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Biomedical subjects

E MacDonald

Publications and source records attributed to E MacDonald.

At least 91 records · Page 5Linked to original sources
PubMed1988

Screening for drugs blocking acetylcholine-activated ion channels and local anaesthetics with the isolated chick biventer cervicis preparation.

A convenient method for screening for drugs that block acetylcholine-activated ion channels, using the isolated chick biventer cervicis preparation is described. Since most of these drugs can only gain access to their site of action when the ion channel is in the open configuration, their effects are potentiated by prior treatment of the preparation with neostigmine. By preventing hydrolysis of acetylcholine, neostigmine enhances the possibility that ion channels will be in the open configuration. Potentiation of their neuromuscular blocking effects by neostigmine is apparently specific for drugs acting this way, other non-depolarizing neuromuscular blocking drugs are usually antagonized by neostigmine. The chick biventer cervicis preparation also contains a second set of accessible ion channels, the so-called voltage-gated channels in the nerve axons which are the site of action of local anaesthetic compounds. It has been observed that addition of local anaesthetics to the bathing solution causes an increase in the potential required to elicit indirect muscle contractions i.e. they induce a shift to the right of the voltage-response curve, a property which may be included in screening procedures with the isolated chick biventer cervicis preparation.

Acetylcholine↗
PubMed1988

Therapeutic applications of drugs acting on alpha-adrenoceptors.

For over a decade it has been known that clonidine and alpha-methyldopa lower blood pressure by activating central and peripheral alpha-2-adrenoceptors and prazosin likewise by antagonizing alpha-1-adrenoceptors. During the 1980s, the number of therapeutic indications for drugs which act via these classes of alpha-adrenoceptors has expanded greatly, particularly the non-cardiovascular applications of drugs acting on alpha-2-adrenoceptors. Novel alpha-2-agonists such as detomidine and medetomidine have been introduced into veterinary medicine as sedative/analgesics. It is possible that these and other compounds with better alpha-2-adrenoceptor selectivity than clonidine may be used in human medicine to ease symptoms of anxiety in drug- and alcohol-related withdrawal syndromes, and as preanaesthetic agents. Several novel alpha-2-adrenoceptor antagonists, such as idazoxan and atipamezole, have been developed with improved selectivity compared to the traditional antagonist at these receptors, yohimbine. At present none of these new compounds are registered for use, but several are undergoing clinical trials for a variety of therapeutic applications such as depression (idazoxan), arousal of animals sedated with alpha-2-agonists (atipamezole), and adult-onset diabetes (DG-5128). The established use of yohimbine in the treatment of male sexual impotence has been reconfirmed and several of the above compounds may be evaluated in the future to treat this disorder.

Adrenergic alpha-Agonists↗
PubMed1987

Alterations in peripheral and central dopamine receptor sensitivity after subchronic treatment with fluphenazine and sulpiride.

The effects of subchronic treatment with the antipsychotic drugs fluphenazine and sulpiride on the sensitivity of peripheral neuronal dopamine receptors and central dopamine autoreceptors were evaluated. The ability of apomorphine, a dopamine agonist, to inhibit electrically induced sympathetic vasoconstriction in pithed rats, and apomorphine-induced inhibition of spontaneous locomotor activity in awake rats were used as indices of peripheral and central dopamine receptor sensitivity, respectively. A single injection of fluphenazine decanoate, a long-acting preparation of fluphenazine, enhanced the central locomotor inhibitory effect of low doses of apomorphine 4 and 6 weeks after drug administration, whereas the antidopaminergic effect on peripheral dopamine receptors was prolonged and persisted at least up to 6 weeks. In another set of experiments rats were treated with fluphenazine hydrochloride and sulpiride for 10 days and subsequently challenged with apomorphine after various withdrawal times. Both antipsychotic drugs augmented the inhibitory effect of apomorphine in the periphery, although the time courses of the potentiation were different. Both treatments also enhanced the locomotor inhibitory effect of apomorphine. These results are in line with our previous finding that long-term treatment with dopamine antagonists can induce neuronal dopamine receptor up-regulation also outside the central nervous system. Peripheral neuronal dopamine receptors thus show similar adaptive responses to long-term blockade as central dopamine autoreceptors, and may serve as a useful experimental model in studies concerned with mechanisms of dopaminergic autoregulation in the central nervous system.

