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Biomedical subjects

David Williams

Publications and source records attributed to David Williams.

At least 73 records · Page 4Linked to original sources
PubMed2004

HIV prevalence in pregnant women in an ethnically diverse population in the UK: 1998-2002.

OBJECTIVE: To describe trends in the prevalence of HIV in an ethnically diverse population of pregnant women in the United Kingdom. METHODS: Data on parental country of birth from national birth registration records were linked to neonatal dried blood spot samples routinely collected for neonatal screening in the North Thames region between 1998 and 2002. Identifiers were subsequently irreversibly deleted prior to establishing maternal HIV status by testing the neonatal samples. RESULTS: A total of 491 213 dried blood spot samples were collected, and 490 879 (99.93%) were tested for HIV. Of these, 1029 were seropositive. There was an overall significant increasing trend (P-value = 0.001) between 1998 and 2002. Maternal region of birth was available for 89.8% of HIV-infected samples, and, among these, 80.5% of mothers were born in sub-Saharan Africa and 11.1% in the UK. The highest prevalences of HIV were in women born in sub-Saharan Africa (2.09%). If both parents were born in the UK, overall seroprevalence was 0.016%. CONCLUSION: HIV infection in pregnant women in the UK continues to occur predominantly in women born in sub-Saharan Africa with prevalence in this group increasing significantly. Although the absolute number of HIV-infected women rose in some other groups, there was no evidence for a statistically significant rise in HIV prevalence in women born outside sub-Saharan Africa. Over 93% of children at risk of vertical transmission of HIV had at least one parent born abroad. This paper underlines the value of data linkage in monitoring HIV prevalence in a diverse population.

Adult↗
PubMed2004

Event-related beta desynchronization in human subthalamic nucleus correlates with motor performance.

Although the basal ganglia play an important role in self-generated movement, their involvement in externally paced voluntary movement is less clear. We recorded local field potentials (LFPs) from the region of the subthalamic nuclei of eight patients with Parkinson's disease during the performance of a warned reaction time task in which an imperative cue instructed the subject to move or not to move. In 'go' trials, LFP activity in the beta frequency band ( approximately 20 Hz) decreased prior to movement, with an onset latency that strongly correlated with mean reaction time across patients. This was followed by a late post-movement increase in beta power. In contrast, in 'nogo' trials the beta power drop following imperative signals was prematurely terminated compared with go trials and reversed into an early beta power increase. These differences were manifest as power increases when go trials were subtracted from nogo trials. In six patients these relative beta power increases in nogo-go difference trials were of shorter latency than the respective reaction time. The findings suggest that, firstly, the subthalamic nucleus is involved in the preparation of externally paced voluntary movements in humans and, secondly, the degree of synchronization of subthalamic nucleus activity in the beta band may be an important determinant of whether motor programming and movement initiation is favoured or suppressed.

Aged↗
PubMed2004

ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis.

The angiotensin-converting enzyme (ACE)-related carboxypeptidase, ACE2, is a type I integral membrane protein of 805 amino acids that contains one HEXXH + E zinc-binding consensus sequence. ACE2 has been implicated in the regulation of heart function and also as a functional receptor for the coronavirus that causes the severe acute respiratory syndrome (SARS). To gain further insights into this enzyme, the first crystal structures of the native and inhibitor-bound forms of the ACE2 extracellular domains were solved to 2.2- and 3.0-A resolution, respectively. Comparison of these structures revealed a large inhibitor-dependent hinge-bending movement of one catalytic subdomain relative to the other ( approximately 16 degrees ) that brings important residues into position for catalysis. The potent inhibitor MLN-4760 ((S,S)-2-[1-carboxy-2-[3-(3,5-dichlorobenzyl)-3H-imidazol4-yl]-ethylamino]-4-methylpentanoic acid) makes key binding interactions within the active site and offers insights regarding the action of residues involved in catalysis and substrate specificity. A few active site residue substitutions in ACE2 relative to ACE appear to eliminate the S(2)' substrate-binding subsite and account for the observed reactivity change from the peptidyl dipeptidase activity of ACE to the carboxypeptidase activity of ACE2.

Amino Acid Sequence↗
PubMed2004

Effects of dexamethasone or celecoxib on biliary toxicity after hepatic arterial infusion of 5-fluorodeoxyuridine in a canine model.

