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Biomedical subjects

S J O'Brien

Publications and source records attributed to S J O'Brien.

At least 91 records · Page 5Linked to original sources
PubMed2000

Infectious health care workers: should patients be told?

The risk of transmission of HIV or hepatitis B from infectious health care workers to patients is low. However, inadvertent exposure causes great concern amongst patients of an infected health care worker. The patients of a Scottish dentist diagnosed hepatitis B e antigen positive were informed by letter of their exposure. A sample of patients was sent a postal questionnaire. Most (56%) respondents reported feeling anxious on receiving the letter but almost all (93%) thought patients should always be informed following treatment by an infectious health care worker, although the risk was very small. We discuss clinical and ethical factors relating to informing patients following exposure to an infectious health care worker. We suggest that a balance should be struck between patients' wishes to know of risks to which they have been exposed, however small, and the professional view that when risks are negligible, patients need not be informed.

Anxiety↗
PubMed2000

Polygenic and multifactorial disease gene association in man: Lessons from AIDS.

In an age when the majority of monogenic human disease genes have been identified, a particular challenge for the coming generation of human geneticists will be resolving complex polygenic and multifactorial diseases. The tools of molecular and population genetic association have much potential as well as peril in uncovering small cryptic genetic effects in disease. We have used a candidate gene approach to identify eight distinct human loci with alleles that in different ways influence the outcome of exposure to HIV-1, the AIDS virus. The successes in these gene hunts have validated the approach and illustrate the strengths and limitations of association analysis in an actual case history. The integration of genetic associations, well-described clinical cohorts, extensive basic research on AIDS pathogenesis, and functional interpretation of gene connections to disease offers a formula for detecting such genes in complex human genetic phenotypes.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Cyclospora infections in England and Wales: 1993 to 1998.

The coccidian protozoon Cyclospora cayetanensis is a treatable cause of prolonged, watery diarrhoea in humans. Microbiology laboratories in England and Wales often restrict testing to those who have recently travelled abroad. Only 44 to 66 laboratory reports of C. cayetanensis are made in England and Wales each year and a large proportion are found to have visited developing countries. Large foodborne outbreaks of infection have arisen in North America among people who have not travelled abroad but no such outbreaks have been identified in the United Kingdom. Public health laboratories in England and Wales were surveyed in 1998 to investigate their procedures for identifying C. cayetanensis. Sixty-eight per cent actively looked for the protozoon, but only half used a recommended method of direct microscopy of formol ether concentrates. National external quality assurance results for all participating UK laboratories were reviewed to assess laboratory proficiency in identification. C. cayetanensis was correctly identified in a wet preparation by 58% of laboratories, the lowest rate for specimens containing a single parasite species. Cyclosporiasis could be acquired in the UK from imported food, but current laboratory procedures might fail to identify it. Ascertainment must improve and awareness needs to be raised among food handlers, public and environmental health workers, laboratory staff, and general practitioners. We recommend that laboratories test all patients with watery diarrhoea for > 1 week for cyclospora, use formol ether concentration and microscopy with a calibrated eyepiece graticule, and confirm diagnoses with the help of a reference laboratory.

Animals↗
PubMed2000

Survey of local authority approaches to investigating sporadic cases of suspected food poisoning.

Local authorities in England were surveyed in 1997 to document their approach to investigating sporadic cases of suspected food poisoning, the data they collect, and their objectives for doing so. Three hundred and nineteen of the 359 authorities (89%) responded. The main objectives stated were to prevent spread of infection, detect outbreaks, educate the public, and identify risk factors for infection. Most outbreaks of food poisoning were detected as a result of complaints from members of the public. Investigation of Salmonella spp and Vero cytotoxin producing Escherichia coli O157 appeared to have a higher priority than campylobacter infection and viral gastroenteritis. Eighty-five per cent (266/311) of local authorities had agreed timescales for investigating cases and 54% (165/306) reported using computer technology to collate and analyse data on sporadic cases of food poisoning. Almost all (243/244) respondents supported the idea of having a new national system for the collation of such data and 79% (244/309) expressed interest in piloting a new standard form for enhanced surveillance of food poisoning.

