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Biomedical subjects

T Almdal

Publications and source records attributed to T Almdal.

At least 37 records · Page 2Linked to original sources

High volume plasma exchange in fulminant hepatic failure.

We investigated the effect of repeated high volume plasma exchange with fresh donor plasma in 11 patients with fulminant hepatic failure, all initially in stage 3 or 4 encephalopathy. A daily exchange of a volume equal to the extracellular volume (20% of body weight) on three consecutive days was intended. We obtained an average of 2.6 exchanges each with a mean volume equal to 16% of the body weight. Five patients (46%, 95% confidence limits 17%-77%) survived, all with acetaminophen induced liver failure. Four of the 6 non-survivors showed a temporary improvement in cerebral function. Two of the patients woke up completely. The 6 non-survivors maintained a stable condition with a systolic blood pressure > 110 mm Hg for a mean of 6.9 days after initiating plasma exchange. Plasma exchange may be considered in acute liver failure in patients with residual liver function before transplantation is finally decided. In addition, plasmapheresis may be used to keep patients with definite liver failure clinically stable until a transplant can be performed.

Acetaminophen↗

Increased hepatic capacity of urea synthesis in acute and chronic uraemia in rats.

We studied whole body nitrogen balance in female rats for 28 days after induction of experimental uraemia by 5 6 nephrectomy and at the same time the kinetics of hepatic urea synthesis by means of the in vivo capacity of urea synthesis. The N-balance of 5 uraemic rats kept in metabolic cages was negative on day 2, and positive but only half of control on day 28. In between, it was normal. The uraemic rats lost weight during the first week, and later only slowly regained their initial weight. The capacity for urea synthesis was determined during alanine loading in 5 unoperated controls, in uraemic rats in groups of 5 on days 2, 7, 14, 21, and 28, and correspondingly in sham operated rats. In the control rats the capacity was 8.9 +/- 0.7 micromol/(min 100 g BW) and the same in sham operated rats. In uraemic rats the capacity increased to 17.1 +/- 2.0 micromol/(min 100 g BW) (p < 0.01) 2 days after partial nephrectomy. On day 7, the capacity fell to 5.5 +/- 1.0 (not different from initial values), and thereafter again gradually increased to 16.5 +/- 1.5 micromol/(min 100g BW) on day 28. The early increase in the capacity may be related to glucagon, that nearly doubled on day 2, but not on day 28. The hepatic capacity for urea synthesis doubles biphasically: acutely and after 4 weeks of experimental uraemia. This may play a role in the reduction in N-balance, since an increase in the capacity implies larger hepatic amino-N conversion at any blood amino-acid concentration.

Journal Article↗

Elective cholecystectomy increases plasma amino-acid clearance and hepatic capacity for urea synthesis for one week.

The importance of the liver in post-operative catabolism was studied in 6 cholecystectomy patients given a mixture of amino-acids as prime-continuous infusionś pre-operatively and on the 1st, 3rd, 6th and 12th post-operative day. The plasma clearance of total alpha-amino-nitrogen and of single amino-acids, the urea-nitrogen synthesis rate, and the functional hepatic nitrogen clearance were calculated. Surgery decreased fasting blood amino-nitrogen concentration by 15% (p < 0.01), and increased the plasma clearance of amino-nitrogen by 30% (P < 0.05) on the 1st, 3rd and 6th post-operative day. Surgery doubled the functional hepatic nitrogen clearance (p < 0.01) on the 1st, 3rd and 6th post-operative day. This indicates that post-operative stress catabolism is partly due to a hepatic condition by which the liver eliminates more amino-nitrogen despite lower amino-acid concentration in the blood, for one week post-operatively.

Journal Article↗

Sex hormones in postmenopausal women with primary biliary cirrhosis.

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p less than 0.05) elevated serum concentrations of estrone and androstenedione and significantly (p less than 0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5 alpha-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone and non-protein-bound testosterone did not differ significantly (p greater than 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher sex hormone binding globulin and estrone sulfate levels compared with noncirrhotic patients with primary biliary cirrhosis. Otherwise, no significant differences were observed between cirrhotic and noncirrhotic patients. The observed changes in steroid concentrations may be a consequence of hepatic dysfunction.

Aged↗

Contradictory effects of uncomplicated versus complicated abdominal surgery on the hepatic capacity for urea synthesis in rats.