Animals↗
PubMed1987

A new rigid bronchoscope for laser fiber application.

A new fiberoptic rigid bronchoscope system, designed especially for laser fiber delivery, provides the endoscopist with an excellent conduit for application of the flexible fiberoptic bronchoscope, while still allowing maintenance of adequate ventilation. This system is designed for treatment of benign and malignant obstructing tumors in the trachea and mainstem bronchi. The bronchoscope will be available in sizes ranging from 6 mm to 10 mm in diameter.

Bronchial Neoplasms↗
PubMed1987

Congenital laryngeal atresia.

Laryngeal atresia is a rare congenital anomaly requiring immediate tracheotomy as a lifesaving measure. A case of subglottic laryngeal atresia is reported and correlated with laryngeal embryogenesis. Three types of laryngeal atresia are described. Although tracheoesophageal fistula is commonly associated with laryngeal atresia, one must be careful not to confuse a pharyngotracheal duct with a tracheoesophageal fistula. A disproportionate number of reported TE fistulas associated with laryngeal atresia may result if an accurate distinction between pharyngotracheal duct and TE fistula is not made.

Diagnosis, Differential↗
PubMed1986

Comparison of free MHPG in rat cerebrospinal fluid with free and conjugated MHPG in brain tissue: effects of drugs modifying noradrenergic transmission.

The changes of free 3-methoxy-4-hydroxyphenylglycol (MHPG) in cerebrospinal fluid (CSF) were compared with the corresponding alterations of free and conjugated MHPG in rat brain tissue after various pharmacological treatments modifying noradrenergic neurotransmission. In addition, the effects of the drug treatments on the concentration of noradrenaline (NA) in brain were determined. alpha-Methyl-p-tyrosine (an inhibitor of tyrosine hydroxylase) induced decreases in free and conjugated MHPG in CSF and brain; the free species appeared to decline more rapidly. Reserpine caused similar biphasic changes in free MHPG in CSF and brain but the rapid and transient initial increase in MHPG-SO4 was very weak. Pargyline (monoamine oxidase inhibitor) induced a sharp decline in the concentration of free MHPG in brain and CSF while MHPG-SO4 in brain definitely decreased more slowly. Relatively similar time courses were seen for all three MHPG parameters after administration of MPV-1248 (alpha 2-antagonist) and clonidine (alpha 2-agonist) i.e., increases and decreases, respectively. The present results support the validity of monitoring drug-induced acute changes in central turnover of NA by repeated measurements of free MHPG levels in rat cisternal CSF.

Adrenergic alpha-Antagonists↗
PubMed1986

Effects of diazepam, tofizopam or phenytoin during foetal development on subsequent behaviour and benzodiazepine receptor characteristics in rats.

The development of rats was studied for 3 postnatal weeks after prenatal medication with diazepam (10 mg/kg/day), phenytoin (50 mg/kg/day), or tofizopam (50 mg/kg twice daily) given by gastric intubation from day 7 to 21 of pregnancy. The treatments had no effect on the litter size. There were also no differences between the groups in a battery of tests for development (negative geotaxis, righting reflex, cliff avoidance, rotarod, passive avoidance), but the activity spurt seen at postnatal days 18-21 was missing in pups of diazepam-treated mothers. The number of benzodiazepine receptors and their affinity for tritiated flunitrazepam developed similarly in all of the rat groups. Thus, the transient changes in motor development seen 2-3 weeks after birth of rats whose mothers received diazepam during pregnancy do not seem to be related to changes in ontogenesis of benzodiazepine receptors.

Animals↗
PubMed1986

Lead does not affect calmodulin-induced activation of calcium-dependent adenosine triphosphatase in human red blood cell membranes.

