Diagnostics and management of sleep-related respiratory disturbances in children with skeletal dysplasia caused by FGFR3 mutations (achondroplasia and hypochondroplasia).

To evaluate the frequency of clinical indicators for sleep-related respiratory disturbances (SRD) and the polysomnographical manifestations of these disorders in children with skeletal dysplasia caused by FGFR3 mutations. From January 1990 to January 2009, 24 patients (22 achondroplasia, 2 hypochondroplasia; 13 boys, 11 girls; age 8 days to 15 years, median age 3.0 years) were examined, including a semi-structured interview, a clinical examination, and a polysomnographic sleep recording (65 polysomnographic sleep recordings (PSG) in 24 patients). We performed PSG in a subgroup of five patients before and after adenoidectomy (AT) and/or tonsilectomy (TE). Daytime symptoms suggestive of SRD (daytime somnolence, attention and concentration problems, behavioural problems, and pallor) were found in 4/24 patients (16.7%). Sleep-related symptoms (snoring, mouth breathing, cyanosis, observed apneas, excessive sweating, enuresis, problems of initiating and maintaining sleep) were present in 18/24 patients (75%). Prior to the first PSG, 11/24 patients (45.8%) had undergone AT, 1/24 (4.2%) TE, 2/24 (8.3%) adenotonsilectomy (ATE), 3/24 (12.5%) liquor drainage, and 6/24 (25%) a craniocervical decompression operation. Clinical examination prior to PSG revealed hypertrophied tonsils in 11/24 patients (45.8%), disturbed nasal breathing in 8/24 patients (33.3), and enlarged cervical lymph nodes as a sign of chronic tonsillitis in 5/24 patients (20.8%). PSG findings were abnormal in 19/24 patients (79.2%) with a nadir of oxygen saturation (pulse oximetry) below 90% and/or a nadir of transcutaneous partial pressure of oxygen below 45 mmHg. Pathologic PSG findings were found in 10/24 patients (41.7%): obstructive sleep apnea syndrome (OSAS) was diagnosed in 8/24 patients (33.3%), central sleep apnea syndrome in 1/24 patients (4.2%), and hypoventilation in 1/24 patients (4.2%). As a consequence, the following therapeutic interventions were performed: AT in 1/24 patients (4.2%), TE in 2/24 (8.3%), ATE in 2/24 (8.3%), and nasal continuous positive airway pressure (continuous positive airway pressure) and bilevel positive airway pressure therapy (bilevel positive airway pressure), respectively, in 3/24 patients(12.5%). SRD, especially OSAS, represent a complication of clinical and prognostic relevance in children with achondroplasia. We therefore think that not only those children with a history suggestive of SRD, but all achondroplastic children should be evaluated by PSG. At least in a part of these patients, the pathophysiological mechanisms of OSAS are connected with the etiology of achondroplasia. Achondroplastic children with OSAS, who do not benefit from AT and/or TE, should be treated with NCPAP therapy.

Hemodynamic responses to exercise in obese children and adolescents before and after overweight reduction.

OBJECTIVE: To determine the change of hemodynamic parameters in graded bicycle exercise testing in obese children before and after overweight reduction. METHODS: Forty-two obese children (mean age 11 years) and 40 healthy, lean children underwent graded bicycle exercise testing (1, 1.5, 2, 2.5 Watt/kg) recording the heart rate (HR) and blood pressure (BP) before exercise (T1), at maximum load (T2), and 6 min after ending the exercise (T3). Furthermore, the increase of the patient's heart rate within each ramp (I-HR) and the individual maximum load (Watt/kg) were recorded. After participating in an one-year outpatient intervention program for obese children, the study group underwent exercise testing again. Furthermore, we analyzed the lipid and insulin levels in the study group before and after overweight reduction and correlated the changes of the hemodynamic parameters to the changes of the insulin and lipid levels. RESULTS: The obese children had significantly (p<0.05) higher systolic blood pressure values at T1, T2, and T3 as compared to the lean children. The I-HR was significantly (p<0.05) higher in the study group. HR and BP at T1, T2, and T3, and the lipid and insulin values improved significantly in the study group after overweight reduction. The changes of HR and BP did not correlate to the changes of insulin and lipids. CONCLUSION: Compared to lean children, obese children demonstrated a significantly lower exercise capacity of the cardiovascular system, which improved after participating in an obesity intervention program. Overweight reduction influences the hemodynamic and metabolic changes of childhood obesity positively and thereby leads to an improvement of the cardiovascular risk factor profile.

