Search PubMed⌕ Search

Biomedical subjects

A Wright

Publications and source records attributed to A Wright.

At least 73 records · Page 4Linked to original sources

Nonpharmacological treatments for musculoskeletal pain.

BACKGROUND: Several types of physical therapy are used in the management of painful musculoskeletal disorders. These treatment modalities can be broadly categorized as electrotherapy modalities (e.g., transcutaneous electrical nerve stimulation), acupuncture, thermal modalities (e.g., moist heat, ultrasound), manual therapies (e.g., manipulation or massage), or exercise. Within each of these broad categories significant variations in treatment parameters are possible. OBJECTIVE: To consider the evidence base for each of these main categories of physical therapy in the management of musculoskeletal pain. METHOD: To consider the available evidence related to clinical effectiveness and then to review evidence from basic science studies evaluating potentially therapeutic effects of the various therapies. RESULTS: There seems to be evidence from basic science research to suggest that many of the therapies could have potentially therapeutic effects. However, there appears to be limited high-quality evidence from randomized clinical trials to support the therapeutic effectiveness of several of the therapies. CONCLUSIONS: There is some preliminary evidence to support the use of manual therapies, exercise, and acupuncture in the management of some categories of musculoskeletal pain. Limitations of the existing research base are discussed and recommendations for areas of future research are provided.

Acupuncture Therapy↗

Development of the fallopian canal in humans: a morphologic and radiologic study.

AIMS: This study investigated the development of the fallopian canal with particular reference to the mode of ossification and dehiscences, sites of incomplete closure around the facial nerve. BACKGROUND: The precise sequence of events surrounding ossification of the tissues around the facial nerve is uncertain. Incomplete ossification results in dehiscence of the adult structure, which places the nerve at increased risk of damage from disease processes in the middle ear and iatrogenic trauma during otologic surgery. METHODS: Twenty-four temporal bones from 12-to 36-week human fetuses were resected. Eight temporal bones from 22-to 36-week fetuses were microsliced to produce 1.5-mm horizontal sections and radiographed. Sixteen temporal bones from 12-to 35-week fetuses were serially microtomed to produce 7-microm slices, which were stained with hematoxylin and eosin. Quantitative and qualitative analyses of these sections were performed to document patterns of closure of the primitive canal and dehiscence formation. RESULTS: The tympanic part of the primitive fallopian canal, the facial sulcus, developed anteroposteriorly from the geniculate fossa to enclose the facial nerve. The mesenchyme that formed the facial sulcus underwent endochondral ossification, while the bone which capped or closed the sulcus developed in membrane. In the tympanic segment, permanent congenital dehiscences were elliptical and about 1 mm in length. CONCLUSIONS: This study clarifies the mode of development of the fallopian canal, with particular reference to dehiscences, and provides a scientific basis for otologic practice.

Facial Nerve↗

Differential gene expression from two transcriptional units in the cag pathogenicity island of Helicobacter pylori.

Infection with Helicobacter pylori strains containing the cag Pathogenicity Island (cag PAI) is strongly correlated with the development of severe gastric disease, including gastric and duodenal ulceration, mucosa-associated lymphoid tissue lymphoma, and gastric carcinoma. Although in vitro studies have demonstrated that the expression of genes within the cag PAI leads to the activation of a strong host inflammatory response, the functions of most cag gene products and how they work in concert to promote an immunological response are unknown. We developed a transcriptional reporter that utilizes urease activity and in which nine putative regulatory sequences from the cag PAI were fused to the H. pylori ureB gene. These fusions were introduced in single copies onto the H. pylori chromosome without disruption of the cag PAI. Our analysis indicated that while each regulatory region confers a reproducible amount of promoter activity under laboratory conditions, they differ widely in levels of expression. Transcription initiating upstream of cag15 and upstream of cag21 is induced when the respective fusion strains are cocultured with an epithelial cell monolayer. Results of mouse colonization experiments with an H. pylori strain carrying the cag15-ureB fusion suggested that this putative regulatory region appears to be induced in vivo, demonstrating the importance of the urease reporter as a significant development toward identifying in vivo-induced gene expression in H. pylori.

Animals↗

Does passive smoking increase the frequency of health service contacts in children with asthma?

