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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 37 records · Page 2Linked to original sources
PubMed2004

A detrimental role for nitric oxide synthase-2 in the pathology resulting from acute cerebral injury.

Nitric oxide (NO) synthesized from the inducible isoform of nitric oxide synthase (NOS-2) has been suggested to play both beneficial and deleterious roles in various neuropathologies. To define the role of nitric oxide in traumatic brain injury, we subjected male mice lacking a functional NOS-2 gene (NOS-2-/-) and their wild-type littermates (NOS-2+/+) to mild or severe aseptic cryogenic cerebral injury. Expression of NOS-2 mRNA and protein was observed in NOS-2+/+ animals following injury. Lesion volume (as measured by histology and brain imaging) and neurological outcome (using motor and cognitive behavioral paradigms) were assessed at various times after injury. While magnetic resonance imaging revealed the extent of edema of the 2 genotypes to be similar, histology showed a reduced (32%) lesion volume in severely injured NOS-2-/- compared with NOS-2+/+ mice. In addition, NOS-2-/- mice showed significant improvements in both contralateral sensorimotor deficits (grid test: p = 0.011) and cognitive function (Morris water maze: p = 0.009) after severe injury compared to their wild-type littermates. This indicates that lesion volume is reduced and neurological recovery is improved after acute traumatic injury in mice lacking a functional NOS-2 gene, and strongly suggests that the post-trauma production of NO from this source contributes to neuropathology.

Acute Disease↗
PubMed2004

Platelet storage solution affects on the accuracy of laboratory tests for platelet function: a multi-laboratory study.

BACKGROUND AND OBJECTIVES: Extent of shape change (ESC) and hypotonic shock response (HSR) have been widely used to characterize the in vitro function of platelets and have been shown to correlate with in vivo viability. These assays have been routinely performed using platelet-poor plasma (PPP) as the test sample diluent. Because of the increasing popularity of storing platelets in synthetic media, it is important to understand the effects of using these synthetic media as test diluents for ESC and HSR measurements. The objective of this study was to determine the effect of using platelet storage solutions vs. plasma for the in vitro testing of ESC and HSR. MATERIALS AND METHODS: Six laboratories participated in this study. Platelets were prepared by apheresis, the platelet-rich plasma (PRP) method, or derived from buffy-coats. Each platelet preparation was divided, half being stored in plasma and the other half in storage solution. ESC and HSR testing were performed in duplicate on days 1 and 5, using each of three diluents: autologous plasma; fresh-frozen plasma; or storage solution. RESULTS: For both ESC and HSR, dilutions made in each of the three diluents yielded significantly different results. Dilutions made in storage solutions were more than 30% lower for ESC and HSR than those made in autologous plasma (P < 0.0001). Dilutions made in thawed fresh-frozen plasma were more than 16% lower for ESC and HSR than those made in liquid autologous plasma (P < 0.0005). CONCLUSIONS: ESC and HSR test results are significantly affected by the test diluent. Platelets should be diluted in plasma (preferably autologous) for the in vitro testing of ESC and HSR, regardless of the media in which they are stored.

Blood Platelets↗
PubMed2004

Evaluation of a pilot second-opinion child telepsychiatry service.

A second-opinion child psychiatry service was piloted for six months in the northern-most two-thirds of Queensland. It provided specialist expertise by telehealth to local multidisciplinary teams of mental health staff. During the study period, 28 videoconferences were performed by the service: nine for administrative purposes, two for educational purposes, and 17 for direct and indirect clinical applications. The mean time between a referral being made and a consultation being performed was 4.7 days (range 1-13). A survey administered to referring and non-referring mental health workers showed that the major barriers to service implementation included the limited allied health applications that were offered, a perceived lack of communication during the implementation phase of the service, and the creation of a new referral network that did not conform to traditional referral patterns in the north of Queensland.

Child↗
PubMed2004

Ethical and legal issues in caring for asylum seekers and refugees in the UK.

Inward migration to the UK remains topical and controversial as numbers continue to increase. Many immigrants have specific health care needs and may shoulder a large burden of infectious disease. Imposition of legal constraints can have a huge impact on the medical care afforded to immigrants. Currently UK policy is to treat, free of charge and with NHS resources, those who fulfil specific criteria. However an increasing number are being asked to pay for their treatment. Many health care professionals are confused as to current legal restrictions and require guidance on the associated ethical issues. We concentrate on provision of care to HIV positive individuals and use cases to illustrate some of the issues. However these issues are equally pertinent to practitioners in all branches of medicine.

Antiretroviral Therapy, Highly Active↗
PubMed2003

Differential gene expression profiles in embryonic, adult-injured and adult-uninjured rat spinal cords.

