Omega-3 fatty acids does not affect physical activity and body weight in primary school children - a double-blind randomized placebo-controlled trial.

It was hypothesized that supplementation of omega-3 fatty acids could increase physical activity (PA) levels, where traditional interventions often fail. The aim of this double-blind, randomized, placebo-controlled trail was to evaluate the effects of 15-week administration of omega-3 fatty acids on objectively measured PA and relative body weight in 8-9 year-old children. The children were randomly assigned to supplementation of omega-3 fatty acids or placebo. Primary outcome was change in PA counts per minute (cpm), and secondly change in body mass index standard deviation score (BMI SDS). Covariance models were applied adjusting for age, gender, weight status, PA and intervention season. Compliance was controlled for by analyzing fatty acid composition in plasma. The intention to treat population consisted of 362 children (omega-3 n = 177, placebo n = 185). No significant effects of omega-3 fatty acids on PA or relative body weight were observed. In covariance models no effects were observed by gender, weight status or change in PA (all p > 0.05), but inactive children increased their PA more than children classified as active at baseline (p < 0.05).

Childhood obesity treatment: telephone coaching is as good as usual care in maintaining weight loss - a randomized controlled trial.

There is a need for more flexible treatment strategies to help patients reach relevant treatment outcomes and adhere better to treatment. The aim of this study was to evaluate the long-term efficacy, in terms of patients' weight status, of replacing usual care (UC) physical visits with more frequent but shorter telephone coaching (TC) sessions as part of a structured childhood obesity treatment. In this controlled study, patients aged 5-14 years from the Södertälje outpatient clinic, Sweden were randomized to either UC or TC over an 18-month period after participating in an initial standard obesity treatment programme. The patients were followed for a mean of 3.7 years. In total, 37 children (UC, n = 18 and TC, n = 19) were included, with a mean (standard deviation, SD) age of 9.5 (2.6) years and a body mass index standard deviation score (BMI SDS) of 2.9 (0.7). The change in BMI SDS did not differ between the groups during the study (P = 0.8). Both groups had similar changes in BMI SDS 3.7 years after the first visit to the clinic, TC = - 0.42 and UC = 0.52 BMI SDS units (P = 0.6 between groups). There were no gender differences. Furthermore, the average time clinicians spent with each patient during the study did not differ between the groups (P = 0.5). No patients were lost to follow-up during the study. In conclusion, the use of TC may offer greater flexibility in the treatment of paediatric obesity as it was non-inferior for both treatment efficacy and the time spent on treatment by healthcare personnel.

Association between impaired fasting glycaemia in pediatric obesity and type 2 diabetes in young adulthood.

OBJECTIVES: In adults, impaired fasting glycemia (IFG) increases the risk for type 2 diabetes mellitus (T2DM). This study aimed to investigate to which extent children with obesity develop T2DM during early adulthood, and to determine whether IFG and elevated hemoglobin A1c (HbA1c) in obese children are risk markers for early development of T2DM. METHODS: In this prospective cohort study, 1620 subjects from the Swedish Childhood Obesity Treatment Registry - BORIS who were ⩾18 years at follow-up and 8046 individuals in a population-based comparison group, matched on gender age and living area, were included. IFG was defined according to both ADA (cut-off 5.6 mmol l(-1)) and WHO (6.1 mmol l(-1)). Elevated HbA1c was defined according to ADA (cut-off 39 mmol l(-1)). Main outcome was T2DM medication, as a proxy for T2DM. Data on medications were retrieved from a national registry. RESULTS: The childhood obesity cohort were 24 times more likely to receive T2DM medications in early adulthood compared with the comparison group (95% confidence interval (CI): 12.52-46). WHO-defined IFG predicted future use of T2DM medication with an adjusted hazard ratio (HR) of 3.73 (95% CI: 1.87-7.45) compared with those who had fasting glucose levels <5.6 mmol l(-1). A fasting glucose level of 5.6-6.0 mmol l(-1), that is, the IFG-interval added by American Diabetes Association (ADA), did not increase the use of T2DM medication more than pediatric obesity itself, adjusted HR=1.72 (0.84-3.52). Elevated levels of HbA1c resulted in an adjusted HR=3.12 (1.50-6.52). More severe degree of obesity also increased the future T2DM risk. CONCLUSION: IFG according to WHO and elevated HbA1c (39-48 mmol l(-1)), but not the additional fasting glucose interval added by ADA (5.6-6.0 mmol l(-1)), can be considered as prediabetes in the obese pediatric population in Sweden.