BACKGROUND: Passive smoking is a major cause of respiratory morbidity in children. However, few studies give accurate estimates of the health effects of passive smoking in children with asthma using an objective measure of exposure. The effects of passive smoking using salivary cotinine levels to measure exposure were investigated. METHODS: A sample of 438 children aged 2-12 years with asthma who had a parent who smoked were recruited in Tayside and Fife, Scotland. Health service contacts for asthma, assessed from GP case records, were used as a proxy for morbidity. RESULTS: A weak U-shaped relationship was found between the salivary cotinine level and health service contacts for asthma: compared with low cotinine levels those with moderate cotinine levels had a reduced contact rate (relative rate (RR) = 0.91, 95% confidence interval (CI) 0.80 to 1.05), whereas high cotinine levels were associated with an increased rate of contact (RR = 1.19, 95% CI 1.05 to 1.37). In contrast, a strong association was seen with the amount the parent reported smoking in front of the child: the higher the level the fewer visits were made for asthma (RR for everyday exposure = 0.66, 95% CI 0.56 to 0.77). This effect was not seen for non-respiratory visits. Demographic factors, age of child, and number of children in the family all had a powerful effect on the number of visits for asthma. The parents' perception of asthma severity was associated with visit frequency independent of actual severity (derived from drug treatment). CONCLUSION: High levels of parental smoking in the home are associated with a reduction in health care contacts for asthma. This could be due to a lack of awareness of asthma symptoms among heavy smokers or a reluctance to visit the GP. Children with asthma who have parents who smoke heavily may not be receiving adequate management.

Asthma↗

Changes in the quality of life of patients receiving antidepressant medication in primary care: validation of the WHOQOL-100.

BACKGROUND: The study arises from the need for good quality of life (QOL) assessment and a new comprehensive generic QOL profile for cross-cultural use. AIMS: To examine changes in the QOL of patients receiving antidepressants from a general practitioner, and to assess the validity and sensitivity of a new QOL measure, the World Health Organization Quality of Life Assessment (100-item version) (WHOQOL-100). METHOD: Patients with moderate depression (n = 106) completed the WHOQOL-100 and Beck Depression Inventory at the start of treatment and again after 6 weeks. RESULTS: Depression decreased significantly over 2 months and 74% reported feeling better. WHOQOL-100 scores increased in 24 of the 25 facets, demonstrating that QOL improves significantly in the 8 weeks following the start of antidepressant treatment. It also shows the instrument's validity and sensitivity to changes in clinical condition. CONCLUSIONS: The UK WHOQOL-100 is confirmed as excellent to good. Antidepressants significantly and comprehensively improve QOL.

Adult↗

Assessment of exposure to organic dust in a hemp processing plant.

The aim of this preliminary study was to assess exposure to various constituents of the organic dust generated during the processing of hemp in a small group of exposed workers. Airborne levels of inhalable dust, endotoxin and soluble protein, and the respirable, thoracic and inhalable fractions of fungal, bacterial and actinomycete contamination were measured in the personal breathing zone of exposed workers. Inhalable dust, endotoxin, fungal and bacterial contamination all exceeded levels found in similar vegetable fibre processing factories, since inhalable dust levels ranged from 10.4 to 79.8 mg/m(3) and inhalable bacterial levels between 4.7 and 190 x 10(6) cfu/m(3). Soluble protein and endotoxin (r=0.99, P<0.0001), endotoxin and inhalable dust (r=0.94, P<0.005) and inhalable dust and protein (r=0.98, P<0.0001) were significantly correlated, suggesting that there was little variation in the composition of the dust from different sites or activities around the workplace. Andersen sampling gave an indication of background microbe levels, although no attempt was made to identify the specific microorganisms as all plates were significantly overgrown. Airborne assessments demonstrated that exposures were highly task specific. For example, sweeping the floor generated the highest exposure levels of total dust, protein, endotoxin, bacteria and fungi. Therefore, we have shown that a modern-day hemp fibre processing plant produces significant quantities of respirable dust which is highly contaminated with endotoxin and microorganisms. This organic dust has the potential to cause a range of ill health problems.

Air Microbiology↗

The measurement of total body potassium in patients on peritoneal dialysis.

