A vicious circle in chronic lymphoedema pathophysiology? An adipocentric view.

Chronic lymphoedema is a disease caused by a congenital or acquired damage to the lymphatic system and characterized by complex chains of pathophysiologic events such as lymphatic fluid stasis, chronic inflammation, lymphatic vessels impairment, adipose tissue deposition and fibrosis. These events seem to maintain and reinforce themselves through a positive feedback loop: regardless of the initial cause of lymphatic stasis, the dysfunctional adipose tissue and its secretion products can worsen lymphatic vessels' function, aggravating lymph leakage and stagnation, which can promote further adipose tissue deposition and fibrosis, similar to what may happen in obesity. In addition to the current knowledge about the tight and ancestral interrelation between immunity system and metabolism, there is evidence for similarities between obesity-related and lymphatic damage-induced lymphoedema. Together, these observations indicate strong reciprocal relationship between lymphatics and adipose tissue and suggest a possible key role of the adipocyte in the pathophysiology of chronic lymphoedema's vicious circle.

Applicability of contrast-enhanced ultrasound in the diagnosis of plantar fasciitis.

Contrast-enhanced ultrasound (CEUS) is used to visualize the microvascularization in various tissues. The purpose of this study was to investigate whether CEUS could be used to visualize the microvascular volume (MV) in the plantar fascia, and to compare the method to clinical symptoms and B-mode ultrasound (US) in patients with plantar fasciitis (PF). Twenty patients with unilateral PF were included and were divided by US in insertional thickening (10), midsubstance thickening (5), and no US changes (5). The MV was measured simultaneously in both heels. Four areas in the plantar fascia and plantar fat pad were measured independently by two observers. Inter- and intra-observer correlation analyses were performed. The asymptomatic heels showed a constantly low MV, and for the whole group of patients, a significantly higher MV was found in the symptomatic plantar fascia and plantar fat pad. Inter-observer correlation as well as intra-observer agreement was excellent. The MV in the plantar fascia and plantar fat pad can be measured reliably using CEUS, suggesting that it is a reproducible method to examine patients with plantar fasciitis.

The blunted effect of glucose-dependent insulinotropic polypeptide in subcutaneous abdominal adipose tissue in obese subjects is partly reversed by weight loss.

BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) appears to have impaired effect on subcutaneous abdominal adipose tissue metabolism in obese subjects. The aim of the present study was to examine whether weight loss may reverse the impaired effect of GIP on subcutaneous abdominal adipose tissue in obese subjects. METHODS: Five obese males participated in a 12-week weight loss program, which consisted of caloric restriction (800 Cal day(-)(1)) followed by 4 weeks of weight-maintenance diet. Before and after weight loss, subcutaneous adipose tissue lipid metabolism was studied by conducting regional measurements of arterio-venous plasma concentrations of metabolites and blood flow (adipose tissue blood flow, ATBF) across a segment of the abdominal adipose tissue in the fasting state and during GIP infusion (1.5 pmol kg(-)(1 )min(-)(1)) in combination with a hyperinsulinemic-hyperglycemic clamp. RESULTS: After weight loss (7.5±0.8 kg), glucose tolerance and insulin sensitivity increased significantly as expected. No significant differences were seen in basal ATBF before (1.3±0.4 ml min(-1) 100 g tissue(-1)) and after weight loss (2.1±0.4 ml min(-1) 100 g tissue)(-1); however, a tendency to increase was seen. After weight loss, GIP infusion increased ATBF significantly (3.2±0.1 ml min(-1) 100 g tissue(-1)) whereas there was no increase before weight loss. Triacylglycerol (TAG) uptake did not change after weight loss. Baseline free fatty acid (FFA) and glycerol output increased significantly after weight loss, P<0.001. During the clamp period, FFA and glycerol output declined significantly, P<0.05, with no differences before and after weight loss. Weight loss increased glucose uptake and decreased FFA/glycerol ratio during the clamp period, P<0.05. CONCLUSIONS: In obese subjects, weight loss, induced by calorie restriction, improves the blunted effect of GIP on subcutaneous abdominal adipose tissue metabolism.

Transmission dynamics and control of Ebola virus disease outbreak in Nigeria, July to September 2014.

We analyse up-to-date epidemiological data of the Ebola virus disease outbreak in Nigeria as of 1 October 2014 in order to estimate the case fatality rate, the proportion of healthcare workers infected and the transmission tree. We also model the impact of control interventions on the size of the epidemic. Results indicate that Nigeria's quick and forceful implementation of control interventions was determinant in controlling the outbreak rapidly and avoiding a far worse scenario in this country.

