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Biomedical subjects

D B Williams

Publications and source records attributed to D B Williams.

At least 19 recordsLinked to original sources
PubMed2006

The quantitative analysis of thin specimens: a review of progress from the Cliff-Lorimer to the new zeta-factor methods.

A new quantitative thin-film X-ray analysis procedure termed the zeta-factor method is proposed. This new zeta-factor method overcomes the two major limitations of the conventional Cliff-Lorimer method for quantification: (1) use of pure-element rather than multielement, thin-specimen standards and (2) built-in X-ray absorption correction with simultaneous thickness determination. Combined with a universal, standard, thin specimen, a series of zeta-factors covering a significant fraction of the periodic table can be estimated. This zeta-factor estimation can also provide information about both the detector efficiency and the microscope-detector interface system. Light-element analysis can also be performed more easily because of the built-in absorption correction. Additionally, the new zeta-factor method has several advantages over the Cliff-Lorimer ratio method because information on the specimen thickness at the individual analysis points is produced simultaneously with compositions, thus permitting concurrent determination of the spatial resolution and the analytical sensitivity. In this work, details of the zeta-factor method and how it improves on the Cliff-Lorimer approach are demonstrated, along with several applications.

Journal Article↗
PubMed2005

Ventilatory responses of healthy subjects to intravenous combinations of morphine and oxycodone under imposed hypercapnic and hypoxaemic conditions.

AIMS: Previous isobolographic analysis revealed that coadministration of morphine and oxycodone produces synergistic antinociception in laboratory rodents. As both opioids can produce ventilatory depression, this study was designed to determine whether their ventilatory effects were synergistic when coadministered to healthy human subjects. METHODS: A placebo-controlled, randomized, crossover study was performed in 12 male volunteers. Ventilatory responses to hypoxaemia and hypercapnia were determined from 1-h intravenous infusions of saline ('placebo'), 15 mg morphine sulphate (M), 15 mg oxycodone hydrochloride (O), and their combination in the dose ratios of 1:2, 1:1, 2:1. Drug and metabolite concentrations in serial peripheral venous blood samples were measured by high-performance liquid chromatography-MS/MS. RESULTS: 'Placebo' treatment was without significant ventilatory effects. There were no systematic differences between active drug treatments on either the slopes or intercepts of the hypoxaemic and hypercapnia ventilation responses. During drug treatment, the mean minute ventilation at PetCO(2) = 55 mmHg (V(E55)) decreased to 74% of the subjects' before treatment values (95% confidence interval 62, 87), 68% (57, 80), 69% (59, 79), 68% (63, 73), and 61% (52, 69) for M15, M10/O5, M7.5/O7.5, M5/O10 and O15, respectively. Recovery was more prolonged with increasing oxycodone doses, corresponding to its greater potency and lower clearance compared with morphine. CONCLUSIONS: Although adverse ventilatory effects of these drugs were found as expected, no unexpected or disproportionate effects of any of the morphine and oxycodone treatments were found that might impede their use in combination for pain management.

Adolescent↗
PubMed2005

Mediastinal adenopathy: finding the answer with endoscopic ultrasound-guided fine-needle aspiration biopsy.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS FNA) is a relatively new imaging modality that has been reported to be useful for mediastinal nodal staging of lung cancer and for the evaluation of mediastinal adenopathy of unknown cause. However, the technique is not commonly used in Australia. METHODS: A retrospective review of all patients who had mediastinal EUS FNA was undertaken. Of a total of 787 patients who had undergone endoscopic ultrasound (EUS) studies from November 1999 to March 2004, 27 patients were identified to have had mediastinal EUS FNA. Details were recorded including study indication, history of malignancy, source of referral, prior attempts for tissue diagnosis, EUS and EUS FNA findings, complications, surgical pathology if available and clinical outcome after diagnosis. RESULTS: Mediastinal EUS FNA was performed on an outpatient basis and no complications were recorded. Diagnostic material was obtained from all patients with a mean number of three passes. Nodal stations sampled included left paratracheal, subcarinal, aortopulmonary window and inferior mediastinum. Indications for the studies included mediastinal adenopathy of uncertain cause (17), lung cancer staging (7) and gastrointestinal cancer staging (3). EUS FNA confirmed malignancy in 16/27 patients, sarcoidosis in three patients, tuberculosis in one patient and seven patients were deemed to have reactive adenopathy. Primary cytopathological diagnosis of malignancy was determined by EUS FNA in nine patients. CONCLUSIONS: EUS FNA is a safe, efficient and effective modality for mediastinal staging of lung cancer and for the diagnosis of mediastinal adenopathy of uncertain origin. EUS FNA has the potential to significantly impact on patient management, avoiding more invasive procedures as well as unnecessary operations.

