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Biomedical subjects

A Leonard

Publications and source records attributed to A Leonard.

At least 37 records · Page 2Linked to original sources

Sister chromatid exchanges in human peripheral blood lymphocytes after ingestion of high doses of arsenicals.

OBJECTIVE: To evaluate the cytogenetic effects following the ingestion of high doses of arsenicals. METHODS: Determination of the mean sister chromatid exchange (SCE) frequency and the population of high-frequency cells (HFC, cells with a high SCE frequency) in the peripheral blood lymphocytes in four patients who ingested 150 mg KAsO2, 1 g, 10 g and 20 g As2O3 respectively. RESULTS: Doses of 10 g and 20 g significantly increased the HFC frequency and produced a shift in the distribution of the cells in accordance with the number of SCEs. The mean frequency of SCEs/cell was affected only after the highest dose (20 g). CONCLUSION: These results strongly suggest that cytogenetic methods are inappropriate for biomonitoring people occupationally exposed to arsenicals.

Adolescent↗

Cognitive recovery in idiopathic normal pressure hydrocephalus: a prospective study.

Idiopathic normal-pressure hydrocephalus remains difficult to treat. Controversy exists as to whether or not shunting can really improve cognitive functions and whether quantified intracranial pressure monitoring (ICP-Mo) can predict postoperative improvement rates. Several studies have drawn attention to the lack of a prospective study concerning the surgical outcome of this condition. We have performed such a study on idiopathic normal-pressure hydrocephalus patients shunted on the basis of ICP-Mo when "high" waves (amplitude > 9 mm Hg) were present. Twenty-three patients underwent surgery. The preoperative and postoperative clinical states were assessed by a quantitative procedure blind to the ICP-Mo results. A clear postshunting improvement was seen in 96% of the patients at 1 year with a statistically significant correlation between high wave relative frequency and the grade of improvement (P < 0.05). At the same time, 66.6% of shunted patients showed a significant improvement in cognitive functions. Complications of shunting were successfully managed without residual deficits in this series. We recommend the use of quantitative ICP-Mo as a criterion for surgery and to predict the improvement grade.

Aged↗

Pepsin hydrolysis of the adherent mucus barrier and subsequent gastric mucosal damage in the rat: effect of diosmectite and 16,16 dimethyl prostaglandin E2.

BACKGROUND AND OBJECTIVE: The gastroduodenal mucus layer is progressively eroded at its luminal surface as a consequence of pepsin mucolysis. Diosmectite binds to gastric mucus and modifies its rheological properties. Prostaglandins are well-known mucus secretagogues. The aim of this study is to describe interactions of diosmectite and 16,16 dimethyl prostaglandin E2 on adherent gastroduodenal mucus and pepsin mucolysis in the rat. METHODS: Instillation of pepsin (1 or 2 mg.mL-1 at pH1 or pH2) into the pylorus ligated stomach of anaesthetised rats resulted in progressive disruption of the adherent mucus layer and a large, significant, increase in soluble degraded mucin compared to that following instillation of HCl pH1 or pH2. Pepsin (2 mg.mL-1), instillation over 2 hours, but not HCl alone, consistently resulted in small focal, haemorrhagic mucosal lesions, significant bleeding into the lumen and histologically, localised punctate ulcers in an otherwise intact epithelium. Diosmectite (500 mg.kg-1) and 16,16 dimethyl prostaglandin E2 were given by oro-gastric intubation. RESULTS: Diosmectite, given 30 minutes beforehand, inhibited breakdown of the adherent gastric mucus barrier by pepsin in vivo. When administered up to 16 hours prior to the experiment, diosmectite prevented pepsin induced gastric mucosal haemorrhage and histological epithelial damage. Substantial amounts of diosmectite (39.6 micrograms/mm2, equivalent in volume to layer 93 microns thick) were bound to the gastric mucosa 30 minutes after administration. Diosmectite (100:1 by weight to enzyme) completely inhibited pepsin hydrolysis of protein in vitro. Topical 16,16 dimethyl prostaglandin E2, 5 micrograms.kg-1 increased the thickness of the adherent mucus layer by two-fold. Both doses of the prostaglandin prevented pepsin induced gastric mucosal haemorrhage and histological epithelial damage. CONCLUSIONS: These results show that both diosmectite and prostaglandin increase the effectiveness of the mucus barrier against mucosal damage by pepsin in vivo.

