Ulnar nerve dislocation in ulnar nerve entrapment at the elbow. Influence on surgical outcome.

Our aim was to assess the incidence of symptomatic ulnar nerve dislocation and its influence on surgical outcome after primary and revision surgeries in ulnar nerve entrapment at the elbow (ulnar neuropathy at the elbow (UNE) or cubital tunnel syndrome). The influence of pre- or intra-operative ulnar nerve dislocation on postoperative outcome was assessed in 548 surgically treated cases (548 nerves) from two hand surgery departments reporting to the Swedish National Quality Registry for Hand Surgery, using QuickDASH, a patient-reported outcome measure (PROM), before surgery and at 3 and 12 months postoperatively, and a doctor-reported outcome measure (DROM), grading as "cured-improved "or "unchanged-worsened," at a median follow-up of 3.0 months [IQR, 1.5-6.0]. 109 of the 548 cases (20%) showed documented pre- or intra-operative ulnar nerve dislocation; more often found at revision (35/75, 47%) than at primary surgery (74/473, 16%) (p < 0.0001). Cases with dislocation presented higher QuickDASH scores at 12 months (p = 0.026). A linear regression model, adjusted for age and gender, predicted higher QuickDASH scores at 12 months postoperatively for cases with dislocation (unstandardized B 11.3 [95% CI 0.4-22.2], p = 0.043). DROM grading as unchanged-worsened at a median 3 months predicted worse QuickDASH scores (p < 0.0001) than in cured-improved cases at 3 (unstandardized B, 18.4 [95% CI 9.4-27.3]) and 12 months (unstandardized B, 18.1 [9.1-27.0]). Primary surgeries had better DROM grading than revision surgeries (p = 0.033; cured-improved, 75% and 63%, respectively), but QuickDASH scores did not differ. Presence of a clinically relevant ulnar nerve dislocation resulted in worse outcome, perhaps due to more extensive surgery with transposition. Nerve dislocation needs attention when treating UNE patients.

Effects of IL-1ß-Blocking Therapies in Type 2 Diabetes Mellitus: A Quantitative Systems Pharmacology Modeling Approach to Explore Underlying Mechanisms.

Recent clinical studies suggest sustained treatment effects of interleukin-1ß (IL-1ß)-blocking therapies in type 2 diabetes mellitus. The underlying mechanisms of these effects, however, remain underexplored. Using a quantitative systems pharmacology modeling approach, we combined ex vivo data of IL-1ß effects on ß-cell function and turnover with a disease progression model of the long-term interactions between insulin, glucose, and ß-cell mass in type 2 diabetes mellitus. We then simulated treatment effects of the IL-1 receptor antagonist anakinra. The result was a substantial and partly sustained symptomatic improvement in ß-cell function, and hence also in HbA1C, fasting plasma glucose, and proinsulin-insulin ratio, and a small increase in ß-cell mass. We propose that improved ß-cell function, rather than mass, is likely to explain the main IL-1ß-blocking effects seen in current clinical data, but that improved ß-cell mass might result in disease-modifying effects not clearly distinguishable until >1 year after treatment.

Linkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins with homogeneous genetic background.

The significant worldwide health burden introduced by tobacco smoking highlights the importance of studying the genetic determinants of smoking behavior and the key factor sustaining compulsive smoking, that is, nicotine dependence (ND). We have here addressed the genetic background of smoking in a special study sample of twins, harmonized for early life events and specifically ascertained for smoking from the nationwide twin cohort of the genetically unique population of Finland. The twins and their families were carefully examined for extensive phenotype profiles and a genome-wide scan was performed to identify loci behind the smoking status, ND and the comorbid phenotype of ND and alcohol use in 505 individuals from 153 families. We replicated previous linkage findings on 10q (max logarithm of the odds (LOD) 3.12) for a smoker phenotype, and on 7q and 11p (max LOD 2.50, and 2.25, respectively) for the ND phenotype. The loci linked for ND also showed evidence for linkage for the comorbid phenotype. Our study provides confirmatory evidence for the involvement of these genome regions in the genetic etiology of smoking behavior and ND and for the first time associates drinking and smoking to a shared locus on 10q.

Importance of processing for physico-chemical and physiological properties of dietary fibre.

