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Biomedical subjects

D Williamson

Publications and source records attributed to D Williamson.

At least 19 recordsLinked to original sources

When is a door not a door? The difference between documented and actual arrival times in the emergency department.

OBJECTIVES: An observational study to determine the difference between documented ambulance arrival times and the actual arrival times of patients from the ambulance into the emergency department. METHODS: In a busy, purpose built, modern emergency department with easy access, we recorded the time that ambulance borne patients were wheeled over the threshold of the clinical area and compared this to the times recorded by the ambulance trusts as the official ambulance arrival times. RESULTS: 352 ambulance arrivals were observed. Data were incomplete in 34 instances (9.5%) and were not included in the analysis. For the remaining 318 arrivals, the median time difference was 2 min 1 s (range 5 s to 21 min 45 s). In a subgroup of chest pain patients (45 patients), the median time difference was 2 min 11 s (range 23 s to 5 min 38 s). The difference between the chest pain group and the remaining patients was not significant (p = 0.528). CONCLUSIONS: There is inevitably some delay between the arrival of an ambulance and the arrival of the patient into a clinical area. This study quantifies that difference. In an era of stringent time related standards, this paper highlights the need for accurate recording of times to enable us to carry out valid audit of these standards. This study supports the redefining of an arrival time as the time when the patient arrives in the clinical area.

Ambulances↗

Identifying barriers to prehospital thrombolysis in the treatment of acute myocardial infarction.

BACKGROUND AND OBJECTIVES: After an acute myocardial infarction (AMI) prehospital thrombolysis (PHT) reduces mortality compared with inhospital thrombolysis. In practice, a relatively small proportion of the total population with AMI receives PHT. This study was designed to identify the current barriers to PHT. METHODS: A retrospective practice review of 57 consecutive patients treated in or before arrival at a district general hospital emergency department. All patients received thrombolysis for an AMI. RESULTS: The main barriers to delivery of PHT appear to be the inclusion and exclusion criteria laid out in the ambulance service central guidelines. Despite recent widening of the inclusion criteria, 54% of patients eligible for immediate treatment on arrival in hospital either received or were eligible for PHT. CONCLUSION: To increase the number of patients who are eligible for PHT these guidelines need to be revised further in line with inhospital criteria for thrombolysis.

Acute Disease↗

Percent body fat measured by BIA and DEXA in obese, African-American adolescent girls.

OBJECTIVE: To compare the estimation of body fat between bioelectrical impedance analysis (BIA) and dual energy X-ray absorptiometry (DEXA) in overweight, African-American female adolescents. SUBJECTS: In total, 54 African-American adolescent female subjects were recruited for Study 1. Each adolescent's body mass index was greater than the 85th percentile and their average body fat was 45% according to DEXA. A total of 26 African-American adolescent female subjects were available for Study 2, and had an average body fat of 26% according to DEXA. MEASUREMENTS: Percent body fat was measured by DEXA and BIA. Seven different BIA equations were tested. Both sets of data were analyzed using Bland-Altman regression analyses, utilizing percent body fat measured by DEXA as the criterion. RESULTS: The Kushner equation provided estimates that were unaffected by body fat in both studies. Estimates were unbiased when applied to the exclusively overweight sample and biased when utilized with the separate sample of normal weight and obese girls. The remaining equations were biased, provided inconsistent estimates across body weight, or were biased and provided inconsistent estimates. Ethnicity-specific and ethnicity-combined equations performed similarly in the obese sample, but became more disparate when applied to a sample encompassing a wider body weight range. The limits of agreement between all BIA equations and the DEXA estimates ranged from 6 to 9%. CONCLUSION: The study suggests that the Kushner BIA equation is appropriate for use with African-American female adolescents across the weight spectrum, while the majority of BIA equations underestimated percent body fat as body fat increased.

Absorptiometry, Photon↗

Effect of hypotension and carbon dioxide changes in an improved genuine closed cranial window rat model.