16,16-Dimethylprostaglandin E2↗

CT appearances of haematomas in the corpus callosum in patients with subarachnoid haemorrhage.

Corpus callosum haematoma is a rare feature in subarachnoid haemorrhage (SAH), which may result from aneurysms of the anterior communicating artery (ACoA) or pericallosal artery (PCA). In 348 patients with aneurysmal SAH, bleeding from ACoA aneurysms in 88 cases produced no abnormality on CT in 7. Blood in the cistern of the lamina terminalis was the most frequent abnormality (76/88); haematomas of the septum pellucidum, confined to patients with ACoA aneurysms, were seen in 26 (30%). Rupture of PCA aneurysms in 12 patients gave rise to blood in the pericallosal cistern, anterior interhemispheric fissure and cistern of the lamina terminalis in 11. There was no blood in the septum pellucidum or the ventricular system in any case, but haematomas in the corpus callosum occurred in 8 (67%). In all of these, blood extended into the anterodorsal aspect of the callosum and spread posteriorly along its dorsal border. An identical, supracallosal pattern was seen in 2 patients (2.5%) with ACoA aneurysms, in whom haemorrhage was more extensive, with a large frontal lobe haematoma extending up from the cistern of the lamina terminalis in 1 and a haematoma of the septum pellucidum, with intraventricular extension in the other. In 8 patients (9%) with ACoA aneurysms a corpus callosum haematoma appeared to result from passage of blood up through the cistern of the lamina terminalis into the septum pellucidum and thence into the ventral aspect of the anterior corpus callosum; blood was present within the cistern, the septum and the ventricles.

Aneurysm, Ruptured↗

Chromosomal aberrations in human lymphocytes induced in vitro by very low doses of X-rays.

This paper presents results of a collaborative experiment between six laboratories which examined the yields of unstable chromosomal aberrations in human lymphocytes induced in vitro by X-rays over the dose range 0-300 mGy. The work included data points of nominal doses of 0, 3, 5, 6, 10, 20, 30, 50 and 300 mGy. Cells from 24 donors were examined and a total of about 300,000 metaphases were scored. The work was undertaken to determine the limits of sensitivity of the system taking into account variations in scoring data due to inter-donor sample and inter-laboratory effects. Despite the existence of these effects, aberration yields significantly in excess of control values were seen at doses greater than 20 mGy and these were consistent with a linear extrapolation from higher doses. Below 20 mGy the observed dicentric yields were generally lower than background, but not significantly so. Excess acentric aberrations, on the other hand, and centric rings, were higher than the controls but the increase was usually not significant. It is concluded that the statistical uncertainties are such that below 20 mGy this technique cannot distinguish between a linear or a threshold model.

Chromosome Aberrations↗

M3-subtype muscarinic receptor that controls intracellular calcium release and inositol phosphate accumulation in gastric parietal cells.

The muscarinic receptor subtype which triggers acid secretion was investigated in isolated rabbit gastric parietal cells. Cytosolic free Ca2+ concentration ([Ca2+]i), measured with the fluorescent indicator FURA-2, increased rapidly after full agonist (carbachol) stimulation (6-8 sec), then returned to an intermediate sustained value. Other M2-agonists, oxotremorine and arecoline, produced a partial [Ca2+]i increase, whereas M1-agonists, pilocarpine and [4-m-chlorophenylcarbamoyloxyl]-2-butynyl-trimethylammonium, were without any significant effect. [Ca2+]i rise was inhibited by selective muscarinic antagonists: atropine greater than 4-diphenylacetoxy-N-methyl-piperidine methbromide greater than quinuclidinylbenzilate (QNB) greater than pirenzepine greater than 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one, this sequence being characteristic of the involvement of an M3-subtype. This inhibition was shown to be stereoselective; dexetimide and (-)QNB were more potent than levetimide and (+)QNB. The IC50 values for inhibition of [Ca2+]i increase by muscarinic antagonists were in good agreement with those obtained for inhibition of phospholipase C activation. In conclusion, the muscarinic receptor that controls acid secretion appears to be of the M3-subtype and the biochemical events coupled to the activation of this receptor system are also controlled through the same subtype.

