Biomedical subjects
Publications and source records attributed to L Jivegård.
Abdominal aortic reconstruction was successfully performed in three kidney transplant patients without the use of any specific measures to protect the kidney transplant during aortic cross-clamping. The cases are discussed in relation to previously published case reports describing various surgical techniques to protect kidney transplants during abdominal aortic reconstruction.
It has been suggested that glycoproteins play an important role as a nucleating agent in the pathogenesis of gallstone formation. Arachidonic acid, by an indomethacin-sensitive mechanism, is known to enhance gallbladder mucus release, suggesting that prostaglandins may regulate gallbladder epithelial release of mucus. In this study, the glycoprotein granules of the principal cells of the mouse gallbladder epithelium were morphometrically analyzed using electron microscopy. It was shown that 5 micrograms of prostaglandin E2, injected into the gallbladder lumen of the anesthetized mouse, reduced the relative volume of glycoprotein granules from 3.0% to 0.7% of the cytoplasmic volume within 20 min, whereas injection of the same amount of the solvent for prostaglandin E2 had no such effect.
1. Endogenous opioid peptides are found in the enteric nervous system in the gastrointestinal tract. The opioid peptide enkephalin, which has anti-secretory action in the small intestine, is also contained in nerves in the gall-bladder wall. 2. In experimental cholecystitis, there is active fluid secretion by the epithelial cells into the gall-bladder lumen, when the intraluminal hydrostatic pressure is low. This fluid secretion to the lumen was abolished by intravenous administration of enkephalin, an effect that was blocked by naloxone pretreatment. The flux of fluid into the lumen was also abolished when the intraluminal hydrostatic pressure was raised to the level initially observed in the inflamed and obstructed gall bladder. Fluid absorption in the normal gall bladder was unaffected by enkephalin. 3. In experimental cholecystitis, naloxone, used as a non-specific antagonist of opiate action, did not affect the gall-bladder mucosal fluid transport observed at a low intraluminal hydrostatic pressure, but it induced fluid secretion when this pressure was high. 4. It is suggested that a raised intraluminal hydrostatic pressure in experimental cholecystitis, which distends the gall bladder, releases endogenous opioids that inhibit active fluid secretion by the gall-bladder epithelial cells. This response may represent a defence mechanism that could be present also in the gastrointestinal tract. In the obstructed and inflamed gall bladder it may prevent progressive distension, ischaemia and perforation of the wall.
Gallbladder mucosal net fluid transport and motility were measured in vivo by a continuous perfusion technique in the anaesthetized cat. Prostaglandin E2, administered to the perfused gallbladder lumen, caused a contraction decreasing gallbladder volume capacity, and induced a secretory response by the mucosa. These effects by prostaglandin E2 were abolished by the nerve-blocking agent tetrodotoxin (administered close intraarterially) and somatostatin (administered intravenously), but not by intravenous hexamethonium. Atropine (administered intravenously) reduced the order of magnitude of the gallbladder contraction in response to prostaglandin E2 but did not affect the secretory response by the mucosa. Neither of these drugs significantly affected gallbladder volume capacity or mucosal fluid transport during basal conditions. Tetrodotoxin did not abolish the gallbladder responses to intravenous cholecystokinin or vasoactive intestinal peptide, peptides known to act directly upon smooth muscle and epithelial cell receptors, respectively. It is suggested that prostaglandin E2 affects gallbladder function in vivo mainly by activation of postganglionic non-cholinergic intramural nerve cells.
Biliary lipids and bilirubin were measured in hepatic and gallbladder bile obtained at routine cholecystectomy in 35 gallstone patients. The gallbladders had opacified at cholecystography and the cystic ducts were patent at operation. The histologic changes in the gallbladder wall were evaluated by an independent pathologist. Increasing abnormality of the gallbladder wall was shown to be associated with reduced gallbladder contents/hepatic bile ratio of biliary lipids and of bilirubin. The concentrating function of the human gallbladder thus appears to be impaired in proportion to the severity of histologic lesions in its wall. Taken together with earlier findings in vitro, this relationship suggests impaired absorption of electrolytes and water by the gallbladder mucosa, or diffusion of biliary constituents from the lumen of the inflamed gallbladder.
