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Biomedical subjects

D M Williams

Publications and source records attributed to D M Williams.

At least 55 records · Page 3Linked to original sources
PubMed2000

Endograft planning without preoperative arteriography: a clinical feasibility study.

PURPOSE: To investigate an alternative method of preprocedural planning for aortic endografting based solely on spiral computed tomography (CT) with 3-dimensional (3D) reconstruction without preoperative arteriography. METHODS: From August 1997 to April 1998, 25 consecutive patients with abdominal aortic aneurysms (AAA) were evaluated for endovascular repair by spiral CT scans (2-mm slice thickness) and computerized 3D model construction. No additional imaging for planning was performed. The aortoiliac dimensions, thrombus load, calcification, and vessel tortuosity were measured and evaluated from the 3D model of the aortoiliac segment. These data were used for selecting the patients; the configuration, diameter, and length of the endograft; and the attachment sites for deployment. RESULTS: Primary procedural success was 92% (23/25). All endografts were deployed as planned, and there were no conversions to open repair. Six patients required adjunctive procedures for delivery system access or for iliac aneurysm exclusion, as predicted by the 3D model. Mean procedural time was 91 minutes (range 24 to 273). Two (8%) type II (side branch) endoleaks both sealed spontaneously within 1 month. No graft-related complications or death occurred, for a 30-day technical success rate of 100%. CONCLUSIONS: This computerized 3D model provided accurate data for preoperative evaluation of the aortoiliac segment for endovascular AAA repair. Satisfactory technical outcomes for aortic endografts can be achieved without the use of preprocedural invasive imaging.

Aged↗
PubMed2000

Preclinical development of keliximab, a Primatized anti-CD4 monoclonal antibody, in human CD4 transgenic mice: characterization of the model and safety studies.

The preclinical safety assessment of biopharmaceuticals necessitates that studies be conducted in species in which the products are pharmacologically active. Monoclonal antibodies are a promising class of biopharmaceuticals for many disease indications; however, by design, these agents tend to have limited species cross-reactivity and tend to only be active in primates. Keliximab is a human-cynomolgus monkey chimeric (Primatized) monoclonal antibody with specificity for human and chimpanzee CD4. In order to conduct a comprehensive preclinical safety assessment of this antibody to support chronic treatment of rheumatoid arthritis in patients, a human CD4 transgenic mouse was used for chronic and reproductive toxicity studies and for genotoxic studies. In addition, immunotoxicity studies were conducted in these mice with Candida albicans, Pneumocystis carinii and B16 melanoma cells to assess the effects of keliximab on host resistance to infection and immunosurveillance to neoplasia. The results of these studies found keliximab to be well tolerated with the only effects observed being related to its pharmacologic activity on CD4+ T lymphocytes. The use of transgenic mice expressing human proteins provides a useful alternative to studies in chimpanzees with biopharmaceutical agents having limited species cross-reactivity.

Animals↗
PubMed2000

Predicting anxiety in competitive sports.

The relationship between attitudes toward winning and competitive anxiety was explored in 59 undergraduate students competing on four different New Jersey-based, NCAA Division III sports teams. In a backward multiple regression analysis, cognitive anxiety was predicted significantly only by self-confidence, while somatic anxiety was predicted significantly by self-confidence and the rated importance of the competition.

Achievement↗
PubMed2000

Porphyromonas gingivalis induces ultrastructural and cytoskeletal changes in adherent human polymorphonuclear leucocytes.

The response of polymorphonuclear leucocytes (PMN) from healthy humans to culture supernatant from the periodontopathogen, Porphyromonas gingivalis, was examined using light, fluorescence and electron microscopy. Exposure of adherent cells to bacterial culture supernatant resulted in a 4-fold increase in the proportion of spread, flattened PMN. Scanning and transmission electron microscopy demonstrated that these cells had long dendritic cytoplasmic projections closely adherent to the substratum, in contrast with the more rounded, less adherent, control PMN. These shape changes were accompanied by a mean reduction in granule density to 57% compared with control cells (p<0.05) and a reduction in F-actin levels to 62% of controls (p<0.001), but no loss of viability and suggest a bacterially-induced mechanism of suppression of PMN motility which is likely to contribute to the pathogenic potential of P. gingivalis.

