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OBJECTIVE To register the results, complications and patient acceptance of bladder tumour operations under local anaesthesia. PATIENTS AND METHODS Intravesical lignocaine was the anaesthesia used in 30 patients with multiple bladder tumour recurrences. The largest tumour was extirpated with large flexible biopsy forceps and the others were fulgurated. RESULTS All visible tumours were extirpated or fulgurated except in one patient, where the operation had to be terminated due to unsatisfactory anaesthesia. All left the hospital within 2 h of surgery. Complications were minor and patient acceptance was very high. CONCLUSION These operations have previously been performed under spinal anaesthesia in this department and the present modification reduced costs by approximately 70%. Patients who had only minor discomfort associated with routine cystoscopy under urethral anaesthesia were well suited for extirpation and fulguration of multiple small tumours under intravesical lignocaine.

Objective To study biopsy quality, complications and patient acceptance when urinary bladder biopsies were taken under local anaesthesia. Patients and methods Multiple large cold-cup urinary bladder biopsies were taken under topical lignocaine anaesthesia in 20 patients who had previously undergone transurethral resection for superficial bladder cancer. Results The procedures were carried out at the outpatient clinic with 0.5-2 h post-operative observation. Patient acceptance was very high and complications were minimal. The quality of the biopsies was consistently high and influenced treatment in the majority of the patients. Conclusion In our department multiple bladder biopsies (mapping) have previously always been performed as a transurethral resection under general or spinal anaesthesia. Operation under intravesical lignocaine anaesthesia with 2 h post-operative observation reduced the costs by 70%.

249 Background: The outcomes of patients with non-muscle-invasive urothelial carcinoma of the bladder (NMIUCB) remain poorly understood. The aim of our study was to identify prognostic factors of cancer recurrence and progression in patients with primary UCB. Methods: We performed a combined analysis on individual data from 4,325 patients with primary NMIUCB. Results: Within a median follow-up of 64 months, 1,960 patients (45.4%) experienced disease recurrence, 498 (11.5%) experienced progression to muscle-invasive stage, 1,155 (26.7%) died of any cause, and 310 (7.2%) died of their cancer. In multivariable Cox regression analysis, advanced age, higher grade, larger tumor size, higher number of tumors, number of prior recurrences, and type of intravesical therapy were independent predictors of disease recurrence and progression. While treatment intravesical chemotherapy was only associated with decreased/delayed cancer recurrence, intravesical BCG therapy was associated with decreased/delayed cancer recurrence and progression. The predictive accuracies of the models for recurrence and progression were 63.5% and 71.3%, respectively. Conclusions: Even in a heterogenous patient population, BCG therapy appears to decrease frequency and delay time to cancer recurrence and progression in patients with NMIUCB. Predictive tools based on combination of multiple clinical variables which capture the biological and clinical potential of nonmuscle-invasive disease could help with patient counseling and individualized risk assessment for adjuvant intravesical therapy and clinical trial design. [Table: see text] No significant financial relationships to disclose.

The effects of 17-beta-oestradiol (E2) and progesterone (P) on insulin sensitivity were determined in oophorectomized (OVX) rats by the euglycaemic hyperinsulinaemic clamp technique combined with measurements of insulin-stimulated 2-deoxy-D-glucose (2-DOG) transport and glycogen synthesis in white and red parts of the gastrocnemius, the extensor digitorum longus and soleus muscles as well as in the liver (only glycogen synthesis). OVX was followed by insulin resistance in the clamp measurements. This was paralleled by a decreased insulin-stimulated content of 2-DOG in muscles, an index of glucose transport. Glycogen synthesis in muscle was also decreased, although to less extent. E2, alone or in combination with P, restored this to values of intact controls, while P alone was followed by insulin resistance. Liver glycogen synthesis was also decreased by OVX but this required combination of E2 and P to be fully restored. It was concluded that particularly E2 plays an important role in the maintenance of normal insulin sensitivity while P alone seems to be followed by insulin resistance, both effects apparently mainly by regulation of glucose uptake in muscle. E2 + P may be of importance for maintenance of normal glycogen synthesis in the liver.

