[Preventive measures against blood-borne pathogens during surgery. Double gloves are effective].
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Biomedical subjects
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Human liver microsomes were found to catalyze 7 alpha-hydroxylation of 27-hydroxycholesterol at a rate of up to about 0.2 nmol/mg protein per min. The product of the reaction, 5-cholestene-3 beta, 7 alpha, 27-triol, was identified by means of combined gas chromatography-mass spectrometry. Liver microsomes from two patients with an upregulated cholesterol 7 alpha-hydroxylase, did not have higher 7 alpha-hydroxylase activity towards 27-hydroxycholesterol than those from untreated patients, suggesting that the 7 alpha-hydroxylase active towards 27-hydroxycholesterol is not the same as that active towards cholesterol. The mitochondrial fraction of liver from untreated patients and patients treated with cholestyramine, had negligible 7 alpha-hydroxylase activity towards 27-hydroxycholesterol less than 0.01 nmol/mg protein per min). The results are in accord with the possibility that there is a pathway to bile acids in human liver in which the first step is a 27-hydroxylation of cholesterol.
The effects of intravenously administered somatostatin and vasoactive intestinal peptide (VIP) on bile secretion were studied in 10 patients with complete biliary fistulas. The two peptides were administered both separately and simultaneously. During the infusion of vasoactive intestinal peptide, bile secretion increased by 85%, whereas during somatostatin infusion it decreased by 40%. When the peptides were administered together, the VIP-induced choleretic effect was not reduced by somatostatin. Vasoactive intestinal peptide infusion increased bicarbonate concentration and output, whereas somatostatin had the opposite effect. The output of chloride also increased following vasoactive intestinal peptide infusion but decreased following somatostatin infusion. The concentration of chloride was unaffected by somatostatin whereas it was decreased by vasoactive intestinal peptide. The output of bile acids was unaffected by vasoactive intestinal peptide and decreased by somatostatin infusion, whereas total lipid concentration increased during somatostatin infusion and decreased when vasoactive intestinal peptide was added. It is concluded that, in man, somatostatin acts on the bile acid-dependent canalicular bile secretion and also, to some extent, on the ductular secretion, whereas vasoactive intestinal peptide acts strictly at the ductular level. The effects of the two peptides on bile secretion are independent of each other.
The effects of intravenously administered vasoactive intestinal peptide (VIP) and secretin on bile secretion were studied in 12 patients with complete biliary fistulas. The two peptides were administered both simultaneously and separately. During VIP infusion bile volume increased by 60%, and during the combined VIP and secretin infusion bile volume increased by another 70%. VIP increased bile bicarbonate concentration by some 30%. Although secretin did not increase the concentration, bicarbonate output increased threefold during secretin infusion but only twofold during VIP infusion. The outputs of bile acids were not significantly affected by the two peptides, whereas the concentrations decreased by 40% and 70% after VIP and secretin, respectively. The canalicular bile flow, measured by [14C]erythritol, was unaffected by VIP infusion, whereas secretin alone and the combination of the two peptides increased the canalicular clearance by 80%. The choleretic effect of VIP thus seems to occur only at the ductular level. Secretin exerts its effect at the ductular level and possibly also at the canalicular level. It is concluded that the two peptides have additive effects on the ductular bile flow.
Age-dependent alterations in the effects of catecholamines on lipolysis were investigated in 25 young (21-35 yr) and 10 elderly (58-72 yr) healthy, nonobese subjects using isolated adipocytes obtained from abdominal subcutaneous tissue. Basal lipolysis was not affected by aging, while the rate of catecholamine-stimulated lipolysis was reduced by 50% in the elderly subjects (P less than 0.005). To elucidate the mechanisms behind this phenomenon lipolysis was stimulated with agents that act at well-defined steps in the lipolytic cascade, from the receptor down to the final step: the activation of the protein kinase/hormone-sensitive lipase complex. All agents stimulated lipolysis at a 50% lower rate in elderly as compared with young subjects (P less than 0.05 or less). However, half-maximum effective concentrations of the lipolytic agents were similar in both groups. The antilipolytic effects of alpha 2-adrenoceptor agonists were also the same in young and old subjects. Moreover, the stoichiometric properties of the beta- and alpha 2-receptors did not change with increasing age. In vivo studies performed on the same individuals likewise demonstrated an impaired lipolytic responsiveness, with 50% lower plasma glycerol concentrations during exercise in the elderly subjects (P less than 0.05), in spite of a normal rise in plasma norepinephrine. The plasma glycerol levels correlated strongly to the glycerol release caused by catecholamine-stimulated lipolysis in vitro in both young and elderly subjects (r = 0.8-0.9, P less than 0.001). In conclusion, a decreased activation of the hormone-sensitive lipase complex appears to be the mechanism underlying a blunted lipolytic response of fat cells to catecholamine stimulation in elderly subjects. This finding may, explain the age-dependent decreased lipolytic response to exercise in vivo.