Community Participation↗
PubMed2000

Evaluation of a pilot standard questionnaire for the enhanced surveillance of sporadic cases of suspected food poisoning.

A national survey of local authorities, carried out in 1997, investigated how they dealt with sporadic cases of suspected food poisoning. A standard questionnaire for recording routine follow up information was then designed and piloted for three months in 30 local authorities in England. The questionnaire captured information on clinical and demographic details and exposure histories such as contact with animals, recreational exposure to water, and travel but was less successful at capturing information on domestic catering practices and food consumption. A successful surveillance questionnaire must be designed carefully to gather essential data without overburdening investigating officers.

England↗
PubMed1999

The promise of comparative genomics in mammals.

Dense genetic maps of human, mouse, and rat genomes that are based on coding genes and on microsatellite and single-nucleotide polymorphism markers have been complemented by precise gene homolog alignment with moderate-resolution maps of livestock, companion animals, and additional mammal species. Comparative genetic assessment expands the utility of these maps in gene discovery, in functional genomics, and in tracking the evolutionary forces that sculpted the genome organization of modern mammalian species.

Animals↗
PubMed1999

Phenotypic expressions of CCR5-delta32/delta32 homozygosity.

OBJECTIVE: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-delta32/delta32 homozygous genotype has phenotypic expressions other than those related to HIV-1. DESIGN: Study subjects were white homosexual men or men with hemophilia who were not infected with HIV-1. In this study, 15 CCR5-delta32/delta32 homozygotes were compared with 201 CCR5 wild-type (+/+) subjects for a wide range of clinical conditions and laboratory assay results ascertained during prospective cohort studies and routine clinical care. CCR5-delta32 genotype was determined by polymerase chain reaction, followed by single-stranded conformational polymorphism analysis. RESULTS: Hypertension and conditions attributable to hemophilia were the only diagnoses frequently found in clinical records of CCR5-delta32/delta32 study subjects. Based on blood pressure measurement and treatment history, CCR5-delta32/delta32 homozygotes had a 2.8-fold higher prevalence of hypertension than age-matched CCR5-+/+ study subjects (95% confidence interval [CI], 1.2-6.4; p = .01); none of the homozygotes had severe hypertension. Hematologic measures were generally similar across the genotypes, but total lymphocyte counts were approximately 20% higher in CCR5-delta32/delta32 study subjects than in CCR5-+/+ study subjects (p < .05). Among patients with hemophilia who were infected with hepatitis C virus (HCV), mean alanine aminotransferase levels were 117% higher among CCR5-delta32/delta32 homozygotes (p < .05), but serum HCV levels did not differ by CCR5-delta32 genotype. CCR5-delta32/delta32 homozygous study subjects had a lower prevalence of antibodies to measles virus than those with other genotypes, but this association was not confirmed in a group of blood donors. The prevalence of antibodies to nine other common viruses, HBV, and HCV was not related to CCR5 genotype. CONCLUSIONS: CCR5-delta32/delta32 homozygotes are generally similar to wild-type persons. Confirmatory investigations are required to determine whether hypertension, increased lymphocyte counts, and higher hepatic enzyme levels in the presence of HCV infection represent true phenotypic expressions of this genotype. CCR5-delta32/delta32 homozygosity does not provide broad protection against viral infections.

Adult↗
PubMed1999

Effects of plasma HIV RNA, CD4+ T lymphocytes, and the chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophiliacs. Hemophilia Growth and Development Study.