The effects of lead (Pb) on the calmodulin activation of human red blood cell membrane calcium-dependent adenosine triphosphatase (Ca-ATPase) were studied in vitro. It was not possible to exclude EGTA from the hemolyzing buffer and retain Ca-ATPase activity and therefore exact concentrations of Pb in the incubation are not known. Nonetheless, nanomolar concentrations of Pb stimulated Ca-ATPase with or without exogenous calmodulin and none of the Pb concentrations tested (1 nM-100 microM) interfered with the calmodulin stimulation of the enzyme. High concentrations of Pb (greater than 10 microM) inhibited Ca-ATPase activity. It is possible that low concentrations of Pb can interfere with calcium dependent processes but the calcium-regulatory protein, calmodulin, is not susceptible to interference by Pb under the conditions used here.

Calcium-Transporting ATPases↗
PubMed1986

Effect of detomidine on the release and turnover of noradrenaline in rat brain.

The effect of detomidine, a novel veterinary sedative/analgesic, on the release and turnover of noradrenaline in rat brain was studied using both in vitro and in vivo techniques. Xylazine was included in the studies for comparison. Rat occipital cortex slices were preloaded with 3H-noradrenaline and the potassium-evoked release of tritium was measured using a superfusion system. Both detomidine and xylazine produced concentration dependent inhibition of stimulation evoked tritium release. A maximal inhibition of 66 and 50% was achieved at detomidine and xylazine concentrations of 1 X 10(-7) and 1 X 10(-6) M, respectively. The dose-response curve of detomidine was shifted to the right in a parallel manner by the selective alpha 2-antagonist idazoxan. Detomidine, while not altering the endogenous levels of noradrenaline, dopamine and 5-hydroxytryptamine, induced a dose-dependent inhibition of noradrenaline turnover as measured by the alpha-methyl-p-tyrosine method. Moreover, detomidine decreased the concentration of MHPG-SO4, the principal metabolite of central noradrenaline, in rat brain. Xylazine was in these tests at least two orders of magnitude less potent than detomidine.

Analgesics↗
PubMed1986

Presynaptic dopamine receptors in the pithed rat: characterization with apomorphine and comparison with central dopamine autoreceptors.

Apomorphine, a dopamine agonist with high affinity for presynaptic dopamine receptors, caused dose-dependent inhibition (10-300 micrograms/kg intravenously) of the stimulation-induced increase in diastolic blood pressure in the pithed rat. This effect of apomorphine could be antagonized with (-)-sulpiride or haloperidol but not with yohimbine or atropine, indicating the involvement of inhibitory dopamine receptors. The alpha-1-adrenoceptor mediated pressor response to phenylephrine (5 micrograms/kg intravenously) was not significantly attenuated by apomorphine. The sensitivity of peripheral presynaptic dopamine receptors was then studied in the cardiovascular system of rats treated subchronically with haloperidol (2 mg/kg, twice daily intraperitoneally for 10 days). The inhibition of sympathetic vasoconstrictor responses exerted by apomorphine was found to be enhanced after subchronic haloperidol treatment suggesting the development of presynaptic dopamine receptor supersensitivity in the periphery. In addition, the previously reported supersensitivity of central dopamine autoreceptors to low doses of apomorphine could be confirmed in behavioural experiments.

Animals↗
PubMed1985

Comparison of the effects of detomidine and xylazine on some alpha 2-adrenoceptor-mediated responses in the central and peripheral nervous systems.

The effects of detomidine, a novel veterinary sedative analgesic, on some alpha 2-adrenoceptor-mediated responses in the central and peripheral nervous systems were studied. In pithed rats, detomidine was a very potent agonist at both pre- and postsynaptic alpha 2-adrenoceptors. Doses of 1.9 micrograms/kg and 6.5 micrograms/kg inhibited electrically induced tachycardia by 50% and increased mean blood pressure by 50 mmHg, respectively. In comparison, xylazine, though similar in specificity, was 40 times less potent than detomidine in this preparation. In unanaesthetized rats, detomidine both caused sedation and induced complex changes in body temperature. Low doses caused decreases in rectal temperature but these were reversed as the dose was increased. The decrease in rectal temperature could be blocked by yohimbine. Prazosin somewhat inhibited but did not eliminate the hyperthermia seen with the very high doses of detomidine. Xylazine caused much more severe falls in rectal temperature which could not be completely antagonized by alpha 2-adrenoceptor blockade. Both detomidine and xylazine caused dose-dependent mydriasis in anaesthetized rats, detomidine being about 10 times more potent than xylazine. The mydriatic effects of detomidine could be prevented by alpha 2- but not by alpha 1-adrenoceptor blockade. It is concluded that detomidine is a potent and rather specific alpha 2-adrenoceptor agonist in the central and peripheral nervous systems. In comparison with xylazine, detomidine has higher potency and greater specificity, especially at central alpha 2-adrenoceptors.

