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Biomedical subjects

L O Dolva

Publications and source records attributed to L O Dolva.

18 recordsLinked to original sources

Oral magnesium supplementation improves metabolic variables and muscle strength in alcoholics.

Magnesium deficiency is common among chronic alcoholics, but the knowledge of oral magnesium supplementation to this group is limited. We, therefore, randomized 49 chronic alcoholics, moderate to heavy drinkers for at least 10 years to receive oral magnesium or placebo treatment for 6 weeks according to a double-blind protocol. Effects on metabolic variables and muscle strength were analyzed. Significant reduction of aspartate-aminotransferase (ASAT), alanine-aminotransferase (ALAT) and gamma-glutamyl-transpeptidase (GGT) were seen after magnesium, whereas no change was observed with placebo. Bilirubin decreased in both groups. Serum Na, Ca, and P increased significantly during magnesium therapy compared with no statistically significant change in the placebo group. Serum K and Mg increased slightly after magnesium supplementation and decreased in the placebo group, resulting in a significant difference between the two groups at the end of the study. Muscle strength increased significantly during magnesium treatment, contrasting to no change with placebo. Blood pressure, heart rate, hematological variables, serum lipids (cholesterol, HDL, TG), glucose tolerance, and creatinine were unchanged in the two groups after treatment. Alcohol consumption was similar before and during the trial and does not explain the differences between the two groups The results shows that short-term oral magnesium therapy may improve liver cell function, electrolyte status, and muscle strength in chronic alcoholics.

Administration, Oral

Magnesium deficiency diagnosed by an intravenous loading test.

Magnesium deficiency is common but difficult to diagnose and to assess in clinical practice. The use of a magnesium loading test was therefore evaluated to diagnose magnesium deficiency in 661 hospitalized patients with medical conditions assumed to interfere with magnesium uptake and excretion. Thirty millimoles of magnesium sulphate were administered intravenously during 8 h as a loading test and related to the urinary excretion in the following 24 h. A group of 30 patients without any known predisposition for magnesium deficiency and a group of 27 healthy volunteers served as controls. The mean (with 95% confidence interval) magnesium retention was 4 (-2-10)% in the control group of patients and 3 (-2-8)% in healthy subjects. A significantly higher retention was observed in all the groups of the patients: atrial fibrillation 18 (11-25)%, other arrhythmias 18 (11-24)%, hypertension 27 (20-33)%, coronary artery disease 25 (20-30)%, congestive heart failure 31 (26-37)%, cerebrovascular events 38 (24-51)%, gastrointestinal disorders 22 (14-29)%, diabetes mellitus 16 (9-22)%, and alcoholics 33 (29-36)%. The percentage of patients with a retention greater than mean + 2 SD of the two control groups varied between 22% and 54% among the different patient groups. The mean serum magnesium among the patient groups was similar to the control group of patients, except for the alcoholics, hypertensives and young healthy controls, who had significantly reduced levels. Magnesium retention was significantly correlated to age and renal function, and among the alcoholics negatively correlated to serum magnesium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Extended experience with recombinant alpha-2b interferon with or without hepatic artery embolization in the treatment of midgut carcinoid tumours. A preliminary report.

Thirty-six patients with histologically verified midgut carcinoid tumours and liver metastases were included in a prospective study with daily interferon therapy 5 x 10(6) IU s.c. for one or two years. All had the primary tumour removed at laparotomy, and whenever technically possible, an embolization of the hepatic arteries was performed prior to interferon start. Recombinant human alpha 2b interferon from Schering-Plough was employed. When interferon was given alone, 24% responded after one year, judged from a 50% reduction in excretion of 5-hydroxyindoleacetic acid in the urine. Three patients had died. Stable disease was found in 43%, while 19% progressed. Survival rate was 40% after 5 years from start of therapy. The median survival time from start of therapy was 3 years and 4 months. When embolization of the liver arteries had been performed prior to the start of interferon treatment, the response rate was 60% after one year, 20% had stable disease and 20% progressed. Survival rate was 75% up to 5 years of observation. We conclude that interferon is an effective treatment of malignant metastatic midgut carcinoid and that survival might be prolonged compared with historical controls. Embolization of the liver arteries seems to increase the response rate after one year. Kaplan-Meier plots suggest prolonged survival when interferon treatment is combined with embolization.

