Biomedical subjects

D W Williams

Publications and source records attributed to D W Williams.

At least 37 records · Page 2Linked to original sources

PubMed2001

Identification of Candida dubliniensis, based on ribosomal DNA sequence analysis.

Differentiation of Candida albicans and the recently described C. dubliniensis has proven difficult due to the high degree of phenotypic similarity of these species. The present study examines sequence variations in the ribosomal DNA (rDNA) intergenic transcribed spacer (ITS) regions of C. albicans (n = 5) and C. dubliniensis (n = 7) strains, with a view to identifying sequence differences that would enable consistent differentiation of these two species by restriction fragment length polymorphism (RFLP) analysis. The ITS1 and ITS2 regions, together with the entire 5.8S rRNA gene of the strains, were amplified by the polymerase chain reaction (PCR), using primers ITS1 and ITS4, PCR products from both C. albicans and C. dubliniensis were of similar size (around 540 bp); however, sequence analysis revealed over 20 consistent base differences between the products of the two species. On the basis of sequence variation, the restriction enzyme MspA1 I was selected and used to differentiate the PCR products of C. albicans and C. dubliniensis by RFLP analysis. MspA1 I yielded two discernible fragments from C. albicans PCR products, whilst those from C. dubliniensis appeared undigested, thereby providing an approach to differentiate the two species.

Candida↗

PubMed2000

Tau and tau reporters disrupt central projections of sensory neurons in Drosophila.

In this paper, the authors report that the expression of tau-based reporter genes causes severe defects in the morphology of sensory neurons in adult Drosophila. Targeted expression of tau-green fluorescent protein (tau-GFP) in sensory neurons, using the galactosidase-4 (GAL4) system, produced a range of characteristic defects in expressing neurons. The defects observed included loss of axons, abnormal axon bundling, reduced sensory arborisations, and axonal swellings (beads). Blind comparisons of adult sensory neurons labelled with tau-GFP or CD8-GFP showed that tau-GFP neurons exhibited many more defects than CD8-GFP-expressing neurons. CD8-GFP was found to induce no significant defects on sensory neuron morphology. Expression of tau-lacZ and human tau in sensory neurons produced defects comparable to those seen with tau-GFP. A developmental study showed that tau-expressing axons grow normally and innervate the correct regions of the neuropil. The absence of these axons later in development suggests that tau-expressing axons are lost after initial ingrowth. Examination of silver-stained sections suggests that the absence of axons is due to axon loss rather than failure of the expression system to label the neurons. The results suggest that the expression of tau-based reporter constructs causes severe defects in sensory neurons, resulting in degeneration. The results also indicate that Drosophila may provide a useful model system for examining the role of tau in neurodegenerative disorders.

Afferent Pathways↗

PubMed2000

Confocal quality imaging of afferent neurons from semi-thin sections of Drosophila ganglia.

The aim of this study was to develop protocols for computer imaging of the thoraco-abdominal ganglion of Drosophila from serial semi-thin sections, in which specific neurons were stained and related to neuropilar structures. The central projections of a subset of transgenically labelled sensory neurons were revealed by immunohistochemistry, while Nomarski optics were used to show motor neuron targets in the neuropil. Digital photomicrographs of each section were aligned and the resultant image stacks rendered into three-dimensional (3D) images that can be rotated in real time. The result is a detailed, in-depth visualization of labelled neurons at a resolution comparable with that in confocal reconstructions, which also allows investigation of their relationships with other components of the neuropil.

Animals↗

PubMed2000

Efficacy of 3 commonly used hearing aid circuits: A crossover trial. NIDCD/VA Hearing Aid Clinical Trial Group.

