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Objective:The aim was to investigate adipose tissue vascular and metabolic effects of an adrenaline infusion in vivo in subjects with and without type 2 diabetes mellitus (T2DM).Design:Clinical intervention study with 1-h intravenous adrenaline infusion.Subjects:Eight male overweight T2DM subjects and eight male weight-matched, non-T2DM subjects were studied before, during and after an 1-h intravenous adrenaline infusion. Adipose tissue blood flow (ATBF) was determined by Xenon wash-out technique, and microvascular volume in the adipose tissue was studied by contrast-enhanced ultrasound imaging. Adipose tissue fluxes of glycerol, non-esterified fatty acids (NEFA), triacylglycerol and glucose were measured by Fick's principle after catherisation of a radial artery and a vein draining the abdominal, subcutaneous adipose tissue.Results:ATBF increased similarly in both groups during the adrenaline infusion. One hour post adrenaline, ATBF was still increased in overweight T2DM subjects. Adrenaline increased microvascular volume in non-T2DM subjects while this response was impaired in overweight T2DM subjects. Adrenaline-induced increase in lipolysis was similar in both groups, but NEFA output from adipose tissue was delayed in overweight T2DM subjects. Glucose uptake in adipose tissue increased in non-T2DM subjects during adrenaline infusion but was unchanged in overweight T2DM subjects. This results in a delayed excess release of NEFA from the adipose tissue in overweight T2DM subjects after cessation of the adrenaline infusion.Conclusion:Capillaries in the adipose tissue are recruited by adrenaline in non-T2DM subjects; however, this response is impaired in overweight T2DM subjects. NEFA, released in adipose tissue during adrenaline stimulation, is insufficiently re-esterified in situ in overweight T2DM subjects, probably owing to increased ATBF after adrenaline infusion and inability to increase adipose tissue glucose uptake.

Lymphoscintigraphy is currently the leading diagnostic modality of lower extremity lymphoedema but has been criticized for being unreliable. Washout rate constants have been investigated and proven to be of diagnostic value in several studies of breast-cancer-related lymphoedema; however, the applicability in lower extremity lymphoedema needs further evaluation. The aim of the study was to verify if washout of (99m) Tc-Human Serum Albumin ((99m) Tc-HSA) is a reliable diagnostic tool in lower extremity lymphoedema.

Vejledningspligt, retighedsinformation, forvaltningslov, ret til viden om rettigheder, ombudsmandspraksis

Den 1. januar 2012 er det 25 år siden forvaltningsloven trådte i kraft. Forvaltningsloven har haft stor betydning for sagsbehandlingen i det offentlige - og dermed også udviklingen af den almindelige forvaltningsret. I den anledning udgives dette festskrift. Redaktionen har bestået af professor dr. jur. Steen Rønsholdt, Københavns Universitet, afdelingschef Jens-Christian Bülow, Justitsministeriet, direktør Jens Møller, Folketingets ombudsmand, og kontorchef Jens Olsen Folketingets Ombudsmand. Specialkonsulent Christian Ougaard. Folketingets Ombudsmand har været redaktionssekretær.

AIM: The aim of the study was to determine the degree of neuropathy (autonomic and somatic) in patients with diabetes mellitus with or without Charcot osteoarthropathy (CA).METHODS: Forty-nine patients with diabetes mellitus type 1 or 2 were investigated. The patient population of interest was the patients with acute Charcot foot (n=17) or chronic Charcot foot (n=7). The inclusion criterion for an acute Charcot foot was a temperature difference of more than 2° between the two feet, oedema of the affected foot, typical hotspots in a bone scintigram and a typical clinical course. In addition, patients with first toe amputation (n=5), a high-risk group for development of CA, and two control groups consisting of diabetes patients with (n=9) or without somatic neuropathy (n=11) were investigated. Regional blood flow in the feet was measured by venous occlusion plethysmography. Quantitation of somatic neuropathy was done by the Neuropathy Disability Score and modified Neuropathy Symptom Score. Quantitation of autonomic neuropathy was done by measurements of local venoarteriolar sympathetic axon reflex in the feet and of heart rate variability during deep breathing and orthostatic challenge.RESULTS: The patients with acute Charcot foot and first toe amputation had an increased blood flow in the affected foot and weakened but not absent venoarteriolar sympathetic axon reflex. In the other patient groups, a normal venoarteriolar sympathetic axon reflex in the feet was found.CONCLUSIONS: Peripheral sympathetic neuropathy is not likely to be the pathophysiologic mechanism behind the hyperemia in the foot during an acute attack of CA. The hyperemia is more likely secondary to local inflammatory events.