Glucose uptake by the intestine and its conversion into 3-carbon compounds in the human intestine in the basal state and after an oral glucose load are not understood. Consequently, we studied the arterial and portal venous concentration differences (A-PV) for glucose and glucogenic substrates in the basal state and 3 h after the ingestion of a 100-g glucose load with the catheter technique. Five patients were studied 3-11 days after surgery for gallbladder disease or cancer of the colon or liver. A-PV for glucose in the basal state was 0.12 +/- 0.02 mM (P less than 0.01), indicating net glucose uptake by extrahepatic splanchnic tissues. No net exchange of lactate or pyruvate was detected, but there was release of alanine and uptake of glutamine. After glucose ingestion, glucose was released by the gut, reflecting absorption of the load (mean A-PV for glucose -2.10 +/- 0.04 mM, P less than 0.01). The arterial glucose concentration rose gradually from 4.6 +/- 0.1 mM before glucose ingestion to a plateau at 9.5 +/- 0.7 mM from 90 to 180 min. Glucose ingestion was accompanied by net lactate and alanine release (A-PV -0.16 +/- 0.06 mM and -48 +/- 7 microM, respectively), whereas A-PV for pyruvate did not change. We conclude that, in postoperative patients, there is a significant net glucose uptake by the gastrointestinal tract in the basal state. Glucose ingestion is accompanied by a small release of lactate and alanine from the intestine. However, the estimated net gut formation of lactate and alanine can play only a minor role in the disposal of an oral glucose load.
In 41 patients, operated upon for common bile duct stones, a temporary bile fistula was achieved by means of a T-tube and a Foley-catheter with an occludable balloon. To learn more about peptide control of bile secretion, 6-8 days after surgery, bile flow was studied before as well as during infusion of the three peptides somatostatin, vasoactive intestinal peptide and secretin. The findings, also presented in Figure 17, were: 1. During somatostatin infusion, bile secretion decreased by 30%, and bile lipid output was reduced by some 10%. The clearance of [14C]-erythritol decreased by 25%, indicating an effect on the bile acid-dependent canalicular bile secretion (Paper I). 2. Vasoactive intestinal peptide (VIP) increased bile secretion by 65%. The concentration of bile lipids decreased, whereas the output was uneffected. The bicarbonate concentration increased, and the concentrations of sodium and potassium were uneffected. [14C]-erythritol clearance was not influenced by VIP infusion. Thus, VIP stimulated bile secretion at the ductular level (Paper II). 3. VIP increased bile secretion by 60%, whereupon secretin increased it by another 70%. Neither of the two peptides effected bile acid output. Both VIP and secretin increased bicarbonate output, whereas only VIP increased the concentration. The clearance of [14C]-erythritol was uneffected by VIP infusion, but increased following secretin, as did the clearance of [14C]-mannitol. Thus, VIP stimulated bile secretion at the ductular level, whereas secretin seemed to stimulate bile secretion both at the ductular level and at the bile acid non-dependent canalicular level (Paper III). 4. Whereas VIP stimulated bile secretion, somatostatin decreased it by some 40%. Even when somatostatin was administered during VIP infusion, no reduction of the VIP-induced choleresis was seen. VIP increased both bicarbonate concentration and output, whereas somatostatin had the opposite effect. The concentration of chloride increased following VIP infusion, but decreased following somatostatin. The output of bile acids was not influenced by VIP infusion and decreased by somatostatin, whereas total lipid concentration increased during somatostatin infusion with a decrease when VIP was added. Thus, somatostatin acts on the bile acid-dependent canalicular bile secretion and also, to some extent, on the ductular secretion. The effects of the two peptides on bile secretion are independent of each other (Paper IV). 5. While fasting, 6-8 days after bile duct surgery, bile secretion averaged 290 microliters/min. Canalicular bile secretion, as measured by the clearance of [14C]-erythritol, constituted some 80% of total bile flow. Maximum de novo synthesis of bile acids was 8.7 mmol/24 h, implying a 8-9 fold stimulation due to interrupted enterohepatic circulation (Paper V). 6. No serious side effects from this method with temporary bile fistulas following bile duct surgery were found. Therefore, the method is recommended for further research on human bile secretion (Paper V).
