Changes in blood lactate concentrations during different treadmill exercise test protocols.

AIM: The purpose of this study was to compare the blood-lactate and heart rate response of three treadmill tests and to define a conversion algorithm. METHODS: Subjects included 19 long-distance runners. The first two tests had increments of 2 km/h every 3 (test3m) or 5 minutes (test5m). The third test (testFm) consisted of four consecutive 2000m-runs. The calculated individual-anaerobic-threshold (IAT) from test3m was defined as speed at the third step of testFm, speed-increments between the four steps were 0.25 m/s. RESULTS: Lactate threshold (LT) did not show significant differences. Speed at IAT in test3m (15.09|*plusmn*|2.29 km/h) was significantly higher than in test5m (14.74|*plusmn*|2.22 km/h), heart rates were nearly identical. Speed and heart rate at 2 mmol/L showed no significant differences. At lactate concentrations of 3 and 4 mmol/L, running-speeds in test3m were significantly higher than in test5m and testFm. Heart rate were the same in test3m and test5m but significantly higher in testFm. CONCLUSION: Taking test3m as basis for determining endurance-performance, an adjustment of test5m can be made by adding 1.8 mmol/l instead of 1.5 mmol/l to the LT to derive the IAT. TestFm shows similar results as test5m, however, standardization is difficult due to variable increment durations.

[Achilles tendon power Doppler sonography in 953 long distance runners - a cross sectional study]. / Powerdopplersonografische Befunde der Achillessehnen von 953 Langstreckenläufern - eine Querschnittsstudie.

AIM: The aim of this cross-sectional study was to assess the frequency of tendinopathy-typical Doppler sonographic changes in the Achilles tendons of long distance runners and to correlate these findings with anamnestic and anthropometric data of the subjects. MATERIALS AND METHODS: 1906 Achilles tendons of 953 long distance runners were examined by ultrasound and power Doppler (Toshiba Aplio SSA-770A/ 80 12 MHz). Ultrasound images (spindle-shaped thickening, hypoechoic/hyperechoic lesions, neovascularizations) were analyzed in relation to the runners' anthropometrical data and history of Achilles tendon complaints. RESULTS: In asymptomatic runners as well as in the overall group, there was a statistically significant correlation between tendon thickness and age, height and weight (CC 0.24 - 0.38, p < 0.001). Runners with current or healed Achilles tendon complaints displayed a statistically significant thickening of the tendons, as well as an increase in hypoechoic lesions and neovascularizations (p < 0.001). While grayscale abnormalities were rarely found in asymptomatic runners (< 10 %), neovascularization was detected in 35 % of healthy test persons using the high-resolution power Doppler "Advanced Dynamic Flow". CONCLUSION: Contrary to frequent assumption, neovascularization is often found in tendons of asymptomatic runners, using modern power Doppler equipment. The pathological relevance of single microvessels in asymptomatic tendons must, therefore, be critically discussed.

Effect of vardenafil, an inhibitor of phosphodiesterase-5, on portal haemodynamics in normal and cirrhotic liver -- results of a pilot study.

BACKGROUND: Dysregulation of the cyclic guanosine 3',5' monophosphate-nitric oxide system is in part responsible for portal hypertension in cirrhosis. AIM: To test the effects of inhibitors of phosphodiesterase-5 on portal haemodynamics. METHODS: To 18 healthy subjects and 18 patients with Child A liver cirrhosis, 10 mg of vardenafil, an inhibitor of phosphodiesterase-5, were administered orally. Doppler sonographic measurements of hepatic and splanchnic blood flow, systemic blood pressure and heart rate were recorded before, 1 h after, and 48 h after the application. Vardenafil plasma levels were determined after 1 h. In five patients, invasive registration of free and wedged hepatic vein pressure was performed. RESULTS: Portal venous flow increased in patients from 0.82 +/- 0.30 L/min (mean +/- s.d.) by 26% (CI: 16-37%, P = 0.0004) and in healthy subjects from 0.75 +/- 0.20 L/min (mean +/- s.d.) by 19% (CI: 9-28%; P = 0.0010). Celiac and hepatic artery resistivity indices rose significantly. Systemic blood pressure decreased slightly in patients. The wedged hepatic venous pressure gradient decreased in four of five patients with liver cirrhosis. Vardenafil plasma levels were higher in patients (14 +/- 10 microg/L) than in healthy subjects (9 +/- 6 microg/L; n.s.). CONCLUSIONS: Inhibition of phosphodiesterase-5 increases portal flow and lowers portal pressure by a decrease in sinusoidal resistance and may be a novel therapeutic strategy for portal hypertension.

