Search PubMed⌕ Search

Biomedical subjects

L Morrison

Publications and source records attributed to L Morrison.

At least 37 records · Page 2Linked to original sources
PubMed2000

Does MRSA affect patient outcomes in the elderly? A retrospective pilot study.

We retrospectively studied admissions to our geriatric acute assessment and rehabilitation ward over a one-year period, to identify those with Methicillin-resistant Staphylococcus aureus (MRSA) and determine whether this affected outcomes. Two hundred and thirty eight admissions of 204 patients were analysed and 9.8% of patients were MRSA positive. Demographics did not differ between MRSA positive and negative patients. Respiratory co-morbidity was more common in MRSA positive patients. Rates of functional decline did not differ between the two groups. Those colonized or infected by MRSA had a significantly longer stay (51.4 vs. 32.2 days, P=0.03), perhaps due to isolation and limited rehabilitation. The virulence of MRSA may be less in these patients, therefore isolation may be inappropriate and counter-productive.

Aged↗
PubMed2000

Improvements of preimplantation diagnosis of aneuploidy by using microwave hybridization, cell recycling and monocolour labelling of probes.

Recent studies indicate that preimplantation genetic diagnosis of aneuploidy significantly reduces spontaneous abortions and increases pregnancy rates in women of advanced maternal age undergoing in-vitro fertilization. A new protocol was developed involving cell recycling (sequential hybridizations) and microwave hybridization of repetitive probes in order to obtain in a few hours enumeration results for chromosomes X, Y, 1, 13, 15, 16, 18, 21 and 22 in single blastomeres. The error rate using this protocol was significantly lower than in previous protocols and the analysis of nine chromosomes can be achieved in a shorter time than before.

Adult↗
PubMed1999

Breast screening: GPs' beliefs, attitudes and practices.

OBJECTIVES: We aimed to describe GPs' knowledge, beliefs and attitudes towards breast screening, and their association with practice-based organizations of breast screening. METHOD: A stratified randomized sample of 158 GPs from within the North-East and North-West Thames Health Regions were interviewed. RESULTS: Sixty-five per cent of GPs report checking the accuracy of invitation lists, and differ from those who do not, in having more knowledge about risk factors for breast cancer. Thirty-seven per cent of GPs report a policy of following up non-attendees for screening and differ from those who do not in three ways: a greater perception of the threat of breast cancer; a greater belief in the importance of GPs' role in increasing attendance of women for breast screening; and, a less-negative attitude towards breast screening. CONCLUSION: Women's attendance for breast screening may be increased by raising GPs' perceptions of the threat of breast cancer, addressing their concerns about breast screening and enhancing their views of the importance of the role of primary care in a national screening programme.

Breast Neoplasms↗
PubMed1999

Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1).

Cerebral cavernous malformations (CCM) are congenital vascular anomalies of the brain that can cause significant neurological disabilities, including intractable seizures and hemorrhagic stroke. One locus for autosomal dominant CCM ( CCM1 ) maps to chromosome 7q21-q22. Recombination events in linked family members define a critical region of approximately 2 Mb and a shared disease haplotype associated with a presumed founder effect in families of Mexican-American descent points to a potentially smaller region of interest. Using a genomic sequence-based positional cloning strategy, we have identified KRIT1, encoding a protein that interacts with the Krev-1/rap1a tumor suppressor, as the CCM1 gene. Seven different KRIT1 mutations have been identified in 23 distinct CCM1 families. The identical mutation is present in 16 of 21 Mexican-American families analyzed, substantiating a founder effect in this population. Other Mexican-American and non-Hispanic Caucasian CCM1 kindreds harbor other KRIT1 mutations. Identification of a common Mexican-American mutation has potential clinical significance for presymptomatic diagnosis of CCM in this population. In addition, these data point to a key role for the Krev-1/rap1a signaling pathway in angiogenesis and cerebrovascular disease.

Blood Vessels↗
PubMed1999

Achieving compliance with pool fencing legislation in New Zealand: a survey of regulatory authorities.

