[Urethral reconstruction in patients with failed hypospadia repair]. / Harnröhrenrekonstruktion bei vorausgegangener Hypospadieoperation.

BACKGROUND: The tasks involved in reconstructing the urethra after failed hypospadias repair range from correction of a trivial meatal stenosis to reconstruction of the entire anterior urethra. OBJECTIVES: To describe pathological findings in the urethra after failed hypospadias repair and the respective surgical methods used for their correction. MATERIALS AND METHODS: The various pathological findings after unsuccessful hypospadias surgery are classified according to their location and complexity. RESULTS: The general rules of reconstruction that should be applied in each particular situation are described. CONCLUSIONS: Successful reconstruction of the urethra in patients with failed hypospadias surgery requires experience and good knowledge of the anatomy of the normal and hypospadic urethra and penis. Mastery of plastic surgical techniques and profound knowledge of the various surgical methods of hypospadias surgery are essential.

Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure.

BACKGROUND AND AIMS: Flow-mediated dilatation of the brachial artery (FMD) is a biomarker of endothelial function and cardiovascular health. Impaired FMD is associated with several cardiovascular risk factors including hypertension and obesity. Various food ingredients such as polyphenols have been shown to improve FMD. We investigated whether consuming resveratrol, a polyphenol found in red wine, can enhance FMD acutely and whether there is a dose-response relationship for this effect. METHODS AND RESULTS: 19 overweight/obese (BMI 25-35 kg m(-2)) men or post-menopausal women with untreated borderline hypertension (systolic BP: 130-160 mmHg or diastolic BP: 85-100 mmHg) consumed three doses of resveratrol (resVida™ 30, 90 and 270 mg) and a placebo at weekly intervals in a double-blind, randomized crossover comparison. One hour after consumption of the supplement, plasma resveratrol and FMD were measured. Data were analyzed by linear regression versus log(10) dose of resveratrol. 14 men and 5 women (age 55 ± 2 years, BMI 28.7 ± 0.5 kg m(-2), BP 141 ± 2/89 ± 1 mmHg) completed this study. There was a significant dose effect of resveratrol on plasma resveratrol concentration (P < 0.001) and on FMD (P < 0.01), which increased from 4.1 ± 0.8% (placebo) to 7.7 ± 1.5% after 270 mg resveratrol. FMD was also linearly related to log(10) plasma resveratrol concentration (P < 0.01). CONCLUSION: Acute resveratrol consumption increased plasma resveratrol concentrations and FMD in a dose-related manner. This effect may contribute to the purported cardiovascular health benefits of grapes and red wine.

Effects of rimonabant, a cannabinoid CB1 receptor ligand, on energy expenditure in lean rats.

OBJECTIVE: To determine the effect of rimonabant on energy expenditure (O2 consumption) in rats at different metabolic states and in cannabinoid CB1 receptor-deficient (CB1R-/-) mice. DESIGN: Animals were exposed to light-dark cycles and fed only during dark cycles. Rimonabant or vehicle was administered together with food (absorptive), following overnight feeding (postabsorptive) or following a whole day of no food (fasting). Indirect calorimetric measurements, physical activity and food intake were measured continuously. RESULTS: Compared with vehicle-treated rats, rats administered 3 and 10 mg kg(-1) rimonabant showed an 18 and 49% increase in O2 consumption, respectively after 3 h. A second dose of rimonabant administered 9-14.5 h after the first one failed to affect O2 consumption, suggesting the development of tolerance. Similarly, stereotypic behaviors and ambulatory activity increased following the first dose but these effects were not observed after the second dose. Respiratory quotients revealed no effect of rimonabant on rates of carbohydrate and fat oxidation. Analysis of the correlation between O2 consumption and physical activity indicated that factors other than increased physical activity may contribute to the increase in O2 consumption. Similar studies in mice demonstrated that wild type but not CB1R-/- mice showed a change in O2 consumption and physical activity following rimonabant administration, suggesting that these effects are mediated by the cannabinoid CB1 receptor. CONCLUSION: Previous studies suggested that reduced food intake alone may not explain the weight reduction observed with rimonabant. Our studies suggest that rimonabant stimulates significant acute energy expenditure in non-obese rodents, which could not be completely accounted for by an increase in physical activity. However, with the observation that there is rapid development of tolerance, these results suggest that there may be additional mechanism(s) that lead to weight loss in these rodents.

[Blue discoloration of hands, numbness of feet, indolent cervical lymph node swelling in a 73-year-old man]. / Blauverfärbung der Hände, Taubheitsgefühl an den Füssen, indolente Lymphknoten- schwellung zervikal bei einem 73-jährigen Mann.

