Biomedical subjects
Publications and source records attributed to D McNamara.
A 61-yr-old patient was referred to our hospital for investigation of pain and tenderness in his left lower limb. Bone scan revealed multiple lesions of tibia and foot, several of which appeared as doughnut-like lesions and corresponded to lytic abnormalities on radiographs. Pathologic examination revealed multiple epithelioid hemangioendothelioma of bone.
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Fourteen substituted derivatives of kynurenic acid were compared for their ability to block ionic currents evoked by N-methyl-D-aspartate (NMDA) plus glycine, or kainate, in voltage-clamped Xenopus oocytes injected with rat brain messenger RNA. Among these analogues there was an excellent correlation between the Ki for displacing [3H]glycine binding to rat brain membranes, and the ability to inhibit ionic currents evoked by glycine/NMDA in Xenopus oocytes. In the oocyte 5,7-dichlorokynurenic acid (5,7-DCK) was a competitive blocker of the glycine recognition site on NMDA receptors, and was more potent (KB 65 nM in Schild analysis) and selective (509-fold more potent vs glycine than kainate) than the prototype glycine antagonist, 7-chlorokynurenic acid, 5,7-DCK also reduced NMDA-induced neuron injury in rat cortical cell cultures.
Cerebral metabolic and behavioral effects of acutely administered nicotine were measured in rats in relation to dose. Nicotine 0.1, 1, or 10 mg/kg or vehicle was administered intraperitoneally to 3-month-old male Fischer-344 rats that had been pretreated with hexamethonium bromide 5 mg/kg i.p. to reduce peripheral autonomic effects. Regional CMRglc (rCMRglc) values were measured, using the quantitative autoradiographic [14C]-2-deoxy-D-glucose method, in 71 brain regions, beginning 3 min after nicotine or vehicle administration. Intensity of body tremor, scored by a blinded rater, was dose related and peaked at 3 min after nicotine injection. rCMRglc rose in a dose-related manner: Nicotine 0.1 mg/kg had no significant effect in any region, whereas 1 mg/kg elevated rCMRglc significantly in 21 regions (mean rise 20%) and 10 mg/kg produced generalized (56 regions) and greater (mean rise 50%) increases in rCMRglc. Nicotine 1 mg/kg activated thalamic nuclei, cerebellum, geniculate nuclei, superior colliculus, median raphe, reticular formation, and the habenulointerpeduncular pathway, but was without effect in the telencephalon. Effects of nicotine in the hindbrain were related anatomically to reported distributions of [3H]nicotine and [3H]acetylcholine but not [125I]alpha-bungarotoxin binding sites, implying that the former ligands label functional nicotine receptors. The pattern of change in rCMRglc after nicotine administration suggests that its cognitive effects in humans are due to augmented arousal/attention and visual processing rather than to direct neocortical or hippocampal activation.
To examine the roles of glycine in neurotoxicity caused by NMDA, primary rat cortical cultures were exposed to 100-300 microM NMDA plus glycine (0-3000 microM) or other glycine analogs in a simple saline solution, and toxicity was assessed by the amount of lactate dehydrogenase (LDH) released from the cultures. NMDA-induced neurotoxicity was abolished by 100 microM D-2-amino-5-phosphonovaleric acid (D-APV), phencyclidine (IC50, 4.1 microM), and Mg (IC50, 7.5 mM), or by reducing [Ca]0 to 0.1 mM. NMDA-induced neurotoxicity could also be abolished by 7-chlorokynurenic acid (IC50, 8.6 microM), suggesting the presence of residual glycine in the culture medium (confirmed by high-performance liquid chromatography measurement). Moreover, in the presence of 30 microM 7-chlorokynurenic acid, glycine, D-serine, D-alanine, beta-fluoro-D-alanine, and 1-aminocyclopropanecarboxylic acid could restore the neurotoxic action of NMDA, and their relative potencies and relative efficacies were the same as measured in electrophysiological assays in Xenopus oocytes or cultured neurons. The addition of greater than 100 microM glycine doubled the excitotoxic effect of NMDA. The potency of glycine was low (EC50, 27 microM), and this effect was not due to a direct action on the NMDA receptor. The above-mentioned agonists were unable to substitute for glycine, even at high concentrations (1 mM). On the other hand, beta-alanine, taurine, and GABA (1 mM) did potentiate NMDA neurotoxicity, and strychnine (IC50, 550 nM) could greatly reduce neurotoxicity in the presence of 1 mM glycine plus 300 microM NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)
Vasospasm of intracranial vessels is difficult to diagnose on clinical ground alone. Still, a clear diagnosis is important because it can impact on surgical timing; and also because it can help evaluate new treatments. Fifteen patients with sub-arachnoid hemorrhage secondary to aneurysm rupture were submitted to a total of 26 tomographic technetium-99m-hexamethyl-propyleneamine oxime (99mTc-HM-PAO) brain examinations that were correlated with temporally close (generally less than 24 hr) angiography or transmission computed tomography (TCT). Nine of 10 angiographically confirmed episodes of spasm and 6 of 6 infarcts seen on angiography or TCT were correctly diagnosed with 99mTc-HM-PAO. One normal scintigraphic exam was angiographically doubtful, one positive 99mTc-HM-PAO study was normal on angiography (sub-radiologic spasm?), one technically poor scintigraphy was positive for spasm on angiograms, and eight exams were normal for spasm with all modalities. We had agreement between tests in 23 of 26 series of exams (88%) obtained in 15 patients. We think that 99mTc-HM-PAO tomography should be useful for the evaluation of patients with suspected vasospasm.