Association between LDL-cholesterol, statin therapy, physical activity and inflammatory markers in patients with stable coronary heart disease.

Evidence suggests that inflammatory parameters such as high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), serum amyloid-A (SAA) and fibrinogen (Fib) are associated with cardiovascular morbidity and mortality. In this study we investigated the association between LDL-cholesterol (LDL-C), lipid lowering drug therapy (LLD) and inflammatory markers in 436 subjects (age 64,2 +/- 4.1 yr, BMI 27,6 +/- 3,9 kg/m2) with coronary heart disease, participating in outpatient exercise groups for cardiac rehabilitation. In a subgroup analysis (n=229), we looked at the respective effects of physical activity (PA) alone and in combination with LLD. For the whole group the levels of inflammatory markers were: hs-CRP 0,31 +/- 0,4 mg/dl; IL-6 2,04 +/- 1,6 pg/ml; SAA 6,26 +/- 14 mg/l; Fib 381 +/- 97 mg/dl. Compared to patients without LLD, those with LLD showed modestly lower concentrations for CRP (-7%) and IL-6 (-12%), (p<0.05, respectively). In patients with an LDL-C < 100 mg/dl, CRP (-12%) and Fib (-8%) were significantly lower (p<0.05, respectively) than in patients with LDL-C > 100 mg/dl. Patients with a high level of PA (PA > or = 3 times/week) exhibited significantly lower values for CRP (-18%), Fib (-11%) and SAA (-37%) (p<0.01, respectively) than patients with a low level of PA (< or = 1 time/week). The combination of a high level of PA, and intake of LLD further reduced CRP (-37%) and SAA (-45%), with no additional decrease in Fib (-10%) (p<0.01, respectively) compared to patients with a low level of PA and taking LLD. The data from this cross-sectional study suggest that factors such as LLD, LDL-C (< 100 mg/dl), and a high level of physical activity are associated with lower levels of inflammatory markers in patients with coronary heart disease. Particularly with respect to CRP and SAA values, a high level of PA in combination with LLD, showed the most pronounced effects. The proof of causality of these findings should further be investigated in randomized controlled trials.

High variation of tioguanine absorption in patients with chronic active Crohn's disease.

BACKGROUND: Tioguanine (thioguanine) has been suggested as a therapeutic alternative for patients with Crohn's disease resistant or intolerant to azathioprine or mercaptopurine. However, pharmacokinetic data on tioguanine in inflammatory bowel disease are missing. AIM: To determine the disposition of three different 40 mg tablet preparations of tioguanine in patients with Crohn's disease. METHODS: Six patients with chronic active Crohn's disease were included in a randomized, cross-over, single-dose study. Pharmacokinetic analysis was based on plasma concentrations of tioguanine during 6 h after dosing. Tioguanine was measured by a validated high-pressure liquid chromatographic method. RESULTS: The areas under the curve (AUC) varied 4-7-fold between patients. In two patients, tioguanine was not detected in plasma following the intake of one of the three tablets; another patient did not absorb tioguanine in two of the three different preparations. No significant differences were found in the AUC and Cmax values between the three tablets. In all patients, there was a second peak in plasma concentration following a meal 3 h after drug administration. CONCLUSIONS: The absorption of tioguanine is highly variable in patients with Crohn's disease, which may be responsible for treatment failure. Therapy with tioguanine may be improved by monitoring tioguanine nucleotides as a surrogate parameter of efficacy.

Remission maintenance by tioguanine in chronic active Crohn's disease.

