Higher chlorzoxazone clearance in obese children compared with nonobese peers.

AIMS: To test the in vivo activity of Cytochrome P450 (CYP) 2E1 in obese children vs. nonobese children, aged 11-18 years. Secondly, whether the activity of CYP2E1 in these patients is associated with NALFD, diabetes or hyperlipidaemia. METHODS: Seventy children were divided into groups by body mass index (BMI) standard deviation score (SDS). All children received 250 mg oral chlorzoxazone (CLZ) as probe for CYP2E1 activity. Thirteen blood samples and 20-h urine samples were collected per participant. RESULTS: Obese children had an increased oral clearance and distribution of CLZ, indicating increased CYP2E1 activity, similar to obese adults. The mean AUC0-∞ value of CLZ was decreased by 46% in obese children compared to nonobese children. The F was was increased twofold in obese children compared to nonobese children, P < 0.0001. Diabetic biomarkers were significantly increased in obese children, while fasting blood glucose and Hba1c levels were nonsignificant between groups. Liver fat content was not associated with CLZ Cl. CONCLUSION: Oral clearance of CLZ was increased two-fold in obese children vs. nonobese children aged 11-18 years. This indicates an increased CYP2E1 activity of clinical importance, and dose adjustment should be considered for CLZ.

Reductions in blood pressure during a community-based overweight and obesity treatment in children and adolescents with prehypertension and hypertension.

Due to the pandemic of childhood obesity and thus obesity-related hypertension, improvements in treatment availability are needed. Hence, we investigated whether reductions in blood pressure (BP) would occur in children with overweight and obesity exhibiting prehypertension/hypertension during a community-based overweight and obesity treatment program, and if changes in body mass index (BMI) are associated with changes in BP. The study included 663 children aged 3-18 years with a BMI ⩾85th percentile for sex and age that entered treatment from June 2012 to January 2015. Height, weight and BP were measured upon entry and every 3-6 months. BMI and BP s.d. scores (SDSs) were calculated according to sex and age, or sex, age and height. Prehypertension was defined as a BP SDS ⩾1.28 and <1.65. Hypertension was defined as a BP SDS ⩾1.65. Upon entry, 52% exhibited prehypertension (11.9%) or exhibited hypertension (40.1%). After 12 months (range: 3-29) of treatment, 29.3% of the children with prehypertension/hypertension were normotensive. Children with systolic prehypertension/hypertension upon entry reduced their systolic BP SDSs by 0.31 (95% confidence interval (CI): 0.70-0.83, P<0.0001). Children with diastolic prehypertension/hypertension upon entry reduced their diastolic BP SDSs by 0.78 (95% CI: 0.78-0.86, P<0.0001). BMI SDS changes were positively associated with BP SDS changes (P<0.0001). Nonetheless, some children reduced BP SDSs while increasing their BMI SDSs, and prehypertension/hypertension developed in 23.3% of the normotensive children despite reductions in BMI SDSs (P<0.0001). These results suggest that community-based overweight and obesity treatment can reduce BP, and thus may help improve treatment availability.

No influence of sugar, snacks and fast food intake on the degree of obesity or treatment effect in childhood obesity.

BACKGROUND: Increased consumption of sweetened beverages has previously been linked to the degree of childhood obesity. OBJECTIVE: The aim of the present study was to assess whether the intake of sweetened beverages, candy, snacks or fast food at baseline in a multidisciplinary childhood obesity treatment program was associated with the baseline degree of obesity or the treatment effect. METHODS: This prospective study included 1349 overweight and obese children (body mass index standard deviation scores (BMI SDS) ≥ 1.64) enrolled in treatment at The Children's Obesity Clinic, Copenhagen University Hospital Holbaek. The children were evaluated at baseline and after up to 5.9 years of treatment (median 1.3 years). RESULTS: Both boys and girls decreased their BMI SDS during treatment with a mean decrease in boys of 0.35 (p < 0.0001) and in girls of 0.22 (p < 0.0001) after 1 year of treatment. There were no associations between the baseline intake of sweetened beverages, candy, snacks, and/or fast food and BMI SDS at baseline or the change in BMI SDS during treatment. CONCLUSIONS: The intake of sweetened beverages, candy, snacks or fast food when entering a childhood obesity treatment program was not associated with the degree of obesity at baseline or the degree of weight loss during treatment.

1H-MRS measured ectopic fat in liver and muscle is associated with the metabolic syndrome in Danish girls but not in boys with overweight and obesity.

