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Biomedical subjects

D Paxton

Publications and source records attributed to D Paxton.

18 recordsLinked to original sources
PubMed2001

An evaluation of community learning disability services for children with a learning disability.

This study outlines the results of a survey carried out with parents of children with a learning disability, general practitioners and community learning disability teams as to the health service needs for this client group. Overall, 40% of parents were very dissatisfied or dissatisfied with the services they received. A number of gaps in service provision were identified. In particular, psychological and behavioural difficulties of children were of major concern to all those involved, but needs in relation to these areas were often unmet or inadequately dealt with. Of greater concern was that some families in the area studied were paying privately for child learning disability clinical psychology services because they had such difficulty in accessing NHS services. Implications for service provision are discussed.

Adolescent↗
PubMed2000

Professional composition of community learning disability teams in Scotland: implications for service provision.

A survey of all trusts in Scotland who provided specialist services to people with learning disabilities was made with a response rate of 100%. An examination was made of the professional composition of the community learning disability teams and the population covered. A disparity was found across Scottish trusts in the professions represented in the community learning disability teams with some professions having no input. Nursing and Clinical Psychology were found to be the two professional groups with largest representation across Scotland and along with Speech and Language Therapy had representation in all of the Teams. A review of some of the factors which have impacted on the role and professional composition of these services is made and the implications discussed.

Community Health Services↗
PubMed1999

Quality here, there and everywhere: the application of a multi-dimensional learning tool to learning disability health services.

The following paper examines the applicability of Maxwell's Multi-dimensional Quality Evaluation model to community learning disability health services. The model defines seven dimensions against which the quality of any given service can be measured: effectiveness, efficiency, economy, equity, access to services, appropriateness and social acceptability. A number of examples in relation to community learning disability services are discussed.

Community Mental Health Services↗
PubMed1997

Intravenous dolasetron mesilate ameliorates postoperative nausea and vomiting.

PURPOSE: To compare the efficacy, safety, and tolerability of dolasetron mesilate with placebo for the treatment of postoperative nausea and vomiting (PONV). METHODS: In a randomized, multicentre, double-blind, placebo-controlled study 337 adult patients undergoing surgery with general anaesthesia received one of four single, doses of dolasetron mesilate iv (12.5, 25, 50, or 100 mg) or placebo. Study medication was administered postoperatively when the patient reported nausea lasting 10 min or when one emetic episode occurred within two hours of the patient's arrival in the recovery room. Efficacy was assessed by the investigators over the 24-hr study period by recording the number and timing of emetic episodes, the severity of nausea, the timing of administration of escape antiemetic medications, and patients' and investigators' satisfaction with antiemetic therapy. RESULTS: The study sample was predominately women, and the surgical procedures were primarily gynaecological. All dolasetron mesilate doses produced higher complete response rates than placebo (P < 0.05). Only approximately one-third of dolasetron patients required escape antiemetic medication compared with more than 50% of patients in the placebo group. Both patient and physician satisfaction with dolasetron treatment was high. The most common adverse event was mild or moderate headache for both placebo-treated patients and dolasetron-treated patients. Clinical laboratory results were unremarkable. CONCLUSION: Single doses of dolasetron mesilate iv, given after the first episode of PONV, were both effective and safe in this adult patient population.

Adolescent↗
PubMed1995

Postoperative emesis following otoplasty in children.

Sixty unpremedicated children aged between 3 and 14 years, scheduled for otoplasty, were randomly divided into one of three groups to receive either ondansetron 0.1 mg.kg-1, droperidol 75 micrograms.kg-1, or placebo at induction of anaesthesia. All patients received a standard general anaesthetic using thiopentone, atracurium and halothane. Opioid analgesia was avoided intra-operatively and infiltration with local anaesthetic was used prior to the start of surgery. Children who received ondansetron were less likely to vomit (15%) than those who received either droperidol (40%) or placebo (60%) (p < 0.01). This group also tolerated oral ingestion of fluids and solids earlier than those who received either droperidol or placebo (p < 0.001). There was no difference between the placebo or droperidol group in the incidence of vomiting or time to ingestion of oral fluids and meals. Three patients in the ondansetron group had a self-terminating nodal rhythm which was not associated with any haemodynamic disturbances. Postoperatively there were no untoward incidents in any of the groups and all patients were discharged home the day after surgery.

Adolescent↗
PubMed1995

Characterisation of angiotensin converting enzyme from different rat vascular beds.