The genuine closed cranial window model, in which the thinned parietal bone constitutes the covering of the preparation, has contributed to a better understanding of the pathophysiological mechanisms in migraine. In its present form, only measurements of the middle meningeal artery (MMA) are performed. The aim of this study was, in addition, to measure pial artery/arteriole (PA) diameter and cortical cerebral blood flux in the same cranial window. The model was evaluated by studying the effects of hypotension and changes in arterial carbon dioxide pressure (PaCO2), because these parameters might influence the interpretation of pharmacological experiments. Out of 23 successful experiments it was possible to measure all three parameters in 19 animals. In four, PA diameter could not be measured, while MMA diameter and local cortical cerebral blood flux (LCBF(Flux)) always could. Haemorrhage-induced hypotension (-64+/-0.8 mmHg) caused an increase of MMA diameter of 11.8+/-8.4%, PA diameter of 61.2+/-7.7% and a decrease in LCBF(Flux) of -36.4+/-2.5%. The decrease in blood pressure did not significantly change the MMA (P=0.38); however, the PA diameter and the LCBF(Flux) were affected (P<0.001). All three parameters were sensitive to hypo- and hypercapnia. In conclusion, we have shown that not only MMA but also PA diameter and LCBF(Flux) can be measured in the same cranial window. Tight control of PaCO2 is essential in pharmacological experiments. If test substances possess hypotensive actions, it may be difficult to interpret whether the PA dilation is caused by the induced hypotension per se or is a direct pharmacological action or a combination. In contrast, the MMA does not autoregulate and MMA diameter changes in pharmacological studies may exclusively be due to direct pharmacological effects.

Animals↗

Mitogen-activated protein kinase (MAPK) pathway activation: effects of age and acute exercise on human skeletal muscle.

The purpose of this investigation was to examine the activation (phosphorylation) and total protein content of MAPK signalling cascade proteins (ERK 1/2, p90RSK, Mnk 1, eIF4E, p38 MAPK, JNK/SAPK, MKP 1) at rest and following exercise, in sedentary young and old men. Eight young (22 +/- 1 years; YM) and eight old (79 +/- 3 years; OM) men underwent a resting muscle biopsy of the vastus lateralis; they then performed a knee extensor resistance exercise session (29 contractions at approximately 70 % of max), followed by a post-exercise biopsy. Western immunoblot analysis demonstrated that the OM had higher resting phosphorylation of ERK 1/2, p90RSK, Mnk 1, p38 MAPK and JNK/SAPK proteins versus YM (P < 0.05). The resistance exercise bout caused an increase in phosphorylation of the ERK 1/2, p90RSK and Mnk 1 proteins (P < 0.05) in the YM. Conversely, the OM had a decrease in ERK 1/2, p90RSK, Mnk 1, p38 MAPK and JNK/SAPK phosphorylation (P < 0.05) after the exercise bout. Neither group showed a change in eIF4E phosphorylation. The total amount of protein expression of the MAPK signalling proteins was not different between the YM and OM, except that there was a higher (P < 0.05) MKP 1 protein content in the OM. This investigation is the first to provide evidence that MAPK proteins are differentially activated at rest and in response to a bout of resistance exercise in skeletal muscle of young and old men. These findings may have implications for other processes (e.g. transcription and translation) involved in skeletal muscle type and growth, when examining the changes occurring with ageing muscle before and after resistance exercise/training.

Adult↗

Assessment of the environmental impact of artificial effluent lagoon in Jiayuguan City of China.

An artificial effluent lagoon for storing wastewater were excavated in Jiayuguan City since 1994. As a part of a demonstration project of Sino-Australia cooperation, an assessment of the environmental impact of the lagoon was carried out. The assessment was based on field and laboratory tests and predictive model. The main impacts from the lagoon site are likely to be on the groundwater system, and, to a lesser extent, on ambient air quality in the vicinity. Currently it is expected that groundwater is being polluted with effluent from the effluent lagoon. Air pollution (odor nuisance) is mainly caused by untreated effluent in the irrigation channel. The impact of high total dissolved salt (TDS) on groundwater is likely to be significant in the long run if the lagoon is continuously used. There is, consequently, no likelihood of contamination of surface water system, particularly of the city water supply system, from infiltration of effluent at the lagoon.

China↗

Comparative expressed sequence hybridization to chromosomes for tumor classification and identification of genomic regions of differential gene expression.

