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Biomedical subjects

David Williams

Publications and source records attributed to David Williams.

At least 109 records · Page 6Linked to original sources
PubMed2003

Pregnancy: a stress test for life.

PURPOSE OF REVIEW: This review describes how the physiological demands of pregnancy act as a maternal stress test that can predict a woman's health in later life. Pregnancy transiently catapults a woman into a metabolic syndrome that predisposes to vascular endothelial dysfunction. Women who are already predisposed to this phenotype develop gestational hypertension or diabetes mellitus, which re-emerge in later life as the metabolic syndrome returns. Pregnancy can also temporarily unmask sub-clinical disease, which may return in later life when the effects of ageing diminish the limited reserves of a vulnerable organ. RECENT FINDINGS: Recent studies have attempted to assess how gestational syndromes affect the risk for a woman of developing a diverse range of diseases in later life. As well as cardiovascular disease and diabetes mellitus, pregnancy can reveal a vulnerability to thyroid and pituitary disorders, liver and renal disease, depression, thrombosis and even cancer. SUMMARY: Although our knowledge of this phenomenon is incomplete, women who have had gestational syndromes, in particular pregnancy-induced hypertension/preeclampsia or gestational diabetes, should make lifestyle changes that will reduce their risk of cardiovascular disease in later life.

Age Factors↗
PubMed2003

The role of the Candida albicans histidine kinase [CHK1) gene in the regulation of cell wall mannan and glucan biosynthesis.

The human pathogen Candida albicans encodes at least three putative two-component histidine kinase signal transduction proteins, including Chk1p and a response regulator protein (Cssk1p). Strains deleted in CHK1 are avirulent in a murine model of hematogenously disseminated disease. The specific function of Chk1p has not been established, but hyphae of the chk1 mutant exhibit extensive flocculation while yeast forms are less adherent to reconstituted human esophageal tissue, indicating that this protein may regulate cell surface properties. Herein, we analyze glucan, mannan and chitin profiles in strains deleted in chk1 (CHK21) compared to a gene-reconstituted strain (CHK23) and a parental strain CAF2. Total alkali-soluble hexose from the cell wall of the chk1 mutant (strain CHK21) was significantly reduced. Western blots of cell wall extracts from CHK21, CHK23 and CAF2 reacted with a Mab to the acid-stable mannan fraction revealed extensive staining of lower molecular mass species in strain CHK21 only. FACE (fluorophore assisted carbohydrate electrophoresis) was used to characterize the oligosaccharide side chains of beta-eliminated (O-linked), acid-hydrolyzed (acid-labile phosphomannan) and acetolysis (acid-stable mannan) extracted fractions of total mannan. The profiles of O-linked as well as the acid-labile oligosaccharides were similar in both CAF2 and CHK21, but the acid-stable oligosaccharide side chains were significantly truncated. We also characterized the beta-glucan from each strain using NMR, and found that both the degree of polymerization and the ratio of (1-3)/(1-6) linkages was lower in CHK21 relative to wild-type cells. The sensitivity of CHK21 to antifungal drugs and inhibitors was unaffected. In summary, our data have identified a new function for a histidine kinase two-component signal protein in a human pathogenic fungus.

Candida albicans↗
PubMed2003

Efficient characterization of retro-, lenti-, and foamyvector-transduced cell populations by high-accuracy insertion site sequencing.

The identification of unknown genomic flanking DNA sequences can be used for the molecular monitoring of retro-, lenti- and foamyviral integration, transgenes in early embryogenesis, insertional mutagenesis, cell fate, and stem cell plasticity. Most existing methods reflect shortcomings in sensitivity and or specificity, thus limiting genomic sequencing of unknown flanking DNA to clonal preparations. The application of linear amplification-mediated PCR (LAM-PCR), a recently developed direct sequencing technique for flanking DNA, should circumvent current limitations in different research fields. This technique combines preamplification of target DNA with a unique succession of enzymatic reactions on solid-phase. Using LAM-PCR, we show the previously unfeasible in vivo retro-, lenti- and foamyvirus integration site analysis in primate peripheral blood hematopoietic cells and human xenograft hematopoiesis. In light of two severe adverse events that occurred in a clinical SCID-X1 gene therapy trial, in vivo monitoring of the reinfused transduced cell pool by integration site analysis will be an important component of each gene transfer and therapy study aimed at clinical use.

