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Biomedical subjects

A Danielsson

Publications and source records attributed to A Danielsson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Gastrointestinal symptoms in myotonic dystrophy.

BACKGROUND: Gastrointestinal complaints may be the initial symptom in myotonic dystrophy (MD). However, the frequency of gastrointestinal symptoms has never been prospectively evaluated. METHODS: Forty patients with MD were interviewed with regard to their GI symptoms with a standardized questionnaire. A group of healthy subjects matched for age and sex served as controls. RESULTS: The most prevalent symptoms were abdominal pain (55%), dysphagia (45%), emesis (35%), chronic or episodic diarrhoea (33%), coughing while eating (33%), and anal incontinence (30%). Twenty-five per cent of the patients considered their GI problems to be the most disabling consequence of the disease, and 28% had GI problems that started before the diagnosis of MD. CONCLUSIONS: GI symptoms are common in patients with MD, may be the initial symptoms, and are often considered to be the most disabling consequence of the disease.

Abdominal Pain↗
PubMed1996

Protective effects of trolox C, vitamin C, and catalase on bromobenzene-induced damage to rat hepatocytes.

BACKGROUND/METHODS: The protective effects of trolox C (water-soluble vitamin E), vitamin C, and catalase on bromobenzene (BB)-induced toxicity to isolated rat hepatocytes were evaluated. The glutathione (GSH) content of the hepatocytes exposed to BB was measured. RESULTS: BB caused acute damage to the cells during 2 h of incubation (short) when BB was added directly to the culture wells, whereas a late-occurring and time-dependent increase in lactate dehydrogenase (LDH) leakage rate was observed during 24 h of incubation (long) when BB was dissolved in a different way. Incubation of the cells with trolox C (0.5-2.0 mM) prevented the hepatocellular damage induced by BB at 2.4 mM during the long-term incubation. Vitamin C (0.1-1.0 mM) had a protective effect on BB-induced toxicity during both the short- (BB, 1.6 mM) and the long- (BB, 2.4 mM) term incubations. Catalase (3200 U/ml) also showed a beneficial effect on the cells during the short-term BB exposure. Trolox C (2.0 mM) and vitamin C (0.5 mM) restored BB-induced GSH depletion in the cells. CONCLUSIONS: BB induced two patterns of LDH leakage from isolated hepatocytes on the basis of different ways of BB exposure and incubation periods. Trolox C, vitamin C, and catalase exerted protective effects on BB-induced toxicity during short- or/and long-term incubations. The effects were concentration-dependent. Restoration of GSH content in BB-exposed hepatocytes suggests that trolox C and vitamin C could reduce GSH consumption during BB metabolism and exert an antioxidant effect.

Analysis of Variance↗
PubMed1995

Colchicine treatment of primary sclerosing cholangitis.

BACKGROUND/AIMS: There is no medical treatment of documented benefit in primary sclerosing cholangitis (PSC). Colchicine has been observed to reduce mortality in primary biliary cirrhosis in one study. The aim of this study was to examine the effect of colchicine in PSC. METHODS: Eighty-four patients with PSC were randomized to receive 1 mg of colchicine daily (n = 44) or placebo (n = 40) in a double-blind 3-year study. The effect of treatment was evaluated through blind scoring of 10 variables in prestudy and poststudy liver biopsy specimens, daily recording of symptoms, and biochemical tests (serum bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, albumin, immunoglobulins, ceruloplasmin, alpha 1-antitrypsin, and plasma prothrombin levels) at 6-month intervals. RESULTS: There was no evidence of a favorable effect of colchicine on survival, symptoms, serum biochemistry, or liver histology in patients with PSC. CONCLUSIONS: One milligram of colchicine daily is ineffective in PSC.

Adult↗
PubMed1995

Sampling variability of percutaneous liver biopsy in primary sclerosing cholangitis.

AIMS: To study sampling variability of percutaneous liver biopsy in primary sclerosing cholangitis (PSC). METHODS: One hundred and twelve biopsy specimens (that is, 56 pairs) from 44 patients with PSC, confirmed by cholangiography, were evaluated blindly. Six different features, qualitative grading of four other features and staging according to Ludwig were assessed. RESULTS: Quantitative sampling variability was confined mainly to just one grade or stage, although 11% (six of 56) of the biopsy specimen pairs differed by more than one stage (7% (one of 15) in pairs > 2 cm in length). Qualitative sampling variabilities were between 18 and 71%. Advanced disease (stages 3 or 4) was missed in 40% (two of five) of the biopsy specimens while cirrhosis was missed in 37%. CONCLUSION: Paired liver biopsy specimens should be taken in clinical studies of PSC using liver histology for evaluation or prognosis.