Lifestyle intervention in obese children with non-alcoholic fatty liver disease: 2-year follow-up study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in obese youth. Lifestyle intervention was demonstrated to improve NAFLD but follow-up studies after end of intervention are lacking. Furthermore the necessary degree of overweight reduction for improvement of NAFLD remains unknown. METHODS: We examined standard deviation score of body mass index (SDS-BMI) and transaminases in 152 obese children with NAFLD diagnosed by ultrasound at baseline, at the end of a 1-year intervention and 2 years after baseline. Within-subject changes of these parameters were compared by participation in the intervention based on physical activity, nutrition education and behaviour therapy. RESULTS: In contrast to 43 children without lifestyle intervention, participation in lifestyle intervention (n = 109) was associated with a significant decrease of transaminases and overweight 1 and 2 years after baseline (1 year: alanine transaminase (ALT) -10 U/l (-14 to -6); aspartate transaminase (AST) -5 U/l (-7 to -3); SDS-BMI -0.23 (-0.30 to -0.16); 2 years: ALT -9 U/l (-12 to -6); AST -6 U/l (-7 to -4); SDS-BMI -0.30 (-0.37 to -0.22); data as mean changes and 95% confidence interval compared to baseline). Any degree of overweight reduction was associated with a significant decrease of NAFLD prevalence. The greatest decrease of NAFLD prevalence (1 year: -89% (95% CI -72% to -100%); 2 years: -94% (95% CI -83% to -100%)) was observed in children with the greatest overweight reduction (SDS-BMI decrease >0.5). CONCLUSIONS: Multidisciplinary lifestyle intervention is effective to improve NAFLD even in the 1-year follow-up after the end of intervention. A minimal reduction of overweight led to an improvement of NAFLD. TRIAL REGISTRATION NUMBER: NCT00435734.

Resistin concentrations before and after weight loss in obese children.

OBJECTIVE: The influences of gender, puberty, and obesity on resistin levels and the longitudinal relationships between insulin resistance, weight loss, and resistin have not yet been studied in childhood. METHODS: Age, pubertal stage, gender, weight status (standard deviation score-body mass index (SDS-BMI)), resistin levels, and insulin resistance index calculated by homeostasis model assessment (HOMA) were evaluated in 63 obese children and compared to 36 lean children of same age, gender, and pubertal stage. Furthermore, we analyzed the changes of weight status (SDS-BMI, percentage body fat based on skinfold measurements), waist-to-hip ratio, resistin, and HOMA over a 1-year period in 38 obese children. RESULTS: The resistin levels did not significantly (P = 0.079) differ between obese (median resistin 8.7 ng/ml) and lean children (median resistin 9.7 ng/ml). Resistin concentrations were independent of age and pubertal stage, but girls demonstrated significantly higher resistin levels than boys (P = 0.021). There were no significant correlations between changes of resistin and changes of SDS-BMI (r = 0.14, P = 0.198), changes of percentage body fat (r = -0.01, P = 0.466), changes of waist-to-hip ratio (r = 0.17, P = 0.141), and changes of insulin resistance index (r = 0.01, P = 0.472) over the 1-year period. The weight loss of > or = 0.5 SDS-BMI in 16 children was associated with a significant decrease in HOMA (P = 0.030), while there was no significant change in resistin levels (P = 0.878). CONCLUSIONS: Girls demonstrated higher resistin concentrations than boys. Our data do not support a relationship between resistin, insulin resistance index, and weight status in childhood.

Circulating soluble leptin receptor, leptin, and insulin resistance before and after weight loss in obese children.