Altered expression of genes can have phenotypic consequences in cancer development and treatment, developmental abnormalities, and differentiation processes. Here we describe a rapid approach, termed comparative expressed sequence hybridization (CESH), which gives a genome-wide view of relative expression patterns within tissues according to chromosomal location. No prior knowledge of genes or cloning is required, and minimal amounts of tissue can be used. Expression profiles are achieved in a manner similar to the identification of chromosomal imbalances by comparative genomic hybridization analysis. The approach is demonstrated to indicate a chromosomal region that harbors overexpressed genes that may be associated with a drug-resistant phenotype. In addition, known and new regions of differential gene expression in both normal tissues and tumor samples from the soft tissue sarcoma group of rhabdomyosarcoma (RMS) are indicated. These regions included 2p24; overexpression of MYCN at 2p24 was confirmed by quantitative reverse transcription-PCR for all of the alveolar RMS cases and did not necessarily correspond to genomic amplification. Evidence including region specific microarray analysis indicated that overexpression of several genes from a region may be required for detection by CESH. This evidence is consistent with clusters of functionally related genes and mechanisms that affect the expression of a number of genes at a particular genomic location. The distinctive CESH profiles demonstrated in different subtypes of RMS show potential for tumor classification.

Chromosomes, Artificial, Yeast↗

The effect of hair loss on quality of life.

BACKGROUND: The aim of this study was to quantify the effect of hair loss on quality of life. Patients were recruited from an alopecia support group, and were assessed using the Dermatology Life Quality Index (DLQI) and an adapted version of the DLQI. Financial utility questions, an abbreviated version of the Center for Epidemiologic Studies Depression Scale and open-ended questions were also used. OBSERVATIONS: Seventy (90% response rate) questionnaires were returned. DLQI scores in responders with hair loss (mean score = 8.3, SD = 5.6, range 0-23, n = 70) were similar to those recorded in severe psoriasis. The hair loss continued to have a significant impact on life quality well after the initial event (median duration of hair loss = 138 months +/- 114; range 7-588, n = 70). Forty per cent of patients also felt dissatisfied with the way in which their doctor dealt with them. CONCLUSIONS: This study specifically identifies the feelings of loss of self-confidence, low self-esteem and heightened self-consciousness in people affected by hair loss.

Adult↗

Healing of an MRSA-colonized, hydroxyurea-induced leg ulcer with honey.

BACKGROUND: With the everincreasing emergence of antibiotic-resistant pathogens, in particular methicillin-resistant Staphylococcus aureus (MRSA) in leg ulcers, a means of reducing the bacterial bioburden of such ulcers, other than by the use of either topical or systemic antibiotics, is urgently required. METHODS: We report the case of an immunosuppressed patient who developed a hydroxyurea-induced leg ulcer with subclinical MRSA infection which was subsequently treated with topical application of manuka honey, without cessation of hydroxyurea or cyclosporin. RESULTS: MRSA was eradicated from the ulcer and rapid healing was successfully achieved. CONCLUSION: Honey is recognized to have antibacterial properties, and can also promote effective wound healing. A traditional therapy, therefore, appears to have enormous potential in solving new problems.

Administration, Topical↗

Mood change through physical exercise in nine- to ten-year-old children.

The present study assessed the effect of two types of physical exercise on the self reported mood of 64 9 and 10-yr.-old children who responded to a self-report mood meassure after two different types of aerobic exercise of 15 min., and after a 15-min. video. Significant increases in positive mood and significant decreases in negative mood were found after each exercise treatment; however, positive mood decreased and negative mood increased following the video treatment. Interestingly, no significant difference in mean mood scores was found between the two exercise treatments. These data suggest that short bouts of physical exercise have psychological benefits for children.

Affect↗

The protein tyrosine phosphatase Shp-2 regulates RhoA activity.

Remodeling of filamentous actin into distinct arrangements is precisely controlled by members of the Rho family of small GTPases [1]. A well characterized member of this family is RhoA, whose activation results in reorganization of the cytoskeleton into thick actin stress fibers terminating in integrin-rich focal adhesions [2]. Regulation of RhoA is required to maintain adhesion in stationary cells, but is also critical for cell spreading and migration [3]. Despite its biological importance, the signaling events leading to RhoA activation are not fully understood. Several independent studies have implicated tyrosine phosphorylation as a critical event upstream of RhoA [4]. Consistent with this, our recent studies have demonstrated the existence of a protein tyrosine phosphatase (PTPase), sensitive to the dipeptide aldehyde calpeptin, acting upstream of RhoA [5]. Here we identify the SH2 (Src homology region 2)-containing PTPase Shp-2 as a calpeptin-sensitive PTPase, and show that calpeptin interferes with the catalytic activity of Shp-2 in vitro and with Shp-2 signaling in vivo. Finally, we show that perturbation of Shp-2 activity by a variety of genetic manipulations results in raised levels of active RhoA. Together, these studies identify Shp-2 as a PTPase acting upstream of RhoA to regulate its activity and contribute to the coordinated control of cell movement.

