An overview of CATs development across the U.K.
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Education↗
Biomedical subjects
G Davidson
Publications and source records attributed to G Davidson.
Candoxatril, an orally active neutral endopeptidase inhibitor, raises plasma atrial natriuretic factor and is natriuretic in essential hypertension.
OBJECTIVE: Candoxatril (UK79,300) is an orally available inhibitor of the neutral endopeptidase (E.C.3.4.24.11) which degrades atrial natriuretic factor (ANF). This study was designed to establish initial safety and efficacy data in essential hypertension for this novel class of drug. DESIGN: A prospective, double-blind, placebo-controlled, single-dose comparison of candoxatril with placebo in a crossover manner. Three doses of candoxatril (10, 50 and 200 mg) were used, with four subjects at each dose level. SETTING: The Medical Research Council Blood Pressure Unit, Western Infirmary, Glasgow, UK (a hospital clinical research unit). PATIENTS: Twelve patients with untreated essential hypertension. Diastolic blood pressure was greater than 95 mmHg on three separate occasions before entry to the study. INTERVENTION: Candoxatril or matching placebo was administered orally in the fasting state. Serial measurements of urinary volume and electrolyte excretion were taken (on each hour, urine volume was replaced with an equivalent volume of water by mouth). Blood pressure and heart rate were recorded for 12 h after drug administration and serial blood samples were taken for measurement of plasma ANF and neurohormone concentrations. MAIN OUTCOME MEASURES: Urine volume and electrolyte concentration; blood pressure; heart rate; plasma atrial natriuretic factor. RESULTS: Plasma ANF concentrations rose significantly in all patients within 2 h of candoxatril administration compared with placebo although peak and integrated ANF levels were similar at all three doses. A significant natriuresis was only seen after 200 mg candoxatril, with a greater cumulative urine sodium excretion over 12 h compared with placebo; this was associated with a greater diuresis over 12 h compared with placebo. After a single oral dose of candoxatril, blood pressure and heart rate remained unchanged. CONCLUSIONS: Candoxatril in a single dose caused no adverse effects in essential hypertension. The drug caused a rise in basal ANF levels at all doses, but natriuresis was only seen with the highest dose used. No change in blood pressure was recorded after acute dosing, and the results of chronic studies with this compound are awaited. Oral inhibitors of ANF degradation may have therapeutic potential in cardiovascular disorders.
Administration, Oral↗
A problem with a laryngeal mask airway.
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Adult↗
Lesions of the tunica media in traumatic rupture of vertebral arteries: histologic and biochemical studies.
Discontinuous non-circumferential lesions of tunica media were observed in four cases of traumatic rupture of the vertebral artery. We hypothesize that these lesions were due to mechanical disruption of smooth muscle cells and the liberation of catabolic enzymes with subsequent degradation of the arterial media. To test this hypothesis, healthy vertebral arteries were incubated with crude extracts of bovine smooth muscle cytosol in attempt to reproduce the histological changes of the arterial media in traumatized vertebral arteries. We observed cytosol-induced degradation of tunica media, characterized by pallor of staining with the Masson's Trichrome method, which was due to catabolic enzyme activity that was effectively inhibited by heat inactivation of the cytosol. The cytosol-induced tinctorial changes were similar to the lesions of the tunica media in naturally-occurring cases of traumatic vertebral artery rupture. We conclude that although vertebral arteries can be ruptured by physical distortion alone, associated lesions of the tunica media are due to in situ trauma-associated release of heat-labile catabolic enzymes.
Adult↗
On-site occupational health nursing services: estimating the net savings: Part I.
1. The following question can be successfully answered with a well developed quantitative assessment model: Is more money likely to be saved from the services of an on-site occupational health nursing program than is expended in providing these services? 2. The focus of this evaluation should be restricted to the net cost savings from the direct substitution of on-site for off-site provision of occupational health nursing services by such programs. 3. The evaluation model requires estimates of five separate factors for each occupational health nursing service provided by such programs that directly substitute for its off-site provision.
Health Education↗
On-site occupational health nursing services: estimating the net savings: Part II.
1. A primary management use of this quantitative assessment model is to estimate the overall net cost savings from operating an entire on-site occupational health nursing program. 2. Another management use of this model is to estimate the net cost savings contributed by individual occupational health nursing services included in the on-site program. 3. The exclusive focus of the model on the net cost savings arising from the direct substitution of on-site for off-site occupational health nursing services can be extended with the application of a break even analysis. 4. A sensitivity analysis can be applied to factors of the model to help overcome the effects of substantial uncertainty concerning their estimates.
Cost Savings↗
Ultrastructure of melatonin-responsive cells in the ovine pars tuberalis.
