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Biomedical subjects

J Wilson

Publications and source records attributed to J Wilson.

At least 19 recordsLinked to original sources

Production cross-sections of 181-186Re isotopes from proton bombardment of natural tungsten.

Cross-sections for the production of (181)Re, (182m)Re, (182g)Re, (183)Re, (184)Re, and (186)Re from proton bombardment of natural tungsten have been measured using the stacked foil technique for proton energies up to 17.6 MeV. Results are compared with the theoretical excitation functions as calculated by the EMPIRE II code (version 2.19) and experimental literature values. Results are in strong agreement with some of the previously reported literature as well at theoretical calculations for multiple reactions providing for more reliable estimates for the (186)W(p,n)(186)Re reaction.

Protons↗

What are the illness perceptions of people with dysphonia: a pilot study.

BACKGROUND: Patients do not respond to treatment in a predictable manner. Individual preconceptions determine help seeking, compliance and treatment outcome, yet clinicians rarely explore these issues. The illness perception approach sees the patient as an active participant in the healthcare process. AIMS: The aim of this study was to investigate the illness perceptions of people with dysphonia. The subsidiary aims were to correlate the Illness Perception Questionnaire with any psychological distress identified and a self-report measure of dysphonia, and to consider any potential implications for patient management. DESIGN: Prospective, cross-sectional observation. SETTING: Primary and secondary care, two general and four community hospitals. PARTICIPANTS: Fifty adult patients with dysphonia due to benign disease completed three self-administered questionnaires, which investigated their illness perceptions, psychological distress and perceptions of the impact of the presenting 'illness'. MEASURES: The dysphonia was categorised as being due to functional (n=40) or organic (n=10) causes. All the voices were rated by an expert listener according to the GRBAS (grade, roughness, breathiness, aesthenia, strain) scale. PARTICIPANTS completed the Illness Perception Questionnaire, the Vocal Performance Questionnaire and the Hospital Anxiety and Depression scale. RESULTS: Patients showed a wide variation in perception of causation. They had no strong perceptions about the causes, consequences or duration of the presenting dysphonia. Functional dysphonics reported greater consequences, lower perceived control and increased anxiety when compared to patients with organic dysphonia. In terms of cure/control, all patients expected treatment to be helpful but this expectancy reduced as time increased. Anxiety was more associated with functional dysphonia, however, only 17 per cent of the subjects in this group showed clinically significant levels of signs of psychological distress. CONCLUSIONS: Lay illness representations often diverge from the clinician's understanding of the presenting problem and strongly influence treatment behaviour. Early exploration of illness perceptions may enhance health behaviour and maximise the impact of intervention.

Adult↗

SPINE high-throughput crystallization, crystal imaging and recognition techniques: current state, performance analysis, new technologies and future aspects.

This paper reviews the developments in high-throughput and nanolitre-scale protein crystallography technologies within the remit of workpackage 4 of the Structural Proteomics In Europe (SPINE) project since the project's inception in October 2002. By surveying the uptake, use and experience of new technologies by SPINE partners across Europe, a picture emerges of highly successful adoption of novel working methods revolutionizing this area of structural biology. Finally, a forward view is taken of how crystallization methodologies may develop in the future.

Crystallography↗

Erythropoietin or darbepoetin for patients with cancer.

