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Biomedical subjects

B Williams

Publications and source records attributed to B Williams.

At least 19 recordsLinked to original sources
PubMed1992

Quantification of beta A4 protein deposition in the medial temporal lobe: a comparison of Alzheimer's disease and senile dementia of the Lewy body type.

The distribution of beta-amyloid protein (beta A4) was examined in the medial temporal lobes from cases of Alzheimer's disease (AD) (n = 13), senile dementia of Lewy body type (SDLT) (n = 12) and age matched controls (n = 9). Using a previously described image analysis technique the extent of beta A4 pathology was determined in ten distinct anatomical sites within the medial temporal lobe. AD and SDLT cases contained very similar amounts of beta A4 in the areas sampled and both contained significantly more beta A4 than the age matched controls, particularly in the dentate and parahippocampal gyri. The similarity of the beta A4 load in the two conditions is in contrast to reported differences in the number of neurofibrillary tangles which can be observed. It is suggested that AD and SDLT represent a spectrum of pathology which centres around the aberrant processing of the beta A4 precursor protein.

Aged↗
PubMed1992

Evaluation of nurse triage in a British accident and emergency department.

OBJECTIVE: To compare formal nurse triage with an informal prioritisation process for waiting times and patient satisfaction. SETTING: Accident and emergency department of a district general hospital in the midlands in 1990. DESIGN: Patients attending between 8:00 am and 9:00 pm over six weeks were grouped for analysis according to whether triage was operating at time of presentation and by their degree of urgency as assessed retrospectively by an accident and emergency consultant. PATIENTS: 5954 patients presenting over six weeks. MAIN OUTCOME MEASURES: Time waited between first attendance in the department and obtaining medical attention, and patient satisfaction measured by questionnaire. RESULTS: Complete data on waiting time were collected on 5037 patients (85%). Only 1213 of the 2515 (48%) patients presenting during the triage period were seen by a triage nurse. Patients in the triage group waited longer than those in the no triage group in all four retrospective priority categories, though differences were significant for only the two most urgent categories (difference in median waiting time 10.5 (95% confidence interval 3.5 to 14) min for category 1 and 8.5 (3 to 12) min for category 2). Responses to the patient satisfaction questionnaire were similar in the two groups except for the question relating to anxiety relating to pain. CONCLUSIONS: This study fails to show the benefits claimed for formal nurse triage. Nurse triage may impose additional delay for patient treatment, particularly among patients needing the most urgent attention.

Adolescent↗
PubMed1992

Demonstration of processing and recycling of biologically active V1 vasopressin receptors in vascular smooth muscle.

The present study examines the binding and postbinding cellular processing and recycling of the V1 arginine vasopressin (AVP) receptor in cultured vascular smooth muscle cells (VSMCs). The surface binding of AVP to VSMCs was temperature dependent and reached equilibrium within 60 min at 4 degrees C. Displacement studies with unlabeled AVP or a specific V1 AVP antagonist revealed a single class of V1 receptors (Bmax, 1.99 pmol [corrected] per mg of protein; Kd, 2.15 nM). Incubation of VSMCs with unlabeled 10 nM AVP to promote receptor internalization resulted in a time- and temperature-dependent loss of AVP surface binding. At 37 degrees C, maximum loss of binding sites (65%) occurred within 20 min. Recovery of AVP binding occurred rapidly (t1/2, 15-20 min at room temperature) and was uninfluenced by inhibiting protein synthesis with cycloheximide. Pretreating VSMCs with chloroquine prevented AVP receptor recycling, indicating that the AVP-receptor complex requires endosomal processing. The biological competence of the recycled AVP receptor was shown by AVP-induced Ca2+ uptake. The results of these studies therefore indicate that, after surface binding, the AVP-receptor complex internalizes and dissociates in an endosomal compartment. It is demonstrated that in VSMCs biologically active V1 AVP receptors recycle back to the cell surface, thus attenuating the loss of AVP surface binding sites.

Animals↗
PubMed1992

Piloting an evaluation of triage.

This paper takes a broad view of the work involved in pilot studies of evaluation research. Drawing on their experience of preparation for a field experiment in a British Accident and Emergency department, which was to evaluate the effectiveness of a nurse triage system, the authors stress the importance of careful observation of the system to be studied, in the environment in which it is to be studied. In addition, the usual evaluations of research instruments which comprise formal pilot studies are included.

