Xenoperfusion of rabbit kidney and the impact of BN 52021: a specific antagonist of platelet-activating factor.
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Animals↗
Biomedical subjects
S Larsen
Publications and source records attributed to S Larsen.
Xenoperfusion of pig kidney with human AB or O whole blood.
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ABO Blood-Group System↗
Ozone depletion and its consequences for the fluence of carcinogenic sunlight.
A slight reduction of the ozone level over the northern hemisphere in the period 1969-1986 has been reported [D. Lindley, Nature (Lond.), 323: 293, 1988]. Ozone measurements performed in Oslo are in agreement with this. However, the ozone level for 1987 and 1988 was above normal, and no negative or positive trend is apparent for the last 10 years. The consequences of an ozone reduction for the fluence rate of carcinogenically effective sunlight was evaluated on the basis of recent action spectra for mutagenesis in cells, carcinogenesis in mice, and erythema induction in humans. Depending on the choice of action spectrum we find amplification factors (defined as percentage increase in yearly fluence of carcinogenically efficient sunlight per percentage reduction of the ozone level) between 1.1 and 1.3 at latitudes between 0 and 20 degrees and between 0.9 and 1.1 for Northern Europe. These estimates are significantly lower than 2.0, which is the value found when the calculations are based on the DNA absorption spectrum (R. B. Setlow, Proc. Natl. Acad. Sci. USA, 71:3363-3366, 1974).
Animals↗
Clinical trial of three therapeutic regimens for bovine mastitis.
An open, block randomised multi-centre clinical trial was performed in Norway during 1985 to 1987 to compare the therapeutic efficacy of three antibiotic regimens against clinical bovine mastitis caused by penicillin-sensitive bacteria. Two regimens consisted of procaine penicillin injected intramuscularly for either three or five days, and the third, the traditional Norwegian regimen, consisted of one intramuscular injection of a combination of procaine penicillin and dihydrostreptomycin followed by one intramammary treatment daily per infected quarter for four days. The study included 621 quarters with infectious mastitis from 439 cows. The most efficient regimen for all bacteria was five days systemic treatment (53.1 per cent cured), and the traditional regimen was second best (46.7 per cent cured). The least efficient regimen consisted of systemic therapy with procaine penicillin for three days (36.9 per cent cured). The difference between the therapeutic efficacies of the three regimens was reduced when the clinical mastitis was severe, and in severe mastitis caused by Staphylococcus aureus the difference was very small.
Animals↗
Long-term effects of lithium on the kidney: functional-morphological correlations.
Correlations between quantitative kidney biopsy findings and clinical renal function in 46 unselected patients treated with lithium for an average of eight years were studied. A significant relationship between maximum renal concentrating capacity and degree of tubular atrophy was found. GFR correlated significantly with sclerotic glomeruli as well as atrophic tubules in patients on a multiple dosage schedule, whereas no relationship was seen in patients receiving lithium in a single daily dose. Thus, renal dysfunction may have a structural basis in a subgroup of lithium-treated patients on a multiple dosage schedule.
Adult↗
Cell-mediated immunity in anorexia nervosa augmented lymphocyte transformation response to concanavalin A and lack of increased risk of infection.
Cell-mediated immunity (CMI) was studied in 33 consecutively admitted patients with anorexia nervosa (AN) who had a mean weight loss of 30%. Clinical infections were not diagnosed in the patients. The acute phase reactant, C-reactive protein, was slightly elevated in only one patient, but was within the normal range in the remainder. The absolute number of T-lymphocytes in peripheral blood was significantly increased (p < 0.01) in the AN-patients compared to the control group while the number of granulocytes was reduced (p < 0.01). However, a significant negative correlation between the relative weight loss and the numbers of both total and T-lymphocytes in the AN-patients was established (p < 0.05). Mitogen stimulation of lymphocytes with phytohemagglutinin (PHA), poke-weed-mitogen (PWM) and concanavalin A (Con A) showed no reduction in the proliferative response in AN-patients compared to the control group. On the contrary, Con A transformation was significantly higher (p < 0.03) in the AN-patients. The lymphocyte response to PWM (p < 0.02) was, however, diminished in the patients with the most advanced weight loss compared to those with the least weight loss.
Journal Article↗
A novel statistical approach to analysis of bleeding patterns during continuous hormone replacement therapy.