OBJECTIVES: To assess the validity of measuring total body potassium (TBK) to estimate fat-free mass (FFM) and body cell mass (BCM) in patients on peritoneal dialysis (PD). METHODS: We studied 29 patients on PD (14 men, 15 women) and 30 controls (15 men, 15 women). We calculated TBK by using a whole-body counter to measure 1.46 MeV gamma-ray emissions from naturally occurring 40K. We measured total body water (TBW) by deuterium oxide dilution, and extracellular water (ECW) from bromide dilution. These measurements allowed us to estimate intracellular water (ICW), fat-free mass dilution (FFM(Dilution)), and body cell mass dilution (BCM(Dilution)). RESULTS: The FFM(TBK) in male PD patients (55.7 +/- 7.0 kg) did not differ from that in male controls (57.0 +/- 10.9 kg). The FFM(TBK) in female PD patients (38.4 +/- 6.8 kg) was less than that in female controls (44.7 +/- 4.5, p < 0.01). The FFM(Dilution) did not differ from the FFM(TBK). Correlation of FFM(TBK) and FFM(Dilution) was r = 0.90, p < 0.0001 for all subjects; r = 0.90, p < 0.0001 for PD patients; and r = 0.90, p < 0.0001 for controls. Bland-Altman comparison of FFM(Dilution) with FFM(TBK) in individuals showed bias 0.6 kg, range -8.5 kg to 9.7 kg for the whole group; bias 1.4 kg, range -7.9 kg to 10.7 kg for PD patients; and bias -0.2 kg, range -9.0 kg to 8.6 kg for controls. The BCM(TBK) in male PD patients (30.1 +/- 4.5 kg) did not differ from that in male controls (31.9 +/- 6.2 kg). The BCM(TBK) in female PD patients (19.0 +/- 4.4 kg) was less than that in female controls (23.1 +/- 2.9 kg, p < 0.01). The BCM(Dilution) results did not differ from those for the BCM(TBK). Correlation of BCM(TBK) and BCM(Dilution) was r = 0.90, p < 0.0001 for all subjects; r = 0.87, p < 0.0001 for PD patients; and r = 0.93, p < 0.0001 for controls. Bland-Altman comparison of BCM(Dilution) with BCM(TBK) in individuals showed bias 0.1 kg, range -5.9 kg to 6.1 kg for the whole group; bias 0.0 kg, range -6.9 kg to 6.9 kg for PD patients; and bias 0.1 kg, range -5.0 kg to 5.2 kg for controls. The [K+]ICW did not differ between PD patients and controls (148.0 +/- 25.1 mmol/L vs 148.1 +/- 14.3 mmol/L, p = nonsignificant). CONCLUSIONS: Total body potassium is a valid, noninvasive technique for measuring FFM and BCM in PD patients. In our PD patient group, depletion of FFM and BCM as compared with controls was identified in the women but not in the men.

Body Composition↗

Evaluation of human cytomegalovirus gene expression in thoracic organ transplant recipients using nucleic acid sequence-based amplification.

BACKGROUND: Human cytomegalovirus (CMV) infection is a major cause of morbidity in transplant patients. Early diagnosis and treatment have been shown to improve outcome. We evaluated the suitability of CMV immediate early, early, and late gene expression detected by nucleic acid sequence-based amplification (NASBA) as markers of CMV infection. METHODS: Blood samples were taken immediately before transplant and every one to two weeks after transplantation for 12 weeks from 50 patients undergoing thoracic organ transplantation. CMV-NASBA was performed and results compared with serology, CMV pp65 antigenaemia (CMV-AG) and the development of clinical CMV infection. Patients received "preemptive" anti-CMV therapy with ganciclovir based on the CMV-AG results. RESULTS: CMV immediate early and early gene expression were detected in 87 and 47%, respectively, of patients without other evidence of CMV infection. CMV late gene expression had a sensitivity of 97% for infection (compared with 83% for CMV-AG P=0.06) and a specificity of 93% (compared with 100% P=NS). Late gene expression occurred at the same time as CMV antigenaemia but 1.1 weeks earlier than the threshold of antigenaemia (CMV-AG>10) used to initiate preemptive therapy. CONCLUSION: NASBA provided a standardized tool for the detection of CMV transcripts with a greater sensitivity than the standard antigenemia test. Detection of immediate early and early gene transcripts was not specific for subsequent infection. CMV late gene expression determined by NASBA was an accurate and early marker of CMV infection. Detection of CMV late gene expression could be used to trigger "preemptive" anti-CMV therapy.

