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Biomedical subjects

R Vaughan

Publications and source records attributed to R Vaughan.

At least 55 records · Page 3Linked to original sources
PubMed1997

HLA-DR and -DQ associations with multiple sclerosis in Turkey.

The DRB, DQA, and DQB subregions of the major histocompatibility complex (MHC) were investigated by polymerase chain reaction and sequence-specific oligonucleotide probe hybridization (PCR/SSO) in 103 multiple sclerosis (MS) patients and 101 healthy controls from Turkey. Significant differences were detected between MS and control populations in the frequencies of DRB1*1501 [29 vs. 14, p = 0.02, odds ratio (OR) = 2.4], DRB1*04 (35 vs. 18, p = 0.01, OR = 2.3), DQB1*0302 (30 vs. 15, p = 0.02, OR = 2.3), DQB1*0602 (27 vs. 10, p = 0.005, OR = 3.2), DQB1*0501 (10 vs. 24, p = 0.01, OR = 0.3), DQA1*0101 (16 vs. 31, p = 0.02, OR = 0.4), and DQA1*0103 (7 vs. 19, p = 0.02, OR = 0.3). These results confirm the proposed positive association of the Dw2 (DRB1*1501 DQA1*0102 DQB1*0602) haplotype with MS in Caucasians in our Turkish population (25 vs. 8, p = 0.003, OR = 3.7). Furthermore, the "putative" haplotype supposed to be more frequent in the MS population of Mediterranean countries, namely DRB1*04 DQA1*03 DQB1*0302, is also associated with MS in Turkey (29 vs. 12, p = 0.006, OR = 2.9). The presence of two different haplotypic associations in MS emphasizes the complexity of the genetic susceptibility to MS in different populations.

Adult↗
PubMed1997

Nickel contamination of gold salts: link with gold-induced skin rash.

Intramuscular chrysotherapy is a well-established treatment for rheumatoid arthritis. Its therapeutic use has been limited by the high incidence of dermatological side-effects. The pathogenic mechanisms of these are unknown, but could include allergic reactions to gold or to nickel contaminating the gold. In order to investigate these mechanisms further, 15 patients, who developed cutaneous eruptions after chrysotherapy, were assessed using skin biopsy and lymphocyte transformation stimulated by gold and nickel salts in vitro. Chrysotherapy induced two main cutaneous eruptions: lichenoid reactions and non-specific dermatitis. Peripheral blood mononuclear cells from patients with lichenoid reaction proliferated to gold salts in vitro, while those who developed non-specific dermatitis responded mainly to nickel. Nickel was a significant contaminant of the gold preparation (sodium aurothiomalate, Myocrisin, Rhone-Poulenc Ltd), amounting to a total of 650 ng after 6 months treatment. We suggest that a significant percentage of skin reactions during chrysotherapy are due to nickel contamination of the gold preparation.

Adult↗
PubMed1997

The association of HLA-DRB genes and the shared epitope with rheumatoid arthritis in Pakistan.

The association of particular HLA-DR alleles and the shared epitope with rheumatoid arthritis (RA) is now well established. The strength of these links varies between races. Furthermore, the proposition that the presence of the shared epitope is indicative of severe disease has been more difficult to sustain in non-Europeans. This study examines the frequency of HLA-DR and HLA-DRB1 amongst Pakistanis for the first time. Using the polymerase chain reaction (PCR) and sequence-specific oligonucleotide probes (PCR-SSOP) and primers (PCR-SSP), HLA-DR phenotype and genotype frequencies were ascertained in 86 RA hospital out-patients and 79 healthy controls matched for age, gender and ethnicity. HLA-DR1 and HLA-DR4 frequency was similar in patients and controls. HLA-DR10 occurred in 26 instances (15%) in RA and in eight (5%) controls (Pcorr = 0.048). HLA-DR2 was also increased in patients (P = 0.053) and its major subtype DR15 was significantly increased (Pcorr = 0.03). HLA-DR5 frequency was 5% in patients and 19% in controls (Pcorr = 0.002). The HLA-DR4 alleles possessing the shared epitope were more common in RA (Pcorr = 0.03) and this difference was enhanced by inclusion of other alleles possessing the shared epitope (Pcorr = 0.002). Shared epitope alleles were observed in 43 (50%) patients and 17 (22%) controls (Pcorr = 0.003). The shared epitope did not distinguish patients with more severe disease, as reflected by pain, joint deformities, disability, rheumatoid factor or X-ray damage. The distribution of HLA-DR alleles in Pakistanis with RA supports the shared epitope hypothesis. In common with other non-European racial groups, HLA-DR4 was not associated with RA. Unlike other groups, there was a weak link of RA with HLA-DR2. A protective effect of HLA-DR5 was apparent. In accord with some other studies, the shared epitope in this hospital out-patient population was not a marker for more severe disease.

