Ethanol preference in Maudsley and RXNRA recombinant inbred strains of rats.
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Alcohol Drinking↗
Biomedical subjects
J A Hannah
Publications and source records attributed to J A Hannah.
Treatment of seizures in patients with learning disabilities.
People with learning disabilities commonly have seizures. Combined electroencephalogram and video investigations improve diagnostic accuracy, while neuroimaging may indicate a role for surgery. When epilepsy is diagnosed, individually tailored care is necessary. Rational antiepileptic drug use is advocated, with emphasis upon the newer agents due to their better tolerability and ease of use. Regular clinical review will prevent over-medicating. Although an optimistic approach can now be adopted, future developments require a more solid evidence base together with a rationality to all aspects of care, including drug therapy, carer education, closer collaboration among specialists, and mutual skill awareness of all involved.
Anticonvulsants↗
Epilepsy and learning disabilities--a challenge for the next millennium?
People with learning disabilities often have seizures in addition to other disorders. Precise diagnosis may be difficult, but accuracy can be improved using electroencephalographic and video investigations. Following the establishment of a diagnosis of epilepsy, individually tailored care is necessary taking into account other health, behavioural and therapeutic issues. Neuroimaging may indicate a need for surgery which should not be automatically excluded as a treatment option. Rational antiepileptic drug use is advised, with emphasis upon the newer agents due to their better tolerance and ease of use. A programme of regular review will prevent over-medicating. Drug therapy may be withdrawn in a seizure-free patient. Realistic goals should be established for each individual coupled with an optimistic approach to care. However, future developments require a solid evidence base combined with rationality in all aspects of management. The community learning disability epilepsy nurse specialist is the key health-care professional who can ensure that a learning disabled individual with epilepsy is able to take full advantage of all available services. Education, closer collaboration and the mutual recognition of skills will ensure more cohesive and comprehensive care for this disadvantaged patient population.
Anticonvulsants↗
Quality assurance study of cardiac isoenzyme utilization in a large teaching hospital.
Guidelines for diagnosis of acute myocardial infarction recommend that, if acute myocardial infarction is suspected, creatine kinase (CK)-MB levels should be measured on admission and again at 12 and 24 hours. In light of these recommendations, we conducted a quality assurance study to determine whether utilization of CK-MB tests in our institution, a large, university-affiliated teaching hospital, was consistent with current guidelines. Also, several years ago, we had established a policy of cancelling lactate dehydrogenase isoenzyme orders if the request originated from an unauthorized location, unless it was approved by a laboratory staff. Since this policy led to a greater than 90% reduction in the requests for lactate dehydrogenase isoenzyme testing, an additional objective was to reevaluate this policy. Of 774 patients evaluated with CK-MB tests, 294 (38%) received only a single test. Of these single tests, 277 had normal results (CK-MB < 5%). For the remaining 17 patients, the single CK-MB test findings were abnormal (CK-MB > 5%) without follow-up testing. Only two CK-MB tests were ordered for 187 patients (24%). Three or more CK-MB tests were obtained in 293 cases (38%). When two or more CK-MB tests were ordered, the time interval between the first and second tests was inappropriately short in 70% and long in 24%. The recommended timing for the third CK-MB was followed in only 4% of cases. Review of 32 cancellations of lactate dehydrogenase isoenzyme tests disclosed that lactate dehydrogenase isoenzyme tests were requested when unnecessary in 26 cases. Despite published guidelines for use of CK-MB for acute myocardial infarction, physicians at our institution continue to use these tests inappropriately by ordering only single CK-MB tests or by ordering repetitions of CK-MB tests at excessively short or long intervals.
Clinical Enzyme Tests↗
A case of Alzheimer's disease with neuropathological findings. 1936.
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Alzheimer Disease↗
Does dopamine regulate aldosterone secretion in the rat?