Somatostatin is a peptide that has anticholeretic properties in the dog. The purpose of the present work was to investigate if somatostatin is an anticholeretic agent in humans also. The effects of intravenous infusion of somatostatin on hepatic bile flow and biliary electrolytes and secretion of biliary lipids were studied in 7 patients with complete biliary drainage who had been operated on for choledocholithiasis. Somatostatin, 250 microgram/h, was found to decrease the hepatic bile secretion by approximately 30%. The peptide also reduced the outputs of bile acids, cholesterol, and phospholipids and the outputs of sodium, potassium, and chloride. The concentrations of the biliary lipids were not significantly changed. Somatostatin inhibited the erythritol clearance in the 2 patients studied by approximately 25%. The present study thus provides evidence that somatostatin inhibits bile formation in humans. It appears as if the reduction in bile production is mainly due to decreased canalicular bile flow. It is possible that this effect of somatostatin is attributable to inhibition of bile acid synthesis or of transport-secretion of bile acids, or both.
The effect of intravenously administered vasoactive intestinal polypeptide on bile secretion was studied in 11 patients with complete biliary drainage. After infusion of vasoactive intestinal polypeptide, bile volume increased by 65%. In the 2 patients investigated, the output of bicarbonate increased by approximately 250% and the concentration by 50%-70%. Vasoactive intestinal polypeptide thus caused a bicarbonate-rich choleresis. The output of biliary lipids was not affected by infusion of vasoactive intestinal polypeptide, whereas the concentration decreased by approximately 40%. The canalicular bile flow, measured by the clearance of [14C]erythritol, was not affected by infusion of vasoactive intestinal polypeptide. The choleretic effect of vasoactive intestinal polypeptide thus seems to occur only at the ductular level. The ductular bile flow was calculated to be stimulated threefold to fourfold.
Fluorescein flowmetry (FF) implies the measurement of a relative capillary blood flow, expressed as an index--that is, the ratio between the maximum fluorescence, obtained during the first circulatory passage of sodium fluorescein (Na-F), and the rise time, defined as the time interval between 10% and 90% of the maximum fluorescence. The aim of this study was to develop FF to be used during endoscopy for the evaluation of ventricular and duodenal mucosal blood flow. FF was applied during gastroduodenoscopy in 38 patients with normal mucosa, as verified by histopathologic examination. The blood flow index did not differ significantly for the mucosa of the fundus, corpus, and antrum. However, when compared with the duodenal mucosa, the blood flow index of the ventricular mucosa was almost twice as high (P less than 0.01). This, in turn, was due to a significantly higher maximum fluorescence in the ventricular mucosa (P less than 0.01), indicating a denser capillary network than in the duodenal mucosa. Since FF is a reliable method, easy to perform and without complications, it is suitable whenever mucosal blood flow warrants measurement during endoscopy.
Prophylactic somatostatin (Stillamin, Serono) was given i.v. to 26 patients for 24 hours (250 micrograms/h) in order to reduce the incidence and severity of hyperamylasemia and pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). Patients who during the preceding year had been subjected to ERCP served as historical controls. The incidence of hyperamylasemia following ERCP was 58% and 57% in somatostatin-treated patients and controls, respectively. There was no significant difference between the serum amylase levels in the controls and in patients given prophylactic somatostatin. No patient developed clinically overt pancreatitis. It is concluded that prophylactic somatostatin does not reduce the incidence or severity of hyperamylasemia following ERCP.
