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T Murphy

Publications and source records attributed to T Murphy.

At least 19 recordsLinked to original sources
PubMed2006

A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson's disease left untreated at diagnosis.

BACKGROUND: The issue of when to start treatment in Parkinson's disease (PD) remains controversial. Some favour treatment at diagnosis while others opt for a "wait and watch" policy. The effect of the latter policy on the self reported health status of people with PD is unknown. AIMS: To record self reported health status through longitudinal use of a validated PD specific questionnaire (PDQ-39) in untreated PD patients in multiple centres in the UK. To compare patients who were left untreated with those who were offered treatment during follow-up. METHODS: A multicentre, prospective, "real life" observational audit based study addressing patient reported outcomes in relation to self reported health status and other sociodemographic details. RESULTS: 198 untreated PD were assessed over a mean period of 18 months. During two follow-up assessments, the self reported health status scores in all eight domains of the PDQ-39 and the overall PDQ-39 summary index worsened significantly (p<0.01) in patients left untreated. In a comparative group in whom treatment was initiated at or soon after diagnosis, there was a trend towards improvement in self reported health status scores after treatment was started. CONCLUSIONS: This study addresses for the first time self reported health status, an indicator of health related quality of life, in untreated PD. The findings may strengthen the call for re-evaluation of the policy to delay treatment in newly diagnosed patients with PD.

Aged↗
PubMed2006

Should every unit have a 24-hour transvaginal ultrasound available?

The purpose of this debate is to argue the merits of whether the availability of 24-hour transvaginal ultrasound service in every unit will help predict and, subsequently, prevent preterm birth. Any new test introduced will need to fulfil certain criteria. It must be acceptable in terms of risk, cost and patient convenience. It must be an improvement over existing alternatives, and it must aid clinicians to improve care. While the 24-hour availability of transvaginal ultrasound to every maternity unit may be useful to research and teaching, there is, as yet, little evidence that a 24-hour transvaginal ultrasound service improves perinatal and maternal morbidity and mortality. Results from our own centre suggest that experienced clinicians can make an acceptable diagnosis of spontaneous preterm labour (PTL) using only history and digital examination. Based on these findings, the availability of 24-hour vaginal ultrasound in every unit cannot be justified for the diagnosis of spontaneous PTL.

Female↗
PubMed2005

Validation of a simple model for predicting liver fibrosis in HIV/hepatitis C virus-coinfected patients.

OBJECTIVES: Recently, several models incorporating laboratory measurements have been validated for use as surrogate markers for liver fibrosis in hepatitis C virus (HCV) mono-infection, the simplest of these being the aspartate aminotransferase (AST) to platelet ratio index (APRI). We evaluated how well the APRI predicts significant hepatic fibrosis in patients with HIV/HCV coinfection. METHODS: Forty-six HIV/HCV-coinfected patients who underwent liver biopsy and had concomitant laboratory measurements (+/-3 months) were included in the study. Significant fibrosis was defined as F2-F4 using Batt and Ludwig scoring (=3 Ishak). APRI=[(AST/upper limit of normal)/platelet count (10(9)/L)] x 100. We used sas proc logistic (SAS Institute, Cary, NC) to calculate the area under the receiver operating curve (ROC) (AUC). Sensitivities, specificities, positive predictive value (PPV) and negative predictive value (NPV) were compared using cut-offs previously identified in the literature. RESULTS: Thirty-three of 46 patients (72%) had significant fibrosis on biopsy. For significant fibrosis, the area under the ROC for the APRI was 0.847+/-0.057. APRI scores >1.5 (the higher cut-off) were 100% specific and 52% sensitive; PPV was 100% and NPV 45%. Scores <0.5 (the lower cut-off) were 82% sensitive and 46% specific in ruling out significant fibrosis (PPV 79%; NPV 50%). CONCLUSIONS: A simple model incorporating readily available laboratory data is highly predictive of significant fibrosis in HIV/HCV coinfection and could serve as a biopsy-sparing measure, thus making treatment more accessible for this population.

Adult↗
PubMed2003

Serum antigen(s) drive the proinflammatory T cell response in acute pancreatitis.