Catheter-directed foam sclerotherapy for insufficiency of the great saphenous vein: occlusion rates and patient satisfaction after one year.

OBJECTIVES: This study aims to describe a technique for catheter-directed foam sclerotherapy (CDS) of great saphenous vein (GSV) insufficiency and report occlusion rate and patient satisfaction after a single treatment. METHODS: About 100 patients were included. The GSV was accessed at knee level. With the method of Tessari 10 mL sclerosant foam was made (2 mL 3% polidocanol and 8 mL air) and delivered along the GSV while the catheter was withdrawn. At two weeks and at one year after treatment the patients were evaluated. RESULTS: CDS was successfully performed in 94 of the 100 patients. After one year, 84% of the patients were satisfied. Seventy percent of the GSV were completely occluded, 14% were partly occluded and 15% were recanalized. No serious side-effects occurred. CONCLUSIONS: CDS is safe. Patient satisfaction is very satisfying and the occlusion rate is promising after a single treatment. Repeated treatments and technical development may achieve higher occlusion rates.

Associations between severity of obesity in childhood and adolescence, obesity onset and parental BMI: a longitudinal cohort study.

OBJECTIVE: To explore the relationship between severity of obesity at age 7 and age 15, age at onset of obesity, and parental body mass index (BMI) in obese children and adolescents. DESIGN: Longitudinal cohort study. SUBJECTS: Obese children (n = 231) and their parents (n = 462) from the Swedish National Childhood Obesity Centre. METHODS: Multivariate regression analyses were applied with severity of obesity (BMI standard deviation score (BMI SDS)) and onset of obesity as dependent variables. The effect of parental BMI was evaluated and in the final models adjusted for gender, parental education, age at onset of obesity, severity of obesity at age 7 and obesity treatment. RESULTS: For severity of obesity at age 7, a positive correlation with maternal BMI was indicated (P = 0.05). Severity of obesity at this age also showed a strong negative correlation with the age at onset of obesity. Severity of obesity at age 15 was significantly correlated with both maternal and paternal BMI (P < 0.01). In addition, BMI SDS at age 15 differed by gender (higher for boys) and was positively correlated with severity of obesity at age 7 and negatively correlated with treatment. Also, a negative correlation was indicated at this age for parental education. No correlation with age at onset was found at age 15. For age at onset of obesity there was no relevant correlation with parental BMI. Children within the highest tertile of the BMI SDS range were more likely to have two obese parents. CONCLUSION: The impact of parental BMI on the severity of obesity in children is strengthened as the child grows into adolescence, whereas the age at onset is probably of less importance than previously thought. The influence of parental relative weight primarily affects the severity of childhood obesity and not the timing.

Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents.

BACKGROUND: The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. RESULTS: We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896+37A>G, c.896+117C>G and c.896+223A>G). We further genotyped c.896+223A>G in 962 subjects, 450 well-characterized obese children and adolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896+223A>G variant between extremely obese children and adolescents and normal weight adolescents (P=0.406, OR=1.154 (0.768-1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P=0.017) and increased degree of insulin resistance (P=0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS. CONCLUSION: These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels.

Systemic white blood and endothelial cell response after revascularization of critical limb ischemia is only influenced in case of ischemic ulcers.

