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D W Williams

Publications and source records attributed to D W Williams.

At least 55 records · Page 3Linked to original sources
PubMed1998

Comparison of effects of antihypertensive drugs on heart rate: changes from baseline by baseline group and over time. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

Baseline heart rate is becoming recognized as a predictor of cardiovascular risk. Various antihypertensive drugs have differing effects on heart rate. A randomized controlled clinical trial of 1292 ambulatory men with stage 1 or 2 hypertension was conducted in 15 Veterans Affairs medical centers. Patients were treated with hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, prazosin, or placebo for up to 2 years. Heart rates were measured at baseline, the end of titration, 1 year, and 2 years. Data were also stratified by baseline heart rate. A subset of patients had heart rate also determined by electrocardiogram. All drugs except prazosin reduced heart rate from baseline; additional small decreases were obtained over time with hydrochlorothiazide and placebo. The decrease initially achieved with clonidine was attenuated over time. The overall reduction in heart rate was greatest for atenolol (-12.2 beats/min) and least for prazosin (+3.8 beats/min). Only atenolol effected a further reduction of heart rate for patients whose baseline rate was < or =65 beats/min. All drugs reduced heart rate when the baseline was > or =85 beats/min. Data derived by electrocardiogram yielded similar results. The drugs used in this study differ in their ability to reduce heart rate, sustain that reduction over time, and to change heart rate in groups with high or low rates at baseline. The importance of these comparative changes as independent cardiac risk factor variables remains to be determined.

Antihypertensive Agents↗
PubMed1998

Immunocytochemical detection of Candida albicans in formalin fixed, paraffin embedded material.

AIM: To assess the ability of the commercially available monoclonal antibody 1B12 (BioGenex, San Ramon, USA) to identify C albicans in formalin fixed, paraffin wax embedded material (FFPE). METHODS: Broth cultures of 20 strains of seven Candida species were resuspended in 4% agarose blocks, fixed in formalin for 24 hours, and embedded in paraffin wax. In addition, 16 blocks of FFPE tissue known to contain periodic acid-Schiff positive fungal hyphae were examined. Antigen retrieval involved microwave treatment of specimens in citrate buffer (0.01 M; pH 6.5) before addition of 1B12 antibody for 24 hours. Bound antibody was subsequently detected using a biotinylated link antibody and a peroxidase conjugated streptavidin. RESULTS: Only C albicans strains were 1B12 positive in the agarose blocks. All FFPE tissue blocks were found to contain 1B12 positive hyphal structures, indicating the presence of C albicans. CONCLUSIONS: The ability to identify candida organisms penetrating the lesional tissue in cases of chronic hyperplastic candidosis will help to clarify the role of individual Candida spp in this important form of oral candidosis.

Antibodies, Monoclonal↗
PubMed1998

A novel technique for assessment of adherence of Candida albicans to solid surfaces.

A novel approach for the assessment of adherence of Candida albicans to translucent acrylic material is described. The method uses the inverted microscope to visualise yeast adhering to acrylic surfaces while the test material remains immersed in buffer. Adherent cells were not subjected to surface tension forces that can occur during drying processes, so that an even distribution of yeast with no aggregation occurred. The process of counting attached yeast was subsequently performed without difficulty. From the 11 C albicans isolates examined, two groups were evident with respect to acrylic adherence: one group of four isolates with an adherence level of 400 yeast/mm2 acrylic, and one group of seven isolates with adherence levels of 1000 yeast/mm2 acrylic.

Acrylic Resins↗
PubMed1998

Laryngeal radionecrosis versus recurrent cancer: a clinical approach.

A group of 38 patients was studied by positron emission tomography utilizing fluorine18-labeled deoxyglucose (FDG-PET) scanning to examine the ability to differentiate postirradiation laryngeal recurrent cancer from radionecrosis. The resulting 79% correct diagnosis showed the technique to be far superior to conventional computed tomography scanning (61%) and clinical examination (43%). An algorithmic approach to evaluating and treating patients with radionecrosis and/or recurrent cancer by utilizing FDG-PET scanning is presented.

Algorithms↗
PubMed1998

The role of gonadectomy and testosterone replacement on thymic luteinizing hormone-releasing hormone production.

