A 343 Italian cohort of patients analysed with array-comparative genomic hybridization: unsolved problems and genetic counselling difficulties.

BACKGROUND: The recent introduction of microarrays for genetic analyses has allowed higher etiological diagnostic rates in patient with intellectual disability (ID), autism spectrum disorders (ASD), epilepsy and multiple congenital anomalies (MCA), because of its resolution. This approach still results of high complexity and some limitations have been reported. In fact, it discloses several variants of unknown significance (VOUS) or incidental findings. In all cases, a massive amount of data is generated, because of this, the analysis and the interpretation is very difficult and often without a definitive conclusion. METHOD: We analysed an Italian cohort of 343 patients with ID, MCA and ASD by array-comparative genomic hybridization. The purpose of this work was to consider the proportion of the chromosomal abnormalities in such cohort and to assess the distribution of the different type of the chromosomal abnormalities concerning their pathogenic significance, their origin and their correlation to these clinical phenotypes. RESULTS: Array-comparative genomic hybridization analysis revealed 76 positive results. Abnormalities were detected in 27.8% of patients with ID, 11.1% with ASD, 10.7% with epilepsy and 19.4% with multiple congenital anomalies. The anomalies were classified in three major groups: group 1 (27 patients) with pathogenic alterations (P group); group 2 (34 patients) with VOUS potentially pathogenic (PP group); and group 3 (13 patients) with VOUS potentially benign (PB group). As expected, comparing the diagnostic groups, we observed a greater number of deletions in the P group and that all the abnormalities of the PB group were inherited. CONCLUSIONS: Our retrospective study resulted in confirming the high detection rate of microarrays. CNV classification remains a complex procedure. The difficulty in CNV classification points out the importance of the patient selection, helping the interpretation of the molecular cytogenetic results.

Food protein-induced enterocolitis syndrome in children: what's known? What's new?

Summary: Food protein-induced enterocolitis syndrome (FPIES) is an under-recognized and frequently misdiagnosed non-IgE mediated food allergy syndrome. Affected infants show gastrointestinal symptoms few hours after ingestion of the incriminating food. Pathophysiology of FPIES has not yet been clearly defined and needs further characterization. The common allergy tests are not helpful for this disorder and tests for food specific IgE are usually negative. A diagnostic oral food challenge (OFC) is the method to confirm the diagnosis of FPIES. This review summarizes what is known about epidemiology, pathophysiology, clinical characteristics and diagnosis and what's new about therapeutic options of FPIES.

Association between markers of endothelial dysfunction and early signs of renal dysfunction in pediatric obesity and type 1 diabetes.

BACKGROUND: To evaluate whether circulating markers of endothelial dysfunction, such as intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO), are increased in youth with obesity and in those with type 1 diabetes (T1D) at similar levels, and whether their levels are associated with markers of renal function. METHODS: A total of 60 obese youth [M/F: 30/30, age: 12.5 ± 2.8 yr; body mass index (BMI) z-score: 2.26 ± 0.46], 30 with T1D (M/F: 15/15; age: 12.9 ± 2.4 yr; BMI z-score: 0.45 ± 0.77), and 30 healthy controls (M/F: 15/15, age: 12.4 ± 3.3 yr, BMI z-score: -0.25 ± 0.56) were recruited. Anthropometric measurements were assessed and a blood sample was collected to measure ICAM-1, MPO, creatinine, cystatin C and lipid levels. A 24-h urine collection was obtained for assessing albumin excretion rate (AER). RESULTS: Levels of ICAM-1 and MPO were significantly higher in obese [ICAM-1: 0.606 (0.460-1.033) µg/mL; MPO: 136.6 (69.7-220.8) ng/mL] and T1D children [ICAM-1: 0.729 (0.507-0.990) µg/mL; MPO: 139.5 (51.0-321.3) ng/mL] compared with control children [ICAM-1: 0.395 (0.272-0.596) µg/mL MPO: 41.3 (39.7-106.9) ng/mL], whereas no significant difference was found between T1D and obese children. BMI z-score was significantly associated with ICAM-1 (ß = 0.21, p = 0.02) and MPO (ß = 0.41, p < 0.001). A statistically significant association was also found between ICAM-1 and markers of renal function (AER: ß = 0.21, p = 0.03; e-GFR: ß = 0.19, p = 0.04), after adjusting for BMI. CONCLUSIONS: Obese children have increased markers of endothelial dysfunction and early signs of renal damage, similarly to children with T1D, confirming obesity to be a cardiovascular risk factor as T1D. The association between ICAM-1 with e-GFR and AER confirm the known the association between general endothelial and renal dysfunction.