Adolescent↗
PubMed1997

A self-help smoking cessation program for inner-city African Americans: results from the Harlem Health Connection Project.

The authors develop and test a culturally sensitive, low-intensity smoking cessation intervention for low-socioeconomic African Americans. African American adult smokers were randomly assigned to receive either a multicomponent smoking cessation intervention comprising a printed guide, a video, and a telephone booster call or health education materials not directly addressing tobacco use. The results of the study were mixed. Although no significant effects were observed for the entire treatment cohort, the results of post hoc analyses suggest that culturally sensitive self-help smoking cessation materials plus a single phone contact can produce short-term cessation rates similar to those reported for majority populations. This conclusion should be tempered by the low completion rate for the booster call and several design limitations of the study.

Adolescent↗
PubMed1997

Changes in psychotropic medication use in nursing homes over a 9-month period.

A 1993 survey of nursing home residents in one part of Sydney was repeated 9 months later. Details of psychotropic medication given to the 1433 residents who survived and remained in the same 38 nursing homes were examined. There were modest reductions in the percentage of residents taking neuroleptics, anxiolytics and hypnotics, but there was an increase from 16.0% to 17.6% in the percentage of residents taking antidepressants. About 65% of those taking psychotropic medication at the initial survey remained on exactly the same dose 9 months later. Most of those taking neuroleptic or antidepressant medication were given relatively small daily doses. Intervention studies are desirable to examine how best to improve prescribing practices.

Drug Prescriptions↗
PubMed1997

Why perinatal mortality cannot be a proxy for maternal mortality.

In recent years, the perinatal mortality rate (PNMR) has been proposed as a proxy measure of maternal mortality, because perinatal deaths are more frequent and potentially more easily measured. This report assesses evidence for an association between these two statistics. This study, based upon data from Matlab, Bangladesh, shows that the maternal mortality ratio (MMR) and the PNMR do not vary together over time, and that the PNMR does not reliably indicate either the magnitude or the direction of change in the MMR from year to year. Statistical analysis shows that the correlation between the PNMR and the MMR is not significantly different from zero. An examination of the major causes of maternal and perinatal deaths indicates that the two measures cannot be expected to vary together. Almost half of perinatal deaths result from causes that do not pose a threat to the mother's life, and almost half of maternal deaths result from causes that do not lead to perinatal death. Monitoring of the PNMR can give an inaccurate picture of maternal mortality and should not be used as a proxy.

Bangladesh↗
PubMed1996

Dopamine transporter immunohistochemistry in median eminence, amygdala, and other areas of the rat brain.

In an extension of our previous work, an antibody directed against a peptide from the N-terminal region of DAT was used to localize specific dopamine transporter immunoreactivity (DAT-IR) in several regions of rat brain. Apparent axons and varicosities were found in the zona incerta, external layer of the median eminence, various nuclei of the amygdala, the cortex-amygdala transition zone, and in periglomerular regions in the olfactory bulb. Apparent stained neuronal perikarya and dendrites were observed in the arcuate nucleus and olfactory bulb. These regions are known to have dopaminergic neurons and innervations, although there was not a perfect correspondence between DAT-IR and the known distribution of dopaminergic neurons. A possible explanation is that different dopamine containing cell groups express different levels of DAT mRNA and protein, as we have previously shown. Also in the tuberoinfundibular neurons, for example, DAT-IR was preferentially localized to distal axons in the median eminence, suggesting intracellular compartmentation.

Amygdala↗
PubMed1996

Genetic and immunological markers in pouchitis.