Emergency Nursing↗
PubMed1992

Comparison of four different methods of evaluation on axially corrected tomograms of the condyle/fossa relationship.

One hundred temporomandibular joints of 50 dry skulls were used to determine whether there was a statistically significantly difference among four different techniques that were employed to assess the condyle/fossa relationship on axially corrected tomograms. A two-way analysis of variance was performed and the results indicated that: (1) a highly significant difference in the condyle/fossa relationship existed (p = 0.002) among the various skulls and (2) no significant difference existed between the four techniques employed to assess the condyle/fossa relationship (p = 1).

Analysis of Variance↗
PubMed1992

Rigid internal fixation and the effects on the temporomandibular joint and masticatory system: a prospective study.

A prospective study of 22 patients who underwent a bilateral sagittal osteotomy to advance the mandible and subsequent rigid internal fixation, were examined for signs and symptoms of temporomandibular joint (TMJ) pain and masticatory dysfunction. A modified Helkimo index was used to analyze the anamnestic, clinical, and occlusal data. In addition, 12 of the cases chosen at random were mounted on a semiadjustable (SAM2) articulator and analyzed with the mandibular position indicator (MPI) to determine the amount and the direction of condylar displacement postoperatively. Anamnestic dysfunction decreased because of a reported decrease in muscular pain, joint noise, headache frequency, and parafunctional habits postoperatively. Clinical dysfunction remained unchanged, with a decrease in muscular soreness but with an increased incidence of joint clicking of 7%. The increased incidence of temporomandibular joint pain postoperatively was 4%. Increase in clinical dysfunction was most often seen in women and older patients. Occlusal dysfunction decreased, with the majority of interferences remaining after surgery as a result of insufficient lingual crown torque of the maxillary buccal segments. Occlusion is thought to have played only a minor role in temporomandibular joint and masticatory dysfunction. Reduction in range of motion was 10%, indicating the added benefit of early mobilization with rigid internal fixation procedures. The MPI study found the condyles inferiorly or inferoposteriorly displaced less than 1 mm from their preoperative position. These findings suggest that rigid internal fixation had no adverse effects on the temporomandibular and masticatory system. The variable responses and results can be attributed, at least in part, to the heterogenous population of patients studied and the variations in surgical techniques employed.

Adolescent↗
PubMed1992

QALYs in mental health: a case study.

The applicability of the Charing Cross health indicator (CH-X) to the field of mental health was investigated in a community setting using descriptive statistics and principal components analysis. The CH-X is based on assessments of (i) distress and (ii) disability. Our results suggest that with respect to quality of life in mental health settings measurements of distress may be of greater importance than disability. In addition, the CH-X may be insensitive to variations in the severity of mental disorder and may primarily reflect physical disability as opposed to social disability. QALYs methodology may require the adoption of a multidimensional measure of health in order to fulfil its proposed role in comparing medical and mental health programmes.

Persons with Disabilities↗
PubMed1992

Single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer.

The single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone have been determined in patients with moderate to severe cancer pain. The mean +/- SD elimination half-life after single-dose administration of intravenous (4.6 mg to 9.1 mg) and oral (9.1 mg) oxycodone was 3.01 +/- 1.37 hours and 3.51 +/- 1.43 hours, respectively. After intravenous administration, the mean +/- SD volume of distribution was 211.9 +/- 186.6 L, and the mean +/- SD total plasma clearance was 48.6 +/- 26.5 L/hr. The mean absolute oral bioavailability of oxycodone was 87%, and the mean +/- SD volume of distribution after oral administration was 249.1 +/- 204.3 L. When administered orally as 10 mg oxycodone hydrochloride every 4 hours, there was no accumulation of oxycodone at steady state and the mean +/- SD steady-state concentration was 34.6 +/- 10.3 micrograms/L. Intravenous oxycodone produced a faster onset of pain relief than oxycodone tablets, but the duration of analgesia was approximately the same (4 hours). However, the incidence of side effects and their severity were significantly higher (p < 0.05) for intravenous oxycodone than for oxycodone tablets. The marked interindividual variation observed in the pharmacokinetics and pharmacodynamics of oxycodone in this study supports the need for individualized dosing regimens.

Administration, Oral↗
PubMed1992

High-temperature short-time heat inactivation of HIV and other viruses in human blood plasma.