Biopsy, Needle↗
PubMed1995

Protective effects of calcium channel blockers on acute bromobenzene toxicity to isolated rat hepatocytes. Inhibition of phenylephrine-induced calcium oscillations.

BACKGROUND AND METHODS: Protective effects of verapamil, nifedipine, diltiazem, and ethylene glycol tetraacetic acid (EGTA) on acute bromobenzene (BB) toxicity to rat hepatocytes were evaluated, and cytosolic [Ca2+]i was monitored in single BB-exposed rat hepatocytes. Additionally, the effect of nifedipine on phenylephrine-stimulated calcium oscillations was investigated. RESULTS: BB at 0.8-2.4 mM increased the lactate dehydrogenase (LDH) leakage rate dose-dependently. Pretreatment with verapamil (25-35 microM), nifedipine (35-45 microM), diltiazem (25 microM), or EGTA (1.5-5 mM) markedly attenuated the BB-induced (1.6 mM) LDH leakage rate during 2 h of incubations. BB did not cause any detectable acute change in [Ca2+]i. BB interfered with phenylephrine-stimulated calcium oscillations, by blocking the oscillations in 58% of the cells and reducing the oscillation frequency in the rest. Nifedipine (100 and 200 microM) blocked the phenylephrine-induced calcium oscillations completely in 55% and 88% of the cells, respectively. CONCLUSIONS: The findings demonstrate that verapamil, nifedipine, diltiazem, and EGTA significantly protect rat hepatocytes against BB toxicity. BB interferes with phenylephrine-stimulated calcium oscillations. Nifedipine inhibits the oscillations at doses higher than those exerting a protective effect.

Animals↗
PubMed1995

Olsalazine versus sulphasalazine for relapse prevention in ulcerative colitis: a multicenter study.

OBJECTIVE: To compare the relapse-preventing effect and the frequency of adverse events of olsalazine and sulphasalazine in sulphasalazine-tolerant patients with ulcerative colitis. METHODS: Patients in remission, with at least two episodes of active disease during the last 5 yr, were randomized to 2 g of sulphasalazine or 1 g of olsalazine daily and were followed for 6-18 months. Relapse rates in the two groups were compared using frequency and life-table analysis. Sixty-nine patients with proctitis, 140 with left-sided colitis, and 113 with subtotal or total colitis were evaluated. RESULTS: In the intention-to-treat analysis, the failure rate (relapses plus withdrawals) was 54.7% in the olsalazine and 47.2% in the sulphasalazine group. In the per-protocol analysis excluding withdrawals, 44.7% relapsed in the olsalazine and 39.3% in the sulphasalazine group. Remission curves did not differ significantly, although at all time intervals the frequency of remission was slightly higher in the sulphasalazine group (p = 0.19 in the intention-to-treat analysis and p = 0.42 in the per-protocol analysis estimated by the log-rank test). Twelve patients (of whom five had diarrhea) in the olsalazine group versus eight patients in the sulphasalazine group discontinued the study because of side effects. CONCLUSION: The relapse-preventing effect of olsalazine and sulphasalazine in sulphasalazine-tolerant patients did not differ. Furthermore, the tolerability of olsalazine, particularly concerning diarrhea, appears to be better than previously reported.

Adult↗
PubMed1994

A comparison of budesonide with prednisolone for active Crohn's disease.