OBJECTIVES: To identify the status of compliance and enforcement of New Zealand's Fencing of Swimming Pools Act (FOSP Act), 10 years after its introduction, and to identify methods for improving both compliance with the act and the process of enforcement. METHODS: A postal questionnaire was sent to all 74 authorities in New Zealand in which they were asked questions about their enforcement of the FOSP Act. Semistructured telephone interviews were conducted with 12 authorities to supplement the data obtained in the postal survey. RESULTS: Based on responses to the survey, it was estimated that there are over 59,000 domestic swimming pools in New Zealand, giving rates of 46 pools/1000 dwellings and 16 pools/1000 persons. The authorities reported that 44% of pools complied with the act, and a further 4% had been granted exemptions. Nineteen per cent of pools were reported to not comply with the act, and the compliance status of a further 33% was not known, or not stated by the authority. Only 9% of authorities had procedures for locating and inspecting pools, while 28% had a programme of reinspection to ensure that pools continued to comply. Pool owner resistance was considered to be the main difficulty with enforcing the act, and nearly half of the authorities believed publicity or education was needed to overcome these barriers. Fifty two per cent of authorities had publicized the act during the 12 months preceding the survey. CONCLUSIONS: Due to ambiguities within the legislation, and differing levels of commitment by authorities to locate pools and monitor compliance, compliance with the FOSP Act is not consistent nationally. If the act were less ambiguous, there would be greater consistency and more enforcement.

Accident Prevention↗
PubMed1999

Intracellular adhesion molecule-1 modulates beta-chemokines and directly costimulates T cells in vivo.

The potential roles of adhesion molecules in the expansion of T cell-mediated immune responses in the periphery were examined using DNA immunogen constructs as model antigens. We coimmunized cDNA expression cassettes encoding the adhesion molecules intracellular adhesion molecule-1 (ICAM-1), lymphocyte function associated-3 (LFA-3), and vascular cell adhesion molecule-1 (VCAM-1) along with DNA immunogens, and we analyzed the resulting antigen-specific immune responses. We observed that antigen-specific T-cell responses can be enhanced by the coexpression of DNA immunogen and adhesion molecules ICAM-1 and LFA-3. Coexpression of ICAM-1 or LFA-3 molecules along with DNA immunogens resulted in a significant enhancement of T-helper cell proliferative responses. In addition, coimmunization with pCICAM-1 (and more moderately with pCLFA-3) resulted in a dramatic enhancement of CD8-restricted cytotoxic T-lymphocyte responses. Although VCAM-1 and ICAM-1 are similar in size, VCAM-1 coimmunization did not have any measurable effect on cell-mediated responses. These results suggest that ICAM-1 and LFA-3 provide direct T-cell costimulation. These observations are further supported by the finding that coinjection with ICAM-1 dramatically enhanced the level of interferon-gamma (IFN-gamma) and beta-chemokines macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and regulated on activation normal T-cell expression and secreted (RANTES) produced by stimulated T cells. Through comparative studies, we observed that ICAM-1/LFA-1 T-cell costimulatory pathways are independent of CD86/CD28 pathways and that they may synergistically expand T-cell responses in vivo.

AIDS Vaccines↗
PubMed1998

Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine.

Nucleic acid immunization has been investigated as immunotherapy for infectious diseases as well as for treating specific types of cancers. In this approach, nucleic acid expression cassettes are directly inoculated into the host, whose transfected cells become the production source of novel and possibly immunologically foreign protein. We have developed a DNA vaccine construct which encodes for PSA by cloning a cDNA for PSA into a mammalian expression vector under control of a CMV promoter. We investigated and characterized the immunogenicity of PSA DNA expression cassettes in mice. PSA-specific immune responses induced in vivo by immunization were characterized by enzyme-linked immunosorbent assay (ELISA), T helper proliferation cytotoxic T lymphocyte (CTL), and flow cytometry assays. We observed a strong and persistent antibody response against PSA for at least 180 days following immunization. In addition, a significant T helper cell proliferation was observed against PSA protein. Using synthetic peptides spanning the PSA open frame, we identified four dominant T helper epitopes of PSA. Furthermore, immunization with PSA plasmid induced MHC Class I CD8+ T cell-restricted cytotoxic T lymphocyte response against tumor cell targets expressing PSA. The prostate represents a very specific functional organ critical for reproduction but not for the health and survival of the individual. Understanding the immunogenicity of PSA DNA immunization cassettes offers insight into the possible use of this tumor-associated antigen as a target for immunotherapy. These results demonstrate the ability of the genetic PSA to serve as a specific immune target capable of generating both humoral and cellular immune responses in vivo.

