Post-thoracotomy Pain Syndrome.

PURPOSE OF REVIEW: This article reviews PTPS demographics, diagnosis, pathophysiology, surgical and anesthetic techniques, and their role in preventing PTPS along with updated treatment options. RECENT FINDINGS: Post-thoracotomy pain syndrome (PTPS) can be incapacitating. The neuropathic type pain of PTPS is along the incision site and persists at least 2 months postoperatively. There is a wide reported range of prevalence of PTPS. There are several risk factors that have been identified including surgical technique and younger age. Several surgical and anesthetic techniques have been trialed to reduce pain after thoracotomy. Multimodal pain control is the suggested long-term treatment plan for patients with PTPS. There are several factors that can be modified to reduce pain and incidence of PTPS during the perioperative period and the use of multimodal analgesia is suggested for the treatment of PTPS.

Understanding the causes of obesity in children with trisomy 21: hyperphagia vs physical inactivity.

BACKGROUND: Individuals with intellectual disabilities are at increased risk of becoming overweight or obese. This is particularly evident in people with trisomy 21 and Prader-Willi syndrome (PWS). Although metabolic factors are known to contribute to obesity in trisomy 21 and hyperphagia plays a primary role in PWS, hyperphagia has not yet been investigated as a possible contributing factor to obesity in trisomy 21. METHODS: Participants comprised three diagnostic groups: trisomy 21 (T21 group), PWS (PWS group) and lifestyle-related obesity (LRO group). They were required to be aged 6-18 years and have a body mass index over the 85th percentile for age and gender. A parent of each participant completed the Hyperphagia Questionnaire and the Children's Leisure Activity Study Survey. Mean scores for each domain and across all domains of the Hyperphagia Questionnaire and the Children's Leisure Activity Study Survey were compared between diagnostic groups using linear regression analysis. RESULTS: The study group consisted of 52 young people (23 men and 29 women) aged 6-18 years (mean 12.5 years; T21 group n = 17, PWS group n = 16 and LRO group n = 19). As hypothesised, the PWS group had the highest mean scores across all domains of the Hyperphagia Questionnaire, and the LRO group had the lowest. Food-seeking behaviour was more pronounced in the PWS group than the T21 group (mean score 13.2 vs. 8.6, p = 0.008). The LRO group spent more hours per week engaged in physical activity (14.7) in comparison with the other groups (9.6 and 9.7), whereas between the groups, differences in time spent in sedentary activities were less pronounced. CONCLUSIONS: Preoccupation with food and low levels of physical activity may contribute to the development of overweight and obesity in some individuals with trisomy 21. These factors warrant consideration in the clinical context.

Annular Lichenoid Dermatitis of Youth: A Report of 2 Cases and a Review of the Literature. / Dermatitis anular liquenoide de la infancia. Descripción de 2 casos y revisión de la literatura.

Annular lichenoid dermatitis of youth is a lichenoid dermatosis of unknown etiology. It mostly affects children and adolescents and has well-defined clinical and histological characteristics that permit a diagnosis. We present 2 new cases of annular lichenoid dermatitis of youth with classical clinical features in 2 girls, aged 2 and 4 years. The histologic findings, however, differed from those reported in the literature in that the lichenoid inflammatory infiltrate was located primarily at the top of the dermal papillae and not at the tips of the rete ridges. In both cases, the lesions regressed spontaneously without treatment.

IGFBP-2 inhibits adipogenesis and lipogenesis in human visceral, but not subcutaneous, adipocytes.