BACKGROUND: Immune cells and cytokines are central to the systemic inflammatory response syndrome and multiple organ failure associated with acute pancreatitis. The specific role of T cells in this response is unclear, and this study focused on evaluating T cell activation and its regulation in patients with acute pancreatitis. METHODS: Peripheral blood samples of 14 patients with acute pancreatitis were obtained within 24 h of the onset of pain, within 48 h and at 1 week. T cell expression of surface markers CD69, CD62L and CD25 was measured. The production of interleukin (IL) 10 and IL-2 in vitro in response to the superantigen Staphylococcus enterotoxin B (SEB) was assessed. Serum samples from these patients were co-cultured with peripheral blood mononuclear cells from volunteers in the presence or absence of cytotoxic T lymphocyte-associated antigen (CTLA) 4 immunoglobulin, a specific inhibitor of antigen-dependent T cell activation. RESULTS: Expression of CD69 was significantly increased in CD3(+) and CD4(+) populations at 48 h and 1 week, and on CD8(+) cells at 1 week. There was a significant increase in the production of SEB-induced IL-2 compared with findings in controls, but no significant IL-10 response. Serum from patients with pancreatitis activated normal T cells. This response was abolished completely by CTLA-4. CONCLUSION: Acute pancreatitis results in the systemic activation of T cells. These cells are primed for a proinflammatory response to antigen stimulation and can be inhibited by antigen-specific T cell blockade. These data indicate that the immunoinflammatory response in acute pancreatitis is fueled by one or more serum antigens and offer prospects for further understanding of the aetiogenesis of pancreatitis.

Acute Disease↗
PubMed2003

Inhalation efficacy of RFI-641 in an African green monkey model of RSV infection.

Human respiratory syncytial virus (RSV) is a major cause of acute upper and lower respiratory tract infections. RFI-641 is a novel RSV fusion inhibitor with potent in vitro activity. In vivo efficacy of RFI was determined in an African green monkey model of RSV infection involving prophylactic and therapeutic administration by inhalation exposure. Inhalation was with an RFI-641 nebulizer reservoir concentration of 15 mg/ml for 15 minutes (short exposure) or 2 hours (long exposure). Efficacy and RFI-641 exposure was determined by collection of throat swabs, nasal washes and bronchial alveolar lavage (BAL) on selected days. The short-exposure group (15 minutes) exhibited no effect on the nasal, throat or BAL samples. The throat and nasal samples for the long-exposure group failed to show a consistent reduction in viral titers. RFI-641 2 hours exposure-treated monkeys showed a statistically significantly log reduction for BAL samples of 0.73-1.34 PFU/ml (P-value 0.003) over all the sampling days. Analysis indicates that the long-exposure group titer was lower than the control titer on day 7 and when averaged across days. The results of this study demonstrate the ability of RFI-641 to reduce the viral load of RSV after inhalation exposure in the primate model of respiratory infection.

Administration, Inhalation↗
PubMed2003

Depsipeptide (FR 901228) promotes histone acetylation, gene transcription, apoptosis and its activity is enhanced by DNA methyltransferase inhibitors in AML1/ETO-positive leukemic cells.

In t(8;21) acute myeloid leukemia (AML), the AML1/ETO fusion protein promotes leukemogenesis by recruiting histone deacetylase (HDAC) and silencing AML1target genes important for hematopoietic differentiation. We hypothesized that depsipeptide (FR901228), a novel HDAC inhibitor evaluated in ongoing clinical trials, restores gene transcription and cell differentiation in AML1/ETO-positive cells. A dose-dependent increase in H3 and H4 histone acetylation was noted in depsipeptide-treated AML1/ETO-positive Kasumi-1 cells and blasts from a patient with t(8;21) AML. Consistent with this biological effect, we also showed a dose-dependent increase in cytotoxicity, expression of IL-3, here used as read-out for silenced AML1-target genes, upregulation of CD11b with other morphologic changes suggestive of partial cell differentiation in Kasumi-1 cells. Some of these biologic effects were also attained in other myeloid leukemia cell lines, suggesting that depsipeptide has differentiation and cytotoxic activity in AML cells, regardless of the underlying genomic abnormality. Notably, the activity of depsipeptide was enhanced by 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor (DNMT). These two agents in combination resulted in enhanced histone acetylation, IL-3 expression, and cytotoxicity, suggesting HDAC and DNMT activities as a potential dual target in future therapeutic strategies for AML1/ETO and other molecular subgroups of AML.