OBJECTIVE: To study the relationships between leptin, soluble leptin receptor (sOB-R), and insulin resistance in obese children before and after weight reduction. METHODS: We determined fasting serum leptin, sOB-R, and insulin resistance index (Homeostasis model assessment (HOMA)) in 36 obese children at baseline and 1 y later and compared them to 72 lean children matched for age, gender, and pubertal stage. The changes of leptin (Deltaleptin) and sOB-R (DeltasOB-R) over the 1 y period were correlated to the changes of HOMA (DeltaHOMA), the changes of weight status, and the changes of percentage body fat (Delta%BF) based on skinfold measurements. Multiple linear regression analyses were conducted for the dependent variables Deltaleptin and DeltasOB-R, including DeltaBMI and DeltaHOMA as independent variables adjusted for age, gender, and pubertal stage. Changes of leptin and sOB-R levels were analyzed in 11 obese children after they had lost weight substantially (decrease SDS-BMI>0.5) and compared to 11 obese children without substantial weight loss matched for age, gender, and pubertal stage. RESULTS: Obese children showed significantly (P<0.001) higher leptin and lower sOB-R levels. Deltaleptin correlated significantly to DeltaSDS-BMI (r=0.28, P<0.05), Delta%BF (r=0.44, P<0.05), and DeltaHOMA (r=0.42, P<0.01), while DeltasOB-R correlated significantly to DeltaSDS-BMI (r=-0.42, P<0.01) and Delta%BF (r=-0.47, P<0.01), but not to DeltaHOMA. In contrast to DeltasOB-R, Deltaleptin correlated significantly to DeltaHOMA (P=0.02) in multiple linear regression analysis. Substantial weight loss led to a significant increase in sOB-R (P=0.02) and to a decrease in HOMA (P=0.02). In children without substantial weight loss, there were no changes in sOB-R, while HOMA (P=0.04) and leptin (P=0.02) increased significantly. CONCLUSIONS: The decrease of sOB-R and the increase of leptin levels in obese children normalized after weight loss. Therefore, these changes are consequences rather than the cause of overweight. In contrast to sOB-R, leptin levels are associated with insulin resistance.

Ghrelin levels before and after reduction of overweight due to a low-fat high-carbohydrate diet in obese children and adolescents.

BACKGROUND: There are conflicting results for ghrelin changes in reduction of overweight. Increasing ghrelin levels in weight reduction are considered to be responsible for compensatory mechanisms that make the reduction of overweight unlikely to be sustained. METHODS: We have analyzed fasting serum ghrelin levels, weighed dietary record and, as biochemical markers of clinically relevant reduction of overweight, leptin, adiponectin and insulin levels and insulin resistance measured by homeostasis model assessment (HOMA) at baseline and after a 1-y outpatient weight reduction program based on a high-carbohydrate and low-fat diet in 37 obese children (median age 10 y). We divided these children into two subgroups according to their degree of weight loss (substantial reduction of overweight: decrease in SDS-BMI > or = 0.5). Furthermore, we analyzed ghrelin levels in 16 normal-weight children. RESULTS: Obese children demonstrated significant (P<0.001) lower ghrelin levels compared to normal-weight children. Daily caloric intake (P = 0.004) and percentage fat content decreased significantly (P<0.001), while percentage carbohydrate content increased significantly (P = 0.003) between baseline and 1-y follow-up in the obese children. The substantial reduction of overweight in 16 children (median SDS-BMI = -0.7) was associated with significant changes in insulin resistance (median decrease of HOMA 27%; P = 0.013), insulin (median decrease 25%, P = 0.036), adiponectin (median increase 15%; P = 0.003), and leptin levels (median decrease 19%; P = 0.023), while there were no significant changes in ghrelin levels (median increase 4%; P = 0.326). In the 21 children without substantial reduction of overweight (median SDS-BMI = -0.3), there were no significant changes in insulin resistance and in insulin, adiponectin, leptin and ghrelin levels. CONCLUSIONS: We conclude that in obese children, low-fat high-carbohydrate diet-induced weight loss does not change ghrelin secretion, but significantly decreases leptin levels, increases adiponectin levels and improves insulin resistance determined by significantly decreased insulin resistance indices as well as lowered serum insulin levels.

Clinical characteristics of type 2 diabetes mellitus in overweight European caucasian adolescents.

