Search PubMed⌕ Search

Biomedical subjects

A B Martin

Publications and source records attributed to A B Martin.

28 records · Page 2Linked to original sources
PubMed1993

Modulation of central noradrenergic function by RS-15385-197.

1. RS-15385-197, a highly potent and selective alpha 2-adrenoceptor antagonist, was examined in a variety of in vitro and in vivo functional tests to assess the selectivity of its interaction with central noradrenergic neurones in the rat. 2. In hypothalamic slices, RS-15385-197 was potent in augmenting K(+)-evoked release of [3H]-noradrenaline, with an EC50 of 9 nM. Idazoxan and yohimbine showed 100 fold less activity. This was due to its antagonist action at presynaptic alpha 2-adrenoceptors, as RS-15385-197 (10 microM), did not directly release [3H]-noradrenaline from cortical slices unlike reserpine (10 microM), and did not inhibit noradrenaline re-uptake into cortical synaptosomes. 3. In vivo, RS-15385-197 (0.5 mg kg-1, p.o.) increased levels of 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the cerebral cortex without modifying levels of 5-hydroxyindoleacetic acid (5-HIAA). This dose, but not a lower dose (0.1 mg kg-1, p.o.) caused beta-adrenoceptor down-regulation in the cortex when administered once daily for 14 days whereas 5-HT2 receptor number was unaltered, indicating a selective effect on noradrenergic transmission. 4. Selective depletion of cortical 5-HT by administration of p-chlorophenylalanine (PCPA; 100 mg kg-1, i.p. for 14 days) or 5,7-dihydroxytryptamine (5,7-DHT; 150 micrograms i.c.v.) prevented the beta-adrenoceptor down-regulation caused by RS-15385-197, indicating that a tonic 5-hydroxytryptaminergic input was required for it to elicit beta-adrenoceptor down-regulation. It was not possible to prevent the loss of activity of RS-15385-197 in these 5-HT-depleted animals by co-administration with the 5-HT1A partial agonist, 8-hydroxy-n-dipropyl aminotetralin (8-OH-DPAT, 0.3 mg kg-1, i.p. twice daily for final 3 days).5. At a dose (1 mg kg-1, p.o.) which completely prevented the hypoactivity produced by clonidine(0.1 mgkg-1, p.o.), RS-15385-197 did not affect behavioural stereotypy induced by 8-OH-DPAT(0.3 mg kg-1, s.c.). Similarly, following chronic dosing with the racemate, RS-15385-196 (3 mg kg-1,p.o., once daily for 14 days), there was no effect on the behavioural and hypothermic response to 8-OH-DPAT (0.5 mg kg-1, s.c.). Therefore, RS-1 5385-197 was selective for central alpha2-adrenoceptors over 5-HT1A receptors in in vivo functional tests.6. Thus, RS-15385-197 was highly selective in interacting with central noradrenergic neurones in the rat in vitro and in vivo. It is therefore currently the agent of choice for investigations of the role of alpha 2-adrenoceptors in the CNS.

Adrenergic alpha-Antagonists↗
PubMed1988

Ultrastructural findings in citrullinaemia in Holstein-Friesian calves.

Ultrastructural findings in the brains and livers of four calves affected with citrullinaemia due to a hereditary deficiency of the urea cycle enzyme arginosuccinate synthetase are described. The calves were affected in the 1st week of life with severe neurological disease characterised by depression, head pressing, stupor, convulsions and coma, accompanied by marked elevation of plasma citrulline and increasing plasma ammonia levels. Lesions included mild to moderate diffuse astroglial oedema in the cerebrocortical grey matter, and mild to severe hepatocellular hydropic change. The onset of the severe neurological signs was correlated with increasing levels of plasma ammonia, and the cerebral lesions were considered consistent with a bovine hyperammonaemic encephalopathy.

Amino Acid Metabolism, Inborn Errors↗
PubMedDate not supplied

Echocardiographic yield in children when innocent murmur seems likely but doubts linger.

