Ultrasound Evaluation of the Peroneal Tendons in an Asymptomatic Elite Military Population: A Prospective Cohort Study.

INTRODUCTION: The purpose of this study was to identify the location of the peroneal tendons in relationship to the fibular groove in an asymptomatic population of elite U.S. Military Service members. MATERIALS AND METHODS: The peroneal tendons of 41 active duty U.S. Army Rangers were examined. Subjects were placed in a lateral recumbent position with the ankle in a resting neutral position to visualize the tendon in a retromalleolar short-axis view. Maximum active ankle eversion followed by gravity inversion was facilitated while the ultrasound probe was maintained in its original position. Distance from the fibrous lateral ridge of the retromalleolar groove to the anterior aspect of the peroneal brevis was measured in the short axis in neutral, eversion, and inversion. RESULTS: The mean sagittal distance and standard deviation was 0.48 ± 0.9 mm. No subjects demonstrated greater than 1 mm difference between positions, and no dislocations were identified. Side-to-side difference and dominant vs nondominant differences were not statistically significant. CONCLUSION: The study demonstrates that the distance between the peroneal brevis and the lateral fibular ridge is consistent throughout extremes of motion. These results further the understanding of peroneal tendon function under dynamic examination. Our findings also establish side-to-side consistency prompting a bilateral examination to help identify abnormal pathology.

Cross-sectional Area of the Achilles Tendon in a Cohort of Elite Military Warriors Using Standard Ultrasound Techniques.

Background: The prevalence of Achilles tendon (AT) pathology is common and can result in disability. Understanding normal AT properties can improve our ability to prevent AT injuries. We examined the cross-sectional area of the AT at multiple levels in an asymptomatic population of Army Rangers. Methods: This is a prospective cohort study composed of 41 voluntarily recruited United States Army Rangers deployed in a combat theater. All subjects were members of the Ranger Regiment participating in more than 20 h of intense bipedal non-sport weekly training with no history of AT pathology. While standing, each subject had bilateral AT calcaneal tuberosity insertions (0 cm) marked, along with skin markings made at 2 cm, 4 cm, and 6 cm superior to the AT insertion. AT diameter was measured at each level in the coronal and sagittal planes using ultrasound. Results: Mean sagittal diameter of the AT was 4.4 mm, 4.3 mm, 4.2 mm, and 3.9 mm at 0 cm, 2 cm, 4 cm, and 6 cm, respectively. Mean coronal diameter of the AT was 19.3 mm, 14.7 mm, 13.8 mm, and 14.5 mm at 0 cm, 2 cm, 4 cm, and 6 cm, respectively. The cross-sectional area was calculated as 0.66 cm2, 0.5 cm2, 0.46 cm2, and 0.44 cm2 at 0 cm, 2 cm, 4 cm, and 6 cm, respectively. Conclusion: Our data suggest that increased non-sport activity may not increase the cross-sectional area of the AT. Identifying the normal diameter at multiple levels throughout the most commonly injured area may improve the provider's ability to identify early disease processes and apply targeted interventions to help slow or prevent progression and possible rupture. Level of Evidence: Level III-V.

Strategies to improve beef tenderness by activating calpain-2 earlier postmortem.

Our objectives were to determine the effect of post rigor calcium chloride injection or freezing on 1) sarcoplasmic calcium concentration and calpain-2 activity of beef longissimus lumborum (LL) and semimembranosus (SM) steaks aged 1, 4, and 14days post-treatment and on 2) Warner-Bratzler shear force, water holding capacity, and consumer acceptability of LL and SM steaks aged 4 and 14days post-treatment. Free calcium levels in the calcium, frozen, and control steaks averaged 1256, 127, and 121µM for the LL and 1520, 120, and 111µM for the SM, respectively. Measurable LL native calpain-2 activity was lower in calcium and frozen steaks than control steaks (P<0.01), while SM native calpain-2 activity was lowest in calcium steaks and intermediate in frozen steaks (P<0.01). LL calcium steaks were more tender (P=0.04) than control steaks. In conclusion, calcium chloride injection and freezing activate calpain-2 earlier postmortem in both muscles and calcium injection improves LL tenderness.

Comparison of Visual Analog Pain Score Reported to Physician vs Nurse.