Glucose-dependent insulinotropic polypeptide has impaired effect on abdominal, subcutaneous adipose tissue metabolism in obese subjects.

OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) appears to have a role in lipid metabolism. Recently, we showed that GIP in combination with hyperinsulinemia and hyperglycemia increases triglyceride uptake in abdominal, subcutaneous adipose tissue in lean humans. It has been suggested that increased GIP secretion in obesity will promote lipid deposition in adipose tissue. In light of the current attempts to employ GIP antagonists in the treatment and prevention of human obesity, the present experiments were performed in order to elucidate whether the adipose tissue lipid metabolism would be enhanced or blunted during a GIP, hyperinsulinemic and hyperglycemic (HI-HG) clamp in obese subjects with either normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). DESIGN: Sixteen obese (BMI>30 kg m(-2)) subjects were divided into two groups, based on their plasma glucose response to an oral glucose challenge: (i) NGT and (ii) IGT. Abdominal, subcutaneous adipose tissue lipid metabolism was studied by conducting measurements of arteriovenous concentrations of metabolites and regional adipose tissue blood flow (ATBF) during GIP (1.5 pmol kg(-1) min(-1)) in combination with a HI-HG clamp. RESULTS: In both groups, ATBF responses were significantly lower than what we have found previously in healthy, lean subjects (P<0.0001). The flow response was significantly lower in the IGT group than in the NGT group (P=0.03). It was not possible to show any increase in the lipid deposition in adipose tissue under the applied experimental conditions and likewise the circulating triglyceride (TAG) concentrations remained constant. CONCLUSION: The applied GIP, HI-HG clamp did not induce any changes in TAG uptake in adipose tissue in obese subjects. This may be due to a blunted increase in ATBF. These experiments therefore suggest that GIP does not have a major role in postprandial lipid metabolism in obese subjects.

The C-terminal extension of exendin-4 provides additional metabolic stability when added to GLP-1, while there is minimal effect of truncating exendin-4 in anaesthetized pigs.

The most striking sequence difference between glucagon-like peptide-1 (GLP-1)(2) and the longer-acting GLP-1 receptor agonist, exendin-4 (Ex-4),(3) is the nine-amino acid COOH-terminal extension of Ex-4. We investigated the contribution of this extension to the survival time of Ex-4. We assessed the overall metabolism of GLP-1, Ex-4, a COOH-terminally extended GLP-1 peptide (GLP-1+Ex(31-39); GLP-Ex),(4) and a COOH-terminally truncated exendin peptide (Ex(1-30)) in anaesthetized, catheterized pigs, with focus on the extraction across the kidneys and a peripheral tissue (a hindleg, representing muscle, adipose- and connective tissue). Peptide analysis was carried out with assays against the mid-region of the peptides, whereby the role of dipeptidyl peptidase-4 (DPP-4)(5) mediated NH(2)-terminal degradation could be disregarded. The half-life of GLP-1 was significantly increased when the COOH-terminal extension of Ex-4 was added (GLP-1 4.8±3.3min; GLP-Ex 19.5±3.3min). In contrast, there was no effect of truncating Ex-4 (Ex-4 32.4±4.1min; Ex(1-30) 28.4±1.7min). Ex-4 and Ex(1-30) were cleared solely by the kidneys at rates corresponding to the glomerular filtration rate (GFR),(6) while GLP-1 and GLP-Ex were cleared by both the kidneys and peripheral tissues. Both extraction rates were, however, significantly reduced with GLP-Ex compared to GLP-1. The renal clearance rate of GLP-1 greatly exceeded GFR, while GLP-Ex was cleared at a rate resembling GFR. In conclusion, the COOH-terminal extension of Ex-4 contributes minimally to the increased survival time of Ex-4, while addition of this sequence to GLP-1 significantly reduces its clearance.

Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects: a possible link between obesity and local tissue inflammation?

The aim of this study was to investigate subcutaneous adipose tissue lymphatic drainage (ATLD) of macromolecules in lean and obese subjects and, furthermore, to evaluate whether ATLD may change in parallel with adipose tissue blood flow. Lean and obese male subjects were studied before and after an oral glucose load. Adipose-tissue blood flow was measured in the anterior subcutaneous abdominal adipose tissue by the (133)Xe-washout technique. ATLD was measured as the disappearance rate of (99m)Tc-labelled nanoaggregated human albumin, during fasting and after an oral glucose load. A significant increase in ATLD was seen after the glucose load in the lean subjects. In the obese subjects, ATLD remained constant throughout the study and was significantly lower compared to the lean subjects. These results indicate a reduced ability to remove macromolecules from the interstitial space through the lymphatic system in obese subjects. Furthermore, they suggest that postprandial changes in ATLD taking place in lean subjects are not observed in obese subjects. This may have a role in the development of obesity-related inflammation in hypertrophic adipose tissue.