The objective of our study was to determine the incidence and nature of heart disease found among children with murmurs clinically ambiguous to an expert examiner. The study was a prospective, blinded evaluation of accuracy of the expert examination using echocardiography as the diagnostic standard. The setting of the study was a pediatric cardiology outpatient department. The study comprised 903 outpatients with heart murmur under 21 years old without prior echocardiography or pediatric cardiology consultation. The intervention was echocardiography as clinically indicated for evaluation of heart murmur of uncertain cause. The outcome measure were a comparison of clinical diagnoses with echocardiographic results. In this clinical population, the presence of heart disease correlated with young age at presentation and with the expert examiner's level of suspicion of heart disease. However, 16 of 187 cases in which specific pathology was unsuspected had disease, and 6 of these 16 have had catheter or surgical intervention. Fourteen of the 16 unsuspected had objective indications for echocardiography and the other 2 were examined to allay anxiety. When evaluating very young outpatients with innocent-sounding murmur or older outpatients with innocent-sounding murmur and disconcerting symptoms, signs, or laboratory results, pediatric cardiologists should have a low threshold for echocardiography. Older outpatients with innocent-sounding murmur seldom have heart disease when anxiety is the only indication for echocardiography.

Age Factors↗
PubMedDate not supplied

Effects of electrocardiography and chest radiography on the accuracy of preliminary diagnosis of common congenital cardiac defects.

The objective of this study was to compare the accuracy of the expert clinical examination for certain common cardiac defects with and without electrocardiogram (EKG) and chest radiogram (x-ray). The design of the study was a prospective, blinded comparison of diagnostic accuracy of the expert examination with and without EKG and x-ray, using echocardiography as the diagnostic standard. The setting of the study was the pediatric cardiology outpatient department. There were 749 outpatients with heart murmur under 21 years of age without prior echocardiography or pediatric cardiology consultation. The intervention was echocardiography as clinically indicated for evaluation of heart murmur of uncertain cause. Measurements were carried out using the incorporation of EKG and x-ray into multiple linear regression models to assess independent associations, if any, with the accuracy of clinical examination. Results were reported as the presence or absence of independent significant impact of availability of EKG and x-ray on examiner's diagnostic accuracy for innocent murmur, ventricular septal defect (VSD), pulmonary stenosis (PS), aortic valve disease, atrial septal defect (ASD), and patent ductus arteriosus. EKG enhanced detection of ASD and may have helped detect PS. X-ray enhanced detection of intermediate to large VSD. X-ray and EKG were otherwise without demonstrable independent advantage for defect-specific diagnosis. Routine use of one or both of these tests in the initial evaluation of heart murmur in the pediatric cardiology clinic should remain an option.

Child↗
PubMedDate not supplied

Neurologic complications of heart transplantation in children.

Neurologic complications can add significant morbidity to otherwise successful orthotopic heart transplantations in children. Complications have been reported to occur in up to 50% of children undergoing heart transplantation. The purpose of this study was to identify the prevalence and outcome of neurologic complications of heart transplantation in children. We reviewed all children who received orthotopic heart transplantation at Texas Children's Hospital from November 1984 to November 1990. Twenty-two patients (ages, 3 weeks to 17 years; mean, 8.5 years) underwent heart transplantation using cardiopulmonary bypass with moderate hypothermia. For analysis, we compared results during the first 3 years of our experience, 1984 through 1987 (group 1), to 1987 through 1990 (group 2). Survival was 45% (5 of 11 patients) for group 1 and 73% (8 of 11 patients) for group 2. A neurologic complication was defined as a change in the neurologic examination and/or status. Neurologic complications included seizures (6 of 22 patients), strokes (3 of 22 patients), unresponsiveness (3 of 22 patients), and change in mental status (2 of 22 patients). Early (within 2 weeks after operation) neurologic complications occurred in 45% (10 of 22 patients), were persistent (sequelae lasting more than 4 months) in 27% (6 of 22 patients), and resulted in death in 9% (2 of 22 patients). Late (after 2 weeks after operation) neurologic complications occurred in 23% (5 of 22 patients), were persistent in 9% (2 of 22 patients), and have occurred in only two survivors. Neurologic factors were not responsible for the cause of death in group 2. No neurologic complications (early or late) were seen in 1 of 11 patients in group 1 as compared with 7 of 11 patients in group 2 (p < 0.015). Serious neurologic morbidity decreased between the two groups after preoperative cyclosporine was avoided and postoperative hypertension was controlled. All survivors are functioning at age-appropriate levels. Although neurologic complications may be frequent, long-term neurologic disability in survivors is rare.

Adolescent↗