BACKGROUND: Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoietin (Epo), darbepoetin (Darbepo) and red blood cell transfusions. OBJECTIVES: The aim of this systematic review was to assess the effects of Epo or Darbepo to either prevent or treat anaemia in cancer patients. SEARCH STRATEGY: We searched the Central Register of Controlled Trials, MEDLINE and EMBASE and other data bases. Searches were done for the periods 01/1985 to 12/2001 for the first review and 1/2002 to 04/2005 for the update. We also contacted experts in the field and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials on managing anaemia in cancer patients that compared the use of Epo/Darbepo (plus transfusion if needed) with observation until red blood cell transfusion was required. DATA COLLECTION AND ANALYSIS: Several reviewers independently assessed trial quality and extracted data. MAIN RESULTS: This update of the systematic review included a total of 57 trials with 9,353 patients. Of these, 27 trials with 3,287 adults were also included in the first Cochrane Review. Thirty trials with 6,066 patients were added during the update process. Use of Epo/Darbepo significantly reduced the relative risk of red blood cell transfusions (RR 0.64; 95% CI 0.60 to 0.68, 42 trials, n = 6,510). On average participants in the Epo/Darbepo group received one unit of blood less than the control group (WMD -1.05; 95% CI -1.32 to -0.78, 14 trials, n = 2,353). For participants with baseline haemoglobin below 12 g/dL haematological response was observed more often in participants receiving Epo/Darbepo (RR 3.43; 95% CI 3.07 to 3.84, 22 trials, n = 4,307). There was suggestive evidence that Epo/Darbepo may improve Quality of Life (QoL). The relative risk for thrombo embolic complications was increased in patients receiving Epo/Darbepo compared to controls (RR 1.67, 95% CI 1.35 to 2.06; 35 trials, n = 6,769). Uncertainties remain whether and how Epo/Darbepo effects tumour response (fixed effect RR 1.12; 95% CI 1.01 to 1.23, 13 trials, n = 2,833; random effects: RR 1.09; 95% CI 0.94 to 1.26) or overall survival (unadjusted and adjusted data: HR 1.08; 95% CI 0.99 to 1.18; 42 trials, n = 8,167). AUTHORS' CONCLUSIONS: There is consistent evidence that administration of Epo/Darbepo reduces the relative risk for blood transfusions and the number of units transfused in cancer patients. For patients with baseline haemoglobin below 12 g/dL (mild anaemia) there is strong evidence that Epo/Darbepo improves haematological response. There is suggestive evidence that Epo/Darbepo may improve QoL. However, there is strong evidence that Epo/Darbepo increases the relative risk for thrombo embolic complications. Whether and how Epo/Darbepo effects tumour response and overall survival remains uncertain.

Anemia↗

Duration of operation as a risk factor for surgical site infection: comparison of English and US data.

T times are used to categorize surgical procedures into long and short durations. They constitute a part of the US National Nosocomial Infection Surveillance (NNIS) risk index that is widely used internationally in surveillance for surgical site infections (SSIs). The objective of this study was to compare the US NNIS T times with data collected in England. The Surgical Site Infection Surveillance Service in England holds data collected by 168 hospitals in 13 categories of surgical procedures between 1997 and 2002. The 75(th) percentile and corresponding T time were calculated from English data and compared with US times. Differences in rates of SSI above and below the T times were compared. Graphical methods were used to assess the cut points that exhibited an association with risk of SSI. The results show that English and US T times were the same for all surgical categories except coronary artery bypass graft and vascular surgery, where the English T time was 4 h. The 75(th) percentile time for hip hemiarthroplasties was 40 min less than for total hip replacements (THR). Although the incidence of SSI in THR was significantly higher in operations lasting for longer than the T time (P<0.05), no association between risk of SSI and T times set at 1, 1.5 or 2 h was observed for hip hemiarthroplasties. In conclusion, operations lasting for longer than the T time were associated with a higher risk of SSI in most categories. In the hip prosthesis category, this association only applied to THR.

Humans↗

An investigation of transmission ratio distortion in the central region of the human MHC.

Transmission ratio distortion (TRD) describes a significant departure from expected Mendelian inheritance ratios that is fundamental to both the biology of reproduction and statistical genetics. The relatively high fetal wastage in humans, with consequent selection of alleles in utero, makes it likely that TRD is prevalent in the human genome. The central region of the human major histocompatibility complex (MHC) is a strong TRD candidate, as it houses a number of immune and regulatory genes that may be important in pregnancy outcome. We used a nonhaplotype-based method to select 13 tagging SNPs from three central MHC candidate regions, and analysed their transmission in 380 newborns and their parents (1138 individuals). A TRD of 54:46 was noted in favour of the common allele of a promoter SNP in the CLIC1 gene (P = 0.025), with a similar distortion using haplotypes across the same gene region (P = 0.016). We also found evidence that markers in the CLIC1 gene region may have been subject to recent selection (P < 0.001). The study illustrates the potential benefits of screening for TRD and highlights the difficulties encountered therein.