CONTEXT: Numerous studies have demonstrated that hearing aids provide significant benefit for a wide range of sensorineural hearing loss, but no carefully controlled, multicenter clinical trials comparing hearing aid efficacy have been conducted. OBJECTIVE: To compare the benefits provided to patients with sensorineural hearing loss by 3 commonly used hearing aid circuits. DESIGN: Double-blind, 3-period, 3-treatment crossover trial conducted from May 1996 to February 1998. SETTING: Eight audiology laboratories at Department of Veterans Affairs medical centers across the United States. PATIENTS: A sample of 360 patients with bilateral sensorineural hearing loss (mean age, 67.2 years; 57% male; 78.6% white). INTERVENTION: Patients were randomly assigned to 1 of 6 sequences of linear peak clipper (PC), compression limiter (CL), and wide dynamic range compressor (WDRC) hearing aid circuits. All patients wore each of the 3 hearing aids, which were installed in identical casements, for 3 months. MAIN OUTCOME MEASURES: Results of tests of speech recognition, sound quality, and subjective hearing aid benefit, administered at baseline and after each 3-month intervention with and without a hearing aid. At the end of the experiment, patients ranked the 3 hearing aid circuits. RESULTS: Each circuit markedly improved speech recognition, with greater improvement observed for soft and conversationally loud speech (all 52-dB and 62-dB conditions, P</=.001). All 3 circuits significantly reduced the frequency of problems encountered in verbal communication. Some test results suggested that CL and WDRC circuits provided a significantly better listening experience than PC circuits in word recognition (P =.002), loudness (P =.003), overall liking (P =.001), aversiveness of environmental sounds (P =.02), and distortion (P =.02). In the rank-order ratings, patients preferred the CL hearing aid circuits more frequently (41.6%) than the WDRC (29.8%) and the PC (28.6%) (P =.001 for CL vs both WDRC and PC). CONCLUSIONS: Each circuit provided significant benefit in quiet and noisy listening situations. The CL and WDRC circuits appeared to provide superior benefits compared with the PC, although the differences between them were much less than the differences between the aided vs unaided conditions. JAMA. 2000;284:1806-1813.

Adult↗

PubMed2000

Placebo-associated blood pressure response and adverse effects in the treatment of hypertension: observations from a Department of Veterans Affairs Cooperative Study.

BACKGROUND: The use of placebo in clinical trials has been vigorously debated. Placebo control may be useful in disease states, such as stage 1 and stage 2 hypertension as defined by the Sixth Report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC VI), in which response rates for placebo are high or close to response rates for effective therapies, or when established interventions have significant adverse effects. OBJECTIVE: To compare rates for the control of blood pressure and adverse effects of placebo vs active treatment in patients with stage 1 and stage 2 hypertension. METHODS: This study is a randomized controlled trial evaluating the blood pressure response and adverse effects of placebo vs 6 active treatments administered in 15 Veterans Affairs hypertension centers. The 1292 subjects of the Veterans Affairs Cooperative Study receiving single-drug therapy for hypertension were randomly allocated to receive treatment with 1 of 6 active drugs (n= 1105) or placebo (n=187). Treatment success was defined as maintaining a diastolic blood pressure of less than 95 mm Hg for at least 1 year. We compared treatment success rates for the control of blood pressure and adverse effects of placebo vs active treatment. Using the Kaplan-Meier method, we also compared rates of discontinuation from placebo vs active drug treatment over time as a result of adverse drug effects and blood pressure exceeding safety limits. RESULTS: At the end of the titration phase, 58 patients who were treated with placebo (31%) achieved a goal diastolic blood pressure lower than 90 mm Hg and 57 (30%) achieved success at 1 year. Older white patients who received placebo had a success rate of 38% vs 23% to 27% for the other age-race subgroups. The rates of discontinuation as a result of adverse drug effects were 13% for patients receiving placebo vs 12% for patients receiving active treatment (P=.40). The rates of discontinuation for blood pressure being too high were 14% for patients receiving placebo vs 7% for patients receiving active treatment (P=.01). CONCLUSIONS: Placebo control provides an important benchmark for both efficacy and adverse effects. It continues to have an appropriate place in certain therapeutic trials, particularly those involving the treatment of stage 1 and stage 2 hypertension.

Adult↗

PubMed2000

FDG PET evaluation of head and neck cancer: value of imaging the thorax.

