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Biomedical subjects

J E Williams

Publications and source records attributed to J E Williams.

At least 73 records · Page 4Linked to original sources

Clozapine attenuates the discriminative stimulus properties of (-)-nicotine.

Rats were trained to discriminate 1.9 mumol/kg (-)-nicotine (0.3 mg/kg) from saline in a standard two-bar operant conditioning paradigm with food reinforcement. The effect of neuronal nicotinic acetylcholine receptor (nAChR) agonists and antagonists were verified, and the participation of dopaminergic receptors subtypes in the expression of the (-)-nicotine cue was investigated with cis-flupentixol (D1-D2 antagonist), haloperidol (D2 antagonist) and clozapine (D4 antagonist). The stereoselectivity of the behavioral response was indicated by the 10-fold less sensitivity to (+)-nicotine in (-)-nicotine-trained rats. (+/-)-Anabasine and (-)-cytisine exhibited partial agonist profiles at the 1.9 mumol/kg dose while (-)-lobeline was devoid of any effect in doses up to 19 mumol/kg. (-)-Lobeline did not show antagonist properties in this paradigm. The nicotinic channel blockers mecamylamine, chlorisondamine and hexamethonium were inactive on their own but mecamylamine and chlorisondamine were able to block the effect of (-)-nicotine. Clozapine attenuated the (-)-nicotine cue while cis-flupentixol and haloperidol were ineffective. Similar doses of cis-flupentixol significantly blocked the locomotor stimulant effect of (-)-nicotine in rats indicating that blockade of dopaminergic receptors was achieved at the doses used in the drug discrimination studies. These data suggest that the discriminative stimulus properties of (-)-nicotine are mediated through neuronal nAChRs and involves the activation of dopaminergic receptors of the D4 subtype.

Alkaloids↗

The implementation of a quality management system in a department of diagnostic radiology.

The quality management systems of the Departments of Diagnostic Radiology of St George's Hospital, London, and Bristol Royal Infirmary (BRI) have been certified with the British Standard 5750. These were the first clinical departments in the UK to be certified to this internationally recognized quality assurance (QA) standard. Quality is a much used term; in this context it is defined as 'fitness for purpose', and quality assurance is the mechanism by which quality is achieved. The paper describes the features of the quality system which have been implemented at St George's Hospital, and how a management concept for manufacturing industries has been adapted successfully to a National Health Service Department. The paper also demonstrates how the quality system has led to the setting and achieving of departmental objectives.

England↗

Abomasal casein infusion enhances the mitogenic activity of serum from protein-restricted steers.

Holstein steers fed protein-restricted diets were used to evaluate protein realimentation and site of serum collection on the ability of calf serum to affect proliferation, protein synthesis and degradation in L6 myoblast cell culture bioassay. In Experiment 1, five steers (average weight 227 kg) received continuous abomasal infusion of 4 L of water or casein (50% of basal dietary nitrogen intake) in a switchback design. Serum was collected 2 d before and after 1, 3, 5, 7 and 9 d of infusion. Abomasal casein infusion increased serum mitogenic activity, nitrogen retention (119%) and total post-ruminal amino acid flow (78%). In Experiment 2, serum was collected from the jugular and femoral veins and the carotid artery before and after 7 d of abomasal casein infusion. Serum from calves abomasally infused with casein increased myoblast proliferation (jugular > femoral > carotid) and protein synthesis and decreased protein degradation in cultured myotubes. The addition of test calf serum inhibited the mitogenic activity of control calf serum. Results suggest that post-ruminal amino acid flow and site of serum collection alter the ability of serum to influence cell culture bioassays.

Amino Acids↗

Continence in patients with spina bifida: long term results.