AIM: The aim of this study was to study the inflammatory response to open revascularization of an ischemic leg in terms of activation of white blood cells (WBC), platelets and endothelial cells. DESIGN: prospective study. METHODS: Venous samples from 21 patients suffering critical limb ischemia (CLI) were drawn before, and 4 weeks after (20 patients) revascularization. Total WBC, differentiated WBC, and platelets were counted. Expression of CD11b/CD18 on granulocytes and monocytes and CD41 on platelets was measured by flow cytometry. Soluble endothelial markers (sICAM-1, sVCAM-1, sE-selectin and sP-selectin) were analysed with ELISA. RESULTS: WBC and granulocyte count decreased in the subgroup of patients with ulcer and gangrene but no change in activation of WBC was recorded. The endothelial marker sICAM-1 decreased while VCAM-1 increased following surgery, most evident in the subgroup with ulcers and gangrene. CONCLUSIONS: This study shows that revascularization of CLI does not significantly influence the inflammatory response in patients with rest pain only, but a limited response of down regulation was found in the ulcer/gangrene patients probably as an effect of healing ulcers.

Inflammatory markers and IL-6 polymorphism in peripheral arterial disease with and without diabetes mellitus.

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis, recognized as an inflammatory disease of the vessel wall, probably accelerated by diabetes mellitus (DM). Elevated interleukin (IL)-6 levels have been associated with increased cardiovascular morbidity and a common polymorphism has been identified in the promoter region of the IL-6 gene. The aim of this prospective study was to investigate inflammatory mediators in PAD patients (+/- DM) and to investigate a possible relationship to the IL-6 gene polymorphism. Five groups of patients (DM, intermittent claudication +/- DM, critical limb ischemia (CLI) +/- DM) and a control group of 20 individuals each were included. Hemoglobin, high sensitive C-reactive protein (hsCRP), creatinine, blood lipids, white blood cells (WBC); CD11b/CD18; vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1), sE-selectin, sP-selectin; IL-6, IL-8, tumour necrosis factor (TNF)alpha, sTNFalpha-R1 and sTNFalpha-R2 were analysed. The IL-6 gene polymorphism was determined in all groups and also compared with 200 healthy controls from a larger study of blood donors. In a multiple regression analysis, adjusted for gender, smoking and age, the effect of CLI was significantly (p < 0.05) associated with elevated levels of the WBC count, hsCRP, proinflammatory cytokines (IL-6, TNFalpha-R1-2) and endothelial (sICAM, sVCAM) and WBC (CD11b gran) markers. The effect of less advanced PAD (intermittent claudication) was related to an increased concentration of sVCAM-1 and the number of monocytes and granulocytes. DM or leg ulcers were not significantly related to any of the markers. No significant difference in frequency of the various IL-6 genotypes was found between the groups or when compared with the group of 200 blood donors (p> 0.3). Activation of cytokines, endothelial cells and WBC was related to the Fontaine stage of PAD but not to the presence of DM or ulcers. No association was found between the polymorphism in the IL-6 promoter region and PAD.

White blood cell and endothelial cell response to endovascular procedures in the leg.

AIM: The longterm patency of endovascular procedures is partly depending on restenosis by intimal hyperplasia, a process depending on inflammatory mechanisms resembling the mechanisms of normal repair and the process of atherosclerosis. The aim of this study was to characterize the inflammatory response of white blood cells (WBC) and endothelial cells following endovascular procedures in the leg. METHODS: Venous blood samples were drawn from a cubital vein before and 2 hours after intervention in 19 patients suffering from peripheral arterial occlusive disease (PAOD). Flow cytometry was used to identify and determine the concentrations of WBC and platelets and to measure CD11b/CD18 on WBC and CD41 on platelets. Soluble endothelial markers (sICAM-1, sE-selectin, sP-selectin and sVCAM-1) were measured by ELISA technique. RESULTS: WBC were downregulated following endovascular procedures. The endothelial cell response was limited and only downregulation of sP-selectin reached significant levels. The results were more evident in the group of patients with critical limb ischemia (CLI) compared to patients with intermittent claudication (IC). CONCLUSION: Endovascular procedures in the leg evoke only a limited response which is depending on the degree of ischemia and the magnitude of the interventional procedure.

Effect of Iloprost infusion on metabolism in critical limb ischemia, utilizing microdialysis. A pilot study.