BACKGROUND: Patients with primary tumors of the head and neck have been reported to have a high rate of synchronous primary tumors of the upper aerodigestive tract. This study was performed to determine whether inclusion of the thorax in the scan volume would be diagnostically useful for positron emission tomography (PET) with [F-18] fluorodeoxy-D-glucose (FDG) in patients with primary tumors of the head and neck. METHODS: FDG PET scans from the midcranium to the diaphragm were obtained on 56 patients with a variety of head and neck tumors on initial examination before definitive therapy. PET findings in the chest were correlated with results of all other imaging studies, biopsy results, and clinical follow-up. RESULTS: In nine studies (16%), areas of increased FDG uptake in the chest were seen and were judged to be tumors. Six of these probably were false-positive results, although one of these six may have been unconfirmed true positives. Of the three confirmed true-positive studies, two were obvious from other routine studies. In only one case did the PET study reveal a significant lesion not found by means of routine evaluation, resulting in a case-finding yield of 2%. If the unconfirmed possible true-positive results are included, the case-finding yield increases to 4%. CONCLUSIONS: No compelling indication was seen for including the chest in PET studies of patients with head and neck cancer.

Adult↗

PubMed2000

Phenotypic characterisation of Candida albicans isolated from chronic hyperplastic candidosis.

The phenotypes of 35 Candida albicans isolates from 19 patients with chronic hyperplastic candidosis (CHC) and 35 isolates from 30 patients with non-CHC infections were compared. Typing was based on carbohydrate assimilation, chemical sensitivity and serology. Eight carbohydrate assimilation profiles were evident with the API-20C system and a single profile predominated for isolates from CHC (17 of 19 patients; 89%) and non-CHC (18 of 30 patients; 63%). Chemical sensitivity tests revealed four profiles with no significant difference between CHC and non-CHC isolates. Serotype A predominated for isolates from both CHC (15 of 19 patients; 79%) and non-CHC (25 of 30 patients; 83%) infections. Boric acid resistance was more prevalent in CHC isolates, although a significant difference was not apparent. In summary, there was no overall difference in the phenotypes of isolates from CHC and non-CHC patients, and clonal restriction of CHC isolates was not demonstrated.

Candida albicans↗

PubMed2000

Isolation and identification of Candida from the oral cavity.

A number of methods of sampling the oral cavity for the presence of candida have been developed. Such techniques play an important role in the diagnosis and management of oral candidosis. In the past, identification of candida isolated from the oral cavity has usually been limited to the genus Candida or to the species C. albicans. However, with the recognition that Candida species differ in the production of putative virulence factors and sensitivity to antifungal agents, greater emphasis has been placed on identification of isolates to species level. As a result a range of commercially available systems for yeast identification can now be used in conjunction with traditional identification procedures.

Antifungal Agents↗

PubMed2000

Macrorestriction fingerprinting of "Streptococcus milleri" group bacteria by pulsed-field gel electrophoresis.

Although isolates of the "Streptococcus milleri" group (SMG) of bacteria are regarded as members of the commensal microflora of the body, they are frequently encountered in purulent infections from a range of body sites. The genetic diversity of 91 epidemiologically unrelated SMG isolates (including 37 commensal strains and 49 disease-associated strains) was analyzed by macrorestriction fingerprinting (MF). The genomes were digested with SmaI and ApaI independently, and fragments were resolved by pulsed-field gel electrophoresis. Similarities between banding profiles were determined, and strains were clustered on this basis into dendrograms. In common with other commensal species that have been examined by MF, considerable genetic diversity was revealed. In addition, the clustering of strains tended to support the current taxonomic position of this heterogeneous group. The present study has shown that MF is a powerful tool for characterization of SMG strains and that its use is likely to be of great value in epidemiological and population genetic studies of this group of bacteria.

DNA Fingerprinting↗

PubMed2000

Consistency in the observation of features used to classify duct carcinoma in situ (DCIS) of the breast.

