A Sjögren's research while affiliated with Lund University and other places

1. A double-blind placebo-controlled study was conducted on the effects of oral terbutaline (beta 2-adrenoceptor agonist) and propranolol (beta 1 beta 2-adrenoceptor antagonist) on basal heat production of skeletal muscle, measured ex vivo by direct microcalorimetry. Terbutaline slow-release 7.5 mg, propranolol 80 mg, and matching placebo were randomly administered twice daily for 1 week to 15 healthy males, using a cross-over design. 2. Resting heat production in biopsied vastus lateralis was lowered by median 27% (P < 0.01) after terbutaline medication as compared with placebo. The cause of this hypometabolism at the cellular level is obscure but may possibly be explained by desensitization of beta 2-receptors. 3. Propranolol decreased the metabolic rate by 17% (P > 0.3); this might imply that the sympathetic nervous system is playing only a minor role in the regulation of basal metabolic rate in muscle, or that up-regulation of beta-receptors had influenced the decline. 4. The muscle utilized about 6% of its total energy for the Na-K pump as assessed after inhibition by ouabain. 5. Serum potassium was significantly lowered by terbutaline and slightly increased by propranolol with no relationship between changes in extracellular levels and muscle content of potassium under resting conditions. Energy values for the Na-K pump in muscle after 1 week of terbutaline or propranolol medication were similar to placebo. The results are not consistent with the hypothesis that decreased serum potassium during continuous beta 2-adrenoceptor agonist treatment is due to a chronically activated Na-K pump, at least not in resting muscle.

Magnesium deficiency may be of importance for the pathogenesis and the clinical outcome of several cardiac disorders, including coronary artery disease and cardiac arrhythmias. Magnesium deficiency is frequently found, and the administration of magnesium has proved to be of therapeutic value in subjects with cardiac diseases.

Pulmonary embolism (PE) leads to an abnormal alveolar deadspace that is expired in synchrony with gas from normally perfused alveoli. This feature of PE separates it from pulmonary diseases affecting the airways, which are characterized by nonsynchronous emptying of compartments with an uneven ventilation/perfusion relationship. An analysis of the single breath test (SBT) for CO2, SBT-CO2, focusing on the late tidal expirate, was made in order to evaluate the feasibility to use the SBT-CO2 for the diagnosis of PE. The test was evaluated in 38 patients with suspected PE where pulmonary angiography showed that nine had PE and 29 did not. It was also tested in a reference population consisting of patients with normal lung function, obstructive lung disease and interstitial lung disease. Previously suggested gas exchange measurements for the diagnosis of PE, ie, the physiologic deadspace fraction, VDphys/VT, and the arterial-to-end-tidal CO2 gradient, P(a-E')CO2, were also evaluated in the groups. SBT-CO, achieved a nearly complete separation between the patients with PE and those without. The other measurements, however, showed a substantial overlap between patients with PE and those with obstructive or interstitial lung disease. The SBT-CO2 is simple and potentially widely available and warrants further study as a routine technique for the diagnosis of PE. (Chest 1989; 96:357–62) SBT = single breath test; fDlate = late dead-space fraction

Wistar rats were fed a low magnesium diet for 8 or 12 weeks, resulting in reduced levels of magnesium in plasma, heart, and skeletal muscle, as compared with pair-fed control rats. The magnesium-deficient rats also had reduced tissue levels of potassium. Coronary arteries and thoracic aorta from magnesium-deficient rats and control rats were incubated in tissue baths and the contractile responses to potassium, 5-hydroxy-tryptamine, and prostaglandin F2 alpha were investigated using a sensitive in vitro system. The concentration-contraction curve, for all agents was shifted to the left in coronary arteries from magnesium-deficient rats. In aorta from magnesium-deficient rats, the pattern of change in reactivity to these agonists was not uniform: the concentration-contraction curve for 5-hydroxytryptamine was shifted to the left, the contractile response to prostaglandin F2 alpha was reduced, while there was no change in the response to potassium. The contractile response to the administration of calcium to calcium-depleted, potassium-depolarized vessels from magnesium-deficient rats was enhanced; the effect was more pronounced in coronary arteries as compared to the aorta. Hence, the vasomotor reactivity of coronary arteries appears to be more sensitive than is the aorta during magnesium-deficient conditions.

