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Biomedical subjects

David Williams

Publications and source records attributed to David Williams.

At least 127 records · Page 7Linked to original sources

MR accuracy and arthroscopic incidence of meniscal radial tears.

OBJECTIVE: A meniscal radial tear is a vertical tear that involves the inner meniscal margin. The tear is most frequent in the middle third of the lateral meniscus and may extend outward in any direction. We report (1) the arthroscopic incidence of radial tears, (2) MR signs that aid in the detection of radial tears and (3) our prospective accuracy in detection of radial tears. DESIGN AND PATIENTS: Three musculoskeletal radiologists prospectively read 200 consecutive MR examinations of the knee that went on to arthroscopy by one orthopedic surgeon. MR images were assessed for location and MR characteristics of radial tears. MR criteria used for diagnosis of a radial tear were those outlined by Tuckman et al.: truncation, abnormal morphology and/or lack of continuity or absence of the meniscus on one or more MR images. An additional criterion used was abnormal increased signal in that area on fat-saturated proton density or T2-weighted coronal and sagittal images. Prospective MR readings were correlated with the arthroscopic findings. RESULTS: Of the 200 consecutive knee arthroscopies, 28 patients had radial tears reported arthroscopically (14% incidence). MR readings prospectively demonstrated 19 of the 28 radial tears (68% sensitivity) when the criteria for diagnosis of a radial tear were truncation or abnormal morphology of the meniscus. With the use of the additional criterion of increased signal in the area of abnormal morphology on fat-saturated T2-weighted or proton density weighted sequences, the prospective sensitivity was 25 of 28 radial tears (89% sensitivity). There were no radial tears described in MR reports that were not demonstrated on arthroscopy (i.e., there were no false positive MR readings of radial tears in these 200 patients). CONCLUSIONS: Radial tears are commonly seen at arthroscopy. There was a 14% incidence in this series of 200 patients who underwent arthroscopy. Prospective detection of radial tears was 68% as compared with arthroscopy when the criteria as outlined by Tuckman et al. were used alone. With the use of the additional criterion of increased signal in the area of abnormal morphology on fat-saturated T2-weighted and proton density weighted sequences, the prospective sensitivity for radial tear detection as compared with arthroscopy was 89% in our series. Fat-saturated proton density and T2-weighted images greatly improve the detection of radial tears as signal intensity changes in radial tears as well as morphologic changes can be utilized for the detection of subtle tears.

Adolescent↗

Pallidal activity recorded in patients with implanted electrodes predictively correlates with eventual performance in a timing task.

Here we seek to establish whether there are activities in the human pallidum that may predict a specific aspect of performance, timing. When recording from two patients with Parkinson's disease and primary generalised dystonia following functional neurosurgery we found that the amplitude of oscillatory pallidal activity occurring prior to the completion of a bimanual timing task was strongly correlated with eventual task duration. The frequency of this oscillatory activity was around 25 Hz. We conclude that the human pallidum may be involved in the prediction of movement timings and that such internal estimates may be reflected in amplitude modulation of oscillatory activity around 25 Hz.

Beta Rhythm↗

Non-traumatic vascular emergencies: imaging and intervention in acute arterial conditions.

Methods of imaging and intervention in acute non-traumatic vascular arterial conditions has changed substantially during recent years. Computed tomography, MRI angiography and, more recently, intravascular ultrasonography (IVUS) have replaced to a large extent conventional diagnostic angiography. An increasing number of patients are treated by endovascular interventions and numerous new treatment methods have been evaluated. Technical development of new equipment and instruments, increasing skill of interventional radiologists and better understanding of events following interventions improve continuously results of the treatment. Radiologic diagnosis and intervention have important roles in the treatment of acute non-traumatic vascular arterial conditions.

Aortic Diseases↗

Status and opportunities for genomics research with rainbow trout.

The rainbow trout (Oncorhynchus mykiss) is one of the most widely studied of model fish species. Extensive basic biological information has been collected for this species, which because of their large size relative to other model fish species are particularly suitable for studies requiring ample quantities of specific cells and tissue types. Rainbow trout have been widely utilized for research in carcinogenesis, toxicology, comparative immunology, disease ecology, physiology and nutrition. They are distinctive in having evolved from a relatively recent tetraploid event, resulting in a high incidence of duplicated genes. Natural populations are available and have been well characterized for chromosomal, protein, molecular and quantitative genetic variation. Their ease of culture, and experimental and aquacultural significance has led to the development of clonal lines and the widespread application of transgenic technology to this species. Numerous microsatellites have been isolated and two relatively detailed genetic maps have been developed. Extensive sequencing of expressed sequence tags has begun and four BAC libraries have been developed. The development and analysis of additional genomic sequence data will provide distinctive opportunities to address problems in areas such as evolution of the immune system and duplicate genes.