Validation of the Italian Quality of Life in Short Stature Youth (QoLISSY) questionnaire.

PURPOSE: The Quality of Life in Short Stature Youth (QoLISSY) questionnaire is a disease-specific instrument developed to assess health-related quality of life (HrQoL) in children with short stature. While the original instrument was simultaneously developed in five European countries, this study describes the results of the Italian QoLISSY translation, cultural adaptation, and validation. METHODS: Focus group discussions and a cognitive debriefing process with children (N = 12) diagnosed with growth hormone deficiency or idiopathic short stature and one parent each, as well as parents of younger children (N = 20) were conducted to examine the linguistic and content validity of the Italian version. Psychometric testing was performed using data from the subsequent field- and re-test (N = 32). RESULTS: The results of the qualitative testing of the Italian sample revealed comparability of content to data of the original five European countries. The following field- and re-test results were psychometrically satisfactory including good item and scale operating characteristics, sufficient evidence of reliability, and acceptable evidence of construct validity. CONCLUSION: In conclusion, the Italian QoLISSY HrQoL-dimensions are comparable to other European countries. The psychometric quality of the Italian QoLISSY version is satisfactory and the instrument is ready for use in Italian patients and their parents.

One-hour post-load plasma glucose levels associated with decreased insulin sensitivity and secretion and early makers of cardiometabolic risk.

PURPOSE: Obese adults with normal glucose tolerance (NGT) but with 1-hour post-load plasma glucose (1hPG) ≥ 155 mg/dl are at higher risk of developing type 2 diabetes (T2D) and cardiometabolic complications. Little information is available for the pediatric population, where recently, a lower cutoff, 132.5 mg/dl, has been suggested as being more sensitive to identify subjects at risk of T2D. Our aim was to assess whether obese Caucasian youth with 1hPG ≥ 132.5 mg/dl have worse insulin sensitivity and secretion and a worse cardiometabolic profile compared to obese youth with 1hPG < 132.5 mg/dl. METHODS: Medical records of 244 (43% male; age: 11.1 ± 2.7years) overweight/obese children and adolescents, who had undergone an oral glucose tolerance test (OGTT), were retrieved. Anthropometric and biochemical data were collected from the hard copy archive. Indexes of insulin resistance (HOMA-IR), insulin sensitivity (WBISI), and insulin secretion (Insulinogenic Index, Disposition Index) were calculated. RESULTS: Of the 244 records analyzed, 215 fulfilled criteria for NGT and had complete biochemical data. Among NGT patients, 42 (19.5%) showed 1hPG ≥ 132.5 mg/dL (high-NGT), while the remaining had 1hPG < 132.5 mg/dL (low-NGT). The high-NGT group showed a higher male prevalence (59.5 vs 37%), lower Disposition Index (0.54 [0.39-0.71] vs 0.79 [0.47-1.43]), and WBISI (0.24 [0.18-0.35] vs 0.33 [0.23-0.50]) than the low-NGT group. High-NGT subjects also showed a trend towards lower HDL-cholesterol and higher triglycerides/HDL-cholesterol ratio (2.13 [1.49-3.41] vs 1.66 [1.24-2.49]). CONCLUSIONS: In overweight/obese NGT Caucasian youth a 1hPG ≥ 132.5 mg/dL was able to identify those with impaired insulin sensitivity and secretion and a trend towards a worse cardio-metabolic profile, a group likely at risk for future T2D.

Compliance with enhanced recovery after surgery criteria and preoperative and postoperative counselling reduces length of hospital stay in colorectal surgery: results of a randomized controlled trial.

