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Biomedical subjects

S O'Rourke

Publications and source records attributed to S O'Rourke.

At least 19 recordsLinked to original sources
PubMed1998

Surgical management of diabetic foot complications: the Far North Queensland profile.

BACKGROUND: Foot complications in diabetes incur huge human and medical costs. There is a high incidence of complicated diabetes mellitus in Far North Queensland, particularly in the indigenous communities. METHODS: An audit of 51 patients admitted to Cairns Base Hospital from July 1992 to December 1994 with diabetic foot complications requiring surgical intervention was performed. RESULTS: The majority of surgical procedures were for serious infections in neuropathic feet precipitated by minor trauma. Surgical procedures included debridement/drainage, minor amputation, major amputation and arterial bypass. Half of the patients required more than one procedure and/or multiple admissions. Average length of stay was 48 days. Indigenous patients were overrepresented in this audited group. CONCLUSIONS: Prevention or minimization of diabetic foot complications can be achieved only through improvement in education and vigilance at all levels of the treatment process from community to hospital. Special attention to the needs of indigenous communities with a high incidence of diabetes must be a feature of any future initiatives.

Aged↗
PubMed1998

Detecting psychiatric morbidity after stroke: comparison of the GHQ and the HAD Scale.

BACKGROUND AND PURPOSE: Mood disorders are common after stroke and may impede physical, functional, and cognitive recovery, making early identification and treatment of potential importance. We aimed to compare the accuracy of the General Health Questionnaire (GHQ-30) and the Hospital Anxiety and Depression (HAD) Scale in detecting psychiatric morbidity after stroke and to determine the most suitable cutoff points for different purposes. METHODS: One hundred five hospital-referred stroke patients completed both the GHQ-30 and HAD Scale 6 months after onset before a blinded psychiatric assessment in which the Schedule for Affective Disorders and Schizophrenia with some supplementary questions was used to determine a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis. Measures were compared in terms of sensitivity, specificity, and receiver operating characteristic curves. RESULTS: No significant differences were found between the GHQ-30 and the HAD Scale in identifying those patients with any DSM-IV diagnosis (P=0.95), grouped depression (P=0.56), or anxiety (P=0.25) disorders. The previously recommended cutoff points for identifying "cases" for the GHQ (4/5) and for the HAD Scale (8/9 and 11/12) were found to be suboptimal in this population. CONCLUSIONS: The GHQ-30 and HAD scale exhibited similar levels of sensitivity and specificity. Data are presented, taking into account the "cost" of false-positives and negatives, to allow a choice of cutoff points suitable for differing situations.

Adolescent↗
PubMed1998

A quantitative study of the emotional outcome of people caring for stroke survivors.

BACKGROUND AND PURPOSE: Although the physical and, to a lesser extent, emotional outcome of stroke survivors has been well documented, there are far fewer data relating to the outcomes of those who care for them. We aimed to describe the outcome of those caring for stroke patients and to identify both patient and caregiver factors that are associated with poor caregiver outcomes. METHODS: As part of a randomized trial to evaluate a stroke family care worker, we identified 417 patients (67% of all referrals to our institution). We followed up 376 survivors of whom 246 identified a caregiver at a 6-month follow-up interview. The patients and caregivers were asked to complete 2 measures of emotional distress ( 30-item General Health Questionnaire [GHQ-30] and Hospital Anxiety and Depression [HAD] Scale). A regression analysis was used to identify factors that were independently associated with poor caregiver outcomes. RESULTS: Fifty-five percent of responding caregivers scored more than 4 on the GHQ-30, indicating that emotional distress is common in this group. Caregivers were more likely to be depressed if the patients were severely dependent (P<0.01) or emotionally distressed themselves (P<0.01). Female caregivers reported more anxiety (median HAD=8) than male caregivers (median HAD=5; P<0.01) but caregivers' levels of anxiety were not so clearly related to the patients' degree of physical disability as their levels of depression. Caregivers suffered more emotional distress if the patients had been dependent before their strokes. CONCLUSIONS: These data may help to identify those caregivers at greatest risk of poor emotional outcomes and thus help in the planning of trials and delivery of interventions aimed at preventing or treating distress among caregivers.

Activities of Daily Living↗
PubMed1997

Evaluation of a stroke family care worker: results of a randomised controlled trial.

