The Copenhagen Muscle Research Centre (CMRC) 1994-2004.

This paper presents an impressionistic summary of the formation, activities, accomplishments, and impact of the Copenhagen Muscle Research Centre (CMRC) from 1994 to 2004. The history of the CMRC is viewed in the context of the goals of the original program, the tradition of excellence in exercise physiology in Copenhagen since the time of August Krogh, and the structure of the center. The key role of Professor Bengt Saltin as a visionary, flexible, and inclusive leader is highlighted.

Metabolic effects of free fatty acids during endotoxaemia in a porcine model--free fatty acid inhibition of growth hormone secretion as a potential catabolic feedback mechanism.

Critical illness and severe inflammation are catabolic states characterised by breakdown of tissue and protein stores, by increased levels of free fatty acids, and by insulin resistance. These metabolic features contribute to morbidity and mortality. Growth hormone and insulin are the two major anabolic hormones. The present study was designed to test whether increased levels of free fatty acids (i) inhibit growth hormone secretion and (ii) induce insulin resistance during acute endotoxin exposure in a porcine model of critical illness. We studied 20 pigs for 6 h during combined anaesthesia and endotoxin infusion and a hyperinsulinaemic glucose clamp to control glucose, insulin, and free fatty acid concentrations. Pigs were randomised to two different continuous infusion rates of Intralipid resulting in different, sustained, and elevated free fatty acid concentrations (1.63 mmol l(-1) vs. 0.58 mmol l(-1), p=0.0002). Concomitantly, we observed reduced growth hormone concentrations in the group with high free fatty acid concentrations (3.5 ng ml(-1) vs. 6.6 ng ml(-1), p<0.003). No difference in insulin sensitivity, measured as the glucose infusion rate necessary to maintain euglycaemia, was observed. We conclude that high levels of free fatty acids reduce circulating growth hormone concentrations in porcine endotoxaemia; this probably constitutes a negative feedback mechanism whereby growth hormone induced-stimulation of free fatty acids release inhibit growth hormone secretion. This mechanism may further contribute to protein loss in critical illness. We found no evidence that the increment of plasma free fatty acids between groups contribute to insulin resistance in critical illness.

[Research as a subject--for research]. / Forskning som genstand--for forskning.

Based on his inaugural lecture as adjunct professor of research policy at the University of Aarhus the author delineates the motives for "science of science", describes the various disciplines in the area, some of the results and some important, but unanswered questions about research.

Oral terbinafine in toenail dermatophytosis. A double-blind, placebo-controlled multicenter study with 12 months' follow-up.

The treatment of onychomycosis has previously often been protracted and unsuccessful. Terbinafine has been shown to be effective in short-term regimens. In this double-blind, placebo-controlled study, 148 patients with toenail dermatophytosis were randomized to treatment with either 250 mg terbinafine daily or placebo for 3 months. An additional treatment was given for 3 months to patients whose infection had not responded. The patients were followed clinically and mycologically through 12 months. After 3 months 82% of the terbinafine-treated group, versus 5% of the placebo group, showed significant improvement, i.e. negative culture and growth of unaffected nail more than 2 mm (p = < 0.0001). After 12 months clinical and mycological cure was seen in 40% of the patients treated with terbinafine for 3 or 6 months, while 67-81% were clinically cured, but with positive microscopy. Side-effects occurred in 13.5% of the terbinafine group, versus 5.4% of the placebo group, and were mild. 250 mg terbinafine daily for 3 months was significantly more effective than placebo. The efficacy did not appear to improve with additional treatment for 3 months.

Atopic dermatitis may be linked to whether a child is first- or second-born and/or the age of the mother.

Five hundred and thirty families with at least 1 child who had been referred to a dermatologist with atopic dermatitis were interviewed in an effort to determine whether factors such as the age of the mother when a child is born and/or birth rank can contribute to the development of atopic dermatitis. The families interviewed had a total of 1,084 children, or an average of 2 children per family. Sixty per cent of the children with atopic dermatitis were under 5 years of age. Ninety-one per cent of them had developed the disease before the age of 3; those most severely affected had developed the disease during the first year of life. In families with 2 children, but only 1 child with atopic dermatitis, the odds ratio for the second child to develop atopic dermatitis was 1.379 (0.025 < p < 0.05). The average maternal age was 24.8 to 25.2 years when giving birth to the first child and 28 years when giving birth to the second child, irrespective of the status of the child. Thus, atopic dermatitis can be related to birth rank or to the age of the mother.