To identify genes that render the adult-injured spinal cord nonpermissive and the embryonic spinal cord permissive to regeneration, we used subtraction hybridization and suppression PCR to generate subtractive cDNA populations representing (1) genes expressed in the embryonic but not in the adult-injured or uninjured spinal cords, (2) genes expressed in the adult-injured but not in the embryonic or adult-uninjured spinal cords, and (3) genes expressed in the embryonic and adult-injured spinal cords but not in the adult-uninjured spinal cord. Between 85 and 98% of the cDNAs identified are differentially represented in each population. Genes in each cDNA population were identified by microarray hybridization. Genes involved in inflammation, apoptosis, and neuroprotection were overrepresented in injured spinal cord cDNA, whereas genes involved in cell signaling and differentiation were overrepresented in the embryonic cDNA. This gene expression profiling suggests new hypotheses regarding the genes involved in inhibition and promotion of spinal cord regeneration.

Aging↗
PubMed2003

An international study of the performance of sample collection from patients.

BACKGROUND AND OBJECTIVES: Collection of a blood sample from the correct patient is the first step in the process of safe transfusion. The aim of this international collaborative study was to assess the frequency of mislabelled and miscollected samples drawn for blood grouping. MATERIALS AND METHODS: Hospitals in 10 countries provided data on sample error rates during a period of at least 3 months, including the last quarter of 2001. Mislabelled samples were defined as those not meeting local criteria for acceptance by the laboratory. Miscollected samples [wrong-blood-in-tube (WBIT)] were defined as samples in which the blood group result differed from the result on file from prior testing. WBIT rates were corrected for the proportion of repeat samples and for undetectable errors occurring as a result of chance collection of blood from the wrong patient with the same ABO group. Participants also completed a questionnaire on current policies regarding sample collection. RESULTS: A total of 71 hospitals completed surveys describing policies related to sample collection. Sixty-two hospitals provided usable data on the frequency of mislabelled and miscollected samples. Mislabelled and miscollected samples were common. Based on results from over 690,000 samples, the median hospital performance resulted in a rate for mislabelling of 1 in every 165 samples (6.1 per 1000; interquartile range 1.2-17 per 1000). The presence of national patient identification systems in Sweden and Finland was associated with rates of miscollected samples that were too low to estimate. Outside these nations, miscollected samples demonstrating WBIT occurred at a median rate of 1 in every 1986 samples (0.5 per 1000; interquartile range <0.3-0.9 per 1000). There was great variation worldwide in the reported frequency of mislabelled samples, probably resulting from variation in policies for sample acceptance. Miscollected samples occurred at a more constant rate. CONCLUSIONS: The rate of mislabelled samples and miscollected samples is 1000-10,000-fold more frequent than the risk of viral infection. Rates of mislabelled samples and WBIT can be tracked as key indicators of performance of an important step in the clinical transfusion process. WBIT episodes represent important 'near-miss' errors. By providing baseline performance data for the collection of patient blood samples, this study may be useful in formulating future national standards of performance for sample collection from patients.

Blood Group Incompatibility↗
PubMed2003

Storage of platelets in additive solutions: a multicentre study of the in vitro effects of potassium and magnesium.

BACKGROUND AND OBJECTIVES: In a preliminary study, the presence of potassium and magnesium in a modified synthetic medium (PAS-III) was found to have a significant influence on platelet metabolism (using apheresis-derived, as well as buffy-coat-derived platelets) when compared with standard PAS-III. The differences included reduced glycolysis, as evidenced by lower consumption of glucose and lower production of lactate, but also better preservation of pH and hypotonic shock response reactivity. The results suggested that storage in modified PAS-III containing 20% plasma was comparable to storage in standard PAS-III containing 30% plasma. To confirm the preliminary results and to evaluate the effects of different preparation protocols, an international multicentre study, which included 11 different sites, was conducted. MATERIALS AND METHODS: Platelets from 30 pools of approximately 20 buffy coat (BC) units each and 24 pooled apheresis platelet units were aliquoted for storage in plasma (reference) or synthetic medium using either a specific additive solution (PAS-III) containing 30% plasma or a modification of PAS-III containing 5.0 mm potassium and 1.5 mm magnesium (PAS-IIIM) and either 30% or 20% plasma. Units were stored at room temperature with agitation for 7 days during which in vitro testing was carried out for biochemical, haematological and functional parameters. RESULTS: Storage of platelets in PAS-IIIM resulted in a reduction in the rate of glycolysis and better retention of pH and hypotonic shock response reactivity. Storage in PAS-IIIM containing 20% plasma appeared to result in the retention of in vitro properties, similar to those observed during storage in standard PAS-III containing 30% plasma. CONCLUSIONS: The results of this study confirm the preliminary results. Similar results were seen with platelets prepared by BC and apheresis methods, despite differences in equipment, the preparation technique and in the final platelet contents achieved in the platelet units. Storage of platelets in PAS-IIIM should be considered to improve platelet function and allow plasma reduction to 20%.

