Biomedical subjects
Publications and source records attributed to S Boesby.
Totally implantable ports have gained popularity as venous access in the treatment of cancer. A case is reported with an uncommon but very serious complication, i.e., cytostatic extravasation secondary to a broken implanted catheter. Guidelines for implantation and remedies are recommended.
In order to investigate hepatic clearance of vasoactive intestinal polypeptide we measured its concentration in blood from the common carotid artery, right atrium and portal vein during orthotopic liver transplantation in six pigs. Just after laparotomy we found a significantly higher concentration of vasoactive intestinal polypeptide in portal plasma compared to that of the right atrium (p less than 0.05). This difference was soon eliminated by a fall in portal concentration, and, apart from fluctuations in portal concentration, no significant gradient between portal and atrial blood was recorded during the remaining part of the operation. When portal concentrations exceeded 30 pmol/l, the median reduction after transhepatic passage was 29% (range 16.8%-63.9%), while portal concentrations less than 30 pmol/l had a median reduction of only 6.3% (range 1.4%-16.5%) (p less than 0.05). No gradient between right atrial and systemic arterial blood was recorded. We suggest that a concentration-dependent clearance of splanchnic vasoactive intestinal polypeptide takes place in the porcine liver.
Plasma glucose, insulin, and C-peptide were measured in seven pigs after intravenous bolus injection of 1 mg glucagon and injection of 15 g glucose on the 1st, 2nd, 4th, and 7th days after orthotopic liver transplantation. Fasting plasma glucose and the glycemic response to glucagon were lower at the first postoperative day than on any other day (P less than 0.05). Glucose clearance after injection of glucose was normal and without day-to-day variation. Plasma insulin and C-peptide concentrations were higher the first day after glucose stimulation (P less than 0.05), but no impairment of insulin secretion was found during the study. We conclude that, apart from low hepatic glucose production on the first postoperative day, glucose homeostasis was sufficient after liver transplantation.
The aminoterminal propeptide of type III procollagen is extracted from the circulation by the liver, and PIIINP is found in bile. This study was performed in order to investigate whether biliary excretion contributes substantially to the hepatic extraction of circulating PIIINP. Hepatic extraction before and during a 4-h period after ligation of the common bile duct was assessed from serum PIIINP concentrations in a systemic artery, the portal vein and a hepatic vein of seven healthy anaesthetized pigs. Seven sham-operated anaesthetized pigs served as controls. Ligation of the bile duct did not cause a decrease in the hepatic extraction ratio of circulating PIIINP. The PIIINP serum levels of the cholestatic pigs and of the controls were similar throughout the investigation period. The PIIINP concentrations in bile were only 10% of the corresponding serum values. Gel filtration of sera showed that the lower PIIINP concentration in the hepatic vein, as compared to the artery and the portal vein was due to a selective decrease in the concentration of the intact propeptide. The study shows that biliary excretion does not contribute significantly to the hepatic extraction of circulating PIIINP in the normal liver. Furthermore, the hepatic extraction of circulating PIIINP preferentially affects the intact propeptide, rather than the somewhat larger PIIINP related molecule in serum.
Results of continuous 12 hour overnight pH monitoring (duration of pH less than 4) were reviewed in 112 patients with heartburn or regurgitation, or both, and in 56 normal subjects. Patients had more reflux than normal subjects. Medically controlled patients (n = 51) had less acid reflux than patients who subsequently underwent reflux surgery (n = 61), but there was a considerable overlap between those two groups. Surgery was followed by a reduction in acid reflux to a value similar to that in normal subjects. Patients in whom surgery was deemed to have failed had more reflux after the operation than those in whom it was successful, but no difference could be found in the preoperative reflux values of these two subgroups. Monitoring pH is not of value in selecting candidates for surgery since the results are not a good predictor of outcome, but it is useful in the objective evaluation of surgical results.
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On the basis of the endoscopic appearance, 71 rectal polyps were assessed as adenomata or non-neoplastic polyps, after which the endoscopic diagnosis was compared with the results of histological examination. The diagnosis based on macroscopic examination of the polyps proved correct in only 62% of the cases. It is concluded that the diagnosis of adenoma cannot be established solely on the proctoscopic appearance of a polyp and, as adenomata are premalignant, removal of all polyps found at proctoscopy is recommended.