OBJECTIVES: Previous studies of the interleukin-1 receptor antagonist (IL-1RN) have found an increased frequency of the associated variable number tandem repeat (VNTR) allele 2 for ulcerative colitis (UC) and further evidence has been reported that this allele is associated with increased severity of several other inflammatory conditions. The HLA type of UC patients has also been implicated in the extent of disease as has the presence of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA). We therefore decided to test the hypothesis that the p-ANCA, HLA type or the presence of the IL-1RN allele 2 in patients who received a restorative proctocolectomy for UC had an effect on the risk of developing pouchitis. PATIENTS: We determined the genotypes of the IL-1RN and HLA DR beta and DQ beta loci for 28 subjects with previous UC and a pouch with no evidence of pouchitis for a minimum of 2 years after formation of an ileo-anal reservoir (mean 6.3 years; range 2-17 years) and 25 subjects with previous UC and pouchitis confirmed by strict histological examination of pouch mucosal biopsy. The IL-1RN genotypes were also determined for 86 healthy controls and 61 unrelated patients with familial adenomatous polyposis (FAP). The p-ANCA status was determined for all 25 pouchitis subjects but only 23/28 non-pouchitis subjects, with 15 unaffected subjects as a negative control. METHODS: The HLA haplotypes of the UC groups were determined by polymerase chain reaction sequence-specific primer (PCR-SSP) typing and the IL-1RN genotypes were determined by PCR and agarose gel electrophoresis. The p-ANCA status was determined by indirect immunofluorescence. RESULTS: A chi 2 of 5.686 with 1 degree of freedom and a P value of 0.0171 using Yates' correction was obtained by comparing the IL-1RN allele frequencies of the combined UC groups to the FAP controls, and a chi 2 of 6.801 with 1 degree of freedom and a P value of 0.0091 comparing the pouchitis group to the FAP controls. The HLA haplotype frequencies did not vary significantly between groups nor did they correlate with p-ANCA status. There were also no significant associations of the p-ANCA status and pouchitis. CONCLUSION: There is an increased frequency of IL-1RN allele 2 in UC, with the majority of the association arising from the pouchitis group, suggesting that the presence of allele 2 in patients with UC affects the disease outcome. However, the HLA frequencies and p-ANCA status do not have any significant associations.

Adult↗
PubMed1995

Psychotropic drug use in Sydney nursing homes.

OBJECTIVE: To determine the pattern of use of psychotropic drugs in Sydney nursing homes. DESIGN: Survey of data from medical records of residents and interviews with residents and staff. SETTING: Central Sydney Health Area, June to December 1993. PARTICIPANTS: All residents of 46 of the 47 nursing homes in the western sector of the health area. MAIN OUTCOME MEASURES: Psychotropic drugs used regularly or as required. Degree of cognitive impairment and depression rated on interview with residents, using Mini-Mental State Examination and Geriatric Depression Scale. Behavioural disturbances reported by staff. RESULTS: Most residents (58.9%) were taking one or more psychotropic drugs regularly and another 7% were prescribed these drugs as required. Neuroleptics were taken regularly by 27.4% and as required by a further 1.4% (at least one dose in the previous four weeks), but doses were equivalent to more than 100 mg/day of chlorpromazine for only 8.8%. Neuroleptics were more likely to be given to residents with greater cognitive impairment and more disturbed behaviour. Other psychotropic drugs in regular use were: benzodiazepines (32.3%); hypnotics (26.6%); antidepressants (15.6%); and anxiolytics (8.6%). At least half of antidepressant doses were subtherapeutic. Of 874 residents who responded to a depression questionnaire, 30% scored as significantly depressed; one-third of these were taking antidepressants. CONCLUSIONS: The percentage of residents in Central Sydney nursing homes who were taking neuroleptics, hypnotics or anxiolytics is among the highest reported from geriatric institutions around the world. Prescribing practices in Australian nursing homes need to be reviewed.

Aged↗
PubMed1995

Evaluation of serum eosinophilic cationic protein as a marker of disease activity in chronic asthma.

BACKGROUND: Serum eosinophil cationic protein (ECP) has been promoted as a direct marker of eosinophilic inflammation of the bronchi, especially helpful in patients with asymptomatic asthma. OBJECTIVE: To evaluate serum ECP against indirect clinical markers of disease activity, we compared symptom score, bronchial obstruction, bronchial responsiveness, and blood eosinophil counts with serum ECP levels in children with symptomatic and asymptomatic chronic asthma and assessed ECP in others with allergic rhinitis alone. METHODS: Twenty-four children with symptomatic asthma, 10 children with asymptomatic asthma, and 16 children with allergic rhinitis were studied. Measurements were made by standardized symptom questionnaire, spirometry, inhalation challenge with histamine or methacholine, blood eosinophil counts, and radioimmunoassay of serum ECP. RESULTS: There was no difference in serum ECP levels between the symptomatic asthma, asymptomatic asthma, or rhinitis groups, and most values were within the normal range. Activated eosinophil counts were higher in subjects with symptomatic asthma than in those with asymptomatic asthma but not in subjects with rhinitis. Serum ECP correlated with eosinophil counts (p < 0.01) but not symptom score, forced expiratory volume in 1 second (FEV1), forced expiratory flow, mid-expiratory phase (FEF25-75), or provocative concentration causing a 20% fall in FEV1 (PC20). Symptom scores correlated with PC20 (p < 0.005) and FEF25-75 (p < 0.01). CONCLUSION: Serum ECP is a poor indicator of disease activity in chronic asthma and cannot differentiate bronchial from nasal inflammation.