AIM: To present the clinical features of Type 2 diabetes mellitus (T2DM) in overweight European Caucasian children and adolescents. METHODS: We report the clinical characteristics of 16 non-syndromal overweight European Caucasian adolescents with T2DM (10 boys, 6 girls, SDS-BMI in median +2.8, range +1.6 to +3.4) treated in 5 specialised centres for obesity and diabetes. RESULTS: None of the adolescents manifested with ketoacidosis. 13 were asymptomatic (3 adolescents with polyuria), 12 showed features of metabolic syndrome (dyslipidaemia or hypertension), 8 demonstrated acanthosis nigricans and 12 had relatives with T2DM. 11 adolescents were extremely obese and all patients were pubertal. Mean age at diagnosis was 14.2 years (range 11.0 - 16.9). Median insulin was 19 microU/ml, insulin resistance index (HOMA) 8.5, C-peptide 2.3 ng/ml, HbA1c 6.9 %, fasting blood glucose 176 mg/dl and blood glucose at 2 hours with the oGTT 229 mg/dl at manifestation. Fasting blood glucose and HBA1c were in the normal range in 4 and 6 adolescents respectively, while oGTT always fitted the diagnosis of T2DM. CONCLUSION: Since T2DM occurred in Caucasian overweight adolescents and is frequently asymptomatic, it is essential that clinicians perform diagnostic procedures to identify T2DM in high-risk groups of overweight Caucasian adolescents (extreme obesity, features of metabolic syndrome, relatives with T2DM).

[Evaluation of the training program "OBELDICKS" for obese children and adolescents]. / Evaluation der Schulung "OBELDICKS" für adipöse Kinder und Jugendliche.

UNLABELLED: The evaluation of treatment programs in obese children and adolescents is uncommon but necessary to prove effectiveness and to improve treatment modalities. We studied the effectiveness of the a one-year structured outpatient training programme "OBELDICKS" consisting of physical exercise, nutrition education and behaviour therapy in 132 participants based on the criterions developed by the Institute of Medicine and German Obesity Group (degree of weight reduction, improvement of comorbidity and health behaviour, minimising of side effects). Furthermore, we analysed degree of overweight (SDS-BMI) two years after the end of the outpatient training (n = 60). - 74 % of participants reduced their overweight (intention to treat). The mean reduction of SDS-BMI was 0.43. 34 % of the participants was not obese any more at end of the training. The degree of overweight was significantly (p < 0.001) lower two years after intervention compared to baseline. The comorbidity was improved (significant reduction of the frequencies of hypertension, dyslipidaemia and hyperuricaemia). The nutrition, exercise and eating habits (cognitive control and disinhibition of control) were significantly improved. Side effects were not found. CONCLUSION: The effectiveness based on the criterions of the Institute of Medicine and the German Obesity Group was proven for the outpatient training "OBELDICKS". Long-term weight reduction can be achieved in most of the obese participating children due to this long-term, specialised treatment.

Adiponectin before and after weight loss in obese children.

Adiponectin is decreased in obesity and seems to be involved in insulin resistance. The influences of age, gender, puberty, and weight loss on adiponectin have not been studied in obese children. We measured body fat mass based on skinfold thickness, age, pubertal stage, gender, adiponectin, and insulin resistance (homeostasis model assessment) in 42 obese children. We analyzed adiponectin and homeostasis model assessment 1 yr later in these obese children and separated them into two groups according to degree of weight loss (decrease in sd score for body mass index, >or=0.5 vs. <0.5). Adiponectin was negatively correlated to percentage body fat (r = -0.44; P = 0.002), insulin resistance (r = -0.33; P = 0.016), and age (r = -0.41; P = 0.003). Adiponectin levels were significantly (P = 0.017) higher in pubertal girls compared with boys, but there was no significant difference in prepubertal children in respect to gender (P = 0.833). Adiponectin was significantly (P < 0.001) lower in pubertal compared with prepubertal children. The significant weight loss in 16 children was associated with a significant increase in adiponectin (P = 0.010) and a decrease in insulin resistance (P = 0.013), whereas there were no changes in the 26 children without significant weight loss. Adiponectin levels in obese children were negatively correlated to age, body fat, and insulin resistance and were decreased in puberty. Significant weight loss led to an increase in adiponectin levels and an improvement of insulin resistance.

Changes in the atherogenic risk factor profile according to degree of weight loss.