Biomarkers↗

Can pre-operative skin marking transfer methicillin-resistant Staphylococcus aureus between patients? A laboratory experiment.

National guidelines state that in patients undergoing operations the site of the procedure should be marked. In clinical practice the same marker is used repeatedly. We are not aware of any investigation regarding the theoretical risk of transferring organisms such as methicillin-resistant Staphyloccocus aureus (MRSA) between patients by a skin marker. In an experimental setting, Penflex and Viomedex skin markers were tested 30 times each after contaminating them with a standard inoculum of MRSA. The survival of the organism on the tip of the markers was assessed by culture on MRSA-indicator nutrient agar plates at 0, 5, 15 and 60 minutes, 24 and 48 hours and at 1, 2, and 3 weeks after contamination. There was a significant difference between the markers, with the Penflex showing no survival of MRSA after 15 minutes whereas the Viomedex product continued to produce MRSA cultures for up to three weeks.

Cross Infection↗

An investigation of the use of the MicroFoss as an indicator of the shelf life of pasteurized fluid milk.

The MicroFoss method was evaluated for its effectiveness as an indicator of fluid milk shelf life. Half-gallon, 2% fat fluid milk samples (n = 90) were obtained from a milk processing plant on 3 occasions postpasteurization and evaluated for shelf life. Sensory evaluation was performed by 3 judges experienced in the use of the American Dairy Science Association scorecard for milk. A score of 5 or less was considered to represent the end of the shelf life of the product. MicroFoss coupled with preliminary incubation (PI) was utilized to estimate the total viable (TVC) and gram-negative counts (GN) in the milk. The MicroFoss functions by using a pH indicator or CO2 production to detect changes in light reflection to estimate bacterial populations. Simple and multiple linear regression analyses were utilized to determine the relationship between MicroFoss (PI-GN and PI-TVC detection times) and product shelf life. It was concluded that using both PI-GN and PI-TVC in a combined algorithm is the optimal way of using MicroFoss as a shelf-life indicator. When PI-TVC was selected in the algorithm, a correlation coefficient of 0.89 existed between PI-TVC and shelf life; PI-GN was used in the algorithm in the place of PI-TVC when its detection time was within 6 h of the detection time of PI-TVC vials. The PI-GN detection times correlated well (r = 0.80) with shelf life, but more importantly, all but one PI-GN sample (n = 50) selected in the algorithm had a shelf life of less than 10 d. This indicates that the PI-GN measurement can be utilized along with PI-TVC detection time to indicate potential shelf-life problems.

Algorithms↗

Electrophysiological and behavioral phenotype of insulin receptor defective mice.

The olfactory bulb expresses one of the highest levels of insulin found in the brain. A high level of expression of the concomitant insulin receptor (IR) kinase is also retained in this brain region, even in the adult. We have previously demonstrated in a heterologous system that insulin modulates the voltage-dependent potassium channel, Kv1.3, through tyrosine phosphorylation of three key residues in the amino and carboxyl terminus of the channel protein. Phosphorylation also induces current suppression of the Kv1.3-contributed current in cultured olfactory bulb neurons (OBNs) of rodents. In order to explore the behavioral importance of this kinase-induced modulation of the channel for the olfactory ability of the animal, mice with a targeted-gene deletion of the insulin receptor were electrophysiologically and behaviorally characterized. Mice heterozygous for the insulin receptor kinase (IR+/-) gene performed the same as wild-type (+/+) mice when challenged with a traditional, non-learning-based task to test gross anosmia. There was also no significant difference across the two genotypes in tests designed to measure exploratory behavior or in a battery of systems physiology experiments designed to assess metabolic energy usage (locomotion, ingestive behaviors, weight, oxygen consumption, and respiratory quotient). Object memory recognition tests suggest that IR+/- mice have an impairment in recognition of familiarized objects; IR+/- mice demonstrate poor performance for both short-term (1 h) and long-term (24 h) memory tests in comparison to that of wild-type mice. Electrophysiological experiments indicate that mitral cell neurons cultured from both heterozygous and homozygous-null mice (IR+/- and IR-/-) have an decreased peak current amplitude compared with that recorded for wild-type (+/+) animals matched for days in vitro (DIV). These data indicate that the loss of one allele of the IR kinase gene modifies the electrical phenotype of the mitral cell neurons in the olfactory bulb without a change in gross olfactory ability. Given our findings that there are no significant changes in metabolic balance of the IR (+/-) mice but some impairment in memory retention, future experiments testing for specific olfactory behaviors or functional deficits in IR-/+ mice models of diabetes will need to either be tasks that do not require learning or will require a different model (such as diet-induced diabetes) that may evoke a stronger phenotype.

