Biomedical subjects

Stephen J Wilson

Publications and source records attributed to Stephen J Wilson.

At least 19 recordsLinked to original sources

PubMed2007

Superficial lumbopelvic muscle overactivity and decreased cocontraction after 8 weeks of bed rest.

STUDY DESIGN: Longitudinal study. OBJECTIVE: To gain insight into the effects of inactivity on lumbopelvic stabilization. SUMMARY OF BACKGROUND DATA: Some authors have suggested a link between inactivity and lumbopelvic (LP) pain. Studies examining the superficial musculature in LP pain have shown overactivity and increased cocontraction. Studies in inactivity (bed rest, microgravity) have shown similar effects on the musculature of the legs. Here we examine the effect of bed rest on superficial LP activity and cocontraction. METHODS: Ten male subjects participated in the "Berlin Bed Rest Study" and underwent 8 weeks of bed rest with a 1-year follow-up. A repetitive knee movement model at four movement speeds in non-weightbearing was used to assess, via electromyography, activity (amplitude-ratios) in five superficial LP muscles and abdominal flexor-lumbar extensor cocontraction for LP stabilization. Testing was conducted at regular intervals during and after bed rest. RESULTS: Analysis of the amplitude-ratio data showed a significant effect of testing date (F = 2.38, P = 0.005). This effect was generalized across all muscles, however (F = 0.59, P = 0.989). During bed rest, subjects exhibited higher levels of activity but lower levels of cocontraction (F = 8.84, P < 0.001), and the changes were still present up to 1 year after bed rest. CONCLUSIONS: The bed rest protocol resulted in the development of superficial muscle overactivity but decreased cocontraction. These changes could reflect dysfunction of central nervous system control of LP stabilization. These changes were still apparent 1 year after bed rest, suggesting a stable change in motor control.

Bed Rest↗

PubMed2006

Heterodimerization of the alpha and beta isoforms of the human thromboxane receptor enhances isoprostane signaling.

Isoprostanes are free radical catalyzed products of arachidonic acid that are elevated in pro-oxidant disease states. Two isoprostanes, 8-isoprostaglandin F(2alpha) (iPF(2alpha)III) and 8-isoprostaglandin E2 (iPE2III), act at the receptor for thromboxane A2 (the TP) to mediate pro-atherogenic effects in vivo. We confirmed dimerization of the human TP isoforms, TPalpha and TPbeta, and determined the impact on isoprostane signaling. No overt changes in ligand binding at the TP were observed as a result of TPalpha/TPbeta coexpression. The response to iPF(2alpha)III or iPE2III was enhanced in HEK293 cells stably coexpressing TPalpha and TPbeta, as measured by inositol phosphate generation or intracellular calcium mobilization, relative to cells expressing TPalpha or TPbeta individually. In contrast, the response to traditional thromboxane analogs was unaltered. Augmented isoprostane signaling was similarly observed in HEK 293 cell transiently transfected with TPalpha and TPbeta. These results indicate that TPalpha/TPbeta dimerization enhances isoprostane-mediated signal transduction.

Calcium↗

PubMed2006

Regulation of thromboxane receptor trafficking through the prostacyclin receptor in vascular smooth muscle cells: role of receptor heterodimerization.

BACKGROUND: Prostacyclin (PGI2) and thromboxane (TxA2) effect disparate outcomes for atherogenesis and the response to vascular injury; PGI2, a vasodilator and inhibitor of platelet aggregation, limits the deleterious actions of TxA2, a vasoconstrictor and platelet activator. Dimerization of their G protein-coupled receptors, IP and TP, evokes a modified cellular response through which IP/TP counter-balance may be effected. We examined the consequence of IP/TP interaction for the regulatory pathways of both receptors. METHODS AND RESULTS: TPalpha overexpressed in HEK293 cells or expressed endogenously in aortic smooth muscle cells (ASMCs) was internalized after selective activation of either TP or IP. Homologous trafficking of TP was unaltered by coexpression of IP. Heterologous sequestration of TPalpha required the physical presence of activated IP, in transfected and native cells, but was independent of IP signaling to adenylyl cyclase. Reciprocal heterologous regulation of IP, via activated TP, was evident in both HEK293 cells and ASMCs. Homologous TP internalization led to receptor retention and degradation. In contrast, when internalization was IP-induced, TPalpha was recycled to the cell surface in coexpressing HEK293 cells, but not in ASMCs, in accord with the postendocytotic pathway of IP. CONCLUSIONS: IP/TPalpha interaction permits reciprocal regulation of receptor endocytosis via the trafficking pathway determined by the activated dimeric partner.