A recent study demonstrated the activity of the feline sphincter of Oddi to be regulated by the distending pressure in the biliary tract via inhibitory nerves running along the common bile duct. In the present study this mechanism was investigated in cats previously subjected to cholecystectomy. An increment in the hydrostatic pressure in the biliary tree from 0 to 20 cmH2O did not affect the function of the sphincter of Oddi in cholecystectomized cats, but relaxed the sphincter in controls and in cats with sham operation. Morphologic study of the nerve arrangement in the feline extrahepatic biliary tract revealed that cholecystectomy is likely to damage pericholedochal nerves. These experimental observations may have relevance for the development of biliary dyskinesia following cholecystectomy in some patients, and suggest that when performing biliary-tract surgery it is important to preserve nerve fibers running along the common bile duct.
Recent research suggests that disturbances in gallbladder mucosal functions are important in the initiation of acute cholecystitis and its progression. Prostaglandins have pathophysiological significance and prostaglandin synthesis inhibitors such as indomethacin inhibit fluid secretion by gallbladder mucosa, reduce distension and relieve pain. Nerves in the gallbladder wall are involved in disturbed mucosal function, and the benefits of opiates may derive from reduction of active fluid secretion in the inflamed and obstructed gallbladder as well as from central analgesic effects.
The normal fluid absorption across the gallbladder mucosa is, in experimental cholecystitis, changed to an active net fluid secretion. This fluid secretion, studied in anesthetized cats, is not abolished by extrinsic gallbladder denervation and is unaffected by atropine but is strongly reduced by intraarterial tetrodotoxin or intraluminal administration of lidocaine hydrochloride. Intravenous somatostatin or hexamethonium administration also reduce this secretion. Indomethacin, known to abolish this fluid secretion, did not further reduce it when administered after nerve blocking agents in the present study. These data demonstrate that the prostaglandin-induced gallbladder fluid secretion in experimental cholecystitis is influenced by intramural nerves. It is suggested that gallbladder inflammation is associated with prostaglandin-induced activation of intrinsic nerves which may stimulate the epithelial cells to fluid secretion. In the obstructed gallbladder, this secretion causes gallbladder distension by increasing the intraluminal pressure. This mechanism may have a key role in the pathophysiology of acute cholecystitis.
Arterial reconstruction is the treatment of choice for patients with severe lower limb ischaemia, but may at times be technically impossible. Thirty-two consecutive patients with impending (n = 24) or already established (n = 8) distal arteriosclerotic or diabetic lower limb gangrene, in whom vascular surgery was either technically impossible or had failed, were treated with epidural spinal electrical stimulation (ESES) for 27 +/- 16 (S.D.) months. All patients had severe rest pain, which was reduced by ESES in 91% of the cases. Improved ulcer healing was noted in 58% of the patients who had skin ulceration. Eighty-three percent of those patients who did not have established gangrene when ESES was started, retained their leg after 1 year, and 54% after 3 years. These results suggest that ESES often provides pain relief and improves skin healing in patients with impending arteriosclerotic or diabetic gangrene in whom vascular surgery is impossible or has failed. Epidural spinal electrical stimulation (ESES) does not affect the progression of established gangrene but may provide pain relief. The observed outcome of severe limb ischaemia in this study could be used to compare with those after arterial reconstruction performed in patients with poor run-off vessels, and may allow us to examine the natural history of this disease when adequate pain relief is provided. The results reported here and the previously reported enhancement of cutaneous blood flow in severely ischaemic extremities by ESES may suggest, that ESES enhances limb salvage by improving skin blood flow.