BACKGROUND: The metabolic syndrome (MetS) is a complication to overweight and obesity, which can be observed already in childhood. Ectopic lipid accumulation in muscle and liver has been shown to associate with the development of insulin resistance and dyslipidemia. Thus, the interaction between MetS and ectopic fat may offer clinical relevance. OBJECTIVES: To investigate the prevalence of MetS, or components hereof, and ectopic fat accumulation in liver and skeletal muscle tissue in children, as well as interactions between these. METHODS: Two-hundred-and-sixteen children and adolescents (95 boys) with overweight/obesity were investigated, as well as 47 controls (22 boys) with normal weight. The assessments included anthropometry, fasting blood biochemistry and blood pressure measurements. Liver and muscle lipid contents were assessed by proton magnetic resonance spectroscopy. RESULTS: We observed an odds ratio in girls with overweight/obesity of 12.2 (95% confidence interval: [3.8; 49.0]) for exhibiting MetS when hepatic steatosis was present, whereas no association was observed in boys with overweight/obesity (odds ratio 0.7 [0.2; 2.7]). The odds ratio of exhibiting MetS in the presence of muscular steatosis was 3.5 [1.4; 9.5] in girls with overweight/obesity and 1.0 [0.2; 5.6] in boys with overweight/obesity. Similar results were seen for girls with overweight/obesity exhibiting concurrent hepatic and muscular steatoses. CONCLUSION: Hepatic and muscular steatoses were associated with MetS among girls, but not among boys with overweight/obesity.

Weight reduction and aortic stiffness in obese children and adolescents: a 1-year follow-up study.

Little is known about the effect of weight reduction on aortic stiffness and especially so in the young. The present study investigates whether weight reduction influences aortic stiffness in obese children and adolescents. Carotid-femoral pulse wave velocity (cfPWV) and augmentation index at heart rate 75 (AIx@HR75) were measured in 72 obese patients aged 10-18 years at baseline and after 1-year of lifestyle intervention (follow-up). We found that although the degree of obesity decreased (Δbody mass index z-score: -0.24±0.45, P<0.0001), cfPWV was higher at follow-up (ΔcfPWV: 0.27±0.47 m s(-1), P<0.0001), which was explained by the increase in age (ß=0.12 ms(-1) per year, 95% confidence interval (CI) 0.07-0.17, P<0.0001) and partly by changes in mean arterial pressure and heart rate. Changes in cfPWV were not related to changes in obesity measures. No significant change was found in AIx@HR75 (ΔAIx@HR75: 2.10±9.73%, P=0.072), but changes in AIx@HR75 were related to changes in abdominal fat (Δwaist/height ratio: ß=50.3, 95% CI 6.7-94.0, P=0.02) and changes in total body fat percent by dual energy X-ray absorptiometry scan (Δtotal body fat (%): ß=0.7, 95% CI 0.1-1.3, P=0.02) when adjusted for gender and relevant baseline confounders. In conclusion, no clear effect of weight reduction was found on aortic stiffness, although changes in AIx@HR75 were associated with changes in both abdominal fat and total body fat percent. The higher cfPWV at follow-up was related to the older age.

Liver fat content investigated by magnetic resonance spectroscopy in obese children and youths included in multidisciplinary treatment.

UNLABELLED: What is already known about this subject • Investigations of non-alcoholic fatty liver disease (NAFLD) by non-invasive imaging procedures have limited evidence. • Thirty percent of obese children are estimated to have NAFLD and implications for future morbidity are uncertain. What this study adds • Many obese children and youths exhibit a high liver fat content as examined by magnetic resonance spectroscopy. • Associations between liver fat content, anthropometry, abdominal adipose tissue distribution and liver enzymes are illustrated. SUMMARY: The study aims to investigate the degree of hepatic steatosis and associations with the amount of abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), anthropometric data and biochemical measures of liver enzymes in children and youths included in obesity treatment. The study included 164 patients, aged 6-20 years, with a body mass index (BMI) above the 90th percentile for sex and age. Liver fat content was measured by magnetic resonance spectroscopy (MRS). SAT and VAT were measured by magnetic resonance imaging. Hepatic steatosis was defined as liver fat content >5% (steatosis-5%) and 9% (steatosis-9%), respectively. Data on waist circumference (WC) and blood samples were available in 124 patients. Steatosis-5% and steatosis-9% were identified in 45% and 27% of the patients, respectively. These patients had increased SAT, VAT, BMI standard deviation score, WC/height ratio, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels. GGT, ALT and VAT were found to be independent risk factors of hepatic steatosis. In this study, a substantial proportion of obese children and youths have hepatic steatosis. Therefore, it is important to examine these subjects for the degree of fat in their liver. Future studies focusing on hepatic steatosis should consider the use of MRS in addition to blood samples.

Effects of photoperiod on sexual maturation and somatic growth in male Atlantic halibut (Hippoglossus hippoglossus L.).