OBJECTIVE: To examine the effect of contact with a stroke family care worker on the physical, social, and psychological status of stroke patients and their carers. DESIGN: Randomised controlled trial with broad entry criteria and blinded outcome assessment six months after randomisation. SETTING: A well organised stroke service in an Edinburgh teaching hospital. SUBJECTS: 417 patients with an acute stroke in the previous 30 days randomly allocated to be contacted by a stroke family care worker (210) or to receive standard care (207). The patients represented 67% of all stroke patients assessed at the hospital during the study period. MAIN OUTCOME MEASURES: Patient completed Barthel index, Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, mental adjustment to stroke scale, and patient satisfaction questionnaire; carer completed Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, caregiving bassles scale, and carer satisfaction questionnaire. RESULTS: The groups were balanced for all important baseline variables. There were no significant differences in physical outcomes in patients or carers, though patients in the treatment group were possibly more helpless less well adjusted socially, and more depressed, whereas carers in the treatment group were possibly less hassled and anxious. However, both patients and carers in the group contacted by the stroke family care worker expressed significantly greater satisfaction with certain aspects of their care, in particular those related to communication and support. CONCLUSIONS: The introduction of a stroke family care worker improved patients' and their carers' satisfaction with services and may have had some effect on psychological and social outcomes but did not improve measures of patients' physical wellbeing.

Activities of Daily Living↗
PubMed1996

HIV disease in children is associated with a selective decrease in CD23+ and CD62L+ B cells.

We characterized the surface phenotype of B cells from HIV+ children in order to better understand the biology of B cell dysregulation. Twenty-nine HIV-infected, twenty-one exposed, and nineteen age-matched control children were studied for expression of CD5, CD10, CD21, CD23, CD25, CD62L, CD71, and CD69. We conclude that, despite persistent high immunoglobulin levels, total B cells decreased as HIV disease progressed, with selective decreases in CD62L+ and CD23+ B cells. This resulted in an increased proportion of usually minor subpopulations of CD62L- and CD23-negative B cells. We did not find significantly altered B cell expression of other activation/immaturity antigens. This suggests an absolute decrease in a subset of antigen-responsive B cells and a disproportionate increase in a subset of hyperstimulated B cells. These findings provide a biological basis for the paradoxical generalized B cell hyperactivity and specific immune unresponsiveness that are characteristic of HIV infection in children.

Antigens, CD↗
PubMed1996

DNA fingerprinting of benign and malignant breast lesions.

Paired blood and breast tissue samples from 96 patients undergoing surgical excision of a breast lesion were subjected to DNA fingerprint analysis using the minisatellite probes 33.6 and 33.15. The 'fingerprints' of the blood and breast DNA were compared. DNA fingerprint changes seen were classified as band additions, band deletions or changes in band intensity. Significantly more DNA fingerprint changes were seen in malignant than in benign lesions (probe 33.6, P<0.01; probe 33.15, P=0.01; both probes, P = 0.04). The frequency of the changes detected in the breast cancers was unrelated to tumour grade or the presence of invasion. DNA ploidy was measured in 70 of the breast carcinomas. DNA fingerprint changes were seen in 41 of these, but flow cytometry detected aneuploidy in only 29 tumours (P=0.04). The DNA fingerprinting technique is unlikely to be useful in differentiating between benign and malignant breast lesions as changes were detected in one of the fibroadenomas studied. However, it may be a useful technique in screening tumour DNA for abnormalities suitable for more detailed analysis.

Breast Diseases↗
PubMed1995

Cytotoxic T cell responses in patients with chronic hepatitis B virus infection undergoing HBe antigen/antibody seroconversion.

Cytotoxic T cells have been identified in the peripheral blood of patients with acute hepatitis B virus infections for a short period after clinical presentation. However, in patients in whom the virus persists these have been difficult to demonstrate. In the chronic infection during HBe antigen clearance, when there has been an exacerbation of the disease, we have been able to demonstrate an MHC class I-restricted cytolytic response directed against the nucleocapsid antigens. In an HLA-A2 patient this was induced in vitro with the peptide p18-27, previously described as an HLA-A2-restricted T cell epitope. In patients of other HLA types, recombinant core antigen was used to induce antigen-specific lysis: statistical analysis of the cytolytic responses of chronically infected patients demonstrated a nucleocapsid antigen-specific lysis in patients who were seroconverting. Removal of CD4+ cells reduced non-MHC-restricted cytolysis, allowing an MHC class I-restricted cytolytic component to be demonstrated.

Amino Acid Sequence↗
PubMed1995

Recombinant vaccinia viruses expressing hepatitis A virus structural polypeptides: detection of an anti-VP0 response in convalescent-phase sera.