Previous work has shown that in humans the dose-limiting toxicity for fluorodeoxyuridine [2-fluoro-5'-deoxyuridine (FdUrd)] when administered by hepatic arterial infusion is biliary sclerosis. The current study was undertaken to attempt to modify this toxicity in a canine model that has been demonstrated to closely mimic the clinical situation. Unlike previous studies using this model, in which animals were sacrificed after extensive fibrosis had already occurred, the current experiments were designed so that observations of pathology were made at an earlier time, when the initial inflammatory injury underlying the fibrotic process was still taking place. Implantable pumps were used to deliver FdUrd into the hepatic artery of animals at a rate of 0.3 mg/kg/day in the presence or absence of 10 mg/week dexamethasone or 100 mg/day of celecoxib for 35 days, at which time the animals were beginning to show signs of toxicity. After evaluation for radiological evidence of biliary obstruction, the animals were sacrificed and portions of their livers were processed for examination of microscopic pathology and 2-bromo-5'deoxyuridine labeling index. Dexamethasone treatment protected the animals from biliary sclerosis determined radiologically, further validating this model as being representative of the response in humans. Similarly the Cox-2 inhibitor, celecoxib, appeared to provide protection against radiological changes of biliary stricture, although possibly to a lesser degree than the resultant from dexamethasone. In addition, FdUrd treatment caused elevation of the DNA 2-bromo-5'deoxyuridine labeling index above control levels in biliary epithelial cells. Dexamethasone and celecoxib each significantly attenuated the FdUrd-induced elevation of DNA labeling index in biliary epithelium. These findings demonstrate the usefulness of this canine model for studying the mechanisms of drug-induced biliary sclerosis and reinforce the hypothesis that blocking inflammation may retard the progression of injury that eventually leads to fibrosis. This study suggests that clinical testing of celecoxib as a preventive for hepatic arterial-FdUrd induced biliary damage could prove valuable.

Alkaline Phosphatase↗
PubMed2004

Long-term outcomes of submandibular gland transfer for prevention of postradiation xerostomia.

BACKGROUND: Xerostomia is a permanent and devastating sequela of head and neck irradiation, and its numerous consequences affect most aspects of the patient's life. A new method of preserving and protecting a single submandibular gland from radiation damage through the Seikaly-Jha procedure (SJP) has recently been described. OBJECTIVE: To report the long-term outcomes of the SJP. DESIGN: Inception cohort. Patients The trial was conducted between February 1, 1999, and February 1, 2002. All patients were followed up through the head and neck cancer clinic at the Cross Cancer Institute. All data were collected by a dedicated research nurse. Salivary function was evaluated at regular intervals with salivary flow studies and questionnaires. RESULTS: Ninety-six patients were enrolled in the study, and 38 had a minimum of 2 years' follow-up. The cohort of 38 patients was composed of 2 groups: 26 patients had preservation of one submandibular gland through the SJP, while the remaining 12 did not. Salivary flow was preserved in the SJP group, in which 83% of patients reported normal amounts of saliva 2 years after radiotherapy, compared with none in the SJP group. There were no disease recurrences on the side of the transferred gland or in the submental space. There were no surgical complications attributed to the transfer procedure. CONCLUSIONS: The SJP prevented xerostomia in 83% of the study patients. The approach appears to be oncologically sound and safe.

Alberta↗
PubMed2004

Metapleural- and postpharyngeal-gland secretions from workers of the ants Solenopsis invicta and S. geminata.

Chemical analyses by GC-MS of the metapleural glands (MG) from workers of Solenopsis invicta and S. geminata revealed for the first time the chemical composition of these glands and showed small differences between the two species. The MG of both species contain oleic, stearic, linoleic, and palmitic acid. Both ants, in addition, have small but significant amounts of hydrocarbons in their MG reservoir, which are the same as those found in their postpharyngeal glands (PPG). The PPG of both species contain alkanes, alkenes, and Me-branched alkanes. Each species is characterized by a specific composition of PPG chemicals with some overlap between species. These results suggest that the MG synthesizes mainly palmitic, linoleic, oleic, and stearic acids in these two ants, whereas PPG contains hydrocarbon mixes that widely vary between these two phylogenetically related species.

Animals↗
PubMed2004

Ethics of research on survivors of trauma.

Essential elements of all research include balance of risks and benefits, unbiased selection of research samples, and assurance of the rights of individual participants. This paper highlights some key ethical issues and summarizes recent evidence relating to participation in, and conduct of, trauma-focused studies with special reference to vulnerable populations (eg, women and children, refugees, survivors of human rights violations, and survivors of trauma in the developing world). A concise ethical framework, rather than rigid guidelines (that may not be applicable to all trauma studies), may be a more useful point of reference for investigators and ethics committees or institutional review boards. Despite the increased empiric data available to inform ethical dilemmas regarding trauma research, more cost-burden analysis research in varying trauma populations and careful investigation of factors that contribute to risk and benefit is required.