We attempted to induce chronic peptic ulcer in the rat by injection of consecutive doses of cysteamine. We investigated the incidence of peptic ulceration and measured gastric mucosal histamine, histamine formation capacity (HFC), plasma gastrin and tissue (oesophagus, duodenum, liver and lung) histamine in rats 1, 7, 14, 21, and 28 days after injection of cysteamine-HCl (300 mg/kg s.c. and 100 mg/kg 8 h later). Saline injections were used in control rats. After 24 h all rats given cysteamine had duodenal ulcers and the ulcer incidences after 7 and 14 days were 60 and 40%, respectively. After Day 21 no ulcers were found. Microscopy revealed ulcer healing seen as epithelialized scars from Day 14 onwards. A rising incidence of gastric metaplasia of the duodenal mucosa was noted from Day 7 after cysteamine treatment, which may have pathophysiological significance. Gastric mucosal histamine was higher and plasma gastrin was lower after 24 h compared with controls and values obtained later in the study. Rats with duodenal ulceration had significantly higher gastric mucosal histamine than those without lesions and control rats. A direct relationship was found between plasma gastrin and HFC in rats given cysteamine. A small but significant increase in histamine content of the liver was also observed after 24 h. No significant changes were found in other tissue specimens. Thus, a rise in gastric histamine is associated with duodenal ulcers in this model.
The concentration of lipids, lipoproteins and apolipoproteins A-I and -B were measured in the plasma of 12 patients with peptic ulcer disease before and after five weeks of treatment with cimetidine. No statistically significant changes were found, but HDL cholesterol and HDL2 cholesterol tended to increase, and VLDL cholesterol and plasma triglycerides tended to decrease. A review of published studies indicates that the data at present are too uncertain to warrant use of cimetidine as a lipoprotein modulating drug.
Eighteen patients were treated for severe symptomatic gastroesophageal reflux with insertion of an Angelchik prosthesis. Three months after the operation all were free of symptoms. Postoperative 12-hour intra-esophageal pH monitoring showed significant reduction in acid reflux. Basal gastroesophageal sphincter pressure did not change significantly. After three years, one of the patients had symptomatic relapse. We conclude that the Angelchik prosthesis is effective in the treatment of symptomatic gastro-esophageal reflux, and that it is an alternative to conventional surgical procedures.
Hepatic and renal clearance of the amino-terminal propeptide of type III procollagen (PIIINP) and of the glycosaminoglycan, hyaluronan (HA) were investigated in a catheterization study of seven healthy anesthetized pigs. Two assays were used, in order to distinguish between the metabolism of different PIIINP-related antigens. One was the PIIINP RIA Kit, which measures the intact propeptide. The other was the PIIINP Fab assay, in which the antibody has an equal affinity to the intact propeptide and to smaller fragments, of which the latter constitutes most of the antigenic activity in serum. Hepatic and gastrointestinal extraction were evaluated from measurements of serum concentrations in the artery, the portal vein and the hepatic vein. We found a significant hepatic extraction of the intact propeptide (extraction ratio 0.14) and of HA (extraction ratio 0.23), but not of smaller PIIINP fragments. No gastrointestinal extraction of any of the tested substances could be demonstrated. Only smaller PIIINP fragments (such as the col 1 fragment) were extracted by the kidneys (the extraction ratio in the PIIINP Fab assay was 0.19). The renal extraction ratio of HA was 0.14. The amounts of PIIINP fragments and of HA extracted by the kidneys were 50- and 3-times the amounts found in urine, respectively, indicating that the col 1 fragment and HA are degraded in the kidneys in addition to urinary excretion. Our results suggest a dynamic turnover of connective tissue-related components with a fast catabolism of circulating components in liver and kidneys.
The exact etiology of carcinoid flushing remains unknown, but the symptoms are probably mediated through release of one or several humoral substances. Flushing seen in fore-gut carcinoids (gastric carcinoids) has been ascribed to excessive histamine release, whereas flushing seen in mid-gut carcinoids (ileal carcinoids) tentatively has been ascribed to excessive release of serotonin, bradykinin, substance P, substance K or eledoisin. In this study plasma histamine was measured in 8 patients with mid-gut carcinoids and carcinoid syndrome using an enzymatic isotopic method in order to evaluate histamine as the vasoactive agent in patients with ileal carcinoid tumours and carcinoid syndrome. All patients had raised plasma histamine values. In patients with mid-gut carcinoids histamine may be one of the substances mediating flushing.