The tissue renin angiotensin system may play a role in cardiovascular pathophysiology. Angiotensin converting enzyme in tissues is now a target for pharmacological inhibition. It is therefore important to determine whether ACE is evenly distributed throughout the vascular tree and whether the enzyme has the same characteristics in different vascular beds. We have thus measured angiotensin converting enzyme density in three functionally different vascular beds with three different methods: the enzyme kinetic assay, a radioligand binding assay and in vitro autoradiography. All three methods demonstrated a significantly higher binding density and activity of ACE in resistance arteries from the mesenteric vascular bed of rats than in microvessels from the brain, or in a conduit artery, the aorta. The dissociation constant (Kd) of the enzyme-radioligand complex was the same in the three functionally different vessel types. Radioligand displacement studies for ACE from plasma and the mesenteric vessels in vitro utilizing a panel of different ACE inhibitors have shown a similar rank order of inhibitory potency suggesting that catalytic sites of ACE were the same in plasma and the mesenteric microvessels. In vivo, the enzyme inhibition in plasma, mesenteric and brain vessels measured by enzyme kinetic and radioligand binding assay were well correlated. There was a similar degree of inhibition between different vessels and tissues (mesenteric vessels, aorta, kidney, left ventricle and coronaries) measured by in vitro autoradiography.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Haemodynamic, renal and hormonal responses to enalkiren in four patients with post-surgical oliguria.

1. The haemodynamic and hormonal responses of four patients with acute post-surgical oliguria (urine output < 0.5 mL/kg per h) were measured in response to the renin inhibitor enalkiren. Enalkiren was infused at 0.01 up to 0.1 mg/kg per h for up to 4 h. 2. Enalkiren infusion was associated with a progressive fall in blood pressure, clinically significant in three of the four patients. Systemic vascular resistance fell in proportion to blood pressure fall. Cardiac output and pulse rate remained unchanged. Effective renal plasma flow rose in all four cases (236 +/- 19 to 327 +/- 38). There was no change in urine flow rate, or urinary sodium excretion. 3. Plasma renin activity (ng angiotensin I/mL per h) fell from 1.9 +/- 0.5 to 0.02 +/- 0.01 (P < 0.04), plasma angiotensin II (pg/mL) fell from 104 +/- 93 to 7.7 +/- 1.5, and plasma aldosterone (ng/dL) fell from 32 +/- 8 to 21 +/- 9 (P = 0.03) at the highest infusion dose. 4. Enalkiren inhibited plasma renin activity with reduced plasma angiotensin II and aldosterone concentrations. This was associated with vasodilation, reduced blood pressure and maintained cardiac output. There was no beneficial effect on renal function in these patients with post-surgical oliguria.

Aldosterone↗
PubMed1992

Characterization of angiotensin converting enzyme in isolated cerebral microvessels from spontaneously hypertensive and normotensive rats.

OBJECTIVE: Abnormalities in the vascular renin-angiotensin system have been hypothesized to contribute to the pathogenesis and complications of hypertension. In animal models of hypertension, there is wide variation in reported vascular angiotensin converting activity, particularly in cerebral microvessels. In this study, we sought to characterize, quantitate and compare cerebral microvessel angiotensin converting enzyme (ACE) in genetically hypertensive rats and normotensive rats. DESIGN: Brain microvascular ACE from 14-week-old spontaneously hypertensive rats (SHR) was measured and compared with ACE from brain microvessels of normotensive Wistar-Kyoto (WKY) controls. METHODS: Isolated cerebral microvascular ACE was measured using two methods, enzyme kinetic assay or radioligand binding assay. RESULTS: In SHR, cerebral microvessel ACE was of similar activity and concentration and had similar ligand binding affinities to WKY rats. Plasma ACE activity was significantly elevated in WKY rats compared with SHR. CONCLUSION: Cerebral microvascular ACE is similar in SHR and WKY rats. Microvascular ACE is unlikely to participate in the pathogenesis or complications of hypertension in this model.

Animals↗
PubMed1992

Two binding sites on angiotensin-converting enzyme: evidence from radioligand binding studies.