Animals↗

Activation of AP-1 and SP1 correlates with wound growth factor gene expression in glucan-treated human fibroblasts.

Glucan is a natural product immunomodulator that has been reported to enhance early wound repair. The mechanism of glucan-stimulated wound repair was thought to be indirect via macrophage release of wound growth factors. However, recent data indicate that there are glucan-specific receptors on human fibroblasts that can modulate cellular function following interaction with the glucan ligand. In this study we examined the effect of glucan on activation of the transcription factors activator protein-1 (AP-1) and specificity protein-1 (Sp1) in normal human dermal fibroblasts. AP-1 and Sp1 are involved in the regulation of cytokine and procollagen genes. In addition, we evaluated the effect of glucan on wound growth factor and vascular endothelial growth factor (VEGF) mRNA expression in primary cultures of normal human dermal fibroblasts. Glucan (1 microg/ml) stimulated fibroblast AP-1 and Sp1 activation in a time-dependent manner, although the temporal kinetics varied between the two transcription factors. AP-1 binding activity was increased (p<0.05) at early time intervals (1, 2, 4, 8 and 12 h), while Sp1 nuclear binding activity was increased (p<0.05) at later time intervals (12, 24, 36 and 48 h). Glucan (1 microg/ml) stimulated fibroblast expression of neurotrophin 3 (NT-3), platelet derived growth factor A (PDGF-A), platelet derived growth factor B (PDGF-B), fibroblast growth factor acidic (aFGF), fibroblast growth factor basic (bFGF), transforming growth factor alpha (TGFalpha), transforming growth factor beta (TGFbeta) and VEGF mRNA at 8 h.

Endothelial Growth Factors↗

Dopamine-dependent changes in the functional connectivity between basal ganglia and cerebral cortex in humans.

We test the hypothesis that interaction between the human basal ganglia and cerebral cortex involves activity in multiple functional circuits characterized by their frequency of oscillation, phase characteristics, dopamine dependency and topography. To this end we took recordings from macroelectrodes (MEs) inserted into the subthalamic nucleus (STN) in eight awake patients following functional neurosurgery for Parkinson's disease. An EEG was also recorded, as were the signals from MEs in the globus pallidus interna (GPi) in two of the cases. Coherence between EEG and ME potentials was apparent in three major frequency bands, 2-10 Hz, 10-30 Hz and 70-85 Hz. These rhythmic activities differed in their cortical topography, although coherence was always strongest over the midline. Coherence between EEG and ME potentials in the 70-85 Hz band was only recorded in patients treated with levodopa. Cortical activity phase led that in the basal ganglia in those oscillatory activities with frequencies <30 Hz. In contrast, STN and GPi phase led cortex in the 70-85 Hz band. The temporal differences in the way in which cortical activity led or lagged behind that in STN/GPi were similar, around 20 ms, regardless of the overall direction of information flow and frequency band. We conclude that the basal ganglia may receive multiple cortical inputs at frequencies <30 Hz and, in the presence of dopaminergic activity, produce a high frequency drive back to the cerebral cortex, in particular the supplementary motor area (SMA).

Adult↗

Organization and administration of the NIDCD/VA Hearing Aid Clinical Trial.

This article describes the organization and administration of the NIDCD/VA Hearing Aid Clinical Trial. The trial involved a total of 360 patients with bilateral, sensorineural hearing loss from eight VA Medical Centers to study three different hearing aid circuits in a three-period, three-treatment crossover design. Strong central coordination of such a complex multi-center clinical trial is essential to its success. The trial took more than 5 years to design, implement, and complete. This timeline is also described.

Clinical Trials as Topic↗

Speech recognition performance of patients with sensorineural hearing loss under unaided and aided conditions using linear and compression hearing AIDS.