[Externalizing the problem--a method in psychiatric treatment]. / Eksternalisering av problemet--en metode i psykiatrisk behandling.

Michael White is an Australian family therapist. He has developed a therapeutical method which he calls "externalizing the problem". According to this method, the patient's problem is given a linguistic designation, for example "the tyrant of anguish", "the tempter of drugs", "the black voice", and is kept outside the dominant identity of the patient. The patient, in time also the family, is invited to a dialogue on the effect of this problem and how to develop strategies to beat "the problem tyrant". The authors have based their work on the thoughts and methods of Michael White. They have used these methods to address a wide range of psychiatric problems. The paper describes the theory behind the methods, and presents a number of clinical examples where they have been used.

[One step forward, one step back. Research policy in the 1990's--a link in a historical sequence]. / Trin foran os, trin bag os. Forskningspolitikken i 1990'erne--et led i et historisk forløb.

A description is presented of the major problems in Danish research in the nineteen nineties, including internationalization, competition, concentration, training of research workers, transparency, connections with the surrounding community and ability of drawing conclusions. Elements in the Danish research system and the research policy are described. Connections are then made with the situations at the end of the nineteen sixties and beginning of the nineteen seventies when the new research council established a considerable part of the basis upon which we build today. Finally, freedom in research and the responsibilities of research and research workers for the community are mentioned.

[Pindborg tumor in the maxillary sinus. An unusual case of atypical facial pain]. / Pindborg-tumor i sinus maxillaris. Et usaedvanligt tilfaelde af atypiske ansigtssmerter.

A woman aged 40 years had experienced left-sided facial pain for some months. Dental treatment did not result in any improvement. X-ray of the maxillary sinus revealed a tooth in the left maxillary sinus. At operation, this was shown to be a calcified epithelial odontogenic tumour (Pindborg tumour).

Antigen-free diet in adult patients with atopic dermatitis. A double-blind controlled study.

The efficacy of an antigen-free diet on the activity of atopic dermatitis was examined in a double-blind study, comprising 33 adults with severe atopic dermatitis. The antigen-free diet (Vivasorb) was compared to a placebo diet during three weeks of hospitalization. Twenty-five patients were evaluable, two of whom had their diet stopped after a few days due to exacerbation. Nine patients improved, while 16 patients were unchanged. Among those who improved five patients had Vivasorb and four placebo diet. In the remaining group 11 patients had Vivasorb and five had placebo. Four patients reported of less pruritus, sleeplessness and antihistamine consumption (three Vivasorb, one placebo) while 21 did not (13 Vivasorb, eight placebo). Thus, there were no significant differences between the groups. Paraclinical studies of circulating eosinophilocytes, serum IgE, orosomucoid, HLA-antigens, and immunofluorescence of skin biopsies showed no differences between the Vivasorb and the placebo groups. The results from the examination of this relatively small number of patients suggest that elementary intolerance plays little role in the etiology of atopic dermatitis in adults.

Orotic acid sodium salt in kidney stones and urinary deposits.

Kidney stones from a plaice, Pleuronectes platessa, have been shown to consist of the sodium salt of orotic acid. Precipitation of orotic acid in human kidneys and urine samples has previously been reported but the precipitates must have been salts, most likely the sodium salt, of orotic acid and not the free acid. This reinterpretation is based on the acid strength of orotic acid and on data for the solubilities of sodium orotate and orotic acid. Sodium orotate is therefore a member on the list of compounds present in human urinary deposits and calculi. X-ray powder diagrams and d-values and IR-spectra of the sodium salt are recorded to facilitate future identifications.

A randomized trial of etretinate (Tigason) in palmoplantar pustulosis.