Adult↗
PubMed1999

Binding of HMG-I(Y) elicits structural changes in a silencer of the human beta-globin gene.

Proteins involved in repression of the human beta-globin gene may be useful in the treatment of sickle cell anemia, in conjunction with therapy to reactivate fetal globin genes. If there is a reciprocal elevation of gamma-globin expression upon repression, this approach could be useful in additional hemoglobinopathies. We previously showed that repression of the beta-globin gene appears to be mediated through two DNA sequences, silencers I and II, and identified a protein termed BP1 which binds to both silencer sequences. In this study, we cloned two cDNAs encoding proteins which bind to an oligonucleotide in silencer I containing a BP1 binding site. These cDNAs correspond to HMG-I and HMG-Y, isoforms regarded as architectural proteins. We demonstrate that binding of HMG-I(Y) to this oligonucleotide causes bending/flexure of the DNA. HMG-I(Y) also binds to a second oligonucleotide containing a BP1 binding site located in a negative control region upstream of the delta-globin gene, suggesting a role for HMG-I(Y) in repression of adult globin genes. Expression studies revealed that HMG-I(Y) is ubiquitously expressed in human tissues that do not express beta-globin, being present in 48 of 50 tissues and six hematopoietic cell lines examined. Furthermore, HMG-I(Y) expression is down-regulated during differentiation of primary erythroid cells. We present a model in which HMG-I(Y) alters DNA conformation to allow binding of repressor proteins, and in which the relative amount of HMG-I(Y) helps to determine the repressive state of the beta-globin gene.

Blotting, Northern↗
PubMed1999

High-resolution pulmonary arterio- and venography using multiple-bolus multiphase 3D-Gd-mRA.

The purpose of this study was to demonstrate selective visualization of pulmonary arteries and veins with high spatial resolution for improved detection of vascular pathologies. Time-resolved pulmonary three-dimensional gadolinium-enhanced magnetic resonance angiograms (3D-Gd-MRA) were acquired with an ultrashort 3D fast low-angle shot (FLASH) sequence (TR/TE 2.3/0.9 msec) using asymmetric k-space sampling in readout, phase-encoding, and partition directions. In a single breath-hold four consecutive acquisitions were performed with a scan time of 6.28 seconds for each phase. A spatial resolution of 1.9 x 1.4 x 2 mm(3) could be achieved for a 12 cm thick 3D volume. To exploit the intrinsic enhancement kinetics of the pulmonary vascular system, the infusion of two gadolinium chelate boli was synchronized with the acquisition of the first and third data sets. This infusion strategy created two predominantly pulmonary arterial and venous data sets with the arterial and venous signal being maximally anti-correlated in time. A further separation of arterial and venous signal could be achieved by means of a correlation analysis. Eight patients with suspected thrombi in the pulmonary veins were studied. The calculated correlation angiographies provided high-quality pulmonary arterio- and venograms. Background signal was completely eliminated, allowing maximum intensity projection analysis of the full data set. In 7/8 patients no venous contamination of the arterial phase and vice versa was found. Patency of the pulmonary arteries and veins could be reliably assessed to the level of the segmental vessels. The combination of ultrafast multiphase 3D-Gd-MRA and dual-bolus injection with a correlation analysis of vascular signal provides high-resolution pulmonary arterio- and venograms. This imaging strategy initiates a new competitor to X-ray angiography.

Adult↗
PubMed1999

Risk analysis for aortic surgery using hypothermic circulatory arrest with retrograde cerebral perfusion.