Contractile responses to prostaglandin F2 alpha, serotonin, noradrenaline, and potassium were examined in isolated intramyocardial arteries of Wistar rats 8 weeks after the induction of diabetes mellitus by administration of streptozotocin (STZ). The concentration-response curves obtained were compared with those noted in vessels both from age- and from weight-matched control rats. Light and electron microscopy did not reveal any major change in coronary artery wall thickness or morphology. There was no difference in the pattern of vasomotor responses between the two control groups. Contractile responses to prostaglandin F2 alpha, and potassium were significantly reduced, while contractile responses to serotonin and noradrenaline were unaltered in coronary arteries from diabetic rats. The vasomotor responses to noradrenaline and potassium showed a biphasic pattern in control vessels, i.e. contraction noted at high agonist concentrations was preceded by slight, but reproducible relaxation at lower concentrations. In diabetic vessels these relaxant responses were absent. The contraction produced by noradrenaline was markedly enhanced by the presence of propranolol in both diabetic and control vessels. Dilator responses to verapamil, diltiazem, nifedipine, papaverine and magnesium were studied in serotonin-precontracted coronary arteries; the concentration-response curves obtained by verapamil and diltiazem were shifted to the right in diabetic vessels. It appears justified to use vessels from age-matched rats as controls when vasomotor reactivity in coronary arteries from STZ-diabetic rats is investigated. The reduction in contractile responses to prostaglandin F2 alpha and potassium, and the reduction or lack of relaxant responses to noradrenaline, potassium, verapamil and diltiazem, in diabetic coronary arteries, indicate a selective modification of the coronary circulation by the diabetic disease.

The magnesium status was evaluated in 30 subjects with Crohn's disease and in 30 controls. Subjects with Crohn's disease had lower concentrations of magnesium in muscle biopsy specimens (p less than 0.001), mononuclear cells (p less than 0.05), and in urine collected during 24 h (p less than 0.001) as compared with controls. After intravenous infusion of 60 mmol magnesium and 80 mmol potassium to 17 subjects with Crohn's disease a significant increase in concentrations of magnesium in muscle specimens (p less than 0.05), mononuclear cells (p less than 0.01), and plasma (p less than 0.01) was noted. The retention of intravenously infused magnesium was significantly higher in subjects with Crohn's disease than in 11 healthy controls (p less than 0.001) and was inversely correlated with the content of magnesium in muscle specimens (r = -0.52; p less than 0.05). The implication of these findings is that analysis of magnesium in muscle specimens and estimation of magnesium retention during an intravenous magnesium infusion are useful to confirm a suspected magnesium deficiency.

Zinc status was evaluated in 30 subjects with Crohn's disease. Intestinal resection had previously been performed in 23 of the subjects. The concentrations of zinc were determined in plasma, erythrocytes, percutaneous muscle biopsies, and in urine collected during 24 hours. The results were compared with those in 19 healthy controls. Most of the patients had a normal zinc status. The levels of zinc were, however, reduced (i.e., less than mean -2 SD for controls) in plasma for five, in erythrocytes for two, and in muscle biopsies for six subjects with Crohn's disease. The mean concentrations of zinc in plasma and erythrocytes were reduced (P less than 0.05), whereas the mean content of zinc in muscle biopsies and the mean urinary excretion of zinc were not significantly different, in subjects with Crohn's disease. The various zinc parameters did not correlate to each other. The results indicate that some subjects with Crohn's disease had an intracellular zinc depletion, which, however, was not reflected by a reduction in levels of zinc in plasma.

The concentrations of magnesium, potassium and zinc were determined in plasma, erythrocytes, muscle biopsies, and in urine collected during 24 hours, in 18 subjects with type II diabetes mellitus (DM). Magnesium was also determined in mononuclear cells. The results were compared with those in 35 (magnesium and potassium analyses) or 26 (zinc analyses) healthy controls. Subjects with type II DM had lower concentrations of magnesium (3.79 +/- 0.32 vs. 4.29 +/- 0.22 mmol/100 g FFDS), potassium (40.5 +/- 5.17 vs. 46.1 +/- 3.81 mmol/100 g FFDS) and zinc (231 +/- 29 vs. 247 +/- 23 ng/mg FFDS) in skeletal muscle. Furthermore, the urinary excretions of magnesium and zinc were higher, as compared with those in healthy controls (5.00 +/- 2.68 vs. 3.62 +/- 1.47 mmol/24 hours, and 683 +/- 285 vs. 326 +/- 205 micrograms/24 hours, respectively). The contents of magnesium, potassium and zinc plasma did not correlate with the corresponding concentrations in skeletal muscle or circulating blood cells, as investigated in healthy controls, diabetics and in all subjects together, implying that the plasma concentrations are not useful in the assessment of electrolyte status. Hence, deficiency of electrolytes frequently occurs, and should be looked for, in subjects with type II DM.