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Biomedical subjects

J Ong

Publications and source records attributed to J Ong.

At least 73 records · Page 4Linked to original sources
PubMed1993

Hereditary tyrosinaemia (HT) type 1A.

Two infants, aged 5 and 6 months, with the chronic form of HT Type 1 A were studied with sonography and CT. The imaging findings mirrored the pathological process. The sonographic findings included marked hepatomegaly, the parenchyma being of increased echogenicity due to fibrosis and fatty infiltration, and containing multiple hypoechoic regenerating nodules of varying sizes. There was marked nephromegaly, with uniform thickening of the renal cortices. Apart from the density measurement of the hepatic nodules and the perfusion status of the liver and kidney, no additional information was added by CT imaging. The diagnosis of HT Type 1 A should be excluded in an infant presented with the described typical sonographic features.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

Prevalence of verocytotoxigenic Escherichia coli serotype O157:H7 in children with diarrhoea attending a Sydney hospital.

Verotoxin producing Escherichia coli, in particular serotype O157:H7, have been implicated as an important cause of acute gastroenteritis in children. This study was undertaken to determine if E. coli O157:H7 is an important cause of acute gastroenteritis in children in metropolitan Sydney. During the period from October 1990 to September 1991, stools from patients presenting with acute diarrhoea to The Children's Hospital, Camperdown, were examined for the presence of common bacterial pathogens. In addition, stools were grown on sorbitol McConkey agar and sorbitol non-fermenting organisms were serotyped with O157 antiserum by slide agglutination. The isolates were then tested with H7 antisera and investigated for the production of verocytotoxin and other pathogenic markers including plasmid-associated EHEC adhesin and chromosomally encoded attachment-effacement gene. Only two strains (isolated from two different patients, 0.1% of specimens tested) were agglutinated by O157 antiserum and both were non-motile (H-). However, both strains produced verotoxin and expressed other virulence markers, suggesting that they were responsible for the diarrhoea. Both patients experienced mild, self limited gastroenteritis. We conclude that E. coli O157:H7 is an uncommon cause of acute gastroenteritis in Sydney children presenting to a children's hospital.

Acute Disease↗
PubMed1992

Differing actions of beta-(2-thienyl)-gamma-aminobutyric acid in central and peripheral preparations.

In the guinea-pig isolated ileum, beta-(2-thienyl)-gamma-aminobutyric acid (BTG; 100-500 microM) reversibly and competitively (pA2 = 4.3 +/- 0.1) antagonised the baclofen-induced (5-100 microM) depression of cholinergic twitch contractions, but not that to adenosine or morphine. By contrast, in rat neocortical slice preparations, BTG (100-500 microM) acted as an agonist, abolishing the frequency and amplitude of spontaneous discharges, sensitive to 2-hydroxysaclofen (100-500 microM). BTG exhibits differential actions at GABAB receptors in brain and periphery.

Animals↗
PubMed1992

Actions of thienyl analogs of baclofen in the guinea-pig isolated ileum.

In guinea-pig isolated ileal preparations, the 5-methylthien-2-yl (5d), 5-bromothien-2-yl (5f) and 5-chlorothien-2-yl (5h) analogs of baclofen depressed twitch responses to field stimulation in a dose-dependent manner. These actions were reversibly and competitively antagonised by 2-hydroxysaclofen but not by naloxone, phentolamine, propranolol or theophylline. The relative potencies (EC50 values) were baclofen (10 microM) greater than 5h (40 microM) greater than 5d (80 microM) greater than 5f (120 microM). These analogs represent a novel class of specific GABAB receptor agonists which, like baclofen, should readily enter the brain.

Animals↗
PubMed1992

Effects of sustained-release nicardipine on regression of left ventricular hypertrophy in systemic hypertension.