We and others have identified luteinizing hormone-releasing hormone (LHRH) in cells of the immune system in both animals and humans. LHRH is an immunostimulant, and testosterone is an immunosuppressant. Because testosterone is known to modulate the concentrations of hypothalamic LHRH, we wondered whether testosterone might also alter the concentrations of rat thymic LHRH. Two weeks after castration or sham castration, adult male rats were implanted with either vehicle or testosterone capsules. All animals were killed 4 days after capsule implantation. Thymic LHRH concentration increased significantly in castrated animals. Testosterone replacement prevented this increase. The concentration of the LHRH precursor, proLHRH, decreased significantly, but testosterone replacement prevented this decrease. Steady-state concentrations of LHRH mRNA were not changed by castration or by hormonal replacement. In contrast to the post-castration increase in thymic LHRH, LHRH content of the hypothalamus decreased significantly. Whereas concentrations of LHRH were lower in the thymus than in the hypothalamus, proLHRH concentrations were much greater in the thymus. These data suggest that gonadal manipulation modulates LHRH molecular processing and its tissue concentration in the thymus in addition to those in the hypothalamus, and that the regulation of LHRH molecular processing by testosterone in the hypothalamus is different from that in the thymus.

Analysis of Variance↗
PubMed1997

Effect of single-drug therapy on reduction of left ventricular mass in mild to moderate hypertension: comparison of six antihypertensive agents. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

BACKGROUND: Antihypertensive drugs may differ in their ability to reduce LV mass. Covariates other than drug selection, such as pretreatment LV mass, body weight, the magnitude of blood pressure reduction, race, and age may modify the response of LV mass to therapy. 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. Patients achieving the goal diastolic blood pressure of <90 mm Hg during drug titration entered a 1-year maintenance period. Longitudinal analysis examined changes from baseline echocardiogram in LV mass at 8 weeks and at 1 year, statistically adjusted for pretreatment LV mass, systolic blood pressure, body weight, sodium excretion, physical activity, race, and age. Significant reductions at 1 year in adjusted LV mass were seen for patients in the highest tertile of pretreatment LV mass treated with hydrochlorothiazide (mean, -42.9; 95% confidence limits, -65.5, -20.2 g), captopril (mean, -38.7; 95% confidence limits, -61.0, -16.4 g), and atenolol (mean, -28.1; 95% confidence limits, -50.9, -5.3 g). These treatment effects differed from those of prazosin, diltiazem, or clonidine. CONCLUSIONS: Antihypertensive drugs have disparate effects on LV mass independent of the magnitude of blood pressure reduction. Patients with adequate blood pressure control on captopril, hydrochlorothiazide, and atenolol show a reduction of LV mass after 1 year of treatment, whereas patients on diltiazem, clonidine, or prazosin do not.

Adrenergic alpha-Antagonists↗
PubMed1997

Left atrial size in hypertensive men: influence of obesity, race and age. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

OBJECTIVES: We sought to determine the relations of left atrial (LA) size to blood pressure, obesity, race, age and left ventricular (LV) mass in hypertension. BACKGROUND: Although obesity, race and age may influence LV mass, their effects on LA size have not been defined in hypertension. METHODS: Left atrial size was measured in 690 men (58% African-Americans) with mild to moderate hypertension (mean [+/-SD] blood pressure 152 +/- 15/98 +/- 6 mm Hg) and a high prevalence of LV hypertrophy. Effects of LV mass, adiposity, race, age, physical activity, height, weight, sodium excretion, plasma renin activity and heart rate were examined. RESULTS: Left atrial size was greater (p < or = 0.0001) in obese (44.2 +/- 5.7 mm) than in overweight (41.6 +/- 5.9 mm) or normal weight (38.9 +/- 6.2 mm) patients. Left atrial enlargement (> or = 43 mm) was present in 56% of obese patients compared with 42% of overweight and 25% of normal weight hypertensive men. As age increased, white patients had a greater LA size than African-American patients. Although there was no relation between LV mass and LA size in normal weight patients, there was a significant positive relation in obese patients. On multiple regression analysis, obesity was the strongest independent predictor of increased LA size. CONCLUSIONS: Obesity is the strongest predictor of LA size in patients with hypertension and amplifies the relation between LA size and LV mass. Race influences effects of age and hypertension on LA size. Because increased LA size and LV mass (also influenced by obesity) are associated with an adverse outcome, these findings underscore the importance of obesity, race and age with regard to the cardiac effects of hypertension.

Aged↗
PubMed1997

Activator effect of coinjected enhancers on the muscle-specific expression of promoters in zebrafish embryos.