We have generated a number of recombinant vaccinia viruses which expressed the hepatitis A virus (HAV) structural polypeptides VP1, VP2, VP3, and VP4, either alone or in combination. The relevant sequences encoding these polypeptides were amplified from cloned cDNA by PCR and then cloned into the insertion vector pGS62. The presence of the HAV structural polypeptide-encoding sequences in the recombinant viruses was confirmed by Southern blot analysis, whilst their transcription and translation were demonstrated by Northern (RNA) blot analysis and immunodetection, respectively. Immunoprecipitation studies using these constructs have detected the presence of an anti-VP0 response in human convalescent sera following HAV infection. The significance of this finding and the usefulness of these constructs in studying cell-mediated immunity during recovery from HAV infection are discussed.

Antibodies, Viral↗
PubMed1994

Local recurrence after simple mastectomy.

A retrospective study was carried out to determine the clinical significance of local recurrence after simple mastectomy and node biopsy for primary operable breast cancer, without postoperative irradiation or systemic adjuvant therapy. Local recurrence was defined as a histologically proven lesion in or deep to the mastectomy skin flaps. A total of 966 patients with a median follow-up of 7 years were reviewed. Of these, 223 (23 per cent) developed local recurrence but half the tumours were small single lesions; 70 women had multiple discrete lesions and 21 diffuse carcinomatous dermal infiltration. Local recurrence showed significant associations with tumour grade, nodal status and the presence of lymphovascular invasion in the primary tumour. A predictive index containing these three variables was constructed. Adjuvant irradiation of the flaps is recommended for patients with high scores; such women would otherwise have a 39 per cent chance of developing local recurrence by 5 years. Different types of local recurrence have different chances of responding to local therapy: 13 per cent of single local recurrences, 32 per cent of multiple spot recurrences and 70 per cent of the diffuse type failed to respond to local therapy. Local recurrence predicts reduced patient survival.

Aged↗
PubMed1994

Crystal and molecular structures of tricyclic neuroleptics.

The X-ray crystal structures of three tricyclic neuroleptics have been completed and are reported herein. These include amitriptyline hydrochloride (I), chlorprothixene hydrochloride (II), and ethopropazine hydrochloride (III). The structures were compared with the structures of similar molecules with similar pharmacological activity. It was found that there is a great deal of flexibility in the structures of these molecules, which makes it difficult to determine the pharmacologically active conformations. Crystallographic data: (I) C20H24NCl, monoclinic space group P2(1)/a, a = 13.812(4) A, b = 9.140(2) A, c = 14.345(4) A, beta = 96.82(2) degrees, Z = 4, final R = 0.059 for 1630 observed (l > 3 sigma(l)) reflections. (II) C18H20NSCl2.CHCl3, monoclinic space group C2/c, a = 29.416(4) A, b = 6.986(1) A, c = 23.374(3) A, beta = 109.78(1) degrees, Z = 8, final R = 0.046 for 1436 observed reflections. (III) C19H25N2SCl, monoclinic space group P2(1)/c, a = 8.849(1) A, b = 14.475(2) A, c = 14.832(1) A, beta = 98.72(1) degrees, Z = 4, final R = 0.039 for 2583 observed reflections.

Antidepressive Agents, Tricyclic↗
PubMed1994

T cell activation in pediatric AIDS pathogenesis: three-color immunophenotyping.

Immune activation is an important component of HIV disease in adults that may reflect a protective host response and/or be a component of immunopathogenesis. The goals of this study were to gain understanding of T cell activation in pediatric HIV disease, to assess the usefulness of T cell activation markers as surrogates for disease progression and/or early identification of infection in infants at risk, and to determine any advantages of three- compared to two-color flow cytometric immunophenotyping for the above assessments. We examined the expression of cell-surface activation antigens on the CD4 and CD8 T cells of 26 HIV-infected and 40 HIV-seronegative age-matched control children. Compared with controls, HIV-infected children showed a slight but not significant decrease in the proportion of CD4 cells that coexpressed CD45RA and L-selectin (mean of 83 vs 75% for < 2 years of age, 76 vs 62% for 2-3 years, 64 vs 56% for > or = 4 years). CD4 cells coexpressing CD38 and HLA-DR were significantly increased in HIV+ children (mean of 2 vs 6% for < 2 years of age, 3 vs 11% for 2-3 years, 2 vs 8% for > or = 4 years). There was a striking and significant increase in the proportion of CD8 cells coexpressing CD38 and HLA-DR (mean of 5 vs. 25% for < 2 years, 10 vs 41% for 2-3 years, 6 vs 31% for > or = 4 years); this double positive population of CD8 cells included cells that were approximately 1 log brighter for the expression of CD38 than for that of CD38 single-positive cells. There was a significant reduction in CD45RA+ CD8 cells (means of 92 vs 71% for < 2 years of age, 88 vs 50% for 2-3 years, 80 vs 57% for > or = 4 years) and an increase in CD57+ CD8 cells (mean of 4 vs 8% for < 2 years of age, 8 vs 22% for 2-3 years, 19 vs 31% for > or = 4 years) in HIV+ children. The inclusion of CD3 as an anchor marker for CD8 cell subsets to limit the analysis to CD3+ CD8 cells did not substantially alter the data nor enhance the differences between infected and control children compared with the analysis of all CD8 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1994