A 73-years old patient came to our outpatient clinic because of a blue discoloration of his hands. Furthermore there was a systemic inflammatory reaction, burning pain and numbness of his feet due to a polyneuropathy, and an indolent enlargement of the cervical lymph nodes. In 1996 and 2001 cervical lymph node resections were done because of localized angiofollicular lymphnode hyperplasia (Castleman's disease). The laboratory values confirmed a systemic inflammatory reaction, a hypothyreosis and a monoclonal gammopathy. A CT-scan showed enlarged cervical, intrathoracic and abdominal lymphnodes and a splenomegaly. So all the criterias for a POEMS syndrome (special form of multiple myeloma) were met with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes. The generalized lymphadenopathy corresponded histologically to the prior mentioned Castleman's disease. The patient responded well to systemic glucocorticoid treatment and today he is asymptomatic.

[Exercise-induced left arm pain and thrombocytosis]. / Belastungsinduzierte Schmerzen im linken Arm und erhöhte Thrombozytenzahl.

We describe the case of a 45-year-old male smoker who presented with an acute anterior wall myocardial infarction and a platelet count on admission of 1030000/mm3. Emergent coronary angiography revealead left anterior wall akinesia caused by a spontaneously resolved thrombosis of the left anterior descending artery with residual stenosis. Primary percutaneous coronary angioplasty and stenting were performed. Postangioplasty course was uneventful. He was diagnosed with essential thrombocythemia based on the findings of marked thrombocytosis of 1,030,000/mm3, splenomegaly and numerous clumping giant megakaryocytes on bone marrow biopsy. In addition to standard therapy with aspirin, heparin, betablocking agent, ACE-inhibitor and statine he received additional anti-platelet therapy with Clopidogrel. Cytoreductive therapy was not necessary.

Natural abundance 13C-NMR spectroscopy for the quantitative determination of fecal fat.

OBJECTIVE: To evaluate 13C-NMR spectroscopy as a method for fat quantitation in human feces without time consuming or unpleasant preparation steps. DESIGN AND METHODS: Stool samples of seven healthy subjects were collected for 18 days before and during oral intake of the inhibitor of gastrointestinal lipases Orlistat. Fecal lipid content was determined first using 13C-NMR, then by conventional gravimetry after homogenization and Bligh & Dyer lipid extraction. RESULTS: The correlation between gravimetry and 13C-NMR was excellent (R2 = 0.91). In repeated measurements, the mean percentage error was 2.8%. On average, 13C-NMR yielded 1.27 g less fat than gravimetry. Orlistat efficacy for fat excretion assessed by 13C-NMR and by gravimetry was 34.3% and 33.9%, respectively. CONCLUSIONS: With a total measurement time of three minutes, 13C-NMR spectroscopy of unprocessed whole stool provides an accurate alternative to gravimetry for assessing total fecal fat excretion. 13C-NMR is superior with regard to practicability and speed.

Habitual fat intake and basal fat oxidation in obese and non-obese Caucasians.

OBJECTIVE: To examine the relationship between habitual fat intake and basal fat oxidation in obese and non-obese Caucasian men and women. METHODS: Habitual fat intake was assessed by 7-day weighed dietary records and resting fat oxidation was determined after an overnight fast in 132 weight stable non-diabetic subjects (38 males, 94 females). All subjects were characterized for weight, height, waist-to-hip ratio, physical activity, plasma glucose and insulin response to an oral glucose load, plasma catecholamine and leptin levels. Under-reporters, defined according to plausibility of the relationship between energy expenditure and energy intake, were excluded from the analyses. RESULTS: The mean age was 53.1+/-10.6 y (19-72 y) and mean body mass index (BMI) was 30.7+/-5.8 kg/m(2) (19.4-45.8 kg/m(2)). Sixty-eight subjects were obese (BMI>30 kg/m(2)). Univariate regression analysis revealed a significant, albeit modest, relationship between absolute fat intake and BMI (r(2)=0.06; P