AIM: The aim of this randomized clinical trial was to compare patients treated using a multimodal approach [enhanced recovery after surgery (ERAS)], with a special focus on counselling, to patients treated in a standard conventional care pathway, who underwent elective colorectal resection. METHOD: In a single-centre trial, adult patients eligible for open or laparoscopic colorectal resection were randomized to an ERAS programme or standard care. The primary end-point was postoperative total hospital stay. Identical discharge criteria were defined for both treatment groups. Secondary end-points included postoperative complications, postoperative C-reactive protein levels, postoperative hospital stay, readmission rate and mortality. All parameters were recorded before operation, on the day of surgery and daily thereafter until discharge. RESULTS: Total hospital stay was significantly shorter among patients randomized to ERAS than among the standard group [median 5 days (range 2-50 days) vs median 8 days (range 2-48 days); P = 0.001]. The two treatment groups exhibited similar outcomes regarding overall major and minor morbidity, reoperation rate, readmission rate and 30-day mortality. There were also no differences in tolerance of enteral nutrition or in the inflammatory response, as reflected by postoperative C-reactive protein levels. CONCLUSION: ERAS care was associated with a significantly shorter length of hospital stay. Without any difference in surgical or general complications, tolerance of enteral nutrition or postoperative C-reactive protein levels, peri-operative information and guidance for ensuring that patients comply with the ERAS approach appear to be important factors to reduce the length of hospital stay.

Increased left atrial size in obese children and its association with insulin resistance: a pilot study.

Subclinical cardiac abnormalities represent predisposing factors for cardiovascular disease (CVD) in obese subjects. The aim of this study was to evaluate early cardiac abnormalities in obese youth and the potential association with insulin resistance (IR). Thirty obese (12 males (M)/18 females (F); age = 11.5 ± 2.4 years; body mass index (BMI)-standard deviation score (SDS) = +2.1 ± 0.5) and 15 normal weight (10 M/5 F; age = 12.8 ± 3.1 years; BMI-SDS = +0.3 ± 0.9) children and adolescents underwent Doppler two-dimensional echocardiographic assessments of left atrial (LA) and ventricular (LV) geometry and LV diastolic function (peak early [E] and late waves, E wave deceleration time, myocardial flow velocities). Homeostasis model assessment of IR (HOMA-IR) was used as an IR index. LA size was increased in obese children, as indicated by higher LA diameter (4.9 ± 0.5 vs 4.1 ± 0.4 cm, p < 0.001), area (14.3 ± 2.5 vs 10.7 ± 2.0 cm(2), p < 0.001), and volume (33.8 ± 10.6 vs 23.7 ± 6.4 ml, p = 0.003). LV mass was also increased in obese children (87.0 ± 16.6 vs 68.8 ± 13.2 g, p = 0.003), who also showed subtle diastolic dysfunctions, as indicated by higher values of E (97.1 ± 14.3 vs 86.2 ± 11.9 cm/s, p = 0.02). All the above parameters were significantly associated with BMI-SDS (p < 0.05). In addition, HOMA-IR was independently associated with LA diameter, area, and volume (ß = 0.314, p = 0.040; ß = 0.415, p = 0.008; ß = 0.535, p = 0.001). CONCLUSION: Obese children feature increased LA size, which emerged to be mainly correlated to, and possibly driven by IR, suggesting an increased CVD risk. WHAT IS KNOWN: Left atrial and ventricular alterations have been reported in obese adults, and they represent predisposing factors for cardiovascular disease. There is some evidence suggesting that obese children show increased left ventricular mass and also increased atrial size, although with conflicting results. WHAT IS NEW: Obese normotensive children showed a moderately increased atrial size, subtle alterations in left cardiac diastolic function, and ventricular mass. An association between insulin resistance and left cardiac changes was found, although its mechanism remains to be determined.

Blood pressure from childhood to adolescence in obese youths in relation to insulin resistance and asymmetric dimethylarginine.