AIM: To determine interobserver and intra-observer agreement in the assessment of cytological grade and intraduct necrosis in pure duct carcinoma in situ (DCIS) of the breast. METHODS: Sixty unselected cases with illustrated diagnostic criteria were circulated to 19 practising histopathologists. RESULTS: Overall agreement was moderate for cytological grade in three categories: 71% agreement; weighted kappa (kappa w), 0.36; intraduct necrosis in three categories (absent, present, extensive): 76% agreement; kappa w, 0.57; and the Van Nuys classification system: 73% agreement; kappa w, 0.48. Agreement was no better among observers participating in the National External Quality Assurance Programme. Intra-observer agreement for cytological assessment (69.6% agreement; kappa w, 0.52) and intraduct necrosis (68.3% agreement; kappa w, 0.48) was moderate, suggesting that individual variation rather than precision of criteria contributes to the lack of agreement. CONCLUSIONS: Moderate agreement on observations can be achieved by non-specialist pathologists, with better agreement on necrosis than cytological grade. There was evidence of consistent individual bias towards over or under scoring cytological grade, which could be corrected with adequate and prompt feedback.

Breast Neoplasms↗

PubMed2000

Methods for imaging labeled neurons together with neuropil features in Drosophila.

We describe staining protocols for serial semithin sections of Drosophila central ganglia that allow visualization of gene expression in particular neurons with counterstaining to display the ganglion architecture. Green fluorescent protein (GFP), expressed in a subset of sensory neurons from a selected enhancer trap line, is visualized by conventional immunohistochemistry with a peroxidase-linked antibody, and neural architecture is revealed by reduced silver staining. This makes visible in histological sections the same GFP-labeled cells seen with confocal microscopy, but with the especial advantage that neuropil structures are also revealed at the level of individual cells and neuron processes. Not only does this allow the physical relationships among intracellularly labeled neurons to be determined by reference to specific features in the neuropil but it also enables a function to be ascribed provisionally to particular regions of neuropil. These methods have particular utility for mapping morphological information on specific neurons in the context of central nervous system architecture, both in adult Drosophila and during development.

Animals↗

PubMed1999

Occult primary tumors of the head and neck: lack of benefit from positron emission tomography imaging with 2-[F-18]fluoro-2-deoxy-D-glucose.

BACKGROUND: Patients who present with squamous cell carcinoma metastatic to cervical lymph nodes and no clinically apparent primary site present a therapeutic dilemma. Positron emission tomography imaging with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG-PET) has been shown to be useful for the examination of known primary tumors. This study was undertaken to determine whether FDG-PET imaging improves detection of occult primary tumors in patients with metastatic squamous cell carcinoma in the lymph nodes of the head and neck. METHODS: Thirteen patients with pathology proven cervical lymph node metastases from clinically occult primary squamous cell carcinomas were evaluated prospectively with FDG-PET, in addition to standard clinical and radiographic techniques, as part of their pretreatment diagnostic evaluation. Direct panendoscopy and biopsy were performed on all patients in an attempt to detect primary tumor sites and to characterize them histologically. RESULTS: A primary squamous cell carcinoma was confirmed after panendoscopy and biopsy in 3 of the 13 patients. The site of the primary tumor was correctly identified with FDG-PET in only one of these three patients. The FDG-PET study suggested a primary tumor location where no tumor was found in 6 of 13 patients; for 5 other of the 13 patients, the FDG-PET results were negative and no primary was found. No primary tumor locations were identified by computed tomography, magnetic resonance imaging, or direct panendoscopy. FDG-PET imaging correctly detected the location of the primary tumor in 1 patient (8%) and provided apparent false-positive results for 6 (46%) of the 13 patients. CONCLUSIONS: FDG-PET imaging did not significantly improve detection of unknown primary squamous cell carcinomas in patients with metastases to lymph nodes of the neck. A high percentage of results were apparent false-positive.