This study investigated the role of dopamine in the control of adrenal steroidogenesis. Adrenaline, noradrenaline and dopamine have been measured in plasma and in the adrenal zona glomerulosa and medulla of rats fed low, normal and high sodium diets and in zona glomerulosa tissue of rats with adrenal regeneration hypertension (ARH). Adrenal concentrations (means +/- SE) of adrenaline, noradrenaline and dopamine in rats fed a normal diet were 1471 +/- 335, 527 +/- 75 and 51 +/- 12 nmol/g in the medulla, and 66 +/- 17, 18 +/- 9 and 6 +/- 1 nmol/g in the zona glomerulosa. The dopamine content of the zona glomerulosa was greater than could be accounted for by simple contamination from the medullary catecholamines and is commensurate with that of tissue with dopaminergic innervation. Adrenal noradrenaline and adrenaline concentrations and plasma catecholamine and corticosterone concentrations were not affected by dietary sodium intake. Plasma aldosterone concentrations were greater than 3030.4, 339.8 +/- 41.5 and 55.2 +/- 11.0 pmol/l in rats fed low, normal and high sodium diets respectively. Five weeks after right adrenalectomy and nephrectomy and left adrenal enucleation, ARH rat systolic blood pressure had increased by 47 mmHg. In the regenerated gland, the concentrations of noradrenaline and adrenaline were negligible but dopamine was present in amounts similar to that of a normal adrenal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Cortex↗
The relative importance of glucocorticoids and mineralocorticoids in the development of adrenal regeneration hypertension in rats.
The adrenocortical tissue which regenerates after adrenal enucleation, and contralateral uninephrectomy and adrenalectomy, resembles histologically zona fasciculata tissue which normally synthesises glucocorticoids. However, increases in blood pressure after enucleation (adrenal regeneration hypertension-ARH] were preceded by a rise in exchangeable body sodium similar to that found with mineralocorticoid-induced hypertension (e.g. DOC/salt rat model). Glucocorticoid involvement in ARH rats was tested, firstly by infusing dexamethasone into control and ARH rats to see whether ACTH suppression would lower blood pressure by reducing adrenocortical activity and, secondly, by infusing dexamethasone into rats with intact adrenals to see whether conditions for ARH (i.e. uninephrectomy and/or saline consumption) pre-disposed rats to the hypertensinogenic properties of glucocorticoids. Low-dose dexamethasone infusions (10 micrograms/day for 5 days) in ARH rats did not affect blood pressure but in control animals caused a significant (P less than 0.01) increase from 128 +/- 3 to 151 +/- 5 mmHg. Corticosterone, 18-hydroxycorticosterone and deoxycorticosterone plasma concentrations were suppressed in both groups by dexamethasone treatment; plasma renin concentrations were lower in ARH rats than in controls. Uninephrectomy or 1% NaCl as drinking fluid did not affect the blood pressure rise induced by sc infusion of 10 micrograms dexamethasone/day for 14 days in rats with intact adrenals. The temporal relationship between blood pressure changes and exchangeable body sodium in ARH rats resembles that in mineralocorticoid-induced hypertension. Glucocorticoid, unlike mineralocorticoid, induced hypertension is not affected by a reduction in renal mass or increased sodium intake.
Adrenal Cortex↗
An analysis of the pressor responses to putative alpha 1 and alpha 2-adrenoreceptor agonists given intravenously to conscious rabbits.
The selectivity of a range of alpha 1 and alpha 2-adrenoreceptor agonists was examined in the conscious rabbit. In this preparation the pressor responses to BHT 920, BHT 933, guanabenz and alpha-methylnoradrenaline were attenuated by idazoxan but not by prazosin. The pressor responses to clonidine and noradrenaline were attenuated by both idazoxan and prazosin while the response to phenylephrine was only significantly attenuated by prazosin. Both an immediate pressor response and a later depressor response to clonidine was observed but there were no depressor components to either BHT 920 or BHT 933 responses. Pressor responses to guanabenz were attenuated on repeated dosing.
Adrenergic alpha-Agonists↗
Pretreatment with aspirin does not influence the pressor response to alpha 2-adrenoceptor agonists in conscious rabbits.