BACKGROUND: Tioguanine may offer an alternative for immunosuppression in chronic active Crohn's disease. Recently, we have shown that tioguanine is effective in inducing rapid remission. AIM: To evaluate the role of tioguanine in the maintenance of remission in chronic active Crohn's disease. METHODS: A follow-up study was performed to investigate the long-term efficacy and safety of and tolerance to tioguanine in chronic active Crohn's disease. Sixteen patients who had successfully received 6-tioguanine for remission induction were enrolled. The reasons for immunosuppressive therapy were steroid dependence (n = 10), steroid refractoriness (n = 6) and intolerance (n = 6) or refractoriness (n = 1) to azathioprine. After remission induction therapy for 6 months, patients were treated for another 6 months with a daily dose of 20-40 mg tioguanine. Primary outcomes were remission (Crohn's disease activity index < 150) and complete steroid reduction in steroid-dependent patients at 12 months. Laboratory controls of white blood count and liver enzymes, as well as erythrocyte tioguanine nucleotide levels, were performed regularly. RESULTS: After 12 months of treatment, 14 of 16 (88%) patients were in remission, and 12 of these were completely free of systemic steroids. Adverse events during maintenance therapy included photosensitivity (one patient), minor viral infections (one), headache (four) and mild alopecia (one). One patient developed elevated liver enzymes, splenomegaly and thrombocytopenia, indicative of nodular regenerative hyperplasia of the liver. CONCLUSIONS: In responders to tioguanine, the drug appears to be very effective in maintaining remission of chronic active Crohn's disease. Unfortunately, long-term hepatotoxicity seems to be an unpredictable and potentially severe adverse drug reaction. Therefore, to date, tioguanine cannot be recommended for general use outside clinical trials.

6-thioguanine--efficacy and safety in chronic active Crohn's disease.

BACKGROUND: : Azathioprine and mercaptopurine are commonly used in chronic active Crohn's disease. They share the disadvantage of a delayed onset of action and potentially serious side-effects, and are metabolized to thioguanine nucleotides which are thought to be the active metabolites. The direct use of 6-thioguanine may offer a more rapid and safer alternative. We conducted an open prospective study to investigate the efficacy and safety of 6-thioguanine in chronic active Crohn's disease. METHODS: : Thirty-seven patients with chronic active Crohn's disease and a Crohn's disease activity index of > 150 were enrolled in this study. Inclusion criteria were steroid dependence (n = 19), steroid refractoriness (n = 9) and/or intolerance (n = 16) or refractoriness (n = 6) to azathioprine. Patients were treated with 40 mg/day of 6-thioguanine for 24 weeks; a dose escalation to 80 mg was allowed at week 12. Remission was defined as a Crohn's disease activity index of < 150 associated with a decrease of > 70 points; response was defined as a decrease of > 70 points in the Crohn's disease activity index. RESULTS: : In the intention-to-treat analysis, 13 of 37 patients achieved remission (35%). Twelve of these 13 patients achieved remission after 4 weeks. Fifty-seven per cent of patients (21/37) achieved a response. The mean Crohn's disease activity index decreased from 284 +/- 74 to 153 +/- 101. 6-Thioguanine was more effective in azathioprine-intolerant than in azathioprine-refractory patients. Twelve of 16 patients intolerant to azathioprine tolerated 6-thioguanine. Adverse events included phototoxicity, pancreatitis, headache, nausea, alopecia, arthralgia, minor infections and reversible elevation of transaminases. Six patients required discontinuation of medication, two because of leucopenia. CONCLUSIONS: : In this patient group with chronic active Crohn's disease, 6-thioguanine appeared to be effective with acceptable short-term toxicity, but long-term controlled trials are clearly needed to further define its role.

Thioguanine-nucleotides do not predict efficacy of tioguanine in Crohn's disease.