An ultra-short-time heating system was used to process blood plasma spiked with various viruses (HIV, vesicular stomatitis virus, encephalomyocarditis virus). Virus reduction and recovery of plasma proteins were measured at various temperatures from 65 to 85 degrees C. Processing at 77 degrees C and 0.006 s resulted in a high level of virus kill, including greater than or equal to 4.4 log10 HIV, while maintaining protein structure and activity essentially intact.

Blood↗
PubMed1992

Syringobulbia: a surgical appraisal.

Syringobulbia is a term which has been clinically applied to brain stem symptoms or signs in patients with syringomyelia. Syringobulbia clefts are found on investigation or at necropsy caused by cutting outwards of the CSF under pressure from the fourth ventricle into the medulla. These should be differentiated from the ascending syringobulbia which may occur from upward impulsive fluid movements in a previously established syringomyelia. Clinical analysis of 54 patients suggests that bulbar features are most often found with neither of the above mechanisms but are due to the effects of pressure differences acting downward upon the hind-brain with consequent distortion of the cerebellum and brainstem, traction on cranial nerves or indentation of the brain-stem by vascular loops. The commonest symptoms in the 54 patients were headache (35), vertigo (27), dysphonia or dysarthria (21), trigeminal paraesthesiae (27), dysphagia (24), diplopia (16), tinnitus (11), palatal palsy (11) and hypoglossal involvement (11). Careful attention to hydrocephalus is advisable before craniovertebral surgery, but the decompression of the hindbrain and the correction of craniospinal pressure dissociation remains the mainstay of surgical treatment. The results of careful surgery are good, 45 of the 54 cases reported improvement. Most of the reported deterioration occurred in a few patients who did conspicuously badly.

Adolescent↗
PubMed1992

Diagnosis of histoplasmosis in patients with the acquired immunodeficiency syndrome by detection of Histoplasma capsulatum polysaccharide antigen in bronchoalveolar lavage fluid.

Diagnosis of histoplasmosis in patients with Acquired Immunodeficiency Syndrome (AIDS) may be established by detection of the organism in lung tissue or bronchoalveolar lavage fluid. In this report we have evaluated the utility of Histoplasma capsulatum polysaccharide antigen (HPA) detection in bronchoalveolar lavage fluid for diagnosis of histoplasmosis. HPA was detected in bronchoalveolar lavage fluid of 19 of 27 cases (70.3%). Of 122 controls with a variety of underlying diseases, HPA was detected in none. Eight of the negative specimens from patients with histoplasmosis were retested after fivefold concentration, and HPA was detected in five. Fivefold concentration of 10 control samples had no effect on HPA level. H. capsulatum was seen by methenamine silver or Giemsa stain in 19 of the 27 (70.3%) and isolated by culture in 24 of 27 (88.9%) cases. Twenty-four of 26 (92.3%) cases had positive cultures from extrapulmonary sites as well. HPA was detected in the urine of 25 (92.6%) and the serum of 23 (88.5%) of the 26 cases. We conclude that HPA detection offers a rapid method for identification of pulmonary histoplasmosis in patients with AIDS and could be a helpful addition to the battery of tests performed on bronchoalveolar lavage fluids in areas where histoplasmosis is endemic.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C.

Early diabetes mellitus is characterized by impaired responses to pressor hormones and pressor receptor downregulation. The present study examined the effect of elevated extracellular glucose concentrations on angiotensin II (AII) and arginine vasopressin (AVP) receptor kinetics in cultured rat vascular smooth muscle cells (VSMC). Scatchard analysis of [3H]AVP and 125I-AII binding to confluent VSMC showed that high glucose concentrations (20 mM) similarly depressed AVP and AII surface receptor Bmax but did not influence receptor Kd. This receptor downregulation was not reproduced by osmotic control media containing either L-glucose or mannitol. Receptor downregulation was maximal at a glucose concentration of 15-20 mM and required 24-48 h for a maximum effect. Normalization of the extracellular glucose concentration allowed complete recovery of AVP and AII binding within 48 h. Receptor downregulation was associated with depressed AVP and AII-stimulated intracellular signaling and cell contraction. High glucose concentrations induced a sustained activation of protein kinase C (PKC) in VSMC, which was prevented by coincubation with H-7. H-7 also markedly attenuated glucose-induced downregulation of AVP and AII receptors on VSMC. This study demonstrates a novel cellular mechanism whereby high extracellular glucose concentrations directly and independently downregulate pressor hormone receptors and their function on vascular tissue via glucose-stimulated PKC activation.

