CYP450 2D6 and 2C19 genotypes in ADHD: not related with treatment resistance but with over-representation of 2C19 ultra-metabolizers.

OBJECTIVES: Cytochrome P450 (CYP450) is a major enzyme system involved in drug metabolism as well as regulation of brain function. Although individual variability in CYP enzymes have been studied in terms of personality traits and treatment effects, no study up to now evaluated CYP polymorphisms in children with attention deficit/hyperactivity disorder (ADHD). We aimed to define the genetic profiles of CYP2D6 and CYP2C19 relevant alleles in children with ADHD according to treatment status and compare the frequencies according to past results. METHODS: Three hundred and seventeen patients with ADHD-Combined Presentation were enrolled; symptom severity was evaluated by parents and clinicians while adverse effects of previous treatments were evaluated with parent and child reports. Reverse blotting on strip assays was used for genotyping and descriptive and bivariate analyses were conducted. A p-value was set at 0.05 (two-tailed). RESULTS: Children were divided into treatment-naïve (n=194, 61.2%) and treatment-resistant (n=123, 38.8%) groups. Within the whole sample PM, EM and UM status according to 2D6 were 3.8% (n=12), 94.3% (n=299) and 21.9% (n=6); respectively. PM, IM, EM and UM status according to 2C19 were 2.5% (n=8), 19.8% (n=63), 48.6% (n=154) and 29.0% (n=92), respectively. No relationship with treatment resistance, comorbidity or gender could be found. Importantly, CYP2C19 UMs were significantly more frequent in ADHD patients compared to previous studies in the general population. CONCLUSIONS: CYPs may be a rewarding avenue of research to elucidate the etiology and treatment of patients with ADHD.

Comparison of ultrasound-guided pulsed radiofrequency versus steroid injection in the treatment of carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most widespread form of nerve entrapment neuropathy results from increase compression pressure of the median nerve at the wrist under the transverse carpal ligament. AIMS: To compare ultrasound (US)-guided median nerve steroid injection and pulsed radiofrequency (PRF) on pain intensity, functional status, and patient satisfaction in the treatment of CTS. METHODS: A total of 90 hands of 59 patients who underwent steroid injection at the level of proximal carpal tunnel or PRF for CTS were retrospectively analyzed. Demographic and clinical characteristics of the patients were recorded. The pain severity was assessed using the Numerical Rating Scale (NRS), and the functional status and clinical outcomes were assessed using the Boston Carpal Tunnel Questionnaire (BCTQ) before the procedure and at Week 1, Month 1, and Month 3 after the procedure. Time to pain relief was evaluated at week 1. Patient satisfaction was evaluated at Month 3. RESULTS: There was no significant difference in the NRS and BCTQ scores between the two treatment methods (p > 0.05 for both). In addition, a significant decrease in the NRS and BCTQ scores were detected at all follow-ups compared to baseline in treatment groups (p < 0.001). The mean time to pain relief was significantly shorter in the PRF group (p < 0.001). Patient satisfaction was similar at Month 3 between the treatment methods (p > 0.05). CONCLUSIONS: Our study results suggest that both US-guided steroid injection to the median nerve and PRF are effective and safe methods in the short-term in the treatment of CTS.

Does Treatment with Dexmedetomidine Intra-articularly Improve Postoperative Pain and Rehabilitation after Anterior Cruciate Ligament Reconstruction?

This study aims to evaluate the analgesic efficacy of dexmedetomidine added to levobupivacaine following anterior cruciate ligament (ACL) surgery. Fifty patients undergoing ACL reconstruction were included. Group DL (dexmedetomidin-levobupivacaine) received 20 mL 0.5% levobupivacaine plus 1 mL (100 µg) dexmedetomidine. Group L (levobupivacaine) patients received 20 mL 0.5% levobupivacaine plus 1 mL saline 10 minutes before tourniquet release. A patient-controlled analgesia (PCA) pump was then connected, delivering 0.5 mg at every 10 minutes and 1-mg morphine and 75-mg diclofenac sodium was used as a rescue analgesic. Postoperative pain was evaluated 0, 2, 4, 6, 12, and 24 hours after extubation at rest and during movement. A rehabilitation program was started after surgery. Postoperative continuous passive motion (CPM) starting time, postoperative leg flexion angle, and straight leg lifting time were evaluated for each group. There were no significant differences between the groups in terms of demographic data and operation time. Morphine consumption, analgesic requirements, and visual analogue scale (VAS) assessments were significantly lower in group DL during the 24-hour period after surgery. The time to start CPM in the postoperative period was significantly shorter in group DL. Passive joint flexion angle was significantly higher in group DL. Postoperative straight leg lifting time was significantly shorter in group DL. Adding dexmedetomidine to the intra-articular levobupivacaine provided better postoperative pain control and improved rehabilitation period after ACL surgery.