Female Wistar rats weighing 217 g were subjected to two types of surgical stress: uncomplicated (hysterectomy) and complicated (spleen and uterus ligated, crushed, and left in situ). Liver function as assessed by amino-N conversion was measured as the capacity for urea-N synthesis preoperatively (control animals) and on Days 1, 3, and 6 postoperatively. Uncomplicated surgery transiently increased the capacity for urea-N synthesis by 30% the first postoperative day (P less than 0.001). Complicated surgery decreased the capacity for urea-N synthesis to 55% throughout the investigation period (P less than 0.001). This was not due to a general change in liver mass since galactose elimination capacity remained constant. The increase in the capacity for urea-N synthesis after uncomplicated surgery is probably due to glucagon since plasma glucagon increased whereas plasma insulin and blood glucose remained unchanged after amino acid loading. The persistent decrease in the capacity for urea-N synthesis in complicated surgery is not due to changes in these regulators: glucagon increased, insulin decreased, and the rats were hypoglycemic. All changes are expected to increase the capacity for urea-N synthesis. The mechanism for the emergence of these two distinct metabolic patterns is not known. The phenomenon is probably important for interpretation of metabolic data on clinical stress.

Amino Acids↗

Effects of hysterectomy and semi-starvation on amino-acid gradients across liver, muscle and gut in rats.

To study the effects of surgical stress and insufficient food intake on amino-acid exchange of liver, gut, and muscle, blood was sampled in random sequence from the aorta, the inferior caval vein, the portal vein, and the hepatic veins in 3 groups of 20 rats each. Control rats were fed ad libitum, hysterectomised rats were studied on the first and third post-operative day, and semi-starved rats were pair-fed to hysterectomised rats to an intake of 13% of control on the first day. Both groups lost 5-8% of body weight. Surgery increased the concentration gradient (release) of urea across liver by 60%, the glucose gradient (release) by 35%, and doubled the concentration gradients (uptake) across liver of alanine, arginine, glycine, lysine, proline, serine, and threonine, and decreased their plasma concentrations. There was no major change in hepatic amino-acid gradients in semi-starved animals, and there was no appreciable change in gradients of single amino-acids across gut or muscle in animals subjected to surgery or semi-starvation. Post-surgical increases in urea synthesis and hepatic uptake of uragenic and gluconeogenic amino-acids are due to the surgical stress and not to the post-operative semi-starvation.

Journal Article↗

Indomethacin prevents the increase in urea synthesis capacity and the weight loss after hysterectomy in rats.

Prostaglandins have been suggested to be mediators of post-operative catabolism. Previous studies have shown that stimulation of urea synthesis contributes to post-operative nitrogen loss. The effect of prostaglandins on this hepatic function was assessed in hysterectomized rats on the first post-operative day by measurements of the Capacity of Urea-N Synthesis (CUNS) with and without indomethacin treatment. Hysterectomy increased CUNS by 1 3 and led to a weight loss of 10 g in one day. Indomethacin prevented the increase in CUNS and the post-operative weight loss in operated animals; it also decreased CUNS by 1 3 in control rats. Blood amino-nitrogen concentration of indomethacin treated hysterectomized rats was 1 3 lower than in untreated animals, indicating an even more marked effect of indomethacin on post-operative tissue amino-acid release than on CUNS. Indomethacin exerts a nitrogen sparing effect, possibly depending on normalization of both post-operative hepatic amino-nitrogen conversion and tissue proteolysis. This may be of clinical importance in controlling post-operative catabolism.

Journal Article↗

Effect of gastrin on liver regeneration after partial hepatectomy in rats.

Gastrin has been shown to be an important trophic hormone for the mucosa of the stomach and the proximal intestine. In the present study the effect of gastrin on liver regeneration after partial hepatectomy in rats was investigated. After partial hepatectomy a significant rise in the concentration of gastrin in portal venous blood was found six, 12, and 18 hours after 70% hepatectomy. The effect of changes in the endogenous gastrin concentration on the liver regeneration was investigated in rats subjected to antrectomy or to fundectomy. Partial hepatectomy was done three weeks after the primary surgery. We found antrectomy to decrease liver regeneration, whereas fundectomy had no effect. Administration of pentagastrin 300 micrograms/kg sc three times daily for two and four days after partial hepatectomy significantly increased the rate of liver regeneration compared with controls. This study suggests that gastrin has a hepatotrophic effect. Whether this effect is caused by a direct action of gastrin on the hepatocytes or it is an indirect effect mediated by for instance insulin, glucagon or epidermal growth factor has to be further investigated.

Animals↗

Vitamin D, parathyroid hormone, and bone mineral content of lumbar spine and femur in primary biliary cirrhosis.