One hundred and forty four questionnaires relating to bladder and bowel control were sent to a random selection of patients with spina bifida throughout the United Kingdom. One hundred and seventeen questionnaires were returned, of which 109 were usable. Twenty eight out of 109 responders had undergone some form of urinary diversion, of whom 20 (71%) were reliably dry. The remaining 81 responders emptied their bladders by a variety of techniques including normal voiding, straining, expression, clean intermittent catheterisation, indwelling catheters, or they dribbled urine continuously. Only 31 (38%) of this group were reliably dry. Ninety four of 109 (86%) responders regularly sat on the toilet to evacuate their bowels and most used some aid such as manual evacuation, laxatives, suppositories, or enemas. Fifty five of 104 (53%) responders soiled regularly, 31 (56%) of whom were also wet. Forty seven per cent of dry patients (24/51) were faecally incontinent. Only 25 of 104 (24%) patients responding to all questions were reliably clean and dry.

Adolescent↗

Development of pulmonary infection in mice inoculated with Blastomyces dermatitidis conidia.

Intratracheal injection of Balb/cByJ mice with 10(4) Blastomyces dermatitidis conida produces chronic pulmonary and disseminated blastomycosis characterized by pyogranulomatous inflammation. To study the evolution of the pulmonary infection, mice were killed at varying intervals after inoculation, their lungs cultured and examined histologically. Nodular intraalveolar infiltrates of macrophages (M phi) were seen on Day 1 with occasional admixed polymorphonuclear leukocytes (PMN). Phagocytized yeast forms within M phi were evident by Day 5. By Day 28 pyogranulomas, which developed first as central microabscesses associated with a peripheral zone of M phi and giant cells containing internalized yeast, were a prominent feature of the infection. Lymphocytic and plasmacytic infiltrates, accumulating next to granulomas, formed the major peripheral component of the granuloma by Day 35. Formation of pyogranulomas was coincident with the host's failure to contain fungal growth measured by the sharp rise in colony-forming units recovered from lungs. Antibody against B. dermatitidis was first detected at Day 35 by enzyme immunoassay, but not until Day 63 by double immunodiffusion. During the 4 wk after inoculation, pulmonary lavage fluid contained > 90% M phi and < 3% PMN. On day 28, PMN rose to 17%, reaching 40% on Day 42. These data contribute to our knowledge of this model and help form the basis for investigations into the roles of fungal pathogenic and host defense mechanisms in blastomycosis.

Animals↗

Effect of injectate temperature and thermistor position on reproducibility of thermodilution cardiac output determinations.

STUDY OBJECTIVE: The purpose of this study was to evaluate the effect of thermistor position with varying injectate temperatures on the reproducibility of thermodilution cardiac output determination. The key hypothesis to be tested was that the positioning of the proximal thermistor at the right atrial port would improve the reproducibility of thermodilution cardiac output determination, independent of injectate temperature. DESIGN: Prospective randomized trial. SETTING: The study was performed in the cardiac catheterization laboratory of the West Haven Veterans Affairs Medical Center. PARTICIPANTS: Twenty consecutive patients undergoing right and left heart catheterizations were enrolled in the study. INTERVENTIONS: Each patient underwent triplicate determination of thermodilution cardiac output measurements under four experimental conditions: (1) ambient or room temperature injectate using an external thermistor in the injectate reservoir; (2) iced injectate using an external thermistor; (3) room temperature injectate using an internal right atrium (RA) thermistor; and (4) iced injectate using an RA thermistor. Reproducibility was assessed by the coefficient of variation (CV) and standard error of the mean percent (SEM%), of the triplicate measurements. MEASUREMENTS AND RESULTS: Using an internal RA thermistor improved the reproducibility of cardiac output determinations independent of injectate temperature. Using room temperature injectate, the CV was 12.8 percent using an external thermistor and 7.9 percent using an internal RA thermistor (p < 0.05). Using iced injectate, the CV was 10.2 percent using an external thermistor and 5.5 percent using an internal RA thermistor (p < 0.05). CONCLUSIONS: Reproducibility of thermodilution cardiac output determinations is improved when injectate temperature is measured internally, at the RA, as opposed to externally in the reservoir. This has clinical implications for determining significant changes in serial cardiac output determinations.

Analysis of Variance↗

Survey of dental implant practice.