AIM: In critical limb ischemia (CLI), the prognosis to keep the leg is poor if revascularisation is not possible. Treatment with prostanoids has proven to be beneficial regarding pain relief, ulcer healing and limb salvage but only in a proportion of patients. Prostanoids exert their effect in different ways e.g. on white blood cells and endothelial cells. No study has so far investigated the effect of prostanoids on the local tissue metabolism. The aim of this study was to investigate if infusion of the prostacyclin analogue, iloprost (PGI2) improves the local metabolism measured by microdialysis technique. METHODS: Eleven patients, 7 men and 4 women, median age 75 years (range 64-89 years), suffering CLI (Fontaine stage III and IV), were included. Patients with insulin dependent diabetes mellitus were excluded. Microdialysis catheters (CMA 60) were inserted subcutaneously in the ischemic leg and in the pectoral region, respectively. An iloprost infusion was given for 6 hours during 3 days preceded by a control day. Registrations of glucose and lactate levels were performed hourly. RESULTS: No significant differences were found in lactate or glucose levels over the treatment period but a trend of increasing glucose and decreasing lactate was observed. Compared to the control day, lactate was significantly lower during (p=0.02) and after (p<0.05) the infusion. This was also true for the reference catheter during the infusion period (p=0.02). CONCLUSIONS: No immediate improvement in glucose or lactate levels in ischemic tissue could be observed after 3 days of iloprost infusion, but a significant lactate decrease was found compared to a previous control day, suggesting a possible metabolic response.

Orlistat treatment in obese prepubertal children: a pilot study.

AIM: This study investigated orlistat treatment in obese prepubertal children with regard to tolerance, safety and psychological well-being. METHODS: 11 healthy, severely obese prepubertal children (age 8.3-12.3 y, body mass index standard deviation score 5.3-9.2) were recruited for a 12 wk open treatment. Before, during and after treatment, the participants were investigated by psychological evaluation, blood chemistry, and parameters reflecting obesity and fat mass. RESULTS: The participants were able to comply with the treatment, as indicated by pill counts and self reports, and expressed a desire to continue the treatment after the study period. Gastrointestinal side effects were mild and tolerable. No negative effects on psychological or physical well-being were detected, and the psychological evaluation demonstrated increased avoidance of fattening food, body shape preoccupation and oral control (p = 0.011). The median weight loss was 4.0 kg (range -12.7 to +2.5 kg, p = 0.016) and was highly correlated to decreased fat mass (regression coefficient 0.953, p < 0.01). CONCLUSION: This pilot study indicates that obese prepubertal children were able to reduce their fat intake to avoid gastrointestinal side effects. Thus, orlistat may be suitable as a component in behaviour-modification programmes for obese children, and the results prompt a placebo-controlled investigation of its effectiveness in promoting weight loss.

Microdialysate metabolites before, during and after vascular surgery for chronic leg ischaemia.

OBJECTIVE: to investigate peripheral metabolism in the leg during bypass surgery for chronic ischaemia. PATIENTS AND METHODS: in eight patients, microdialysis catheters were placed in the anterior and posterior tibial muscles, subcutaneously in the leg and, for reference, subcutaneously in the pectoral region. Tissue glucose, glycerol and lactate levels were measured between induction of anaesthesia and the first postoperative day. RESULTS: glucose levels increased postoperatively at all four sites. Glycerol levels decreased during the day of surgery. Glycerol was significantly lower in the leg than in the pectoral region. Muscle lactate increased after anaesthesia, but before proximal clamping, and no further significant intra-operative increase was observed. Post-operatively, lactate decreased to baseline levels. Subcutaneous lactate levels followed the changes observed in muscle but did not reach statistical significance. CONCLUSION: bypass surgery for chronic ischaemia temporarily worsens ischaemic metabolism in the leg.

Peripheral arterial disease. Contrast-enhanced 3D MR angiography of the lower leg and foot compared with conventional angiography.