Animals↗

PubMed2006

Antimicrobial use control measures to prevent and control antimicrobial resistance in US hospitals.

OBJECTIVE: Clinical practice guidelines and recommended practices to control use of antibiotics have been published, but the effect of these practices on antimicrobial resistance (AMR) rates in hospitals is unknown. The objective of this study was to examine relationships between antimicrobial use control strategies and AMR rates in a national sample of US hospitals. DESIGN: Cross-sectional, stratified study of a nationally representative sample of US hospitals. METHODS: A survey instrument was sent to the person responsible for infection control at a sample of 670 US hospitals. The outcome was current prevalences of 4 epidemiologically important, drug-resistant pathogens, considered concurrently: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, ceftazidime-resistant Klebsiella species, and quinolone (ciprofloxacin)-resistant Escherichia coli. Five independent variables regarding hospital practices were selected from the survey: the extent to which hospitals (1) implement practices recommended in clinical practice guidelines and ensure best practices for antimicrobial use, (2) disseminate information on clinical practice guidelines for antimicrobial use, (3) use antimicrobial-related information technology, (4) use decision support tools, and (5) communicate to prescribers about antimicrobial use. Control variables included the hospitals' number of beds, teaching status, Veterans Affairs status, geographic region, and number of long-term care beds; and the presence of an intensive care unit, a burn unit, or transplant services. A generalized estimating equation modeled all resistance rates simultaneously to identify overall predictors of AMR levels at the facility. RESULTS: Completed survey instruments were returned by 448 hospitals (67%). Four antimicrobial control measures were associated with higher prevalence of AMR. Implementation of recommended practices for antimicrobial use (P < .01) and optimization of the duration of empirical antibiotic prophylaxis (P < .01) were associated with a lower prevalence of AMR. Use of restrictive formularies (P = .05) and dissemination of clinical practice guideline information (P < .01) were associated with higher prevalence of AMR. Number of beds and Veterans Affairs status were also associated with higher AMR rates overall. CONCLUSIONS: Implementation of guideline-recommended practices to control antimicrobial use and optimize the duration of empirical therapy appears to help control AMR rates in US hospitals. A longitudinal study would confirm the results of this cross-sectional study. These results highlight the need for systems interventions and reengineering to ensure more-consistent application of guideline-recommended measures for antimicrobial use.

Anti-Bacterial Agents↗

PubMed2006

Internalization and recycling of the human prostacyclin receptor is modulated through its isoprenylation-dependent interaction with the delta subunit of cGMP phosphodiesterase 6.

Prostacyclin, the major cyclooxygenase-derived product of arachidonic acid formed in the vasculature, mediates its potent anti-thrombotic and anti-proliferative effects through its G protein-coupled receptor (GPCR) termed the IP. Unlike many GPCRs, agonist-induced internalization of the IP occurs in an arrestin/GPCR kinase-independent manner. However, deletion of the IP COOH-terminal region prevented internalization suggesting that protein interactions at this region are involved in IP regulation. Using the COOH-terminal region of IP as bait we identified the delta subunit of cGMP phosphodiesterase 6 (PDE6delta) as a novel hIP-interacting protein in two independent yeast two-hybrid screens. Interaction of IP and PDE6delta was confirmed by co-immunoprecipitation in HEK293 cells, and in HEPG2 cells, which endogenously express neither IP nor PDE6delta. IP isoprenylation was critical for this interaction, as PDE6delta was unable to associate with an isoprenylation-deficient mutant IP (IPSSLC). PDE6delta overexpression altered the temporal pattern of agonist-induced internalization of IP, but not IPSSLC, in HEPG2 cells, increasing initial internalization but facilitating the return of IP to the cell surface despite the continued presence of agonist. Depletion of PDE6delta using short interfering RNA abolished cicaprost-induced IP internalization in human aortic smooth muscle cells. Recycling of IP, but not IPSSLC, upon agonist removal was facilitated by overexpression of PDE6delta. Thus PDE6delta interacts specifically with IP to modulate receptor trafficking.

