Drug treatment for acute upper gastrointestinal bleeding.
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Biomedical subjects
Publications and source records attributed to R Shields.
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Since previous reports have suggested that somatostatin may be of value in the control of acute variceal haemorrhage, we compared its efficacy with that of injection sclerotherapy in a randomised controlled clinical trial. Eighty consecutive patients with endoscopically-proven severe variceal bleeding were randomised to injection sclerotherapy (n = 41) or somatostatin (n = 39) given as a continuous infusion of 250 micrograms/h for 5 days plus daily bolus administration of 250 micrograms. The efficacy of injection sclerotherapy and somatostatin infusion in controlling haemorrhage and preventing rebleeding (censored at 5 days), mortality (censored at 28 days) and complications was compared. The aetiology of the portal hypertension and transfusion requirements was similar between the two groups, but there were more patients with severe liver disease (Child's C) in the somatostatin group. There was no significant difference between the two treatments in the initial (p = 1.0) or overall control of bleeding (p = 0.58). Furthermore, somatostatin was as effective as injection sclerotherapy in controlling bleeding in patients with severe liver disease or in those actively bleeding at the time of their endoscopy. The relative risk of rebleeding whilst receiving somatostatin compared to injection sclerotherapy was 1.39 [95% Confidence Interval (CI) 3.73; 0.52], but this was reduced to 0.98 (95% CI 0.37; 2.67) when readjusted for Child's grading, the only prognostic factor shown to be of significance. Mortality was not significantly different between the two groups of patients (p = 0.31). The relative risk of dying whilst receiving somatostatin compared to injection sclerotherapy was 1.6 (95% CI 3.93; 0.66) but was reduced to 1.03 (95% CI 0.47; 2.47) when adjusted for Child's grading, the only significant prognostic factor. Complications in the somatostatin group were minor and less frequent than after injection sclerotherapy. The results of this study indicate that somatostatin is a safe treatment, which is as effective an endoscopic injection sclerotherapy for acute variceal bleeding.
Surgical management of massive upper gastrointestinal bleeding after failed medical treatment may be hazardous because of diffuse bleeding from several sites, further complicated in some patients by intercurrent disease, age, or previous surgery. Experience with combined somatostatin and octreotide therapy in five such patients is described. All were treated initially with either intravenous somatostatin (250 micrograms/hour) or octreotide (Sandostatin) (50 micrograms/hour) for periods ranging from three to five days, after which they were given subcutaneous octreotide (50 or 100 micrograms three times daily). Bleeding was controlled by this regimen in all cases. The patients were all discharged from hospital on either ranitidine (n = 4) or omeprazole (n = 1). Repeat endoscopy at the end of the treatment period with somatostatin and octreotide (n = 1) or four weeks after discharge (n = 3) showed complete healing of the bleeding sites. Somatostatin and octreotide may be of value in controlling severe upper gastrointestinal bleeding in patients in whom surgery is hazardous because of bleeding from several peptic lesions further complicated in some by intercurrent disease or age.
Recent evidence indicates that muscle ischemia and activation of the muscle chemoreflex are the principal stimuli to sympathetic nerve activity (SNA) during isometric exercise. We postulated that physical training would decrease muscle chemoreflex stimulation during isometric exercise and thereby attenuate the SNA response to exercise. We investigated the effects of 6 wk of unilateral handgrip endurance training on the responses to isometric handgrip (IHG: 33% of maximal voluntary contraction maintained for 2 min). In eight normal subjects the right arm underwent exercise training and the left arm sham training. We measured muscle SNA (peroneal nerve), heart rate, and blood pressure during IHG before vs. after endurance training (right arm) and sham training (left arm). Maximum work to fatigue (an index of training efficacy) was increased by 1,146% in the endurance-trained arm and by only 40% in the sham-trained arm. During isometric exercise of the right arm, SNA increased by 111 +/- 27% (SE) before training and by only 38 +/- 9% after training (P less than 0.05). Endurance training did not significantly affect the heart rate and blood pressure responses to IHG. We also measured the SNA response to 2 min of forearm ischemia after IHG in five subjects. Endurance training also attenuated the SNA response to postexercise forearm ischemia (P = 0.057). Sham training did not significantly affect the SNA responses to IHG or forearm ischemia. We conclude that endurance training decreases muscle chemoreflex stimulation during isometric exercise and thereby attenuates the sympathetic nerve response to IHG.
Sixteen patients with persistent (n = 11) or recurrent (n = 5) variceal bleeding after injection sclerotherapy and balloon tamponade were treated with an intravenous infusion of somatostatin 250 micrograms/h. Somatostatin infusion successfully controlled the bleeding in 15 of the 16 patients but one rebled after 72 h of treatment. In one patient with poor liver function (Child's C) bleeding was not controlled by somatostatin, further injection sclerotherapy or balloon tamponade of the oesophagus. The results of this study, although uncontrolled and with a small number of patients, suggest that somatostatin is a very effective treatment for the control of post-injection sclerotherapy variceal bleeding.