Adult↗
PubMed2005

The Australian EEG database.

The Australian EEG Database is a web-based de-identified searchable database of 18,500 EEG records recorded at a regional public hospital over an 11-year period. Patients range in age from a premature infant born at 24 weeks gestation, through to people aged over 90 years. This paper will describe the history of the database, the range of patients represented in the database, and the nature of the text-based and digital data contained in the database. Preliminary results of the first two studies undertaken using the database are presented. Plans for sharing data from the Australian EEG database with researchers are discussed. We anticipate that such data will be useful in not only helping to answer clinical questions but also in the field of mathematical modeling of the EEG.

Adolescent↗
PubMed2003

Progressive increase in incidence and prevalence of multiple sclerosis in Newcastle, Australia: a 35-year study.

The prevalence of multiple sclerosis (MS) in Newcastle, Australia increased significantly between 1961 and 1981 and the incidence of the disease also increased between the decades 1950-1959 and 1971-1981. The present study sought to determine whether there has been a further increase in the frequency of MS in the subsequent 15 years, and to examine the potential factors underlying this change. The incidence, prevalence and clinical profile of multiple sclerosis were therefore re-examined in Newcastle, Australia in 1996 using comparable diagnostic criteria and methods to those employed in studies in the same region in 1961 and 1981. There has been a significant progressive increase in prevalence from 19.6 to 59.1 per 100,000 population and a significant increase in incidence from 1.2 to 2.4 per 100,000 population from 1961 to 1996. The most pronounced increase in prevalence was in females and in the age-group over 60 years, and there was also an increased incidence in females aged 20-29 years. There was little change in the age of disease onset, but duration of disease in females had increased substantially. The significant increase in prevalence is attributed to increased incidence, particularly in females; and to increased survival. Although such trends in prevalence have been observed in the Northern Hemisphere, this is the first such study in the Southern Hemisphere to show a longitudinal increase in prevalence and incidence over a period of this duration.

Adolescent↗
PubMed2001

Relationship between calnexin and BiP in suppressing aggregation and promoting refolding of protein and glycoprotein substrates.

Calnexin (CNX) is a membrane protein of the endoplasmic reticulum that has been defined primarily as a lectin, yet is capable of functioning as a molecular chaperone with non-glycosylated proteins in vitro. Here, we assess the relative contributions of the oligosaccharide- and polypeptide-binding sites of CNX to its in vitro chaperone functions by comparing it with the Hsp70 chaperone of the endoplasmic reticulum, BiP. Both proteins were equally effective in preventing the aggregation of non-glycosylated citrate synthase, indicating that the polypeptide-binding site of CNX is capable of functioning at a level similar to that of Hsp70. However, when confronted with glycoprotein substrates, the lectin site of CNX provided a significant advantage over BiP in suppressing aggregation. CNX also cooperated with BiP and the J domain of Sec63p in the ATP-dependent refolding of glycoprotein and non-glycosylated substrates. The lectin site of CNX was essential for refolding of the glycoprotein. These findings reinforce the function of CNX as a bona fide chaperone and illustrate how its lectin site confers advantages relative to other chaperones when confronted with glycoprotein substrates.

Adenosine Triphosphate↗
PubMed2001

Bone mineral density response to estrogen replacement in frail elderly women: a randomized controlled trial.

CONTEXT: Although hormone replacement therapy (HRT) is an established approach for osteoporosis prevention, little is known about the osteoprotective effects of HRT in frail elderly women. OBJECTIVE: To determine whether HRT increases bone mineral density (BMD) in frail elderly women. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted in a US university-based research center from September 1995 to August 2000. PARTICIPANTS: Sixty-seven women aged 75 years or older with mild-to-moderate physical frailty. INTERVENTION: Participants were randomly assigned to receive conjugated estrogens, 0.625 mg/d, plus trimonthly medroxyprogesterone acetate, 5 mg/d for 13 days (n = 45), or matching placebo (n = 22), for 9 months. MAIN OUTCOME MEASURES: The primary outcome measure was 9-month change in BMD of the lumbar spine and hip, measured by dual-energy x-ray absorptiometry. Secondary outcomes were changes in markers of bone turnover. RESULTS: Based on intention-to-treat analyses, HRT resulted in significantly larger increases in BMD of the lumbar spine than placebo (mean change, 4.3% vs 0.4%; between-group difference, 3.9%; 95% confidence interval [CI], 3.5%-4.3%) and total hip (mean change, 1.7% vs -0.1%; between-group difference, 1.8%; 95% CI, 1.5%-2.1%). Compared with placebo, HRT resulted in significant decreases in serum bone-specific alkaline phosphatase levels (mean change, -24% vs 6%; between-group difference, -30%; 95% CI, -26% to -33%) and urine N-telopeptide levels (mean change, -48% vs 4%; between-group difference, -52%; 95% CI, -47% to -55%). CONCLUSIONS: In physically frail elderly women, 9 months of HRT significantly increased BMD compared with placebo in clinically important skeletal regions. Further studies are needed to determine whether these osteogenic effects of HRT in elderly women are associated with a reduction in osteoporotic fractures.