Tumor necrosis factor-alpha--308 G/A polymorphism in obese Caucasians.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is expressed primarily in adipocytes, and elevated levels of this cytokine have been linked to obesity and insulin resistance. Recently, the A allele of a polymorphism in the 5'-flanking region of the TNF-alpha gene (G-308A) has been reported to be more frequent in obese than in lean subjects and has also been associated with increased expression of this cytokine in fat tissue and influences fat mass and insulin resistance. We, therefore, examined the relationship between this variant and obesity in a German Caucasian population. SUBJECTS AND METHODS: We genotyped 176 index subjects recruited within the framework of the BErG (Berlin Ernährung Geschwister)- Study for the TNF-alpha-G-308A polymorphism. Subjects were characterized for weight, height, waist and hip circumference, body mass index (BMI), body composition, glucose tolerance, leptin and angiotensinogen levels. RESULTS: The frequency of the -308A allele (0.18) was similar to that reported previously and genotype distribution was in Hardy-Weinberg equilibrium (GG, n=118; GA, n=53; AA, n=5). There was a significant difference in allele frequencies of the polymorphism by BMI quartiles (I,<27.3 kg/m2; II, 27.3-31.9 kg/m2; III, 31.9-36.5 kg/m2; IV,>36.5 kg/m2, in each quartile n=44) with -308A allele carriers having a higher BMI than G allele carriers (P=0.013). Despite previous smaller studies that have related insulin resistance to the G-308A polymorphism, we found no relationship between glucose and insulin response during an oral glucose tolerance test (OGTT) and the polymorphism. Furthermore, none of the plasma parameters were related to the polymorphism. CONCLUSION: Our findings support the hypothesis that the G-308A polymophism of the TNF-alpha gene is associated with BMI. The G-308A polymorphism may, therefore, represent a genetic marker for increased susceptibility for obesity in Caucasians.

Hypothesis: Beta-adrenergic receptor blockers and weight gain: A systematic analysis.

One of the arguments put forward against the primary use of beta-blockers has been concern about adverse metabolic effects, such as unfavorable effects on lipids or insulin sensitivity. Another less-appreciated potential drawback is their propensity to cause weight gain in some patients. In 8 evaluable prospective randomized controlled trials that lasted >/=6 months, body weight was higher in the beta-blocker than in the control group at the end of the study. The median difference in body weight was 1.2 kg (range -0.4 to 3.5 kg). A regression analysis suggested that beta-blockers were associated with an initial weight gain during the first few months. Thereafter, no further weight gain compared with controls was apparent. There was no relationship between demographic characteristics and changes in body weight. Based on these observations, the first-line use of beta-blockers in obese hypertensive patients should be reviewed. Obesity management in overweight hypertensive patients may be more difficult in the face of beta-blocker treatment.

Kinetic analysis of the thermic effect of food and its relationship to body composition in humans.

The course of energy expenditure after a meal can vary widely with regard to the slope of onset, amplitude, and duration of the thermic effect. The aim of the present study was to explore the relationship between the thermic effect of food (TEF), as characterized by kinetic analysis of postprandial energy expenditure, body composition, and variables related to the metabolic syndrome including central obesity, hypertension, and glucose tolerance. A total of 181 men and women (body mass index [BMI] range, 19.4 to 52.2 kg/m2) were characterized for body composition, blood pressure, oral glucose tolerance, and energy expenditure after a test meal. Energy expenditure, as measured by indirect calorimetry, was analyzed over a 6-hour period by 3-parameter curve fitting using equations derived from kinetics describing a biphasic reaction involving 2 consecutive first-order reactions (A-->B-->C). Apart from total thermic effect of food (TEFk), the curve also provided an estimate of time of peak (Tp) and amplitude of peak (Ap) for each subject. Multiple stepwise regression analysis with TEFk, Ap, and Tp as dependent variables showed significant effects of sex, age, body weight, body fat, beta-blockade, and body composition on TEF curve parameters. Cluster analysis based on Tp shown 2 distinct clusters with significant differences in age and body fat mass. This study shows that kinetic analysis of postprandial energy expenditure can be used to examine the determinants of the time course of the thermic effect of food in man.

Resting metabolic rate and substrate use in obesity hypertension.

There is substantial evidence that obesity is a prime risk factor for the development of hypertension. Although hyperinsulinemia and an increased activity of the sympathetic nervous system have been implicated in the pathogenesis of "obesity hypertension," their effects on energy metabolism have not been studied thus far. In the present study, we therefore examined resting metabolic rate (RMR) and basal substrate oxidation in subjects with obesity and obesity-related hypertension. A total of 166 subjects were characterized for RMR and basal substrate use through indirect calorimetry. Blood pressure was measured at rest and with 24-hour ambulatory monitoring. Blood samples were collected for the measurement of plasma catecholamines, leptin, and the insulin response to an oral glucose load. In our study population, 116 subjects were defined as hypertensive and 91 were defined as obese. Hypertensive patients under beta-adrenergic blockade (n=42) had a significantly lower RMR than did patients without beta-blockade (P<0. 05) and were therefore excluded from further analyses. Univariate regression analysis revealed a significant relationship between RMR and body fat mass, as well as body fat-free mass, in both groups. Compared with obese normotensive control subjects (n=27), obese hypertensives (n=43) had a 9% higher RMR (P<0.05), higher plasma catecholamine (P<0.05) and leptin (P<0.05) levels, and an increased insulin response to oral glucose (P<0.01). Together, these findings are compatible with the idea that chronic neurogenic and metabolic adaptations related to obesity may play a role in the development of obesity hypertension in susceptible individuals.