BACKGROUND AND PROPOSE: Hypertension is the most important cardiovascular complication of obesity, even during childhood. Several studies have demonstrated that there is a natural progression of hypertension from childhood to adulthood. However, there are no data reporting a potential worsening in blood pressure (BP) already moving from the pre-pubertal to the pubertal period in obese youths. The aim of this study was to evaluate early change in BP and its relation to insulin resistance (IR) and asymmetric dimethylarginine (ADMA). METHODS: Thirty obese children underwent a first assessment when they were pre-pubertal (visit_1) and were re-evaluated after a mean of 4.5 years (visit_2). At both visits, anthropometric parameters were assessed, blood samples were collected for measurement of insulin, glucose and ADMA and a 24-h ambulatory BP monitoring was performed. RESULTS: At visit_2, the study participants presented increased HOMA-IR and ADMA compared to visit_1 (HOMA-IR: 3.6 ± 2.8 vs 2.8 ± 1.4, p = 0.01; ADMA: 1.57 ± 0.78 vs 0.77 ± 0.52 µmol/l, p < 0.001). Values of 24-h systolic and diastolic BP SDS (0.86 ± 0.79 vs 0.42 ± 0.83, p = 0.001; -0.45 ± 0.82 vs 0.08 ± 0.51, p = 0.001) were significantly increased at visit_2 compared to visit_1. At both visits, BMI-SDS, HOMA-IR and ADMA were associated with 24-h BP. In addition, over-time changes in IR and ADMA influenced changes in systolic blood pressure and diastolic blood pressure from childhood to adolescence (p < 0.05). CONCLUSIONS: Changes in BP already occur moving from the pre-pubertal to the pubertal period in obese children, and modifications in insulin resistance and ADMA seem to be implicated in this early progression in BP.

Longitudinal Assessment of Blood Pressure in School-Aged Children: A 3-Year Follow-Up Study.

The purpose of this study was to assess the prevalence of abnormal blood pressure in a population of school children during a 3-year follow-up period and its relationship with obesity. Anthropometric and blood pressure data were collected from a population of Italian school children during three consecutive years. During each year blood pressure measurements were repeated three times, at intervals of 1 week. A total of 564 school-children [311 boys; mean (SD) age 8.8 ± 1.4 years] were recruited. During each year, systolic and diastolic blood pressure decreased from visit 1 to visit 3 (p < 0.001). This was associated with a decline in the percentage of prehypertension/hypertension from visit 1 to visit 3. An abnormal blood pressure value in at least one study visit was found in 8.8-17 % of children, whereas the prevalence of hypertension at all three study visits was between 5.2 and 7.8 %, and that of prehypertension at all three visits was between 2.8 and 3.8 %. High blood pressure was more frequent in obese children. In this population of school children the percentage of prehypertension/hypertension remarkably varied when based on one versus three annual assessments, thus emphasizing the importance of repeated measurement before making a diagnosis of abnormal blood pressure. Adiposity was confirmed to be a determinant of high blood pressure.

Influence of the Mediterranean diet on carotid intima-media thickness in hypercholesterolaemic children: a 12-month intervention study.

BACKGROUND AND AIMS: The Mediterranean diet has been recognised as having a protective role on the cardiovascular system due to its low lipid and high antioxidant content. Lipid profile and oxidant status represent two important risk factors related to endothelial dysfunction, even at early stages of cardiovascular diseases. The aim of the study was to evaluate the influence of a 12-month Mediterranean diet on the variation of lipid profile and carotid intima-media thickness (cIMT) in pre-pubertal hypercholesterolaemic children. METHODS AND RESULTS: We performed a cross-sectional study comparing lipid profile and cIMT in a group of 68 pre-pubertal children (36 with hypercholesterolaemia and 32 controls). In addition, in the hypercholesterolaemic children a 12-month intervention programme with a Mediterranean diet was started to evaluate the variation of lipid profile and cIMT. At baseline, hypercholesterolaemic children showed a significantly higher cIMT (both right and left carotid artery) compared to controls (both p < 0.05). After 12 months of diet intervention, a significant reduction of total cholesterol, LDL-cholesterol and cIMT was documented (all p < 0.05). Furthermore, at the end of follow-up, delta body mass index-Standard Deviation score and delta LDL-cholesterol were significantly and independently related to the changes of cIMT (both p < 0.05). CONCLUSION: The Mediterranean diet represents a valid approach in the treatment of hypercholesterolaemia even during childhood.