Adolescent↗
PubMed1995

Recognition of a unique peptide epitope of the mycobacterial and human heat shock protein 65-60 antigen by T cells of patients with recurrent oral ulcers.

T cell epitopes of the 65-kD heat shock protein (hsp) were investigated in patients with recurrent oral ulcers (ROU). Peripheral blood mononuclear cells were stimulated with overlapping synthetic peptide (15ers), derived from the sequence of the 65-kD hsp of Mycobacterium tuberculosis. Specific lymphoproliferative responses were stimulated only with peptide 91-105 in ROU, compared with healthy or disease controls (P < 0.01). This was confirmed by studying 760 short term cell lines generated with the 65-kD hsp and then stimulated with the peptides. The frequency of short term cells lines responding to peptide 91-105 in ROU was significantly greater than in healthy (P < 0.0001) or disease controls (P < 0.01). A comparative investigation with the homologous human 60-kD hsp peptide 116-130 also showed significantly greater lymphoproliferative responses in ROU than in healthy (P < 0.01) or disease controls (P < 0.001). The potential involvement of the T cell epitope 91-105 in the pathogenesis of ROU is supported by finding a significant increase in the lymphoproliferative responses stimulated with peptide 91-105 during the stage of ulceration, compared with remission in 9/11 patients studied sequentially (P < 0.05). The results suggest that oral ulceration might be initiated by the microbial hsp peptide 91-105 stimulating the mucosal Langerhans cells, which may generate autoreactive T cell clones primed to the homologous peptide 116-130.

Adult↗
PubMed1995

Mental health services in Sydney nursing homes.

Senior nursing staff of the 58 nursing homes in one health area of Sydney were interviewed concerning mental health services and staff education. One or more psychiatrically trained staff were employed in 45 per cent of the nursing homes. Most nursing homes received services from a psychiatrist or another mental health professional, but the average time per month provided by them to see residents was less than one hour in 18 (31 per cent), one to two hours in 16 (28 per cent), and three hours or more in only 11 (19 per cent). Forty-four (76 per cent) wanted more mental health services to be provided, especially for advice on management of disturbed behaviour. A substantial number of the nursing homes (at least 28 per cent) provided no ongoing education to their staff about dementia or other psychiatric problems. There is good reason to encourage greater use of mental health professionals in Sydney nursing homes; enhanced funding of area psychiatric services for elderly people is desirable to allow these services to be more readily available.

Aged↗
PubMed1994

Drug resistant tuberculosis in Auckland 1988-92.

AIM: To report the prevalence of drug-resistant Mycobacterium tuberculosis in Auckland. METHOD: Review of all M tuberculosis culture positive cases from January 1988 to December 1992. Ethnicity was recorded from the national Paxus medical information data base and drug sensitivity results from the Green Lane Hospital tuberculosis reference laboratory. The clinical details of all patients with drug resistant tuberculosis were extracted from hospital case records. RESULTS: Of the 417 patients with positive cultures, 43 (10%) had isolates resistant to one or more antituberculous drugs. Only 4 patients had multidrug-resistant organisms (defined as resistance to at least isoniazid and rifampicin) and there is no evidence that this is an increasing problem. Resistance rates were highest in those previously treated for M tuberculosis, and those born in, or likely to have acquired their organism from, Samoa, all other Pacific Islands, or South East Asia. CONCLUSIONS: Drug resistant M tuberculosis is a problem in Auckland but rates and patterns are little different from 1980-1982. Multidrug-resistance is not yet a problem in Auckland, as it is in the United States of America. Ways of maintaining this situation are discussed.

Antitubercular Agents↗
PubMed1994

Localization of ligand-induced phosphorylation sites to serine clusters in the C-terminal domain of the Dictyostelium cAMP receptor, cAR1.

