Steen Levin Nielsen

Mechanisms of edema formation in myxedema--increased protein extravasation and relatively slow lymphatic drainage.

We assessed extravascular accumulation of albumin and fluid in primary myxedema by measuring metabolic turnover and transcapillary escape of 131I-labeled human albumin in seven patients. In the hypothyroid state, we found a low plasma volume (P less than 0.05), a reduced rate of albumin synthesis and catabolism (P less than 0.01), an increased transcapillary escape rate of albumin (P less than 0.01), a remarkable increase in the extravascular mass of albumin (1500 micronmol; P less than 0.01) and a longer mean transit time through the extravascular spaces in primary myxedema than in other states of generalized edema (P less than 0.05). All variables returned to normal during l-thyroxine treatment. The extravascular accumulation of albumin, and presumably of all other plasma proteins, is important in the generalized edema typically found in myxedema. Inadequate lymphatic drainage may also explain the formation of exudates in the serous cavities that are well known in myxedema.

Raynaud phenomena and finger systolic pressure during cooling

Finger systolic pressure (FSP) can be measured after finger cooling with a water perfused double-inlet-plastic cuff on the midphalanx of a finger and a mercury-in-rubber strain gauge on the outer phalanx. After finger cooling to 20, 15 and 10 degree C eighteen females with primary Raynaud phenomena had a significantly greater reduction in FSP than twenty-two normal females, but only eleven of the eighteen females (60%) with Raynaud phenomena showed digital arterial closure. Standardized body cooling for 20 min before finger cooling enhanced the reaction in both groups. As only females with Raynaud phenomena showed digital artery closure, the diagnostic value of a combined finger and body cooling test in primary Raynaud phenomena is high. The reproducibility of the test is acceptable.

Treatment with angiotensin-converting-enzyme inhibitor for epirubicin-induced dilated cardiomyopathy

BACKGROUND Anthracycline chemotherapy in cancer can cause severe, frequently fatal congestive heart failure (CHF), the first-line treatment for which is diuretics and digoxin. We have studied the use of an angiotensin-converting-enzyme (ACE) inhibitor added as a third agent. METHODS In an observational study in hospital and as outpatients, 92 patients with advanced breast cancer were treated with epirubicin at a cumulative dose of 360 to 1000 mg/m2 (median 1000). Of 85 evaluable, nine developed life-threatening CHF at 1.5 to 13 months after ending epirubicin. Left ventricular ejection fraction (LVEF) decreased from normal to 18 to 35%. All received frusemide and digoxin, and then, after transient clinical relief, enalapril or ramipril (initially 1.25 mg orally daily, increasing to 10-15 mg after 4-6 weeks). FINDINGS Eight of the nine patients deteriorated while on digoxin/diuretic. Within 3 months of starting the ACE inhibitor in these patients, LVEF had increased to normal or near normal. Only one patient died in heart failure. Follow-up ranged from 11 to 42 months (median 26). The ACE inhibitor was well-tolerated, with no first-dose hypotension, except for one patient who discontinued treatment after 6 months because of persistent cough. Two others discontinued treatment with their ACE inhibitor after 22 and 28 months because they felt well. Survival in the nine patients was similar to that of those who did not develop CHF. INTERPRETATION Our experience suggests that treatment of anthracycline-induced CHF with an ACE inhibitor should start soon after clinical improvement on digoxin/diuretic regardless of the severity of symptoms rather than waiting for clinical deterioration.

Prevalence of primary Raynaud phenomena in young females

A questionnaire concerning Raynauds phenomenon was sent to eighty-five females (aged 21--50 years) working as physical therapists at municipal hospitals in Copenhagen. Fifteen of sixty-seven healthy young females (22%, 95% confidence limits 13--34%) were classified as having Raynaud phenomena in its primary form. Twenty-four persons underwent a detailed clinical investigation with measurement of blood pressure at the arm and fingers with cuff techniques. Cold provocation test on one finger was carried out after moderate body cooling. Of eight subjects being classified from the questionnaire as having Raynaud phenomena, six showed closure of the digital arteries at the local cold provocation, and all had an exaggerated response. A group complaining of cold fingers showed a greater reduction in finger blood pressure during local cooling than the normal group, but none showed closure. A questionnaire can separate the groups if Raynaud phenomena is defined by appearance of white and dead fingers on cold exposure with frequent cold or bluish fingers.

The absorption of subcutaneously injected short-acting soluble insulin: influence of injection technique and concentration.