Carcinoid Tumor

[Beta blockaders and physical performance. Limiting factors].

Beta blockers are known to cause reduced exercise performance in hypertensive and healthy subjects. Additive effects of selective blockade of beta-1 and beta-2 receptor subtypes seems to account for the total reduction in exercise capacity observed with non-selective beta-1,2 blockade. The mechanism is as yet undefined. The magnitude of the reduction is dependent of type of exercise and level of fitness. Hemodynamic parameters, substrate delivery to the working muscles, mental factors, and interference with potassium homeostasis may be involved.

Adrenergic beta-Antagonists

Effect of beta-adrenergic blockade on hormonal responses during continuous and intermittent exercise.

The modifying effect on exercise performance and neuroendocrine response of the nonselective beta blocker timolol (10 mg b.i.d. for 5 days) and the beta 1-selective beta blocker metoprolol (100 mg b.i.d. for 5 days) was studied. The hormones studied were growth hormone, prolactin, cortisol, renin, epinephrine, dopamine, and norepinephrine. The response was studied during short-term maximal dynamic exercise, using two different exercise protocols; continuous (n = 11) and intermittent (n = 9) bicycle ergometry, in normal healthy young men. Accumulated work on placebo was nearly identical in the two studies, but was significantly reduced by 10.4% and 6.6% with timolol and by 4.7% and 6.7% with metoprolol, during continuous and intermittent exercise, respectively. During continuous exercise, accumulated work was 5.8% lower (p less than 0.05) with timolol than with metoprolol. The hormonal plasma concentrations of all hormones except renin were higher during continuous exercise than during intermittent exercise. Beta blockade had no effect on baseline hormonal levels, but the response was markedly changed during exercise. Maximum epinephrine, cortisol, and prolactin responses increased after beta blockade; dopamine remained nearly unchanged; while the renin responses were attenuated. Norepinephrine concentrations were slightly increased during continuous exercise by beta blockade and rose in direct proportion to the increase in workload. During intermittent exercise, maximum norepinephrine levels were significantly reduced by beta blockade compared with placebo. Thus the effect of beta 1-selective and nonselective beta receptor blockade on circulating hormones does not seem to explain the reduced exercise capacity following beta blockade.

Adrenergic beta-Antagonists

Interaction of naloxone and timolol on maximal exercise capacity and the subjective perception of fatigue.

The effect on exercise performance and on the subjective perception of fatigue of the opioid receptor blocker naloxone, the nonselective beta-blocker timolol, and the combination of these two was studied in a double-blind randomized cycle ergometry test in healthy young men. Cumulative work at exhaustion was reduced by 25% after timolol (P less than 0.002) and by 34% after naloxone/timolol (P less than 0.02) but not after naloxone, compared with placebo. Naloxone alone had no influence on the subjective perception of fatigue (Borg scale rating), but significantly higher ratings were obtained by timolol and by naloxone/timolol. The present study does not support the hypothesis that opioid peptides are of importance for maximal exercise capacity and subjective perception of fatigue during short-term dynamic exercise in healthy young men.

Adult

Thyrotropin-releasing hormone antagonism of ethanol inebriation.

The effect of ethanol [1 g/kg per orally (p.o.) during 1 hr] after thyrotropin-releasing hormone (TRH) pretreatment (five doses of 20 mg p.o. during 30 hr preceding ethanol intake) was studied in a placebo-controlled, double-blind design in 11 healthy subjects. Computerized reaction tests measuring errors and reaction time, as well as clinical testing and a self evaluation (modified Osgood test) were performed before, 75, 150, and 225 min after ethanol intake. TRH treatment did not influence blood ethanol concentrations. The effect of ethanol to produce errors was substantially reduced in all three reaction tests after TRH treatment compared to placebo treatment. The reaction times were slightly increased in simple and four choice reaction tests and up to 20% increased in a complex test in the TRH-ethanol situation compared to the placebo-ethanol situation. The effects caused by ethanol were also significantly reduced in three clinical tests and in two subjective tests of inebriation by TRH treatment compared to placebo treatment. In conclusion the study demonstrated that several acute effects of ethanol intake in humans were reduced by TRH pretreatment which did not interfere with the blood ethanol concentration versus time curve.