Absorptiometry, Photon↗
PubMed2001

The lectin chaperone calnexin utilizes polypeptide-based interactions to associate with many of its substrates in vivo.

Calnexin and calreticulin are molecular chaperones of the endoplasmic reticulum that bind to newly synthesized glycoproteins in part through a lectin site specific for monoglucosylated (Glc(1)Man(7-9)GlcNAc(2)) oligosaccharides. In addition to this lectin-oligosaccharide interaction, in vitro studies have demonstrated that calnexin and calreticulin can bind to polypeptide segments of both glycosylated and nonglycosylated proteins. However, the in vivo relevance of this latter interaction has been questioned. We examined whether polypeptide-based interactions occur between calnexin and its substrates in vivo using the glucosidase inhibitor castanospermine or glucosidase-deficient cells to prevent the formation of monoglucosylated oligosaccharides. We show that if care is taken to preserve weak interactions, the block in lectin-oligosaccharide binding leads to the loss of some calnexin-substrate complexes, but many others remain readily detectable. Furthermore, we demonstrate that calnexin is capable of associating in vivo with a substrate that completely lacks Asn-linked oligosaccharides. The binding of calnexin to proteins that lack monoglucosylated oligosaccharides could not be attributed to nonspecific adsorption nor to its inclusion in protein aggregates. We conclude that both lectin-oligosaccharide and polypeptide-based interactions occur between calnexin and diverse proteins in vivo and that the strength of the latter interaction varies substantially between protein substrates.

Animals↗
PubMed2001

Effects of hormone replacement therapy on serum lipids in elderly women. a randomized, placebo-controlled trial.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death among older women. In observational studies, the incidence of CHD has been reduced in postmenopausal women who take hormone replacement therapy (HRT). A low serum level of high-density lipoprotein (HDL) cholesterol is one of the risk factors predictive of death from CHD. OBJECTIVE: To determine the effects of HRT on serum lipid and lipoprotein levels in elderly women. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University research center. PARTICIPANTS: 59 sedentary women 75 years of age or older. INTERVENTION: Participants were assigned to 9 months of oral therapy with placebo or conjugated estrogens, 0.625 mg/d, plus trimonthly medroxyprogesterone acetate, 5 mg/d for 13 days. MEASUREMENTS: Serum lipid and lipoprotein levels. RESULTS: After 9 months of treatment, women in the HRT group compared with women in the placebo group had decreased low-density lipoprotein cholesterol levels (mean change [+/-SD], -0.47 +/- 0.69 mmol/L [-18.2 +/- 26.5 mg/dL] vs. -0.06 +/- 0.32 mmol/L [-2.2 +/- 12.2 mg/dL], respectively; between-group difference, 0.41 mmol/L [95% CI, 0.09 to 0.74 mmol/L], 16 mg/dL [95% CI, 3.5 to 28.5 mg/dL]; P = 0.01) and increased HDL cholesterol levels (mean change, 0.21 +/- 0.27 mmol/L [8.1 +/- 10.5 mg/dL] vs. 0.06 +/- 0.11 mmol/L [2.4 +/- 4.3 mg/dL], respectively; between-group difference, 0.15 mmol/L [CI, 0.008 to 0.29 mmol/L], 5.7 mg/dL [CI, 0.8 to 10.6 mg/dL]; P = 0.02). The observed changes were independent of age at menopause onset, baseline lipid values, body weight, waist circumference, percentage body fat, and peak aerobic power. CONCLUSIONS: In women 75 years of age or older, HRT improved the lipoprotein profile to the extent observed previously in younger postmenopausal women. Further studies are needed to evaluate whether these effects protect against CHD in this population.

Aged↗
PubMed2001

Effects of hormone replacement therapy on cognitive performance in elderly women.