In order to elucidate the pathogenesis and degree of osteopoenia in primary biliary cirrhosis (PBC) we conducted a cross-sectional study of 47 non-selected female patients with biopsy-proven PBC. Bone mineral content (BMC) of the lumbar spine, femoral neck and femoral shaft was determined using dual photon absorptiometry. Compared to healthy females of corresponding decades the PBC patients exhibited significantly decreased mean BMC-values in lumbar spine (88%, P less than 0.05) and femoral neck (92%, P less than 0.05) but not in femoral shaft (96%, NS). Bone mineral content was not significantly associated with duration of liver disease, impairment of liver function (serum concentrations of albumin, clotting factors II + VII + X, bilirubin, alkaline phosphatase galactose elimination capacity or histology), variables reflecting calcium homeostasis (serum concentrations of ionized calcium, parathyroid hormone, vitamin D binding protein, 25-hydroxy vitamin D3 and 1,25-dihydroxy vitamin D3) or previous treatment with glucocorticosteroids. In view of our negative findings we suggest that future studies in this field should focus on physical activity and female sex hormones as determinants for the prevention of osteopoenia in females with primary biliary cirrhosis.

Adult↗

Decrease in ureagenesis by partial hepatectomy does not influence acid-base balance.

It has been suggested that urea synthesis participates directly in body pH homeostasis by removal of bicarbonate. To elucidate this hypothesis sodium bicarbonate or sodium chloride was infused (11.5 mumol/min) for 90 min into control rats and into rats that had undergone an 85% hepatectomy immediately before starting the infusion. Urea synthesis rate was 2.6 +/- 0.3 mumol/min (mean +/- SE) in controls, and was significantly (P less than 0.01) reduced to 1.0 +/- 0.2 mumol/min in partially hepatectomized rats. At the start of bicarbonate infusion, pH was 7.38 and 7.34 in control and partially hepatectomized rats, respectively, and at the end of infusion, pH was 7.56 and 7.51. Standard bicarbonate at start of bicarbonate infusion was 21.9 and 21.3 mM in controls and partially hepatectomized, respectively, and it increased to 32.7 and 29.9 mM at end of infusion. In saline-infused rats a slight decrease of approximately 0.05 pH units was observed during the experiment, but again no difference emerged between control and partially hepatectomized rats. It is concluded that a major role of the liver in the regulation of acid-base balance is unlikely.

Acid-Base Equilibrium↗

Cerebral blood flow and liver function in patients with encephalopathy due to acute and chronic liver diseases.

The purpose of the present investigation was to study changes in cerebral blood flow (CBF) in hepatic encephalopathy, to ascertain whether this was related to the changes in liver function and whether these changes gave any prognostic information. CBF, determined by the intravenous xenon-133 method, and liver functions, assessed by the prothrombin index, bilirubin concentration, and the galactose elimination capacity, were studied in patients with acute fulminant liver failure and in patients with encephalopathy due to chronic liver diseases--that is, cirrhosis of various etiologies. The CBF range in healthy young subjects (age, 23-42 years) was 44-61 ml/100 g/min; in patients with grade I + II encephalopathy (mean +/- SEM) it was 32.8 +/- 3.6 ml/100 g/min in acute (n = 4; age, 28 +/- 8 years) and 37.0 +/- 3.3 ml/100 g/min in chronic liver patients (n = 10; age, 51 +/- 2 years). In grade III + IV encephalopathy it was 28.7 +/- 3.8 ml/100 g/min in acute (n = 8; age, 28 +/- 3 years) and 32.9 +/- 3.7 ml/100 g/min in chronic patients (n = 12; age, 49 +/- 3 years). CBF did not correlate with the liver function and was of no prognostic value. The liver function was markedly reduced in all the patients, without any differences between patients with acute or chronic liver diseases or the different degrees of hepatic encephalopathy. In conclusion, a marked reduction of the CBF was seen in hepatic encephalopathy, irrespective of the etiology of the disease.

Adult↗

Dexamethasone increases the capacity of urea synthesis time dependently and reduces the body weight of rats.

Rats of 230 g were treated with 0.1 mg of dexamethasone twice daily for 2 days (n = 5) and 14 days (n = 9). Controls received isotonic saline. During the first week of dexamethasone treatment the rats lost weight rapidly (up to 9 g/day). The weight loss diminished during the second week of treatment. The fasting blood insulin concentration increased sevenfold in the dexamethasone-treated rats. Fasting blood glucagon and glucose concentrations were not different from controls. In the dexamethasone-treated rats the fasting alpha-amino-N concentrations were lower: 4.0 +/- 0.3 mmol/l (mean +/- SEM) versus 6.8 +/- 0.3 mmol/l in controls. The capacity of Urea-N Synthesis, determined during alanine loading was: after 2 days of treatment 14.7 +/- 1.7 mumol/(min 100 g), after 14 days of treatment 7.9 +/- 0.8 mumol/(min 100 g), and in controls 7.5 +/- 1.0 mumol/(min 100 g) (mean +/- SEM). In conclusion, glucocorticoid treatment leads to a transient change in the liver function as to hepatic amino-N conversion, implying that more amino-N than normal is eliminated as urea-N after 2 days of treatment. This may contribute to the early, but not the late body weight loss.