Impact of a weight loss program on migraine in obese adolescents.

BACKGROUND AND PURPOSE: Increased headache frequency and severity have been observed in obese populations, but the real impact of a weight loss treatment on headache has not been studied. We investigated this issue in a sample of obese adolescents. METHODS: In all, 135 migraineurs, aged 14-18 years, with body mass index (BMI) ≥ 97 th percentile, participating in a 12-month-long program, were studied before and after treatment. The program included dietary education, specific physical training, and behavioral treatment. RESULTS: Decreases in weight (P < 0.01), BMI (P < 0.01), waist circumference (P < 0.01), headache frequency (P < 0.01) and intensity (P < 0.01), use of acute medications (P < 0.05), and disability (P < 0.05) were observed at the end of the first 6-month period and were maintained through the second 6 months. Both lower baseline BMI and excess change in BMI were significantly associated with better migraine outcomes 12 months after the intervention program. CONCLUSIONS: Significant improvements in both adiposity and headache data were observed in obese adolescents with migraine who participated in a 12-month-long interdisciplinary intervention program for weight loss. Initial body weight and amount of weight loss may be useful for clinicians to predict migraine outcomes.

Macrovascular angiopathy in children and adolescents with type 1 diabetes.

Diabetes represents one of the most common diseases globally. Worryingly, the worldwide incidence of type 1 diabetes (T1D) is rising by 3% per year. Despite the rapid increase in diabetes incidence, recent advances in diabetes treatment have been successful in decreasing morbidity and mortality from diabetes-related retinopathy, nephropathy, and neuropathy. In contrast, there is clear evidence for the lack of improvement in mortality for cardiovascular diseases (CVDs). This emphasizes the importance of focusing childhood diabetes care strategies for the prevention of CVD in adulthood. Furthermore, although most work on diabetes and macrovascular disease relates to type 2 diabetes, it has been shown that the age-adjusted relative risk of CVD in T1D far exceeds that in type 2 diabetes. As T1D appears predominantly during childhood, those with T1D are at greater risk for coronary events early in life and require lifelong medical attention. Because of the important health effects of CVDs in children and adolescents with T1D, patients, family members, and care providers should understand the interaction of T1D and cardiovascular risk. In addition, optimal cardiac care for the patient with diabetes should focus on aggressive management of traditional cardiovascular risk factors to optimize those well-recognized as well as new specific risk factors which are becoming available. Therefore, a complete characterization of the molecular mechanisms involved in the development and progression of macrovascular angiopathy is needed. Furthermore, as vascular abnormalities begin as early as in childhood, potentially modifiable risk factors should be identified at an early stage of vascular disease development.

Role of ultrasonography in the diagnosis and follow-up of pediatric eosinophilic gastroenteritis: a case report and review of the literature.

Eosinophilic gastroenteritis (EG) is a rare disease characterized by the infiltration of one or more layers of the digestive tract by eosinophilic leukocytes. The diagnosis is confirmed by histological examination of a characteristic biopsy, but radiological features are useful for diagnostic suspicion. We report the case of an adolescent boy with recurrent epigastric pain, nausea and vomiting, in whom sonographic features and eosinophilia of the peripheral blood suggested the diagnosis of EG. Moreover, we reviewed the radiological features of EG with particular regard to the role of sonography in the diagnosis and follow-up of EG, especially in children. We emphasize the utility of sonography in pediatric patients presenting with gastrointestinal symptoms, since it may provide useful information in a quick, inexpensive and noninvasive way. Ultrasonographic detection of features such as bowel wall thickness, ascites and peritoneal nodules may be largely suggestive of EG and may prevent other invasive exams and abdominal surgery. Ultrasonography can also be easily used in the follow-up of these patients, and may obviate the frequent and potentially dangerous exposure to radiation.

Management of diabetic ketoacidosis in children and adolescents in sub-Saharan Africa: a review.