BACKGROUND: Patients with active Crohn's disease are often treated with corticosteroids, but the treatment has many side effects. Budesonide is a potent, well-absorbed corticosteroid, but because of a high rate of first-pass metabolism in the liver, its systemic bioavailability is low. METHODS: We conducted a randomized, double-blind, 10-week trial comparing the efficacy and safety of an oral controlled-release form of budesonide with the efficacy and safety of prednisolone in 176 patients with active ileal or ileocecal Crohn's disease (88 patients in each treatment group). The dose of budesonide was 9 mg per day for eight weeks and then 6 mg per day for two weeks. The dose of prednisolone was 40 mg per day for two weeks, after which it was gradually reduced to 5 mg per day during the last week. RESULTS: At 10 weeks, 53 percent of the patients treated with budesonide were in remission (defined as a score < or = 150 on the Crohn's disease activity index), as compared with 66 percent of those treated with prednisolone (P = 0.12). The mean score on the Crohn's disease activity index decreased from 275 to 175 in the budesonide group and from 279 to 136 in the prednisolone group (P = 0.001). Corticosteroid-associated side effects were significantly less common in the budesonide group (29 vs. 48 patients, P = 0.003). Two patients in the prednisolone group had serious complications (one had intestinal perforation and one an abdominal-wall fistula). The mean morning plasma cortisol concentration was significantly lower in the prednisolone group than in the budesonide group after 4 weeks (P < 0.001) and 8 weeks (P = 0.02) of therapy, but not after 10 weeks. CONCLUSIONS: Among patients with active Crohn's disease, both controlled-release budesonide and prednisolone are effective in inducing remission. In this trial, prednisolone reduced scores on the Crohn's disease activity index more, whereas with budesonide there were fewer glucocorticoid-associated side effects and less suppression of pituitary-adrenal function.

Adult↗
PubMed1994

Insulin secretion in pancreatic islets from rats with cirrhosis.

Cirrhosis was induced in rats by subcutaneous injections of CCl4 for 13 or 17 weeks. The morphology of the pancreatic islets from the CCl4-treated rats was found to be normal. The CCl4-treated rats had lower fasting serum glucose levels and higher serum insulin levels than the controls. After an oral glucose load (3 g/kg body weight), glucose levels in CCl4-treated rats stayed within the normal range, whereas the serum insulin levels remained higher with a delayed decline of insulin with time. In vitro perifusion of islets from the CCl4-treated rats showed that the response to 16.7 mmol/l glucose was reduced with both lower total insulin output and stimulated insulin output, whereas the patterns of first and second phase of insulin release did not differ. The insulin content of the perifused islets was not affected by 13 weeks of CCl4 treatment. Islets from rats treated with CCl4 for 17 weeks showed normal secretory response to 20 mmol/l L-arginine. Taken together, the results, showing normal or reduced capacity for insulin secretion, suggest that the hyperinsulinemia accompanying CCl4-induced cirrhosis is not due to increased secretion of the pancreatic islets. It may rather be associated with decreased insulin degradation by the liver with cirrhosis.

Animals↗
PubMed1994

Oral budesonide for treatment of autoimmune chronic active hepatitis.

OBJECTIVES: To see if budesonide, a second generation glucocorticosteroid with a high topical effect and a high first-pass metabolism of 90% in the healthy liver, can induce biochemical remission in autoimmune chronic active hepatitis before being metabolized, and further to study the effect on endogenous plasma cortisol levels and corticosteroid-related side effects. PATIENTS AND DESIGN: Thirteen patients with autoimmune chronic active hepatitis (11 females) were treated openly for up to 9 months by oral budesonide capsules. The initial dose was 6-8 mg (mean 6.3 mg) daily for 6-10 weeks, and then the dose was individualized. RESULTS: The pre-treatment values of alanine aminotransferase and immunoglobulin (IgG) were 7.1 +/- 1.2 mukat/L (mean +/- S.E.M.) and 26.4 +/- 3.9 g/L, respectively. After 6 weeks of treatment, significant decreases in alanine aminotransferase (to 2.1 +/- 0.9 mukat/L) and immunoglobulin (to 18.4 +/- 2.4 g/L) were recorded. After 9 months the corresponding values (n = 9) were 1.2 +/- 0.9 mukat/L and 15.9 +/- 1.3 g/L, respectively. The mean value of plasma cortisol remained within normal ranges or was only slightly subnormal for the whole group (364 +/- 44 nmol/L at start, 165 +/- 46 after 6 weeks and 138 +/- 48 after 9 months). However, significantly reduced plasma cortisol levels were found in patients with biopsy-proven liver cirrhosis. CONCLUSION: Oral budesonide appears to decrease liver inflammation in autoimmune chronic active hepatitis while causing a low frequency of systemic side effects and a marginal reduction in plasma cortisol in noncirrhotic patients over a study period of 9 months.

Adult↗
PubMed1994

Budesonide versus prednisolone retention enemas in active distal ulcerative colitis.

