Biomedical subjects
Publications and source records attributed to D L Morris.
Peritoneal Echinococcus granulosus in gerbils was treated with albendazole. Both early and late infections were studied; response to albendazole therapy and the ability of the parasite to recover after treatment was found to depend on dose and length of therapy. Even after treatment at 50 mg/kg for 2 months late infections retained the ability to recover over 3 months.
Short case reports are presented of two patients seen in the U.K. with 'parasitic' obstructive jaundice. In one case the parasite involved was Clonorchis, and in the other it was Echinococcus. Both these parasites are uncommon in this country.
Cotton rats with Echinococcus multilocularis infections of one month's standing were treated for six months with albendazole (50 mg kg-1 day-1), or praziquantel (500 mg kg-1 day-1), or both drugs simultaneously. The germinal layer of albendazole-treated cysts differed little from control tissue apart from marginal increase in cyton vesiculation and the presence of small lamellated residual bodies. Protoscolex tissue appeared unaffected. The germinal layer of praziquantel-treated cysts differed markedly from control tissue, with increased vesiculation and mitochondrial number in those with intact germinal layers, and disintegration and detachment of the layer in other cysts. Protoscoleces were necrotic. After combined therapy, the germinal layer was either intact but with increased vesiculation and residual bodies present, or was disintegrating and detaching from the laminated layer.
Serum levels of albendazole sulphoxide in gerbils infected with Echinococcus granulosus and treated with albendazole (20 or 50 mg kg-1 day-1) by gavage were dose dependent, whereas albendazole administered in feed at a rate equivalent to 80 mg kg-1 day-1 achieved serum levels calculated to be equivalent to those produced by administration of 40 mg kg-1 day-1 by gavage. This regimen, over a three-month period, was effective and reduced parasite weight to 4.6% of that in control gerbils, and the treated parasite tissue showed ultrastructural changes ranging from severe accumulation of residual bodies to total disintegration of the germinal layer.
Compton backscatter imaging (CBI) is a technique that uses x-rays scattered from the closed-chest surface of the heart to obtain high frequency (5 msec) and high precision (+/- 0.1 mm SD) measurements of regional surface displacements and velocities. These measurements are acquired in a three-dimensional format that allows the reconstruction of the epicardial surface and the creation of color coded displacement and velocity maps at many time points during the cardiac cycle. Applications of the technique are shown to characterize detailed regional normal wall displacement and velocity patterns, and the significant alteration of those patterns after coronary embolization. The technique is also applied to the characterization of early diastolic wall dynamics. CBI measurements show that a brief and somewhat paradoxical inward displacement of the anterior ventricular wall occurs during early diastole in normal canines. The wall dynamics associated with this inward displacement suggest a brief collapse of the ventricle subsequent to aortic valve closure. Diastolic collapse velocities and displacements are significantly altered subsequent to coronary occlusion with mean and maximum collapse velocities decreasing by 50% and concomitant inward displacements decreasing by 40%. Data acquisition with CBI is non-invasive, does not require contrast agents or radioisotopes, and uses low irradiation levels (125 kVp, 3-5 ma). The average radiation dose to the heart for a typical study is 250 mrem, significantly lower than that of other radiation based imaging techniques.
The efficacy of albendazole (50 mg/kg/d), mebendazole (50 mg/kg/d) and praziquantel (500 mg/kg/d) against established intraperitoneal infections of Echinococcus multilocularis in gerbils was compared by monitoring parasite weight and making ultrastructural observations on treated and untreated material. Praziquantel was the most active protoscolicidal agent, reducing protoscolex viability to less than 2%, although it did not inhibit cyst growth. Albendazole was the most effective agent in reducing cyst growth and was, when compared with other regimes significantly more effective than mebendazole (p less than 0.05), praziquantel (p less than 0.01) or untreated controls (p less than 0.01).