Adult↗
PubMed2004

Physical demands and injuries to the upper extremity associated with the space program.

Hand and upper-extremity overuse and repetitive injuries in astronauts have been and continue to be a common problem in the space program. The demands on upper-extremity use in the astronaut training program, the zero-gravity environment, the extreme temperature conditions of space, the effects of space travel on human physiology/anatomy, and the constraints and pressures of space suits and gloves all can negatively impact upper-extremity function in ways that can result in overuse/repetitive injuries. Future plans for space exploration include endeavors that will continue and even increase the demands on the hand and upper extremity.

Astronauts↗
PubMed2004

Pelvic fracture patterns and their corresponding angiographic sources of hemorrhage.

The association between pelvic arterial injuries and associated fracture patterns has been investigated directly in a post mortem study and indirectly in an earlier clinical study evaluating an overall management approach to pelvic fractures. One previous report has correlated the angiographic findings of a group of patients with pelvic ring disruptions. The authors' study was designed to further define the anatomic sites of hemorrhage associated with specific pelvic ring injury patterns and evaluate patient survival in each of these groups.

Aged↗
PubMed2004

Monochromatic ocular wavefront aberrations in the awake-behaving cat.

Measurement of wavefront aberrations in human eyes has become a reliable, quantitative way of assessing the optical impact of experimental and corrective ocular manipulations. Wavefront measures have also been performed in several other species, but never in cats, an animal model of choice for many ocular studies. Our goal in this study was to measure wavefront aberrations reliably in live, awake-behaving cats in a manner that is directly comparable to that used in human subjects. Six adult cats (felis cattus) were trained to fixate small targets on a computer screen. A compact Shack-Hartmann wavefront sensor was aligned with each animal's pupil center and line of sight during fixation. Wavefront images were then collected from which the cats' ocular aberrations were measured up to tenth order Zernike polynomials over a 6 mm pupil. Results show that cat and human ocular wave aberrations were very similar. Second order Zernike modes accounted for more than 90% of the total wave aberration. In agreement with our observation that cat ocular optics were comparable with those of humans, the half height width of both the cat and human higher order point spread function was about 0.95 degrees. These results form a solid basis for future wavefront sensing studies aiming to quantify the effects of ocular manipulations in experimental animals.

Animals↗
PubMed2004

Prescribing for osteoporosis following the use of inhaled and oral glucocorticoids in general practice.

AIMS: Systemic absorption from inhaled glucocorticoids may lead to bone loss. We determined the extent to which their use alone and in addition to short courses of oral glucocorticoids was associated with increased prescribing for osteoporosis in a large general practice population. METHODS: In a cohort study with follow-up of co-prescribing of antiosteoporotic drug therapy in the Irish national prescribing database (1.1 million people over 16 years), we identified 32 081 patients who received inhaled glucocorticoids alone during a 12-month period (following an identical lead-in period). We determined the odds ratio (OR), adjusting for age and gender for the co-prescription of bisphosphonates or other antiosteoporotic therapy with inhaled glucocorticoids by logistic regression. RESULTS: The adjusted OR (95% confidence interval) for co-prescribing of bisphosphonates and all inhaled glucocorticoids was 1.87 (1.71, 2.04); 1.58 (1.41, 1.78) for inhaled beclomethasone, 2.11 (1.75, 2.54) for inhaled budesonide and 3.29 (2.65, 4.1) for inhaled fluticasone. The ORs were significantly increased when patients who also received oral glucocorticoids were included and greater still in those under 45 years: 14.03 (10.6, 18.6). The results remained significant when the effects of comorbidity were adjusted for. The odds of receiving bisphosphonate therapy increased linearly with increasing exposure to inhaled glucocorticoids during the study period. CONCLUSIONS: Treatment with inhaled glucocorticoids in general practice is associated with an increased risk of co-prescribing for antiosteoporotic therapy in a potency- and a dose-related manner. Exposure to a course of oral glucocorticoids doubles this risk. These results suggest that the systemic effects on bone mineral density from using inhaled glucocorticoids may be clinically relevant but may also reflect prescribers' concerns for the development of osteoporosis in these patients.

Administration, Inhalation↗
PubMed2004

Psychosocial factors in medical and psychological treatment avoidance: the role of the doctor-patient relationship.