Animals↗

Sensitivity and specificity of electrodiagnostic criteria for CIDP using ROC curves: comparison to patients with diabetic and MGUS associated neuropathies.

INTRODUCTION: Electrodiagnostic testing plays a key role in the characterization of neuropathies. To this end, sets of electrodiagnostic criteria have been proposed to define chronic inflammatory demyelinating polyneuropathy (CIDP). These criteria sets differ because of the number of data points within the sets, the number of required abnormal measures within a criterion, and the cutoff value of each measure. OBJECTIVE: To evaluate the sensitivity and specificity of the published criteria for defining CIDP in comparison to diabetic polyneuropathy (DMPN) and monoclonal gammopathy of undetermined significance associated neuropathies (MGUS-PN). DESIGN/METHODS: Electrodiagnostic studies of 21 patients with biopsy proven CIDP, 35 patients with MGUS-PN, and 82 patients with DMPN were analyzed. Data were compared against 4 different published criteria sets. Receiver operator characteristic (ROC) curves were used to determine the ideal threshold values for individual electrodiagnostic parameters. RESULTS/CONCLUSION: None of the currently published criteria sets could adequately separate CIDP from DMPN and MGUS-PN. Analysis of our data using ROC curves shows that the best discrimination was achieved using the following criteria: (1) FWL>145%ULN in one nerve or 110%ULN in two nerves in separate nerve roots. (2) Motor CV<90%LLN in four nerves with at least one nerve <70%LLN. Furthermore, proximal-to-distal amplitude ratio alone is not adequate to define conduction block. Although electrodiagnostic studies are important for evaluating CIDP, these studies by themselves cannot be used to define this neuropathy.

Adult↗

Risk assessment of chemicals and pharmaceuticals in the pediatric population: a workshop report.

ATSDR and RIVM organized an Expert Panel Workshop on the Differences Between Children and Adults and Their Relevance to Risk Assessment. The workshop was held in June 2003, in Brussels, Belgium. The purpose of the workshop was to identify data gaps in current scientific knowledge related to children's health and to recognize areas of mutual interest that would serve as the basis for upcoming ATSDR/RIVM cooperative projects. The aim for both agencies is a better understanding of the issues related to children's health, and the improvement of scientifically based (chemical) risk assessment in children. Topics discussed included clinical trials/toxicity studies, testing in juvenile animals, PBPK modeling in children, and children's risk assessment.

Animals↗

Models for explaining the homeopathic healing process: a historical and critical account of principles central to homeopathy.

The success of Homeopathy in curing many diseases has been a serious challenge to science. Nineteenth century explanations for the healing process of Homeopathy cannot withstand the scrutiny of modern science and need to be abandoned or modified. The surviving propositions are discussed. A biocybernetic model with multilevels of electromagnetic feedback loops offers a hope of explaining the healing process. This model, its explanation of the healing process and experimental support are elaborated.

Biophysical Phenomena↗

Adverse impact of surgical site infections in English hospitals.