There is considerable loss of DM during wet heat treatment of vegetables, leading to an increase in dietary fibre. Correction for the loss of DM indicates that the effects on total dietary fibre are minor. There is, however, depolymerization of the dietary fibre polysaccharides. The degradation is related to the severity of the heat treatment. Souring, freezing and mild microwave treatment have no effects. The viscosity is in general related to the extent of polymerisation. Microwave treatment has different effects on various cultivars of green beans, and the addition of salt (NaCl and CaCl2) to the boiling water changes the physico-chemical properties of soluble fibre in carrots, depending on the cation. The higher viscosity of the soluble fibre in raw carrots may partly explain the lower glucose and hormonal responses observed in healthy subjects when compared with blanched and microwave-cooked carrots. In studies on rats the amount of butyric acid in the distal colon has been shown to be higher with dietary components containing high amounts of resistant starch. Further, the fermentability is lower and the butyric acid concentration higher with composite foods than with the corresponding purified fibre fractions. In human studies the faecal concentration of butyric acid has been shown to increase in patients with ulcerative colitis when [beta-glucan-enriched oat bran (20 g fibre) is added to the diet for 12 weeks. Also, an improvement of symptoms was reported.

Combinations of indigestible carbohydrates affect short-chain fatty acid formation in the hindgut of rats.

The fermentability and pattern of short-chain fatty acids (SCFA) formed in the hindgut of rats given various combinations of dietary fibers (DF) and resistant starch (RS) were investigated. Highly fermentable indigestible carbohydrates, i.e., guar gum (GG), pectin (Pec) and high amylose cornstarch (HAS), and a DF with a relatively high resistance to fermentation, i.e., wheat bran (WB), were included. The substrates were studied individually or as mixtures (GG + Pec, GG + WB and HAS + WB, 1:1, wt/wt indigestible carbohydrate basis) at a total concentration of 100 g indigestible carbohydrates/kg diet and fed to rats for 13 d. Rats fed Pec had a high proportion of acetic acid in the cecum (76 +/- 2% of total SCFA), whereas those fed GG had the highest proportion of propionic acid (31 +/- 4%, P <0.0005). Rats fed GG and Pec had low proportions of butyric acid (6 +/- 1 and 10 +/- 1%, respectively), whereas those fed both had a higher proportion of butyric acid (15 +/- 3%, P < 0.05). Consequently, the cecal butyric acid pool was twice as high in rats fed the GG + Pec mixture (44 +/- 9 micro mol) as in those fed the individual components (19 +/- 2 and 21 +/- 3 micro mol, respectively, P < 0.05). Rats fed HAS with WB had a greater fecal excretion of SCFA (184 +/- 19 micro mol/d) than those fed the individual components (77 +/- 10 and 116 +/- 12 micro mol/d in rats fed HAS and WB, respectively P < 0.05), suggesting that incorporation of WB delayed the site of fermentation of HAS to the distal part of the hindgut. In conclusion, the combination of indigestible carbohydrates may affect both SCFA patterns and the site of SCFA release in the rat hindgut.

Content of short-chain fatty acids in the hindgut of rats fed processed bean (Phaseolus vulgaris) flours varying in distribution and content of indigestible carbohydrates.

Red kidney beans (Phaseolus vulgaris) processed to differ in distribution and content of indigestible carbohydrates were used to study hindgut fermentability and production of short-chain fatty acids (SCFA). Bean flours with low or high content of resistant starch (RS), mainly raw and physically-inaccessible starch, were obtained by milling the beans before or after boiling. Flours containing retrograded starch and with a high or low content of oligosaccharides were prepared by autoclaving followed by freeze-drying with or without the boiling water. Six diets were prepared from these flours yielding a total concentration of indigestible carbohydrates of 90 or 120 g/kg (dry weight basis). The total fermentability of the indigestible carbohydrates was high with all diets (80-87 %). Raw and physically-inaccessible starch was more readily fermented than retrograded starch (97-99 % v. 86-95 %; ). Non-starch glucans were fermented to a lesser extent than RS, but the fermentability was higher in the case of autoclaved (50-54 %) than boiled beans (37-41 %). The distribution between acetic, propionic and butyric acid in the caecum was similar for all diets, with a comparatively high percentage of butyric acid (approximately 18). However, with diets containing the high amounts of RS, the butyric acid concentration was significantly higher in the distal colon than in the proximal colon ( and for the high- and low-level diets respectively), whereas it remained constant, or decreased along the colon in the case of the other diets. Furthermore, the two diets richest in RS also promoted the highest percentages of butyric acid in the distal colon (24 and 17 v. 12 and 12-16 for the high- and low-level diets respectively).