BACKGROUND: 6-Thioguanine-nucleotides seem to be the active metabolites of thiopurine therapy, and their monitoring has been considered a useful tool for optimizing response in inflammatory bowel diseases. Tioguanine (thioguanine) therapy results in much higher levels of 6-thioguanine-nucleotide levels when compared with azathioprine or mercaptopurine. AIM: To elucidate the influence of 6-thioguanine-nucleotide and methylated 6-thioguanine-nucleotide levels under tioguanine on efficacy and toxicity in Crohn's disease. METHODS: 6-Thioguanine-nucleotide and methylated 6-tioguanine-nucleotide levels were measured regularly in 26 Crohn's disease patients treated with tioguanine. Nucleotide levels were related to efficacy and toxicity. RESULTS: 6-Thioguanine-nucleotide levels rose very high [median 1241 pmol/8 x 10(8) red blood cells (range 313-1853)]. Methylated 6-thioguanine-nucleotide levels were detected in all patients [491 pmol/8 x 10(8) red blood cells (154-1775)]. 6-Thioguanine-nucleotide and methylated 6-thioguanine-nucleotide concentrations correlated significantly (r = 0.7, P < 0.0001). Nucleotide levels from patients achieving remission (n = 14) did not differ significantly from non-remitters (n = 12) [6-thioguanine-nucleotide: 1077 (599-2160) vs. 1210 (534-4665); methylated 6-thioguanine-nucleotide: 510 (214-1222) vs. 421 (145-1284)]. One patient with intermediate thiopurine S-methyltransferase activity experienced bone marrow toxicity upon dose escalation parallel with excessively high thioguanine-nucleotide levels. CONCLUSIONS: 6-Thioguanine-nucleotide as well as methylated 6-thioguanine-nucleotide levels under tioguanine therapy were not related to efficacy. This suggests that monitoring of 6-thioguanine-nucleotide levels is not a useful tool to predict response to thiopurines.

Demonstration of estrogen and progesterone receptors as well as Ki-67 and p-145 antigens in single tumor cells from blood and pleural effusions using a slide assay.

We describe a slide assay that allows the demonstration of antigens localized in the nucleus from isolated white blood cells as well as from single tumor cells derived from malignant effusions. With the antibodies Ki-67 and anti-p-145 an increased rate of nuclear and nucleolar staining resulted in cells from highly malignant lymphomas. An almost identical reaction was obtained when tumor cells from malignant effusions were tested. Cells isolated from the blood of patients with leukemic spread of lymphomas of low malignancy yielded a weak staining comparable to that of normal mesothelial cells from non-tumorous cavity fluids. The detection of estrogen and progesterone receptors (ER and PR) localized in the cell nucleus can be achieved by the same assay. The reaction is enhanced by incubation of the tumor cells for 30 min at 37 degrees C prior to fixation. Pleural effusions from 20 patients with breast cancer were tested. ER was positive in 13 and PR was positive in 12 of the 20 samples. In 5 cases there was a divergent reaction with ER and PR antibody. The hormone receptors of the primary tumor were known in 15 (ER) and 14 (PR) patients, respectively. In each cohort there was only one case with a negative reaction of the primary tumor and a positive reaction with the isolated tumor cells from the pleural effusions. These results indicate that the demonstration of hormone receptor proteins in cells from malignant effusions is possible and that there is a correlation with the status of the primary site of cancer.

The gastrointestinal system--an essential target organ of the athlete's health and physical performance.

An athlete's ability to reach maximum performance is a direct result of physical and muscular performance, muscular and systemic stress tolerance, control and regulation of immune function, and adaptation to physical stress. In this complex sense, the gastrointestinal (GI) tract is also part of the system that controls and regulates adaptation and regeneration of the athlete. A well-balanced GI immune system and an optimized immune competence may protect the athlete from harmful pathogens; it may also protect against dietary as well as inhaled antigens. However, under conditions of mechanical and biochemical stress, the integrity of the GI mucosal block, particularly the epithelial hood, can be damaged, leading to a pathological uptake of toxic or immunogenic substrates. This may occur in endurance athletes, since gut symptomatology, nausea, vomiting, pain, bloating, diarrhea, cramping, and bleeding can be observed in up to half of all participants in endurance events. In addition, composition of stool and fecal microflora in endurance athletes has shown that there may be a specific need for nutritional support for mucosal immunity in highly trained but chronically stressed athletes. Proper diet during training and competition is a significant factor in guarding against GI symptoms and exercise-induced gastrointestinal side effects that may compromise immune competence and physical performance. The present review presents some important suggestions on the possible role of the GI tract in human performance and stress tolerance, and offers new insights about the influence of food quality on the immune system of the gut.

Treatment of refractory hepatic hydrothorax with transjugular intrahepatic portosystemic shunt: long-term results in 40 patients.