Animals↗

Ultrasound imaging of forearm fractures in children: a viable alternative?

OBJECTIVE: A pilot study to investigate whether ultrasonography can be reliably used to demonstrate uncomplicated greenstick and torus fractures in children. METHOD: Children between the ages of 2 and 14 years with a high clinical suspicion of a non-articular, undisplaced forearm fracture were included. Ultrasound imaging of the injury was performed by a consultant radiologist who gave an immediate report. Standard radiographs of the forearm were then obtained and the patient treated in the normal way. The radiograph was formally reported on at a later date. RESULTS: 26 patients were included. There was an absolute correlation between the ultrasound and radiographic findings. The procedure was well tolerated. CONCLUSION: Ultrasound seems effective for detecting uncomplicated forearm fractures in children. The procedure is easy to perform and the images easy to interpret. A larger study will now be undertaken to confirm these initial findings.

Adolescent↗

Effect of resistance training on single muscle fiber contractile function in older men.

The purpose of this study was to examine single cell contractile mechanics of skeletal muscle before and after 12 wk of progressive resistance training (PRT) in older men (n = 7; age = 74 +/- 2 yr and weight = 75 +/- 5 kg). Knee extensor PRT was performed 3 days/wk at 80% of one-repetition maximum. Muscle biopsy samples were obtained from the vastus lateralis before and after PRT (pre- and post-PRT, respectively). For analysis, chemically skinned single muscle fibers were studied at 15 degrees C for peak tension [the maximal isometric force (P(o))], unloaded shortening velocity (V(o)), and force-velocity parameters. In this study, a total of 199 (89 pre- and 110 post-PRT) myosin heavy chain (MHC) I and 99 (55 pre- and 44 post-PRT) MHC IIa fibers were reported. Because of the minimal number of hybrid fibers identified post-PRT, direct comparisons were limited to MHC I and IIa fibers. Muscle fiber diameter increased 20% (83 +/- 1 to 100 +/- 1 microm) and 13% (86 +/- 1 to 97 +/- 2 microm) in MHC I and IIa fibers, respectively (P < 0.05). P(o) was higher (P < 0.05) in MHC I (0.58 +/- 0.02 to 0.90 +/- 0.02 mN) and IIa (0.68 +/- 0.02 to 0.85 +/- 0.03 mN) fibers. Muscle fiber V(o) was elevated 75% (MHC I) and 45% (MHC IIa) after PRT (P < 0.05). MHC I and IIa fiber power increased (P < 0.05) from 7.7 +/- 0.5 to 17.6 +/- 0.9 microN. fiber lengths. s(-1) and from 25.5 to 41.1 microN. fiber lengths. s(-1), respectively. These data indicate that PRT in elderly men increases muscle cell size, strength, contractile velocity, and power in both slow- and fast-twitch muscle fibers. However, it appears that these changes are more pronounced in the MHC I muscle fibers.

Aged↗

Preparing the wound bed--debridement, bacterial balance, and moisture balance.

Successful diagnosis and treatment of patients with chronic wounds involve holistic care and a team approach. The integration of the work of an interdisciplinary care team that includes doctors, nurses, and allied health professionals with the patient, family, significant others, and caregivers offers an optimal formula for achieving wound resolution. Such an approach challenges practitioners and everyone participating in wound care to integrate data and information that arise from a number of sources and mitigating factors. In this article, the authors define the changing paradigm that links treatment of the cause and focuses on three components of local wound care: debridement, wound-friendly moist interactive dressings, and bacterial balance. The authors demonstrate that the treatment of chronic wounds can be accomplished through a series of recommendations and rationales based on the literature and their experience. These recommendations lay the groundwork for thorough assessment and evaluation of the wound.

Algorithms↗

The von Willebrand factor-glycoprotein Ib/V/IX interaction induces actin polymerization and cytoskeletal reorganization in rolling platelets and glycoprotein Ib/V/IX-transfected cells.