Acetylcholine↗

Comparative analysis of health risk assessments for municipal waste combustors.

Quantitative health risk assessments have been performed for a number of proposed municipal waste combustor (MWC) facilities over the past several years. This article presents the results of a comparative analysis of a total of 21 risk assessments, focusing on seven of the most comprehensive methodologies. The analysis concentrates on stack emissions of noncriteria pollutants and is comparative rather than critical in nature. Overall, the risk assessment methodologies used were similar whereas the assumptions and input values used varied from study to study. Some of this variability results directly from differences in site-specific characteristics, but much of it is due to absence of data, lack of field validation, lack of specific guidelines from regulatory agencies, and reliance on professional judgment. The results indicate that carcinogenic risks are more significant than chronic non-carcinogenic risks. In most instances polychlorodibenzodioxins, polychlorodibenzofurans, and cadmium contribute more significantly to the total carcinogenic risk from MWC stack emissions than other contaminants. In addition, the contribution to total risk of all indirect routes of exposure (ingestion and dermal contact) exceeds that of the direct inhalation route for most studies reviewed.

Animals↗

Intracellular coupling of prostaglandin inhibition of acid secretion in isolated rabbit gastric parietal cells.

Acid secretion from isolated rabbit gastric parietal cells can be stimulated by gastric secretagogues, histamine (cyclic-AMP pathway) and carbachol (inositol phosphate pathway). Prostaglandins (PG) from E series are potent inhibitors of acid secretion. The intracellular mechanism of this inhibition was examined by using a stable PGE1-analogue, misoprostol. Aminopyrine (AP) accumulations due to histamine, IBMX and forskolin were dose-dependently inhibited by misoprostol, whereas a weak but significant biphasic effect on carbachol-induced AP accumulation was observed. The cyclic-AMP formation induced by histamine and IBMX were also inhibited by misoprostol in a non-competitive way. The potent effect of forskolin on cyclic-AMP levels was not modified by misoprostol in parietal cells, whereas it was potentiated in non-parietal cells. The inhibitory effect of misoprostol on AP accumulation was reduced by incubation of parietal cells with Bordetella pertussis toxin (IAP) but not with Cholera toxin (CT). Pretreatment of the cells with IAP did not alter cyclic-AMP levels of resting and histamine-stimulated parietal cells but abolished the inhibitory effect of misoprostol. Treatment with CT increased basal and histamine-stimulated cyclic-AMP levels and masked the inhibitory effect of misoprostol. The biphasic effect of misoprostol on carbachol-stimulated AP accumulation in parietal cells was confirmed on carbachol-stimulated phospholipase C activity and on [Ca2+]i stimulated by carbachol. These data confirm a direct and specific effect of the prostanoid on the Gi-subunit of the adenylate cyclase coupled to the histamine H2-receptor, and a biphasic effect on the phospholipase C pathway of the parietal cells.

1-Methyl-3-isobutylxanthine↗

Calcium involvement in the muscarinic response of the gastric parietal cell.