OBJECTIVE: To determine the effects of 9 months of hormone replacement therapy (HRT) on cognitive performance in women aged 75 years and older. METHODS: A 9-month randomized, double-blinded, placebo-controlled parallel trial. Fifty-two elderly postmenopausal women (age range 75-91 years) without known contraindications to HRT or evidence of dementia or depression were enrolled. Participants were randomly assigned in a 1:2 ratio to placebo or conjugated estrogens at 0.625 mg/d plus trimonthly medroxyprogesterone acetate at 5 mg/d for 13 days (HRT). Main outcome measures were change from baseline and rate of change from baseline for the following psychometric tests: Verbal Fluency Test, Weschler Paired Associate Learning and 20 min Delayed Recall, Trailmaking A and B Tests, Cancellation Random Letter and Random Form Tests. RESULTS: At baseline, women in the HRT group reported a younger age of onset of menopause and a higher prevalence of hysterectomy, but otherwise did not differ from women in the placebo group. After 9 months of treatment, there were no significant group differences for any of the cognitive performance measures. The lack of an observed group-by-time difference for all cognitive tests remained after controlling for age of onset of menopause, education, and previous hysterectomy. CONCLUSIONS: Although conclusions are limited by small sample size and the relatively short duration of treatment, results suggest that 9 months of estrogen replacement in combination with trimonthly progestin does not improve cognitive performance in women over 75 years who do not have dementia or depression.

Aged↗
PubMed2001

Reduction of ovarian torsion 1 week after embryo transfer in a patient with bilateral hyperstimulated ovaries.

OBJECTIVE: To report a rare case of unilateral ovarian torsion 1 week after embryo transfer in a patient with bilateral hyperstimulated ovaries. DESIGN: Case report and literature review. SETTING: Reproductive Endocrine division in a university teaching hospital. PATIENT(S): Infertility patients undergoing IVF-ET. INTERVENTION(S): Laparoscopic reduction of adnexa 1 week after ET. MAIN OUTCOME MEASURE(S): Successful preservation of the affected adnexa. RESULT(S): Delivery of 3.324 kg male infant with preservation of the affected ovary. CONCLUSION(S): Untwisting of the affected ovary at laparoscopy without aspiration reduction of cystic masses is appropriate. The outcome of the pregnancy (even very early) in patients with torsion of the adnexa may be favorable after a laparoscopic unwinding of the affected adnexa.

Adnexa Uteri↗
PubMed2001

Successful in vitro fertilization pregnancy after conservative management of endometrial cancer.

OBJECTIVE: To report a successful IVF pregnancy in an infertile couple after conservative treatment of endometrial cancer. DESIGN: Case report and literature review. SETTING: University teaching hospital. PATIENT(S): A 29-year-old infertile white woman. MAIN OUTCOME MEASURE(S): Successful pregnancy after conservative management of endometrial cancer. INTERVENTION(S): Grade 1 endometrial adenocarcinoma diagnosed at hysteroscopy, followed by dilatation and curettage (D&C). On follow-up D&C, pathologic examination was normal after high-dose progesterone therapy. The patient subsequently underwent an IVF cycle with transfer of three blastocysts. RESULT(S): The patient delivered triplets by cesarean section. Laparoscopic-assisted vaginal hysterectomy and bilateral salpingo-oophorectomy was then done. No residual endometrial cancer was evident in the hysterectomy specimen, but a 1.1-cm cystic mixed endometrioid and clear cell-type adenocarcinoma was discovered in the left ovary. The patient is doing well after 3 cycles of chemotherapy; her CA-125 level is normal. The triplets are also doing well. CONCLUSION(S): In carefully chosen situations, deferring surgery in infertile patients with endometrial cancer may be a viable option permitting subsequent successful pregnancy.

Adenocarcinoma↗
PubMed2001

Evidence for distinct conformations of the two alpha 1 subunits in diazepam-bound GABA(A) receptors.

Benzodiazepines allosterically modulate GABA(A) receptors to increase currents induced by submaximal GABA concentrations. Benzodiazepine-induced conformational changes in the transmembrane domain increase the reactivity of cysteines substituted for a subset of residues in the alpha(1) subunit M3 membrane-spanning segment. With the cysteine-substitution mutant alpha(1)F296Cbeta(1)gamma(2) we previously noted that p-chloromercuribenzenesulfonate (pCMBS(-)) modification in the presence of diazepam potentiated subsequent GABA-induced currents. In contrast, pCMBS(-) modification in the presence of GABA caused inhibition of subsequent responses. We now show that in the presence of diazepam, pCMBS(-) only reacts with the engineered cysteine in one of the two alpha subunits; whereas, in the presence of GABA, pCMBS(-) reacts with the cysteine in the other alpha subunit, or with both cysteines. This implies that the two alpha subunits have distinct conformations in the diazepam-bound state. Based on analysis of single channel kinetic data, others have hypothesized that diazepam only alters the GABA affinity of one of the two GABA binding sites. The results presented here provide structural evidence to support the hypothesis that diazepam binding only alters the conformation of one of the two alpha subunits in a GABA(A) receptor and provides new insights into the mechanism of allosteric potentiation by benzodiazepines.