A linear histogram method was employed to analyze brain images of glucose uptake obtained by positron emission tomography in patients with dementia of the Alzheimer type and in control subjects. A line was drawn by computer which traversed the image of a brain slice taken at 70 mm above and parallel to the inferior orbitomeatal line, and rCMRglc was plotted as a function of distance along this line in 3 brain areas: frontal, sensorimotor and parietal. Peak rCMRglc values were significantly decreased in moderately-to-severely demented patients relative to healthy age-matched controls, but not in mildly demented patients. Furthermore, both the mildly and the more severely demented patients differed from controls in having reduced ratios of parietal association to sensorimotor peak rCMRglc. The variances of right-left metabolic asymmetries did not differ significantly between Alzheimer patients and controls. Severity of dementia, as evaluated by scores on the Mini-Mental State Examination, correlated with ratios of peak rCMRglc in frontal and parietal cortex to that in sensorimotor cortex. These results indicate that measures of focal peak rCMRglc do not discriminate between mildly demented patients and controls, whereas focal ratios of rCMRglc, where the denominator corresponds to rCMRglc from a relatively spared region, provide useful measures of metabolic dysfunction in the early stages of Alzheimer's disease.
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1. At least two components of neuraminidase can be distinguished on the basis of thermolability and sedimentability by using the artificial fluorogenic substrate 4-methylumbelliferyl N-acetyl-alpha-D-neuraminate. 2. In crude homogenates, thermodenaturation at 25 degrees C showed a biphasic curve corresponding to component A (half-life, 21 min) and B (half-life, 85 min). The two components were partially resolved by centrifugation. A being soluble and B sedimentable. Both had similar pH-activity curves (pH optimum, 4.4), Km values (A, 0.10 mM; B, 0.06 mM) and molecular weight as determined by radiation inactivation (A, 67000; B, 63000). 3. The soluble A form was still aggregated or bound to membranous debris since almost all neuraminidase activity was eluted near or at the void volume of a Sephacryl S-300 column. 4. Both soluble and sedimentable fractions of placenta hydrolysed the GD1A ganglioside and N-acetyl-neuraminyl-D-lactose linearly for 12 h but no fetuin hydrolysis was detected. 5. The neuraminidase activity with the artificial fluorogenic substrate was inhibited by N-acetylneuraminyl-D-lactose but not by the GD1A ganglioside. These preliminary results suggest that there exist two closely related enzymes hydrolysing both the artificial substrate and N-acetylneuraminyl-D-lactose and a third one hydrolysing the GD1A ganglioside exclusively.
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The intestinal brush-border disaccharidases most resistant to pancreatic protease digestion in vitro are lactase and trehalase. When compared to maltase and sucrase, they are also those which showed the largest increase during development of guinea pig fetuses. These results suggest that pancreatic proteases may play a role in the control of brush-border disaccharidase activities during fetal development.
Case history of a 54 yr old lady with acute viral hepatitis who developed cryptogenic organising pneumonitis. The patient was receiving corticosteroids at the time of onset of symptoms.
BACKGROUND: The diagnosis of Helicobacter pylori is an essential element in the management of many common gastrointestinal pathologies. Previously diagnosis was dependent on the availability of endoscopic biopsy samples. The advent of non invasive assays such as the C13Urea breath test and Elisa serology have enabled diagnosis and treatment to be undertaken in the primary care setting. The isolation of Helicobacter pylori antigen from stool has led to the development of a new non-invasive test. AIM: A prospective study was designed to assess and compare the performance of Premier Platinum HpSA with current gold standard tests. METHODS: Consecutive patients undergoing a gastroscopy for investigation of dyspepsia at the Meath and Adelaide hospitals were enrolled. At endoscopy gastric biopsies were taken for histology, microbiology and rapid urease testing. In addition all subjects had C13UBT, serology and stool tests performed. Individuals who were H. pylori positive received standard proton pump inhibitor based triple therapy. Following treatment all tests, apart from serology were repeated. RESULTS: 54 patients were enrolled, 46 per cent were H. pylori positive. HpSA had a sensitivity and specificity and positive and negative predicted values of 96 per cent, 75 per cent and 80.6 per cent, 75.8 per cent respectively and compared favourably with all other tests. The sensitivity and specificities of the other tests were, histology 79.2 per cent and 100 per cent, culture 68 per cent and 100 per cent, rapid urease test 75 per cent and 100 per cent, serology 75 per cent and 96 per cent and C13 urea breath test 100 per cent and 96.6 per cent. CONCLUSION: The detection of H. pylori antigen in stool by means of a HpSA assay is a new and effective non-invasive means of diagnosis which can be performed in a routine laboratory setting. It is simple to perform and has possible advantages over other non-invasive tests, detecting actual antigen indicating current active infection.
The efficacy of second-line antiepileptic drugs (AEDs) was evaluated in the treatment of 66 patients with complex partial seizures who had previously failed first-line AEDs. Methsuximide, valproate, or clorazepate had eliminated seizures in 11% of the patients at the end of the study. However, these good results deteriorated on longer follow-up and were not expected to be permanent. It is recommended that suitable patients with partial epilepsy be referred for surgical evaluation after failing the first-line AEDs, and that second-line AEDs be reserved for nonsurgical candidates.
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