Blood Component Removal↗
PubMed2003

Maintaining patient access to GUM clinics: is it compatible with appointments?

OBJECTIVES: To determine whether a planned change from a walk-in service to a system in which 35% of appointments were prebooked and 65% obtained on the day, preserved access to the service for patients with, or at risk of, STIs. To describe patients' attitudes and behaviours in relation to accessing the clinic, and relate these to disease status and other epidemiological factors. To evaluate the effect of the change on clinical outcomes. To develop a tool for evaluating access to services. METHOD: A natural experiment was studied, in which a cohort of patients attending just before the change in appointments policy (phase 1) was compared with a cohort following the change (phase 2). A questionnaire was administered to all new patients, and linked to disaggregated epidemiological and demographic data and case notes. RESULTS: The age, ethnic, symptom status, and disease mix of the clinic did not change significantly, and more patients were seen in phase 2. Time from telephoning to being seen did not change. Under 25s and Afro-Caribbeans used prebooked appointments less than others. Partner notification improved and HIV testing rates increased, while staff preferred the new system. CONCLUSION: This specific appointment system in a GUM clinic preserved access for high risk groups. However, this may not generalise to systems with a higher proportion of prebooked appointments.

Adult↗
PubMed2003

Determinants of disclosure of genital herpes to partners.

OBJECTIVE: To identify factors which determine whether and when patients will disclose infection with genital herpes to sexual partners. METHODS: The sample was 26 women and 24 men attending a herpes clinic in a sexually transmitted disease clinic. Semistructured interviews yielded quantitative data and also qualitative data which were subjected to content analysis. RESULTS: Characteristics of partners were very important in determining whether disclosure occurred. Respondents were less likely to tell partners regarded as casual. Perception of the likely reaction of partners was important in deciding whether to tell. Many respondents assumed that they were not infectious if they were not currently having an attack or if they were taking antiviral medication. The decision whether to tell tended to be based on considerations of likely discovery and of honesty towards the partner rather than control of transmission. Of patient characteristics only self rated depressed mood was related to disclosure to the most recent partner. CONCLUSIONS: Perception of the partner and anticipated partner response is crucially important in determining whether and when disclosure of genital herpes infection occurs.

Adult↗
PubMed2003

Treating sexually transmitted infections in primary care: a missed opportunity?

OBJECTIVES: To explore patterns of primary care attendance, barriers to the use of primary care, and views on services in a population of first time genitourinary medicine (GUM) clinic attenders. METHOD: A cross sectional survey of new patients attending a mainly walk-in outer London GUM clinic, in which responses were linked to clinical data. RESULTS: 40.5% of all patients and 39.9% of those with an STI had already seen a GP for their current problem. This did not vary with age or symptom status. Duration of symptoms was highly significantly longer in patients who had attended a GP than in patients who attended a GUM clinic in the first instance. When patients who had not seen a GP were asked the reason for this, a third of responses cited the convenience of a GUM clinic or difficulty in accessing primary care services, while only 3% cited embarrassment and only 2% examination or gender issues. CONCLUSION: Many patients initially attend GP services for STIs, and primary care is therefore already an important setting with potential for STI control. However, delay in treatment through attendance at primary care, and barriers in access to primary care, need to be addressed in the planning of future services.

Adult↗
PubMed2002

Uncoupling of bone turnover following hip replacement.

Studies using total hip replacement surgery as a model for acute hip injury have shown that bone mineral density of the proximal femur decreases 6-18% in the 6 months following surgery. To examine the acute biochemical mechanism associated with bone loss, we measured two indicators of bone formation [serum osteocalcin (OC), serum bone-specific alkaline phosphatase (BSAP)], as well as two markers for bone resorption [urine and serum N-telopeptide cross-linked collagen type 1 (NTx)], in 20 patients (10 men, 10 women, mean age 59.4 years) prior to hip replacement and 1-2 days postsurgery. The average OC value (ng/ml) decreased by 57.3% following surgery (7.5 +/- 4.3 to 3.2 +/- 1.1, P <0.001), and the average BSAP level (U/L) decreased by 27.6% (19.9 +/- 5.6 to 14.4 +/- 3.7, P <0.001). In contrast, levels of urine NTx (nmol BCE/mmol Cr) did not change significantly after the surgery (73.9 +/- 47.2 to 70.1 +/- 29.7). In addition, there was no change in serum NTx (nmol BCE) after surgery (11.8 +/- 2.3 to 11.8 +/- 3.0). Six months after surgery, bone mass had not changed significantly from baseline. These findings suggest that there is an uncoupling of bone turnover following hip replacement surgery which is characterized by significant reductions in bone formation without compensatory decreases in bone resorption, potentially leading to bone loss. Longer periods of follow-up are needed to assess long-term bone mass changes.