The influence of extracellular Ca2+ on the mediation of carbachol stimulation in isolated rabbit gastric parietal cells was studied. Removing Ca2+ from extracellular medium caused a 42% decrease of the aminopyrine accumulation due to carbachol with the same EC50 value (approximately 5 microM). A short time depletion in extracellular calcium suppressed the carbachol-dependent Ca2+ influx without affecting Ca2+ release from internal stores (fura-2 measurements). Similarly, the production of inositol phosphates under cholinergic stimulation was reduced by 29%. A rapid increase in Ins(1,4,5)P3 was obtained 5 s after carbachol stimulation, and this increase was not changed in Ca2(+)-depleted medium. In contrast, a 20 min incubation with carbachol caused a 50% reduction in both basal and carbachol-stimulated inositol phosphate accumulations. In conclusion, phospholipase C activation, intracellular Ca2+ release and aminopyrine accumulation were sequentially observed following carbachol stimulation of the isolated gastric parietal cell and extracellular calcium contributed to sustain this acid secretory response.

Aminopyrine↗

Risk factors for PTSD and other diagnoses in a general sample of Vietnam veterans.

This study examined the contribution of premilitary, military, and postmilitary risk factors to posttraumatic stress disorder (PTSD) and other postwar diagnoses in a sample of Vietnam veterans. PTSD was explained primarily by war stressors, including threat to life and exposure to grotesque death, but premilitary and postmilitary factors also contributed to the likelihood of a current diagnosis of PTSD. Panic disorder was also highly predicted by war experiences, whereas prewar functioning played a stronger role in several non-PTSD diagnoses. The study supported the notion that PTSD is specifically linked to intense stressors. Mechanisms for interactions among risk factors are discussed.

Adult↗

Spontaneous perforation of the extrahepatic biliary tree in infancy. A case report.

Spontaneous perforation of the bile duct in infancy is rare, with less than 55 cases described in the literature to date. The authors report the case of a 30-day-old neonate who presented with a 2-week history of progressive abdominal distension and intermittent jaundice. Disofenin technicium 99m sequential scintiscanning provided a preoperative noninvasive confirmation of the diagnosis of biliary ascites secondary to spontaneous perforation of the extrahepatic biliary tract. Distal common bile duct atresia was identified intraoperatively, and end-to-side Roux-en-Y hepaticojejunostomy was performed, with an uneventful postoperative recovery. The etiology, diagnosis, and treatment of spontaneous neonatal biliary perforation is discussed.

Ascites↗

Global aphasia without hemiparesis following prerolandic infarction.

Acute global aphasia without hemiparesis (GAWH) is said to result from the association of 2 separate lesions in the anterior and posterior left hemisphere language areas. We present 2 unusual cases of GAWH whose CTs revealed only a single lesion of the posterior part of F2 and F3. There was good recovery of verbal communicative abilities. Functional disconnection of posterior language areas seems responsible for this syndrome in such cases.

Aged↗

Inverted papilloma of bladder: clinical significance.

Based on 15 cases of inverted urothelial papilloma, we present the clinical significance of these lesions in view of the current literature. An inverted papilloma should raise suspicion with respect to the whole urothelial surface. However, approaching every lesion of this type as a (pre-)neoplastic tumor does not seem justified, since 90 percent of all cases reported so far do not present any clinical or histologic feature of malignancy. Some factors, such as the patient's history, eventually associated urothelial carcinomas, or histologic features of malignant transformation within an inverted papilloma, must be taken into consideration. If no single indication in favor of malignancy has been disclosed, we believe follow-up with yearly endoscopic investigations, in addition to regular urine cytologies, may suffice.

Aged↗

Chronic bacterial prostatitis: 10 years of experience with local antibiotics.

Direct transperineal infiltration of the prostate with antibiotics was performed in 24 selected patients with refractory chronic bacterial prostatitis. Diagnosis had been made following a modification of the classical lower tract localization studies. Remission periods of at least 6 months were obtained in 71 per cent of these patients after 1 or 2 infiltrations, while 6 of 24 (25 per cent) required several procedures to assume a long-term remission state and 1 (4 per cent) failed therapy (patient 24490). Seven patients had relapse after remission periods ranging from 13 months to 7 years. The last culture in 3 patients was positive. The value of the method compared to other therapeutic alternatives in the management of chronic bacterial prostatitis is discussed.

Adult↗