UNLABELLED: Postprandially, the blood flow and uptake of non-esterified fatty acids increase concomitantly in the abdominal subcutaneous adipose tissue in healthy subjects. In insulin-resistant subjects, this postprandial blood flow increase is blunted. We have previously found that the postprandial adipose tissue blood flow (ATBF) increase is accompanied by capillary recruitment in healthy subjects. The aim of the present study was to investigate whether the postprandial capillary recruitment in adipose tissue is affected in type 2 diabetes mellitus. Eight type 2 diabetic overweight male subjects and eight age- and weight-matched healthy subjects were studied. Contrast-enhanced ultrasound imaging was applied to study the microvascular volume in abdominal subcutaneous adipose tissue and in forearm skeletal muscle in the fasting state and 60, 120 and 180 min after a 75-g oral glucose load. Abdominal subcutaneous ATBF was measured using (133) Xenon washout technique, and forearm skeletal muscle blood flow was assessed by venous occlusion plethysmography. In the healthy, overweight subjects, ATBF increased and concomitantly capillary recruitment took place after glucose ingestion. No significant changes were found in the ATBF or in capillary recruitment in the type 2 diabetic subjects. There was no significant blood flow or microvascular blood volume changes in forearm skeletal muscle in either of the groups.CONCLUSION: After an oral glucose load, the abdominal ATBF and microvascular blood volume changes in abdominal subcutaneous adipose tissue are impaired in overweight type 2 diabetic subjects compared to weight-matched healthy subjects.

BACKGROUND: The aim of this article is to illustrate the possible applications of (18)F-fluorodeoxyglucose positron emission tomography/computer tomography ((18)F-FDG PET/CT) in chronic extremity lymphedema and its complications.METHODS AND RESULTS: (18)F-FDG PET/CT findings in a rare case of Stewart-Treves Syndrome (STS), angiosarcoma secondary to chronic extremity lymphedema, are presented. Lymphedema of the extremities is a debilitating disease characterized by chronic swelling due to interstitial edema caused by insufficient lymphatic drainage capacity. Progression with skin thickening, subcutaneous fibrosis, and increased adipose tissue volume is common. Chronic inflammation has been suggested as a key pathophysiologic component. STS is a rare complication with a very poor prognosis; however, early diagnosis and radical treatment is associated with increased survival. Thus, accurate pretreatment staging is paramount. (18)F-FDG PET/CT is highly sensitive in detecting increased glucose metabolism as seen in many types of cancer and inflammation. The role of (18)F-FDG PET/CT in the management of lymphedema and its complications has to our knowledge yet to be described. This case documents high (18)F-FDG uptake in STS, but is at the same time an example of the low specificity of this imaging modality.CONCLUSIONS: We suggest that (18)F-FDG PET/CT has the potential to become an important tool in the staging and treatment planning of Stewart-Treves syndrome. Furthermore, (18)F-FDG-accumulation may be a sensitive tool in detecting low grade inflammation in the skin and subcutis, which has been suggested to cause tissue remodeling in lymphedema progression. However, further studies are needed to elucidate this theory.

To measure bone mineral density in patients with diabetes mellitus and the complication Charcot osteoarthropathy (CA).

Lymphoedema of the lower extremities is a chronic debilitating disease that is often underdiagnosed. Early diagnosis and treatment is paramount in reducing the risk of progression and complications. Lymphoedema has traditionally been defined as interstitial oedema and protein accumulation because of a defect in the lymphatic drainage; however, some findings suggest that the interstitial protein concentration may be low in some types of lymphoedema. Primary lymphoedema is caused by an inherent defect in the lymphatic vessels or lymph nodes. Secondary lymphoedema is caused by damages to the lymphatic system most often caused by cancer or its treatment. Many of the underlying pathophysiological mechanisms have yet to be elucidated. Many methods have been developed for examination of the lymphatic system. Lymphoscintigraphy is presently the preferred diagnostic modality. Lack of consensus regarding protocol and qualitative interpretation criteria results in a too observer dependent outcome. Methods for objectifying the scintigraphy through quantification have been criticized. Depot clearance rates are an alternative method of quantification of lymphatic drainage capacity. This method however has mostly been applied on upper extremity lymphoedema. The aim of this review is to provide a literature-based overview of the aetiology and pathophysiology of lower extremity lymphoedema and to summarize the current knowledge about lymphoscintigraphy and depot clearance techniques. The abundance of factors influencing the outcome of the examination stresses the need for consensus regarding examination protocols and interpretation. Further studies are needed to improve diagnostic performance and understanding of pathophysiological mechanisms.