BACKGROUND: Retrospective analysis of 144 patients undergoing aortic arch reconstruction using hypothermic circulatory arrest (HCA) with retrograde cerebral perfusion (RCP) for cerebral protection was performed. METHODS: The diagnosis, procedure, and anatomic site of the arch anastomosis were analyzed to see if they were independent predictors of mortality or morbidity. In addition age, gender, HCA-RCP times, preoperative malperfusion (both treated and untreated), surgical status, and redo surgery status were also examined to determine their influence on the incidence of death and complications. Both multivariate and univariate analysis were performed using linear regression and cross-tabulation with either chi2 or Fisher's exact test where appropriate. RESULTS: Preoperative surgical status (emergent) and the presence of untreated preoperative malperfusion were the only variables that were significant independent predictors for mortality (p <0.05). No variable was significant for the prediction of stroke or other complications. The severity of surgery had no bearing on the patient outcome. CONCLUSIONS: Complex aortic surgery using HCA-RCP can be performed with acceptable risk to the patients.

Adult↗
PubMed1999

Diagnosis of pulmonary embolism: comparison of CT angiography and MR angiography in canines.

PURPOSE: To compare the sensitivity and specificity of helical computed tomographic angiography (CTA), CTA with multiplanar reconstructions (MPR)/three-dimensional-shaded surface display (3D-SSD), and gadolinium-enhanced magnetic resonance angiography (MRA) for pulmonary embolism (PE) detection. MATERIALS AND METHODS: Gelatin sponge emboli were introduced into the femoral veins of seven dogs and conventional digital subtraction angiography (CA), CTA, and MRA performed. Images from CTA, CTA with MPR/3D-SSD, and MRA were reviewed for the presence of PE in lobar and segmental arteries, and subsegmental zones. Postmortem angiography and CA were the gold standard. RESULTS: There were 50 emboli in the 294 vessels/zones analyzed. The sensitivity of CTA for the two readers was 76% (95% confidence interval [CI]; 64%-88%) and 64% (95% CI; 50%-78%), and for the two MRA readers was 52% (95% CI; 38%-66%) and 48% (95% CI; 34%-62%). CTA was more sensitive than MRA when PE were subdivided by vessel caliber. Specificity was high for CTA and MRA among all readers (98.8%-99.6%). MPR/3D-SSD did not improve results of axial CT. MRA perfusion defects were 46% and 47% sensitive and 100% specific. Interobserver agreement was high for CTA and MRA (kappa 0.92 and 0.93, respectively). The average diameter of vessels with emboli was 3.7 mm +/- 1.06. CONCLUSION: Helical CTA is more sensitive than three-dimensional gadolinium-enhanced MRA for the detection of PE. Both CTA and MRA are highly specific for PE detection and demonstrate high interobserver agreement. MPR/3D-SSD did not increase CTA performance over axial images alone.

Angiography↗
PubMed1999

Unplanned work absence following outpatient colonoscopy.

The authors investigated the incidence of unplanned work absence the day following outpatient colonoscopy and examined factors associated with missing work. A total of 250 patients were studied. Patient demographic information, the length of the procedure, time of day the exam was performed, and the amount and type of sedation medication used was obtained at the time of the procedure. The incidence and reasons for missing work were elicited via a phone survey 7 days postprocedure. Ten patients (4%) had an unplanned work absence the day after their colonoscopy. No complications were noted. Feeling sleepy and weak or abdominal pain and bloating were the most common reasons for missing work. In univariate analyses, patients with an unplanned work absence were more likely to be younger (p = 0.009), and female (p = 0.02) compared with patients who returned to work. No statistically significant differences were found with regard to the amount of sedation medication used, the length of the procedure, or whether the procedure was performed in the morning or afternoon. Unplanned work absence is low following outpatient colonoscopy in a community-based practice. Female gender and younger age are associated with a higher likelihood of missing work. Postprocedure work absence may have a greater economic impact than procedure-related complications.