Adult

Liver cell necrosis and regeneration following injections of carbon tetrachloride. Effects of the thyrotropin-releasing hormone and somatostatin.

Mice were given 10 micrograms somatostatin or 25 micrograms TRH intraperitoneally 10 min before s.c. injection of 2 or 20 mg CCl4. The extent of liver cell necrosis and nuclear size were measured by the electronic Mini Mop method and the extent of necrosis and nuclear pleomorphism were estimated by a visual linear analogue scale of 100 mm, and compared to plasma concentrations of ASAT and ALAT. Pre-treatment with TRH or somatostatin resulted in significant reduction in the extent of necrosis 24 h after CCl4-injections (25%), with a lowering of ASAT from 13209 +/- 2955 U/l to 5144 +/- 924 after TRH and to 6186 +/- 966 after somatostatin, and of ALAT from 14343 +/- 3209 to 7718 +/- 1727 and 6494 +/- 1253 U/l, respectively. After 3 days the necroses were reduced from 16.5 +/- 1.7% by the Minimop method to 1.4 +/- 0.5% (90%) in mice given CCl4 alone, and from 12.3 +/- 1.7% to 3.8 +/- 1.2% in mice pretreated with TRH, and from 12.3 +/- 1.8% to 3.8 +/- 1.7% (70%) in mice pretreated with somatostatin. The plasma concentrations of ASAT and ALAT were reduced correspondingly. After 5 days no necroses were seen, and the plasma ASAT and ALAT were normal. After 6 months of weekly injections of TRH or somatostatin before 20 mg CCl4 the liver cell nuclear size (10.5 and 9.7 0.3 mu 2) was similar to that after CCl4 alone (9.7 0.3 mu 2), and twice that of controls (4.6-5.4 0.1 mu 2). Liver cell necrosis was not seen. The plasma concentrations of ASAT (131 8.6-162 11.3) and ALAT (98 8-104 9 Iu/l) were similarly 2-3 times those in controls. TRH and somatostatin thus reduced liver cell injury and delayed regeneration after single injections of CCl4. After 6 months of weekly injections no effects were observed.

Animals

The importance of potassium and lactate for maximal exercise performance during beta blockade.

Changes in femoral vein pH, lactate, glucose and potassium were studied in a double-blind randomized, short-term, dynamic cycle ergometry exercise test on six healthy male subjects after administration of non-selective (timolol), beta-1-selective (atenolol) beta blocker or placebo. The exercise intensity was increased in steps of 200 kpm/min every 2 min until exhaustion. During submaximal exercise, potassium concentrations in blood from the exercising leg muscles increased progressively with increasing exercise intensity, and was significantly higher for any given exercise level following timolol as compared to placebo administration. The potassium concentrations following atenolol were in-between those of timolol and placebo. Despite reduced working capacity after non-selective beta blockade, almost identical potassium concentrations were reached at exhaustion irrespective of treatment regimens (placebo: 6.3, range 5.8-6.8 mmol/l; atenolol: 6.5, range 6.1-7.3 mmol/l and timolol: 6.4, range 6.2-6.8 mmol/l). The increase in s-lactate concentrations was similar across all treatments, and rose in proportion to the increase in the exercise intensity. A biphasic increase in lactate was observed with identical breaking points (anaerobic threshold) irrespective of treatment regimens. There was no difference in glucose concentrations between the treatment regimens. The marked increase in serum potassium during maximal exercise coincides with leg muscle fatigue and may, by its effect on the muscle cell membrane potential, limit the maximal working capacity following beta blockers. The rise in serum potassium may curtail the use of maximal exercise test as an index of cardiac performance in healthy young subjects.