We investigated the role of glucose-dependent insulintropic polypeptide (GIP) in the regulation of gastric emptying (GE), appetite, energy intake (EI), energy expenditure (EE), plasma levels of triglycerides (TAG), and free fatty acids (FFA) in humans. First, 20 healthy males received intravenous infusion of GIP (0.8 pmol.kg(-1).min(-1)) or saline for 300 min during and after a fixed meal (protocol 1). GE was measured using paracetamol, appetite sensations using visual analog scales, EE using indirect calorimetry, and EI during a subsequent ad libitum meal (at 300 min). Next, 10 healthy males received intravenous infusions of Intralipid, glucose, or Intralipid plus glucose, with and without GIP (1.5 pmol.kg(-1).min(-1)) for 300 min (protocol 2). In protocol 1, GIP did not have any effect on GE, EI, EE, removal of TAG, or FFA and did not influence the subjective feeling of hunger, satiety, fullness or prospective food consumption compared with saline. In protocol 2, no difference was seen in the plasma TAG on Intralipid + GIP/saline and Intralipid + glucose + GIP/saline days. FFA concentrations were lower on Intralipid + glucose + GIP/saline days (P <0.05) compared with Intralipid + GIP/saline days and on Intralipid + GIP day (P <0.004) compared with Intralipid + saline day. Insulin increased on all GIP days compared with saline days (P <0.05). In conclusion, while confirming its insulinotropic effects, these data suggest that GIP does not affect GE, appetite, energy intake, EE, or the clearance rate of the applied TAG formulation in humans. However, both insulin and GIP lower post-Intralipid FFA concentration, GIP probably via stimulation of insulin secretion, increasing FFA reesterification.

Udgivelsesdato: 2009-Apr, BACKGROUND: Nicotine released from tobacco smoke causing reduction in blood flow has been suggested as causative for postoperative wound complications in smokers, but the mechanism remains unknown. MATERIALS AND METHODS: In eight healthy male smokers and eight ex-smokers, the cutaneous and subcutaneous blood flow (QBF, SqBF) was assessed by Laser Doppler and 133Xe clearance. Tissue oxygen tension (TO(2)) was measured by a LICOX O(2)-electrode. Tissue glucose and lactate (Tgluc, Tlact) were assessed by microdialysis. The parameters were studied after intravenous infusion of 1.0 mg nicotine, smoking of one cigarette, arterial occlusion, and reperfusion. RESULTS: Nicotine infusion decreased SqBF from 4.2 +/- 2.0 to 3.1 +/- 1.2 mL/100 g tissue/min (P < 0.01), whereas QBF was 21.7 +/- 8.6 and 22.7 +/- 9.6 Arbitrary Units (AU), respectively (P = 0.21). TO(2) increased from 49.3 +/- 12.0 to 53.9 +/- 12.0 mm Hg (P = 0.01). Tgluc and Tlact remained unaffected. Smoking decreased SqBF from 4.2 +/- 2.0 to 2.7 +/- 1.2 mL/100 g tissue/min (P < 0.01). QBF decreased from 23.4 +/- 9.2 to 20.3 +/- 7.4 AU (P < 0.01), and TO(2) decreased from 53.9 +/- 12.0 to 48.4 +/- 11.1 mm Hg (P < 0.01). Following smoking, Tgluc decreased from 0.7 +/- 0.1 to 0.6 +/- 0.1 ng/mL (P < 0.01), and Tlact increased from 0.2 +/- 0.1 to 0.3 +/- 0.2 ng/mL (P < 0.01). The observed alterations were similar in smokers and ex-smokers. CONCLUSIONS: Nicotine has a limited vasoactive effect in the skin and subcutis unlikely to be explained by smoking, which distinctly decreases tissue blood flow, oxygen tension, and aerobe metabolism independent of smoking status.

Udgivelsesdato: 2008-Mar, During prolonged adrenaline infusion, lipolysis peaks within 30 min and thereafter tends to decline, and we hypothesized that the stimulation of local adipose tissue alpha2-adrenergic receptors accounts for this decline. The lipolytic effect of a prolonged intravenous adrenaline infusion combined with local infusion of the alpha2-blocker phentolamine in superficial and deep abdominal subcutaneous adipose tissue and in preperitoneal adipose tissue was studied in seven healthy subjects. The interstitial glycerol concentration in the three adipose tissue depots was measured by the microdialysis method. Regional adipose tissue blood flow was measured by the (133)Xe clearance technique. Regional glycerol output (lipolytic rate) was calculated from these measurements and simultaneous measurements of arterial glycerol concentrations. Adrenaline infusion increased lipolysis in all three depots (data previously published). Phentolamine infusion did not augment lipolysis in the subcutaneous depots while it increased the lipolytic rate in the preperitoneal depot. It is concluded that alpha2-adrenergic receptors do not have a significant effect on subcutaneous adipose tissue lipolysis during high circulating adrenaline concentrations, and the decrease in lipolysis in subcutaneous adipose tissue under prolonged adrenaline stimulation is thus not attributed to alpha2-adrenergic receptor inhibition of lipolysis. However, in the preperitoneal adipose tissue depot, alpha2-adrenergic receptor tone plays a role for the lipolytic rate obtained during prolonged adrenaline stimulation.