Absenteeism↗
PubMed1999

The effect of a sodium lauryl sulfate-free dentifrice on patients with recurrent oral ulceration.

OBJECTIVE: Sodium lauryl sulphate (SLS) is the most commonly used detergent in dentifrices. Recent reports have suggested that it may exacerbate conditions with compromised epithelial integrity. The aim of this study was to compare the effect of an SLS-free dentifrice and an SLS-containing dentifrice on recurrent oral ulceration (ROU). DESIGN: A double-blind crossover clinical trial was carried out during which subjects used an SLS dentifrice for 8 weeks and an SLS-free dentifrice for 8 weeks. Each phase was preceded by a 2-week washout period. SETTING: A UK dental teaching hospital. SUBJECTS AND METHODS: Forty-seven subjects completed the trial. They were all in the age range 10-62 years, had regularly recurrent oral ulceration reporting at least one to two ulcers per month and had normal levels of vitamin B12, ferritin and folate. MAIN OUTCOME MEASURES: The trial phases were compared for the following ulcer parameters--number of ulcer days, total pain scores, number of ulcer episodes, and number of ulcers. Additional parameters compared were the number of ulcers per episode, ulcer duration, total pain per episode and ulcer size. RESULTS: None of the ulcer parameters measured was significantly affected by the use of the SLS-free dentifrice as compared with the SLS dentifrice. CONCLUSION: SLS-free dentifrice had no significant effect on ulcer pattern in the ROU study group.

Adolescent↗
PubMed1999

An immunohistochemical study of keratin expression in ameloblastoma from a Kenyan population.

OBJECTIVES: Ameloblastomas appear to exhibit biological heterogeneity and, except in the case of malignancy, histological appearances that do not always allow their behaviour to be predicted. The aim of this study was to assess keratin expression in African ameloblastomas and to correlate this with their clinical and histological features. MATERIALS AND METHODS: Expression of simple keratins 7, 8, 18 and 19; cornification keratins 1 and 10; basal and differentiation keratins 5 and 14 and hyperproliferation-related keratins 6 and 16 in 14-39 cases of ameloblastoma was assessed by immunohistochemical methods. RESULTS: There was patchy expression of keratin 7 in the suprabasal and stellate reticulum-like cells in some cases. All cases showed similar weak expression for keratins 8 and 18 in suprabasal and stellate reticulum-like cells but none showed keratin 1 or 10 expression. There was intense expression of keratins 5, 14 and 19 by all tumour cells suggesting that they may retain basal cell characteristics with a potential for proliferation. No consistent relationship was seen between histological types and keratin expression pattern. However, keratins 6 and 16, expressed by suprabasal and stellate reticulum-like cells, showed a marked variation within and between cases, with the highest levels of expression in squamous strands. CONCLUSIONS: We propose that squamous strands may represent the sites of most active growth within individual tumours and expression of keratins 6, 16 and 19 may be predictors of rapid growth. There is a need for further investigation of this in longitudinal clinical studies.

Adolescent↗
PubMed1999

Targeted disruption of fibronectin-integrin interactions in human gingival fibroblasts by the RI protease of Porphyromonas gingivalis W50.