Animals↗
PubMed1998

CD8 positive T cells influence antigen-specific immune responses through the expression of chemokines.

The potential roles of CD8(+) T-cell-induced chemokines in the expansion of immune responses were examined using DNA immunogen constructs as model antigens. We coimmunized cDNA expression cassettes encoding the alpha-chemokines IL-8 and SDF-1alpha and the beta-chemokines MIP-1alpha, RANTES, and MCP-1 along with DNA immunogens and analyzed the resulting antigen-specific immune responses. In a manner more similar to the traditional immune modulatory role of CD4(+) T cells via the expression of Th1 or Th2 cytokines, CD8(+) T cells appeared to play an important role in immune expansion and effector function by producing chemokines. For instance, IL-8 was a strong inducer of CD4(+) T cells, indicated by strong T helper proliferative responses as well as an enhancement of antibody responses. MIP-1alpha had a dramatic effect on antibody responses and modulated the shift of immune responses to a Th2-type response. RANTES coimmunization enhanced the levels of antigen-specific Th1 and cytotoxic T lymphocyte (CTL) responses. Among the chemokines examined, MCP-1 was the most potent activator of CD8(+) CTL activity. The enhanced CTL results are supported by the increased expression of Th1 cytokines IFN-gamma and TNF-alpha and the reduction of IgG1/IgG2a ratio. Our results support that CD8(+) T cells may expand both humoral and cellular responses in vivo through the elaboration of specific chemokines at the peripheral site of infection during the effector stage of the immune response.

AIDS Vaccines↗
PubMed1998

Angiotensin-converting enzyme genotypes and risk for myocardial infarction in women.

OBJECTIVES: We tested for an association between the angiotensin-converting enzyme (ACE) DD polymorphic genotype and myocardial infarction (MI) in a sample group composed exclusively of women. BACKGROUND: The human ACE gene occurs with either an insertion (I allele) or a deletion (D allele) of a 287-base pair (bp) Alu element. Part of the variance in serum ACE levels may be accounted for by this polymorphism. Also, the DD genotype has been associated with an increased risk of MI in predominantly male populations. However, the risk in women is poorly defined. METHODS: Genomic DNA was extracted from buffy coat blood using a phenol/chloroform method. Angiotensin-converting enzyme alleles were identified using primers to bracket the insertion region in intron 16. Amplification using polymerase chain reaction allowed identification of a 490-bp (I allele) or a 190-bp (D allele) product, or both. RESULTS: Allelic and genotypic frequencies in control subjects were similar to those reported in mostly male populations, and frequencies of genotypes were in the Hardy-Weinberg equilibrium. In contrast, the distribution of genotypes in patients with MI diverged from the equilibrium. Specifically, DD genotypic frequency was increased in women with (n = 141) versus without (n = 338) a previous MI (39% vs. 29%, odds ratio [OR] 1.54, 95% confidence interval 1.02 to 2.32, p < 0.04). Risk was particularly increased in women <60 years old (OR 2.04, p < 0.05). In contrast, the DD genotype did not predict angiographic coronary artery disease. CONCLUSIONS: Consistent with findings in male-dominated populations, a modest association of the ACE DD genotype with MI was found in women. The basis for this association requires further study.

Aged↗
PubMed1998

Preimplantation diagnosis of the aneuploidies most commonly found in spontaneous abortions and live births: XY, 13, 14, 15, 16, 18, 21, 22.

The present preimplantation diagnosis test is able to screen for the most common aneuploidies from single blastomeres in about five hours with a 15 per cent misdiagnosis. This means that the risk of spontaneous abortion and trisomic offspring for women of advanced maternal age could be reduced to the same level as younger women for whom prenatal diagnosis is usually not necessary. Better probes and more fluorochromes could improve the success rate of the test.