Acetylation↗
PubMed2003

Interleukin-7 levels may predict virological response in advanced HIV-1-infected patients receiving lopinavir/ritonavir-based therapy.

OBJECTIVES: To examine the relationship between levels of the T-cell regulatory cytokine interleukin-7 (IL-7) and CD4 cell counts during immune reconstitution and to assess its prognostic value in advanced HIV-1-infected patients receiving lopinavir/ritonavir-based therapy. METHODS: Thirty-six HIV-1-infected adults who completed 48 weeks of follow-up visits were included in this prospective study. Patients having failed two or more antiretroviral therapy regimens were treated with lopinavir/ritonavir-based therapy. An enzyme-linked immunosorbent assay was used to determine IL-7 plasma levels, flow cytometry was used to analyse cell surface antigens, and polymerase chain reaction was used to quantify plasma HIV-1. RESULTS: Pretreatment IL-7 levels were elevated in all patients (mean 11.0 pg/mL) and were negatively correlated with CD4 cell counts and age (r=-0.59, P<0.001 and r=-0.57, P<0.001, respectively). During the course of treatment, IL-7 levels decreased by 34% while CD4 cell numbers progressively increased by 88%. Multivariate regression analysis showed that only pretreatment IL-7 levels predicted viral load at 48 weeks when controlling for baseline CD4 cell counts, viral load and patient demographics. CONCLUSIONS: These findings are consistent with regulation of T-cell recovery by IL-7, and suggest that IL-7 measurements might be used to predict virological response.

Adult↗
PubMed2001

Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity.

PURPOSE: Rituximab has been reported to have little activity in small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) and to be associated with significant infusion-related toxicity. This study sought to decrease the initial toxicity and optimize the pharmacokinetics with an alternative treatment schedule. PATIENTS AND METHODS: Thirty three patients with SLL/CLL received dose 1 of rituximab (100 mg) over 4 hours. In cohort I (n = 3; 250 mg/m(2)) and cohort II (n = 7; 375 mg/m(2)) rituximab was administered on day 3 and thereafter three times weekly for 4 weeks using a standard administration schedule. Cohort III (n = 23; 375 mg/m(2)) administered rituximab similar to cohort II for the first two treatments and then over 1 hour thereafter. RESULTS: A total of 33 CLL/SLL patients were enrolled; only one patient discontinued therapy because of infusion-related toxicity. Thirteen patients developed transient hypoxemia, hypotension, or dyspnea that were associated with significant changes in baseline interleukin-6, interleukin-8, tumor necrosis factor alpha, and interferon gamma compared with those not experiencing such reactions. Infusion-related toxicity occurred more commonly in older (median age 73 v 62 years; P =.02) patients with no other pretreatment clinical or laboratory features predicting occurrence of these events. The overall response rate was 45% (3% CR, 42% PR; 95% CI 28% to 64%). Median response duration for these 15 patients was 10 months (95% CI, 6.8-13.2; range, 3 to 17+). CONCLUSION: Rituximab administered thrice weekly for 4 weeks demonstrates clinical efficacy and acceptable toxicity. Initial infusion-related events seem to be cytokine mediated and resolve by the third infusion making rapid administration possible. Future combination studies of rituximab with other therapies in CLL seem warranted.

Aged↗
PubMed2001

The BACE gene: genomic structure and candidate gene study in late-onset Alzheimer's disease.

Alzheimer's disease (AD) pathology is characterized by beta-amyloid plaques and neurofibrillary tangles. Studies of autosomal dominant early-onset AD mutations suggest that beta-amyloid overproduction is sufficient to cause AD. Recently, the BACE gene, which encodes beta-secretase, the rate limiting enzyme in beta-amyloid formation, has been identified. Since this gene is a strong candidate gene for late-onset AD because of its function, we have characterized its genomic organization and identified two polymorphisms. Neither of these polymorphisms were associated with AD risk in genetic association studies comparing autopsy-confirmed late-onset AD cases and age-matched non-demented controls. Thus, we find no evidence that this locus influences risk for late-onset AD.

3' Untranslated Regions↗
PubMed2001

The experience of caregiving for severe mental illness: a comparison between anorexia nervosa and psychosis.