A major obstacle in modern, intensive aquaculture is the precocious maturation of male fish, leading to decreased somatic growth and reduced filet quality. Effects of photoperiod on sexual maturation and growth in male Atlantic halibut were therefore examined. In June 1996, 1300 1+ fish of both sexes were distributed in two indoor tanks supplied with continuous light (LL) or a simulated natural photoperiod (SNP). In December 1996 and June 1997, 200 individuals were exchanged between the tanks creating six experimental groups that were followed until June 1998. LL stimulated growth and accelerated timing of first maturation by approximately 3 months. LL also appeared to interrupt circannual rhythmicity in sexual maturation. Sexual maturation led to reduced growth from 3 months pre-spawning and throughout the spawning season. Males that did not mature during the experiment attained the highest final body weight. All males reared on LL from June 1997 reached sexual maturity the following season. In contrast, only 26% of the males matured in the group transferred from LL to SNP in June 1997, and this group also had the highest final body weight. The results indicate a possible route for reducing the problem of precocious maturation in male halibut.

[Prednisolone treatment of respiratory syncytial virus infection. A randomized, controlled trial of 147 children]. / Prednisolonbehandling af respiratorisk syncytial virusinfektion. En randomiseret, kontrolleret undersøgelse af 147 børn.

OBJECTS: Our objective was to evaluate the effect of systemic prednisolone as an adjunct to conventional treatment with beta 2-agonist, fluid replacement and respiratory support in hospitalized infants younger than 24 months with respiratory syncytial virus (RSV) infection. METHODS: The study was randomized, double-blind and placebo-controlled. During the winter of 1995-96, 147 infants less than two years of age hospitalized with RSV infection were allocated to treatment with either systemic prednisolone mixture 2 mg/kg daily or placebo for 5 days. RESULTS: Our main outcome measures were: 1. Acute effect variables: duration of stay in hospital, use of medicine and supportive measures while in hospital. 2. At follow-up one month after discharge: duration of illness, start in day care center, morbidity and use of medicine. 3. At follow-up one year after discharge: morbidity, use of medicine and skin prick tests with allergens. CONCLUSION: Prednisolone treatment had no effect on any of the outcome measures. We find our results in agreement with the largest studies reported earlier; therefore, corticosteroid, whether by systemic route or by inhalation, should not be prescribed to infants with RSV infection.

Prednisolone treatment of respiratory syncytial virus infection: a randomized controlled trial of 147 infants.

OBJECTIVE: To evaluate the effect of systemic prednisolone as an adjunct to conventional treatment with beta2-agonist, respiratory support, and fluid replacement in hospitalized infants <24 months of age with respiratory syncytial virus (RSV) infection. METHODS: The study was randomized, double-blind, and placebo-controlled. During the winter of 1995-1996, 147 infants <2 years of age, hospitalized with RSV infection, were allocated to treatment with either systemic prednisolone mixture 2 mg/kg daily or placebo for 5 days. MAIN OUTCOME MEASURES: The acute effect variables were duration of stay in hospital, use of medicine, and supportive measures while in hospital. At follow-up 1 month after discharge, the acute effect variables were duration of illness, start in day care center, morbidity, and use of medicine. At follow-up 1 year after discharge, the acute effect variables were morbidity, use of medicine, and skin prick tests with allergens. RESULTS: Prednisolone treatment had no effect on any of the outcome measures. CONCLUSIONS: Our randomized prospective study in infants hospitalized with acute RSV infection showed no effect of systemic prednisolone treatment either in the acute state of RSV infection, nor in the follow-up 1 month and 1 year after admission to hospital. We find our results in agreement with the largest studies reported earlier; therefore, corticosteroid, whether by the systemic route or by inhalation, should not be prescribed to infants with RSV infection.

Gray-scale sonographic characterization of aminoglycoside-induced nephrotoxicosis in a canine model.

RATIONALE AND OBJECTIVES: The diagnostic usefulness of gray-scale sonography was evaluated in a canine model of aminoglycoside-induced nephrotoxicosis. METHODS: Sonography was performed before and during the onset and progression of nephrotoxicosis induced by administration of a toxic dosage of gentamicin. Subjective visualization of increased renal cortex echogenicity (IRCE) was objectified with digital image analysis methods. Results of both subjective and objective evaluation were correlated with clinicopathologic tests and renal cortex biopsy obtained concurrently. RESULTS: Subjective visualization of IRCE was associated with significant nephrotoxicosis and was superior to serum creatinine elevation in nephrotoxicity detection. Objective detection of IRCE improved nephrotoxicity detection sensitivity to that of increased urine enzymuria. CONCLUSIONS: Based on the above results, subjective visualization of IRCE in patients with aminoglycoside-induced nephrotoxicity may occur before azotemia and is suggestive of significant renal dysfunction; application of digital image analysis methods may lead to earlier sonographic recognition of nephrotoxicity.