Platelet adhesion to sites of vascular injury is initiated by the binding of the platelet glycoprotein (GP) Ib-V-IX complex to matrix-bound von Willebrand factor (vWf). This receptor-ligand interaction is characterized by a rapid on-off rate that enables efficient platelet tethering and rolling under conditions of rapid blood flow. We demonstrate here that platelets adhering to immobilized vWf under flow conditions undergo rapid morphological conversion from flat discs to spiny spheres during surface translocation. Studies of Glanzmann thrombasthenic platelets (lacking integrin alpha(IIb)beta(3)) and Chinese hamster ovary (CHO) cells transfected with GPIb/IX (CHO-Ib/IX) confirmed that vWf binding to GPIb/IX was sufficient to induce actin polymerization and cytoskeletal reorganization independent of integrin alpha(IIb)beta(3). vWf-induced cytoskeletal reorganization occurred independently of several well characterized signaling processes linked to platelet activation, including calcium influx, prostaglandin metabolism, protein tyrosine phosphorylation, activation of protein kinase C or phosphatidylinositol 3-kinase but was critically dependent on the mobilization of intracellular calcium. Studies of Oregon Green 488 1, 2-bis(o-amino-5-fluorophenoxy)ethane-N,N,N',N-tetraacetic acid tetraacetoxymethyl ester-loaded platelets and CHO-Ib/IX cells demonstrated that these cells mobilize intracellular calcium in a shear-dependent manner during surface translocation on vWf. Taken together, these studies suggest that the vWf-GPIb interaction stimulates actin polymerization and cytoskeletal reorganization in rolling platelets via a shear-sensitive signaling pathway linked to intracellular calcium mobilization.

Actins↗

Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370.

This study investigated whether the selective 5HT1F receptor agonist LY334370 has other possible antimigraine mechanisms in addition to the proposed inhibition of dural plasma extravasation. LY334370 (up to 10(-5) M) had no vasoconstrictor effects on human cerebral arteries in vitro. It had no effect (up to 10 mg kg-1, i.v.) on neurogenic vasodilation of dural blood vessels produced by electrical stimulation of the dura mater in anesthetized rats. Nor had it any effect (at 3 mg kg-1, i.v.) on the hyperalgesia produced by injection of carrageenan into the paw of conscious rats or on nociceptive reflex responses in the spinalized, decerebrate rabbit (up to 3 mg kg-1, i.v.), indicating that it has no general analgesic properties. However, it significantly inhibited activation of second-order neurons in the trigeminal nucleus caudalis produced by electrical stimulation of the dura mater in anesthetised rats at 3 mg kg-1, i.v. These results provide evidence to suggest that LY334370 has a central mechanism of action in blocking the transmission of nociceptive impulses within the trigeminal nucleus caudalis and that this may represent a mechanism through which it has its antimigraine effect.

Animals↗

Platelet adhesion receptors: novel targets for anti-thrombotic therapy.

The critical role of platelets in the development of the acute coronary syndromes is now well recognised, and a great deal of effort has therefore focused on elucidating the key adhesion receptors mediating platelet-vessel wall and platelet-platelet interactions. The vascular adhesion protein von Willebrand factor (vWf) plays a key role in supporting platelet adhesion to the damaged vessel wall and binds to two adhesion receptors on the platelet surface, the glycoprotein (GP) Ib-V-IX complex and glycoprotein IIb-IIIa. The GP Ib-V-IX complex is a unique adhesion receptor which enables platelets to roll on a vWf matrix under conditions of rapid blood flow as well as transducing signals leading to the activation of GP IIb-IIIa. This latter receptor binds to a distinct site on vWf and is essential for stabilising platelet adhesion to the site of vessel wall injury. In addition to supporting platelet adhesion, GP IIb-IIIa plays a key role in a number of other platelet responses including platelet spreading, aggregation, the release of procoagulant-rich microvesicles, and clot retraction. Given its central role in platelet function GP IIb-IIIa has become an attractive target for the development of novel anti-thrombotic agents. In this paper, we consider the advantages of inhibitors of GP IIb-IIIa compared with other established anti-platelet drugs including aspirin and ticlopidine, and also discuss some potential problems associated with the inhibition of GP IIb/IIIa and other platelet adhesion receptors.

Abciximab↗