BACKGROUND/OBJECTIVE: IGF-binding protein (IGFBP)-2 is the principal IGFBP produced by white adipocytes during adipogenesis, and circulating levels are reduced in obesity. Overexpression of IGFBP-2 in transgenic mice prevents obesity, but depot-specific effects of IGFBP-2 on adipo/lipogenesis are unknown. The present study aimed to investigate whether IGFBP-2 affects adipo/lipogenesis in a depot-specific manner and explore potential mechanisms. METHODS: Following adipocyte characterisation, IGFBP-2 levels were measured from human subcutaneous and visceral preadipocytes, and IGFBP-2 dose-responses were then undertaken with exogenous IGFBP-2 in an in vitro IGF-I-free system to examine adipo/lipogenesis. Following this, both types of adipocytes were transfected with human siRNA IGFBP-2 to assess auto-/para-/intra-crine effects, with and without additional add-back IGFBP-2. To elucidate the potential mechanisms, visceral preadipocytes were treated with either wild-type or Heparin Binding Domain (HBD)-mutant IGFBP-2 (which is unable to bind to cell-surface components), and experiments were also undertaken using Echistatin (an integrin receptor blocker). Outcomes included gene expression profiles, protein levels and phosphorylation and lipid staining. RESULTS: Human visceral adipocytes produced significantly more IGFBP-2 than subcutaneous adipocytes. Subsequent dose-responses to IGFBP-2 demonstrated significant reductions in adipo/lipogenesis in visceral, but not subcutaneous, adipocytes in response to increasing IGFBP-2. Silencing IGFBP-2 resulted in exaggerated adipo/lipogenesis in visceral, but not subcutaneous, adipocytes, an effect completely inhibited by add-back IGFBP-2. These effects occurred in the absence of changes in IGF-I levels. HBD-mutant IGFBP-2 had reduced effects compared with wild-type IGFBP-2. Wild-type IGFBP-2 increased phosphorylation of focal adhesion kinase (FAK) and decreased phosphatase and tensin homolog (PTEN) levels, suggestive of integrin-mediated signalling. Blockade of this signalling, using Echistatin, completely negated the effects of IGFBP-2 on visceral adipo/lipogenesis. CONCLUSION: IGFBP-2 inhibits both adipogenesis and lipogenesis in visceral, but not subcutaneous, adipocytes. This depot-specific impairment appears to be independent of IGF-I and involves cell-surface association of IGFBP-2 and activation of integrin signalling pathways.

Longitudinal investigation of adenovirus 36 seropositivity and human obesity: the Cardiovascular Risk in Young Finns Study.

BACKGROUND/OBJECTIVES: Adenovirus-36 (Adv-36) infection is associated with exaggerated adipogenesis in cell culture and the development of obesity in animal models and humans, but a causal relationship remains unproven. Our objective was to determine whether serological evidence of Adv-36 infection in childhood and/or adulthood is associated with adult obesity. SUBJECTS/METHODS: Paired plasma concentrations of Adv-36 antibodies were measured by a novel enzyme-linked immunosorbent assay in a subgroup (n=449) of the Cardiovascular Risk in Young Finns Study in childhood (mean age 11.9 years) and adulthood (mean age 41.3 years). The study group included (1) individuals who had maintained normal-weight status (2) those who became obese adults from a normal-weight status in childhood and (3) those that were overweight/obese as a child and obese as an adult. RESULTS: Mean (s.d.) time between baseline and follow-up was 29.4 (3.2) years (range 21-31 years). A total of 24.4% of individuals who were normal weight throughout life were seropositive for Adv-36 during child and/or adulthood as compared with 32.3% of those who became obese adults (P=0.11). Those who became obese in adulthood were more likely to be Adv-36 seropositive as adults compared with those who maintained normal weight (21.3% vs. 11.6%, P=0.02). This difference was mediated by a decline in Adv-36 seropositivity between child and adulthood in those maintaining normal weight. No differences were observed in body mass index across the life course, nor in waist circumference in adult life, between those who were Adv-36 seronegative or seropositive at any age. CONCLUSIONS: Individuals who gained weight across the life course were more likely to be Adv-36 seropositive in adult life than those who did not gain weight. However, analysis of change in weight status in relation to Adv-36 positivity did not support a causal role for Adv-36 in the development of obesity.

The role of pharmacotherapy in the prevention and treatment of paediatric metabolic syndrome--Implications for long-term health: part of a series on Pediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni.

The metabolic syndrome (MetS) is defined as a clustering of risk factors predisposing to the future development of cardiovascular disease and Type 2 diabetes mellitus (T2DM). Its clinical relevance, above and beyond recognition and treatment of each of the component parts, is still hotly debated--especially within paediatric medicine. Prevention and treatment strategies for adult MetS focus on weight management, as obesity and insulin resistance are known to be at the central axis of the definition, alongside pharmacotherapy of integrally linked conditions such as hypertension and dyslipidaemia. In children and adolescents, however, opportunities for pharmacotherapy are currently limited and interventions aimed at weight management remain the sole treatment paradigm in the majority of cases. This is primarily due to a lack of long-term data relating to the degree of cardiovascular disease and T2DM risk from paediatric MetS, as well as concerns relating to safety and side effect profiles of currently available pharmacotherapies in those who are still growing and developing. Coupled with continuing concern about the recently recognised adverse effects of past and proposed anti-obesity drugs, this indicates that a new era of pharmacotherapy for paediatric MetS is unlikely to be imminent. In fact, the overall paucity of effective current interventions for paediatric MetS is concerning, especially given the fact that approximately 25-33% of all obese paediatric patients likely harbour the condition. It is therefore essential at the present time to concentrate efforts on properly testing the safety and efficacy of currently available products in well-constructed randomised controlled trials in obese adolescents. However, not all obese children and adolescents appear equally at-risk of long-term, weight-related morbidity and a change in emphasis is possibly warranted--one that moves away from simple weight reduction for all and more to a model of reducing long-term risk of cardiovascular disease and T2DM in those at greatest metabolic risk.