Statistical studies repeatedly have shown an association between systemic insulin resistance and a preponderance of highly glycolytic, relatively insulin-insensitive muscle fibers as well as a low density of muscle capillaries. The nature of the relationship between these observations is, however, not clear. Female rats were made hyperinsulinemic for 7 days by implantation of osmotic minipumps. Elevated adrenergic activity and secretion of glucocorticoids were controlled by another minipump with propranolol and adrenalectomy was controlled with glucocorticoid substitution. This resulted in hyperinsulinemia and moderate hypoglycemia, the latter probably counteracted by overeating and increased glucagon secretion, as indicated by increased body weight and lower liver glycogen contents, respectively. Systemic insulin sensitivity was increased and measured with a hyperinsulinemic-euglycemic clamp technique. This was paralleled by an elevated glucose utilization estimated as uptake of 2-deoxyglucose in parametrial, retroperitoneal, and inguinal adipose tissues and the soleus and extensor digitorum longus muscles. Glycogen synthesis was also elevated in the soleus muscle. Muscle fiber composition changed with hyperinsulinemia and elevated 2-deoxyglucose uptake toward more fast-twitch, type II, particularly type IIb fibers, whereas the proportion of slow-twitch, type I fibers, diminished. Capillary density was elevated per unit muscle surface area as well as per muscle fiber. This was paralleled by increased insulin sensitivity systemically and in muscles. These results suggest that muscle fiber composition alterations may be a consequence rather than a cause of hyperinsulinemia and that capillarization rather than fiber composition is of importance for insulin sensitivity in muscle.

Middle-aged men with abdominal obesity were treated in a double-blind study with moderate doses of transdermal preparations of testosterone (T), dihydrotestosterone (DHT), or placebo. This resulted in moderately elevated T concentrations and marked decreases in follicle stimulating and luteinizing hormones in the group treated with T, while the DHT group showed elevated DHT, markedly lower T values, and less diminution of gonadotropin concentrations. In the group treated with T visceral fat mass decreased (measured by computerized tomography) without significant changes in other depot fat regions. Lean body mass did not change. In the group treated with T, glucose disposal rate, measured with the euglycemic hyperinsulinemic clamp method, was markedly augmented. Plasma triglycerides, cholesterol, and fasting blood glucose concentrations as well as diastolic blood pressure decreased. There were no such changes in the DHT or placebo treatment groups. The men treated with T reported increased well-being and energy. In none of the groups did prostate volume, specific prostate antigen concentration, genito-urinary history, or urinary flow measurement change. It is suggested that supplementation of abdominal obese men with moderate doses of T might have several beneficial effects.

Over the last ten years an increased knowledge on the relationships between body composition and health has been achieved. The health hazards of being obese have finally been proven and several studies have also indicated an increased morbidity and mortality among extemely lean subjects (review, ref.1.2). Furthermore, relationships between the adipose tissue (AT) distribution and cardiovascular risks have been demonstrated (review, ref. 1,2). Most of these studies have used just weight and height or. in the case of cross-sectional studies, simple two-compartment models based on density, total body potassium and/or total body water to describe the body composition. Similarly, the AT distribution has been estimated from skinfold- and waist/hip-circumference ratios (W/H) in most studies. Some cross-sectional studies have used single or a small number of computed tomography (CT) scans to determine visceral and subcutaneous AT areas. In a stricter sense, not even this is sufficient, since AT areas can not be expressed as a percentage of the total AT volume and therefore regional area determinations can not describe the AT distribution or changes of this distribution. As shortly summarized below we have used CT for total as well as regional volume determinations of AT. muscles and other organs. This organ-oriented approach has certain advantages over traditional body composition techniques which only give constituents such as fat, water, potassium, nitrogen or calcium.