BACKGROUND: Diabetic ketoacidosis (DKA) is a complex metabolic state of hyperglycaemia, ketosis, and acidosis. Diabetes in sub-Saharan Africa is, in many patients a serious disease with a poor prognosis. Most deaths, however, are due to preventable causes. OBJECTIVE: To improve knowledge on the management of DKA in sub-Saharan Africa. DATA SOURCES: Literature review from different published sources. DATA SYNTHESIS: Health systems in sub-Saharan Africa are currently organised for the treatment of episodes of illness and not long-term conditions like diabetes. Therefore the high rates of DKA is essentially due to lack of training of health professionals, lack of facilities in most hospitals, lack of public awareness as well as lack of health education to individual patients/families. In addition erratic insulin supply coupling with infections, low parental education, poor insulin storage and lack of facilities for self monitoring of blood glucose. CONCLUSION: A complex unfavourable social and economic environment is the basis of the high prevalence of DKA in sub-Saharan Africa. Several episodes of DKA can be prevented by effective public awareness programmes and education to healthcare providers.

Levetiracetam monotherapy for childhood occipital epilepsy of gastaut.

OBJECTIVES: The aim of this open label pilot study was to evaluate the efficacy and tolerability of levetiracetam (LEV) as 'de novo' monotherapy in children and adolescents with late onset childhood occipital epilepsy-Gastaut type (COE-G). MATERIAL AND METHODS: Twelve patients suffering from COE-G were enrolled in this prospective study. The age of seizures onset ranged from 6.1 to 16.2 years with a peak of frequency at mean (+/-SD) 10.54 +/- 2.77 years. Therapy with LEV was started at 10 mg/kg/day and, after titration, the final dose was generally achieved within 4 weeks and ranged from 20.7 to 45.2 mg/kg/day. RESULTS: At the 6 month evaluation, 11 (91.6%) of the 12 patients studied were seizure free, and one (8.3%) showed four additional episodes. Electroencephalography (EEG) activity was normal in six (54.5%) patients, unchanged in two (18.1%) children, and in four (33.3%) patients sporadic occipital abnormalities persisted. At the 12-month evaluation all patients were completely seizure free. Four patients (33.3%) continued to show some EEG abnormalities, while eight (72.8%) patients had normal EEG. At the 18-month evaluation all patients were seizure free and 10 patients (83.3%) showed a complete normalization of EEG abnormalities. DISCUSSION: Monotherapy with LEV was effective and well tolerated in patients with COE-G. Nevertheless, prospective, large, long-term double-blind studies are needed to confirm these findings.

Episodic spontaneous hypothermia potentially triggered by hyperinsulinemia.

Episodic spontaneous hypothermia is an infrequent disorder, the pathogenic mechanisms of which have not been completely clarified, although alterations in the serotoninergic system have been suggested. We report the history of a girl with episodes of dizziness and shivering associated with a body temperature lower than 35 degrees C since the age of 10 months. At the age of 11 years, she was admitted to a local hospital and an oral glucose tolerance test showed high total insulin levels. Hypoglycemia secondary to hyperinsulinemia was suspected, and a low-carbohydrate (simple) diet was proposed without results. Due to the recurrence of the episodes, episodic spontaneous hypothermia triggered by hyperinsulinemia was suspected, and treatment with flunarizine, a drug considered the first line in the treatment of migraine-related disorders, was started with a resulting reduction in the episodes. A new endocrinological evaluation showed decreased insulin secretion. In our patient, the success of the therapy might be due to the well-known effect of calcium antagonists in inhibiting serotonin uptake and thereby regulating serotonin levels after hyperinsulinism. This case suggests hyperinsulinemia as a potential mechanism for episodic spontaneous hypothermia, probably mediated by an interaction between insulin and the serotoninergic system.

Growth and puberty in children with HIV infection.