Patellofemoral pain and the mechanomyographic responses of the vastus lateralis and vastus medialis muscles.

The purpose of this investigation was to examine the influence of patellofemoral pain (PFP) on the amplitude of the mechanomyographic (MMG) and electromyographic (EMG) signals from the vastus lateralis and vastus medialis muscles of the quadriceps femoris. Nine females reporting current signs and symptoms of PFP and 8 healthy females service as the control (CTL) group volunteered to participate in this study. Participants completed maximal and submaximal (25, 50, 75% MVC) isometric muscle actions of the quadriceps femoris at a leg flexion angle of 45 degrees below the horizontal plane of the lever arm. The involved limb for the PFP group and the dominant limb for the CTL group were selected for testing and all submaximal force levels were randomized. There was no (p > 0.05) group difference in EMG amplitude response for any muscle at any % MVC level. For the MMG amplitude, however, there was a main effect (p < 0.05) for group where the control group demonstrated greater MMG amplitude for each muscle. These findings suggest that the presence of PFP influenced mechanical aspect of muscle function as measured by MMG, but not the electrical properties (EMG). MMG may provide unique insight into the intrinsic effects on muscle function due to PFP.

Elevated glucose concentrations during an oral glucose tolerance test are associated with the presence of metabolic syndrome in childhood obesity.

AIMS: To investigate whether changes in glucose concentrations during an OGTT in obese children reflect the presence of peripheral insulin resistance and/or cardiovascular risk factors more closely than single measurements of fasting plasma glucose (FPG). METHODS: One hundred and twenty-two obese children attending our Paediatric Obesity Service underwent formal OGTTs, following the measurement of blood pressure and fasting levels of insulin, glucose and lipid profiles in the majority. Fasting insulin was used as a surrogate measure of insulin sensitivity. Three different child-specific definitions for metabolic syndrome were used to identify clustering of cardiovascular risk factors in 65 of these children. RESULTS: In the whole group, 10.7% had IGT but changes in glucose during the OGTT were not influenced by age, sex, pubertal status or raw (or age- and sex-adjusted) body mass index (BMI). During the OGTT, FPG, glucose at 60 min and area under the glucose curve correlated highly with fasting insulin. Children with metabolic syndrome (defined using any of three definitions) had comparable FPG levels to those without metabolic syndrome, but they demonstrated significantly elevated glucose levels at 60 min. On sub-group analysis, obese children with normal carbohydrate metabolism were significantly more likely to have a 1 h glucose level > or = 7.8 mmol/l if they had metabolic syndrome (P = 0.026). CONCLUSIONS: These data suggest that an elevated 1 h post-load glucose measurement is seen in obese children who have a coexistent clustering of cardiovascular risk factors.

Childhood obesity.

The prevalence of childhood obesity continues to increase worldwide. Its presence is associated with significant adverse effects on health including an increased propensity to type II diabetes, cardiovascular, respiratory, and liver disease. In the vast majority of children, obesity is lifestyle-related, yet there is a dearth of evidence on how to best develop effective prevention and treatment strategies. This review outlines the importance of childhood and adolescent growth on long-term health, the definitions used to define obesity in children (along with up-to-date prevalence data), causes and consequences, and aspects of prevention and management.

Serum IGFBP-2 levels are associated with reduced insulin sensitivity in obese children.