Aorta↗

PubMed2006

A computational system to optimise noise rejection in photoplethysmography signals during motion or poor perfusion states.

Photoplethysmography (PPG) signals can be used in clinical assessment such as heart rate (HR) estimations and extraction of arterial flow waveforms. Motion artefact and/or poor peripheral perfusion can contaminate the PPG during monitoring. A computational system is presented here to minimise these two intrinsic weaknesses of the PPG signals. Specifically, accelerometers are used to detect the presence of motion artefacts and an adaptive filter is employed to minimise induced errors. Zero-phase digital filtering is engaged to reduce inaccuracy on the PPG signals when measured from a poorly perfused periphery. In this system, a decision matrix adopts the appropriate technique to improve the PPG signal-to-noise ratio dynamically. Statistical analyses show promising results (maximum error < 7.63%) when computed HR is compared to corresponding estimates from the electrocardiogram. Hence, the results here suggest that this dual-mode approach has potential for use in relevant clinical measurements.

Artifacts↗

PubMed2006

Implementing an animated geographic information system to investigate factors associated with nosocomial infections: a novel approach.

BACKGROUND: Two million Americans acquire an infection in the hospital each year, resulting in an estimated 88,000 patient deaths per year. OBJECTIVE: Our objective was to describe our initial experience using an animated geographic information system (GIS) to investigate factors associated with nosocomial transmission of resistant organisms. We used a descriptive study at a university-affiliated, county, teaching hospital. We studied all patients and nursing staff on 4 adult, general medicine wards from June through August 2004. RESULTS: We developed and implemented GIS software. GIS-generated animations demonstrated inappropriate patient placement for 19% of patients with methicillin-resistant Staphylococcus aureus and insufficient time for hand hygiene in 14% (6248) of health care provider-patient contacts. CONCLUSION: Animated GIS can uncover previously hidden factors that contribute to the spread of nosocomial infections. This technology may become a useful adjunct for the prevention of nosocomial transmission of infectious agents.

Computer Graphics↗

PubMed2006

Translating evidence into practice to prevent central venous catheter-associated bloodstream infections: a systems-based intervention.

BACKGROUND: The central venous catheter (CVC) is a necessary, yet inherently risky, modern medical device. We aimed to carry out a systems-based intervention designed to facilitate the use of maximal sterile barrier precautions and the use of chlorhexidine for skin antisepsis during insertion of CVC. METHODS: All patients in whom a CVC was inserted at a medical-surgical intensive care unit at a university-affiliated public hospital were included in a before-after trial. The standard CVC kit in routine use before the intervention included a small sterile drape (24" by 36") and 10% povidone-iodine for skin antisepsis. We special ordered a customized kit that, instead, included a large sterile drape (41" by 55") and 2% chlorhexidine gluconate in 70% isopropyl alcohol. Both the standard kit in use before the intervention and the customized kit included identical CVCs. Baseline data included the quarterly CVC-associated bloodstream infection (BSI) rates during the 15 months before the intervention. Comparison data included the quarterly CVC-associated BSI rates during the 15 months after we instituted exclusive use of the customized kit. RESULTS: The mean quarterly CVC-associated BSI rate decreased from a baseline of 11.3 per 1000 CVC-days before the intervention to 3.7 per 1000 CVC-days after the intervention (P < .01). Assuming direct costs of at least 10,000 dollars per CVC-associated BSI, we calculated resultant annualized savings to the hospital of approximately 350,000 dollars. CONCLUSION: Infection control interventions that rely on voluntary changes in human behavior, despite the best intentions of us all, are often unsuccessful. We have demonstrated that a systems-based intervention led to a sustained decrease in the CVC-associated BSI rate, thereby resulting in improved patient safety and decreased cost of care.

Bacteremia↗

PubMed2006

Screening of obstructive and central apnoea/hypopnoea in children using variability: a preliminary study.