Animals↗
PubMed1985

Exophiala jeanselmei infection in a postrenal transplant patient.

We report a case of Exophiala jeanselmei infection in a postrenal transplant patient. He had verrucous lesions on the thigh and abdomen in which clinical and histologic changes resembled those characteristic of chromoblastomycosis. However, the morphologic features of the fungus seen in the tissue sections made it necessary to diagnose this case as phaeohyphomycosis. The patient was treated successfully by complete excision of the lesion on the abdomen and with oral ketoconazole.

Adult↗
PubMed1984

Sensitivity of RBC membrane Ca2+-adenosine triphosphatase to calmodulin stimulation. Variations in patients with bipolar affective disorders.

The sensitivity of RBC membrane (RBCM) Ca2+-adenosine triphosphatase (Ca2+-ATPase) to calmodulin stimulation was repeatedly studied in healthy volunteers and in 12 patients with affective disorders. Whereas control response was relatively stable, the patients showed great variability. This phenomenon was not due to formation of resealed vesicles in the RBCM nor to the quantity of calmodulin remaining in the RBCM preparations present in the cells before hemolysis. Changes in calmodulin sensitivity did not correlate with changes of mood or of drug treatment. When Ca2+-ATPase was relatively unresponsive to calmodulin, considerable enzyme activity was maintained at low calcium concentrations without calmodulin. In samples showing a large response to calmodulin, virtually no enzyme activity was detected at low calcium concentrations without exogenous calmodulin. Thus, calcium dependence and calmodulin sensitivity of the Ca2+-ATPase appeared to correlate positively with each other. As a similar phenomenon has been linked to changes in the composition of membrane phospholipids responsible for the regulation of Ca2+-ATPase activity, variations in baseline activity and calmodulin-induced stimulation of this enzyme may represent a fundamental defect in systems regulating membrane phospholipid composition.

Adult↗
PubMed1984

Neurological involvement with Whipple's disease.

Whipple's disease is an inflammatory illness primarily afflicting middle-aged men. Although originally seen as a disease of intestinal malabsorption, it may affect any body system causing numerous signs and symptoms. These are due to infiltration of macrophages containing sickleform particles which stain PAS-positive. Definitive diagnosis is made by biopsy, and treatment is with broad-spectrum antibiotics. There seems to be an infectious component to the disease although defective immunologic responses may be implicated. Exact etiology is unknown. Although a rare illness, there has recently been increased recognition of this disease. Neurological involvement occurs with dissemination of lesions to the nervous system. Symptoms are quite varied but most often include dementia. As is apparent from the patient history, early diagnosis and treatment is imperative. Even without symptoms, there should probably be treatment for central nervous system involvement since neurological manifestations are often fatal. The case study presented illustrates a multisystem illness. The neurological presentation includes peripheral neuropathy, cranial nerve involvement, brainstem dysfunction, endocrine disturbance, thalamic or pituitary symptoms, and changes in cerebral function. Nursing measures reinforce the importance of the role of primary nursing for patient care and the necessity of comprehensive nursing care plans. Management problems were alleviated by providing consistency and continuous orientation, by involving the patient and his family in the plan of care, and by establishing a safe and consistent environment. Nursing process can improve and enhance patient responses, family coping ability, and the quality of care given. A "difficult" patient can help to expand nursing knowledge as well as promote personal growth and satisfaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