PURPOSE: To determine whether contrast-enhanced 3D MR angiography (CE MRA) could replace digital subtraction angiography (DSA) for the evaluation of atherosclerotic peripheral vascular disease of the lower leg and foot. MATERIAL AND METHODS: Thirty-five patients with symptoms of atherosclerotic disease of the leg were examined prospectively with CE MRA of the foot and the lower legs as well as with DSA from the aorta to the pedal arches. The MRA technique was focused on optimal imaging of the arteries of the foot. RESULTS: The agreement between CE MRA and DSA for grading of stenosis was moderate to good (weighted kappa-values 0.48-0.80). The sensitivity of CE MRA for detection of significant stenosis (> or = 50%) was 92% and the specificity was 64% with DSA as gold standard. CONCLUSION: CE MRA is a fairly accurate method for the demonstration of atherosclerotic disease below the knee including the pedal arches. It can replace DSA for the assessment of distal arteries in patients with impaired renal function. However, image quality and resolution still needs to be improved before CE MRA can become the method of choice in all patients.

Perspective on contemporary burn surgery and burn care in Sweden.

Burn surgery has gone through revolutionary changes during the last century, even the most severe burns can now be safely treated. Modern surgical treatments have been followed by improvements in intensive burn care and anaesthesiology. These developments have allowed immediate surgery within 24 hours of the injury to take place in our centre, therefore obtaining advantageous results in shortening hospital stay, improving patient's functional results and simplifying the treatment itself. This treatment is economically beneficial as well. In future we count on rapid development of a new discipline, tissue engineering, which should take a greater role in burn care.

Percutaneous transluminal angioplasty of crural arteries: diabetes and other factors influencing outcome.

OBJECTIVE: to evaluate the efficacy of percutaneous transluminal angioplasty (PTA) of the crural arteries. PATIENTS AND METHODS: a retrospective review of patients treated with PTA of at least one crural artery during an 8-year period (1990--1997). RESULTS: one hundred and fifty-five legs in 140 consecutive patients (mean age 74 years, range 38--91 years) were treated. In 76% a more proximal lesion was also treated. After 1 year, results were significantly better in non-diabetics (improvement rate of 66% vs 32%p <0.05). The outcome for patients with a combination of diabetes, heart disease and renal disease was significantly worse compared to all other patients with an improvement rate of only 9% after 1 year. Patients alive and not amputated at 1 year were significantly more common (p <0.05) among non-diabetics (90%), compared to diabetics (66%). The 1-year mortality for the whole group was 15%, significantly higher for diabetic patients (p =0.04). CONCLUSION: PTA of crural arteries produces reasonably good results in non-diabetic patients. Diabetic patients were doing worse than non-diabetics after a year, though 1-month results were not significantly different. Patients with diabetes, heart disease and renal disease make a high-risk group that has a significantly worse outcome.

Different effect on axonal outgrowth of application of non-absorbable or absorbable tubes around a nerve repair.

We studied regeneration distance of rat sciatic nerve, with the sensory pinch reflex test and immunocytochemical staining for neurofilaments, four to 21 days after transsection, repair, and enclosure of the repair site in either a non-absorbable silicone tube or an absorbable polyglycolic acid (PGA) tube. The size of both tube-types was carefully selected so that they did not compress the repaired nerve. The opposite nerve was repaired and not inserted in a tube (control). The regeneration distances in repaired nerves enclosed in silicone tube were significantly longer than the control side at all time points, a result not seen when PGA tube was used. The number of proliferating non-neuronal cells (incorporation of 5-bromodeoxyuridine (BrdU)) was studied just proximal to the site of nerve repair after six days. Numerous stained cells were seen, but there where no significant differences between the groups. We conclude that outgrowth of sensory axons after transsection and repair of rat sciatic nerve with sutures can be increased by enclosing the site of repair in a silicone tube but not in a PGA tube. The effect is probably not related to the number of proliferative non-neuronal cells.

Utility of an intervention scoring system in documenting effects of changes in burn treatment.