Limited utility of the phenylephrine-nitroprusside sigmoid curve method of measuring baroreflex function after myocardial infarction.

BACKGROUND: Conventional testing of baroreflex function with phenylephrine bolus injection measures reflex vagal tone. OBJECTIVE: To evaluate an alternative pharmacological method of baroreflex testing, which might provide more comprehensive evaluation of the baroreflex function in patients with uncomplicated myocardial infarction. METHODS: Forty-eight patients, aged 59 +/- 7 years, were evaluated 5-7 days after myocardial infarction and after 6 weeks of rehabilitation. Baroreflex testing was performed with 10-14 incremental injections of nitroprusside and phenylephrine. The peak heart rate and blood pressure point from each injection were fitted to a four parameter (upper plateau, lower plateau, gain and median blood pressure) sigmoid logistic function. The baroreflex sensitivity (BRS) was also measured by conventional linear analysis of the response of the R-R interval to the initial rise in systolic blood pressure induced by phenylephrine bolus injection. RESULTS: Non-linear curve fitting of four logistic curve parameters was possible for results from 91% of tests; in the remaining tests the upper plateau was held constant at the maximum heart-rate response to allow estimation of the other three parameters. When all four parameters had been estimated, the gain parameter could not be precisely determined (the coefficient of variation of the gain parameter was 85 +/- 10%). The upper (R = 0.72, P < 0.001) and lower plateaux (R = 0.76, P < 0.001) were strongly related to the resting heart rate and weakly related to measures of heart-rate variability. There was also a significant inverse correlation between the lower plateau and the BRS (R = -0.57, P < 0.001). The gain parameter was not related to the BRS or any measure of the heart-rate variability. After 6 weeks' rehabilitation there was a significant decrease in the lower plateau (from 54 +/- 2 to 48 +/- 1 beats/min, P < 0.001), an increase in BRS (from 9.4 +/- 0.8 to 12.1 +/- 0.8 ms/mmHg, P < 0.001) and no change in the other three sigmoid curve parameters. CONCLUSIONS: Non-linear curve fitting of the heart-rate-blood-pressure relationship for patients after myocardial infarction is feasible but technical limitations and the lack of correlation between the gain parameter and other measures of autonomic function suggest that this method has limited usefulness. The lower plateau is related strongly to the BRS; both are vagal measures of cardiac autonomic function.

Influence of orally and rectally administered propionate on cholesterol and glucose metabolism in obese rats.

It has increasingly been suggested that the short-chain fatty acids (SCFA) acetic, propionic and butyric acids, derived from colonic fermentation of dietary fibre and other indigestible carbohydrates, exert different physiological effects. Formation of propionic acid is discussed in terms of beneficial effects on glucose and cholesterol metabolism. The aim of the present study was to evaluate possible metabolic effects of propionic acid and to differentiate between effects mediated in the upper gastrointestinal tract and those mediated in the hind-gut. For this purpose, obese hyperinsulinaemic (fa/fa) rats were studied during a 19 d test period. Sodium propionate was either fed orally through the diet (1 g/d), or infused rectally (0.15 g/d) to animals given diets high in cholesterol (20 g/kg) and saturated fat (130 g/kg). At the end of the test period total liver cholesterol pools were 20% lower (P < 0.01) in rats given dietary or rectally infused propionate (481 and 484 mg respectively) compared with the control group (614 mg). This was due to lower liver weights (P < 0.05) in propionate-treated animals, 15.5 and 15.3 g, v. 18.2 g in the control group, and no differences were noted in hepatic cholesterol concentrations. The urinary glucose excretion was measured during days 15-19 and was found to be lower (P < 0.05) in rats fed with propionate (23 mg) compared with the control group or the group infused rectally (39 and 38 mg respectively). In addition, fasting plasma glucose concentrations decreased significantly (P < 0.05) over the test period. It is concluded that orally supplied propionate affects both glucose and cholesterol metabolism as judged from lowered urinary glucose excretion, fasting blood glucose and liver cholesterol pools. On the other hand, propionate administered to the hind-gut at a physiologically relevant level reduces the hepatic cholesterol pool.