BACKGROUND: The visual analog scale (VAS) is considered a reliable and validated measure of patient-reported acute pain. Patient-reported outcome measures are becoming the standard of care throughout the orthopedic community, but interpretation and clinical applications are still under investigation. The aim of the current study was to compare preoperative patient-reported VAS scores reported at the same visit to nursing staff and the treating surgeon. Our hypothesis was that there would be no difference in the scores reported. METHODS: This study is a retrospective cohort of 201 consecutive foot and ankle patients treated by a single surgeon. The patients were asked to rate their pain intensity by the nursing staff and then by the surgeon using a standard horizontal VAS 0 to 10, from "no pain" to the "worst pain." Differences in reported pain values were analyzed. RESULTS: The results demonstrate that patients reported higher pain scores to the surgeon in 81% of the encounters, nursing staff 8%, and equal 11%. On average, the VAS score reported to the surgeon was significantly ( P < .05) higher than that reported to the nursing staff. CONCLUSION: The current study found a statistically significant higher patient-reported pain score to the treating surgeon compared to the nursing staff. While the exact cause is unclear, the discrepant pain scores call into question the validity of the VAS, considered a fifth vital sign and standard outcome measure in an outpatient clinic setting. LEVEL OF EVIDENCE: Level III, comparative study.

Factors in serum from type 2 diabetes patients can cause cellular insulin resistance.

This pilot study was aimed to investigate whether there are humoral factors in serum from type 2 diabetic subjects that, in addition to glucose, insulin and free fatty acids are able to induce or contribute to peripheral insulin resistance with respect to glucose transport. Isolated subcutaneous adipocytes from 11 type 2 diabetic subjects and 10 nondiabetic controls were incubated for 24-h in medium supplemented with 25 % serum from a control or a type 2 diabetic donor, in the presence of a low (5 mM) or a high (15 mM) glucose concentration, respectively. After the incubation period glucose uptake capacity was assessed. Serum from type 2 diabetic donors, compared to serum from controls, significantly reduced the maximal insulin eff ect to stimulate glucose uptake (approximately 40 %, p < 0.05) in adipocytes from control subjects, independent of surrounding glucose concentrations. Glucose uptake capacity in adipocytes isolated from type 2 diabetic subjects was similar regardless of culture condition. No significant alterations were found in cellular content of key proteins in the insulin signaling cascade (insulin receptor substrate-1 and -2, and glucose transporter 4) that could explain the impaired insulin-stimulated glucose transport in control adipocytes incubated with serum from type 2 diabetic donors. The present findings indicate the presence of biomolecules in the circulation of type 2 diabetic subjects, apart from glucose, insulin, and free fatty acids with the ability to induce peripheral insulin resistance. This further implies that even though normoglycemia is achieved other circulating factors can still negatively affect insulin sensitivity in type 2 diabetic patients.

Sex- and depot-specific lipolysis regulation in human adipocytes: interplay between adrenergic stimulation and glucocorticoids.

The purpose of this investigation was to explore interactions between adrenergic stimulation, glucocorticoids, and insulin on the lipolytic rate in isolated human adipocytes from subcutaneous and omental fat depots, and to address possible sex differences. Fat biopsies were obtained from 48 nondiabetic subjects undergoing elective abdominal surgery. Lipolysis rate was measured as glycerol release from isolated cells and proteins involved in lipolysis regulation were assessed by immunoblots. Fasting blood samples were obtained and metabolic and inflammatory variables were analyzed. In women, the rate of 8-bromo-cAMP- and isoprenaline-stimulated lipolysis was approximately 2- and 1.5-fold higher, respectively, in subcutaneous compared to omental adipocytes, whereas there was no difference between the two depots in men. Dexamethasone treatment increased the ability of 8-bromo-cAMP to stimulate lipolysis in the subcutaneous depot in women, but had no consistent effects in fat cells from men. Protein kinase A, Perilipin A, and hormone sensitive lipase content in adipocytes was not affected by adipose depot, sex, or glucocorticoid treatment. In conclusion, catecholamine and glucocorticoid regulation of lipolysis in isolated human adipocytes differs between adipose tissue depots and also between sexes. These findings may be of relevance for the interaction between endogenous stress hormones and adipose tissue function in visceral adiposity and the metabolic syndrome.

Insulin action and signalling in fat and muscle from dexamethasone-treated rats.

Glucocorticoids initiate whole body insulin resistance and the aim of the present study was to investigate effects of dexamethasone on protein expression and insulin signalling in muscle and fat tissue. Rats were injected with dexamethasone (1mg/kg/day, i.p.) or placebo for 11 days before insulin sensitivity was evaluated in vitro in soleus and epitrochlearis muscles and in isolated epididymal adipocytes. Dexamethasone treatment reduced insulin-stimulated glucose uptake and glycogen synthesis by 30-70% in epitrochlearis and soleus, and insulin-stimulated glucose uptake by approximately 40% in adipocytes. 8-bromo-cAMP-stimulated lipolysis was approximately 2-fold higher in adipocytes from dexamethasone-treated rats and insulin was less effective to inhibit cAMP-stimulated lipolysis. A main finding was that dexamethasone decreased expression of PKB and insulin-stimulated Ser(473) and Thr(308) phosphorylation in both muscles and adipocytes. Expression of GSK-3 was not influenced by dexamethasone treatment in muscles or adipocytes and insulin-stimulated GSK-3beta Ser(9) phosphorylation was reduced in muscles only. A novel finding was that glycogen synthase (GS) Ser(7) phosphorylation was higher in both muscles from dexamethasone-treated rats. GS expression decreased (by 50%) in adipocytes only. Basal and insulin-stimulated GS Ser(641) and GS Ser(645,649,653,657) phosphorylation was elevated in epitrochlearis and soleus muscles and GS fractional activity was reduced correspondingly. In conclusion, dexamethasone treatment (1) decreases PKB expression and insulin-stimulated phosphorylation in both muscles and adipocytes, and (2) increases GS phosphorylation (reduces GS fractional activity) in muscles and decreases GS expression in adipocytes. We suggest PKB and GS as major targets for dexamethasone-induced insulin resistance.