Volumetric high-resolution CT in the diagnosis of interstitial lung disease and bronchiectasis: diagnostic accuracy and radiation dose.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracy and radiation dose of volumetric high-resolution CT in the diagnosis of interstitial lung disease and bronchiectasis when four contiguous sections were acquired at each of three levels. The potential benefits were weighed against the increased radiation dose of multiple scans. SUBJECTS AND METHODS: High-resolution CT scans of four contiguous sections were obtained at each of three locations (the aortic arch, the carina, and 2 cm above the diaphragm) in 50 consecutive patients (mean age, 44 years old) with known or suspected interstitial lung disease or bronchiectasis who were referred for evaluation with high-resolution CT. Each individual scan was analyzed for the presence of motion-induced streaking, blurring, or doubling. The diagnostic information contained in each set of four scans was compared with that contained in the first of the four scans in the set. RESULTS: Motion degraded at least one of the four images in each set in 69 (46%) of 150 volumetric acquisitions. When the full set of four images was considered instead of just the first scan from the set, the number of motion-free studies in patients with suboptimal respiratory suspension was increased by 40% (from 99 to 139). Diagnostic accuracy was improved as more features were identified on contiguous scans: the sensitivity of the first scan compared with that of the complete set of four scans was 84% for the detection of bronchiectasis, 97% for ground-glass opacity, 88% for honeycombing, 88% for septal thickening, and 86% for nodular opacities. Although the integral radiation exposure for a set of four CT scans was 2.8 times that of a single scan obtained with standard technique, peak skin exposure was unchanged. Slightly increased image noise with the reduced technique compromised diagnostic ability in 6% of studies. CONCLUSION: The use of volumetric high-resolution CT increased diagnostic accuracy, particularly for bronchiectasis at the lung bases, without increasing peak skin radiation exposure. With the availability of four contiguous scans per anatomic level, the subjective confidence in interpretation and number of motion-free studies also increased.

[Does achalasia predispose to cancer of the esophagus?]. / Disponerer achalasia til esophaguscancer?

In a follow-up study of 147 patients with achalasia of the esophagus treated by myotomy, 146 patients were traced (58 female and 88 male patients aged 4 to 83 years; median 46 years). The living persons were contacted in writing or by telephone. The mean follow-up time after the operation was 23.2 years (range, six to 41 years). The cause of death was established for 71 patients. There were three postoperative deaths and two deaths following recurrence. In comparison with the Danish population, the 66 remaining patients were found to have a relatively higher cancer mortality (34.9% percent). Contrary to the expected less than one, ten of 23 patients who died of cancer had a malignant tumor in the esophagus. The mortality rate after 30 years was 66.1 percent, 11.9 percent of the deaths caused by esophageal cancer. It is concluded that there is a connection between achalasia and cancer of the esophagus that ought to be considered in the treatment and follow-up of patients with achalasia.

Does achalasia predispose to cancer of the esophagus?

In a follow-up study of 147 patients with achalasia of the esophagus treated by myotomy, 146 patients were traced (58 female and 88 male patients aged 4 to 83 years [median, 46 years]). The living persons were contacted in writing or by telephone. The mean follow-up time after the operation was 23.2 years (range, 6 to 41 years). The cause of death was established for 71 patients. There were three postoperative deaths and two deaths following recurrence. In comparison with the Danish population, the 66 remaining patients were found to have a relatively higher cancer mortality (33.8 percent). Contrary to the expected less than one, ten of 23 patients who died of cancer had a malignant tumor in the esophagus. The mortality rate after 30 years was 66.1 percent, 11.9 percent of the deaths caused by esophageal cancer. It is concluded that there is a connection between achalasia and cancer of the esophagus that ought to be considered in the treatment and follow-up of patients with achalasia.

Follow-up of patients with large bowel cancer: a critical evaluation.

A study of 102 consecutive patients hospitalized for large bowel cancer in the period 1975-1976 was performed to evaluate the hospital's follow-up programme in such cases. The overall five-year survival rate was 32%. New pathologic changes (previously unknown malignant or benign tumour) were found in 42% of the patients. The incidence of new pathology was highest among patients with tumours of Dukes' category C, followed by Dukes' B and A, respectively. The probability of new pathology detection was high in the first two years after primary operation for colonic cancer and thereafter the risk seemed to be small. This phenomenon appeared to be general, irrespective of Duke's stage and whether or not curative resection had been performed. Consumption of hospital resources did not seem to prolong patient survival, most resources being used for patients with short survival. More emphasis should be placed on detection of operable metastatic disease, or curable synchronous and metachronous pathology within the first two years after curative resection for large bowel cancer.