High Depression Symptoms and Burnout Levels Among Parents of Children with Autism Spectrum Disorders: A Multi-Center, Cross-Sectional, Case-Control Study.

The diagnosis of autism spectrum disorder (ASD) in a child affects family processes, increases parenting stress and marital conflicts, and may lead to parental psychopathology. It may also affect the prognosis for their children. The aim of this study is to determine depression and burnout levels as well as their predictors among parents of children with ASD compared with those of healthy children. We also sought to evaluate rate of complementary and alternative medicine (CAM) interventions among parents and explore the associations of this phenomenon in an exploratory fashion. 145 children with ASD and 127 control children were enrolled along with their mothers and fathers. Beck Depression Inventory and Maslach Burnout Inventory were used to evaluate parents' depression symptoms and burnout levels. Symptoms of children with ASDs were evaluated according to the Childhood Autism Rating Scale by the clinicians. Family, child and CAM variables were screened by means of a sociodemographic data form. Descriptive, bivariate and correlation analyses were used in statistical evaluations. Predictors of burnout were evaluated with multiple regression analysis. Burnout and depression levels among parents of children with ASD were significantly elevated compared to controls. Burnout levels of mothers were significantly elevated compared to fathers while depression scores of fathers were significantly elevated compared to mothers. Maternal burnout was significantly predicted by presence of functional speech in child while paternal burnout was significantly predicted by paternal vocation. Maternal depression was associated with paternal depression, lack of speech in child and attendance of child to special education services. Paternal depression was associated with autistic symptom severity and maternal depression. More than half the parents sought CAM interventions. Education level did not affect search for CAM interventions while both maternal and paternal psychopathology and presence of epilepsy among children increased use of CAM methods. Psychological support should be provided to both mothers and fathers of a child receiving a diagnosis of ASD. Addressing parents' burnout and stress levels and facilitating their negotiation of knowledge on etiology and treatments for ASD may be beneficial for the family unit as a whole.

Cytokine expression profiles in Autism spectrum disorder: A multi-center study from Turkey.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in communication and social interaction as well as restricted interests and repetitive behaviors. The pathogenesis of ASD is not completely understood, but a growing body of research has demonstrated that the immune response may be a contributing factor in the etiology and/ or ontogeny of ASD. The aim of this study was to determine the expression levels of IL-1ß, IL-1α, IL-4, IL-6, IL-17, TNF-α and TGF-ß in peripheral blood mononuclear cells of children with ASD and healthy controls in order to determine the contributions of cytokines to ASD. Within the study timeframe, 195 children with ASDs (80.5% male) and 162 controls (73.6% male) were enrolled. Most children with ASD had a comorbid disorder (n = 114, 58.5%), with the most common diagnoses as Intellectual Developmental Disorder (IDD, n = 64, 32.8%) and ADHD (n = 64, 32.8%). The majority of children with ASD had severe autistic symptoms as evaluated via Childhood Autism Rating Scale (CARS, n = 130, 64.6%). The mean CARS score in the ASD sample was 40.8 (S.D. = 7.6). The patients with ASD were found to have significantly higher levels of IL-6 (p < 0.001) and significantly lower levels of IL-17 (p < 0.05, all Bonferroni corrected). Treatment tended to affect IL-4 levels. Lastly, discriminant function analysis (DFA) revealed that a combination of IL-6, IL-17 and IL-1α correctly classified 56.6% of cases. Despite extensive immunological evidence suggesting immune system aberrations, further research is required to clarify the relationship between immune profiles and ASD symptoms.

Amenorrhea as a Side Effect of Low Dose Aripiprazole: An Adolescent Case.

Amenorrhea, oligomenorrhea, galactorrhoea, gynecomastia, infertility, and sexual dysfunction may arise as a consequence of hyperprolactinemia. Hyperprolactinemia is one of major side effects of treatment with antipsychotics, but aripiprazole is known as a dopamine stabilizer antipsychotic which can be used to improve hyperprolactinemia. In this report, it was described that an adolescent patient experienced amenorrhea after adding very low dose aripiprazole to ongoing fluoxetine treatment regime for major depressive disorder. Additionally, this case showed that the patient recovered from the amenorrhea with replacement of aripiprazole with quetiapine.

Migraine and associated comorbidities are three times more frequent in children with ADHD and their mothers.