OBJECTIVES: This study compared speech recognition performance on the Northwestern University Auditory Test No. 6 (NU-6) and the Connected Speech Test (CST) for three hearing aid circuits (peak clipping [PC], compression limiting [CL], and wide dynamic range compression [WDRC]) in adults with symmetrical sensorineural hearing loss. The study also questioned whether or not hearing aid benefit for the three circuits was dependent upon the speech level and the signal-to-babble ratio (S/B) and upon the degree and slope of hearing loss. DESIGN: Unaided speech recognition performance for NU-6 and CST materials presented from a loudspeaker at 0 degrees was measured during Visit 1, and both unaided and aided performance was measured at 3-mo intervals during Visits 2 to 4. The NU-6 was presented in quiet at a conversational speech level of 62 dB SPL. The CST was presented in 10 listening conditions-three S/B (-3, 0, and 3 dB) at each of three speech levels (soft speech at 52 dB SPL, conversational speech at 62 dB SPL, and loud speech at 74 dB SPL) and in quiet at 74 dB SPL. Uncorrelated multi-talker babble was presented from two loudspeakers at 45 degrees on each side of the main speaker. Hearing aid benefit was examined for 360 subjects divided into four groups of hearing loss, pure tone average <40 dB HL and slope <10 dB/octave or >10 dB/octave and hearing loss >40 dB HL for the two slope categories. RESULTS: Hearing aid benefit (aided minus unaided performance) measured on the NU-6 in quiet exceeded 31 rau for all three circuits. Although small statistical advantages were found for the WDRC, the differences were approximately 2% and are not considered clinically relevant. Unaided CST performance showed a complex relationship between presentation level and signal-to-babble ratio that was further confounded by the degree of hearing loss. For the two mild hearing loss groups and for each of the three nominal signal-to-babble ratios, CST performance decreased by 20 rau for the -3 dB S/B to 6 rau for the 3 dB S/B as speech level increased from 52 to 74 dB SPL. In contrast, unaided performance increased by 32 to 13 rau with signal level for all signal-to-babble ratios for the two >40 dB hearing loss groups. Overall, aided CST performance exceeded unaided performance for all 10 conditions. As expected, hearing aid benefit was greatest (27 rau) for soft speech and smallest for loud speech (6 rau). Differences among the hearing aid circuits were small with only one significant difference; the WDRC at 62/0 was poorer by 3 rau than the other two circuits. When the CST data were analyzed as a function of hearing loss, five pair-wise comparisons were significant. In contrast to the unaided performance, aided performance for all hearing loss groups decreased as presentation level increased, even though the signal-to-babble ratio was constant. CONCLUSIONS: All three hearing aids circuits provided benefit over the unaided condition in both quiet and noise. The greatest benefit was measured for soft speech in the more severe hearing loss groups. Although only small differences were measured among the three hearing aid circuits, significant differences favored the PC and CL circuits over the WDRC in the mild hearing loss groups and favored the WDRC over the PC in the more severe, sloping hearing loss group. An interesting interaction between speech level, signal-to-babble ratio, degree of hearing loss, and amplification was found. For a constant signal-to-babble ratio, recognition performance decreased as speech level increased from 52 to 74 dB SPL. The effect was most marked in the milder hearing loss groups and in the aided conditions, and occurred at even the lowest speech levels.

Adult↗

Correlates of self-perceptions of spirituality in American adults.

To advance knowledge in the study of spirituality and physical health, we examined sociodemographic, behavioral, and attitudinal correlates of self-perceptions of spirituality. Participants were a nationally representative sample of 1,422 adult respondents to the 1998 General Social Survey. They were asked, among other things, to rate themselves on the depth of their spirituality and the depth of their religiousness. Results indicated that, after adjustment for religiousness, self-perceptions of spirituality were positively correlated with being female (r = .07, p < .01), having a higher education (r = .12, p < .001), and having no religion (r = .10, p < .001) and inversely correlated with age (r = -.06, p < .05) and being Catholic (r = -.08, p < .01). After adjustment for these sociodemographic factors, self-perceptions of spirituality were associated with high levels of religious or spiritual activities (range in correlations = .12-.38, all p < .001), low cynical mistrust, and low political conservatism (both r = -.08, p < .01). The population was divided into 4 groups based on their self-perceptions of degree of spirituality and degree of religiousness. The spiritual and religious group had a higherfrequency of attending services, praying, meditating, reading the Bible, and daily spiritual experience than any of the other 3 groups (all differences p < .05) and had less distress and less mistrust than the religious-only group (p < .05 for both). However, they were also more intolerant than either of the nonreligious groups (p < .05 for both) and similar on intolerance to the religious-only group. We conclude that sociodemographicfactors could confound any observed association between spirituality and health and should be controlled. Moreover, individuals who perceive themselves to be both spiritual and religious may be at particularly low risk for morbidity and mortality based on their good psychological status and ongoing restorative activities.