METHODS: Efficacy and safety of the topically acting glucocorticosteroid budesonide retention enema (2.3 mg/115 mL) were compared with prednisolone disodium phosphate enema (31.25 mg/125 mL) in patients with active distal ulcerative colitis. The study was a randomized, multicentre trial, with two parallel groups and single-blind to the investigator. One hundred patients with active ulcerative colitis, not reaching beyond the splenic flexure as determined by endoscopy, were treated for up to 8 weeks. RESULTS: Forty-five patients were randomized to receive budesonide and 55 to prednisolone. Both treatment groups improved significantly in terms of endoscopic and histological scoring during the study, but there were no statistically significant differences between the two groups. Clinical remission, defined as no more than three daily bowel movements without blood and endoscopically non-inflamed mucosa, was achieved in 16% of the patients in the budesonide group after four weeks and in 24% in the prednisolone group (N.S.). After 8 weeks treatment the clinical remission rate in the groups had increased to 36% for budesonide and 47% for prednisolone (N.S.). Mean morning plasma cortisol levels were unchanged in the budesonide group, whereas they were significantly suppressed in the prednisolone group after 2, 4 and 8 weeks (P < 0.0001). Side effects were mild and rare in both groups. CONCLUSIONS: Treatment with budesonide enema in active distal ulcerative colitis was comparable, regarding efficacy, to treatment with conventional prednisolone enema. A prolongation of the treatment time from 4 to 8 weeks doubled the clinical remission rate in both groups. However, budesonide may be preferable to prednisolone since it causes less systemic effects as reflected by a lack of plasma cortisol suppression.

Adult↗
PubMed1994

Malnutrition and gastrointestinal dysfunction as prognostic factors for survival in familial amyloidotic polyneuropathy.

OBJECTIVES: To describe the evolution of nutritional and neurological complications in a Swedish population of patients with familial amyloidotic polyneuropathy, and to identify prognostic factors and useful tests for monitoring the progress of the disease. DESIGN: Prospective and retrospective study of patients with familial amyloidotic polyneuropathy. SETTING: Tertiary referral centre. SUBJECTS: Twenty-seven patients with familial amyloidotic polyneuropathy, and a symptomatic onset before the age of 50. MAIN OUTCOME MEASURES: Age at onset, duration of disease before death, serum albumin, body mass index (BMI), duration and grade of peripheral neuropathy and gastrointestinal disturbances. Faecal fat, xylose test and 75selenohomocholic acid-taurine (SeHCAT) test were used for assessment of malabsorption. RESULTS: Thirteen patients died during the study period after a disease duration of between 9 and 18 years (mean 13). A short time interval between the onset of neurological and of gastrointestinal symptoms had greater impact on survival than age at onset in this selected group of patients (r = 0.65; P = 0.017). Malnutrition was evaluated by multiplying the [body weight (kg)/height2 (m)] with the serum albumin to compensate for oedema. This modified body mass index (mBMI) was significantly correlated to the number of years before death (r = 0.89; P < 0.0005) and to the duration of gastrointestinal symptoms (r = -0.66; P < 0.0005), but not to duration of disease (r = -0.2; P = 0.20). Polyneuropathy was graded according to functional capacity from I to IV (PND score) and was correlated to the number of years before death and mBMI, but not to serum albumin. The SeHCAT test for bile acid malabsorption was significantly correlated to the duration of gastrointestinal symptoms and to mBMI (r = -0.67; P = 0.0003 and r = -0.62; P = 0.003, respectively). CONCLUSION: The investigation disclosed that a short time interval between the onset of neurological and of gastrointestinal symptoms is associated with a decreased survival time. The mBMI was closely related to time before death, duration of gastrointestinal disturbances, malabsorption and functional capacity. The mBMI appears to be well suited to monitoring disease progress and gives prognostic information.

Adult↗
PubMed1994

Inhibition of hepatic fibrogenesis: a review of pharmacologic candidates.