The effects of a sustained-release formulation of the calcium antagonist nicardipine on left ventricular (LV) mass, Doppler transmitral velocity profiles and plasma neurohumoral studies were analyzed in patients with mild to moderate systemic hypertension. A double-blind placebo control phase in 28 patients was carried out for 6 weeks with a subgroup of 13 subsequently entering an open-label long-term phase for 1 year. Nicardipine produced a significant decrease in systolic and diastolic pressure over the 6-week phase (158 +/- 15 to 142 +/- 9 mm Hg, and 100 +/- 5 to 89 +/- 9 mm Hg, respectively, both p less than 0.001). No significant differences in Doppler measures of mitral inflow or echocardiographic measures of LV function, wall thickness or mass were noted in the 6-week phase of the study. Although nicardipine increased both norepinephrine and renin values after the first dose, these levels had returned to baseline in most patients after 6 weeks. In addition, there was no evidence for stimulation of adrenomedullary activity because nicardipine had no effect on epinephrine or dopamine-B-hydroxylase levels at first dose or after 6 weeks. In the 13 patients treated for 1 year, systolic and diastolic pressure remained significantly decreased compared with pressure before therapy (135 +/- 9 vs 147 +/- 15 mm Hg, and 85 +/- 6 vs 97 +/- 9 mm Hg, both p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1992

Pilot study to evaluate impact of a policy of adjuvant chemotherapy for high risk stage 1 malignant teratoma on overall relapse rate of stage 1 cancer patients.

A total of 41 patients with stage 1 malignant teratoma of the testis treated from January 1986 to June 1990 was entered into a pilot study of 2 courses of adjuvant cisplatin-based combination chemotherapy. Of the patients 22 had a high or intermediate risk of relapse according to the Medical Research Council (United Kingdom) prognostic factor analysis and surveillance was instituted for 19 patients with a low relapse risk. The overall relapse rate in this group of patients (median followup 2 years) was 9.7% (5% in the adjuvant group and 16% in the surveillance group), which was significantly better than the 35% rate in the historical series treated by surveillance from 1980 to 1985 and equaled or was possibly better than that reported from adjuvant retroperitoneal lymph node dissection. Justification for consideration of 1 course of adjuvant treatment for such cases is reviewed, and the need for examination of such an approach in a neoadjuvant setting with either lymph node dissection or surveillance is examined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Reliability of the amplitude of the return-sweep velocity of eye movements during reading.

A Beckman Type RM Dynograph was used to record the eye movements of 26 professional college men, once without spectacle corrections and then with plano lenses on a trial frame, during reading equivalent print at a distance of 33 cm. Amplitudes of the return-sweep velocity on these two trials were used to calculate an equivalent form reliability coefficient. A Pearson r of 0.88 indicates that their reliability is moderately high, meaning that both the desirable as well as the undesirable reading habits are probably deeply rooted by college, and imply that any reading remediation or improvement training should be performed at some much earlier stages to be efficiently effective.

Adult↗
PubMed1991

Short-chain baclofen analogues are GABAB receptor antagonists in the guinea-pig isolated ileum.

A new series of GABAB receptor antagonists, based on short-chain baclofen analogues has been investigated. In guinea-pig isolated ileal preparations, the GABAB receptor-mediated, baclofen-induced depression of cholinergic twitch responses was reversibly and competitively antagonised by the short-chain baclofen analogues 3-amino-3-(p-chlorophenyl)propionic acid (apparent pA2 = 3.5), 2-amino-2-(p-chlorophenyl)ethanephosphonic acid (apparent pA2 = 3.8), and 2-amino-2-(p-chlorophenyl)ethanesulphonic acid apparent pA2 = 4.0). The corresponding des-chloro analogues were all less active. These compounds represent another class of GABAB receptor antagonists which may cross the blood-brain barrier.

Aminoethylphosphonic Acid↗
PubMed1991

Role of dopamine and GABA in the control of motor activity elicited from the rat nucleus accumbens.