Animals↗
PubMed2003

Serum glucan levels are not specific for presence of fungal infections in intensive care unit patients.

Fungal infections in the critically ill patient are difficult to diagnose and are associated with a high mortality rate. A major obstacle to managing fungal infection is the lack of a reliable clinical assay that will rapidly identify patients with fungal sepsis. Glucans are polymers of glucose that are found in the cell wall of fungi and certain bacteria. Glucans are also released from the fungal cell wall into the extracellular milieu. Several studies have reported that detection of fungal glucan in serum or plasma is useful in the diagnosis of mycoses. However, recent studies have questioned the clinical utility of this assay. In this study, we examined serum glucan levels in intensive care unit (ICU) patients and attempt to correlate serum glucan levels with the presence of fungal infection. Following attainment of informed consent, serum was harvested from 46 ICU patients with confirmed fungal infections, confirmed bacterial infections, or no evidence of infection. Sera from eight healthy volunteers served as control. Serum glucan was assayed with a glucan-specific Limulus assay. Serum glucan levels were increased (69.6 +/- 17 pg/ml; P < 0.001) in ICU patients versus the normal (11.5 +/- 1.3 pg/ml) and noninfected ICU (27.4 +/- 17 pg/ml) controls. However, serum glucan levels were not different in patients with confirmed fungal infections versus those with confirmed bacterial infections. Thus, serum glucan levels did not show a correlation with the presence of fungal infections and do not appear to be specific for fungal infections. However, the assay may be useful as a negative predictor of infection.

Glucans↗
PubMed2003

The Aberfan disaster: 33-year follow-up of survivors.

BACKGROUND: Experiencing life-threatening events often contributes to the onset of such psychiatric conditions as post-traumatic stress disorder (PTSD). Children can develop PTSD; however, there is controversy over whether PTSD symptoms decrease or persist over time. AIMS: To examine the long-term effects of surviving the 1966 Aberfan disaster in childhood. METHOD: Survivors (n=41) were compared with controls (n=72) matched for age and background. All were interviewed using the Composite International Diagnostic Interview, measures of current health and social satisfaction, and the General Health Questionnaire. The survivor group also completed the Impact of Event Scale to assess current levels of PTSD. RESULTS: Nineteen (46%; 95% CI 31-61) survivors had had PTSD at some point since the disaster, compared with 12 (20%; 95% CI 10-30) controls (OR=3.38 (95% CI 1.40-8.47)). Of the survivors,12 (29%; 95% CI 15-43) met diagnostic criteria for current PTSD. Survivors were not at a significantly increased risk of anxiety, depression or substance misuse. CONCLUSIONS: Trauma in childhood can lead to PTSD, and PTSD symptoms can persist for as long as 33 years into adult life. Rates of other psychopathological disorders are not necessarily raised after life-threatening childhood trauma.

Adult↗
PubMed2003

Usefulness of the simultaneous acquisition of spatial harmonics technique during MRI of the shoulder.