The effect of injection technique on the absorption of subcutaneously injected short-acting insulin [125I labeled Actrapid (MC), Novo, Copenhagen, Denmark] was investigated in insulin-dependent diabetic patients. In one side of the abdomen insulin was given with a fixed standard technique. In the other side of the abdomen the temperature of the injected insulin, the depth of injection, and the duration of injection were varied. Furthermore, we compared the absorption of U40 and U100 insulin by giving either 8 U of the two insulins or 0.1 ml of both insulins simultaneously to the patients in either side of the abdomen. With regard to the injection technique the only significant finding was a faster absorption rate with deep (12 mm) than with superficial (3 mm) injection. The absorption of U100 insulin was significantly slower than of U40 insulin, when given in the same amount (8 U) as well as in the same volume (0.1 ml).

Diffusion and polymerization determines the insulin absorption from subcutaneous tissue in diabetic patients

In 23 diabetic patients, the disappearance from subcutaneous tissue of 125I-labelled short-acting insulin and of 133Xe (measuring subcutaneous blood flow (SBF] were registered simultaneously. Alterations in the SBF were produced either by orthostatic changes or by application of local heat or cold. The insulin absorption rate was related to the SBF in a curvilinear way with an almost linear relation at SBF below 2-3 ml . (min . 100 g)-1, whereas at SBFs above the value the insulin absorption rate increased less than proportional to SBF. Capillary diffusion capacity of the injected insulin was 0.0145-0.0874 ml . (min . 100 g)-1; indicating that insulin is absorbed in a polymeric form. This was supported by studies of insulin diffusion in agar gel at 37 degrees C, showing that insulin in the normal pharmacological concentration diffuses as a molecule of about 46,000 MW. In conclusion, the absorption of short-acting soluble insulin is curvilinearly related to the SBF. This can be explained by a diffusion-limited transport of insulin in the interstitial space, and increasing transcapillary transport of insulin at increasing blood flow rates caused by recruitment of capillaries, thus increasing exchange surface area and decreasing diffusion distance.

Controlled double-blind trial of the clinical effect of nifedipine in the treatment of idiopathic Raynaud's phenomenon

Twenty-six patients with idiopathic Raynauds phenomenon participated in a double-blind, crossover clinical trial comparing the clinical effect of nifedipine with that of placebo. Four patients discontinued the study because of side effects and one patient defaulted at the return visit. Nifedipine significantly reduced frequency and severity of attacks (p less than 0.01). In an overall evaluation of drug effectiveness, 19 of 21 patients preferred nifedipine to placebo (p less than 0.01). Nifedipine proved to be effective in the treatment of idiopathic Raynauds phenomenon, but side effects should be expected in some 30%.

Relationship of Subcutaneous Adipose Tissue Blood Flow to Thickness of Subcutaneous Tissue and Total Body Fat Mass

Adipose tissue blood flow (ATBF, expressed per unit tissue weight) was measured in the subcutaneous layer on the anterior abdominal wall in 196 subjects at rest, using the local 133Xenon washout method. With increasing amount of fat in the body ATBF decreased significantly, until a lower level was found in moderate and severe obesity, where ATBF was constant and independent of the body weight. The relationship between ATBF (ml/100 g/min) and amount of fat in the body is assumed to reflect a varying fat cell size. Regression analysis showed a significantly lower ATBF in females than in males. This difference could not be explained by the greater adiposity in females as compared to males. A significant increase in ATBF found during a 3-day period of total fasting emphasizes the importance of metabolic and neurohumoral factors in the regulation of ATBF in man.

Prazosin treatment of primary Raynaud's phenomenon

SummaryIn a double blind study, prazosin, a specific adrenergic alpha1-receptor antagonist, or placebo were given to 15 females with primary Raynauds phenomenon. At a low dose (1 mg twice daily) 5 out of 7 of the prazosin-treated patients reported a reduction of attacks induced by cold (p<0.05). This was not confirmed by a cold provocation test which showed no improvement at finger temperatures of 15 or 10°C. The highest tolerated dose in the prazosin-treated patients varied from 2–8 mg daily, and the greatest number of side effects was recorded in this group (p<0.05). None of the patients experienced complete relief from cold-induced attacks. It was concluded either that Raynauds phenomenon is not only caused by stimulation of alpha1-receptors in digital arteries, or the clinically achievable blockade was insufficient to prevent attacks.

Scintigraphic control of pulmonary embolism.

Pulmonary embolism was diagnosed by combined perfusion and ventilation scintigraphy in 30 patients. A control examination 6 months later revealed pulmonary embolism or infarction in 8, in spite of conventional treatment. Therefore, patients treated for pulmonary embolism should be reexamined 3 to 6 months after diagnosis.