BACKGROUND: The aim of this study was to examine the experience of care giving for people with anorexia nervosa and to compare it with the experiences of those people who care for a person with a psychotic illness. METHOD: Carers (parents, siblings and husbands) of people with eating disorders who had experienced an episode of inpatient care for anorexia nervosa (n=71) were given the General Health Questionnaire and the Experience of Caregiving Inventory. A sample of carers (N=68) of people with a psychotic illness from the community were used as a comparison group. A subgroup of the carers (n=20) of people with anorexia nervosa were asked to write about their experiences. RESULTS: The clinical samples had a similar duration of illness, but the patients with anorexia nervosa were significantly younger and a larger proportion were living at home. The general health scores were significantly higher in the carers of anorexia nervosa and they experienced higher levels of difficulties in most areas of caregiving. A variety of variables from the Caregiving Inventory contributed to the level of psychological distress, accounting for 36% of the variance. The themes of guilt and shame were additional dimensions that were addressed in the letters. CONCLUSIONS: Carers of people with anorexia nervosa are challenged by the difficulties their role produces.

Adult↗
PubMed2001

[D-Leu(1)] microcystin-LR, a new microcystin isoplated from waterbloom in a Canadian prairie lake.

A previously undescribed cyclic heptapeptide hepatotoxin was isolated from a cyanobacteria waterbloom collected in Pakowki Lake, Alberta, Canada (49 degrees 20'N and 110 degrees 55'W). The compound was characterized by amino acid analysis, ESIMS/CID/MS, (1)H and (13)C NMR, and UV spectroscopy. Structure of the new microcystin was assigned as [D-Leu(1)]microcystin-LR (1). The amino acid composition is the same as microcystin-LR (2) except for D-Leu and L-Leu in 1 instead of D-Ala and L-Leu in 2. This is the first microcystin identified, among the 64 known microcystins, that has both a D- and L-Leu amino acid. Toxicity as measured by the protein phosphatase inhibition activity of 1 is similar to microcystin-LR. The presence of microcystins in waterblooms from this lake is discussed in relation to the almost yearly bird mortalities that have occurred there since 1995.

Chromatography, High Pressure Liquid↗
PubMed2001

Speech after repair of isolated cleft palate and cleft lip and palate.

The speech of children with isolated cleft palate (CP) repaired by one surgeon has been compared with the speech of children with some form of unilateral cleft lip and palate (CLP) repaired by the same surgeon. All palate repairs included an intravelar veloplasty. We identified 57 children (5--12 years old) with cleft palates repaired in infancy, of which three patients with other medical problems were excluded. Of the 54 patients, 44 (81%) attended for review (27 CP, 17 CLP). Video recordings were analysed by two speech and language therapists, using the Cleft Audit Protocol for Speech. The CP patients had no evidence of permanent fistulas. Final speech outcomes were similar for CP and CLP patients. Intelligibility was normal in 10 (37%) CP and nine (53%) CLP patients. Mild consistent hypernasality was present in five (18.5%) CP and four (23.5%) CLP patients. No patients had moderate or severe hypernasality or nasal emission. Mild consistent hyponasality was present in five (18.5%) CP and five (29%) CLP patients. Moderate consistent hyponasality was present in one (4%) CP patient. Dysphonia was present in eight (30%) CP and seven (41%) CLP patients. Cleft-type characteristics were noted in 11 (41%) CP and nine (53%) CLP patients. No CLP patients but 10 (37%) CP patients had required a pharyngoplasty (P=0.004, Fisher's exact test). Possible reasons for this (age, cleft type, surgeon and surgery) are discussed.

Child↗
PubMed2001

Electronic communication in ethics committees: experience and challenges.

Experience with electronic communication in ethics committees at two hospitals is reviewed and discussed. A listserver of ethics committee members transmitted a synopsis of the ethics consultation shortly after the consultation was initiated. Committee comments were sometimes incorporated into the recommendations. This input proved to be most useful in unusual cases where additional, diverse inputs were informative. Efforts to ensure confidentiality are vital to this approach. They include not naming the patient in the e-mail, requiring a password for access to the listserver, and possibly encryption. How this electronic communication process alters group interactions in ethics committees is a fruitful area for future investigation.

Chicago↗