Alkaline Phosphatase↗
PubMed2002

Determinants of improvement in epicardial flow and myocardial perfusion for ST elevation myocardial infarction; insights from TIMI 14 and InTIME-II.

BACKGROUND: When evaluating new reperfusion regimens for ST elevation MI, it is important to adjust for factors that influence the likelihood of achieving normal epicardial flow and complete ST resolution. METHODS AND RESULTS: A total of 610 patients from TIMI 14 contributed to the angiographic analyses. The electrocardiographic analyses were based on 544 patients from TIMI 14 and 763 patients from InTIME-II. For each hour from onset of symptoms to initiation of pharmacological reperfusion, the odds of achieving TIMI 3 flow at 90 min or complete ST resolution at 60-90 min decreased significantly (P=0.03). Anterior location of infarction was associated with a reduction in the odds of achieving TIMI 3 flow or complete ST resolution. The use of abciximab as part of the reperfusion regimen significantly increased the odds of TIMI 3 flow (P=0.01) and ST resolution (P<0.001). The fibrinolytic administered (alteplase, reteplase, lanoteplase) did not influence the odds of TIMI 3 flow or ST resolution after adjusting for time to treatment, infarct location, and use of abciximab. CONCLUSIONS: The influence of time from symptoms on epicardial flow and STRES reinforces the need for increased efforts to reduce treatment delays in patients with ST elevation MI. The significant benefits of abciximab with respect to facilitation of epicardial and myocardial reperfusion are evident even after adjusting for time to treatment and infarct location. To adjust for determinants of success of reperfusion regimens, phase II trials evaluating new drug combinations should consider using a randomization scheme that stratifies patients based on infarct location and time from symptoms.

Abciximab↗
PubMed2001

Prognostic significance of BAG-1 expression in nonsmall cell lung cancer.

The purpose of this study was to evaluate the expression of BAG-1 in a cohort of patients with nonsmall cell lung cancer (NSCLC). The intensity and subcellular distribution of BAG-1 expression were correlated with overall survival. Tumor samples were collected from 85 patients diagnosed with NSCLC between 1993-1995 in St. John's, Newfoundland. Expression of BAG-1 was determined by immunohistochemistry using polyclonal anti-BAG-1 antibody. There was significant variation in the immunohistochemical staining patterns of BAG-1, including nonstaining and staining of either the cytoplasm, nucleus or both. Univariate Cox regression analysis showed that those patients whose tumor overexpressed BAG-1 had a significant reduction in the risk of death (hazard ratio = 0.53, p = 0.03). The survival advantage of patients with BAG-1 overexpression tumor was also demonstrated by Kaplan-Meier analysis and log-rank tests (median survival 30.10 months versus 17.04 months, p = 0.05). In addition, multivariate Cox regression analysis showed that patients whose tumor exhibited intense cytoplasmic staining had a further reduction of the risk of death (hazard ratio = 0.42, p = 0.03) and this effect was independent of age, stage and histology. All stages were included in the analysis. Our preliminary data strongly indicate that further investigation is warranted to better define the role of BAG-1 as an independent prognostic factor in NSCLC.

Adult↗
PubMed2001

BRFU, a TFIIB-like factor, is directly recruited to the TATA-box of polymerase III small nuclear RNA gene promoters through its interaction with TATA-binding protein.

The human snRNA genes transcribed by RNA polymerase II (pol II) and III (pol III) have different core promoter elements. Both gene types contain similar proximal sequence elements (PSEs) but differ in the absence (pol II) or presence (pol III) of a TATA-box, which, together with the PSE, determines the assembly of a pol III-specific pre-initiation complex. BRFU is a factor exclusively required for transcription of the pol III-type snRNA genes. We report that recruitment of BRFU to the TATA-box of these promoters is TATA-binding protein (TBP)-dependent. BRFU in turn stabilizes TBP on TATA-containing template and extends the TBP footprint both upstream and downstream of the TATA element. The core domain of TBP is sufficient for BRFU.TBP.DNA complex formation and for interaction with BRFU off the template. We have mapped amino acid residues within TBP and domains of BRFU that mediate this interaction. BRFU has no specificity for sequences flanking the TATA-box and also forms a stable complex on the TATA-box of the pol II-specific adenovirus major late promoter (AdMLP). Furthermore, pol III-type transcription can initiate from an snRNA gene promoter containing an AdMLP TATA-box and flanking sequences. Therefore, the polymerase recruitment is not simply determined by the sequence of the TATA-box and immediate flanking sequences.

Amino Acids↗