Children with perinatal HIV infection may present with clinical features of endocrine dysfunction such as growth failure and pubertal delay. Pediatric care providers and pediatric endocrinologists should implement appropriate preventive, screening, and therapeutic strategies to maximize survival and quality of life in these children. Growth and pubertal delay can be exacerbated by a variety of treatable infectious, endocrine, nutritional, and immunological disorders. Timely diagnosis and appropriate treatment of these conditions may lead to improvement or even normalization of growth and puberty. HIV-infected children with advanced disease should undergo periodic growth evaluation, including GH levels, IGF-I, IGF binding protein 3 and androgens, in order to identify subclinical endocrine dysfunction. However, little is known about the association between HIV infection and endocrine dysfunction in children. Highly active antiretroviral therapy may also be associated with endocrine dysfunction with consequences on growth and puberty. Growth retardation and pubertal delay are always seen in children with advanced HIV infection and are often related to the proinflammatory milieu found in advanced AIDS. Growth and pubertal impairment are markers of advanced disease and require proper evaluation. A dysregulation of the hypothalamic-pituitary axis, toxic or allergic drug reactions may play a role in growth and pubertal delay of HIV-infected children. These dysfunctions require careful monitoring, in order to assess metabolic alterations that may be important in regulation of growth among HIV infected children. Better understanding of the mechanisms leading to impairment of growth and puberty in children with perinatal HIV-1 infection might lead to appropriate treatment when required.

Enhanced recovery after colorectal surgery. Results from a prospective observational two-centre study.

BACKGROUND AND AIMS: Enhanced recovery after surgery (ERAS) has reduced the median hospital stay from 8-10 days with traditional peri-operative routines to four days. The aim of the present study was to introduce the principles of ERAS in our hospital and measure the effect on hospital stay, complications and quality of life after discharge from hospital. MATERIAL AND METHODS: 94 consecutive patients, 40 males, 54 females, median age 66 years, were included in a prospective non-randomised observational study at Haukeland University Hospital and Haugesund Hospital from October 2000 until February 2003. After a three-month preparation period, the principles of ERAS were implemented. The results were evaluated with questionnaires and by follow-ups 8-10 and 30 days after surgery. The results were compared to the results of colorectal surgery before introduction of accelerated recovery. RESULTS: 45 (48%) and 73 (78%) patients were discharged within three and five days after surgery with ERAS, compared to zero and seven (5%) patients with traditional recovery. The complication rate with ERAS was 31%, and the readmission rate was 15%. After one week, 57% had resumed their daily activities at home. After 30 days, 65% of the patients had resumed their normal and leisure activities. CONCLUSION: After a proper preparation period, ERAS principles may be implemented in surgical department, and is followed by a reduced median hospital stay and rapid return to normal daily activities for most patients after colorectal surgery.

Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1.

PDZ domain-containing proteins play an important role in the targeting and localization of synaptic membrane proteins. Here, we report an interaction between the PDZ domain-containing protein PICK1 and monoamine neurotransmitter transporters in vitro and in vivo. In dopaminergic neurons, PICK1 colocalizes with the dopamine transporter (DAT) and forms a stable protein complex. Coexpression of PICK1 with DAT in mammalian cells and neurons in culture results in colocalization of the two proteins in a cluster pattern and an enhancement of DAT uptake activity through an increase in the number of plasma membrane DAT. Deletion of the PDZ binding site at the carboxyl terminus of DAT abolishes its association with PICK1 and impairs the localization of the transporter in neurons. These findings indicate a role for PDZ-mediated protein interactions in the localization, expression, and function of monoamine transporters.

Genetic animal models: focus on schizophrenia.

The neurobiology of schizophrenia remains poorly understood. Symptoms of schizophrenia are classically thought to be associated with an imbalance of the dopaminergic system. However, the contribution of other neurotransmitters, in particular glutamate, has been increasingly appreciated. The role of individual components of neurotransmitter systems in aberrant behaviors can be experimentally tested in transgenic animals. Dopamine transporter knockout mice display persistently elevated dopaminergic tone and therefore might be appropriate substrates to evaluate the dopamine hypothesis. Similarly, NMDA receptor-deficient mice can be used to evaluate the glutamate hypothesis of schizophrenia. In this review we discuss how such animal models might be relevant for understanding the neurochemical underpinnings of certain manifestations of schizophrenia.