AIM: Polysomnography (PSG) is the current standard protocol for sleep disordered breathing (SDB) investigation in children. Presently, there are limited reliable screening tests for both central (CE) and obstructive (OE) respiratory events. This study compared three indices, derived from pulse oximetry and electrocardiogram (ECG), with the PSG gold standard. These indices were heart rate (HR) variability, arterial blood oxygen de-saturation (SaO2) and pulse transit time (PTT). METHODS: 15 children (12 male) from routine PSG studies were recruited (aged 3-14 years). The characteristics of the three indices were based on known criteria for respiratory events (RPE). Their estimation singly and in combination was evaluated with simultaneous scored PSG recordings. RESULTS: 215 RPE and 215 tidal breathing events were analysed. For OE, the obtained sensitivity was HR (0.703), SaO2 (0.047), PTT (0.750), considering all three indices (0) and either of the indices (0.828) while specificity was (0.891), (0.938), (0.922), (0.953) and (0.859) respectively. For CE, the sensitivity was HR (0.715), SaO2 (0.278), PTT (0.662), considering all indices (0.040) and either of the indices (0.868) while specificity was (0.815), (0.954), (0.901), (0.960) and (0.762) accordingly. CONCLUSIONS: Preliminary findings herein suggest that the later combination of these non-invasive indices to be a promising screening method of SDB in children.

Adolescent↗

PubMed2005

Pulse transit time changes observed with different limb positions.

Pulse transit time (PTT) is a non-invasive measure of arterial compliance. It can be used to assess instantaneous blood pressure (BP) changes in continual cardiovascular measurement such as during overnight respiratory sleep studies. In these studies, periodic changes in limb position can occur randomly. However, little is known about their possible effects on PTT monitored on the various limbs. The objective of this study was to evaluate PTT differences on all four limbs during two positional changes (lowering and raising of a limb). Ten healthy adults (seven male) with a mean age of 27.0 years were recruited in this study. The results showed that the limb that underwent a positional change had significant (p < 0.05) local PTT differences when compared to its nominal baseline value, whereas PTT changes in the other remaining limbs were insignificant (p > 0.05). The mean PTT value measured from a vertically-raised limb increased by 42.7 ms, while it decreased by 28.1 ms with a half-lowered limb. The PTT differences observed during positional change can be contributed to by the complex interactions between hydrostatic pressure changes, autonomic and local autoregulation experienced in these limbs. Hence the findings herein suggest that PTT is able to reflect local circulatory responses despite changes in the position of other limbs. This can be useful in prolonged clinical observations where limb movements are expected.

Adaptation, Physiological↗

PubMed2005

Estimation of breathing interval from the photoplethysmographic signals in children.

Two important parameters that are generally under continual observation during clinical monitoring are heart rate (HR) variability and breathing interval (BI) of patients. Current HR monitoring during night-long childhood respiratory sleep studies is well tolerated but BI monitoring requires instrumentation, like nasal cannula, that can be less accommodating for children. In this study, BI was extracted from the photoplethysmographic (PPG) signals using a two-stage signal processing technique termed zero-phase digital filtering. Eight children (7 male) aged 8.6 +/- 2.6 years were recruited to perform two breathing activities: during tidal and with customized externally applied inspiratory resistive loading (IRL). The accuracy of BI derived from the PPG signals was compared with that estimated by a calibrated air pressure transducer in children. Statistical analysis revealed that mean BI attained from the PPG signals were significantly related during tidal breathing (r(2) = 0.76; range 0.61-0.83; p < 0.05) and with the IRL (r(2) = 0.79; range 0.68-0.85; p < 0.05) in the absence of motion artefacts. Preliminary findings herein suggest that besides having the capability to monitor HR and arterial blood oxygen saturation measurements, the PPG signals can be used to derive BI for children. This can be an attractive alternative for children who are more disturbed by intrusive techniques in prolonged clinical monitoring.

Algorithms↗

PubMed2005

Variability in time delay between two models of pulse oximeters for deriving the photoplethysmographic signals.