The consequences of the introduction of a program of consistent use of topical antimicrobials and early aggressive excision of deep burn wounds by utilizing a comprehensive, computerized patient registry/therapeutic intervention scoring system, were investigated. Prospectively, the clinical course, mortality, outcome and hospital costs were compared for the year preceding (89 patients) and the 4 years following (226 patients) the introduction of the new treatment program. It was found that mortality decreased from 10.1 to 4.6% after change in therapy (P<0.001), despite an increase in mean burn extent. The length of hospital stay per % burn surface area declined from 1.2 to 1.0 days (P<0.001). The number and complexity of therapeutic interventions and the associated costs, also declined. Patients in the new treatment program had a better level of physical and psychosocial function at follow up. In conclusion, the introduction of a program of consistent use of topical antimicrobials and early, aggressive surgical excision was associated with an improved outcome at lesser cost. The combined registry-intervention scoring system permits ready analysis of results using data entered on a daily, near-real time basis.

Effects of growth hormone treatment in obese prepubertal boys.

Childhood obesity is associated with several abnormalities of the GH axis, including decreased spontaneous secretion, decreased response to exogenous secretagogues, and altered pulsatile pattern of secretion. In adults, GH treatment reduces abdominal obesity and improves insulin sensitivity, as well as blood lipid profiles. Whether GH has similar effects in obese children has not been investigated previously. In this study, seven prepubertal severely obese boys aged 10-12 yr were treated with GH for 6 months and followed for an additional 6 months. No diet or exercise modifications were initiated. Body fat percentage decreased from 51.3% to 46.1% after treatment (P = 0.03). Frequently sampled iv glucose tolerance tests revealed an increased responsivity of the acute insulin secretion (P = 0.04) and a nonsignificant trend toward improved insulin sensitivity. In isolated adipocytes, the maximum isoprenaline- and terbutaline-induced lipolysis were increased approximately 2.5-fold (P = 0.02). The sensitivity of the adipocytes to isoprenaline was unchanged, whereas the sensitivity to terbutaline was increased (P = 0.04). No effect was observed on basal or insulin-stimulated lipogenesis. In conclusion, GH treatment for 6 months of obese prepubertal boys reduces body fat, possibly, via stimulation of catecholamine-induced lipolysis, without negative effects on glucose homeostasis.

Response of inflammatory markers to balloon angioplasty in peripheral arterial occlusive disease.

OBJECTIVES: To study the inflammatory response to balloon angioplasty (PTA). DESIGN: Prospective study. MATERIALS: Blood samples were drawn for cytokine analysis from 10 patients undergoing PTA before, after 60 min and 6 h after the balloon inflation. Adhesion molecules were analysed in 14 patients undergoing PTA and in seven patients undergoing angiography only. Arterial samples were taken in eight patients, before PTA, immediately after and 15 min later. Venous samples were taken in six patients and in the group undergoing angiography only. The sampling was before, 60, 90 and 120 min after the procedure. As controls served 15 patients with no signs of peripheral arterial disease. METHODS: Cytokines (IL-6, TNF-alpha) were analysed using ELISA. Adhesion molecule expression on WBC was measured by flow cytometry. RESULTS: A significant increase of IL-6 in the sample taken 6 h after the last balloon inflation was seen in five patients. TNF-alpha was raised only in one patient. The group of patients with peripheral arterial occlusive disease (PAOD) expressed pre-interventionally a higher level of adhesion molecules on WBC compared to the controls. The expression of adhesion molecules (CD11b/CD18) was significantly decreased after PTA. CONCLUSION: Only a very limited cytokine response is caused by PTA reflecting the small surgical trauma. PTA results in a downregulation of detectable CD11b/CD18 expression on WBC in the circulation, which may reflect removal of activated cells through adhesion and extravasation.

The functional result two years after a microsurgical penile replantation. Case report.

We describe the technique of microsurgical penile replantation and a case followed up after two years. The patient was a young man with decompensated schizophrenia who emasculated himself with a kitchen knife. A particularly good functional result was achieved including restoration of sensation in the penile shaft and in the glans, and return of erectile capacity.