BACKGROUND/AIMS: Hepatic hydrothorax is a complication of portal hypertension secondary to ascites. In this study, we investigated retrospectively the effects of the transjugular intrahepatic portosystemic shunt (TIPS) on hepatic hydrothorax refractory to diuretic treatment. METHODS: Forty patients (Child-Pugh class B, 24 patients; Child-Pugh class C, 16 patients) with hydrothorax refractory to diuretic treatment, pleurocenteses or pleurodesis were included. The TIPS implantation was successful in all patients, who were then followed for 16 +/- 14 months (range 1 day-54 months). RESULTS: TIPS reduced the portosystemic pressure gradient from 26 +/- 6 to 10 +/- 5 mmHg. In the 17 patients whom we followed for 12 months or longer, improvements were found for the Child--Pugh score (8.6 +/- 1.8 v. 6.7 +/- 1.5), serum albumin concentration (3.1 +/- 0.5 v. 3.6 +/- 0.5 g/l), and urinary sodium excretion (22 +/- 29 v. 89 +/- 43 mmol/24 h) (P< 0.05). Two patients developed severe hepatic encephalopathy requiring shunt occlusion. Hydrothorax improved in 82% of patients and resolved in 71% of patients. Fifty per cent of patients developed shunt insufficiency within 7 +/- 9 months, contributing to a probability of relapse-free 1-year survival of 35%. In these patients, shunt revision resulted in a secondary response rate of 82.3%. The 1-year survival was 64%. Both hydrothorax response and survival showed a significant inverse correlation with age over 60 years (P< 0.01 and P< 0.003, respectively) but not with other biomedical variables. CONCLUSION: TIPS is effective for hydrothorax refractory to diuretic treatment and other standard interventions to bridge the time to transplantation. Patients older than 60 years have a poor response and short survival.

Prevention of infectious complications after transjugular intrahepatic portosystemic shunt in cirrhotic patients with a single dose of ceftriaxone.

BACKGROUND/AIMS: Patients with cirrhosis of the liver are prone to bacterial infections. Therapeutic interventions such as endoscopic sclerotherapy increase the risk of bacterial infections in these patients. Following insertion of a transjugular intrahepatic portosystemic shunt (TIPS), the incidence of severe bacterial infections was recently shown to be 20% after elective procedures. This finding suggests antibiotic prophylaxis with the TIPS procedure. Antibiotic prophylaxis using cefotiam or cefotaxime/ampicillin did not significantly reduce infectious complications. The aim of the present study was therefore to investigate the efficacy of two different doses of a long-acting cephalosporin in prevention of bacterial infection after TIPS. METHODOLOGY: Eighty-two patients with cirrhosis (age: 52 +/- 2 years) who underwent elective TIPS were randomized to receive a single i.v. dose of either 1 g or 2 g Ceftriaxone 1 hour before the intervention. Patients with evidence of or suspected infections and patients on antibiotic therapy within 7 days prior to TIPS were excluded. Body temperature was monitored t.i.d. for 1 week and white blood count (WBC) and C-reactive protein (CRP) were determined before TIPS and 1 day and 1 week after TIPS. RESULTS: Only 2 of 82 patients (2.6%) showed signs of infection following TIPS insertion: One of 40 patients receiving 1 g Ceftriaxone and 1 of 42 patients receiving 2 g Ceftriaxone prior to TIPS developed temperature > 38.5 degrees C. In the latter patient this was due to pneumonia. This patient received antibiotic treatment with imipenem for 10 days. Temperature in the other patient normalized within 12 hours and he did not require antibiotic treatment. No significant differences in temperature, WBC and CRP between the different doses of Ceftriaxone were observed. CONCLUSIONS: Prophylactic treatment with Ceftriaxone reduces the reported incidence of bacterial infections after TIPS in patients with cirrhosis of the liver. Prophylaxis with 1 g Ceftriaxone seems as efficacious as 2 g.

[Current views on the importance of physical activity]. / Fett abbauen--Muskeln stählen: Gewichtskontrolle ist nicht nur FdH.

To improve the individual health profile and to solve the growing overweight problem, a long-term change in the lifestyle to one which includes an energetically balanced combination of diet and activity is essential. Physical activity and the muscles involved are the primary means by which body composition and energy turnover are regulated. A state of imbalance has decisive consequences on the development of atherogenic and inflammatory risk factors. Additionally, the aging process is significantly influenced by the long-term retention or loss of muscle mass. The Deutsche Gesellschaft für Sportmedizin und Prävention (German Society for Sports Medicine and Prevention, a registered association) offers within the concept of a therapeutic lifestyle change, an educational program for overweight adults (M.O.B.I.L.I.S.).