Between October 1997 and June 2001, 140 English hospitals participating in the surveillance of surgical site infection (SSI) with the Nosocomial Infection National Surveillance Service (NINSS) reported 2832 SSIs following 67 410 surgical procedures in nine defined categories of surgery. Limb amputation had the highest incidence of SSI with 14.3 SSIs per 100 operations. For all categories of surgery, except knee prosthesis (P=0.128), there was a linear increase in the incidence of SSI when the American National Nosocomial Infections Surveillance risk index increased. Superficial incisional SSI was more common than deep incisional and organ/space SSI, and accounted for more than half of all SSIs for all categories of surgery. The postoperative length of stay (LOS) was longer for patients with SSI, and when adjusted for other factors influencing LOS, the extra LOS due to SSI ranged from 3.3 days for abdominal hysterectomy to 21.0 days for limb amputation, and was at least nine days for the other categories. The additional cost attributable to SSI ranged from pound959 for abdominal hysterectomy to pound6103 for limb amputation. Deep incisional and organ/space SSI combined incurred a greater extra LOS and cost than superficial incisional SSI for all categories of surgery, except limb amputation. The crude mortality rate was higher for patients with SSI for all categories of surgery but, after controlling for confounding, only patients with SSI following hip prosthesis had a mortality rate that was significantly higher than those without SSI [odds ratio (OR)=1.8, P=0.002]. However, the adjusted mortality rate for patients with deep incisional and organ/space SSI compared with those without SSI was significantly higher for vascular surgery (OR=6.8, P<0.001), hip prosthesis (OR=2.5, P=0.005) and large bowel surgery (OR=1.8, P=0.04). This study shows that the adverse impact of SSI differs greatly for different categories of surgery, and highlights the importance of measuring the impact for defined categories rather than for all SSIs and all surgical procedures.

Amputation, Surgical↗

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci.

Experimental evidence implicates interferon gamma (IFNgamma) in protection from and resolution of chlamydial infection. Conversely, interleukin 10 (IL10) is associated with susceptibility and persistence of infection and pathology. We studied genetic variation within the IL10 and IFNgamma loci in relation to the risk of developing severe complications of human ocular Chlamydia trachomatis infection. A total of 651 Gambian subjects with scarring trachoma, of whom 307 also had potentially blinding trichiasis and pair-matched controls with normal eyelids, were screened for associations between single-nucleotide polymorphisms (SNPs), SNP haplotypes and the risk of disease. MassEXTEND (Sequenom) and MALDI-TOF mass spectrometry were used for detection and analysis of SNPs and the programs PHASE and SNPHAP used to infer haplotypes from population genetic data. Multivariate conditional logistic regression analysis identified IL10 and IFNgamma SNP haplotypes associated with increased risk of both trachomatous scarring and trichiasis. SNPs in putative IFNgamma and IL10 regulatory regions lay within the disease-associated haplotypes. The IFNgamma +874A allele, previously linked to lower IFNgamma production, lies in the IFNgamma risk haplotype and was more common among cases than controls, but not significantly so. The promoter IL10-1082G allele, previously associated with high IL10 expression, is in both susceptibility and resistance haplotypes.

Alleles↗

Lactate threshold responses to a season of professional British youth soccer.

OBJECTIVE: To examine the changes in aerobic endurance performance of professional youth soccer players throughout the soccer season. METHODS: Nine youth soccer players were tested at six different time points throughout the soccer season by sub-maximal blood lactate assessment, using an incremental treadmill protocol. Whole blood lactate concentration and heart frequency (Hf) were determined at each exercise stage. Running velocities at the first lactate inflection point (v-T(lac)) and at a blood lactate concentration of 4 mmol l(-1) (v-4mM) were determined. RESULTS: Running velocity at the two lactate thresholds increased from the start of pre-season training to the early weeks of the competitive season, from 11.67 (0.29) to 12.96 (0.28) km h(-1) for v-T(lac), and from 13.62 (0.25) to 14.67 (0.24) km h(-1) for v-4mM (p<0.001). However, v-T(lac )and v-4mM when expressed relative to maximum heart frequency (Hf(max)) remained unchanged. The Hf to blood lactate concentration relationship was unchanged after the pre-season training period. The two expressions of lactate threshold did not reveal differences between each other. CONCLUSION: Running velocity at v-T(lac )and v-4mM increased significantly over the pre-season period, but v-T(lac )and v-4mM were unchanged when expressed relative to Hf(max). This finding may indicate that increased endurance performance may be mainly attributable to alterations in Vo(2max). Although lactate assessment of soccer players is useful for determining endurance training adaptations in soccer players, additional assessment of the other two determinants of endurance performance (Vo(2max) and running economy) may provide more useful information for determining physiological adaptations resulting from soccer training and training interventions.

Adolescent↗

Improvement in the clinical cure rate of outpatient management of pelvic inflammatory disease following a change in therapy.