Adult↗

Monocyte-derived CD1a+ and CD1a- dendritic cell subsets differ in their cytokine production profiles, susceptibilities to transfection, and capacities to direct Th cell differentiation.

We describe a phenotypically and functionally novel monocyte-derived dendritic cell (DC) subset, designated mDC2, that lacks IL-12 synthesis, produces high levels of IL-10, and directs differentiation of Th0/Th2 cells. Like conventional monocyte-derived DC, designated mDC1, mDC2 expressed high levels of CD11c, CD40, CD80, CD86, and MHC class II molecules. However, in contrast to mDC1, mDC2 lacked expression of CD1a, suggesting an association between cytokine production profile and CD1a expression in DC. mDC2 could be matured into CD83+ DC cells in the presence of anti-CD40 mAbs and LPS plus IFN-gamma, but they remained CD1a- and lacked IL-12 production even upon maturation. The lack of IL-12 and CD1a expression by mDC2 did not affect their APC capacity, because mDC2 stimulated MLR to a similar degree as mDC1. However, while mDC1 strongly favored Th1 differentiation, mDC2 directed differentiation of Th0/Th2 cells when cocultured with purified human peripheral blood T cells, further indicating functional differences between mDC1 and mDC2. Interestingly, the transfection efficiency of mDC2 with plasmid DNA vectors was significantly higher than that of mDC1, and therefore mDC2 may provide improved means to manipulate Ag-specific T cell responses after transfection ex vivo. Taken together, these data indicate that peripheral blood monocytes have the capacity to differentiate into DC subsets with different cytokine production profiles, which is associated with altered capacity to direct Th cell differentiation.

Antigen-Presenting Cells↗

Functional probing of the human glucocorticoid receptor steroid-interacting surface by site-directed mutagenesis. Gln-642 plays an important role in steroid recognition and binding.

To elucidate which amino acids in the glucocorticoid receptor ligand-binding domain might be involved in determining steroid binding specificity by interaction with the D-ring of glucocorticoids, we have performed site-directed mutagenesis of the four amino acids Met-560, Met-639, Gln-642, and Thr-739 based on their proximity to the steroid in a model structure. Mutations of these residues affected steroid binding affinity, specificity, and/or steroid-dependent transactivation. The results indicate that these residues are located in close proximity to the ligand and appear to play a role in steroid recognition and/or transactivating sensitivity, possibly by changes in the steroid-dependent conformational change of this region, resulting in the formation of the AF-2 site. Mutation of Gln-642 resulted in a marked decrease in affinity for steroids containing a 17alpha-OH group. This effect was alleviated by the presence of a 16alpha-CH(3) group to a varying degree. Thr-739 appears to form a hydrogen bond with the 21-OH group of the steroid, as well as possibly forming hydrophobic interactions with the steroid. Met-560 and Met-639 appear to form hydrophobic interactions with the D-ring of the steroid, although the nature of these interactions cannot be characterized in more detail at this point.

Animals↗

Repaired coarctation: a "cost-effective" approach to identify complications in adults.

OBJECTIVES: The study was done to determine the most "cost-effective" approach to follow adults after repair of coarctation of the aorta. BACKGROUND: Recoarctation and/or aneurysm formation following surgical repair or angioplasty for coarctation of the aorta carry a significant morbidity and mortality. Various screening tests to detect such complications are used, but little is known of their sensitivities and specificities; as a consequence, the most "cost-effective" approach to follow such patients is undefined. METHODS: Retrospective analysis was done on the sensitivity and specificity of symptomatology, physical examination, electrocardiogram, chest radiograph, exercise testing and transthoracic echocardiography to detect recoarctation and/or aneurysm formation in 84 adult patients following surgical repair or angioplasty of coarctation of the aorta, using magnetic resonance imaging (MRI) as the gold standard test. RESULTS: Echocardiography had the highest sensitivity in detecting recoarctation (87%) and chest radiograph the highest sensitivity in detecting aneurysm formation (67%). Combined clinical visit and echocardiography had a high sensitivity for diagnosing recoarctation and/or aneurysm formation (97%), but performing a clinical visit and an MRI on every patient without any prior screening test emerged as the most "cost-effective" strategy. CONCLUSIONS: The most "cost-effective" approach to diagnose complications at the site of repair in patients after surgical repair or balloon angioplasty of coarctation of the aorta appears to be the combination of clinical assessment and MRI scan on every patient. If MRI resources are scant, performing a clinical assessment plus a transthoracic echocardiography and an MRI on patients with positive results is an acceptable alternative.