Purified angiotensin-converting enzyme (ACE) from rat lung and testis, membrane preparations of ACE from lung, kidney, and testis, and ACE from plasma were used in radioligand binding studies, to seek evidence for two binding sites in ACE of somatic origin, as predicted by molecular biology studies. 125I-Ro 31-8472, a radioiodinated hydroxy derivative of cilazaprilat, and 125I-351A, a radioiodinated p-hydroxybenzamidine analogue of lisinopril, were used as radioligands. Autoradiographic study of renal ACE using 125I-Ro 31-8472 or 125I-351A showed the same distribution of radioligand binding across kidney sections and identical radioligand binding for purified lung and testis ACE by Western blot, confirming that the same protein bound both radioligands. Analysis of displacement of 125I-Ro 31-8472 binding from ACE by ACE inhibitors 351A and lisinopril yielded biphasic curves for pulmonary, renal, and plasma ACE and a monophasic curve for ACE from the testis. Analysis by LIGAND suggested two binding sites in ACE from plasma or somatic sources and one binding site in ACE of testicular origin, as predicted by molecular biology studies. Displacement of 125I-351A binding from lung and testis ACE by Ro 31-8472 and 351A was monophasic. LIGAND analysis revealed interaction with a single class of binding sites on lung and testis ACE, in agreement with previous studies using 125I-351A. Equilibrium dissociation constants (Kd) for the carboxyl-terminal (KdI) and amino-terminal (KdII) binding sites of purified ACE, using 125I-Ro 31-8472, were similar for Ro 31-8472 (lung kdI, 65 +/- 7 pM; KdII, 175 +/- 38 pM) but were clearly different for 351A (lung KdI, 19 +/- 2 pM; KdII, 2771 +/- 489 pM; p less than 0.01). Cell membrane-associated somatic ACE and plasma ACE, which is devoid of a carboxyl-terminal hydrophobic anchor region, had similar absolute values and differences in 351A binding affinities at the two ACE binding sites. Kd in testis was 46 +/- 6 pM for Ro 31-8472 and 16 +/- 3 pM for 351A, corresponding to estimates at the carboxyl-terminal binding site of somatic ACE. The 65-200-fold reduction in 351A binding affinity at the amino binding site may limit the detection of two binding sites on somatic ACE by 125I-351A radioligand binding analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Measurement of angiotensin converting enzyme induction and inhibition using quantitative in vitro autoradiography: tissue selective induction after chronic lisinopril treatment.

Angiotensin converting enzyme (ACE) inhibitors lead to induction of ACE in animals and humans. This complicates the use of ACE enzymatic activity as an index of inhibition in plasma or tissues after chronic administration of ACE inhibitors. We have, therefore, developed a method for ACE measurement by in vitro autoradiography using an 125I-labelled inhibitor to quantitate total ACE and the concentration of free (not inhibited) ACE in tissues after prolonged administration of ACE inhibitors to rats. Measurements made on unprocessed tissue sections reflect residual free ACE activity in the presence of the unlabelled inhibitor. In a parallel series of adjacent sections, the ACE inhibitor is dissociated from the enzyme by reversibly denaturing the enzyme by zinc chelation. This is followed by reconstitution of the active enzyme by zinc ion replacement and measuring total enzyme concentration. This technique permits measurement of the extent of ACE inhibition and induction. This method was evaluated in tissues of rats following chronic oral administration of lisinopril (10 mg/kg per day) for 2 weeks. The pattern of ACE inhibition was similar to that seen in our previous acute studies. However, induction of ACE was found to be organ specific; plasma total ACE increased 1.75-fold and total ACE in the lung increased by 30% compared with untreated animals, but there was no demonstrable change in total ACE concentration in the kidney, adrenal or aorta. Despite this, during chronic treatment with lisinopril, ACE activity in all of these organs was inhibited with low levels of free ACE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1991

Angiotensin-converting enzyme in macro- and microvessels of the rat.

1. Angiotensin-converting enzyme (ACE) was measured in the aorta, cerebral and mesenteric microvessels of Wistar-Kyoto rats using a specific radioligand assay. 2. Ligand binding studies revealed a four-fold increase in concentration of ACE in mesenteric microvessels, compared with aorta or brain microvessels. The dissociation constant (Kd) was similar in all tissues. 3. The effects of oral administration of the ACE inhibitor S9650 on vascular ACE in vivo were measured. 4. S9650 produced a dose-dependent inhibition of vascular ACE from brain and mesenteric microvessels.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

High salt diet ameliorates effects of angiotensin converting enzyme inhibition in spontaneously hypertensive streptozotocin diabetic rats.

1. To dissociate the effects on the development of diabetic renal injury of angiotensin converting enzyme (ACE) inhibition per se, and a reduction in systemic blood pressure, we have studied the effects of chronic ramapril treatment in streptozotocin diabetic spontaneously hypertensive rats, with modulation of the hypotensive effect by a high salt diet. 2. Three weeks following uninephrectomy and induction of diabetes with streptozotocin, spontaneously hypertensive rats were allocated to three treatment groups. Groups 1 and 2 received 1% sodium chloride and Group 3 water as drinking solution. Groups 2 and 3 received 0.4 mg/kg per day ramapril in drinking solution over the subsequent 2 month study period. 3. Sodium chloride drinking solution (1%) completely prevented any hypotensive effect of ramapril. Blood pressure was reduced in Group 3 rats over the entire period of study, when compared with Group 2 rats (P less than 0.001). 4. Urinary protein excretion progressively increased in Group 1 and 2 rats, and was significantly reduced (P less than 0.001) in Group 3. After 2 months treatment, urinary protein (expressed as mean and s.e.m.) was 160 +/- 30 mg/day in Group 1, 240 +/- 50 mg/day in Group 2, and 60 +/- 11 mg/day in Group 3. 5. Angiotensin converting enzyme inhibition per se was not associated with a reduced protein excretion in diabetic nephropathy, requiring concomitant control of systemic blood pressure to become renoprotective.

Animals↗