Functional receptors for melatonin have been localized and characterized on the pars tuberalis (PT) of a number of mammalian species, but the cell-type responsive to melatonin is unknown. The ultrastructure of the ovine pars tuberalis has been examined and these findings correlated with the functional response of the gland to melatonin. This study revealed that two secretory cell types predominate in the ovine PT, which differ in the abundance of dense-core granules. The most abundant of the cells are either agranular or very sparsely granulated and represent 90% of the total population, with the remaining 10% being composed of cells with abundant dense-core vesicles. Few follicular cells were observed. This ratio of secretory cell-types persisted in primary culture, with the two types non-separable by Percoll gradient centrifugation. Using forskolin, as a non-specific stimulant of adenylate cyclase, melatonin was shown to inhibit the formation of cyclic AMP by 80-90% in cells both before and after Percoll centrifugation. The results demonstrate that the agranular secretory cells of the ovine pars tuberalis are the melatonin responsive cell-type of this gland.
Animals↗
Low-grade astrocytoma of the tectal region as an unusual cause of knee pain: case report.
A 12-year-old boy was investigated for knee pain and contractures, and was found to have an intraspinal tumor of a lumbar nerve root and a tumor in the tectal region, both low-grade astrocytomas. We postulated that the tectal region astrocytoma metastasized to the lumbar intraspinal region. After surgery, the child underwent focal irradiation to the posterior fossa supplemented by craniospinal irradiation and a boost dose to the region of the lumbar spinal tumor. A low-grade astrocytoma rarely presents as spinal metastasis. This case may represent the first of a primary tectal low-grade astrocytoma manifesting as a symptomatic spinal mass.
Astrocytoma↗
Intracellular signalling in the ovine pars tuberalis: an investigation using aluminium fluoride and melatonin.
The effect of aluminium fluoride (AlF4-) has been studied on inositol phosphate accumulation, calcium mobilization, cyclic AMP production and [2-125I]iodomelatonin binding in ovine pars tuberalis cells. These cells have high-affinity receptors for, and respond to, melatonin through inhibition of forskolin-stimulated adenylate cyclase. In the presence of 10 mM LiCl, AlF4- stimulated the net accumulation of inositol monophosphate and inositol bisphosphate. Consistent with these findings, AlF4- increased intracellular calcium; although this response was attenuated in calcium-depleted medium, indicating that the calcium response comprises both intracellular and extracellular components. Melatonin was ineffective on either basal or AlF4(-)-stimulated turnover of inositol phosphates. In concordance with the inositol phosphate response, melatonin had no effect on either the AlF4(-)-stimulated or the basal calcium levels. AlF4- blocked the increase in cyclic AMP stimulation by 1 microM forskolin, being as effective as melatonin, achieving approximately 90% inhibition. AlF4- also attenuated the binding of [2-125I]iodomelatonin to ovine pars tuberalis membranes by 15%. At the concentration used, these results are consistent with the interpretation that AlF4- activates many G protein-mediated responses, and thus imply that the inhibitory pathway for cyclic AMP predominates over the stimulatory arm, whereas there can only be a stimulatory pathway linked to phosphoinositide metabolism in ovine pars tuberalis cells.
Aluminum↗
First aid training--some questions answered.
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Adult↗
The atriopeptidase inhibitor UK 69,578 increases atrial natriuretic factor and causes a natriuresis in normal humans.
The endopeptidase EC 3.4.24.11 (atriopeptidase) degrades atrial natriuretic factor (ANF). Intravenous administration of UK 69,578 (0.025 to 10.0 mg/kg), a new specific atriopeptidase inhibitor, in 16 normal volunteers produced a two- to three-fold rise in endogenous ANF. Peak levels were reached within 2 h declining to control values by 8 h. The rise in ANF was associated with an increase in urine volume and mean urinary sodium excretion rose from 64.9 mmoles/8 h after placebo to 116.1 mmoles/8 h after 10 mg/kg UK 69,578. Despite the natriuresis, plasma active renin concentration was suppressed for up to 8 h. We conclude that inhibition of the endopeptidase EC 3.4.24.11 in humans elevates endogenous ANF and causes a natriuresis and may offer a novel therapeutic approach to the treatment of hypertension and cardiac failure.
Adult↗
A comparison of calcium pentagastrin and TRH tests in screening for medullary carcinoma of the thyroid in MEN IIA.