The transient expression of reporter gene constructs in embryos provides a powerful tool to characterise cis-acting transcriptional elements of the genes involved in development. In the present study, we have analysed the expression pattern of several muscle-specific and ubiquitous regulatory sequences in microinjected zebrafish embryos. By using a fast and reproducible coinjection strategy, the mosaic expression of lacZ reporter gene was monitored in wholemount embryos injected with sequences containing putative enhancer elements and a carp myosin heavy chain promoter/lacZ reporter construct. We have found that a 0.9-kb myosin heavy chain (MyHC) proximal promoter containing several putative myogenic regulatory factors (MRF) binding sites is sufficient to restrict lacZ expression to the skeletal muscle fibres of prim-6 stage zebrafish embryos. Expression of a rat-derived foetal myosin light chain enhancer (MyLC) and different fragments of a carp beta-actin regulatory region together with the MyHC promoter were compared by accumulating the type, number and spatial distribution of beta-galactosidase-expressing cells on an expression map. beta-galactosidase activity increased similarly whether the MyLC enhancer was ligated to the promoter/ reporter construct directly or when coinjected as a separate fragment whilst skeletal muscle specificity was retained. The coinjection of two different forms of the beta-actin regulatory elements also showed a marked effect on the MyHC promoter activity. The coinjection of putative enhancers with minimal promoter constructs and subsequent analysis of the transient expression pattern in the developing embryos provides a rapid and simple technique to identify cis acting activator elements of genes expressed in the vertebrate embryo.

Actins↗
PubMed1997

Adherence of Candida albicans to experimental denture soft lining materials.

STATEMENT OF PROBLEM: Colonization of denture soft lining materials by Candida albicans can result in clinical problems. Two experimental silicone soft lining materials have been developed and demonstrate good physical properties. PURPOSE OF STUDY: The aim of this study was to determine the extent of candidal adherence to these materials compared with a commercially available soft lining material and an acrylic resin denture base. MATERIAL AND METHODS: The experimental materials were constructed in a stainless-steel mold, and their surface energies were determined with a dynamic contact angle analyzer. The adherence of three strains of C. albicans was determined with an in vitro assay. In addition, one test strain was used to determine the effect on adherence of precoating the materials with whole saliva. RESULTS: Adhesion to all materials was strain variable, with the lowest adherence recorded for the two experimental materials. Decreased adherence was also apparent after precoating the materials with saliva. Correlation between surface energy of the material and the degree of candidal adhesion was seen for one strain, but no correlation was seen for the other two strains. CONCLUSION: Adherence of C. albicans to the two experimental silicone soft lining materials was significantly less than that for an acrylic resin denture base and a commercially available soft lining material.

Acrylic Resins↗
PubMed1997

An imager's guide to normal neck anatomy.

Neck anatomy is quite complex and presents a daily challenge to the head and neck radiologist. The goal of this article is to help the practicing radiologist understand the basic anatomy of the neck. The major emphasis of this article is on the neck spaces as delimited by the various layers of the deep cervical fascia. A discussion of neck surface anatomy is also included followed by a description of the major blood vessels, nerves, and lymphatics within the extracranial head and neck. The technical aspects of neck imaging are briefly mentioned, and normal CT and MRI images of the neck are provided. Finally, a few normal variants are illustrated.

Humans↗
PubMed1997

Characterisation of the inflammatory cell infiltrate in chronic hyperplastic candidosis of the oral mucosa.

The inflammatory cell infiltrate in biopsy material of chronic hyperplastic candidosis (CHC) from the oral mucosa was characterised using immunocytochemical techniques. Nine specimens were stained for human kappa and lambda immunoglobulin light chains, CD68 antigen (macrophages), lysozyme (macrophages, granulocytes), CD3 antigen (T-lymphocytes), CD20 antigen (B-lymphocytes) and leucocyte common antigen (LCA). In addition, these and a further 13 specimens were also examined for immunoglobulin (Ig)-containing cells (IgA, IgG and IgM). The density of the infiltrate varied considerably between cases; T-lymphocytes were the dominant cell type (53.9%), with fewer B-lymphocytes (8.2%) and macrophages (14.2%). Many Ig-containing cells were seen, and although IgG-containing cells predominated, (60.8%, SD +/- 9.0) there was a high proportion of IgA-containing cells (36.7%, SD +/- 9.1) with few IgM-containing cells (2.5%, SD +/- 3.0). Many neutrophils, together with smaller numbers of T-lymphocytes and macrophages, were seen in the epithelium. It is suggested that mucosal defence to Candida infection involves a cell-mediated reaction in which there is recruitment of macrophages and local production of immunoglobulin with a prominent IgA component.

Adult↗
PubMed1997

Systolic function in hypertensive men with concentric remodeling.