BackgroundChanges in lifestyle have resulted in an epidemic development of obesity-related diseases that challenge the healthcare systems worldwide. To develop strategies to tackle this problem the focus is on diet to prevent the development of obesity-associated diseases such as cardiovascular disease (CVD). This will require methods for linking nutrient intake with specific metabolic processes in different tissues.Methodology/principal findingLow-density lipoprotein receptor-deficient (Ldlr -/-) mice were fed a high fat/high sugar diet to mimic a westernized diet, being a major reason for development of obesity and atherosclerosis. The diets were supplemented with either beef or herring, and matched in macronutrient contents. Body composition, plasma lipids and aortic lesion areas were measured. Transcriptomes of metabolically important tissues, e.g. liver, muscle and adipose tissue were analyzed by an integrated approach with metabolic networks to directly map the metabolic effects of diet in these different tissues. Our analysis revealed a reduction in sterol metabolism and protein turnover at the transcriptional level in herring-fed mice.ConclusionThis study shows that an integrated analysis of transcriptome data using metabolic networks resulted in the identification of signature pathways. This could not have been achieved using standard clustering methods. In particular, this systems biology analysis could enrich the information content of biomedical or nutritional data where subtle changes in several tissues together affects body metabolism or disease progression. This could be applied to improve diets for subjects exposed to health risks associated with obesity.

Hallmarks of high-fat Western diet intake, such as excessive lipid accumulation in skeletal muscle and liver as well as liver fibrosis, are investigated in tissues from mice using nonlinear microscopy, second harmonic generation (SHG), and coherent anti-Stokes Raman scattering (CARS), supported by conventional analysis methods. Two aspects are presented; intake of standard chow versus Western diet, and a comparison between two high-fat Western diets of different polyunsaturated lipid content. CARS microscopy images of intramyocellular lipid droplets in muscle tissue show an increased amount for Western diet compared to standard diet samples. Even stronger diet impact is found for liver samples, where combined CARS and SHG microscopy visualize clear differences in lipid content and collagen fiber development, the latter indicating nonalcoholic fatty liver disease (NAFLD) and steatohepatitis induced at a relatively early stage for Western diet. Characteristic for NAFLD, the fibrous tissue-containing lipids accumulate in larger structures. This is also observed in CARS images of liver samples from two Western-type diets of different polyunsaturated lipid contents. In summary, nonlinear microscopy has strong potential (further promoted by technical advances toward clinical use) for detection and characterization of steatohepatitis already in its early stages.

The effects of cortisol on insulin sensitivity were examined in rats with the euglycaemic, hyperinsulinaemic clamp technique. Uptake of 2-deoxyglucose and incorporation of glucose into glycogen was followed in the white gastrocnemius, extensor digitorum longus, red gastrocnemius and soleus muscles as well as the liver (only glycogen synthesis). Maximal velocity and fractional velocity of the insulin-sensitive part of glycogen synthase (FV %) was measured in the muscles, as well as muscle fibre composition and capillary density. After 24 h exposure to cortisol, insulin sensitivity was diminished in the clamp measurements. This was paralleled by a decrease in glycogen synthesis in the most insulin-sensitive red gastrocnemius and Soleus muscles, but not in the white gastrocnemius or extensor digitorum longus muscles or the liver, and no effect was seen on 2-deoxyglucose uptake in muscles. FV % was markedly inhibited in all muscles. After 48 h exposure to cortisol, glycogen synthesis was markedly inhibited in all muscles, and 2-deoxyglucose uptake in all except the least insulin-sensitive muscle, WG. No changes in muscle morphology were found. These results suggest that the insulin resistance caused by cortisol is elicited in a stepwise manner, starting with an inhibition in the glycogen synthesis system in insulin-sensitive muscles, later including all muscles as well as 2-deoxyglucose uptake. This occurs without changes in morphology.