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Twenty-two patients who experienced a severe haemorrhage from either oesophagitis (n = 8) or ulcers (n = 14) following injection sclerotherapy of their oesophageal varices were treated with intravenous administration of somatostatin (250 micrograms/h). Somatostatin was effective in controlling haemorrhage and preventing rebleeding in all eight patients bleeding from oesophagitis and in 12 of the 14 patients bleeding from oesophageal ulcers. In two patients with ulcers, haemorrhage persisted despite two periods of concominant balloon tamponade and somatostatin infusion and bleeding was eventually controlled by repeated hourly bolus injections of the hormone for 24 h superimposed on the continuous infusion. The results of this study suggest that somatostatin is an effective and safe treatment for the control of bleeding from either oesophagitis or ulcers following injection sclerotherapy of oesophageal varices.
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Scintigraphic studies of the oropharyngeal transit of a liquid bolus were performed in 15 healthy controls, 12 patients with symptoms of oral-pharyngeal dysphagia, and 13 patients with neuromuscular disease, who did not have dysphagia. Gamma camera imaging of the head, neck, and upper thorax was undertaken, in the lateral projection, during the swallowing of the radiolabeled bolus of water. Inspection of summed images permitted the selection of regions of interest (ROI) to represent the mouth, pharynx, and upper esophagus. Transit times between each ROI were calculated and compared. Significant prolongation of bolus transit time between the mouth and esophagus was present in both patients with and without dysphagia (0.59 +/- 0.38 sec and 0.33 +/- 0.7 sec; mean +/- SD, respectively) compared with controls (0.26 +/- 0.04 sec P less than 0.001, P less than 0.01, respectively, Mann-Whitney U test). Repeat studies in 25 individuals indicated that the transit measurements were more reproducible between swallows in normal subjects than in patients with symptoms. Deglutitive scintigraphy provides a noninvasive technique for the quantitative study of swallowing and its disorders.
In the light of the control of expenditure and changes in radiopharmaceutical costs, changes in study protocols, new investigation procedures and inappropriate placing in Korner categories, the BNMS Council set up a working party to derive an agreed set of costings for Nuclear Medicine techniques. Using data from three hospitals with additional information from another nine, we have agreed the 1988 cost of individual nuclear medicine procedures in the UK. These figures include staffing (radiopharmacy, nursing, physics, medical including consultant), radiopharmaceuticals and other consumables, indirect costs (secretarial, administrative, portering), variable overheads (service contracts, stationery) and fixed overheads (rates, lighting, heating, building and engineering). Capital costs, equipment and buildings were not included. Because figures include salary and overhead costs they are difficult to compare with the majority of other previous nuclear medicine costings, apart from Bretland et al., or with data for other imaging modalities. Comparison of these costings with Korner schedules shows marked overlap between the Korner groups. Such groups therefore form a poor method of costing nuclear medicine procedures. We propose alternative groupings.
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In a planned sequential policy for the emergency control of continued bleeding from oesophageal varices, oesophageal transection was performed after failure of conservative treatment, including injection sclerotherapy. In 15 patients who underwent emergency oesophageal transection, bleeding was controlled by operation in the majority (87 per cent), but 11 of the 15 patients died in hospital. Mortality in patients with poor liver function (Child's C) was 100 per cent, the majority of deaths resulting from hepatic and renal failure. The results of this study suggest that emergency oesophageal transection to control acute variceal haemorrhage is associated with a poor prognosis in patients with poor liver function and questions its role in a sequential emergency treatment policy.
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The T cell antigen receptor is likely to play a role in both positive and negative selection in the thymus. Three populations of thymocytes can be distinguished by the level of expression of the CD3-alpha/beta-chain heterodimer of the T cell antigen receptor (CD3/Ti alpha/beta) complex. Cells which fail to express these receptors or express low levels of receptors are contained in a population of thymocytes which express low levels of the CD5 antigen and are predominantly CD4+/CD8+. Thus, these cells appear to be relatively immature phenotypically. In contrast, the cells which express high levels of CD3/Ti alpha/beta co-express high levels of CD5 and are predominantly contained in the more mature single positive cells which express either CD4 or CD8. With the calcium-sensitive dye, Indo-1, and immunofluorescence, we demonstrated that, despite the relative phenotypic immaturity of cells which express low levels of CD3/Ti alpha/beta, these antigen receptors are able to mediate transmembrane signaling when stimulated with CD3 monoclonal antibodies. Although increases in calcium were observed in these CD3/Ti alpha/beta-low expressing cells in response to anti-CD3, no proliferative response was observed, even in the presence of phorbol myristate acetate. Proliferative responses were observed in the more mature cells which express high levels of CD3/Ti alpha/beta. These results suggest that, rather than a defect in the functional capability of the antigen receptor complex to mediate transmembrane signaling events, cellular responses to signals generated by the antigen receptor may differ at various stages of thymocyte development.
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Concanavalin A (Con A), which together with phorbol myristate acetate (PMA) can activate the human T cell line Jurkat to produce interleukin 2 (IL 2), is shown to depend on the expression of the T3/T cell antigen receptor heterodimer (T3/Ti) complex to induce activation. alpha-methyl mannoside was able to reverse all of the observed effects of Con A on intracellular biochemical events. Therefore, ligand-receptor occupancy appears to be required for sustaining biochemical events associated with triggering the T3/Ti complex. Studies of the time-dependent requirements for the two stimuli required for activation revealed that simultaneous stimulation with both Con A and PMA is required for 2 to 4 hr for the cell to commit itself to activation, as measured by the appearance of secreted IL 2. This 2- to 4-hr requirement correlated precisely with the appearance of IL 2 mRNA, and the appearance of IL 2 transcripts depended on protein synthesis during this critical time period.