The application of 1.2 and 12.0 micrograms/side of the GABAA receptor agonist 3-aminopropane sulphonic acid bilaterally into the nucleus accumbens (Acb) of rats nonsignificantly depressed locomotor activity as assessed in automated Animex activity cages, while the highest dose (60 micrograms/side) significantly stimulated activity. The GABAA receptor antagonists picrotoxinin (0.0625 and 0.125 micrograms/saide) and bicuculline (0.895 micrograms/side) produced forward locomotion around the cage accompanied by a number of other behaviours. The GABAB agonist baclofen (0.023 and 0.092 micrograms/side) induced a short-lasting (18 min) locomotor depression. None of the GABAB antagonists tested (2-hydroxysaclofen 2.6 micrograms/side, two novel beta-(benzo[b]furan) analogues of baclofen 9G or 9H each 6.8 micrograms/side, 4-aminobutylphosphonic acid 1.32 micrograms/side and phaclofen 0.535 and 2 micrograms/side) significantly affected locomotor activity. In rats pretreated with reserpine and alpha-methyl-p-tyrosine, picrotoxinin (0.0625 and 0.125 micrograms/side) did not significantly alter locomotor activity. Furthermore, when picrotoxinin (0.0625 micrograms/side) was combined with either the selective dopamine (DA) D1 agonist SKF38393 or the selective D2 agonist quinpirole, no significant alteration in locomotor function occurred. When SKF38393 and quinpirole were coadministered, significant stimulation occurred which was further enhanced by the addition of picrotoxinin. It is concluded that GABAA receptors, together with D1 and D2 receptors, play a major role in modulating the control of motor function by the Acb of rats.

Animals↗
PubMed1990

The actions of 2-hydroxy-saclofen at presynaptic GABAB receptors in the rat hippocampus.

The actions of 2-hydroxy-saclofen (2-OH-S), a recently developed analog of baclofen, were studied at presynaptic GABAB receptors in the rat hippocampal slice. Baclofen (0.5-20 microM) reduces the amplitude of excitatory postsynaptic potentials (EPSPs) recorded from hippocampal CA1 pyramidal neurons. In the presence of 200-500 microM 2-OH-S, the synaptic depressant action of baclofen is significantly reduced. These data show that 2-OH-S is an effective antagonist at presynaptic GABAB receptors on excitatory terminals in the hippocampus.

Animals↗
PubMed1990

3-Aminopropanephosphinic acid is a potent agonist at peripheral and central presynaptic GABAB receptors.

The actions of the GABA analog 3-aminopropanephosphinic acid (3-APA) were studied in the guinea-pig isolated ileal preparation and at synapses between cultured rat hippocampal neurons. Like the GABAB receptor agonist, baclofen, 3-APA inhibited the electrically evoked ileal twitch. The EC50 for 3-APA was 0.8 microM; the EC50 for baclofen was 9 microM. In addition, the depressant responses to 3-APA and baclofen were blocked by the GABAB receptor antagonists phaclofen, saclofen, 2-hydroxy-saclofen and delta-aminovaleric acid. 3-APA also mimicked the presynaptic action of baclofen at GABAergic synapses between embryonic rat hippocampal neurons in culture. 3-APA reduced the amplitude of inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) by greater than 50% at a concentration of 1 microM, while baclofen reduced synaptic transmission to a similar degree at 10 microM. 3-APA did not alter membrane conductance, nor did the drug alter postsynaptic responses to GABA. These data show that 3-APA is a potent agonist at presynaptic GABAB receptors in the periphery and on GABAergic neurons from the central nervous system. The activity of 3-APA at central postsynaptic GABAB receptors remains to be studied.

Amino Acids↗
PubMed1990

Inhibition of baclofen binding to rat cerebellar membranes by phaclofen, saclofen, 3-aminopropylphosphonic acid and related GABAB receptor antagonists.

The inhibition of the binding of the GABAB agonist [3H](-)-baclofen to rat cerebellar membranes by some sulfonic and phosphonic acid analogues of GABA has been studied. These analogues have been shown to act as GABAB antagonists in the rat cortical wedge and the guinea-pig isolated ileum preparations. The order of potency of phaclofen (IC50 118 microM), 2-hydroxysaclofen (IC50 5.1 microM) and saclofen (IC50 7.8 microM) as inhibitors of [3H](-)-baclofen binding was similar to the order of potency of these compounds as GABAB antagonists, whereas 3-aminopropylphosphonic acid (IC50 1.5 microM) and 4-aminobutyl-phosphonic acid (IC50 3.9 microM) were much more potent than anticipated from their relatively weak GABAB antagonist actions. These results indicate that inhibition of [3H](-)-baclofen binding to rat cerebellar membranes does not reflect antagonist activity at GABAB receptors seen in the rat cortical wedge preparation or the guinea-pig isolated ileum preparation. This may indicate a heterogeneity of GABAB binding and receptor sites.