Hypertensive patients with concentric remodeling (relative wall thickness > or = 0.45 and normal left ventricular [LV] mass index) may have poor outcomes. It is unclear whether systolic function abnormalities, shown to be present in some patients with concentric LV hypertrophy (increased LV mass index and relative wall thickness > or = 0.45), are also present in patients with concentric remodeling. To assess LV pump, chamber, and myocardial function in hypertensive men with concentric remodeling, clinical and echocardiographic data of 118 hypertensive men with concentric remodeling were compared with data from 104 hypertensive men with normal relative wall thickness and normal LV mass index. Chamber function was assessed by relating endocardial fractional shortening to end-systolic circumferential stress, myocardial function was assessed by relating midwall fractional shortening to circumferential stress, and pump performance was assessed by stroke volume (Teichholz method). Compared with hypertensive men with normal relative wall thickness, concentric-remodeling patients had lower stroke volume (84 +/- 20 versus 111 +/- 20 mL, P < .001). Endocardial shortening was no different between the two groups (38 +/- 7% versus 40 +/- 7%, P=NS), but midwall shortening was lower in patients with concentric remodeling (20 +/- 3% versus 22 +/- 3%, P < .001), despite lower end-systolic stress (81 +/- 25 versus 117 +/- 37 g/cm2, P < .001). Endocardial and midwall stress-shortening regression plots classified 28% and 42%, respectively, of the concentric remodeling patients below the fifth percentile of hypertensive patients with normal geometry. These data indicate that indexes of chamber and myocardial function are lower than those observed in hypertensive patients with normal geometry. Thus, indices of chamber, myocardial, and pump performance indicate potential abnormalities in systolic function in men with concentric remodeling.

Aged↗
PubMed1997

Jurkat cell proliferative activity is increased by luteinizing hormone-releasing hormone.

Jurkat cells were used to study the immunomodulatory role of luteinizing hormone-releasing hormone (LHRH) in immune cells. The Jurkat cell, a human mature leukemic cell line, phenotypically resembles resting human T lymphocytes and has been widely used to study T cell physiology. The data from this study demonstrate that the Jurkat cell concentration of immunoreactive LHRH was 210 +/- 36 pg/10(6) cells and that of proLHRH was 188 +/- 27 pg/10(6) cells (means +/- S.E.M.). The authenticity of this LHRH immunoreactivity is documented in two ways. First, both Jurkat LHRH and proLHRH immunoreactivity demonstrate dilutional parallelism with hypothalamic LHRH and proLHRH. Second, Jurkat lysates show LHRH bioactivity by releasing luteinizing hormone from rat anterior pituitary cells in culture. The presence of substantial amounts of LHRH in medium in which Jurkat cells were cultured for 72 h indicated that LHRH can be released from the cells. Using specific primers to exons 2 and 4 of the LHRH gene, we have found that Jurkat cells (like human T cells) express LHRH mRNA. The LHRH agonist, des-Gly10,D-Trp6-LHRH ethylamide, significantly increases the proliferative activity of Jurkat cells, as assessed by tritiated thymidine incorporation, from 15980 +/- 1491 c.p.m. in control to 28934 +/- 3395, 30457 +/- 3861 (P = 0.05 vs control) or 35299 +/- 5586 c.p.m. (P < 0.01 vs control) with 10(-11), 10(-9) or 10(-7) M agonist respectively. LHRH antagonist, [D-pGlu1,D-Phe2,D-Trp3,6]-LHRH, at a concentration of 10(-8) M decreases Jurkat cell proliferative activity form 17145 +/- 526 c.p.m. in control medium to 10653 +/- 1323 c.p.m. (P = 0.05). Co-incubation with the LHRH antagonist completely inhibits the proliferative stimulation induced by the LHRH agonist. Furthermore, applying monoclonal LHRH antibody to Jurkat cells inhibits the cell proliferative activity assessed by tritiated thymidine incorporation from 19900 +/- 2675 c.p.m. in control to 15680 +/- 2254, 15792 +/- 1854 and 9700 +/- 908 c.p.m. in media with 1:40, 1:20 and 1:10 dilution of purified antibody respectively (P < 0.01, 1:10 dilution compared with control). In addition, the cAMP level in LHRH-stimulated Jurkat cells is decreased to 74, 27 and 57% of control levels after 15, 30 and 45 min respectively of exposure to 10(-7) M LHRH agonist. In summary, Jurkat cells produce, process and release immunoreactive and bioactive LHRH, as do normal human T cells. Endogenous and exogenous LHRH increase Jurkat cell proliferative activity, and cAMP may be involved in LHRH-induced Jurkat cell proliferation. The Jurkat cell may be a useful model with which to study the role of LHRH in human T cell function.

Animals↗
PubMed1997

FDG PET in head and neck cancer.