Adult↗

Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors.

The HMG-CoA reductase inhibitors (statins) are effective in both the primary and secondary prevention of ischaemic heart disease. As a group, these drugs are well tolerated apart from two uncommon but potentially serious adverse effects: elevation of liver enzymes and skeletal muscle abnormalities, which range from benign myalgias to life-threatening rhabdomyolysis. Adverse effects with statins are frequently associated with drug interactions because of their long-term use in older patients who are likely to be exposed to polypharmacy. The recent withdrawal of cerivastatin as a result of deaths from rhabdomyolysis illustrates the clinical importance of such interactions. Drug interactions involving the statins may have either a pharmacodynamic or pharmacokinetic basis, or both. As these drugs are highly extracted by the liver, displacement interactions are of limited importance. The cytochrome P450 (CYP) enzyme system plays an important part in the metabolism of the statins, leading to clinically relevant interactions with other agents, particularly cyclosporin, erythromycin, itraconazole, ketoconazole and HIV protease inhibitors, that are also metabolised by this enzyme system. An additional complicating feature is that individual statins are metabolised to differing degrees, in some cases producing active metabolites. The CYP3A family metabolises lovastatin, simvastatin, atorvastatin and cerivastatin, whereas CYP2C9 metabolises fluvastatin. Cerivastatin is also metabolised by CYP2C8. Pravastatin is not significantly metabolised by the CYP system. In addition, the statins are substrates for P-glycoprotein, a drug transporter present in the small intestine that may influence their oral bioavailability. In clinical practice, the risk of a serious interaction causing myopathy is enhanced when statin metabolism is markedly inhibited. Thus, rhabdomyolysis has occurred following the coadministration of cyclosporin, a potent CYP3A4 and P-glycoprotein inhibitor, and lovastatin. Itraconazole has been shown to increase exposure to simvastatin and its active metabolite by at least 10-fold. Pharmacodynamically, there is an increased risk of myopathy when statins are coprescribed with fibrates or nicotinic acid. This occurs relatively infrequently, but is particularly associated with the combination of cerivastatin and gemfibrozil. Statins may also alter the concentrations of other drugs, such as warfarin or digoxin, leading to alterations in effect or a requirement for clinical monitoring. Knowledge of the pharmacokinetic properties of the statins should allow the avoidance of the majority of drug interactions. If concurrent therapy with known inhibitors of statin metabolism is necessary, the patient should be monitored for signs and symptoms of myopathy or rhabdomyolysis and the statin should be discontinued if necessary.

Animals↗

Catheters, materials and infection.

The possible influence of catheter material on infection rates, particularly in relation to the use of central venous catheters, has been a controversial matter for many years. Some of the factors that control the occurrence of infection are considered in this article.

Anti-Bacterial Agents↗

Medical nanotechnology: how small can we go?

Medical devices are becoming more sophisticated and, in common with instrumentation in many other disciplines, are becoming more compact. This article addresses the question of how small these devices need to be for them to have a significant impact on our ability to provide functioning interfaces with tissues. The significance of recent developments in materials and materials fabrication is also highlighted.

Biotechnology↗

To test or not to test: the value of biological safety testing.

Each year, thousands of tests are conducted on biomaterials to check whether they are biologically safe and suitable for use in medical devices. This article addresses the question of whether or not these tests are necessary, or in fact, useful.

Biocompatible Materials↗

New metals for old: benefits and concerns.

Several new medical devices are incorporating new metallic materials into their structures. This article describes some generic issues that influence the benefit-risk characteristics of these materials.

Biocompatible Materials↗

Even more opinions on PVC and broader lessons.

A Scientific Committee of the European Commission has addressed possible toxicity concerns of plasticised poly(vinylchloride) in certain medical devices and has reached conclusions that are different from those adopted by some other organisations. This article discusses the basis for these opinions.

Diethylhexyl Phthalate↗