CD8+ lymphocyte activation at human immunodeficiency virus type 1 seroconversion: development of HLA-DR+ CD38- CD8+ cells is associated with subsequent stable CD4+ cell levels. The Multicenter AIDS Cohort Study Group.

Subsets of activated CD8+ lymphocytes defined by membrane expression of the activation antigens HLA-DR and CD38 were counted by three-color flow cytometry in homosexual men who subsequently became seropositive for human immunodeficiency virus type 1 (HIV). Profound CD8+ cell activation was seen in all subjects at seroconversion and 6 and 12 months later. The HLA-DR+ CD38+ CD8+ cell population, which has potent direct HIV cytotoxic T cell activity, was markedly elevated at seroconversion in all subjects. In some men, these levels remained elevated throughout the first year of infection. During the next 5 years, these men had stable CD4+ cell levels, whereas the others did not. Long-term survivors (seropositive for 9 years, > 800 CD4+ cells/mm3) also had elevated levels of this subset, despite few other activated CD8+ cells. Thus, selective elevation of HLA-DR+ CD38- CD8+ cells was a marker of subsequent stable HIV disease.

ADP-ribosyl Cyclase↗
PubMed1994

Phenotypically defined memory CD4+ cells are not selectively decreased in chronic HIV disease.

Simultaneous measurements of phenotypically defined memory CD4+ cells and in vitro proliferation to three recall antigens (Ags; tetanus toxoid, influenza, and Candida albicans) were performed in 53 HIV-seropositive subjects and 39 HIV-seronegative controls. The results indicate that the low proliferative responses to recall Ags of those who were HIV infected could be partly, but not fully, explained by a decrease of phenotypically defined memory CD4+ cells. This is, to our knowledge, the first report of experiments that simultaneously measured memory CD4+ cell numbers and function and then examined whether the low responses observed in seropositive subjects could be explained by low numbers of phenotypically defined memory CD4+ cells. A central finding of the study, which argues against prevailing dogma, was that within the CD4+ lymphocyte population, the proportion of cells displaying the memory phenotype was not selectively decreased in HIV-seropositive subjects as compared with the proportion of these cells in seronegative homosexual controls. An entirely new finding of the study was that AIDS patients, many of whom were unresponsive to all three recall Ags tested, actually had a significant increase in the proportion of CD4+ cells with the memory phenotype, and this fraction approached 100% in subjects with CD4+ cell numbers that were near zero. A final observation of the study, possible because some patients were on zidovudine (ZDV), was that there was no evidence that ZDV treatment led to an increased proliferative response to recall Ags in vivo. An in vitro study also found no effect of ZDV, dideoxycytidine (ddC), or azido-dideoxyuridine (AZU) on proliferative responses to recall Ags.

CD4-Positive T-Lymphocytes↗
PubMed1993

Circulating HIV-specific CD8+ cytotoxic T cells express CD38 and HLA-DR antigens.