In our extensive experience with FDG PET imaging in head and neck cancer, we have found the technique to be of high accuracy but of limited usefulness. This seeming paradox arises from several causes. Competing techniques such as CT, MR imaging, and even clinical examination already have good accuracy. In addition, high-resolution studies such as CT and MR imaging provide information required for treatment planning that is unavailable from FDG PET images. The high cost of FDG PET militates against its use in this setting, in which only a small marginal gain can be expected. In the special problem areas in which FDG PET might be expected to offer unique advantages, such as screening for second primary lesions, searching for unknown primary lesions, or differentiating benign salivary rumors from malignant lesions, the results of FDG PET have been disappointedly poor. Of these special problem areas, only the question of accuracy in finding occult primary lesions appears unresolved and in need of further study. The single application in which FDG PET appears to be advantageous is the posttherapy setting. In this setting, the technique is definitely superior to alternative methods of determining tumor recurrence and differentiating posttherapy sequelae such as radiation necrosis from tumor recurrence. We believe that considerable opportunity remains for further research on the use of FDG PET in head and neck cancer. Other agents such as 11C-methionine for example, might improve the diagnostic accuracy of FDG PET in some of the problem areas that we have identified, such as the early postirradiation period. We currently have such a study under way. Also, because FDG PET offers a unique way to measure tumor metabolism, further investigation of the use of FDG PET tracers to evaluate various biologic parameters such as proliferation rates or tumor hypoxia are needed. Such studies could provide a noninvasive technique to identify which fractionation schemes or combinations of therapy might be useful for individual patients. A final caveat is in order. Although our findings of the usefulness (and lack thereof) of FDG PET in head and neck cancer may be disappointing to many, these results should not be generalized to other applications of FDG PET in oncology. Each tumor type and setting presents its own specific problems, and in some instances FDG PET offers unique advantages over other imaging techniques. A good example is the setting of primary lung cancer, in which FDG PET appears clearly superior to all other methods of pretherapy screening [19-20].

Adult↗
PubMed1997

Imaging of laryngeal cancer.

Modern laryngeal imaging with CT scans or MR images provides critical information about primary tumor extent and the status of the neck nodes. This information is complementary to the physical examination and is essential for treatment planning purposes in all but the smallest laryngeal malignancies. This article focuses on the modalities available for laryngeal cancer imaging, the strengths and weaknesses of those modalities, the imaging anatomy of the larynx, and key imaging features of laryngeal cancer. Also briefly discussed are neck nodes, the post-treatment appearance of the neck, and the problem of tumor recurrence.

Contrast Media↗
PubMed1997

Proteinuria in mild to moderate hypertension: results of the VA cooperative study of six antihypertensive agents and placebo. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

The prevalence and natural history of severe proteinuria in mild to moderate hypertension are not completely defined. We screened 1635 men with a history of hypertension and randomized 1292 with untreated diastolic blood pressure (DBP) 95-109 mmHg to single-drug treatment with either hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem-SR, prazosin, or placebo in a double-blind prospective trial. Twenty-seven of 1635 patients (1.7%) satisfying clinical criteria for primary hypertension were found to have developed proteinuria > 1000 mg/24 hours and were removed from the study. Follow-up data were obtained on 19 of these 27 patients. One patient was found to have focal segmental sclerosis and progressed to end-stage renal disease. Three other patients developed severe (serum creatinine > 3.5 mg/dl) chronic renal failure (one with diabetic nephropathy), one progressed from serum creatinine 1.4 to 2.2 mg/dl, but 14 of the 19 remained with stable serum creatinine < 2.0 mg/dl on follow-up for 6-9 years. Data were available for 1076 of 1155 (93%) treated study patients at end titration, 522/600 (87%) at one year and 322/444 (73%) at two years. There were significant associations for proteinuria with obesity and higher systolic blood pressure. There was a trend toward significant difference in mean 24-hour protein excretion rates at baseline between black (127 mg) and white (139 mg) patients (p = 0.07). There were no statistically significant changes in urinary protein excretion/24 hours between or within the different treatment groups (including placebo). Eighteen patients were removed from the study during the active treatment phase for proteinuria > 1000 mg/24 hours: hydrochlorothiazide 4, placebo 3, diltiazem 3, prazosin 3, atenolol 2, clonidine 2, and captopril 1. We conclude: (1) the prevalence of severe (> 1 g/24 hours) proteinuria in the hypertensive population is significant but does not necessarily imply a poor prognosis; (2) mean 24-hour urinary protein excretion rates did not vary in response to the different classes of antihypertensive drugs; and (3) there was no drug-specific increase in proteinuria detected in this study.

Adult↗