Previous studies have shown that continuous oral oestrogen-progestogen therapy, which is a relatively new treatment regimen, does not induce endometrial hyperstimulation. However, bleeding disturbances are common during the early months of therapy and in the present study we used both conventional methods of statistical analysis and a stochastic model to describe the bleeding patterns. Four groups of 15 post-menopausal women were given different oral formulations continuously for 1 yr. The oestrogen component in all cases was 2 mg 17 beta-estradiol. The progestogen used was norethisterone acetate at a dose of either 1 mg or 0.5 mg (Groups A and B) or megestrol acetate at a dose of either 5 mg and 2.5 mg (Groups C and D). Each woman kept a daily record of all bleeding episodes, 80% of which occurred during the first 4 mth of therapy. Analysis of variance showed that the high doses of the two progestogens were associated with less spotting and menstrual-like bleeding than the low doses. Stochastic analysis of the bleeding data confirmed that women on the high progestogen doses experienced fewer bleeding episodes than those on the low doses. It also showed that women receiving the high progestogen doses who weighed under 67 kg or had had their last menstruation over 5 yr previously bled less than the other women in the high-dose groups.
Adult↗
Effect of catecholamines and insulin on plasma volume and intravascular mass of albumin in man.
1. The effect of intravenous catecholamine infusions and of intravenous insulin on plasma volume and intravascular mass of albumin was investigated in healthy males. 2. Physiological doses of adrenaline (0.5 microgram/min and 3 microgram/min) increased peripheral venous packed cell volume significantly; intravenous noradrenaline at 0.5 microgram/min had no effect on packed cell volume, whereas packed cell volume increased significantly at 3 micrograms of noradrenaline/min. No significant change in packed cell volume was found during saline infusion. 3. During adrenaline infusion at 6 micrograms/min, packed cell volume increased, plasma volume decreased and intravascular mass of albumin decreased significantly. During noradrenaline infusion at 6 micrograms/min, packed cell volume increased and plasma volume decreased, but intravascular mass of albumin did not change. 4. Application of a hyperinsulinaemic, euglycaemic glucose clamp led to an increase in transcapillary escape rate of albumin and a decrease in intravascular mass of albumin. Packed cell volume remained constant, while plasma volume, measured by radiolabelled albumin, decreased. 5. We conclude that the previously reported changes in packed cell volume, plasma volume, intravascular mass of albumin and transcapillary escape rate of albumin during hypoglycaemia may be explained by the combined actions of adrenaline and insulin.
Adult↗
Blood lead-blood pressure relations: alcohol intake and hemoglobin as confounders.
A cohort of 1,052 persons (504 men and 548 women) born in 1936 and residing in the Glostrup area, Denmark, underwent a comprehensive physical examination in 1976 at age 40 years, and 966 underwent a complete reexamination five years later. The examinations included blood lead concentration and blood pressure assessment under careful quality control. Complete blood lead and blood pressure data were available for 861 of these subjects (451 men and 410 women). The median blood lead levels were 13 and 9 micrograms/100 ml at age 40 years and 9 and 6 micrograms/100 ml at age 45 years in men and women, respectively. A slightly increased blood lead concentration was seen at age 40 years in women with a systolic blood pressure above 140 mmHg and/or a diastolic blood pressure above 90 mmHg. Systolic blood pressure in men and women and diastolic blood pressure in women correlated significantly with log blood lead at age 40 years but not at age 45 years, a doubling in blood lead being associated with an increase in blood pressure of 3 mmHg or less. Of nine potential confounders assessed, only blood hemoglobin and alleged alcohol intake were significantly associated with both blood lead and blood pressure. If one or both confounders were entered into a multiple regression analysis, all associations between blood lead and blood pressure became nonsignificant, in some cases with a negative regression coefficient. In addition, the blood lead:hemoglobin ratio was poorly associated with blood pressure, particularly in individuals with a low alcohol intake. Because both hemoglobin level and alcohol intake appear to be biologically plausible confounders, any independent effect of low-level lead exposure on blood pressure could not be determined.
Adult↗
Psychophysical and electrophysiological testing of retinal function. Macular recovery time and oscillatory potentials in normal subjects.