Insulin-like growth factor binding protein 2 (IGFBP-2) may represent a critical link between body composition and insulin sensitivity. We investigated the relationship between circulating IGFBP-2 levels, body composition, insulin sensitivity, energy intake and physical activity in children with obesity. Children were recruited via the Weight Management Service at the Royal Children's Hospital, Melbourne, as part of the Childhood Overweight BioRepository of Australia (COBRA). Comprehensive anthropometric, biochemical and environmental data were collected and compared to serum IGFBP-2 levels (measured by enzyme-linked immunosorbent assay). Multiple regression modelling was used to assess the influence of circulating IGFBP-2 levels on anthropometric and biochemical measures. One hundred and ninety-four children were included in this study (46% male). Circulating IGFBP-2 negatively correlated with age, anthropometric measures, blood pressure and insulin concentration. Positive associations were observed between insulin sensitivity index-homeostasis model assessment (ISI-HOMA) and serum IGFBP-2. In multiple regression modelling, IGFBP-2 significantly contributes to variance in systolic blood pressure (-19%, P < 0.05), circulating triglycerides (-16%, P < 0.05) and ISI-HOMA (18%, P < 0.05). No associations were observed between dietary energy intake or physical activity and IGFBP-2 levels. Circulating IGFBP-2 levels in children with obesity correlate inversely with body mass and markers of metabolic dysfunction, and positively with insulin sensitivity. These findings suggest that reduced levels of IGFBP-2 may play an important role in the pathogenesis of obesity complications in early life.

What does a diagnostic label of 'polycystic ovary syndrome' really mean in adolescence? A review of current practice recommendations.

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, with many women initially presenting during adolescence. Diagnosis during this period is particularly challenging, yet many emphasize the importance of an early diagnosis given the long-term metabolic and reproductive health consequences associated with the syndrome. The objective of this study was to review the current literature to determine whether the diagnostic label 'PCOS' is necessary to effectively manage adolescent girls presenting with features of the syndrome. A literature search was conducted (PubMed, Medline, Informit Health and the Cochrane Database of Systematic Reviews) identifying papers addressing the diagnosis and management of PCOS during adolescence. Articles were selected based on date of publication, relevance of material and the quality of evidence presented. A total of 427 papers were screened, with 40 of these selected from the initial search. A subsequent 154 were included from manual review of reference lists from key papers identified in the initial search. Current guidelines recommend treating the individual manifestations of PCOS. In doing so, there is good evidence identifying that this approach adequately targets the underlying metabolic and reproductive changes associated with the syndrome. This suggests that providing a diagnostic label of PCOS is not actually necessary to effectively manage adolescent girls with features of this syndrome.

The effect of antidepressants and antipsychotics on weight gain in children and adolescents.

Psychiatric illness in the paediatric population is increasing and the weight effect of medications for these problems is often unclear. A comprehensive literature search was undertaken to identify studies reporting weight in relation to antipsychotic and antidepressant use in children and adolescents. From 636 articles, 42 were selected for review. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) do not cause weight gain and may lead to improvements in weight status over the short, but not, long term. Antipsychotics were generally associated with weight gain. In drug comparison studies, risperidone had a larger weight gain effect than lithium, divalproex sodium and pimozide. Studies assessing the weight-protective effects of augmentation therapy with metformin or topiramate show less weight gain with addition of these agents. In conclusion, prescribing of SSRIs and SNRIs may be associated with improvements in weight status in children and adolescents but trials assessing their use in obesity, outside of established psychiatric illness, are limited and still experimental. Youth prescribed antipsychotic medication should be monitored for exaggerated weight gain and in those where obesity is a pre-existing concern agents other than olanzapine, clozapine and risperidone may be advantageous.

IGFBP-2: The dark horse in metabolism and cancer.

The ubiquitous nature of the IGF system, expressed early in embryonic development throughout postnatal and adult life, indicates a key role for this system in human biology. Studies of transgenic mice over-expressing components of the IGF system or mice with disruptions of the same genes have clearly shown that the IGF system plays an important role in vivo. The activity of the IGF ligands, elicited via their receptors and transduced by various intracellular signal pathways, is modulated by the IGFBPs. Among all the IGFBPs, IGFBP-2 has been implicated in the regulation of IGF activity in the nervous system, peripheral tissue and organs. Besides binding to IGFs in the circulation, these IGF-regulatory activities of IGFBP-2 involve interactions with components of the extracellular matrix and cell surface proteoglycans and integrin receptors. In addition to these "local" peri-cellular activities of IGFBP-2, it became evident that IGFBP-2 exerts other key functions within the cell. In the cytoplasm IGFBP-2, most likely in the absence of the IGFs, interacts with regulatory proteins including transcription factors and cytoplasm-nuclear transporters. Within the nucleus IGFBP-2, directly or indirectly, promotes transcriptional activation of specific genes. These intrinsic activities of IGFBP-2 are mediated via specific functional domains. All of these IGFBP-2 activities, intrinsic or dependent on IGFs, contribute to its functional roles in growth/development, metabolism and malignancy as evidenced by studies in IGFBP-2 animal models and also by many in vitro studies. Finally, preclinical studies have demonstrated that IGFBP-2 administration can be beneficial in improving metabolic responses (inhibition of adipogenesis and enhanced insulin sensitivity), while blockade of IGFBP-2 appears to be an effective approach to inhibiting tumor growth and metastasis.