Fluid secretion by the gallbladder mucosa is suggested to have a key pathophysiological role in acute cholecystitis, since it causes distension of the obstructed gallbladder. The present study investigates the actions of loperamide on the gallbladder function in experimental cholecystitis. Gallbladder fluid transport and motility were studied in vivo with a continuous perfusion technique. A net fluid secretion by the gallbladder mucosa was seen in cats in which cholecystitis was induced whereas there was a net fluid absorption from the gallbladder lumen in the control animals. The net fluid secretion in experimental cholecystitis was inhibited by loperamide (1 mg/kg), an effect that was blocked by naloxone (1 mg/kg), suggesting an involvement of specific opiate receptors. Loperamide (1 mg/kg) relaxed the normal gallbladder but had no significant effects on its fluid absorption. Since loperamide reduces mucosal fluid secretion in experimental cholecystitis without contracting the gallbladder wall, it is suggested that this peripherally acting opiate agonist could be useful in the treatment of patients with acute cholecystitis.
In experimental cholecystitis there is a net fluid secretion into the gallbladder lumen and an increased release of prostaglandins. Indomethacin and opiates are known to inhibit this mucosal fluid secretion. Intraluminal or intra-arterial administration of prostaglandin E2 reduces basal gallbladder fluid absorption or induces a net fluid secretion to the lumen and also contracts the normal gallbladder. The use of a continuous perfusion technique in anaesthetized cats in this study shows that the effects of prostaglandin E2 on gallbladder function are blocked by intravenous morphine and loperamide. Naloxone does not affect the gallbladder responses to PGE2 administration. As a mechanism of action it is suggested that opiates inhibit secretory and contractile nerves that are activated by prostaglandins in the gallbladder wall. The findings suggest that the pain relieving effects of opiates in cholecystitis and biliary pain partly are due to blocking of the effects by prostaglandins on gallbladder function.
Immunoreactive VIP was detected in the gallbladder lumen and in the arterial blood and venous effluent from the gallbladder in fasting cats. During perfusion of the gallbladder in vivo there was a constant basal intraluminal secretion of VIP. The VIP concentration in the luminal effluent exceeded that in plasma supporting the notion that there was a release from the gallbladder tissue. The rate of secretion was significantly increased during efferent electrical stimulation of the peripheral cut end of the cervical vagal nerves, after blockade with atropine. A similar increase in concentration of VIP was seen in the venous effluent from the gallbladder. The results suggest a local release of VIP from intrinsic neurons within the gallbladder wall. This release is increased in response to activation of non-cholinergic fibres in the vagus nerves, suggesting a role for VIP in regulation of gallbladder functions.
Both experimental cholecystitis and luminal distension inhibit fluid absorption and stimulate motor activity in the gall bladder. These functional alterations are mimicked by exogenous prostaglandins (PGs) and inhibited by potent cyclooxygenase inhibitors, but direct evidence of a primary role of endogenous PGs is not available. Therefore, experiments in the cat were carried out in which the effects of lyso-phosphatidylcholine (lysoPC; 0.5-2.0 mmol/l), implantation of cholesterol stones, and raised intraluminal pressure in the gall bladder lumen were assessed. The gall bladder was perfused in vivo at a constant rate by a buffer solution. PGE2 was determined in the effluent by a radioimmunological method validated by gas chromatography-mass spectrometry. PGE2 output was markedly (p less than 0.01) raised (13.9 +/- 2.6 vs 1.1 +/- 0.5 ng/h; n = 10) during lysoPC perfusions and this response was inhibited by 66% (p less than 0.02) after indomethacin administration (2 mg/kg iv). A significant (p less than 0.05) increase in PGE2 output occurred six weeks after implantation of gall stones (3.7 +/- 1.5 ng/h; n = 6) and in response to distension of the normal gall bladder wall (3.6 +/- 1.2 ng/h; n = 6). These findings support the theory that PGs play an important pathophysiologic role in biliary tract disease.