When Dictyostelium cells are stimulated with cyclic adenosine 3',5'-monophosphate (cAMP), the major surface cAMP receptor expressed in early development, cAR1, undergoes a rapid phosphorylation and parallel decrease in electrophoretic mobility which may serve to regulate the activity of this G protein-coupled receptor. Biochemical analyses indicate the electrophoretic mobility shift is caused by phosphorylation of serine residues within the C-terminal cytoplasmic domain. The 18 serines of this domain are grouped in four clusters, designated 1 to 4 (in N- to C-terminal order). Two approaches were taken to determine the distribution of phosphorylation sites among the serine clusters. First, a proteolytic analysis of the C-terminal domain was performed. Second, mutants lacking various combinations of the serine clusters were created by site-directed mutagenesis and their abilities to undergo ligand-induced modification were determined. Both approaches yielded corroborative results consistent with the following model: the stimulus induces the addition of approximately two phosphates to cluster 1 and one to cluster 2; basal phosphorylation occurs predominantly in cluster 3 and to a lesser extent in cluster 2; and cluster 4 is not phosphorylated. The phosphorylation-deficient receptor mutants should be useful for establishing the role of ligand-induced phosphorylation of cAR1 in chemotaxis, cell-cell signaling, and gene expression.

Amino Acid Sequence↗
PubMed1993

T cell epitope expression of mycobacterial and homologous human 65-kilodalton heat shock protein peptides in short term cell lines from patients with Behçet's disease.

T cell epitopes of the 65-kDa heat shock protein (HSP) were mapped in patients with Behçet's disease (BD), by stimulating T cells with the overlapping synthetic peptides derived from the sequences of the Mycobacterium tuberculosis 65-kDa HSP. Significant lymphoproliferative responses were stimulated with four HSP peptides in BD, as compared with the related disease (recurrent oral ulcers), unrelated disease, and healthy controls (p < 0.05 to 0.005). In order to assess the relative frequency of sensitized lymphocytes by these peptides, 7353 short term cell lines were generated from the lymphocytes of patients and controls. Peptides 111-125, 154-172, and 311-325 (p < 0.001) and peptide 219-233 (p < 0.02) yielded significantly greater frequency of STCL in BD than in healthy and disease controls. All but peptide 154-172 stimulated only the CD4+ subset of T cells, although there was no evidence that reactivity to the selected peptides is restricted by DR2 to DR7 Ag. HLA-B51 is significantly associated with BD, but there was no evidence that B51 was a restricting element, when B51+ patients were compared with B51- patients with BD, and with B51+ healthy control subjects. A comparative investigation was then carried out between the corresponding mycobacterial and human HSP peptides. Similar or higher lympho-proliferative responses were stimulated by the human peptides compared with the mycobacterial peptides. These results suggest that the four peptide determinants within the 65-kDa HSP might be involved in the pathogenesis of BD. Whereas the high microbial load and associated stress proteins found in oral ulceration of BD may initiate an immune response to these conserved epitopes, expression of autoreactive T cell clones might be stimulated by immunodominant T cell epitopes of endogenous HSP which may induce immunopathologic changes.

Adult↗
PubMed1993

A molecular and serologic analysis of the major histocompatibility complex and complement component C4 in systemic sclerosis.

OBJECTIVE: To investigate the contributions of the major histocompatibility complex (MHC) and C4 alleles to systemic sclerosis (SSc), and to pulmonary fibrosis and autoantibody expression in SSc, by analysis at the DNA level. METHODS: One hundred fifteen patients with SSc were tested serologically for alleles of the class I MHC loci, and were tested for class II alleles (DRB, DQA, and DPB) by a combination of restriction fragment length polymorphism (RFLP) analysis and oligonucleotide probes with polymerase chain reaction amplification. C4 was studied by protein phenotyping and RFLP analysis in 80 patients. Correlations were made between disease status, pulmonary fibrosis, and expression of anticentromere antibodies (ACA) and anti-Scl-70. RESULTS: The C4A-null phenotype was found to provide the strongest disease association factor of the MHC region (P = 0.000064, relative risk [RR] = 2.8, etiologic fraction [EF] = 32.1). The primary MHC susceptibility allele was found to be DQA2 (Pcorr = 0.0009, RR = 2.5, EF = 35.6), which is in linkage disequilibrium with both DR3 and DR11. DR2 was protective, but only for female patients (P = 0.0021, RR = 0.42, protective fraction = 19.4). DR52a was the primary MHC allele associated with pulmonary fibrosis in SSc patients. Expression of ACA was associated with the presence of either DR1 or DR4 (P = 0.0015, RR = 6.7, EF = 78.0). Anti-Scl-70 expression correlated with an acidic residue of DP beta (DPB1:69:E) (P = 0.0063, RR = 4.6, EF = 53.1). CONCLUSION: Of all the potential markers of disease susceptibility analyzed, the C4A locus was the strongest. C4AQ0 and DQA2 are independent susceptibility factors for SSc. The development of pulmonary fibrosis in SSc patients can be predicted using combined MHC and autoantibody analysis. The MHC alleles associated with the expression of disease-specific autoantibodies are not markers for disease susceptibility.

Alleles↗