BACKGROUND: The atherogenic risk factor profile in obese subjects is characterised by hypertension, reduced high density lipoprotein (HDL) cholesterol, increased low density lipoprotein (LDL) cholesterol and triglycerides, and insulin resistance. AIMS: To examine the amount of weight reduction required to improve the atherogenic profile. METHODS: Changes of systolic and diastolic blood pressure, HDL and LDL cholesterol, triglycerides, and insulin resistance, based on the HOMA model over a one year period were studied in obese children, who attended the intervention programme "Obeldicks". The children were divided into four groups according to the change in body mass index standard deviation score (SDS-BMI): group I, increase in SDS-BMI; group II, decrease in SDS-BMI <0.25; group III, decrease in SDS-BMI > or =0.25-<0.5; group IV, decrease in SDS-BMI > or =0.5. RESULTS: A total of 130 children (mean age 10.7 years, range 4-15; mean SDS-BMI 2.5, range 2.0-4.0) were studied. The four groups did not differ in age, gender, or degree of overweight (SDS-BMI). An increasing SDS-BMI (group I: n = 20) was followed by a significant increase in insulin resistance (HOMA). Systolic and diastolic blood pressure, LDL cholesterol, triglycerides, and insulin resistance (HOMA) decreased significantly while HDL cholesterol increased significantly in group IV (n = 37). LDL cholesterol also decreased significantly in group III (n = 40); there was no significant change of the other parameters in groups I, II, and III. CONCLUSION: Over a time period of one year increasing weight in obese children leads to an increase in insulin resistance. Weight loss is associated with an improvement in the atherogenic profile and in insulin resistance, but only if the SDS-BMI decreases by at least 0.5 over a one year period.

Coenzyme Q10 reduces the toxicity of rotenone in neuronal cultures by preserving the mitochondrial membrane potential.

Defects in mitochondrial energy metabolism due to respiratory chain disorders lead to a decrease in mitochondrial membrane potential (DeltaPsim) and induce apoptosis. Since coenzyme Q10 (CoQ10) plays a dual role as an antioxidant and bioenergetic agent in the respiratory chain, it has attracted increasing attention concerning the prevention of apoptosis in mitochondrial diseases. In this study the potential of CoQ10 to antagonize the apoptosis-inducing effects of the respiratory chain inhibitor rotenone was explored by video-enhanced microscopy in SH-SY5Y neuroblastoma cells. The cationic fluorescent dye JC-1 which exhibits potential-dependent accumulation in mitochondria was used as an indicator to monitor changes in DeltaPsim. The relative changes in fluorescence intensity after incubation with rotenone for 15 minutes were calculated. Pre-treatment with CoQ10 (10 or 100 microM) for 48 h led to a significant reduction of rotenone-induced loss of DeltaPsim. These results suggest, that cytoprotection by CoQ10 may be mediated by raising cellular resistance against the initiating steps of apoptosis, namely the decrease of DeltaPsim. Whether these data may provide new directions for the development of neuroprotective strategies has to be investigated in future studies.

Predictors to success in outpatient training in obese children and adolescents.

OBJECTIVE: The treatment of obese children and adolescents is not yet satisfactorily effective. It is not clear which participants can profit by a long-time outpatient therapy. DESIGN: Longitudinal, clinical intervention study based on a 1-y outpatient training programme consisting of physical exercise, nutrition course and behaviour therapy for children and their parents. SUBJECTS: A total of 75 obese children (age 7-15 y; standard duration scores of body mass index(SDS-BMI)+1.9-+3.8). MEASUREMENTS: We characterised the participants as to their willingness to change their behaviour (changes in weight status, number of attempts at therapy, participation in exercise groups), somatic characteristics (BMI of children and family members, gender, age), socioeconomic status (level of education of the children and their parents, working mother), exercise and dietary habits, dietary intake as well as the quality of dietary records. These factors were related to the success of the treatment using a multiple logistic regression. RESULTS: A total of 27 (37%) of the children were unsuccessful after treatment. For 48 (63%) of the children, there was a median weight loss of about 0.4 SDS-BMI (range -0.2 to -1.1). The only significant difference (P<0.0001) between these successful children and the unsuccessful ones was that they had taken part in the exercise groups before training began. CONCLUSION: A training for the obese children and their parents enables the majority of the participants to reduce weight. Previous participation in exercise groups can be considered as a predictor to success of the treatment.