Adrenergic beta-Antagonists

Treatment of malignant metastatic midgut carcinoid tumours with recombinant human alpha2b interferon with or without prior hepatic artery embolization.

Nineteen patients with histologically verified midgut carcinoid tumours and liver metastases were included in a prospective study with daily recombinant human alpha 2b interferon injections of 5 million IU subcutaneously for 1 year. All had as much as possible of the primary tumour removed at laparotomy. Whenever technically possible (in seven cases), an embolization of the hepatic arteries was performed before interferon start. The response rate of the combined embolization and interferon treatment (n = 7) was 86% after 1 year, as judged from either a 50% reduction in excretion of 5-hydroxy-3-indoleacetic acid in the urine or a 50% reduction in the area of the largest liver metastasis as evaluated by computed tomography. All patients experienced an improvement in diarrhoea and/or flushing. When interferon was given alone (n = 12), 40% responded on the basis of objective criteria (50% after 6 months), whereas an improvement in either diarrhoea or flushing was experienced by 70% (75% after 6 months). In this group one patient had died and one had decided to withdraw after 6 months, at which time both were responders. We conclude that interferon seems to be an effective treatment of malignant metastatic midgut carcinoid tumours and that embolization of the liver arteries seems to increase the response rate, as judged after 1 year.

Adult

Recombinant alpha-2 interferon with or without hepatic artery embolization in the treatment of midgut carcinoid tumours. A preliminary report.

Nineteen patients with histologically verified midgut carcinoid tumours and liver metastases were included in a prospective study with daily interferon therapy 3 mill IU x m-2 subcutaneously for one year. All had the primary tumour removed at laparotomy, and whenever technically possible, an embolization of the hepatic arteries was performed prior to interferon start. Recombinant human alpha-2b interferon from Schering was employed. When interferon was given alone for one year 40% responded, judged from either a 50% reduction in excretion of 5-hydroxy-indoleacetic acid in the urine or a 50% reduction in the area of the largest liver metastasis, as evaluated by computer tomography. One patient died later on and one withdrew from therapy of her own will; both were responders at the evaluation at 6 months. When prior embolization of the liver arteries had been performed, the response rate was 85% after one year. When diarrhoea and/or flushing was evaluated, 70% had response on interferon alone, while all patients experienced improvement after the combined procedure. We conclude that interferon is an effective treatment of malignant metastatic midgut carcinoid and that embolization of the liver arteries seems to increase the response rate.

Carcinoid Tumor

Difference between beta-1-selective and non-selective beta-blockade during continuous and intermittent exercise.

Limiting factors of maximal exercise performance are not clearly defined. In order to differentiate between various factors, maximal exercise was studied during continuous (n = 12) and intermittent (n = 9) exercise. The non-selective beta-blocker timolol (10 mg b.i.d. for 5 days) was compared double-blind and placebo controlled with the beta-1-selective beta-blocker metoprolol (100 mg b.i.d. for 5 days), with respect to effect on maximal exercise tolerance. Total cumulated work was comparable during continuous and intermittent exercise. Timolol and metoprolol reduced maximal exercise performance. No difference was observed between the two beta-blockers during intermittent exercise. The non-selective beta-blocker caused a greater reduction in exercise performance (10.4%) than the beta-1-selective beta-blocker (4.7%) (P less than 0.05) during continuous exercise. Maximal heart rate was higher with metoprolol than timolol during continuous exercise. The non-selective beta-blocker caused a slightly greater inhibition of lipolysis than the beta-1 selective one. No significant differences in glucose concentrations were observed between the treatment regimens. Exercise caused a marked increase in serum potassium concentrations. Beta-blockade caused further increase in potassium at any given workload. This study indicates that maximal working capacity is comparable during continuous and intermittent exercise. Beta-1-selective and non-selective beta-blockade reduce the maximal working capacity, non-selective more than beta-1-selective. Substrate availability was not responsible for the beta-blocker induced reduction of the working capacity. The rate of rise in serum potassium was significantly higher during beta-blockade and may, therefore, be a limiting factor for the maximal working capacity.