Research advances in oral implantology have led to the development of several implant systems and to an increasing utilization of oral implants by dental practitioners. The purpose of this study was to conduct a survey of dental practitioners using implants in their practices, in order to determine their educational qualifications, to profile their practice in implants, and to evaluate the outcomes of implant therapy. The typical general practitioner in this study received dental implant training mainly from continuing education courses sponsored by a dentist experienced in implantology, spent 12 months or more in receiving formal instruction/training in implant dentistry, practiced state-of-the-art dental implantology, provided both surgical and restorative phases, used an endosseous implant system most of the time, and presented 5- and 10-year success rates of more than 90% for dental implant therapy. No clinically significant correlations were found between the 5- and 10-year success rates and the nature of the dental implant training, the amount of time spent for instruction and training in implant dentistry, or the type of dental implant system used.

Adult↗

Randomized controlled trial of the effect of the Royal College of Radiologists' guidelines on general practitioners' referrals for radiographic examination.

BACKGROUND: The Royal College of Radiologists' guidelines aim to encourage more appropriate use of diagnostic radiology and so reduce the use of clinically unhelpful x-ray examinations. AIM: The object of this study was to conduct a randomized controlled trial of the introduction of the guidelines into general practice. METHOD: A total of 62 practices (170 general practitioners) referring patients to St George's Hospital, London for diagnostic radiology were randomly allocated into two groups. Guidelines were sent to the 30 practices in the intervention group. Radiological referral patterns were compared in both groups before and after the introduction of guidelines. RESULTS: Practices which had received guidelines requested significantly fewer examinations of the spine, and made a significantly higher proportion of requests which conformed to the guidelines compared with practices which had not received the guidelines. There were no significant differences in the proportion of forms giving physical findings or in the proportion of positive findings at radiology. CONCLUSION: Introduction of guidelines can influence general practitioners' radiological referrals in the short term. Wider use of guidelines might help to reduce unnecessary irradiation of patients.

Adolescent↗

Cranial computed tomography of elderly patients: an evaluation of its use in acute neurological presentations.

We assessed the use of cranial computed tomography (CT) in elderly patients with acute neurological deficit and its influence on patient management. Clinical notes from 100 consecutive CT referrals from geriatric admissions presenting with acute neurological deficit were reviewed and categorized according to clinical presentation. CT results and subsequent therapy were recorded. Twenty of the patients had treatable lesions (in 6 out of 14 patients with signs atypical of stroke and 7 out of 19 patients with acute confusion). These two groups contained 68% of all treatable lesions found. Forty-four scans yielded no new diagnostic information; these included all scans for transient ischaemic attacks and for progression of stroke. The remaining scans yielded information regarding pathology but did not alter patient management. CT is a valuable first-line investigation in elderly patients presenting with signs atypical of stroke and unexplained confusion but may be less useful in patients with other presentations.

Acute Disease↗

Marrow B-cell precursors are increased in lymphomas or systemic diseases associated with B-cell dysfunction.

Marrow regeneration is known to be associated with an increase in immature B cells, including CD10+ cells. A similar phenotype has been seen in some children with unusual cytopenias. This article describes 21 adult patients not recovering from chemotherapy, who had increased CD10+ cells in their marrows. These cells had the relatively uniform scatter properties of small lymphocytes by flow cytometry, and by multiparameter analysis were found to have a distinct phenotype in that they were CD19+, lacked surface immunoglobulin, and heterogeneity expressed CD20. In two of three patients tested, some but not all of these early B cells were TdT+. CD10+ cells accounted for 10-76% of total mononuclear cells. All 21 patients had some systemic illness. Thirteen patients had a diagnosis of lymphoma (three Hodgkin's, ten non-Hodgkin's); all ten of the latter were extranodal and seven of seven phenotyped cases were B-cell lymphomas. Seven patients had autoimmune disease (one also had lymphoma) and one had the acquired immunodeficiency syndrome with mycobacterial infection of the marrow. One patient with a history of a "viral illness" had a lymph node showing atypical lymphoid hyperplasia with progressive transformation of germinal centers. Examination of marrow core biopsies in these patients showed a proliferation of small lymphocytes ranging from a barely perceptible diffuse increase to numerous lymphoid aggregates. The extensive lymphocytosis seen in two marrows suggested a diagnosis of lymphoma on morphologic grounds alone, but neither these patients nor any others had B-cell clonal excess. The presence of this phenotype suggests nonspecific stimulation of marrow B-cell precursors associated with systemic B-cell activation in either an immunologic or neoplastic disorder. Presence of this unusual phenotype does not imply involvement of marrow by B-cell neoplasia.