Therapeutic attempts with anti-fibrotic drugs are still at an experimental stage. The clinical efficacies of most agents listed in Table II have not been proved. Some potential agents, such as colchicine, analogues of PGE, gamma-interferon, inhibitors of prolyl hydroxylase, malotilate, and PUL, must be further evaluated in controlled clinical trials. In addition, almost all anti-fibrotic agents, except HOE 077, are neither liver-nor fibrosis-specific. Some site-directed (targeted) drug delivery systems, drug-loaded vesicle carrier systems, like liposomes and erythrocyte ghosts, which selectively affect the extracellular matrix-producing cells, may improve efficacy and reduce adverse effects if they can be carriers for anti-fibrotic agents. Developments in biochemistry, immunohistochemistry, and molecular biology have considerably advanced our understanding of pathogenic mechanisms of hepatic fibrosis. With the development of available pathologic and serologic markers for ongoing fibrogenesis, experimental and clinical anti-fibrotic trials have become more active. Some therapeutic strategies have chosen targets for interference in collagen metabolism. In vivo inhibition of Ito cell activation has been a focus for the anti-fibrotic studies (70). In the present review an update of pharmacologic intervention in the process of metabolic pathways of collagen, the main extracellular matrices in both interstitium and basement membrane, has been summarized. Several drugs or biochemical agents that act on different steps of collagen synthesis, crosslinking, and breakdown are listed and discussed briefly. Moreover, agents that inhibit other matrix components are also involved in the review.(ABSTRACT TRUNCATED AT 250 WORDS)

Colchicine↗
PubMed1994

Eating a meal increases the clearance of ethanol given by intravenous infusion.

We studied the effect of eating a meal on the rate of ethanol elimination (clearance) from the blood after giving 0.4 g/kg by intravenous infusion to six female and six male volunteers. Half of the subjects had eaten breakfast whereas the other half had fasted overnight. After the first infusion of alcohol, those who had fasted ate lunch, and all the volunteers received a second infusion with the same dose of ethanol. The blood ethanol concentration was measured repeatedly for up to 180-240 min after the start of each experiment. Intake of food (lunch or breakfast) increased the clearance of ethanol by about 60% (P < 0.001). Alcohol intoxication was less pronounced at the end of the ethanol infusions preceded by eating a meal (P < 0.01). Gender had no significant effect on the rate of ethanol elimination. We conclude that eating a meal increases the rate of ethanol elimination even when alcohol is given by intravenous infusion.

Adult↗
PubMed1994

Cancer risk in primary biliary cirrhosis: a population-based study from Sweden.

A cohort of 559 patients in Sweden who satisfied predetermined criteria for the diagnosis of primary biliary cirrhosis was followed with respect to the incidence of cancer during the period of 1958 to 1988. The mean follow-up time from the time of primary biliary cirrhosis diagnosis was 9.0 +/- 5.4 yr. During the follow-up period, 148 patients died and the primary cause of death was liver insufficiency. An overall excess risk for cancer, standardized incidence ratio 1.6; 95% confidence interval, 1.1 to 2.2, was found in the cohort. In contrast to previous reports, we found no excess risk for breast cancer (standardized incidence ratio, 0.9; 95% confidence interval, 0.3 to 2.1). The number of hepatocellular cancers in the primary biliary cirrhosis cohort did not significantly differ from expected (standardized incidence ratio, 2.91; 95% confidence interval, 0.4 to 10.5).

Adult↗
PubMed1993

Pharmacokinetics of budesonide enema in patients with distal ulcerative colitis or proctitis.

Pharmacokinetic data obtained after one dose of a 2-mg budesonide enema were compared with data obtained after the last dose of four weeks of daily treatment in 24 patients with active distal ulcerative colitis or proctitis. This open multicentre study involved 28 eligible patients. Sigmoidoscopy and biopsy scores improved significantly (P < 0.002) during the four-week treatment period. Maximal plasma concentration (Cmax) of budesonide was 2.1 nmol/L 1.3 h after the first dose and 2.5 nmol/L 1.2 h after the last dose; the difference was not significant. The area under the curve (AUC) of plasma concentration vs. time was after the first dose 9.7 nmol h/L and after the last dose 11.6 nmol h/L (P < 0.03). The small increase in AUC may be attributed to improved absorption. During the last dose interval, minimal plasma concentration was below the limit of quantitation in most subjects. The Cmax and AUC of budesonide increased slightly after four weeks of treatment, but budesonide did not accumulate. Mean morning plasma cortisol values did not change significantly during treatment (P = 0.083), although a small change in cortisol levels between the first visit (pre-treatment) and last visit was positively correlated to the Cmax of budesonide measured at the last visit (P = 0.012).

Administration, Topical↗