[Physical activity and dyslipoproteinemia]. / Triglyzeride sinken, HDL-Wert steigt, LDL-Cholesterin formiert sich neu. Wenn Adipöse loslaufen, kommt auch ihr Lipidprofil in Bewegung.

The positive influence of regular physical activity on lipoprotein metabolism and, hence, on the risks for atherogenesis has been documented in controlled studies. Although the levels of total and LDL cholesterol (LDL) usually change only slightly through physical activity, there is a clear change in the LDL composition with a reduction in the atherogenic small dense LDL particle. An activity-induced increase for HDL cholesterol (HDL) between 4 and 29% and a reduction in the triglyceride (TG) level between 4 and 37% are described. To achieve this, it is necessary to increase energy consumption by 1000-1200 kcal/week and to attain an energy consumption of ca. 2500 (> 2000) kcal/week, optimum ca. 3500 kcal/week.

Endoscopic diagnosis of acute intestinal GVHD following allogeneic hematopoietic SCT: a retrospective analysis in 175 patients.

Diagnosis of acute intestinal GVHD (aGVHD) following allogeneic hematopoietic cell transplantation is based on clinical symptoms and histological lesions. This retrospective analysis aimed to validate the 'Freiburg Criteria' for the endoscopic grading of intestinal aGVHD. Grade 1: no clear-cut criteria; grade 2: spotted erythema; grade 3: aphthous lesions; and grade 4: confluent defects, ulcers, denudation of the mucosa. Having excluded patients with infectious diarrhea, we evaluated 175 consecutive patients between January 2001 and June 2009. Setting a cutoff between grade 1 (no change in therapy) and grade 2 (intensification of immunosuppression), macroscopy had a sensitivity of 89.2% (95% confidence interval (CI): 80.4-94.9%), a specificity of 79.4% (95% CI: 69.6-87.1%), a positive-predictive value of 79.6% (95% CI: 70.0-87.2%) and a negative-predictive value of 89.0% (95% CI: 80.2-94.9%). In all, 20% of patients with aGVHD in the lower gastrointestinal tract (GIT) had lesions only in the terminal ileum. In all patients with aGVHD ≥2 of the upper GIT, typical lesions were also found in the lower GIT. Ileo-colonoscopy showed the highest diagnostic yield for aGVHD. In conclusion, the 'Freiburg Criteria' for macroscopic diagnosis of intestinal aGVHD provide high accuracy for identifying aGVHD ≥2.

[Usefulness of probiotics in prevention and therapy]. / Sinnvoller Einsatz von Probiotika in Prävention und Therapie.

Probiotics exert distinct effects on the intestinal mucosa and the immune system that can be used in preventive and therapeutic settings. There is evidence to support the use of probiotics in necrotizing enterocolitis in preterm infants and pouchitis. Furthermore, the immunomodulatory effects of probiotics seem to ameliorate atopic diseases, in particular atopic dermatitis. The efficacy of probiotics has been shown comparable to Mesalazine regarding the maintenance of remission in ulcerative colitis. In addition there is evidence that probiotics are useful in the prevention of pouchitis or in therapy of irritable bowel syndrome. Recent data indicate that commensals and probiotics could play a role in nutrient fermentation and energy metabolism and may be helpful in the prevention and therapy of obesity.

Glycaemic and insulinaemic properties of some German honey varieties.

The glycaemic and insulinaemic response to different German honey varieties have not been studied so far. Eight German honey grades differing in their floral source and carbohydrate composition were tested. Isoglucidic test meals (25 g carbohydrate) and a 25 g glucose reference were given to 10 clinically and metabolically healthy, fasting individuals (31.5+/-8.1 years of age (mean+/-s.d.), two women). Glycaemic and insulinaemic index were calculated by the recommended FAO/WHO measure. Five of the eight tested honey varieties show a low glycaemic index below 55; for six of the eight tested varieties, the glycaemic load was lower than 10 (portion size of 20 g honey). Glycaemic index and insulinaemic index correlated significantly with the fructose content of honey varieties. The results show that glycaemic index and insulinaemic response depend on the fructose content of honey. Therefore, specific honey varieties may be recommended for subjects with impaired glucose tolerance instead of saccharose in food preparations.