Animals↗
PubMed1990

Effects of potassium channel blockers on baclofen-induced suppression of paroxysmal discharges in rat neo-cortical slices.

Baclofen reduced the frequency and aborted the bursts of spontaneous paroxysmal discharges in rat neocortical slices maintained in magnesium-free medium. This action was prevented by pretreatment with barium or caesium, which each increased the ictaform burst frequency, amplitude and duration. 4-Amino-pyridine also increased the burst frequency but reduced the amplitude and did not completely prevent the action of baclofen. Evidently baclofen suppresses such discharges by opening potassium channels normally involved in limiting the burst activity.

4-Aminopyridine↗
PubMed1990

Thioether analogues of baclofen, phaclofen and saclofen.

Analogues of baclofen, phaclofen and saclofen, incorporating a sulfur atom within the methylene chain, have been tested against responses induced by baclofen for activity at gamma-aminobutyric acid-B (GABAB) receptor sites, using a number of preparations including the guinea-pig isolated ileum and vas deferens, rat brain cortical slices and displacement of (-)-[3H]baclofen in rat cerebellar membranes. Results indicate that 2-([2-amino-1-(4-chlorophenyl)ethyl]thio)ethanephosphonic acid 2d is the most active of the new compounds. 2d is some 2-5 times weaker than phaclofen as a GABAB antagonist and approximately half as potent as phaclofen as an inhibitor of GABAB binding.

Animals↗
PubMed1990

Differing actions of baclofen and 3-amino-propylphosphinic acid in rat neocortical slices.

Rat neocortical slices maintained in Mg2(+)-free Krebs medium developed spontaneous paroxysmal discharges which were attenuated or suppressed by the gamma-aminobutyric acid-B (GABAB) receptor agonist baclofen, occasionally accompanied by a slight hyperpolarisation, and antagonised by the specific GABAB-receptor antagonist, 2-OH-saclofen. Over the same dose range, the GABA-analogue 3-amino-propylphosphinic acid (3-APA) caused a marked, prompt hyperpolarisation with little or no effect on the frequency of the discharges, although their amplitude was attenuated. In the presence of 2-OH-saclofen, 3-APA still induced a hyperpolarisation but the amplitude of the discharges was no longer affected. This marked difference in action between baclofen and 3-APA in the rat neocortical slices suggests there may be a heterogeneity of GABAB-receptors.

Animals↗
PubMed1990

GABA-receptors in peripheral tissues.

Gamma-aminobutyric acid (GABA) and its receptors are found in a wide range of peripheral tissues, including parts of the peripheral nervous system, endocrines, and non-neural tissues such as smooth muscle and the female reproductive system. In all these, both GABAA- and GABAB-receptor types are found, with good evidence for a physiological role in the gut, pancreatic islets and the urinary bladder. In some tissues, the pharmacology of GABA-induced actions is quite atypical and should be further explored with the newer ligands and modulators for GABAA- and GABAB-receptors.

Animals↗
PubMed1990

Alternatives to radiotherapy in the management of seminoma.

In a period from January 1978 to January 1989, 114 patients with seminoma have been managed, primarily in studies aimed at examining alternatives to radiotherapy. In a pilot study of single agent platinum in 27 previously untreated patients with metastatic seminoma, 82% remain progression-free and 89% alive and disease-free at 5 years compared with 81% progression-free and 88% alive and disease-free in a selected group of 16 previously untreated patients who received platinum-based combination treatment. Results from a pilot study of surveillance in 26 patients with stage 1 seminoma showed that 27% developed evidence of further disease (5 relapses, 2 second tumours) by 3 years, with all relapse patients salvaged by subsequent treatment. Because of the slow pace of relapse compared with malignant teratoma, with relapses occurring after 2 years, a pilot study was initiated to evaluate the effect of 2 courses of adjuvant carboplatin. The results to date in 25 patients suggest that with the use of modern antiemetics this regimen is as well tolerated as prophylactic radiotherapy. With a median follow-up of 16 months there has been 1 relapse subsequently salvaged by combination chemotherapy. A radomised trial is now justified to assess the quality of life and late toxicity of this approach compared with prophylactic radiotherapy.

Adolescent↗