5 patients with palmoplantar pustulosis (PPP) were randomized to 8 weeks of daily treatment with either oral etretinate, 1 mg/kg b.w. or placebo. Good or moderate effect was obtained in 18 or 20 patients on etretinate compared o 6 of 21 patients on placebo (p less than 0.001). Etretinate proved to be significantly superior to placebo with regard to influence on the individual symptoms and signs of pustulosis. All patients on etretinate experienced some side effects from the mucous membranes, but they were generally mild. Treatment was discontinued after 4 weeks in 3 patients for reasons unrelated to treatment, in 4 for lack of effect (all on placebo) and in 2 for side effects (both or etretinate). Etretinate is a good alternative to other systemic treatments of PPP.

The naevoid basal cell carcinoma syndrome. Clinical, biochemical and radiological aspects.

Eight living patients with the nevoid basal cell carcinoma syndrome (NBS) underwent a clinical and radiological examination, and data on a deceased patient was included. Cerebral CT-scannings were performed on eight patients, and calcification in the falx and tentorium cerebelli was found in all patients but one. Congenital hydrocephalus or agenesis of the corpus callosum could not be demonstrated. Laboratory results, including serum levels of alpha 1-antitrypsin and alpha 2-macroglobulin, haptoglobin, inorganic phosphorus, alkaline phosphatase and calcium, were normal in all patients but two. It is postulated that elevated serum alkaline phosphatase in patients with NBS is correlated to the presence of growing odontogenic keratocysts.

The influence of topical steroid application on tuberculin skin reactions in healthy persons.

Thirty-seven healthy persons were studied in order to evaluate the influence of topical steroid application on tuberculin skin reactions. Four areas measuring 4 cm in diameter were each treated with 50 micrograms of hydrocortisone cream 1%, or 50% micrograms of halcinonide (Halog) cream 0.1%, or 50 micrograms of unguentum cetacei simplex (cold cream), or not treated. The creams were applied once daily for 3 days before and one day after a tuberculin skin test. After 24 and 48 hours the area of induration were measured. We observed that application of unguentum cetacei simplex increased the size of the induration at the 24-hour reading, but not after 48 hours. Hydrocortisone cream 1% gave the same effect, whereas halcinonide cream (Halog) 0.1% caused ischaemia of the skin and reduced the induration of the skin test after 24 hours, but not after 48 hours. In 12 persons we found that simple rubbing of the skin with halcinonide cream base did not affect the size of the tuberculin skin reaction. In the present study we found that even very potent local steroid application on intact skin could only delay the development of tuberculin skin reactions, but could not diminish their size.

Effects of carbon dioxide and oxygen on the regulation of photosynthetic carbon metabolism by ammonia in spinach mesophyll cells.

Photosynthetic carbon metabolism of isolated spinach mesophyll cells was characterized under conditions favoring photorespiratory (PR; 0.04% CO(2) and 20% O(2)) and nonphotorespiratory (NPR; 0.2% CO(2) and 2% O(2)) metabolism, as well as intermediate conditions. Comparisons were made between the metabolic effects of extracellularly supplied NH(4) (+) and intracellular NH(4) (+), produced primarily via PR metabolism. The metabolic effects of (14)CO(2) fixation under PR conditions were similar to perturbations of photosynthetic metabolism brought about by externally supplied NH(4) (+); both increased labeling and intracellular concentrations of glutamine at the expense of glutamate and increased anaplerotic synthesis through alpha-ketoglutarate. The metabolic effects of added NH(4) (+) during NPR fixation were greater than those during PR fixation, presumably due to lower initial NH(4) (+) levels during NPR fixation. During PR fixation, addition of ammonia caused decreased pools and labeling of glutamate and serine and increased glycolate, glyoxylate, and glycine labeling. The glycolate pathway was thus affected by increased rates of carbon flow and decreased glutamate availability for glyoxylate transamination, resulting in increased usage of serine for transamination. Sucrose labeling decreased with NH(4) (+) addition only during PR fixation, suggesting that higher photosynthetic rates under NPR conditions can accommodate the increased drain of carbon toward amino acid synthesis while maintaining sucrose synthesis.