Acquired Immunodeficiency Syndrome↗

Effect of lung volume on lung resistance and elastance in awake subjects measured during sinusoidal forcing.

BACKGROUND: Although lung volume may be changed by certain procedures during anesthesia and mechanical ventilation, dependence of the dynamic mechanical properties of the lungs on lung volume are not clear. Based on studies in dogs, the authors hypothesized that changes in lung mechanics caused by anesthesia in healthy humans could be accounted for by immediate changes in lung volume and that lung resistance will not be decreased by positive end-expiratory airway pressure if tidal volume and respiratory frequency are in the normal ranges. METHODS: Lung resistance and dynamic lung elastance were measured in six healthy, relaxed, seated subjects during sinusoidal volume oscillations at the mouth (5 mL/kg; 0.4 Hz) delivered at mean airway pressure from -9 to +25 cmH2O. Changes in lung volume from functional residual capacity were measured with inductance plethysmographic belts. RESULTS: Decreases in mean mean airway pressure that caused decreases in lung volume from functional residual capacity comparable to those typically observed during anesthesia were associated with significant increases in both dynamic lung elastance and lung resistance. Increases in mean mean airway pressure that caused increases in lung volume from functional residual capacity did not increase lung resistance and increased dynamic lung elastance only above about 15 cmH2O. CONCLUSIONS: Increases in dynamic lung elastance and lung resistance with anesthesia can be explained by the accompanying, acute decreases in lung volume, although other factors may be involved. Increasing lung volume by increasing mean airway pressure with positive end-expiratory pressure will decrease lung resistance only if the original lung volume is low compared to awake, seated functional residual capacity.

Adult↗

Plasma growth hormone, insulin-like growth factor, insulin, and thyroid hormone association with body protein and fat accretion in steers undergoing compensatory gain after dietary energy restriction.

Eighteen Chianina crossbred steers were used to examine the interrelationship between hormonal status and empty body protein (EBPRT) and fat (EBFAT) accretion during an 88-d controlled realimentation (REAL; DMI was adjusted weekly on an individual BW basis) period. Body composition was determined by monitoring endogenous whole-body 40[K]. At the end of restriction (REST) and on d 31 and 59 of REAL blood samples were taken and analyzed for concentrations of growth hormone (GH), IGF-I, IGF-II, insulin (INS), thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3), nonesterified fatty acids (NEFA), glucose, and urea nitrogen. Depositions of EBPRT and EBFAT were decreased (P < .001) in REST (92 d) animals compared with nonrestricted (NR) controls. During REST, plasma levels of glucose, IGF-I, INS, T4, T3, and rT3 were decreased (P < .05); plasma urea nitrogen (PUN), NEFA, and GH levels were increased (P < .05), and IGF-II concentrations were similar between REST and NR steers. A transient compensatory response in BW gain and protein deposition occurred in repleted steers between d 35 and 62 of REAL. During this period, PUN levels markedly declined (P < .01) in REAL steers and glucose concentration increased (P < .01) to levels similar to those in NR controls. This response prevailed even though apparent digestible nutrients were decreased in repleted animals. During energy repletion, plasma levels of T4, T3, rT3, IGF-I, and INS were positively, and of GH was negatively, correlated with EBPRT and EBFAT gain in repleted animals. Unlike IGF-I, IGF-II was not correlated with compensatory body growth. These results suggest that compensating steers are more metabolically efficient; rapid body tissue gain occurs during a period of reduced nutrient digestibility. Additionally, plasma levels of IGF-I, GH, INS, and thyroid hormones, but not of IGF-II, are markedly affected by alteration of energy intake and are highly correlated with empty body gain and protein deposition in compensating late-maturing steers.