Which goal for fluid therapy during colorectal surgery is followed by the best outcome: near-maximal stroke volume or zero fluid balance?

BACKGROUND: We aimed to investigate whether fluid therapy with a goal of near-maximal stroke volume (SV) guided by oesophageal Doppler (ED) monitoring result in a better outcome than that with a goal of maintaining bodyweight (BW) and zero fluid balance in patients undergoing colorectal surgery. METHODS: In a double-blinded clinical multicentre trial, 150 patients undergoing elective colorectal surgery were randomized to receive fluid therapy after either the goal of near-maximal SV guided by ED (Doppler, D group) or the goal of zero balance and normal BW (Zero balance, Z group). Stratification for laparoscopic and open surgery was performed. The postoperative fluid therapy was similar in the two groups. The primary endpoint was postoperative complications defined and divided into subgroups by protocol. Analysis was performed by intention-to-treat. The follow-up was 30 days. The trial had 85% power to show a difference between the groups. RESULTS: The number of patients undergoing laparoscopic or open surgery and the patient characteristics were similar between the groups. No significant differences between the groups were found for overall, major, minor, cardiopulmonary, or tissue-healing complications (P-values: 0.79; 0.62; 0.97; 0.48; and 0.48, respectively). One patient died in each group. No significant difference was found for the length of hospital stay [median (range) Z: 5.00 (1-61) vs D: 5.00 (2-41); P=0.206]. CONCLUSIONS: Goal-directed fluid therapy to near-maximal SV guided by ED adds no extra value to the fluid therapy using zero balance and normal BW in patients undergoing elective colorectal surgery.

Reduction in plasma leucine after sprint exercise is greater in males than in females.

There is a pronounced gender difference in the accumulation of plasma ammonia after sprint exercise. Ammonia is a key intermediate in amino acid metabolism, which implies that gender-related differences in plasma and muscle amino acid concentrations after sprint exercise exist. To study this, three bouts of 30-s sprint exercise were performed by healthy females (n=8) and males (n=6). Blood leucine and muscle leucine were collected over the exercise period. Basal arterial plasma and skeletal muscle leucine were 40% higher in males than females (P<0.010 and P<0.020). Plasma, but not muscle, leucine decreased by sprint exercise and more so in males than females (g × t: P=0.025). Increase in ammonia was higher in males than females in both plasma and muscle (g × t: P<0.001 and P=0.003). An opposite pattern was shown for plasma glutamine, where an increase was found in females (P<0.001), but not in males. In conclusion, the lower plasma ammonia after sprint exercise in females seems to be explained by a lower accumulation of ammonia in skeletal muscle and by a buffering of ammonia in the form of glutamine in females. The greater reduction in plasma leucine in males seems to be related to their greater increase in muscle ammonia after sprint exercise.

Vascular and metabolic effects of adrenaline in adipose tissue in type 2 diabetes.

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 (133)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.

The dynamics of the microcirculation in the subcutaneous adipose tissue is impaired in the postprandial state in type 2 diabetes.

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.

The 1918-1920 influenza pandemic in Peru.

BACKGROUND: Increasing our knowledge of past influenza pandemic patterns in different regions of the world is crucial to guide preparedness plans against future influenza pandemics. Here, we undertook extensive archival collection efforts from three representative cities of Peru-Lima in the central coast, Iquitos in the northeastern Amazon region, Ica in the southern coast-to characterize the temporal, age and geographic patterns of the 1918-1920 influenza pandemic in this country. MATERIALS AND METHODS: We analyzed historical documents describing the 1918-1920 influenza pandemic in Peru and retrieved individual mortality records from local provincial archives for quantitative analysis. We applied seasonal excess mortality models to daily and monthly respiratory mortality rates for 1917-1920 and quantified transmissibility estimates based on the daily growth rate in respiratory deaths. RESULTS: A total of 52,739 individual mortality records were inspected from local provincial archives. We found evidence for an initial mild pandemic wave during July-September 1918 in Lima, identified a synchronized severe pandemic wave of respiratory mortality in all three locations during November 1918-February 1919, and a severe pandemic wave during January 1920-March 1920 in Lima and July-October 1920 in Ica. There was no recrudescent pandemic wave in 1920 in Iquitos. Remarkably, Lima experienced the brunt of the 1918-1920 excess mortality impact during the 1920 recrudescent wave, with all age groups experiencing an increase in all cause excess mortality from 1918-1919 to 1920. Middle age groups experienced the highest excess mortality impact, relative to baseline levels, in the 1918-1919 and 1920 pandemic waves. Cumulative excess mortality rates for the 1918-1920 pandemic period were higher in Iquitos (2.9%) than Lima (1.6%). The mean reproduction number for Lima was estimated in the range 1.3-1.5. CONCLUSIONS: We identified synchronized pandemic waves of intense excess respiratory mortality during November 1918-February 1919 in Lima, Iquitos, Ica, followed by asynchronous recrudescent waves in 1920. Cumulative data from quantitative studies of the 1918 influenza pandemic in Latin American settings have confirmed the high mortality impact associated with this pandemic. Further historical studies in lesser studied regions of Latin America, Africa, and Asia are warranted for a full understanding of the global impact of the 1918 pandemic virus.