Insulin resistance, endocrine function and adipokines in type 2 diabetes patients at different glycaemic levels: potential impact for glucotoxicity in vivo.

OBJECTIVE: To evaluate the interplay between hyperglycaemia, insulin resistance, hormones and adipokines in patients with type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: Ten patients with T2DM with good glycaemic control (G), 10 with poor control (P) and 10 nondiabetic control subjects (C) were matched for sex (M/F 6/4), age and body mass index. A hyperinsulinaemic, euglycaemic clamp was performed and cytokines and endocrine functions, including cortisol axis activity were assessed. RESULTS: Patients with diabetes were more insulin resistant than group C, and group P exhibited the highest degree of insulin resistance (P = 0.01, P vs C). Tumour necrosis factor (TNF)-alpha levels were elevated in patients with diabetes (P = 0.05) and group P had the highest levels of fasting serum cortisol (P = 0.05), nonesterified fatty acids (NEFA; P = 0.06) and C-reactive protein (CRP; P = 0.01). Adiponectin levels were lower in the P group. In partial correlation analyses, significant associations were found: glycaemic level (HbA1c) with insulin resistance, TNF-alpha, CRP and basal and ACTH-stimulated cortisol levels, insulin resistance with plasma NEFA, TNF-alpha and stimulated cortisol levels. CONCLUSION: Poor glycaemic control in patients with T2DM was associated with insulin resistance and with elevated TNF-alpha, CRP and basal as well as stimulated cortisol levels. Inflammatory mediators, e.g. TNF-alpha, may contribute to insulin resistance in hyperglycaemic patients with T2DM and this might be a partial explanation for glucotoxicity.

Glucocorticoids down-regulate glucose uptake capacity and insulin-signaling proteins in omental but not subcutaneous human adipocytes.

Visceral adiposity is associated with insulin resistance and type 2 diabetes. This study explores the metabolic differences between s.c. and visceral fat depots with respect to effects in vitro of glucocorticoids and insulin on glucose uptake. Adipocytes from human s.c. and omental fat depots were obtained during abdominal surgery in 18 nondiabetic subjects. Cells were isolated, and metabolic studies were performed directly after the biopsies and after a culture period of 24 h with or without dexamethasone. After washing, basal and insulin-stimulated [14C]glucose uptake as well as cellular content of insulin signaling proteins and glucose transporter 4 (GLUT4) was assessed. Omental adipocytes had an approximately 2-fold higher rate of insulin-stimulated glucose uptake compared with s.c. adipocytes (P < 0.01). Dexamethasone treatment markedly inhibited (by approximately 50%; P < 0.05) both basal and insulin-stimulated glucose uptake in omental adipocytes but had no consistent effect in s.c. adipocytes. The cellular content of insulin receptor substrate 1 and phosphatidylinositol 3-kinase did not differ significantly between the depots, but the expression of protein kinase B (PKB) tended to be increased in omental compared with s.c. adipocytes (P = 0.09). Dexamethasone treatment decreased the expression of insulin receptor substrate 1 (by approximately 40%; P < 0.05) and PKB (by approximately 20%; P < 0.05) in omental but not in s.c. adipocytes. In contrast, dexamethasone pretreatment had no effect on insulin-stimulated Ser473 phosphorylation of PKB. GLUT4 expression was approximately 4-fold higher in omental than s.c. adipocytes (P < 0.05). Dexamethasone treatment did not alter the expression of GLUT4. In conclusion, human omental adipocytes display approximately 2-fold higher glucose uptake rate compared with s.c. adipocytes, and this could be explained by a higher GLUT4 expression. A marked suppression is exerted by glucocorticoids on glucose uptake and on the expression of insulin signaling proteins in omental but not in s.c. adipocytes. These findings may be of relevance for the interaction between endogenous glucocorticoids and visceral fat in the development of insulin resistance.

Insulin can enhance GLUT4 gene expression in 3T3-F442A cells and this effect is mimicked by vanadate but counteracted by cAMP and high glucose--potential implications for insulin resistance.