OBJECTIVE: The simultaneous acquisition of spatial harmonics (SMASH) technique is a parallel imaging technique that uses fewer echoes than conventional techniques to obtain the desired resolution. Production of images occurs more quickly with parallel imaging than with conventional imaging. This study assesses the usefulness of the SMASH technique for MRI of the shoulder. SUBJECTS AND METHODS. Five experienced musculoskeletal radiologists prospectively interpreted MRIs of the shoulder in 50 consecutive patients. All patients underwent a complete MRI examination of the shoulder on a 1.5-T commercially available scanner. Axial fat-saturated proton density-weighted, coronal T1-weighted, and coronal and sagittal fat-saturated T2-weighted sequences were performed. Patients also underwent SMASH T2-weighted imaging in the coronal and sagittal planes. Coronal and sagittal SMASH T2-weighted imaging took approximately 50% as long to complete compared with conventional T2-weighted imaging. Each radiologist interpreted MRIs of the shoulder without knowing whether the images were obtained using the SMASH or the fat-saturated T2-weighted technique. Twenty-eight of the 50 patients also underwent subsequent arthroscopy, and the results were compared with MRI interpretations based on SMASH and fat-saturated T2-weighted images. RESULTS: We found no intraobserver variability between the interpretations of SMASH imaging and the interpretations of fat-saturated T2-weighted imaging. Of the 28 patients who also underwent subsequent arthroscopy, 19 were found to have full-thickness supraspinatus tendon tears and nine had superior labral anterior-to-posterior lesions. All arthroscopic findings correlated with prospective MRI interpretations. CONCLUSION: SMASH imaging allows significant time savings compared with fat-saturated T2-weighted MRI. We found that the use of the SMASH technique did not affect the MRI interpretation or the clinical outcome of patients.

Adult↗
PubMed2003

Comparison of high-field-strength versus low-field-strength MRI of the shoulder.

OBJECTIVE: Previous studies have reported similar results of shoulder MRI versus arthroscopy for high-field-strength (1.5-T) and low-field-strength (0.2-T) units. We report our experience with the accuracy of high- versus low-field-strength units versus arthroscopy for detection of supraspinatus tendon tears and labral tears in the same patients. SUBJECTS AND METHODS. Three musculoskeletal radiologists prospectively interpreted shoulder MRIs from 40 patients who had a complete shoulder MRI examination on a 0.2-T system and limited imaging on a 1.5-T unit. Proton-density axial and fat-saturated T2-weighted coronal and sagittal sequences were performed. Each radiologist interpreted the open unit images first and the high-field-strength images second. Results from 28 patients who also underwent arthroscopy were also compared with the MRI interpretations. All scans were then retrospectively reinterpreted by consensus of the three reviewers, who were unaware of the patient's name, results of previous MRI, or arthroscopy report (if any). RESULTS: High-field-strength images altered reviewers' interpretations of low-field-strength scans for nine of 40 patients. In four patients, full-thickness supraspinatus tendon tears could be diagnosed definitively on the high-field-strength unit but not on the open unit. Three labral tears and two superior labral anteroposterior lesions could be depicted definitively on the high-field-strength unit but not on the open unit. All tears were confirmed at arthroscopy. CONCLUSION: High-field-strength MRI units provide better spatial and contrast resolution and allow more accurate interpretations than low-field-strength units; these findings may affect clinical treatment.

Arthroscopy↗
PubMed2003

Complications of rotator cuff surgery in which bioabsorbable anchors are used.

OBJECTIVE: This study assessed the utility of MRI in patients with new or persistent pain after surgery with bioabsorbable rotator cuff anchors. SUBJECTS AND METHODS. Three musculoskeletal radiologists prospectively reviewed MRIs of 30 patients with pain after rotator cuff repair with fixation by rotator cuff anchors. Each radiologist described the location of the rotator cuff anchors and whether the supraspinatus tendon was intact or not. MRI findings were correlated with second-look arthroscopy. Consensus MRI interpretations by the three radiologists were obtained retrospectively. RESULTS: Of the 30 patients, nine had dislodgement of the rotator cuff anchors from the humeral head along with a full-thickness supraspinatus tendon retear. The dislodged rotator cuff anchor position could be determined on coronal and sagittal MRIs, providing the orthopedic surgeon a preoperative map for tendon reattachment and retrieval of the dislodged rotator cuff anchor. Four patients had loose rotator cuff anchors but intact supraspinatus tendons. Three patients had supraspinatus tendon retears, but the rotator cuff anchors were intact. In all 16 patients, arthroscopic findings confirmed MRI findings. Fourteen patients had intact rotator cuff anchors and intact supraspinatus tendons on MRI. Of these 14 patients, five had second-look arthroscopy confirming MRI findings. CONCLUSION: MRI is useful in the assessment of patients with persistent or new-onset pain after supraspinatus tendon repair with rotator cuff anchors. MRI provides a presurgical map for second-look arthroscopy to assess retear of the supraspinatus tendon and also aids in retrieval of dislodged rotator cuff anchors.