In experimental cholecystitis a net secretion of fluid to the gallbladder lumen is seen in animals with morphological signs of acute inflammation. This fluid secretion, which increases the intraluminal pressure in the obstructed gallbladder, is suggested to be influenced by non-cholinergic intramural gallbladder nerves activated by prostaglandins. In the present study in vivo we show that this fluid secretion, measured by a perfusion technique, is markedly inhibited by electrical activation of the splanchnic nerves that contain adrenergic fibres to the gallbladder and by intravenous administration of an alpha 2-adrenergic agonist, demonstrating that this fluid secretion can be modulated by activation of alpha 2-adrenergic receptors. In patients with an obstructed gallbladder outlet, inhibition of this secretion may reduce gallbladder distension and thus relieve biliary pain. The results suggest that pharmacological activation of adrenergic mechanisms could be useful in the treatment of cholecystitis and biliary pain.
In an analysis of 236 consecutive patients with acute limb ischemia treated as embolic event, using only the Fogarty catheter, 30 cases of arterial thrombosis were identified. This group was compared with 92 patients with true embolism. Surgical failure was significantly more common in the thrombosis than in the embolism group (50% vs. 13%). The rate of hospital deaths was high (27%) among the patients with thrombosis, and there was close correlation (r = +0.76) between early postoperative gangrene and early death in these patients, but not in those with embolism. Severe ischemia, advanced age and surgical failure were significant risk factors for mortality in the patients with thrombosis. The authors conclude that early identification of these patients is important, that risk factors should be evaluated and that operations should be done by surgeons accustomed to procedures for adequate revascularization, since simple thrombectomy is associated with high rates of failure and mortality.
The cystic duct was ligated and gallstones were implanted into the gallbladder in cats. Five to eighteen weeks later the hydrostatic pressure in the gallbladder lumen was measured after laparotomy, and fluid transport across the gallbladder epithelium was studied and compared to the microscopic gallbladder morphology. Instead of the normal absorption many of these gallbladders continuously secreted fluid to the lumen and had raised intraluminal hydrostatic pressure (61 +/- 8 SEM, mmHg). Morphological signs of acute gallbladder inflammation were common (47%) in gallbladders with mucosal fluid secretion, but were never seen in those that absorbed fluid (p less than 0.05). Gallbladder mucosal fluid transport correlated with a histological score of the inflammation (r = +0.68, p less than 0.01). Gallbladder fluid secretion decreased when the intraluminal pressure was experimentally raised to the initially observed level, demonstrating mechanisms counteracting the secretion in this situation. An increased intraluminal pressure is suggested to be involved in the pathophysiology of acute cholecystitis.
Peripheral vascular disease of the extremities causes ischemic pain and, at times, skin ulcerations and gangrene. It has been suggested that epidural spinal electrical stimulation (ESES) could improve peripheral circulation. Since 1978 we have used ESES in 34 patients with severe limb ischemia; all had resting pain and most had ischemic ulcers. Arterial surgery was technically impossible. Twenty-six patients had arteriosclerotic disease, one had Buerger's disease, and seven had severe vasospastic disorders. Ninety-four per cent of the patients experienced pain relief. ESES healed ulcers in 50% of those with preoperative nonhealing skin ulcerations. Seventy per cent of the patients showed improved skin temperature recordings. Only 38% of the stimulated arteriosclerotic patients underwent amputations during a mean followup period of 16 months, as compared to 90% of a comparable group of unstimulated patients. ESES is very promising in severe limb ischemia where reconstructive surgery is impossible or has failed.
Administration of morphine or its derivatives is the traditional way to treat biliary pain. Despite the common use of morphine and its analogues in patients with cholecystitis and biliary pain, their effects on the function of the inflamed gallbladder are not known. In the present study it is demonstrated that morphine usually contracts the normal gallbladder but does not influence the fluid transport across the mucosa. In experimental cholecystitis morphine and enkephaline do not further contract the gallbladder but, by specific opioid receptors, reduce the inflammatory fluid secretion by the mucosa. In case of obstruction of the gallbladder, fluid secretion by the mucosa will distend its wall and induce biliary pain. It is suggested that the pain-relieving effect of morphine in cholecystitis and attacks of biliary pain is mediated not only by a central analgesic effect but also by an influence on the function of the inflamed gallbladder.