UNLABELLED: It is well-established that high levels of cAMP or glucose can produce insulin resistance. The aim of this study was to characterize the interaction between these agents and insulin with respect to adipose tissue/muscle glucose transporter isoform (glucose transporter 4, GLUT4) gene regulation in cultured 3T3-F442A adipocytes and to further elucidate the GLUT4-related mechanisms in insulin resistance. Insulin (10(4) microU/ml) treatment for 16 h clearly increased GLUT4 mRNA level in cells cultured in medium containing 5.6 mM glucose but not in cells cultured in medium with high glucose (25 mM). 8-Bromo-cAMP (1 or 4 mM) or N(6)-monobutyryl cAMP, a hydrolyzable and a non-hydrolyzable cAMP analog, respectively, markedly decreased the GLUT4 mRNA level irrespective of glucose concentrations. In addition, these cAMP analogs also inhibited the upregulating effect of insulin on GLUT4 mRNA level. Interestingly, the tyrosine phosphatase inhibitor vanadate (1-50 microM) clearly increased GLUT4 mRNA level in a time- and concentration-dependent manner. Furthermore, cAMP-induced inhibition of the insulin effect was also prevented by vanadate. In parallel to the effects on GLUT4 gene expression, both insulin, vanadate and cAMP produced similar changes in cellular GLUT4 protein content and cAMP impaired the effect of insulin to stimulate (14)C-deoxyglucose uptake. In contrast, insulin, vanadate or cAMP did not alter insulin receptor (IR) mRNA or the cellular content of IR protein. IN CONCLUSION: (1) Both insulin and vanadate elicit a stimulating effect on GLUT4 gene expression in 3T3-F442A cells, but a prerequisite is that the surrounding glucose concentration is low. (2) Cyclic AMP impairs the insulin effect on GLUT4 gene expression, but this is prevented by vanadate, probably by enhancing the tyrosine phosphorylation of signalling peptides and/or transcription factors. (3) IR gene and protein expression is not altered by insulin, vanadate or cAMP in this cell type. (4) The changes in GLUT4 gene expression produced by cAMP or vanadate are accompanied by similar alterations in GLUT4 protein expression and glucose uptake, suggesting a role of GLUT4 gene expression for the long-term regulation of cellular insulin action on glucose transport.

The role of Escherichia coli O 157 infections in the classical (enteropathic) haemolytic uraemic syndrome: results of a Central European, multicentre study.

To assess the importance of infection by Verotoxin (VT) producing Escherichia coli (VTEC) in children with HUS in Central Europe, stool and/or serum samples obtained from 147 patients from 28 paediatric centres were prospectively examined for the presence of VTEC and the kinetics of faecal VT titres (FVT), and for VT neutralization titres and antibodies against E. coli O 157 lipopolysaccharide, respectively. Ninety-two percent of the patients had classic (enteropathic) HUS (E+ HUS). Evidence of VTEC infection was obtained in 86% of them. VTEC/FVT were identified in 55/118 E+ cases (47%). A prominent feature was the frequent isolation of sorbitol-fermenting, VT2-producing E. coli O 157.H-.VT1 (C600/H19) was neutralized by 9%, and VT2 (C600/933W) by 99% of the initial serum samples from E+ patients, compared to 3% (VT1) and 100% (VT2) from age-related controls. Fourfold titre rises against VT1 and/or VT2 were observed in 13/70 (19%), and significantly elevated O 157 LPS IgM and/or IgA antibodies in 106/128 (83%) of the E+ patients. The ubiquitous VT2 neutralizing principle in the serum of HUS patients as of healthy controls warrants further investigations.

Lead in bone: storage site, exposure source, and target organ.

The primary site of lead storage is in bone but relatively little attention has focused on this physiological compartment. Recent advances in measurement technology now permit the direct in vivo quantitative measurement of lead in bone, and this measure has great use in clinical and epidemiologic studies. Lead in bone is not a physiological sink, but can be mobilized back into the circulation in response to normal or pathological changes in mineral metabolism. Bone lead may be a significant source of target organ exposure under certain conditions, such as pregnancy, kidney disease, and menopause. Finally, the accumulation of lead in bone cells may have toxic consequences for bone status, and some of the mechanisms by which lead could affect bone mineral metabolism may also play a role in other target organ effects of lead.

The semiotics of gender.

The semiotics of gender are investigated in this article for the purpose of exploring the way that deep unconscious motives in relationship to cultural biases give rise to gender concepts. Theories of semiotic processes, including Jacques Lacan's concept of the psychoanalytic signifier, are explained briefly and applied to the signs of gender. The article concludes that gender concepts develop out of biology, unconscious feelings, and social patterning, and are not given, natural, and irrevocable.