Pulse oximetry is commonly used as an arterial blood oxygen saturation (SaO2) measure. However, its other serial output, the photoplethysmography (PPG) signal, is not as well studied. Raw PPG signals can be used to estimate cardiovascular measures like pulse transit time (PTT) and possibly heart rate (HR). These timing-related measurements are heavily dependent on the minimal variability in phase delay of the PPG signals. Masimo SET Rad-9 and Novametrix Oxypleth oximeters were investigated for their PPG phase characteristics on nine healthy adults. To facilitate comparison, PPG signals were acquired from fingers on the same hand in a random fashion. Results showed that mean PTT variations acquired from the Masimo oximeter (37.89 ms) were much greater than the Novametrix (5.66 ms). Documented evidence suggests that 1 ms variation in PTT is equivalent to 1 mmHg change in blood pressure. Moreover, the PTT trend derived from the Masimo oximeter can be mistaken as obstructive sleep apnoeas based on the known criteria. HR comparison was evaluated against estimates attained from an electrocardiogram (ECG). Novametrix differed from ECG by 0.71+/-0.58% (p<0.05) while Masimo differed by 4.51+/-3.66% (p>0.05). Modern oximeters can be attractive for their improved SaO2 measurement. However, using raw PPG signals obtained directly from these oximeters for timing-related measurements warrants further investigations.

Adult↗

PubMed2005

Predictive regression equations and clinical uses of peripheral pulse timing characteristics in children.

Studies have shown that increased arterial stiffening can be an indication of cardiovascular diseases like hypertension. In clinical practice, this can be detected by measuring the blood pressure (BP) using a sphygmomanometer but it cannot be used for prolonged monitoring. It has been established that pulse wave velocity (PWV) is a direct measure of arterial stiffening but its usefulness is hampered by the absence of non-invasive techniques to estimate it. Pulse transit time (PTT) is a simple and non-invasive method derived from PWV. However, limited knowledge of PTT in children is found in the present literature. The aims of this study are to identify independent variables that confound PTT measure and describe PTT regression equations for healthy children. Therefore, PTT reference values are formulated for future pathological studies. Fifty-five Caucasian children (39 male) aged 8.4 +/- 2.3 yr (range 5-12 yr) were recruited. Predictive equations for PTT were obtained by multiple regressions with age, vascular path length, BP indexes and heart rate. These derived equations were compared in their PWV equivalent against two previously reported equations and significant agreement was obtained (p < 0.05). Findings herein also suggested that PTT can be useful as a continuous surrogate BP monitor in children.

Anthropometry↗

PubMed2005

Instructed smoking expectancy modulates cue-elicited neural activity: a preliminary study.

In recent years, research applying functional neuroimaging to the study of cue-elicited drug craving has emerged. This research has begun to identify a distributed system of brain activity during drug craving. A review of this literature suggested that expectations regarding the opportunity to use a drug affected the pattern of neural responses elicited by drug cues. Using functional magnetic resonance imaging (fMRI), we examined the effects of smoking expectancy on the neural response to neutral (e.g., roll of tape) and smoking-related (a cigarette) stimuli in male cigarette smokers deprived of nicotine for 8 hr. As predicted, several brain regions (e.g., the anterior cingulate cortex) exhibited differential activation during cigarette versus neutral cue exposure. Moreover, we found that subregions of the prefrontal cortex (i.e., ventromedial, ventrolateral, and dorsolateral prefrontal cortices) showed cue-elicited activation that was modulated by smoking expectancy. These results highlight the importance of perceived drug use opportunity in the neurobiological response to drug cues.

Adult↗

PubMed2005

Use of pulse transit time to distinguish respiratory events from tidal breathing in sleeping children.

STUDY OBJECTIVES: Currently, esophageal pressure monitoring is the "gold standard" measure for inspiratory efforts, but its invasive nature necessitates a better tolerated and noninvasive method to be used on children. Pulse transit time (PTT) has demonstrated its potential as a noninvasive surrogate marker for inspiratory efforts. The principle velocity determinant of PTT is the change in stiffness of the arterial wall and is inversely correlated to BP. Moreover, PTT has been shown to identify changes in inspiratory effort via the BP fluctuations induced by negative pleural pressure swings. In this study, the capability of PTT to classify respiratory events during sleep as either central or obstructive in nature was investigated. SETTING AND PARTICIPANTS: PTT measure was used in adjunct to routine overnight polysomnographic studies performed on 33 children (26 boys and 7 girls; mean +/- SD age, 6.7 +/- 3.9 years). The accuracy of PTT measurements was then evaluated against scored corresponding respiratory events in the polysomnography recordings. RESULTS: Three hundred thirty-four valid respiratory events occurred and were analyzed. One hundred twelve obstructive events (OEs) showed a decrease in mean PTT over a 10-sample window that had a probability of being correctly ranked below the baseline PTT during tidal breathing of 0.92 (p < 0.005); 222 central events (CEs) showed a decrease in the variance of PTT over a 10-sample window that had a probability of being ranked below the baseline PTT of 0.94 (p < 0.005). This indicates that, at a sensitivity of 0.90, OEs can be detected with a specificity of 0.82 and CEs can be detected with a specificity of 0.80. CONCLUSIONS: PTT is able to categorize CEs and OEs accordingly in the absence of motion artifacts, including hypopneas. Hence, PTT shows promise to differentiate respiratory events accordingly and can be an important diagnostic tool in pediatric respiratory sleep studies.

