October of 1998, the Beth Israel-Deaconess was awarded one of 19 contracts from the National Library of Medicine (NLM) to develop, implement and test a telemedicine application to support the care of Very Low Birth Weight Infants. This project is the only one to focus on the care of newborns. We believe that this project will provide a new national approach to managing the care of high-risk newborns by leveraging evolving communication technology.

Computer Security↗