Real-time contrast-enhanced ultrasound determination of microvascular blood volume in abdominal subcutaneous adipose tissue in man. Evidence for adipose tissue capillary recruitment.

The adipose tissue metabolism is dependent on its blood perfusion. During lipid mobilization e.g. during exercise and during lipid deposition e.g. postprandial, adipose tissue blood flow is increased. This increase in blood flow may involve capillary recruitment in the tissue. We investigated the basic and postprandial microvascular volume in adipose tissue using real-time contrast-enhanced ultrasound (CEU) imaging in healthy normal weight subjects. In nine subjects, CEU was performed in abdominal subcutaneous adipose tissue and in the underlying skeletal muscle after a bolus injection of ultrasound contrast agent to establish the reproducibility of the technique. In nine subjects, the effect of an oral glucose load on blood flow and microvascular volume was measured in abdominal subcutaneous adipose tissue and forearm skeletal muscle. ¹³³Xe washout and venous occlusion strain-gauge plethysmography was used to measure the adipose tissue and forearm blood flow, respectively. Ultrasound signal intensity of the first plateau phases was 27 ± dB in the abdominal subcutaneous adipose tissue and 18 ± 2 dB (P < 0.05) in the underlying skeletal muscle. The reproducibility of the measurements was good with a 4% coefficient of variation in both tissues. Blood flow and the change in signal intensity as a measure of the microvascular volume increased significantly and simultaneously in abdominal subcutaneous adipose tissue after glucose intake. The forearm blood flow and muscle signal intensity remained constant. It is concluded that the microvascular volume and changes in volume in abdominal subcutaneous adipose tissue can be assessed using CEU with good reproducibility. Postprandial capillary recruitment takes place in abdominal subcutaneous adipose tissue.

Effects of aging on human skeletal muscle after immobilization and retraining.

Inactivity is a recognized compounding factor in sarcopenia and muscle weakness in old age. However, while the negative effects of unloading on skeletal muscle in young individuals are well elucidated, only little is known about the consequence of immobilization and the regenerative capacity in elderly individuals. Thus the aim of this study was to examine the effect of aging on changes in muscle contractile properties, specific force, and muscle mass characteristics in 9 old (61-74 yr) and 11 young men (21-27 yr) after 2 wk of immobilization and 4 wk of retraining. Both young and old experienced decreases in maximal muscle strength, resting twitch peak torque and twitch rate of force development, quadriceps muscle volume, pennation angle, and specific force after 2 wk of immobilization (P < 0.05). The decline in quadriceps volume and pennation angle was smaller in old compared with young (P < 0.05). In contrast, only old men experienced a decrease in quadriceps activation. After retraining, both young and old regained their initial muscle strength, but old had smaller gains in quadriceps volume compared with young, and pennation angle increased in young only (P < 0.05). The present study is the first to demonstrate that aging alters the neuromuscular response to short-term disuse and recovery in humans. Notably, immobilization had a greater impact on neuronal motor function in old individuals, while young individuals were more affected at the muscle level. In addition, old individuals showed an attenuated response to retraining after immobilization compared with young individuals.

Long-term exendin-4 treatment delays natural deterioration of glycaemic control in diabetic Goto-Kakizaki rats.