Abdomen↗

PubMed2005

The safety and efficacy of the administration of recombinant activated factor VII in major surgery and trauma patients.

Recombinant activated Factor VII (rFVIIa) has been successfully used in the treatment of haemophilia A and B with associated inhibitors for some years. Activated Factor VII binds to activated platelets independently of tissue factor. The resulting stimulation of an exaggerated early thrombin burst at sites of vascular injury makes it an attractive potential treatment for massive, uncontrolled bleeding associated with surgery and trauma. This article describes the evidence relating to surgery and trauma. The lack of large, controlled trials of rFVIIa means that a definitive recommendation regarding its use cannot be made at present. However, in the context of clearly defined protocols and balanced treatment strategies, rFVIIa may have a role in traumatic bleeding. Large scale, randomised controlled trials in trauma are required, as is further work on the safety profile of rFVIIa with an independent international safety monitoring committee.

Drug Costs↗

PubMed2005

The safety and efficacy of the use of vasopressin in sepsis and septic shock.

Sepsis remains a significant problem and cause of morbidity and mortality in intensive care. Vasopressin infusions are currently used as rescue therapy for the treatment of vasodilatory, catecholamine-resistant septic shock. At present, there are no large randomised, controlled trials in the literature investigating vasopressin in this role, although two such studies are currently ongoing in Canada. This review outlines the pathophysiology of sepsis and that of vasopressin in sepsis and reviews the available evidence for the use of vasopressin in sepsis and septic shock. A review of the safety data for vasopressin in this indication is included. Recommendations for the use of vasopressin in septic shock, along with suggestions for the direction of further work in the field are presented.

Clinical Trials as Topic↗

PubMed2004

Dimerization of the human receptors for prostacyclin and thromboxane facilitates thromboxane receptor-mediated cAMP generation.

Prostacyclin (PGI(2)) and thromboxane (TxA(2)) are biological opposites; PGI(2), a vasodilator and inhibitor of platelet aggregation, limits the deleterious actions of TxA(2), a vasoconstrictor and platelet activator. The molecular mechanisms involved in the counterregulation of PGI(2)/TxA(2) signaling are unclear. We examined the interaction of the receptors for PGI(2) (IP) and TxA(2) (TPalpha). IP-induced cAMP and TP-induced inositol phosphate generation were unaltered when the receptors were co-expressed in HEK 293 cells (IP/TPalpha-HEK). TP-cAMP generation, in response to TP agonists or a TP-dependent isoprostane, iPE(2)III, was evident in IP/TPalpha-HEK and in aortic smooth muscle cells, but not in cells expressing either receptor alone, or in IP-deficient aortic smooth muscle cells. Augmentation of TP-induced cAMP generation, with the IP agonist cicaprost, was ablated in IP-deficient cells and was independent of direct IP signaling. IP/TPalpha heterodimers were formed constitutively when the receptors were co-expressed, with no overt changes in ligand binding to the individual receptor sites. However, despite inefficient binding of iPE(2)III to either the IP or TPalpha, expressed alone or in combination, robust cAMP generation was evident in IP/TPalpha-HEK, suggesting the formation of an alternative receptor site. Thus, IP/TPalpha dimerization was coincident with TP-cAMP generation, promoting a "PGI(2)-like" cellular response to TP activation. This represents a previously unknown mechanism by which IP may limit the cellular effects of TP.

8-Bromo Cyclic Adenosine Monophosphate↗