Hypotension and cardiac arrhythmia are commonly seen during liver transplantation both in man and in experimental animals. The cardiovascular changes may be explained by release of vasoactive substances, e.g. histamine, into the systemic circulation. Abdominal operations are followed by an increased histamine concentration in portal blood. If the liver clears excess histamine from the splanchnic system, an increased histamine concentration should not be found in the systemic circulation. We measured plasma histamine in peripheral arterial blood, blood from the right atrium and portal blood in different phase of liver transplantation in ten pigs. Histamine concentration increased in the portal vein in the anhepatic phase (basal 15.85 pmol/ml to 34.67 pmol/ml, median, p less than 0.05) but no changes were found in arterial or right atrium samples. Venous and later arterial revascularisation were not followed by any changes in histamine concentration in arteria and right atrium samples. We conclude that the transplanted liver can eliminate splanchnic histamine and that histamine is unlikely to be involved in the cardiovascular changes which are seen after revascularisation of the liver.
Intestinal calcium-binding protein (CaBP) (molecular weight 10,000) was measured by a specific enzyme-linked immunoadsorbent assay in duodenal biopsies of 94 patients (aged 20-89 years). The patients were examined for complaints of upper abdominal dyspepsia, but no significant pathology was found by gastroduodenoscopy. The median amount of CaBP in duodenal biopsies was 6.0 micrograms/mg of cytosolic protein with a coefficient of variation of 0.6. No change in the amount of CaBP per mg of cytosolic protein was observed with age. A significant correlation (P less than 0.001) was found between the concentration of CaBP and s-1,25-dihydroxyvitamin D (1,25(OH)2D). The amount of CaBP per mg of cytosolic protein did not correlate with immunoreactive parathyroid hormone in serum, and no relation between CaBP and the specific activity of alkaline phosphatase of the mucosal biopsies was found. The results of the present study show a wide variation in the amount of the 10 kDa CaBP in duodenal biopsies of humans and no change with age. Further, a correlation between s-1,25(OH)2D and CaBP was found.
The aminoterminal propeptide of type III collagen was monitored in serum during liver transplantation in nine pigs. The aim was to investigate whether removal of the liver causes any changes in the serum concentration of the propeptide. Another connective tissue component, hyaluronan, a glycosaminoglycan known to be degraded in the liver endothelial cells, was also measured. Removal of the liver caused a significant increase in the concentration of the intact propeptide as well as of hyaluronan. Gel filtration confirmed the increase in the amount of intact propeptide. However, another large propeptide-related antigen, eluted near the void volume, appeared in the antigen profile during the anhepatic phase. This peak probably represents the propeptide still attached to the collagen molecule (pN collagen). The findings indicate that the liver is involved in the degradation of the propeptide and of larger propeptide-holding proteins.
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Bradykinin concentrations in peripheral venous blood were measured in seven patients with carcinoid syndrome. The diagnosis was based on typical symptoms and raised urinary excretion of 5-hydroxy-3-indole acetic acid; the carcinoid tumour was verified histologically. Two patients were flushing constantly and the other patients had flushing attacks two to 10 times daily. Several blood samples were taken at weekly intervals from six of seven patients. During 30 sampling procedures the patients were flushing during sampling in 12 instances. Bradykinin was measured by a sensitive solid phase radioimmunoassay technique. Blood bradykinin concentration was normal in all patients. Bradykinin is unlikely to be the vasoactive mediator of flushing.
The aim of this study was to investigate oesophageal peristalsis and gastro-oesophageal function in normal subjects after 4 days of cisapride 10 mg p.o. 3 times/day and 10 mg 1.5 h before the investigation. The study was carried out in a double-blind cross-over design with coded cisapride or placebo tablets. Basal sphincter pressure increased after cisapride (p less than 0.002). The peristaltic pressure amplitude in the oesophageal body as well as the duration and velocity of the peristaltic pressure wave were measured after wet swallows. No changes were found. Intragastric pH was unchanged after cisapride. No effect was found on the result of a standard acid clearing test. Plasma concentration of cisapride did not correlate with any of the other variables. Oral cisapride increases fasting gastro-oesophageal sphincter pressure, but does not influence oesophageal peristalsis, acid clearing or intragastric pH in normal subjects.