Administration, Oral

The effects of naloxone and timolol on plasma catecholamine levels during short-term dynamic exercise.

In order to study the role of opioid- and betareceptors on exercise-induced catecholamine responses, the effects of acute intravenous administration of 1 and 4 mg naloxone and of the non-selective betablocker timolol 2 mg of on circulating concentrations of adrenalin, noradrenaline and dopamine during exercise to exhaustion were examined in eight normal, healthy young men, using a double-blind, randomized, placebo-controlled design. During maximal exercise, adrenalin levels increased from 71 +/- 17 to 821 +/- 235 pg/ml (p less than 0.05), noradrenaline from 355 +/- 58 to 4235 +/- 1031 pg/ml (p less than 0.05), and dopamine from 72 +/- 20 to 178 +/- 44 pg/ml (p less than 0.05). Naloxone did not influence basal or exercise-induced noradrenaline responses. Timolol clearly augmented peak adrenalin concentration at maximal exercise capacity (1543 +/- 510 pg/ml, p less than 0.05). Basal noradrenaline level was increased (546 +/- 86 pg/ml, p less than 0.05), while exercise-induced noradrenaline level was reduced (2954 +/- 594 pg/ml, p less than 0.05) in proportion to the reduction in maximal exercise capacity during timolol treatment. Neither naloxone nor timolol affected dopamine levels. No additive effect was seen with the combination of naloxone and timolol. It is concluded that the opioid peptides are probably not involved in noradrenaline and dopamine responses, whereas betablockers change the catecholamine response to short-term maximal exercise.

Adrenergic beta-Antagonists

Thyrotrophin-releasing hormone inhibits the pentagastrin stimulated gastric secretion in man. A dose response study.

Actions of thyrotrophin-releasing hormone (TRH) have generally been confined to the central nervous system (CNS). We have studied the effect of increasing doses of TRH i.v. (8, 40, 200 and 1000 microgram/h) on pentagastrin-stimulated gastric secretion in ten normal individuals. All doses caused stepwise inhibition of gastric juice (volume), acid and pepsin output. When employing the largest dose of i.v. TRH (1000 microgram/h) the inhibition was 44% for gastric volume, 51% for acid output and 57% for pepsin output. This study shows that TRH inhibits gastric secretion, and indicates that TRH has actions outside the CNS in man.

Adult

Actions of thyrotropin-releasing hormone on the gastrointestinal function in man. II. Inhibition of pentagastrin-stimulated acid secretion.

The pentagastrin-stimulated gastric volume and acid output were measured with and without an i.v. thyrotropin-releasing hormone (TRH) infusion (666 microgram/h). TRH inhibited the pentagastrin (6 microgram/kg s.c.) stimulated volume to 67.5 +/- 8.4% (p less than 0.01) and the acid output to 65 +/- 8.4% of control infusion values (mean +/- S.E.M.). It is concluded that TRH inhibits the pentagastrin-stimulated gastric secretion in man.

Adult

Actions of thyrotropin-releasing hormone on gastrointestinal functions in man. III. Inhibition of gastric motility in response to distension.

The intragastric pressure/volume relationship has been measured in six healthy volunteers. Increased gastric motility was achieved by gastric distension, by stepwise increasing the volume from 0--600 ml. When thyrotropin-releasing hormone (TRH), 0.04 mg/h, was infused concomitantly in the individuals, gastric motility was significantly inhibited (p less than 0.05) and, with 1 mh/h of TRH, nearly abolished compared with the saline control test. The basal pressure was unaffected at 0.04 mg/h, whereas a significant rise was seen after 1 mg/h of TRH (p less than 0.05) compared with the control test. In three of the subjects the effect of rapid injection of TRH (0.2 mg), followed by infusion of TRH (0.6 mg/h), on the stimulated gastric motility was analysed. After the injection of TRH, almost no motor activity was observed during the 15-min observation period. It is concluded that TRH has a potent inhibiting effect on gastric motility, and the possible physiological role of TRH in the gastric regulation in man is discussed.

Adult