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Injection sclerotherapy is widely used in the treatment of oesophageal varices. However, few studies have compared the local toxicity of sclerosant agents which may be important if serious local complications are to be avoided. In this study the depth of injury caused by submucosal injection of increasing concentrations of sodium tetradecyl sulphate, polidocanol, 5% ethanolamine oleate and 5% varicosid in rabbits stomach, has been compared by histopathological examination. Macroscopic ulceration was seen in 14.6% of injection sites. Increasing concentrations of sodium tetradecyl sulphate and polidocanol produced increasingly extensive microscopic inflammation. Five percent varicosid caused more inflammation than 5% ethanolamine and only 3% polidocanol and 5% varicosid caused full thickness inflammation. Only 5% ethanolamine produced inflammation consistently confined to the mucosa and submucosa. On the basis of this study we feel that 5% ethanolamine is the most suitable agent for injection sclerotherapy.
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The aim of this study was to examine the effect of pH on the measurement of carcino-embryonic antigen (CEA), and to assess the efficacy of a combination of serum and gastric juice levels of CEA and Carbohydrate Antigen 19.9 (CA 19.9) in the diagnosis of gastric carcinoma. An initial experiment was performed to determine the effect of pH on the CEA assay. There was a direct linear relationship between pH and the concentration of CEA measured by the assay, such that as hydrogen ion concentration increased, the apparent concentration fell. The correct value was measured at pH 7. Seventy-six normal patients with non-malignant upper gastro-intestinal disorders, and 49 patients with gastric carcinoma were studied, two of which were 'early' gastric carcinomas. All patients underwent upper GI endoscopy, and at this examination blood and gastric juice were taken for analysis. A 'normal range' was constructed as a 95% confidence interval for each of the antigens in serum and gastric juice. The highest sensitivity was achieved using a combination of the two antigens, CEA and CA 19.9 in gastric juice and serum, with a sensitivity of 95.7% and a specificity of 50%. This combination of assays could have value in a screening programme for gastric cancer.
A 2 mm fibreoptic choledochoscope with a disposable (resterilisable) flexible section was evaluated in 25 cadavers and 13 patients undergoing cholecystectomy. It was possible to pass the instrument via the cystic duct (CD) into the common bile duct (CBD) in 23 out of 25 cadavers and in 12 out of 13 patients. The CD diameter in cadavers was 2.4 mm (SD 0.5). Optical clarity was excellent and it was easy to pass into the duodenum, but proximal passage required mobilisation of the CD/CBD junction. This instrument may be a useful adjunct or even an alternative to intraoperative cholangiography.
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Following the observation that many critically ill patients cannot maintain their gastric juice pH below 4 without treatment a study was performed to measure the gastric juice pH in such patients and relate it to other clinical data. The case notes of 64 patients who had been admitted to the intensive care unit and taken part in two trials of ranitidine treatment were reviewed. During those trials gastric juice was aspirated hourly and the pH and volume measured. In this study the values recorded during a six hour untreated control phase were used. Data on age, diagnosis, treatment, outcome, episodes of hypoxia, episodes of hypotension, and use of inotropic drugs were also reviewed. Full data were available for 61 patients: 27 had a mean baseline pH of greater than 5 during the control phase and 34 a mean baseline pH of less than 5. Significantly more of those with a high pH suffered hypotension (21/27 v 13/34) and received inotropic drugs (16/27 v 8/34). These findings suggest that hypotension in critically ill patients adversely affects gastric exocrine function; prophylaxis with drugs that can improve gastric mucosal blood flow may be more effective than with antacids.
The gastrointestinal hormone, gastrin, was examined for its trophic effect on the growth of colorectal and gastric tumour cells. All of the freshly disaggregated colorectal and gastric human adenocarcinomas responded to pentagastrin in 24 h cultures in vitro. Two newly established adenocarcinoma cell lines showed a response to pentagastrin at passage 2 but not at passage 6. Long-established cell lines did not respond to pentagastrin; however, upon synchronization of the human gastric cell line, MKN45, a trophic growth response with gastrin-17 was observed. This response was enhanced when the same cell line was grown as a xenograft in nude mice and then examined in vitro for gastrin dependence; this dependence was gradually reduced on further in vitro passaging. These results indicate that trophic responses to gastrin are lost during in vitro culture and may be underestimated by using long-established tumour cell lines. However, as all of the early cultures of colorectal and gastric tumours respond trophically to gastrin, perhaps gastrin-receptor blockers may be an important therapeutic modality for these patients.