Animals↗

Monocyte functions in diabetes mellitus.

The aim of this study was to investigate the functions of monocytes obtained from 14 patients with diabetes mellitus (DM) compared with those of monocytes from healthy individuals. It was found that the total number of circulating monocytes in the 14 diabetic patients was lower than that from the healthy individuals. Phagocytosis of Candida albicans was decreased in the monocytes from the patients, whereas pinocytosis of acridine and phagocytosis of latex and sheep red blood cells were normal. The chemotactic response towards casein was enhanced. The possible consequences of these findings for the elucidation of concomitant infections in diabetic patients are discussed.

Adult↗

Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats.

The role of epidermal growth factor on liver regeneration after partial hepatectomy in rats was investigated. After a 70% hepatectomy in rats, the concentration of epidermal growth factor in portal venous blood was unchanged compared with unoperated controls. However, small amounts of epidermal growth factor could be identified in portal venous blood after intestinal instillation of epidermal growth factor. Brunner's glands and the submandibular glands secrete epidermal growth factor. Extirpation of Brunner's glands decreased liver regeneration, whereas removal of the submandibular glands had no effect on liver regeneration. Epidermal growth factor antiserum reduced liver regeneration significantly. Oral or s.c. administration of epidermal growth factor had no effect on liver regeneration, whereas epidermal growth factor enhanced the effect of insulin and glucagon on liver regeneration. The results suggest that endogenous epidermal growth factor participates in stimulation of liver regeneration after partial hepatectomy in rats. Epidermal growth factor given together with insulin and glucagon had a synergistic effect on liver regeneration which suggests that liver regeneration in the rat is controlled by multiple regulatory peptides.

Animals↗

Bacteremia in patients suffering from cirrhosis.

In a five-year retrospective study, there were 57 episodes of bacteremia among 1623 admissions (3.5%) of patients suffering from cirrhosis. Gram-positive bacteria were found in 70% of the episodes, gram-negative bacteria in 30%. All of the gram-positive bacteria found were fully sensitive to methicillin and to gentamicin. The gram-negative bacteria found were all sensitive to gentamicin, but only 50% were sensitive to ampicillin. The distribution between gram-positive and gram-negative bacteria was the same, irrespective of whether the patients acquired the infection inside or outside the hospital. More than 50% of the patients suffered from one or more of the following complications of cirrhosis: ascites, encephalopathy and haematemesis. Twenty-one patients died within seven days after the bacteremia was diagnosed. Bacteremia is a serious complication of advanced cirrhosis, and it is recommended that adequate antibiotic treatment is started when septicemia is suspected.

Adolescent↗

Xylitol normalizes the accelerated hepatic capacity for conversion of amino nitrogen to urea nitrogen in diabetic rats.

In diabetes, the capacity of urea nitrogen synthesis, ie, a substrate-independent measure of the hepatic conversion of amino nitrogen to urea nitrogen, is increased. Xylitol decreases urea synthesis in normal rats. Capacity of urea nitrogen synthesis and nitrogen balance were measured during intravenous alanine loading in control rats, rats with experimental diabetes (streptozocin 75 mg/kg), and rats with experimental diabetes infused with xylitol to 1 mmol/L. In control rats, capacity of urea nitrogen synthesis was 9.4 +/- 1.1 mumol/min per 100 g of body weight, and nitrogen balance -2.7 +/- 1.2 mumol/min per 100 g of body weight. In the diabetics, these values were markedly increased to 26.6 +/- 1.9 and -16.3 +/- 2.1 mumol/min per 100 g of body weight, respectively (p < 0.01). The infusion of xylitol normalized these values to 11.2 +/- 1.0 and -3.6 +/- 2.1 mumol/min per 100 g of body weight for capacity of urea nitrogen synthesis and nitrogen balance, respectively. Xylitol did not change glucagon or insulin. Xylitol improved the nitrogen economy of uncontrolled diabetic rats by decreasing urea synthesis. The mechanism is not settled, but it does not involve insulin or glucagon.

Amino Acids↗