It has proved relatively easy to demonstrate pressor responses mediated via alpha 2-adrenoceptors in-vivo and in whole blood perfused vascular beds, but not in in-vitro work. The possibility that platelet alpha 2-adrenoceptor activation, with subsequent release of vasoactive prostanoids, contributes to the pressor response to alpha 2-adrenoceptor agonists was investigated. The pressor response to the alpha 2-adrenoceptor agonist BHT 920 (Alefexole) was compared in rabbits pretreated with distilled water or aspirin (3 X 200 mg kg-1 by gavage). Aspirin pretreatment had no significant effect on responses to BHT 920; thus, prostanoid formation does not appear to be an important mechanism contributing to postsynaptic alpha 2-adrenoceptor activation.
Adrenergic alpha-Agonists↗
RX781094, a new potent alpha 2 adrenoceptor antagonist. In vivo and in vitro studies in the rabbit.
1. RX781094 [2-(2-(1,4-benzodioxanyl))-2-imidazoline HCl] is a new alpha 2 adrenoceptor selective antagonist. Its effects on cardiovascular response "in vivo" before and after administration of alpha 1 and alpha 2 adrenoceptor agonists have been studied in conscious and anaesthetized rabbits. The affinity of RX781094 for alpha 1 and alpha 2 adrenoceptors has been investigated "in vitro" in radioligand binding studies. 2. Intravenous injection of RX781094 caused an immediate short lived pressor response which was attenuated by alpha 1 and alpha 2 adrenoceptor antagonists; it also caused a prolonged bradycardia. 3. Pretreatment with intravenous RX781094 inhibited the hypotensive response to both intravenous and intracisternal clonidine in a dose dependent manner. 4. RX781094 also showed a dose dependent inhibition of the acute pressor response to the alpha 2 adrenoceptor selective agonist guanabenz. 5. Pressor dose response curves to noradrenaline, a mixed alpha 1/alpha 2 adrenoceptor agonist were shifted to the right after RX781094 whereas those to the alpha 1 adrenoceptor agonist phenylephrine were unchanged. 6. RX781094 was more effective at displacing specifically bound 3H clonidine than 3H prazosin in membrane preparations from rabbit brain. 7. These observations are consistent with a selective alpha 2 adrenoceptor antagonist effect of RX781094 at central and peripheral adrenoceptors in the rabbit.
Adrenergic alpha-Agonists↗
Peripheral alpha 1- and alpha 2-adrenoreceptor mechanisms in blood pressure control.
Peripheral alpha-adrenoreceptors can be characterized as alpha 1 or alpha 2, depending on their affinity for agonists and antagonists. Alpha 2-adrenoreceptors, probably located postsynaptically on smooth muscle of resistance vessels, contribute to the pressor responses to intravenously given norepinephrine. Studies with the noncompetitive alpha-adrenoreceptor antagonist phenoxybenzamine suggest that there are important differences in the regulation of the two types of receptors. The slower recovery alpha 1-adrenoreceptor binding sites and the more rapid recovery of responses suggest the presence of "spare" alpha 1- but not alpha 2-adrenoreceptors.
Adrenergic alpha-Agonists↗
Environmental influences on the failure to drink in inbred rats with an ethanol preference.
To investigate the environmental influences on the initiation of voluntary consumption of 10% ethanol (EtOH) in rats with differing genetic susceptibility to excessive EtOH consumption, Maudsley reactive (MR/Har) and nonreactive (MNRA/Har) inbred rats were observed in different types of caging environments. Singly housed male and female rats of both strains living in Observational (O) cages drank markedly less EtOH during 3 weeks of two-bottle choice than did rats living in standard-control (C) individual cages. When male rats had a preexisting moderate or heavy pattern of EtOH intake (manipulated through prior EtOH experience), moving to the O cage did not reduce EtOH intake. To investigate the nature of the above cage effect (the reduced initiation of EtOH consumption), we compared the manner in which food had been distributed (traditional food hopper in C cages versus loose distribution in O cages) independently of cage type. The results showed that MR/Har male rats that obtained food through a hopper in both O or C cages drank significantly more EtOH than rats that had food loosely distributed in the O or C cages. The results suggest that differences in the mode of food procurement and caging can play a large role in whether the phenotype for excessive EtOH intake is expressed in the acquisition of an EtOH preference in genetically vulnerable rats.
Alcohol Drinking↗