We have investigated the effects of plasma HIV RNA, CD4+ T lymphocytes and chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophiliacs. We prospectively observed during follow-up 207 HIV-infected hemophiliacs in the Hemophilia Growth and Development Study. Plasma HIV RNA was measured on cryopreserved plasma from enrollment using the Chiron Corporation bDNA (version 2.0) assay. Genoytpe variants CCR2b-641 and CCR5-delta32 were detected using standard molecular techniques. Those with the mutant allele for CCR2b, and to a lesser extent CCR5, had lower plasma HIV RNA, and higher CD4+ T lymphocytes than did those without these genetic variants. After controlling for the effects of plasma HIV RNA and CD4+ T lymphocytes, those with the CCR2b mutant allele compared with those wild-type, had a trend toward a lower risk of progression to AIDS, adjusted relative hazard of 1.94 (95% confidence interval [CI], 0.9-4.18; p = .092), and AIDS-related death, relative hazard 1.97 (95% CI, 0.98-4.00; p = .059). We conclude that plasma HIV RNA, CD4+ T lymphocytes, and CCR genotypes are correlated, and the protective affect of CCR2b against HIV disease progression is not completely explained by plasma HIV RNA or CD4+ T-lymphocyte number.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Reduced risk of AIDS lymphoma in individuals heterozygous for the CCR5-delta32 mutation.

Non-Hodgkin's lymphoma (NHL) has been increasing in frequency in the industrialized world, but the environmental and genetic factors that contribute to susceptibility are not known. B-cell lymphomas represent a major cause of morbidity and mortality in HIV-infected individuals. The identification of a deletion in the CCR5 chemokine receptor gene that alters the risk for infection and progression to AIDS led us to examine a potential role of this gene in AIDS lymphoma. A matched case-control analysis was performed using all eligible NHL cases in the Multicenter AIDS Cohort Study. Patients were matched for age, study center, time AIDS-free, and slope of the CD4+ T-cell decline. The CCR5-delta32 allele was found to be associated with a 3-fold lower risk of NHL among individuals after controlling for time of infection and progression toward AIDS. The CCR5 gene was not associated with a difference in risk for Kaposi's sarcoma, another common malignancy in AIDS patients, or opportunistic infections. Costimulation of normal phorbol 12-myristate 13-acetate-treated B cells with the CCR5 ligand RANTES induced a proliferative response, indicating that RANTES is a mitogen for B cells. Taken together, these findings suggest that the CCR5 gene plays a role in the risk of NHL in HIV-infected patients, perhaps through a mechanism involving a decreased response of B cells to the mitogenic activity of RANTES.

AIDS-Related Opportunistic Infections↗
PubMed1999

Development of a feline whole genome radiation hybrid panel and comparative mapping of human chromosome 12 and 22 loci.

A 5000-rad whole genome radiation hybrid panel is described for the domestic cat, derived from irradiated male feline fibroblasts fused to a recipient hamster cell line. A panel of 93 cell lines has an estimated retention frequency of 0.39 (range 0.13-0.71) based upon PCR typing of 54 feline markers. To test the panel's utility, we determined the order of 16 Type I (coding gene) loci, 14 Type II (microsatellite) loci, and 1 endogenous retroviral element on feline chromosomes B4 and D3. Assessment of marker order derived from the RH panel was compared to assignments of the same loci using interspecies backcross mapping data, human homologue positions, and human-cat chromosome painting homologies. Assessment of concordant and discordant marker order for these loci provides improved resolution into the evolution of subchromosomal genome organizations and the methods to track them in these species.

Animals↗
PubMed1999

A genetic linkage map of microsatellites in the domestic cat (Felis catus).

Of the nonprimate mammalian species with developing comparative gene maps, the feline gene map (Felis catus, Order Carnivora, 2N = 38) displays the highest level of syntenic conservation with humans, with as few as 10 translocation exchanges discriminating the human and feline genome organization. To extend this model, a genetic linkage map of microsatellite loci in the feline genome has been constructed including 246 autosomal and 7 X-linked loci. Two hundred thirty-five dinucleotide (dC. dA)n. (dG. dT)n and 18 tetranucleotide repeat loci were identified and genotyped in a two-family, 108-member multigeneration interspecies backcross pedigree between the domestic cat (F. catus) and the Asian leopard cat (Prionailurus bengalensis). Two hundred twenty-nine loci were linked to at least one other marker with a lod score >/=3.0, identifying 34 linkage groups. Representative markers from each linkage group were assigned to specific cat chromosomes by somatic cell hybrid analysis, resulting in chromosomal assignments to 16 of the 19 feline chromosomes. Genome coverage spans approximately 2900 cM, and we estimate a genetic length for the sex-averaged map as 3300 cM. The map has an average intragroup intermarker spacing of 11 cM and provides a valuable resource for mapping phenotypic variation in the species and relating it to gene maps of other mammals, including human.