Absorbable Implants↗
PubMed2003

Endotoxins and medical devices: the significance of dead bacteria.

There has been some recent speculation that endotoxins, the toxic molecules that are present in the cell wall of certain bacteria, could play a role in the development of tissue reactions to medical devices. This article discusses the basis for this speculation.

Biocompatible Materials↗
PubMed2003

A dangerous place to live: from the fog of war to the slime of technology.

This article addresses the need for constant vigilance against clever and adaptive enemies, specifically the battle against infections. Medical devices are susceptible to infection and risk management needs to be considered in the context of the underlying science and common sense.

Bacterial Infections↗
PubMed2003

The Dunlop phenomena: a lesson in risk management from an unlikely source.

Modern production processes are designed to minimise chances of error and poor judgement, yet sometimes events occur that initially seem trivial, but ultimately prove fatal. In these circumstances, associations between cause and effect can become distorted and are often difficult to overcome.

Attitude of Health Personnel↗
PubMed2003

Good news and bad news: the cost of mending a broken heart.

The approval of a new treatment protocol known as "destination therapy" highlights the realities of today's health economics. This article discusses the technology, the economics and the philosophy of the newly approved left-ventricular-assist systems.

Cost-Benefit Analysis↗
PubMed2003

The engineering of an artery.

Tissue engineering is seen by some to be a high-risk area that has yet to deliver any clinical success. This article addresses one particular area of high risk, the tissue-engineered artery, and discusses some of technical and clinical factors that are involved.

Arteries↗
PubMed2003

Revisiting the definition of biocompatibility.

My main conclusion is that the original Williams' definition of biocompatibility still stands with respect to individual materials, but we have to move to more specific definitions within each of the varied applications of biomaterials such as those described above, and more will follow. It is time for the discussion and definition of biocompatibility to move from a materials base to an applications base.

Biocompatible Materials↗
PubMed2003

Year-end perspectives: the introduction of new technologies.

The regulatory process for medical devices works well for products that involve incremental change to conventional technologies. The situation is not so clear when radically new technologies are introduced into clinical practice. This article discusses some of the issues that are involved and proposes some new solutions.

Biomedical Technology↗
PubMed2002

Assessment of neurocognitive impairment after off-pump and on-pump techniques for coronary artery bypass graft surgery: prospective randomised controlled trial.

OBJECTIVE: To assess neurocognitive impairment after the off-pump and on-pump techniques for coronary artery bypass graft surgery in patients with triple vessel disease. DESIGN: Randomised controlled trial. SETTING: University Hospital of Wales, Cardiff. PARTICIPANTS: 60 patients undergoing coronary artery bypass graft surgery for triple vessel disease prospectively randomised to the off-pump or on-pump technique. MAIN OUTCOME MEASURES: Change in scores in nine standard neuropsychometric tests administered preoperatively and at 1 and 10 weeks postoperatively. RESULTS: The on-pump group showed a significantly greater deterioration in scores for two and three tests at 1 week and 10 weeks postoperatively, respectively, than the off-pump group. The on-pump group also showed a significantly higher incidence of major deterioration in one of the tests both 1 week and 10 weeks postoperatively. The incidence of neurocognitive impairment at 1 week postoperatively was 27% (8 out of 30) in the off-pump group and 63% (19 out of 30) in the on-pump group (P=0.004); and at 10 weeks postoperatively was 10% (3 out of 30) in the off-pump group and 40% (12 out of 30) in the on-pump group (P=0.017). CONCLUSION: Off-pump coronary artery bypass graft surgery results in less neurocognitive impairment than the on-pump technique.

Cognition Disorders↗