We evaluated different aspects of 1) psychophysical and 2) electrophysiological testing procedures of retinal function, represented by macular recovery time (nyctometry) and oscillatory potentials (electroretinography), respectively. Ninety healthy males, aged 18-28 years, were used in the study. We registered two different phases of macular recovery time, IRT: initial recovery time (less than 40 sec) and AUC: area under the curve (less than 120 sec) and both individual and summed nodes of oscillatory potentials (OPs). A significant effect of training was observed in monocular registration of IRT and AUC (P less than 0.01), and the superiority of binocular recovery was numerically compared to monocular recovery (P less than 0.01). The inter-variability (coefficient of variation) of IRT was high (40%) in both monocular and binocular registrations, while AUC had a smaller variability binocularily than monocularily (33% vs 21%). The inter-variability of OPs was low (16%). Intra-variability, between first and second eye tested, showed highly correlated values in IRT, AUC and OPs (r = 0.51-0.82; P less than 0.004), while IRT/AUC was not correlated to amplitudes of OPs. The results emphasize that selecting one eye, mean of two eyes or both eyes are critical for accuracy and validity in psychophysical testing of visual performance.
Adolescent↗
Passive transfer of antiviral antibodies restricts replication of Aleutian mink disease parvovirus in vivo.
When mink kits were infected neonatally with a highly virulent strain of Aleutian disease virus (ADV), 100% of both Aleutian and non-Aleutian genotype mink died of interstitial pneumonia characterized by permissive ADV infection of alveolar type II cells. Treatment of infected kits with either mink anti-ADV gamma globulin or mouse monoclonal antibodies against ADV structural proteins reduced mortality by 50 to 75% and drastically reduced the severity of clinical signs. Interestingly, mink kits that survived the acute pulmonary disease all developed the chronic form of immune complex-mediated Aleutian disease. Thus, the antibodies directed against ADV structural proteins were capable of modulating the in vivo pathogenicity from an acute fulminant disease to a chronic immune complex-mediated disorder. The mechanism of this modulation was examined by strand-specific in situ hybridization. We found that the number of ADV-infected type II cells was the same in both untreated and antibody-treated kits. However, in the treated kits, viral replication and transcription were restricted at the cellular level. These data suggested that antibodies prevented acute viral pneumonia by restricting the intracellular level of viral replication and that the relevant antigenic determinants were contained within the viral structural proteins. The restricted levels of viral replication and transcription seen in antibody-treated mink kits resembled the levels observed in infected adult mink and suggested a role of antiviral antibodies in development of persistent infection and chronic immune complex disease.
Acute Disease↗
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↗
Optimal assessment of gastrointestinal side effects induced by non-steroidal anti-inflammatory drugs. Endoscopic lesions, faecal blood loss, and symptoms not necessarily correlated, as observed after naproxen and oxindanac in healthy volunteers.
Gastrointestinal side effects caused by naproxen and oxindanac (a developmental non-steroidal anti-inflammatory drug) were compared by combined endoscopy and determination of faecal blood loss in 16 healthy male volunteers in a randomized, double-blind, crossover study. Individual daily faecal blood loss was determined by means of 51Cr-labelled erythrocytes. Gastroduodenoscopy was performed before and after administration of naproxen, 750 mg/day, and oxindanac, 600 mg/day, for 1 week each. A washout period of at least 3 weeks was inserted between drug periods. Visual analogue scales (VAS) were used for endoscopic assessment of lesions and subjective complaints. Mean faecal blood loss increased from a base line 0.48 ml/24 h to 1.59 ml/24 h with naproxen (p less than 0.01) and from 0.56 ml/24 h to 1.31 ml/24 h with oxindanac (p less than 0.01). VAS scores for gastroduodenal lesions increased significantly with both drugs. Naproxen caused a significantly greater increase than oxindanac (p less than 0.05). There was no correlation between gastrointestinal blood loss and endoscopic findings. Subjective symptoms were correlated to faecal blood loss with naproxen, but not to endoscopic findings. No such correlations were observed for oxindanac. Naproxen caused a significant prolongation of bleeding time (p less than 0.01), whereas the increase caused by oxindanac was not significant (p = 0.09).
Anti-Inflammatory Agents, Non-Steroidal↗
Comparison of the gastrointestinal side effects of naproxen formulated as plain tablets, enteric-coated tablets, or enteric-coated granules in capsules.