AIM: The glucagon-like peptide-1 (GLP-1) receptor agonist, exendin-4, has previously been shown to delay the onset of diabetes when administered to Goto-Kakizaki (GK) rats in the prediabetic period. The present study aimed to evaluate whether long-term administration of exendin-4 to GK rats in the diabetic period would improve their diabetes and how glycaemic control was affected following drug wash-out. METHODS: Glycaemic control was assessed in diabetic GK rats during 12 weeks of exendin-4 or vehicle treatment. Moreover, some animals were followed for an additional 9 weeks without treatment. RESULTS: Glycaemic control was seen to deteriorate in vehicle-treated animals, as assessed by increased glycated haemoglobin A1c (HbA1c), whereas HbA1c improved in exendin-4-treated animals. Following an additional 9 weeks without treatment, glycaemic control in exendin-4-treated animals remained below baseline value and thus remained significantly lower than that of vehicle-treated animals. Following exendin-4 administration, oral glucose tolerance tests revealed greatly reduced glucose and insulin excursions compared with vehicle-treated animals, whereas following overnight drug wash-out, only little difference was seen, suggesting that the improvement in glycaemic control may have been obtained primarily by increased postprandial control. No significant differences were observed in pancreatic islet morphology or islet hormone content. CONCLUSIONS: Exendin-4 treatment improved glycaemic control in diabetic GK rats, independent of changes in beta-cell mass. Additionally, progression of the disease seemed to be delayed because the improvement in HbA1c was still apparent 9 weeks after cessation of treatment.

A comparative study of the 1918-1920 influenza pandemic in Japan, USA and UK: mortality impact and implications for pandemic planning.

Historical studies of influenza pandemics can provide insight into transmission and mortality patterns, and may aid in planning for a future pandemic. Here, we analyse historical vital statistics and quantify the age-specific mortality patterns associated with the 1918-1920 influenza pandemic in Japan, USA, and UK. All three countries showed highly elevated mortality risk in young adults relative to surrounding non-pandemic years. By contrast, the risk of death was low in the very young and very old. In Japan, the overall mortality impact was not limited to winter 1918-1919, and continued during winter 1919-1920. Mortality impact varied as much as threefold across the 47 Japanese prefectures, and differences in baseline mortality, population demographics, and density explained a small fraction of these variations. Our study highlights important geographical variations in timing and mortality impact of historical pandemics, in particular between the Eastern and Western hemispheres. In a future pandemic, vaccination in one region could save lives even months after the emergence of a pandemic virus in another region.

Development of an in vitro skin permeation model simulating atopic dermatitis skin for the evaluation of dermatological products.

Atopic dermatitis (AD) skin has a defective barrier function as indicated by increased transepidermal water loss (TEWL). In order to test potential new formulations for AD, it was our aim to develop a skin permeation model simulating AD skin by inducing barrier impairment to otherwise healthy skin simulating the barrier properties of AD skin as evaluated by TEWL measurements. Pig ear skin was mounted to Franz-type diffusion cells. Skin barrier impairment was induced by tape strippings. As the number of strips increased, higher TEWL values were obtained. By performing 25 tape strippings, the TEWL value within the range reported for involved skin of AD patients was reached. The in vitro skin permeation of fusidic acid and betamethasone-17-valerate was found to correlate with the number of tape strippings used to remove stratum corneum cell layers. A comparison of the permeability of fusidic acid and betamethasone-17-valerate from Fucicort cream to a new Fucicort Lipid formulation was studied with intact (0 strippings) and barrier-impaired skin simulating involved AD skin (25 strippings). As opposed to intact skin, no statistically significant difference through barrier-impaired skin was found for fusidic acid and betamethasone-17-valerate for the two formulations. This is in accordance with the clinical results of an international multicentre study and thus confirms the predictability of the model.

Evaluation of Tc-99m-tetrofosmin single-photon emission computed tomography for detection of chronic exertional compartment syndrome of the leg.

Chronic exertional compartment syndrome (CECS) of the leg is a common, painful condition related to exercise and associated with increased muscle compartment pressure (CP). Invasive methods are currently the method of choice for diagnosing the condition. We investigated the use of Tc-99m-tetrofosmin perfusion single-photon emission computed tomography (SPECT) as a diagnostic tool compared with the gold standard, muscle CP measurement. In 14 subjects perfusion SPECT and CP were measured before and immediately after exercise leading to pain in the lower legs. Six subjects had increased pressures indicating the presence of CECS. In three (50%) of these muscular hypoperfusion was observed by perfusion SPECT. In eight subjects with normal CPs SPECT suggested muscular hypoperfusion. Because of the low diagnostic rates, sensitivity 50% and specificity 63%, Tc-99m-tetrofosmin perfusion SPECT seems not to be a useful method for diagnosing CECS.