Adipose Tissue↗

Supplemental protein influences on carbohydrate degradation and bacterial 16S ribosomal ribonucleic acid.

This research examined the mechanism by which soybean protein stimulates growth of mixed ruminal anaerobes and degrades structural polysaccharides in vitro. Soybean meal, isolated soy protein, or branched-chain VFA was added to orchardgrass hay substrate in Experiment 1. Cell-wall degradation increased 14.5% over that of the control by protein addition. Protein addition resulted in 1.3- to 1.5-fold increases in bacterial growth. Hybridization with a 16S probe specific for Fibrobacter succinogenes indicated that protein addition did not influence the proportion of this species. For in vitro Experiment 2, optimal protein for cell-wall degradation was 2 g/L in cultures containing tall fescue hay. To determine whether protein stimulated microbial colonization of plant cell wall (Experiment 3), orchardgrass hay was placed in 14-L fermentors; treatments were control, NH3 N (2 g of N/L), or isolated soy protein (2 g of N/L). Addition of protein and NH3 N increased the extent of cell-wall disappearance 9.7% above control. Protein and ammonia improved cell-wall digestion, but protein had the greatest stimulatory effect on prokaryote growth with no preferential effect of F. succinogenes.

Ammonia↗

Surgical relief of snoring due to palatal flutter: a preliminary report.

We describe our experience in the surgical treatment of 32 patients with severe snoring. In the first 16 patients we used the standard surgical procedure of uvulopalatopharyngoplasty (UPP) but found this unsatisfactory because of its radical nature, complications and uncertain outcome. We therefore investigated the mechanics of snoring in the laboratory as a help in devising a more effective operation. These studies have shown that there are several methods by which snoring can be generated but that palatal flutter is probably the most important. The dominant parameters in the generation of flutter of the palate are its length and stiffness. Any removal of tissue to shorten the palate as in UPP inevitably risks impairing its function, so we chose the stiffening alternative. Using the laser, a central longitudinal strip of mucosa was removed from the surface of the soft palate which healed by fibrosis, producing the required stiffening. The early results of this new procedure show that snoring has been eliminated or greatly reduced in 14 of 16 patients and that apart from local pain there have been no complications.

Adult↗

The practice of complete denture prosthodontics by selected dental graduates.

Graduates of a dental school in the southeastern United States were surveyed for the procedures they used in practicing complete denture prosthodontics. Of the 530 graduates representing 15 graduating classes, 80% returned the questionnaires. Most respondents (94.8%) made complete dentures, but only 3.5% devoted more than 20% of their practice time to this phase of prosthodontics. In practice, the average graduate performed approximately one half of the techniques that had been judged academically to be clinically essential. Compliance decreased proportionately with the number of years in practice. Factors affecting compliance include the influence of peer practitioners and continuing education courses. The content of the predoctoral curriculum needs to be reviewed for its relevancy to continuing education and to dental practice.

Centric Relation↗

Changes in concentration of adenosine triphosphate and adenosine diphosphate in individual preimplantation sheep embryos.

Concentrations of ATP and ADP were measured in 156 sheep embryos by means of an ultramicrofluorescence assay. Stages of preimplantation development measured included unfertilized oocytes through blastocyst-stage embryos. ATP concentrations remained constant through the 8-cell stage; then ATP decreased significantly (p < 0.025) at the morula stage and remained low through the blastocyst stage. ADP concentrations did not change throughout the embryonic stages measured. Decreased levels of ATP with constant levels of ADP caused the ATP:ADP ratio to decrease significantly (p < 0.025) between the 8-cell and morula stages. We suggest that the increase in glucose uptake by sheep embryos observed at the morula stage of development may be due, in part, to a decrease in the ATP:ADP ratio.

Adenosine Diphosphate↗