Udgivelsesdato: 2007-Sep, To determine whether blockade of the exercise-induced increase in growth hormone (GH) secretion may affect the regional lipolytic rate in the post-exercise recovery period, the aim of the present experiments was to study the effect of infusion of the somatostatin analogue octreotide on the s.c., abdominal adipose tissue metabolism, before, during and after exercise in healthy, fasting, young male subjects. The adipose tissue net releases of fatty acids and glycerol were measured by arterio-venous catheterizations and simultaneous measurements of adipose tissue blood flow with the local Xe-clearance method. Nine subjects were studied during 1-h basal rest, and then during continuous octreotide infusion during 1-h rest, 1-h exercise at 50% of maximal oxygen consumption and 4-h post-exercise rest. A control study on seven subjects was performed under similar conditions but without octreotide infusion. The results show that octreotide infusion during rest increased lipolysis and fatty acid release from the abdominal, s.c. adipose tissue. The exercise-induced increase in lipolysis and fatty acid release does not seem to be affected by octreotide when compared with the control study without octreotide infusion while the post-exercise increase in lipolysis is inhibited by octreotide, suggesting that the exercise-induced increase in GH secretion plays a role for the post-exercise lipolysis in s.c., abdominal adipose tissue.

Subcutaneous adipose tissue lipolysis was studied in vivo by Fick's arteriovenous (a-v) principle using either calculated (microdialysis) or directly measured (catheterization) adipose tissue venous glycerol concentration. We compared results during steady-state (rest and prolonged continuous exercise), as well as during non-steady-state (onset of exercise and early exercise) experimental settings. Fourteen healthy women [age: 74 +/- 1 (SE) yr] were studied at rest and during 60-min continuous bicycling at 60% of peak O(2) uptake. Calculated and measured subcutaneous abdominal adipose tissue venous glycerol concentrations increased substantially from rest to exercise but were similar both at rest and during later stages of exercise. In contrast, during the initial approximately 40 min of exercise, calculated glycerol concentration was significantly lower (approximately 40%) than measured adipose tissue venous glycerol concentration. Despite several methodological limitations inherent to both techniques, the results strongly suggest that microdialysis and catheterization provide similar estimates of subcutaneous adipose tissue lipolysis in steady-state experimental settings like rest and continuous prolonged exercise. However, during shorter periods of exercise (<40 min), the results from the two techniques may differ quantitatively in the studied subjects. Caution should, therefore, be taken when lipolysis is evaluated, based on results obtained by the two techniques under non-steady-state conditions.

Udgivelsesdato: 2002-Sep-15, This study was conducted to investigate the role of splanchnic and adipose tissue in the regulation of fatty acid (FA) metabolism at rest, during 1 h of semi-recumbent cycle exercise at 60 % of maximal power output and 3 h of recovery. In six post-absorptive healthy volunteers catheters were placed in a radial artery, hepatic vein and a subcutaneous vein on the anterior abdominal wall. Whole body, and regional splanchnic and adipose tissue FA metabolism were measured by a constant infusion of the stable isotopes [U-(13)C]palmitate and [(2)H(5)]glycerol and according to Fick's principle. The whole body rate of extracellular FA reesterification was similar at rest and during exercise (approximately 290 micromol min(-1)) and increased during recovery to a plateau of 390 micromol min(-1). FA and triacylglycerol (TAG) uptake by adipose tissue was undetectable, but a constant but small glycerol uptake of approximately 25 nmol (100 g)(-1) min(-1) was observed. From the FA taken up by the splanchnic area, 13 % was oxidized, 5-11 % converted to ketone bodies, and approximately 35 % incorporated in TAG released both at rest and at the third hour of recovery from exercise. Splanchnic FA reesterification could account for 51 % and 58 % of whole body extracellular FA reesterification, of which half was accounted for by TAG released from the splanchnic area, at rest and in recovery, respectively. In conclusion, in the post-absorptive state, adipose tissue contributes very little to extracellular FA reesterification and splanchnic reesterification can account for 50-60 %, implying that FA reesterification in other tissues is important. The extracellular FA reesterification rate does not change with exercise but is higher during recovery. Furthermore, the uptake of glycerol by adipose tissue indicates that adipose tissue can metabolize glycerol.