During a 12 year period 38 patients underwent various palliative biliodigestive procedures for unresectable pancreatic carcinoma. Jaundice, upper abdominal pain and weight loss was present in 82%, 53% and 40% of the patients respectively. Serum bilirubin was elevated in 95% of patients, on average almost 9 times the upper limit of normal. Alcaline phosphatase was elevated in 97% of patients, on average almost 5 times the upper normal limit. Fourteen patients died without leaving hospital, 10 within one month, for an inhospital mortality of 36.8%. For the remaining 24 patients mean survival was slightly more than 7 months. Only 4 patients survived for more than one year. Palliation thus was short but reasonably good as judged by decrease in serum bilirubin and alcaline phosphatase levels.
Two elderly patients with massive bleeding from jejunal diverticulosis are reported. Scintigraphy revealed the bleeding source. Emergency resection of the involved portion of jejunum cured the patients. Few such cases have been published. Although very rare, one must always have in mind jejunal diverticula to be the source of gastrointestinal haemorrhage.
Fifteen patients with history of biliary colic, induceable by cholecystokinin, but normal oral cholecystogram and ultrasonogram were studied prior to and after cholecystectomy. Fasting duodenal bile, obtained preoperatively after administration of cholecystokinin, and gallbladder bile obtained at operation were analyzed. The lipid composition as well as the cholesterol saturation were within the range seen in gallstone-free subjects. The total lipid concentration of gallbladder bile was normal, whereas that of duodenal bile was reduced by about 50%, indicating a less efficient gallbladder emptying. In 10 of the 15 patients, the analysis of the excised gallbladder displayed macro- or microscopic abnormalities; two patients had cholesterol gallstones. At re-examination 9-27 months after the operation, 12 of the patients were completely symptom-free and two patients reported a clear improvement while on still had unchanged symptoms. It is concluded that cholecystectomy is the treatment to prefer in patients with "acalculous" biliary pain, induceable by cholecystokinin.
Two cases of metastasis from breast carcinoma to the small intestine are discussed. The literature is reviewed and the macroscopic view of the tumours is discussed.
Nine patients with bleeding oesophageal varices, who had not responded to aggressive conservative treatment, underwent emergency transabdominal oesophageal transection and reanastomosis using a mechanical stapling instrument. According to the classification of Child, 2 were graded as Class A, 4 as Class B, and 3 as Class C. Successful control of haemorrhage was achieved in all patients. Three patients died 15-33 days postoperatively. Causes were hepatic failure, sepsis and circulatory insufficiency. Recurrent variceal bleeding occurred in one patient after 15 and 23 months. One patient bled from the oesophageal wall were a clips had slipped after 17 months. One patient required postoperative dilatation due to oesophageal stricture. There was no anastomotic leakage and no cases of hepatic encephalopathy. One patient died after 26 months from an intercurrent disease. The remaining 5 patients are alive and free from symptoms related to varices 6, 20, 24, 25 and 32 months postoperatively. When other measures prove ineffective, transection with the EEA instrument can be recommended to control exsanguinating haemorrhage from oesophageal varices. It seems to be a useful additional procedure to those already in use. For definite assessment and conclusion, however, more experience from additional operations must be gained and longer follow-up is required.
In sixteen patients subjected to intestinal surgery, the transport of sodium fluorescein (Na-F) was measured between the mucosal and serosal-muscular layers. Experiments were carried out in intestinal anastomosis by fluorescein flowmetry (FF). The blood-flow index of the mucosal layer was about twice the serosal-muscularis, per unit tissue volume. The temporal changes in fluorescence pattern from the two layers showed that more than 90% of Na-F, eliminated from the mucosal layer, was transported to the serosal-muscular layers. In six patients, in whom Na-F was instilled intraluminarily, fluorescence was seen on the outside of the intestine after 3 min. However, when the circulation was stopped before Na-F was instilled, no fluorescence was seen, this suggests that the transport was not only due to diffusion but also to convection. The results suggest that functional serially-coupled exchange vessels may exist within the intestinal wall, and that Na-F is transported both by convection and diffusion.
In eight patients subjected to abdominal surgery, the effect of intravenous cimetidine (Tagamet) on hepatic arterial blood flow and portal blood flow was studied, utilizing electromagnetic blood flowmetry. Following cimetidine an increase in hepatic arterial blood flow concomitant with a decrease in mean arterial pressure were detected. Calculated hepatic artery vascular resistance was therefore significantly decreased by 28% after 2 min and 17% after 10 min. There was no change in portal blood flow. It is suggested that this effect of cimetidine is due to increased plasma histamine levels after acute H2 receptor blockade.