We studied the gastrointestinal side effects of three formulations of naproxen in 18 healthy male volunteers. In a Latin-square design crossover study, the subjects received 500 mg naproxen twice daily for 7 days as plain tablets, enteric-coated tablets, or enteric-coated granules in capsules. The 51Cr-EDTA absorption test was performed before and at the end of each drug period, to evaluate changes in the distal gut. The test dose was instilled distally in the duodenum to prevent lesions in the stomach from interfering with the evaluation. Upper endoscopy was performed at the same intervals, scoring changes in the middle and distal duodenum separately from findings in the stomach and duodenal bulb. The nature and severity of adverse effects were recorded for each treatment period. Non-parametric methods were used for statistical evaluation. All drugs induced a significant increase in 51Cr-EDTA absorption, but we did not detect any difference between the three formulations. All formulations were associated with a significant increase in all the endoscopic findings monitored. Enteric-coated tablets induced significantly less lesions than enteric-coated granules in the stomach and duodenal bulb, and an advantage over plain tablets was indicated. No difference was seen in the middle and distal duodenum. The proximal endoscopic scores were not correlated to those found in the middle and distal duodenum. Evaluation of the small and large bowel should probably be included in clinical studies of NSAIDs, but our findings suggest that the importance of transfer of mucosal lesions to the distal gut by enteric coating may have been overemphasized.
Adult↗
A double-blind comparison of gastrointestinal effects of ibuprofen standard and ibuprofen sustained release assessed by means of endoscopy and 51-Cr-labelled erythrocytes.
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Adult↗
Sucralfate for prevention of naproxen-induced mucosal lesions in the proximal and distal gastrointestinal tract.
To study the protective effect of Sucralfate on Naproxen-induced mucosal lesions, 16 healthy, male volunteers were given Naproxen 500 mg b.i.d. together with Sucralfate 2 g b.i.d. or placebo in a double-blind, crossover study. Drug periods were 1 week, with a 3-week wash out in between. Mucosal lesions in stomach and duodenum were assessed by upper endoscopy before and after each drug period, using a visual analogue with separate scoring of mid- and distal duodenal lesions. 51Cr-EDTA absorption tests were performed to demonstrate possible changes in distal gut permeability. In addition, subjective symptoms were registered. Both drug periods induced significant lesions in the stomach and duodenum. Statistically speaking, fewer changes were found in the stomach and duodenal bulb after Sucralfate co-administration, whereas no significant reduction of lesions was seen in the distal duodenum. The 51Cr-EDTA absorption was increased in both periods, indicating deleterious effects to distal parts of the gut, but our results did not demonstrate Sucralfate-mediated protection from these changes. Symptoms were modest, and equal in the two periods. We conclude that Sucralfate may offer protection in the gastric and proximal duodenal mucosa, but no such protective effect was seen distally to the duodenal bulb.
Absorption↗
Cimetidine tablets or suspension for the prevention of gastrointestinal mucosal lesions caused by non-steroidal, anti-inflammatory drugs.
We compared the protection offered by cimetidine 400 mg b.i.d. as tablets or suspension vs. placebo, in Naproxen-induced gastrointestinal damage in 17 healthy males. Upper endoscopy was performed before and after each drug period, with separate evaluation of duodenal mucosa distal to the duodenal bulb. 51Cr-EDTA absorption tests were done to assess distal mucosal integrity, and symptoms were registered. All regimens caused a significant increase in mucosal damage (p less than 0.01). Cimetidine tablets gave a significantly lower damage score than placebo for gastritis/duodenitis and hemorrhagic lesions in the stomach/duodenal bulb, and for the sum of scores in both scoring regions (p = 0.02). Cimetidine suspension was not significantly different from placebo for any of the endoscopic parameters. The 51Cr-EDTA absorption was significantly increased after all drug periods. However, there was no difference between the three drug combinations. Symptoms reported were mild and equal in the three groups. Cimetidine tablets offered protection against Naproxen-induced mucosal damage, primarily in the stomach and duodenal bulb, but lacked any effect on permeability changes. Cimetidine suspension was not significantly different from placebo in any respect.
Absorption↗
A preliminary trial of high-dose intravenous immunoglobulin to a patient with euthyroid ophthalmopathy.
A patient with serious euthyroid infiltrative ophthalmopathy was treated with oral glucocorticoids for five years. The course of the disorder was characterized by recurrent exacerbations during attempts to reduce the dose of systemic glucocorticoids. Intravenous infusion with high-dose immunoglobulin gave immediately favourable regression of the lesion, without side-effects. Possible modes of action of high-dose immunoglobulin treatment are discussed.
Adult↗