Carcinoma, Squamous Cell↗

PubMed1999

Effects of antihypertensive single-drug therapy on heart rate. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

Heart rate increasingly is being recognized either as an independent risk factor for a wide variety of cardiovascular disorders or as a surrogate marker for them. We analyzed the changes in heart rate associated with antihypertensive therapy with six drugs and placebo from the VA Cooperative Study on Single-Drug Therapy. These results were published previously (American Journal of Hypertension 1998;11:597-601). This paper provides a summary of the earlier publication with the addition of three figures not previously published. Atenolol had the greatest effect on heart rate reduction, followed by clonidine and diltiazem-SR. Hydrochlorothiazide and captopril were associated with small reductions in heart rate over time, whereas prazosin increased heart rate. Patients whose blood pressure was controlled by placebo had a 3.1 beats/min reduction of heart rate at 2 years. When the baseline heart rate was 65 beats/min or less, all drugs increased the heart rate except for atenolol, which further reduced it. Although it is clear that each of the six drugs used in our study had a different effect on heart rate, we cannot state that drug-induced reduction in heart rate per se confers a decrease in cardiovascular risk.

Antihypertensive Agents↗

PubMed1999

Adherence of Candida albicans to oral epithelial cells differentiated by Papanicolaou staining.

OBJECTIVE: To examine the relative adherence of Candida albicans to oral epithelial cells differentiated by Papanicolaou staining. METHODS: Oral epithelial cells were collected from 10 healthy adults (five male, five female) and counted. Equal volumes of oral epithelial cells and candida were mixed and incubated. The epithelial cells from this mix were collected by filtration through 10 microns polycarbonate membrane filters. Cells retained on the membrane filters were stained with crystal violet followed by Papanicolaou stain. The number of yeast attached to each of 100 red, orange, and green staining oral epithelial cells was determined by direct microscopic examination. RESULTS: C albicans had a higher level of adherence (p < 0.001) to red staining oral epithelial cells (mean (SD) number of candida attached to 100 oral epithelial cells 562 (159)) than to cells staining either orange (105 (47)) or green (161 (66)). CONCLUSIONS: Oral epithelial cell variability for candidal adherence is confirmed. The technique provides an opportunity to examine the relation between oral epithelial cell type and oral candidosis in specific groups, such as tobacco smokers, where increased epithelial cell keratinisation and candidal colonisation has been reported.

Adult↗

PubMed1999

Persistent larval sensory neurons in adult Drosophila melanogaster.

Using a combination of lineage tracing and laser ablation, we have identified a segmentally repeated array of embryonically produced sensory neurons that persist through metamorphosis into adult stages of Drosophila development. The persistent sensory neurons are found in all unfused abdominal segments, but there is segment-specific variation in the number of neurons observed. There are 12 persistent neurons in the first abdominal segment (A1), 18 in the second (A2), and 16 in segments A3-A7. Most are internal sensory neurons (dendritic arborization neurons and bipolar dendrite neurons), but two are associated with external sensilla on the sternite. All of these neurons and their axons define specific adult sensory pathways in the periphery and their locations and persistence through metamorphosis suggest a role in guiding the growth of adult sensory and motor axons.

Age Factors↗

PubMed1999

Deoxyribonucleic acid typing methods for medically important microorganisms.

The ability to type microorganisms to a sub-species level plays an essential role in the diagnosis, treatment and control of human infection. Traditionally, differentiation of microorganisms has involved analysis of phenotypic markers. However, these methods are not universally applicable to all microorganisms, and results may be influenced by environmental factors. Recent developments in DNA analysis, together with the limitations of phenotypic methods, have resulted in an increasing use of procedures based on DNA analysis for the typing of clinically important microorganisms. The aim of this review is to provide an overview of the advantages and disadvantages of the genetic typing techniques currently available.