CD38, a molecule with multilineage distribution but unknown function, and the MHC class II molecule HLA-DR (DR) have markedly elevated levels of expression on CD8+ cells of HIV-infected people. This study investigated the expression of CD38 and DR Ag on circulating HIV-specific CD8+ CTL in HIV-seropositive subjects. Purified CD8+ lymphocytes from 22 participants in the University of California at Los Angeles Multicenter AIDS Cohort Study were screened for CTL activity against autologous EBV-immortalized lymphoblast targets infected with vaccinia vectors that carried HIVIIIB gag, pol, and env genes. Sixty-seven percent (14 of 21), 64% (14 of 22), and 9% (2 of 22), respectively, of the subjects had HIV-specific CD8+ CTL activity against gag, pol, and env proteins. CD8+ cells from 11 of the subjects who had high CTL activity were then FACS-separated using three-color immunofluorescence sorting. Circulating DR-CD38- CD8+ cells had little activity. Highly purified DR+CD38+ CD8+ cells had higher HIV-specific CTL activity than other CD8+ cells. DR+CD38- or DR-CD38+ CD8+ cells also mediated significant activity, but only about half as much on a per cell basis as DR+CD38+ CD8+ cells. This is the first report that the CD38 molecule is expressed in vivo on Ag-specific CD8+ CTL, and confirms previous reports that DR is expressed on these cells. Both asymptomatic HIV-seropositive subjects (144 +/- 132/mm3) and AIDS patients (253 +/- 178/mm3) had markedly elevated levels of DR+CD38+ CD8+ cells compared with the levels in HIV-seronegative controls (7 +/- 3/mm3). However, the level of anti-HIV CTL activity was not correlated with the level of DR+CD38+ CD8+ cells, indicating that enumeration of this lymphocyte population by flow cytometry most likely will not be a useful surrogate for measuring functional CTL activity. Low levels of HIV-specific CTL activity, especially against gag, were correlated with lower CD4+ cells numbers, suggesting that the loss of CD8+ T cell cytotoxic activity against HIV that has been reported to occur with advancing HIV disease progression may reflect in part the extent of CD4+ cell immunodeficiency in HIV-infected subjects.

ADP-ribosyl Cyclase↗
PubMed1993

A prospective randomized trial comparing manual and automated endoscope disinfection methods.

OBJECTIVE: To compare the efficacy of endoscope disinfection using automated and manual systems. DESIGN: Prospective randomized trial. SETTING: A 1,000-bed tertiary care referral center. METHODS: All endoscopes underwent a three-stage decontamination process including brushing and cleaning with water and detergent, manual or automated disinfection with 2% glutaraldehyde, and 70% alcohol rinse with forced air drying. Cultures were obtained from endoscopes from both groups before and after alcohol rinse and then after overnight storage. RESULTS: Cultures from 8/30 (27%) automated and 11/30 (37%) manually disinfected (P = 0.58) endoscopes grew gram-negative bacteria and/or nontuberculous mycobacteria before the alcohol rinse. After alcohol rinse, 3 (10%) of 30 automated and 8 (27%) of 30 manually disinfected endoscopes remained contaminated (P = 0.28). Manually disinfected endoscopes were contaminated more frequently with coliform bacteria, whereas endoscopes undergoing automated disinfection were more frequently contaminated with nontuberculous mycobacteria, but the differences were not statistically significant. After alcohol rinse and forced air drying, there was no difference in contamination rates between freshly disinfected endoscopes and those stored overnight (7/30 (23%) versus 4/30 (13%), P = 0.50). Colonoscopes and duodenoscopes were contaminated more often than gastroscopes (P = 0.00001). CONCLUSION: The persistent endoscope contamination after manual and automated disinfection indicates the importance of developing more reliable and effective disinfection methods.

Automation↗
PubMed1993

Activation and differentiation antigens on T cells of healthy, at-risk, and HIV-infected children.

We examined the T-lymphocyte phenotypes of 67 human immunodeficiency virus (HIV)-infected children (P-1 or P-2) and 65 age-matched, healthy, control children stratified into four groups from < 1 to > or = 5 years of age to determine expression of antigens associated with cell activation/differentiation. Immunophenotyping was performed by laser flow cytometry using two-color immunofluorescent labeling. Although the control children showed a decline in total CD4 cell percent with age, the HIV-infected children in all age groups showed significantly decreased CD4 cell numbers compared with the age-matched controls. However, the slope of the CD4 cell decline with age was not significantly different in HIV-infected and control children. The CD4 cell decrease in infected children was reflected in both the CD45RA+ (naive) and CD45RA- (memory) CD4 cell subsets, although the CD45RA+ cells were decreased in greater proportion. Results assessing CD4 cells for expression of the L-selectin (Leu8) molecule were similar to those for CD45RA. The overall CD8 cell percentage was significantly increased in HIV-infected children compared with controls in all age groups. This was due primarily to increases in CD8 cells that were CD38+, CD57+, HLA-DR+, or CD45RA-. In a retrospective analysis of data from 23 P-0 children, we compared phenotype results from 5 children who were HIV+ with those 18 who were HIV-. Although the phenotypic changes seen in the 5 HIV+ children paralleled those described above for P-1 and P-2 subjects, there was no significant difference in the values for HIV+ compared with HIV P-0 children. Although the phenotypic alterations described did not appear to be diagnostic markers in P-0 children, they may serve as useful adjuncts for the evaluation of HIV-infected children.

ADP-ribosyl Cyclase↗