Thyroid hormones before and after weight loss in obesity.

BACKGROUND: Little is known about changes in thyroid function in obese children. An influence of leptin on thyroid hormone synthesis has been proposed. AIMS: To examine thyroid function and leptin concentrations in obese children. METHODS: Triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), and leptin were measured in 118 obese children (aged 4.5-16 years); thyroid function was also determined in 107 healthy children of normal weight. T3, T4, and TSH were analysed in 55 obese children who had achieved weight reduction and in 13 obese children who had not achieved weight reduction after one year based on normal energy diet. RESULTS: TSH, T3, and T4 were significantly higher in obese children compared to those of normal weight. Twelve per cent of the obese children had TSH, 15% had T3, and 11% had T4 concentrations above the twofold standard deviation of normal weight children. The degree of overweight correlated with T3, T4, and TSH. Thyroid hormones did not correlate significantly with leptin. A reduction in overweight showed a significant decrease in T3, T4, and leptin serum concentrations, but there was no significant change in TSH. CONCLUSION: Peripheral thyroid hormones (T3, T4) and TSH are moderately increased in obese children; weight reduction leads to a long term decrease in the peripheral thyroid hormones but not in TSH. There is no necessity to treat the increased serum TSH.

[Pain control in German pediatric oncology. An inventory]. / Schmerzkontrolle in der pädiatrischen onkologie in Deutschland. Eine Bestandsaufnahme]

As part of a nationwide quality improvement programme, our aim is the assessment of the quality of pain control in German paediatric oncology to tailor the intervention to specific needs. Here we report on the results of a questionnaire-based nationwide survey which addressed the head of the department, one supervising physician, one ward physician, one nurse, and one psychologist/social worker in each of the 76 german paediatric oncology departments. 210/380 health care professionals of 60/76 departments responded to the survey. According to 17% of the physicians (41% of the nurses, p = 0.004) there still exists '(very) often' pain despite pain therapy. Procedures are seen as the main causes of pain. According to 58% of the heads of the department and supervising physician (35% of the nurses and ward physicians, p = 0.005), faces scales are regularly used to score pain intensity. In 80% of the departments a written therapy protocol addressing procedure-related, or postoperative pain is lacking. When larger and smaller departments are compared, in former ones the significantly preferred routes for opioid administration are i. v., or oral for slow release preparations (p = 0.01). The i. m. route is exclusively used in smaller departments. In the treatment of neuropathic pain, only 5% of the physicians regard morphine, but 25% of them regard antidepressants and antiepileptics as ineffective. Only 72% of the physicians (39% of the nurses, p = 0.001) are convinced that during opioid-based pain therapy addiction 'seldom/never' developes. Nurses are less satisfied with pain therapy than are physicians, and they feel more frequently that pain therapy '(very) often' starts too late (p <0.005). The questionnaire revealed obvious deficits in both physicians' and nurses' knowledge regarding pain therapy. Deficits were also addressed by the health care professionals themselves.

[Ambulant training programs for obese children. Criterions of comparison for the development of valid therapy recommendations]. / Ambulante Adipositasschulungen im Kindesalter - Vergleichskriterien zur Entwicklung validierter Behandlungsempfehlungen.

Valid knowledge concerning structure and contents of an ambulant training program for obese children and adolescents suggested by experts is still missing. In 1999/2000, we assessed a survey based on defined criterions in the "Arbeitsgemeinschaft für pädiatrische Diäthetik (APD)" and investigated the literature to cover and to compare based on defined criterions the spectrum of ambulant treatment models in Germany to advance guidelines for therapy in obese children. 13 ambulant training programs were detected. Training of children aged 8 to 12 years and their parents based on diet, behavioural treatment and sports therapy over couple of months without great experiences and without complete financing by health insurance were in common. Time volume of the training programs widely varies. In the seven evaluated training programs, up to one third of the patients broke off, while more than two third of the children successfully finished the training programs. The comparison of the programs failed on missing data concerning the collective, missing or different evaluation criteria, sometimes low number of patients and not standardised calculation of overweight. The survey reflects the often low experiences and the heterogeneous, insufficient evaluation of ambulant treatment models in Germany and demonstrates the great requirement of research. The schedule of criterions facilitates the comparison of programs to develop valid ambulant training programs for obese children.