Bacterial Typing Techniques↗

PubMed1998

Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

CONTEXT: Renin profiling and age-race subgroup may help select single-drug therapy for stage 1 and stage 2 hypertension. OBJECTIVE: To compare the plasma renin profiling and age-race subgroup methods as predictors of response to single-drug therapy in men with stage 1 and 2 hypertension as defined by the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. DESIGN: The Veterans Affairs Cooperative Study on Single-Drug Therapy of Hypertension, a randomized controlled trial. SETTING: Fifteen Veterans Affairs hypertension centers. PATIENTS: A total of 1105 ambulatory men with entry diastolic blood pressure (DBP) of 95 to 109 mm Hg, of whom 1031 had valid plasma and urine samples for renin profiling. INTERVENTIONS: Randomization to 1 of 6 antihypertensive drugs: hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem (sustained release), or prazosin. MAIN OUTCOME MEASURE: Treatment response as assessed by percentage achieving goal DBP (<90 mm Hg) in response to a single drug that corresponded to patients' renin profile vs a single drug that corresponded to patients' age-race subgroup. RESULTS: Clonidine and diltiazem had consistent response rates regardless of renin profile (76%, 67%, and 80% for low, medium, and high renin, respectively, for clonidine and 83%, 82%, and 83%, respectively, for diltiazem for patients with baseline DBP of 95-99 mm Hg). Hydrochlorothiazide and prazosin were best in low- and medium-renin profiles; captopril was best in medium- and high-renin profiles (low-, medium-, and high-renin response rates were 82%, 78%, and 14%, respectively, for hydrochlorothiazide; 88%, 67%, and 40%, respectively, for prazosin; and 51%, 83%, and 100%, respectively, for captopril for patients with baseline DBP of 95-99 mm Hg). Response rates for patients with baseline DBP of 95 to 99 mm Hg by age-race subgroup ranged from 70% for clonidine to 90% for prazosin for younger black men, from 50% for captopril to 97% for diltiazem for older black men, from 70% for hydrochlorothiazide to 92% for atenolol for younger white men, and from 84% for hydrochlorothiazide to 95% for diltiazem for older white men. Patients with a correct treatment for their renin profile but incorrect for age-race subgroup had a response rate of 58.7%; patients with an incorrect treatment for their renin profile but correct for age-race subgroup had a response rate of 63.1% (P = .30). After controlling for DBP and interactions with treatment group, age-race subgroup (P<.001) significantly predicted response to single-drug therapy, whereas renin profile was of borderline significance (P= .05). CONCLUSIONS: In these men with stage 1 and stage 2 hypertension, therapeutic responses were consistent with baseline renin profile, but age-race subgroup was a better predictor of response.

Adult↗

PubMed1998

Effect of single-drug therapy on reduction of left atrial size in mild to moderate hypertension: comparison of six antihypertensive agents.

BACKGROUND: Cardiac effects of hypertension include increased left ventricular (LV) mass and LV hypertrophy, as well as increased left atrial size, a predictor of stroke and atrial fibrillation. Although literature on reduction of LV mass with antihypertensive therapy is extensive, little information is available on effects of treatment on left atrial size. METHODS AND RESULTS: Patients with mild to moderate hypertension (diastolic blood pressure 95 to 109 mm Hg) were randomly allocated to treatment with atenolol, captopril, clonidine, diltiazem, hydrochlorothiazide, or prazosin in a double-masked trial. Two-dimensional targeted M-mode echocardiography was used to assess left atrial size and LV mass at baseline, 8 weeks, and 1 and 2 years. Longitudinal analysis examined changes in left atrial size from the baseline study, statistically adjusting for age, race, pretreatment left atrial size and LV mass, and serial measurements of systolic blood pressure, body weight, urinary sodium excretion, and physical activity score. Without adjustment for covariates, only hydrochlorothiazide was associated with decreases in left atrial size from baseline at 8 weeks (-1.0 +/- 5.2 mm; P=0.052), 1 year (-2.0 +/- 5.1 mm; P=0.02), and 2 years (4.6+/-7.2 mm; P=0.002). After adjustment for effects of covariates, patients with normal left atrial size had greater reduction (-3.3 mm) in left atrial size at 2 years with hydrochlorothiazide than with any other drug. For patients with left atrial enlargement, left atrial size decreased significantly with hydrochlorothiazide, atenolol, clonidine, and diltiazem at 1 year and with all treatments at 2 years. However, reduction at 2 years was greater with hydrochlorothiazide than with captopril or prazosin. CONCLUSIONS: Antihypertensive drugs differ in their effects on left atrial size. Hydrochlorothiazide was associated with greater overall reduction of left atrial size than other drugs effective for the treatment of hypertension. Reduction of left atrial size with therapy is in part independent of factors known to influence left atrial size, including LV mass and reduction of LV mass with treatment. The clinical benefit of reducing left atrial size with antihypertensive treatment remains to be determined.

Aged↗