OBJECTIVE: In the United Kingdom many genitourinary medicine clinics use oral doxycycline and metronidazole to treat pelvic inflammatory disease (PID). A retrospective case note review of PID treatment at our department in 2000 showed that the clinical cure rate (CCR) was only 55% with oral doxycycline and metronidazole for 2 weeks. We therefore added ceftriaxone 250 mg intramuscularly to the doxycycline and metronidazole for treating PID. We have repeated the review and compared the results with those from 2000. METHODS: All patients diagnosed as having PID between 1 July 2002 and 31 December 2002 were identified. These episodes were diagnosed on clinical presentations of pelvic pain, vaginal discharge or bleeding, and cervical motion tenderness on physical examination. The CCR was defined as patients who fully resolved their symptoms and signs during 2 week and 4 week follow up. The results were compared with those from 2000. RESULTS: Women receiving ceftriaxone, doxycycline, and metronidazole had a CCR of 72%. In 2000 the CCR for women receiving only doxycycline and metronidazole was 55%. There were only 8% non-responders in 2002 compared with 18% in 2000. Comparing CCR and non-response rate, in 2002 there was a significant improvement in cure rate, OR 3.01 (95% CI 1.28 to 7.47) p = 0.009. Using an intent to treat analysis and including the defaulters as treatment failures there was still a significant improvement in cure rate, OR 2.03 (95% CI 1.18 to 3.50) p = 0.009. CONCLUSIONS: The treatment of PID with ceftriaxone, doxycycline, and metronidazole gave a significantly higher CCR than doxycycline and metronidazole. Our experience would suggest that doxycycline and metronidazole alone is not a suitable regimen for treatment of PID in the United Kingdom.

Ambulatory Care↗

A survey of sexual and reproductive health in men with cystic fibrosis: new challenges for adolescent and adult services.

BACKGROUND: Improved survival dramatically alters the consequences of adult co-morbidities in men with cystic fibrosis (CF) such as male infertility. Few studies have systematically addressed the impact of sexual and reproductive health issues in these men or considered the implications for healthcare delivery. METHOD: A descriptive cohort study was undertaken using a sexual and reproductive health survey of men from a large adult CF centre, including men with lung transplantation. RESULTS: The mean (SD) age of the 94 men (response rate 75%) was 30.5 (7.6) years. 94% knew that men with CF had reduced fertility. Men first heard about infertility later than desired (p<0.001) and only 53% heard from their preferred source. Men who were told about infertility when older were more likely to be upset than those told earlier (p<0.01). 53% of men had undergone semen analysis: 68% of men who had not been tested wanted semen analysis. 73% believed semen analysis should occur before 18, but the youngest age of testing was 24 years. In adolescence, one in three men had assumed they did not need to use condoms and one in 10 had confused infertility with impotence. 66% of men wanted more information on reproductive options and 84% wanted children. Seventeen men were parents by natural conception (n = 1), micro-epididymal sperm aspiration (n = 6), donor sperm (n = 9), and through step children (n = 1). CONCLUSIONS: Men with CF desire more sexual and reproductive health information. Earlier discussion of sexual and reproductive health is indicated in paediatric settings, and semen analysis should be routinely offered. In adult services greater discussion of reproductive health options is indicated.

Adolescent↗

A comprehensive approach for evaluating telemedicine-delivered multidisciplinary breast cancer meetings in southern Scotland.

Multidisciplinary team (MDT) meetings for decisions on cancer management are a cornerstone of UK cancer policy. We have proposed a comprehensive methodology to assess the clinical and economic effectiveness of telemedicine in this setting, which is being tested in a randomized breast cancer trial. Pre- and post-telemedicine assessment includes attitudes to and expectations of telemedicine, based on semistructured interviews. The communication content of videotapes of the MDT meeting is being scored using Borgatta's revised Interaction Process Analysis System. The technical performance of the telemedicine equipment is reported on a standardized pro forma. A short questionnaire captures key elements of professional satisfaction for each patient discussion (consensus on future management, confidence in and sharing of decision), added value of linkage, group atmosphere, overall conduct of the meeting and compliance with SIGN guidelines. A cost-minimization analysis will be used for economic assessment.

Attitude of Health Personnel↗