Animals↗
PubMed1999

HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage.

A selective advantage against infectious disease associated with increased heterozygosity at the human major histocompatibility complex [human leukocyte antigen (HLA) class I and class II] is believed to play a major role in maintaining the extraordinary allelic diversity of these genes. Maximum HLA heterozygosity of class I loci (A, B, and C) delayed acquired immunodeficiency syndrome (AIDS) onset among patients infected with human immunodeficiency virus-type 1 (HIV-1), whereas individuals who were homozygous for one or more loci progressed rapidly to AIDS and death. The HLA class I alleles B*35 and Cw*04 were consistently associated with rapid development of AIDS-defining conditions in Caucasians. The extended survival of 28 to 40 percent of HIV-1-infected Caucasian patients who avoided AIDS for ten or more years can be attributed to their being fully heterozygous at HLA class I loci, to their lacking the AIDS-associated alleles B*35 and Cw*04, or to both.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Rapid radiation events in the family Ursidae indicated by likelihood phylogenetic estimation from multiple fragments of mtDNA.

The bear family (Ursidae) presents a number of phylogenetic ambiguities as the evolutionary relationships of the six youngest members (ursine bears) are largely unresolved. Recent mitochondrial DNA analyses have produced conflicting results with respect to the phylogeny of ursine bears. In an attempt to resolve these issues, we obtained 1916 nucleotides of mitochondrial DNA sequence data from six gene segments for all eight bear species and conducted maximum likelihood and maximum parsimony analyses on all fragments separately and combined. All six single-region gene trees gave different phylogenetic estimates; however, only for control region data was this significantly incongruent with the results from the combined data. The optimal phylogeny for the combined data set suggests that the giant panda is most basal followed by the spectacled bear. The sloth bear is the basal ursine bear, and there is weak support for a sister taxon relationship of the American and Asiatic black bears. The sun bear is sister taxon to the youngest clade containing brown bears and polar bears. Statistical analyses of alternate hypotheses revealed a lack of strong support for many of the relationships. We suggest that the difficulties surrounding the resolution of the evolutionary relationships of the Ursidae are linked to the existence of sequential rapid radiation events in bear evolution. Thus, unresolved branching orders during these time periods may represent an accurate representation of the evolutionary history of bear species.

Animals↗
PubMed1999

Equine synteny mapping of comparative anchor tagged sequences (CATS) from human Chromosome 5.

Comparative anchor tagged sequences (CATS) from human Chromosome 5 (HSA5) were used as PCR primers to produce molecular markers for synteny mapping in the horse. Primer sets for 21 genes yielded eight horse-specific markers, which were mapped with the UC Davis horse-mouse somatic cell hybrid panel into two synteny groups: UCD14 and UCD21. These data, in conjunction with earlier human chromosome painting studies of the horse karyotype and synteny mapping of horse microsatellite markers physically mapped by FISH, confirm the assignment of UCD21 to ECA21 and suggest that UCD14 is located on ECA14. In addition, our results can be used to substantiate previously published data which indicate that ECA21 contains material orthologous to HSA5p and HSA5q, and to propose an approximate region for an evolutionary chromosomal rearrangement event.

Animals↗
PubMed1999

Sural nerve entrapment after injury to the gastrocnemius: a case report.

A 43-year-old man developed progressive calf pain and paresthesias after a strain of the right gastrocnemius muscle. Physical examination revealed sensory loss in the distribution of the sural nerve with a positive Tinel's sign in the posterior calf in the region of his previous injury. Electrodiagnostic studies revealed prolongation of the sural distal latency with reduction of the sensory nerve action potential amplitude. Magnetic resonance imaging of the lower right leg demonstrated abnormal signal in the right medial gastrocnemius consistent with a subacute hematoma. Surgical exploration revealed entrapment of the sural nerve in scar tissue beneath the deep fascia of the gastrocnemius. Surgical release of the nerve resulted in complete resolution of symptoms and full return of sensation by the 3-month follow-up point. A brief review of the literature is presented.

Action Potentials↗