A community sample of 1106 adults was examined to assess the impact of the doctor-patient relationship on participants' avoidance of treatment for a recognized medical or psychological problem. Of five aspects of participants' previous experience with their physicians, all but waiting time predicted participants' self-reported treatment avoidance. In two logistic regression models participants who felt their physicians listened more to their concerns were less likely to avoid treatment for both medical and psychological problems during the previous 12 months. These findings suggest that patients' perceptions of how they are treated by physicians may help explain why many people delay or avoid healthcare treatment, even when faced with a significant health problem.

Adolescent↗
PubMed2004

Prevalence of meniscal radial tears of the knee revealed by MRI after surgery.

OBJECTIVE: Meniscal resection decreases the ability of the meniscus to evenly distribute forces placed on it. These forces are oriented centrifugally on the meniscus by normal weight-bearing and are distributed by circumferentially oriented fibers. This alteration may predispose the knee to radial tears after surgery. SUBJECTS AND METHODS: One of three musculoskeletal radiologists prospectively interpreted 100 consecutive postoperative MRI examinations of the knee. A prospective MRI report was generated for the referring orthopedic surgeon, and prospective MRI interpretations were correlated with arthroscopic findings (n = 63). MRI examinations on those patients who underwent second-look arthroscopy were retrospectively reviewed by three musculoskeletal radiologists who reached a consensus on the prevalence of new postoperative meniscal radial tears. MRI criteria for radial tear diagnosis were used as outlined by Tuckman et al.: truncation, abnormal morphology, lack of continuity, absence of the meniscus, or any combination of those criteria on one or more MR images. An additional criterion used was abnormal increased signal in that area on T2-weighted images. RESULTS: Thirty-two of the 100 patients had meniscal radial tears on prospective MRI interpretations. In 29 of these 32 patients, second-look arthroscopy confirmed meniscal radial tears in the areas described on the MRI examinations. Five additional radial tears were shown on second-look arthroscopy that were not seen on prospective MRI interpretations. Two of those additional five radial tears were seen on consensus retrospective MRI review. CONCLUSION: In this study, a 32% prevalence of meniscal radial tears in the postoperative knee was present on prospective MRI interpretations as opposed to a reported 14% prevalence in the nonoperated knee. Meniscal resection decreases the ability of the meniscus to evenly distribute forces placed on it. This circumstance may increase the prevalence of meniscal radial tears in the postoperative knee. New meniscal radial tears are common in patients presenting with pain after knee surgery.

Adolescent↗
PubMed2004

Usefulness of simultaneous acquisition of spatial harmonics technique for MRI of the knee.

OBJECTIVE: Simultaneous acquisition of spatial harmonics (SMASH) is a parallel-imaging technique that uses fewer echoes than conventional techniques to obtain the desired resolution. Images are produced in a shorter time period using the SMASH technique than conventional techniques. This study assesses the usefulness of the SMASH technique in the MRI evaluation of the knee. SUBJECTS AND METHODS. Three experienced musculoskeletal radiologists prospectively interpreted MR images of the knee in 50 consecutive patients. All patients underwent a complete MRI examination of the knee on a 1.5-T MRI scanner. Sagittal proton density fat-saturated and coronal T1-weighted images were obtained. In addition, fat-saturated T2-weighted images were obtained in the coronal, sagittal, and axial planes. SMASH T2-weighted imaging in the coronal, axial and sagittal planes took 6 min 38 sec, whereas fast spin-echo conventional T2-weighted imaging took 11 min 45 sec to obtain images in the same planes. Each radiologist interpreted the knee MR examinations prospectively and was unaware whether the images had been obtained using the SMASH T2-weighted or fat-saturated T2-weighted technique. The radiologists provided a report. The three radiologists independently performed a retrospective review of both the fat-saturated T2-weighted and SMASH T2-weighted images. The radiologists were blinded as to which sequence was fat-saturated T2-weighted and which was SMASH T2-weighted. They were asked to reinterpret the images and determine whether either of the T2-weighted sequences altered the original interpretation. RESULTS: There was no intraobserver variability in MRI interpretations with the use of SMASH imaging as compared with fat-saturated T2-weighted images. Thirty-four patients underwent arthroscopy after imaging. Findings at arthroscopy in those patients were as follows: 28 meniscal tears, 12 anterior cruciate ligament tears, and nine chondral defects. In some patients, multiple abnormalities were detected on MRI. All arthroscopy findings correlated with prospective MRI interpretations. CONCLUSION: The use of SMASH T2-weighted imaging as opposed to fat-saturated T2-weighted imaging results in a significant decrease in imaging time (> 5-min decrease for each knee examination) without affecting the MRI interpretation or patient clinical outcome.

Adult↗
PubMed2004

Shoulder MR arthrography: which patient group benefits most?