Cell surface integrins mediate interactions between cells and their extracellular matrix and are frequently exploited by a range of bacterial pathogens to facilitate adherence and/or invasion. In this study we examined the effects of Porphyromonas gingivalis proteases on human gingival fibroblast (HGF) integrins and their fibronectin matrix. Culture supernatant from the virulent strain W50 caused considerably greater loss of the beta1 integrin subunit from HGF in vitro than did that of the beige-pigmented strain W50/BE1. Prior treatment of the W50 culture supernatant with the protease inhibitor Nalpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) blocked its effects on cultured cells, indicating that this process is proteolytically mediated. Purified arginine-specific proteases from P. gingivalis W50 were able to mimic the effects of the whole-culture supernatant on loss of beta1 integrin expression. However purified RI, an alpha/beta heterodimer in which the catalytic chain is associated with an adhesin chain, was 12 times more active than RIA, the catalytic monomer, in causing loss of the alpha5beta1 integrin (fibronectin receptor) from HGF. No effect was observed on the alphaVbeta3 integrin (vitronectin receptor). The sites of action of RI and RIA were investigated in cells exposed to proteases pretreated with TLCK to inactivate the catalytic component. Use of both monoclonal antibody 1A1, which recognizes only the adhesin chain of RI, and a rabbit antibody against P. gingivalis whole cells indicated localization of RI on the fibroblasts in a clear, linear pattern typical of that seen with fibronectin and alpha5beta1 integrin. Exact colocalization of RI with fibronectin and its alpha5beta1 receptor was confirmed by double labeling and multiple-exposure photomicroscopy. In contrast, RIA bound to fibroblasts in a weak, patchy manner, showing only fine linear or granular staining. It is concluded that the adhesin component of RI targets the P. gingivalis arginine-protease to sites of fibronectin deposition on HGF, contributing to the rapid loss of both fibronectin and its main alpha5beta1 integrin receptor. Given the importance of integrin-ligand interactions in fibroblast function, their targeted disruption by RI may represent a novel mechanism of damage in periodontal disease.

Animals↗
PubMed1999

Synthetic interposition grafts of the thoracic aorta: postoperative appearance on serial CT studies.

PURPOSE: To determine the normal postoperative appearance of thoracic aortic interposition grafts on serial CT studies and to document CT detectable complications. MATERIALS AND METHODS: The 235 CT studies in 114 patients with one or more thoracic aortic interposition grafts were analyzed for the presence or absence of felt rings, felt pledgets, low-attenuation material surrounding the graft, pseudoaneurysm, and dissection flap. A graft was present in the ascending aorta in 93 patients, in the descending aorta in 25, and in the arch in 11. RESULTS: Low-attenuation material was seen adjacent to the ascending graft in 55%-82% of patients and adjacent to the descending graft in 60%-79% of patients, showing diminishing frequency and thickness over time. CT scans in 30 of 53 patients showed residual low-attenuation material adjacent to the graft more than 1 year after surgery. CT scans in four of 93 patients with ascending grafts and one of 25 patients with descending grafts showed a pseudoaneurysm. CONCLUSION: CT studies obtained after aortic interposition grafting show characteristic findings. Knowledge of the type of operative procedure and typical location and CT appearance of surgical materials used is important to correctly diagnose or exclude postoperative complications following thoracic aortic interposition grafting.

Aorta, Thoracic↗
PubMed1998

Low-latitude glaciation and rapid changes in the Earth's obliquity explained by obliquity-oblateness feedback.

Palaeomagnetic data suggest that the Earth was glaciated at low latitudes during the Palaeoproterozoic (about 2.4-2.2 Gyr ago) and Neoproterozoic (about 820-550 Myr ago) eras, although some of the Neoproterozoic data are disputed. If the Earth's magnetic field was aligned more or less with its spin axis, as it is today, then either the polar ice caps must have extended well down into the tropics-the 'snowball Earth' hypothesis-or the present zonation of climate with respect to latitude must have been reversed. Williams has suggested that the Earth's obliquity may have been greater than 54 degrees during most of its history, which would have made the Equator the coldest part of the planet. But this would require a mechanism to bring the obliquity down to its present value of 23.5 degrees. Here we propose that obliquity-oblateness feedback could have reduced the Earth's obliquity by tens of degrees in less than 100 Myr if the continents were situated so as to promote the formation of large polar ice sheets. A high obliquity for the early Earth may also provide a natural explanation for the present inclination of the lunar orbit with respect to the ecliptic (5 degrees), which is otherwise difficult to explain.

Atmosphere↗