Angiotensin II↗
PubMed1992

Characterization of glucose-induced in situ protein kinase C activity in cultured vascular smooth muscle cells.

The VSMC is an important target for the injurious effects of hyperglycemia in vivo. PKC plays a key role in the regulation of VSMC contraction and growth. This study examines whether elevated extracellular glucose concentrations (10-30 mM [180-540 mg/dl]) activate PKC in cultured rat VSMCs in vitro. A new, rapid, and highly specific assay was used to determine in situ PKC activity in digitonin-permeabilized VSMCs. PKC activity in VSMCs responded rapidly to variations in extracellular glucose concentrations. PKC was activated significantly within 10 min of exposure to D-glucose (20 mM) versus glucose (5 mM). Moreover, with continued exposure to D-glucose (20 mM), PKC activation was sustained for up to 48 h. Reducing D-glucose concentrations to 5 mM restored PKC activity to control values within 1 h. PKC activation was also glucose-concentration dependent. A threshold of only 15 mM (270 mg/dl) was required to significantly and maximally activate PKC in VSMC. PKC was not activated in the presence of osmotic control media that contained either elevated mannitol or L-glucose concentrations. In marked contrast to the sustained PKC activation induced by D-glucose in VSMCs, the normal physiological PKC response to the pressor hormones, AII and AVP, was short-lived and returned to base line within minutes. Sustained PKC activation in the presence of elevated D-glucose concentrations in vitro could disturb the normal physiological regulation of VSMC function and growth and thereby may contribute to the apparent vasotoxicity of hyperglycemia in vivo.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Effect of elevated extracellular glucose concentrations on calcium ion uptake by cultured rat vascular smooth muscle cells.

Blood flow autoregulation is impaired in early diabetes mellitus, predisposing the microvasculature to injury. Blood flow autoregulation is in part a myogenic response that is critically dependent on Ca2+ uptake via voltage-sensitive calcium channels in vascular smooth muscle cells (VSMC). Recent evidence suggests that impairment of blood flow autoregulation in diabetes may be responsive to variations in glycemic control. The present study thus examined the independent effect of an elevated extracellular glucose concentration on Ca2+ uptake by cultured rat VSMC in vitro. A threshold glucose concentration of 15-20 mmol/l markedly and maximally depressed basal and voltage sensitive Ca2+ channel activated (BAY K 8644, 10(-7) M) Ca2+ uptake. This effect was apparent within 3 h of incubating VSMC with the high glucose medium and was maximal after 48 h incubation. Osmotic control media containing either mannitol or L-glucose did not inhibit Ca2+ uptake by VSMC, thus confirming the effect was specific for elevated extracellular glucose concentrations and unrelated to changes in extracellular osmolality. Glucose-induced inhibition of basal and voltage-sensitive transmembrane fluxes of Ca2+ in VSMC may provide a metabolic mechanism for impaired calcium-dependent blood flow autoregulatory responses in early diabetes mellitus.

Animals↗
PubMed1992

The generation of cellular diversity in the cerebral cortex.

We have studied cell lineage in the rat cerebral cortex using retroviral vectors. With this technique, the virus is used to introduce a marker gene into dividing precursor cells such that their fate can be followed. We have studied cell lineage by using this method in the following ways. First, we have labelled germinal cells of the cerebral cortex in vivo during the period of neurogenesis. Second, we have grown cortical precursor cells in dissociated cell culture, and used the viral labelling technique to follow their development in vitro. Both types of study have shown that by the time neurogenesis is under way, the majority of precursor cells are restricted to the production of a single cell type: neurones, astrocytes, or oligodendrocytes. The only exception is a cell we call the N-O cell because it has the ability to generate both neurones and oligodendrocytes. These data suggest that the ventricular zone, the germinal layer of the embryonic cortex, is a mosaic of different precursor cells each with a different restricted potential. However, this restriction of potential of cortical precursor cells does not extend to their ability to contribute to more than one cortical lamina or cytoarchitectonic area. The precursors of both neurones and grey matter astrocytes contribute cells to multiple layers of the cortex. Moreover, in the hippocampal formation, neuronal precursors can contribute cells to more than one hippocampal field.

Aging↗