OBJECTIVE: We sought to compare the diagnostic accuracy of conventional MRI versus MR arthrography of the shoulder in the assessment of high-performance athletes (professional baseball players) and to compare our findings in these patients with the conventional MRI and MR arthrographic findings in an age-matched control group of nonprofessional athletes. MATERIALS AND METHODS: Conventional MRI and MR arthrographic examinations of the shoulder in 20 consecutive professional baseball players with shoulder pain were reviewed retrospectively by two musculoskeletal radiologists in consensus. These interpretations were compared with retrospective consensus interpretations of conventional MRI and MR arthrographic examinations of the shoulder obtained in a control group of 50 consecutive nonprofessional athletes with shoulder pain. MR images were assessed for full- or partial-thickness supraspinatus tendon tears, superior labral anteroposterior (SLAP) tears, and anterior or posterior labral tears. RESULTS: In the 20 consecutive professional athlete patients, two full-thickness and six partial-thickness undersurface supraspinatus tendon tears were seen on MR arthrography but not seen on conventional MRI as well as six SLAP tears, two anterior labral tears, and one posterior labral tear. Three patients had both SLAP tears and full- or partial-thickness supraspinatus tendon tears. Of 14 patients with findings on MR arthrography that were not seen on MRI, 11 had arthroscopic correlation. In all 11, arthroscopic findings confirmed findings on MR arthrography. In the group of 50 nonprofessional athlete patients, five had additional findings on MR arthrography not seen on conventional MRI: two anterior labral tears, two partial-thickness supraspinatus tendon tears, and two SLAP tears. One patient had both a partial-thickness supraspinatus tendon tear and a SLAP tear seen on MR arthrography. The five patients with additional findings on MR arthrography had arthroscopy. In all five, arthroscopic findings confirmed the findings on MR arthrography. CONCLUSION: MR arthrography is considerably more sensitive for detection of partial-thickness supraspinatus tears and labral tears than conventional MRI. MR arthrography showed injuries in addition to those seen on conventional MRI in 14 of 20 patients in the high-performance athlete group. These results suggest high-performance athletes may be a subgroup of patients for whom MR arthrography yields considerably more diagnostic information than conventional MRI.

Adolescent↗
PubMed2004

Detection of meniscal tears and marrow lesions using coronal MRI.

OBJECTIVE: The usefulness of coronal images in addition to sagittal images for detection of additional meniscal injuries or bone lesions has been questioned. Some authors believe meniscal tears are rarely seen only in the coronal plane. We performed a retrospective review of coronal and sagittal MR images of the knee to determine whether coronal imaging resulted in the detection of any additional meniscal tears or bone lesions when compared with sagittal MRI of the knee alone. MATERIALS AND METHODS: Two musculoskeletal radiologists retrospectively reviewed 200 consecutive sets of MR images of the knee by consensus. Both observers recorded their retrospective findings on sagittal proton density images, sagittal and coronal T2-weighted images, and coronal T1-weighted images. Findings recorded were those of meniscal tears, bone marrow abnormalities, and bone lesions. RESULTS: On these 200 consecutive sets of MR images of the knee, 114 meniscal tears were shown. Ninety-three meniscal tears were shown on sagittal proton density images only. One hundred fourteen meniscal tears were seen on sagittal proton density and coronal T1- and T2-weighted images. Use of coronal images resulted in the confident detection of 21 additional meniscal tears not well seen on sagittal proton density images alone. Twelve of the 21 additional meniscal tears were seen on coronal T1- and T2-weighted images. Nine of the 21 additional meniscal tears were seen only on coronal T1-weighted images. Most of these additional meniscal tears were in the body of the meniscus. These 21 additional meniscal tears were confirmed arthroscopically. Eight marrow lesions were well characterized only on coronal T1-weighted images. Five were osteochondral lesions, one was an intraosseous hemangioma, and two were microfractures. CONCLUSION: Coronal MR images of the knee allowed better detection and characterization of some meniscal tears than sagittal images alone. Radial meniscal tears, bucket-handle tears, and horizontal tears in the body of the meniscus may be difficult to characterize in the sagittal plane alone. Use of coronal T1-weighted images, rather than coronal T2-weighted or sagittal proton density images alone, allows accurate characterization of some additional marrow lesions. The addition of a T1-weighted sequence in the coronal plane adds only 1 min 30 sec to the scanning time.

Adolescent↗
PubMed2004

Taking the nickel out of the medicine.

Several important alloys used in medical technology contain nickel, an element that has significant metallurgical qualities but serious toxicological concerns. This article addresses the question of whether it makes sense to try to eliminate the nickel from these alloys.

Biocompatible Materials↗