Short stature in a mother and daughter caused by familial der(X)t(X;X)(p22.1-3;q26).

Deletions of the terminal Xp regions, including the short-stature homeobox (SHOX) gene, were described in families with hereditary Turner syndrome and Léri-Weill syndrome. We report on a 10-2/12-year-old girl and her 37-year-old mother with short stature and no other phenotypic symptoms. In the daugther, additional chromosome material was detected in the pseudoautosomal region of one X chromosome (46,X,add(Xp.22.3)) by chromosome banding analysis. The elongation of the X chromosome consisted of Giemsa dark and bright bands with a length one-fifth of the size of Xp. The karyotype of the mother demonstrated chromosome mosaicism with three cell lines (46,X,add(X)(p22.3) [89]; 45,X [8]; and 47,X,add(X)(p22.3), add(X)(p22.3) [2]). In both daughter and mother, fluorescence in situ hybridization (FISH), together with data from G banding, identified the breakpoints in Xp22.1-3 and Xq26, resulting in a partial trisomy of the terminal region of Xq (Xq26-qter) and a monosomy of the pseudoautosomal region (Xp22.3) with the SHOX gene and the proximal region Xp22.1-3, including the steroidsulfatase gene (STS) and the Kallmann syndrome region. The derivative X chromosome was defined as ish.der(X)t(X;X)(p22.1-3;q26)(yWXD2540-, F20cos-, STS-, 60C10-, 959D10-, 2771+, cos9++). In daughter and mother, the monosomy of region Xp22.1-3 is compatible with fertility and does not cause any other somatic stigmata of the Turner syndrome or Léri-Weill syndrome, except for short stature due to monosomy of the SHOX gene.

Chronic osteomyelitis in childhood: is surgery always indicated?

BACKGROUND: Presently, most children with chronic osteomyelitis undergo surgery with the inherent risk of damage to their growth plate. We demonstrate a treatment regimen based on imaging procedures focussing on antibiotics in order to reduce the rate of surgical interventions. PATIENTS AND METHODS: We retrospectively evaluated all 11 patients with clinically suspected chronic osteomyelitis who were treated at our institution from 1989 to 1995. Patients underwent open biopsy and surgical treatment only if imaging procedures showed signs indistinguishable from malignancy, or if they were highly suggestive for the presence of pus, joint infection or osteonecrosis. The patients were followed up for a minimum of 3 years. RESULTS: All five patients treated solely with antibiotics recovered completely. Three patients were subjected to open biopsy and surgical treatment since they showed radiological signs indistinguishable from malignancy, and two patients due to pus or osteonecrosis. In follow-up, there was one relapse of chronic osteomyelitis 11 months after the first treatment course with surgery and antibiotics. One patient suffering from Ewing's sarcoma as detected by open biopsy was excluded. CONCLUSION: Our diagnostic procedure was useful to reduce the rate of surgery. Surgical treatment of chronic osteomyelitis is not always neccessary especially in cases of missing necrosis, joint infection and abscess as demonstrated by the complete recovery of our patients treated solely with antibiotics.

Diagnosis and management of juvenile hyperthyroidism in Germany: a retrospective multicenter study.

This retrospective multicenter study was designed to survey the management of childhood and adolescent hyperthyroidism in six pediatric endocrinological units in Germany. Fifty-six patients aged between 1.1 and 17.0 yr (median 10.5 yr) were enrolled. Data were collected retrospectively from the patients' records by a trained pediatric endocrinologist using standardized questionnaires. After the diagnosis of hyperthyroidism was established on the basis of clinical and biological findings, treatment with antithyroid drugs (carbimazole, methimazole, thiamazole, propylthiouracil) was started in all patients. In 55/56 of the patients treated with antithyroid drugs, euthyroidism was achieved (98%). However, 26 patients (47%) were still hyperthyroid after discontinuation of the medication. Eight children with continued hyperthyroidism ultimately underwent subtotal thyroidectomy 13-136 (median 28) months after the initial diagnosis. Management principles of the participating centers were heterogeneous. As a consequence, prospective multicenter studies are urgently needed to establish clear standards for the diagnosis and therapy of childhood hyperthyroidism.