Abortion, Spontaneous↗
PubMed1998

Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens.

Immunization with nucleic acids has been shown to induce both antigen-specific cellular and humoral immune responses in vivo. We hypothesize that immunization with DNA could be enhanced by directing specific immune responses induced by the vaccine based on the differential correlates of protection known for a particular pathogen. Recently we and others reported that specific immune responses generated by DNA vaccine could be modulated by co-delivery of gene expression cassettes encoding for IL-12, granulocyte-macrophage colony-stimulating factor and the co-stimulatory molecule CD86. To further engineer the immune response in vivo, we investigated the induction and regulation of immune responses following the co-delivery of pro-inflammatory cytokine (IL-1 alpha, TNF-alpha, and TNF-beta), Th1 cytokine (IL-2, IL-12, IL-15, and IL-18), and Th2 cytokine (IL-4, IL-5 and IL-10) genes. We observed enhancement of antigen-specific humoral response with the co-delivery of Th2 cytokine genes IL-4, IL-5, and IL-10 as well as those of IL-2 and IL-18. A dramatic increase in antigen-specific T helper cell proliferation was seen with IL-2 and TNF-alpha gene co-injections. In addition, we observed a significant enhancement of the cytotoxic response with the co-administration of TNF-alpha and IL-15 genes with HIV-1 DNA immunogens. These increases in CTL response were both MHC class I restricted and CD8+ T cell dependent. Together with earlier reports on the utility of co-immunizing using immunologically important molecules together with DNA immunogens, we demonstrate the potential of this strategy as an important tool for the development of more rationally designed vaccines.

AIDS Vaccines↗
PubMed1998

Spontaneous abortions are reduced after preconception diagnosis of translocations.

PURPOSE: Preimplantation genetic diagnosis of translocations has seldom been attempted. Recently, a genetic test based on analyzing polar bodies at the methaphase stage, following fluorescent in situ hybridization with commercially available whole-chromosome painting DNA probes has been presented. Here we report the use of this method in seven couples in whom the female was a carrier of one of these balanced translocations: 45,XX,der (13q;14q)(q10;q10) (two cases), 46,XX,t(4;14)(p15.3;q24), 45,XX,der(14q;21q) (q10;q10), 46,XX,t(7;20)(q22;q11.2), 46,XX,t(9,11)(p24;q12), 46,XX,t(14;18)(q22;q11), and 46,XX,t(3;8)(q11;q11). METHODS: The original method was improved in two ways. First, centromeric probes for one or both chromosomes involved in the translocation were added to avoid misdiagnosis caused by possible confusion of first polar body monovalent chromosomes (with two chromatids each) with single chromatids. Second, for cases with terminal translocations where commercially available probes do not cover telomere sequences, a telomere probe labeling the translocated fragment was added. RESULTS: A total of 26 abnormal, 18 balanced, and 22 normal eggs was detected. Nine normal and seven balanced embryos were transferred, resulting in eight (50%) implanting, of which one spontaneously aborted. To date, the remainder have produced karyotypically normal or balanced babies and ongoing pregnancies. The rate of spontaneous abortions after preimplantation genetic diagnosis (12.5%) was significantly reduced (P < 0.001) compared to natural cycles in the same patients (95%). CONCLUSIONS: With the above improvements, the test can characterize any translocation of maternal origin and produce a high pregnancy rate and an apparently low frequency of spontaneous abortion.

Abortion, Spontaneous↗
PubMed1998

Scoring criteria for preimplantation genetic diagnosis of numerical abnormalities for chromosomes X, Y, 13, 16, 18 and 21.