Intravenous injections of calcium gluconate and pentagastrin (CPG) or TRH were compared as secretagogues for calcitonin (CT) in screening for medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia type IIA (MEN IIA). Administration of CPG resulted in a prompt increase in plasma CT in all five patients with MTC studied, one of whom had a normal baseline value (peak 412-371,000 ng/l, 636-4847% above basal). TRH produced a rise in plasma CT levels only in MTC patients with elevated basal values; the magnitude of increase was less than that observed with CPG (peak 168-17,200 ng/l, 113-180% above basal). CT levels did not rise above 300 ng/l with either test in four unaffected first-degree relatives of MEN IIA patients, three subjects with sporadic unilateral phaeochromocytomas and five controls with essential hypertension. CPG remains the CT secretagogue of choice in screening for MTC in MEN II A.
Adult↗
Monte Carlo simulation of HIV infection in an intravenous drug user community.
Intravenous drug users are crucial to the understanding and control of human immunodeficiency virus (HIV) transmission. We have developed a population-based simulation of a community of intravenous drug users. This model was implemented using Monte Carlo techniques, which permit great flexibility in creating realistic social structures, to describe the needle-sharing network of drug users. We present the baseline behavior of this model in a generic community and demonstrate the model's utility for assessing public health interventions. Our early results demonstrate the powerful effects of social networks on HIV transmission and the importance of prevalence levels in assessing the effectiveness of interventions in the drug-injecting community.
Equipment Contamination↗
Guanine nucleotides regulate the affinity of melatonin receptors on the ovine pars tuberalis.
The effect of guanine nucleotides and related analogues on the binding of 2-[125I]-melatonin to membranes prepared from ovine pars tuberalis was studied. Dose-dependent inhibition of 2-[125I]-melatonin binding was observed, with an order of potency of GTP gamma S much greater than Gpp(NH)p greater than GTP = GDP. GMP, cyclic GMP and ATP had negligible effects. Analysis of saturable binding revealed that GTP gamma S (1 microM) promoted an apparent reduction in receptor density of about 50%, without a concomitant change in receptor affinity. These results are consistent with a melatonin receptor existing in an equilibrium between high- and low-affinity states, with GTP and related analogues able to cause a shift in the equilibrium in favour of the lower-affinity form. The sensitivity of 2-[125I]-melatonin binding to guanine nucleotides implies the presence of a melatonin receptor on the ovine pars tuberalis, the action of which is mediated via a G protein.
Animals↗
Health insurance and welfare reentry.
This study presents a theoretical model of welfare reentry that examines the importance of private health insurance in determining whether working recipients terminated from Aid to Families with Dependent Children (AFDC) as a result of the Omnibus Budget Reconciliation Act returned to welfare over a two-year period. Our empirical results suggest that the lack of private health insurance is a statistically significant and quantitatively important determinant of welfare reentry. Since the vast majority of the terminated families remained off welfare, however, these results suggest the difficulty of meeting the health needs of the employed uninsured.
Adolescent↗
Allocative efficiency of case managers for the elderly.
This study presents an analysis of the allocative efficiency of case managers for the community-based elderly in an environment in which case management and a range of home and community-based services were available and directly linked to a mandatory preadmission screening program for nursing home applicants. We collected data for a one-year follow-up period on client placement, health and functional status, informal support, and use of health and social services for clients in two urban and two rural counties that participated in the Minnesota Pre-Admission Screening/Alternative Care Grants Program (PAS/ACG). We found that among those receiving ACG-supported services, the relationship between variation in the level of support for home and community-based services and the length of time elderly clients remained in the community suggested that case managers were allocating home and community-based services in a reasonably efficient manner. This finding offers support for using case managers to target services to the elderly.
Activities of Daily Living↗
The occupational first aider--a profile.
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Adult↗
Anti-gliadin antibody specificity for gluten-derived peptides toxic to coeliac patients.
The specificities of serum and intestinal antibodies from coeliac and normal individuals towards gluten-derived peptides, known to be toxic in coeliac disease, has been investigated. Though untreated coeliacs had high serum antibody levels towards gliadin and some gluten-derived peptides, antibody specificities to various toxic gluten-derived peptides were similar to normal patients. Further, no significant binding in any patient group was found to the alpha-gliadin-derived peptides B1342 (Wieser, Belitz & Ashkenazi, 1984) or the 12 amino-acid A-gliadin peptide (Kagnoff, 1985). There appears to be no direct relationship between the toxicities and the antigenic reactivity of gluten-derived peptides. Thus, the intestinal damage in coeliac disease is probably not primarily caused by antibody-dependent mechanisms. The specificities of several monoclonal antibodies which bound to wheat prolamins as well as prolamins from other coeliac-toxic cereals have also been investigated with these toxic gluten-derived peptides, in order to identify possible common epitopes. No monoclonal antibody tested bound the B1342 and 12-amino-acid A-gliadin peptide. However the monoclonal antibodies which were specific for the coeliac-toxic cereal prolamins did show the strongest binding to other coeliac-toxic gluten-derived peptides.
Adult↗