Adolescent↗

Significant association between a silent polymorphism in the neuromedin B gene and body weight in German children and adolescents.

Neuromedin B has been shown to exert an inhibiting effect on food consumption in rats. The corresponding gene NMB maps to chromosome 15q22.3-q23, a region expected to contain a gene for the Bardet-Biedl syndrome type 4 (BBS4). Based on its map position and the putative function of the encoded peptide, NMB can be considered as a candidate gene both for BBS4 and the development of human obesity. To examine its involvement in these phenotypes, we determined the genomic structure of human NMB, and performed a mutation screen in its coding region. In genomic DNA of six BBS4 patients and in a large population sample, two sequence variants were detected: a g.253C-->A transversion creating a P73T substitution and a g.401G-->A silent mutation changing the stop codon TGA into stop codon TAA. A case-control study with 92 extremely obese patients and 94 underweight students revealed a significant association between the g.401G-->A polymorphism and body weight (adjustedp = 0.03), which was confirmed in a validation sample consisting of 95 extremely obese patients, and 95 normal weight and 48 underweight individuals (Mann-Whitney p = 0.02). These results suggest a contribution of NMB or a gene in its close vicinity to genetic weight control in humans.

Adolescent↗

A new technique for the selective recording of extensor carpi radialis longus and brevis EMG.

Tennis Elbow or Lateral Epicondylalgia is manifested by pain over the region of the lateral epicondyle of the humerus, related to use of the wrist extensor muscles. Extensor carpi radialis longus (ECRL) and brevis (ECRB) have been implicated in the dysfunction associated with Lateral Epicondylalgia. For muscles in the human forearm, particularly those in close proximity, selective recordings are nearly impossible without the use of fine wire, indwelling electrodes. These can be inserted in precise locations and have small recording areas. Standard electromyography texts indicate, however, that the activity of ECRL and ECRB cannot be distinguished, even with intramuscular electrodes. We present a new technique for determining the most appropriate sites at which to insert intramuscular electrodes for selective recordings of ECRB and ECRL. The location of ECRB and ECRL was measured on 10 cadaver specimens, 5 right arms and 5 left arms. The distance from the muscle origin to (1) insertion, (2) largest portion of the muscle belly, (3) most proximal fibres and (4) most distal fibres were measured and expressed relative to forearm length. The mean distance and 95% confidence interval was calculated for each of the four measures. These data indicated a significant separation of the belly of each muscle along the length of the forearm. These relative distances were used to mark electrode insertion points on three volunteers. Fine wire electrodes were used to record the electromyogram in three participants. Each participant was required to perform isometric contractions to produce (1) wrist extension torque, (2) radial deviation torque, (3) elbow flexion torque and (4) finger extension. The electromyographic recordings show clear differentiation of ECRB and ECRL with the relative activation patterns reflecting the underlying anatomical organisation of the two muscles. This technique provides an important objective method that can be used in conjunction with manual muscle testing to provide a means of ensuring accurate intramuscular electromyographic recording from these two muscles.

Cadaver↗

Genetic correction of sickle cell disease: insights using transgenic mouse models.

Sickle cell disease is a hereditary disorder characterized by erythrocyte deformity due to hemoglobin polymerization. We assessed in vivo the potential curative threshold of fetal hemoglobin in the SAD transgenic mouse model of sickle cell disease using mating with mice expressing the human fetal Agamma-globin gene. With increasing levels of HbF, AgammaSAD mice showed considerable improvement in all hematologic parameters, morphopathologic features and life span/survival. We established the direct therapeutic effect of fetal hemoglobin on sickle cell disease and demonstrated correction by increasing fetal hemoglobin to about 9-16% in this mouse model. This in vivo study emphasizes the potential of the SAD mouse models for quantitative analysis of gene therapy approaches.

Anemia, Sickle Cell↗