Allosteric Regulation↗
PubMed2001

X-ray spectral simulation and experimental detection of phosphorus segregation to grain boundaries in the presence of molybdenum.

A fundamental limitation of X-ray energy-dispersive (EDS) spectrometry is the detection and quantitative analysis of characteristic X-rays from one element, in the presence of an overlapping peak from another element. This problem is particularly acute when the unambiguous detection of one element is crucial to ensuring the mechanical performance of the material, such as the presence of an embrittling species. This paper addresses the specific problem of defining the conditions of specimen composition and thickness under which phosphorus can be detected in the presence of molybdenum, since the Mo L1 and the P Kalpha elemental peaks are separated by 2eV. This separation is significantly below the resolution limit of X-ray spectrometry in the electron microscope. Simulations of the X-ray spectra from low-alloy steels have been performed via Desk-Top Spectrum Analyzer and compared with experimental measurements on a field-emission gun VG HB 603 dedicated scanning transmission electron microscope.

Electron Probe Microanalysis↗
PubMed2001

Fertility treatment in the forty and older woman.

PURPOSE: To determine the outcomes and logical progression of fertility treatment in women forty years and older using their own oocytes. METHODS: This was a retrospective study in which 401 completed treatment cycles in 152 women aged forty and older were reviewed. RESULTS: Assisted reproductive technology (ART) cycles (n = 58) were reviewed, comprising both in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). Intrauterine insemination (IUI) cycles (n = 343) were reviewed, consisting of 38 unstimulated natural cycle-IUI (NC-IUI), 194 clomiphene citrate-IUI (CC-IUI), and 111 injectable gonadotropins-IUI (INJ-IUI) cycles. The live birth rate of 15.5% for ART cycles was significantly higher than the live birth rate of 3.2% seen for all IUI cycles (p = 0.0007). There were no differences among treatment groups in spontaneous abortion, preterm delivery, or ectopic pregnancy rates. CONCLUSIONS: For women > or = 40 years of age who wish to use their own eggs, ART offers the best chances for conception and delivery.

Adult↗
PubMed2001

Electron energy-loss near-edge structure -- a tool for the investigation of electronic structure on the nanometre scale.

Electron energy-loss near-edge structure (ELNES) is a technique that can be used to measure the electronic structure (i.e. bonding) in materials with subnanometre spatial resolution. This review covers the theoretical principles behind the technique, the experimental procedures necessary to acquire good ELNES spectra, including potential artefacts, and gives examples relevant to materials science.

Journal Article↗
PubMed2001

Frail older women's participation in a trial of hormone replacement therapy: perceived benefits and concerns.

OBJECTIVE: The aim of this study was to identify the reasons that were important to frail older women's decisions to participate or not participate in a clinical trial of hormone replacement therapy (HRT). DESIGN: We conducted a cross-sectional study of a community-based sample of physically frail women > or = 75 years old, who were recruited to participate in an intervention trial of HRT. Participants were randomized 2:1 to either HRT or placebo, respectively. Questionnaires measured participants' reasons for participation and nonparticipants' reasons for declining. Five-point scaled responses to questionnaire items ranged from least to most important or least to most concerned. RESULTS: Sixty-nine women participated (84% white, 16% African American) in the trial. Nonparticipants (n = 41) were older, on average, than participants (83.8+/-4.2 vs. 82.2+/-3.6 years; p = 0.04). Important reasons for participation were reducing risk for Alzheimer's disease and osteoporosis, having more energy, improving self-care ability, and benefiting other women. Fear of cancer from postmenopausal estrogen was the predominant concern of 46% of nonparticipants and 78% of participants (p = 0.08). Recommendation against participation or use of estrogen by a woman's personal physician was the most prevalent additional reason given for nonparticipation. CONCLUSIONS: Disease prevention and improving self-care abilities were most important to participants. Fear of cancer was not a greater concern for nonparticipants than for participants. The role of the physician in older women's decision-making about use of postmenopausal estrogen seems to be important.

Aged↗