Fluorescence in-situ hybridization (FISH) for application in preimplantation genetic diagnosis (PGD) of aneuploidy has been used successfully, but stringent scoring criteria to score FISH signals have not been developed. In the present study a FISH protocol to simultaneously enumerate chromosomes X, Y, 13, 16, 18, and 21 was used to evaluate two different scoring criteria. The criteria consider hybridization signal size, shape, and vicinity to other signals and nuclear diameter. For this purpose, 74 embryos (412 blastomeres) donated for research had most or all of their cells analysed. The least error-prone criterion (9%) was selected for use in PGD cases. Some probes produced more errors than others, and these criteria may provide clues to improve these probes. The same probe solution was applied to 55 PGD cases and a total of 307 embryos. Of the non-transferred embryos, 67 were fully reanalysed and 1.5% (1/67) of them were falsely diagnosed as normal, while 19% (13/67) were falsely diagnosed as abnormal. Twelve of the patients became pregnant after PGD.

Aneuploidy↗
PubMed1997

Beds not bombs.

Explore the source record for details and available documents.

Global Health↗
PubMed1997

Epidemiology of nematodosis in Romney lambs selectively bred for resistance or susceptibility to nematode infection.

Field trials were undertaken to compare nematode population dynamics, lamb productivity and levels of breech soiling in experimental flocks of Romney lambs selectively bred for increased resistance or susceptibility to nematode infection. In each year of the 2 year study, spring-born ewe lambs derived from Wallaceville Animal Research Centre's divergent nematode-resistant and nematode-susceptible breeding lines were grazed as separate flocks on matched farmlets from weaning (at 3 months old) until they were approximately 10-11 months old. Allocation of farmlets was reversed between Years 1 and 2 of the study to account for any possible paddock-related effects. Within each year both flocks were subjected to identical management conditions, including anthelmintic treatment (which was administered only when the overall mean faecal worm egg count measured across both genotypes reached 1500 eggs g-1). In both years, by mid-autumn (April) nematode larval infestation levels on pasture were approximately 5-6-fold greater on the farmlet grazed by susceptible (S) genotype lambs than on that grazed by their resistant (R) counterparts (Year 1: 2506 cf. 544 larvae kg-1 herbage; Year 2: 431 cf. 74 larvae kg-1 herbage). This led to 51-fold and 56-fold differences in faecal egg count between R and S lambs by late autumn (May) and winter (July) in Years 1 and 2, respectively. Although mean growth rates were similar in the R and S lambs over summer (while pasture infestation levels on the farmlets were still in the process of diverging), significantly higher growth rates occurred in the R than in the S lambs over autumn-winter in both years of the study (P < 0.01). In contrast, no significant differences in growth rate occurred in either year between male lambs derived from the nematode-resistant and nematode-susceptible breeding lines which were grazed together on another area of the Wallaceville farm from weaning until late autumn. Despite the substantially lower pasture infestation levels encountered by the R ewe lambs, they nevertheless temporarily suffered more breech soiling (dags) than their S counterparts (P < 0.01) in both years. Yearling fleece-weights of the R and S genotypes did not differ significantly in either year. Although the results of our study confirmed that there are potentially significant epidemiological benefits to be derived from breeding sheep for resistance to nematode infection, these benefits did not appear to be associated with large advantages in animal performance. Further work is needed to establish how these results should be interpreted with respect to anthelmintic drench requirements of genetically resistant animals.

Animals↗
PubMed1997

Hypertension, serum angiotensinogen, and molecular variants of the angiotensinogen gene among Nigerians.

BACKGROUND: We evaluated the association among the M235T and T174M variants of the angiotensinogen (AGT) gene, plasma AGT, and hypertension status in a sample of Nigerians. METHODS AND RESULTS: Participants were selected from the extremes of the blood pressure distribution obtained from the population survey of 2509 men and women aged 25 to 74 years. Cases (hypertensive subjects) were individuals who had high blood pressure or were taking antihypertensive medication, and control subjects were individuals with low blood pressure who had never taken antihypertensive medication. We found a significant association between the M235T variant and plasma AGT level. Hypertensive subjects had higher plasma AGT levels compared with control subjects. The allele frequencies of the two variants were similar in the hypertensive patients and the control subjects. CONCLUSIONS: The consistent relationships observed between the M235T variant and the protein product and between plasma level of the protein and hypertension status in different ethnic groups provide some evidence for a biochemical mechanism linking DNA variation in the renin-angiotensin system with the hypertension phenotype.

Adult↗