Home versus hospital deliveries: follow up study of matched pairs for procedures and outcome. Zurich Study Team.

OBJECTIVE: To assess procedures and outcomes in deliveries planned at home versus those planned in hospital among women choosing the place of delivery. DESIGN: Follow up study of matched pairs. SETTING: Antenatal clinics and reference hospitals in Zurich between 1989 and 1992. SUBJECTS: 489 women opting for home delivery and 385 opting for hospital delivery; the women comprised all those attending members of the study team for antenatal care and those attending the reference hospital for antenatal care who could be matched with the women planning home confinement. MAIN OUTCOME MEASURES: Need for medication and incidence of interventions during delivery (caesarean section, forceps, vacuum extraction, episiotomy), duration of labour, occurrence of severe perineal lesions, maternal blood loss, and perinatal morbidity and death. RESULTS: All women were followed up from their first antenatal visit till three months after delivery. Referrals during pregnancy (n = 37) and labour (70), changes of mind (15 home to hospital, eight hospital to home), and 17 miscarriages resulted in 369 births occurring at home and 486 in hospital. During delivery the home birth group needed significantly less medication and fewer interventions whereas no differences were found in durations of labour, occurrence of severe perineal lesions, and maternal blood loss. Perinatal death was recorded in one planned hospital delivery and one planned home delivery (overall perinatal mortality 2.3/1000). There was no difference between home and hospital delivered babies in birth weight, gestational age, or clinical condition. Apgar scores were slightly higher and umbilical cord pH lower in home births, but these differences may have been due to differences in clamping and the time of transportation. CONCLUSION: Healthy low risk women who wish to deliver at home have no increased risk either to themselves or to their babies.

Effects of L-carnitine supplementation on physical performance and energy metabolism of endurance-trained athletes: a double-blind crossover field study.

A double-blind crossover field study was performed to investigate the effects of acute L-carnitine supplementation on metabolism and performance of endurance-trained athletes during and after a marathon run. Seven male subjects were given supplements of 2 g L-carnitine 2 h before the start of a marathon run and again after 20 km of the run. The plasma concentration of metabolites and hormones was analysed 1 h before, immediately after and 1 h after the run, as well as the next morning after the run. In addition, the respiratory exchange ratio (R) was determined before and at the end of the run, and a submaximal performance test was completed on a treadmill the morning after the run. The administration of L-carnitine was associated with a significant increase in the plasma concentration of all analysed carnitine fractions (i.e. free carnitine, short-chain acylcarnitine, long-chain acylcarnitine, total acid soluble carnitine, total carnitine) but caused no significant change in marathon running time, in R, in the plasma concentrations of carbohydrate metabolites (glucose, lactate, pyruvate), of fat metabolites (free fatty acids, glycerol, beta-hydroxybutyrate), of hormones (insulin, glucagon, cortisol), and of enzyme activities (creatine kinase, lactate dehydrogenase). Moreover, there was no difference in the result of the submaximal performance test the morning after the run. In conclusion, acute administration of L-carnitine did not affect the metabolism or improve the physical performance of the endurance-trained athletes during the run and did not alter their recovery.

[Information value of 2 color tests in the determination of alanine and aspartate-aminotransferases in liver and biliary tract diseases]. / Informationswert zweier Farbteste zur Bestimmung der Alanin- und Aspartrat-Aminotransferase bei Leber-Gallenwegs-Erkrankungen

On the basis of examinations of altogether 197 patients the results of the changes of GOT and GPT were compared with the old and new colour tests of the AWD Dresden in normal histology, virus hepatitis, fatty liver, liver cirrhosis and posthepatic occlusion. Though the new colour test reveals a higher sensitivity, the differential diagnosis between selected liver diseases, especially virus hepatitis and posthepatic occlusion syndrome have become more difficult. The cause for this is the less significant separability between the individual regions of reference.