An assessment of pancreatic endocrine function and insulin sensitivity in patients with transient neonatal diabetes in remission.

AIMS: To examine derived indices of beta cell function, peripheral insulin sensitivity, and the pancreatic response to intravenous glucose loading in children with a previous history of transient neonatal diabetes currently in remission, repeated after a period of two or more years. METHODS: The standard intravenous glucose tolerance test (IVGTT) was used to measure the first phase insulin response (FPIR) cumulatively at one and three minutes. In addition, fasting insulin and glucose values were used to estimate insulinogenic indices (beta cell function) and QUICKI (insulin sensitivity). PATIENTS: Six patients with known previous transient neonatal diabetes currently in remission with no exogenous insulin requirement were tested. Control data from 15 children of a similar age were available for derived fasting indices of beta cell functional capacity and insulin sensitivity. RESULTS: One child had a subnormal insulin secretory response to intravenous glucose that remained abnormal two and four years later. The other children had relatively normal or entirely normal responses over two years. Measures of beta cell function and insulin sensitivity in the fasting state showed comparable results to those obtained from normal controls. CONCLUSIONS: Most children with transient neonatal diabetes in remission have no evidence of beta cell dysfunction or insulin resistance in the fasting state, although they might have been expected to show subtle defects given the tendency to relapse in adolescence. Measures of insulin response to intravenous glucose loading are often normal but suggest future recurrence if profoundly abnormal.

Results and complications of laparoscopic cholecystectomy in childhood.

BACKGROUND: The purpose of our study was to evaluate the results and complications of laparoscopic cholecystectomy in a case series of 110 infants. METHODS: Over a 5-year period (1993-98), we performed laparoscopic cholecystectomy in 110 pediatric patients. Surgery was performed at different institutions by three different surgeons. The patient population was composed of 69 girls and 41 boys; their ages ranged from 1 to 16 years (median, 8.5). All of the 110 children had symptomatic cholelithiasis, which was confirmed at ultrasound examination. An associated pathology was present in 27 patients (sickle cell disease in 17 cases, hereditary spherocytosis in seven cases, thalassemia in three); the other 83 infants were affected by idiopathic cholelithiasis. In 107 patients, the operation was performed using four ports; in three patients, it was done using five ports. In three patients, we also performed a concomitant splenectomy. RESULTS: Median duration of simple cholecystectomy was 45 min (range, 25-75) and hospital stay ranged from 1 to 10 days (median, 2). Only 15 children required drainage. We had 17 complications in our series (15.5%), including a gallbladder perforation during dissection in 11 patients, a fall of stones into the abdominal cavity during extraction in one patient, and a trocar orifice infection in the postoperative period in five patients. At a maximum follow-up of five years (range, 1-5), all patients were doing well. CONCLUSION: Laparoscopic cholecystectomy in children seems to be as effective as open surgery in cases of symptomatic cholelithiasis. In pediatric patients more than in adults, an accurate and precise dissection and a sound knowledge of possible congenital biliary abnormalities are essential to avoid any kind of complication.

Convergence and Consistency of Fuzzy c-means/ISODATA Algorithms.

The fuzzy c-means/ISODATA algorithm is usually described in terms of clustering a finite data set. An equivalent point of view is that the algorithm clusters the support points of a finite-support probability distribution. Motivated by recent work on the hard version of the algorithm, this paper extends the definition to arbitrary distributions and considers asymptotic properties. It is shown that fixed points of the algorithm are stationary points of the fuzzy objective functional, and vice versa. When the algorithm is iteratively applied to an initial prototype set, the sequence of prototype sets produced approaches the set of fixed points. If an unknown distribution is approximated by the empirical distribution of stationary, ergodic observations, then as the number of observations grows large, fixed points of the algorithm based on the empirical distribution approach fixed points of the algorithm based on the true distribution. Furthermore, with respect to minimizing the fuzzy objective functional, the algorithm based on the empirical distribution is asymptotically at least as good as the algorithm based on the true distribution.