OBJECTIVE: Attention deficit and hyperactivity disorder (ADHD) is a neuro-developmental disorder related to internalizing and externalizing disorders as well as somatic complaints and disorders. This study was conducted to evaluate the prevalence of headache subtypes, epilepsy, atopic disorders, motion sickness and recurrent abdominal pain among children and adolescents with ADHD and their parents. METHODS: In a multi-center, cross-sectional, familial association study using case-control design, treatment naïve children and adolescents between 6 and 18 years of age diagnosed with ADHD according to the DSM-5 criteria as well as age- and gender-matched healthy controls and their parents were evaluated by a neurologist and analyzed accordingly. RESULTS: 117 children and adolescents with ADHD and 111 controls were included. Headache disorder diagnosis was common for both patients and healthy controls (59.0% vs. 37.8%), with a significantly elevated rate in the ADHD group (p = 0.002). Migraine was found in 26.0% of ADHD patients and 9.9% of healthy controls. Tension headache was found in 32.4% of ADHD patients and 27.9% of healthy controls. Headache diagnosis was also found to be significantly more common in mothers of children with ADHD than control group mothers (90.5% vs. 36.6%, p < 0.001). CONCLUSION: Headache diagnoses and specifically migraines were significantly more common among children with ADHD and their mothers, while recurrent abdominal pain was elevated in both parents and ADHD patients. Migraine is an important part of ADHD comorbidity, not only for children but also for mothers. Motion sickness may be reduced among families of ADHD probands.

Developmental delays and psychiatric diagnoses are elevated in offspring staying in prisons with their mothers.

The aim of the study was to describe the sociodemographic and clinical features of the mothers and their offspring staying with them in prison. The study was planned as a cross-sectional, single-center study of mothers residing in Tarsus Closed Women's Prison of Turkish Ministry of Justice along with their 0 to 6 years old offspring. Mothers were evaluated via Structured Clinical Interview for DSM-IV Axis I Disorders. A psychologist blind to maternal evaluations applied the Denver Developmental Screening Test II (DII-DST). Children/mothers were also evaluated by a child and adolescent psychiatrist via K-SADS-PL. Twenty-four mothers with a mean age of 29.3 years were included. Most common diagnoses in mothers were nicotine abuse (n = 17, 70.8%), specific phobia (n = 8, 33.3%), alcohol abuse (n = 7, 29.2%) and substance abuse (n = 5, 20.8%). Twenty-six children (53.9% female) were living with their mothers in prison, and the mean age of those was 26.3 months. Results of the D-II-DST were abnormal in 33.3% of the children. Most common diagnoses in children were adjustment disorder (n = 7, 26.9%) separation anxiety disorder (n = 3, 11.5%) and conduct disorder (n = 2, 7.7%). A multi-center study is necessary to reach that neglected/under-served population and address the inter-generational transmission of abuse, neglect, and psychopathology.

Hiccup Due to Aripiprazole Plus Methylphenidate Treatment in an Adolescent with Attention Deficit and Hyperactivity Disorder and Conduct Disorder: A Case Report.

Our case had hiccups arising in an adolescent with the attention deficit and hyperactivity disorder (ADHD) and conduct disorder (CD) after adding aripiprazole treatment to extended-release methylphenidate. Actually, antipsychotics are also used in the treatment of hiccups, but studies suggest that they can cause hiccups as well. Within 12 hours of taking 2.5 mg aripiprazole added to extended-release methylphenidate at a dose of 54 mg/day, 16-year-old boy began having hiccups in the morning, which lasted after 3-4 hours. As a result, aripiprazole was discontinued and methylphenidate was continued alone because we could not convince the patient to use another additional drug due to this side effect. Subsequently, when his behavior got worsened day by day, his mother administered aripiprazole alone again at the dose of 2.5 mg/day at the weekend and continued treatment because hiccup did not occur again. But when it was administered with methylphenidate on Monday, hiccup started again next morning and lasted one hour at this time. In conclusion, we concluded that concurrent use of methylphenidate and aripiprazole in this adolescent led to hiccups.

Achalasia as a complication of bulimia nervosa: A case report.

OBJECTIVE: Oesophageal achalasia is a medical condition characterised by oesophageal aperistalsis, an increased resting pressure with partial or incomplete relaxation of the lower oesophageal sphincter. Bulimia nervosa (BN) is an eating disorder manifested by binge eating attacks followed by recurrent inappropriate compensatory behaviours, such as self-induced vomiting and excessive exercise. Dysphagia, regurgitation, vomiting, retrosternal pain, heartburn, weight loss, avoidance of eating, consumption of large amount of liquids and aberrant eating behaviours are symptoms of both achalasia and BN. Owing to these common signs and symptoms, oesophageal achalasia can be misdiagnosed as an eating disorder. In addition, oesophageal achalasia can occur as a complication of BN. It is often difficult to distinguish organic and psychological vomiting or comorbidity because of overlapping of the symptoms. CASE REPORT: We report the case of a patient who developed oesophageal achalasia following severe, repetitive vomiting as a complication of BN. CONCLUSION: We want to raise awareness regarding the development of a medical illness in the presence of a psychiatric disorder. Importantly, physicians should have a fundamental knowledge of these two diseases regarding their clinical patterns to differentially diagnose one or both disorders as quickly as possible.

Tibia stress fracture secondary to obsessive compulsive disorder.

Obsessive compulsive disorder (OCD) is a chronic psychiatric disorder characterized by obsessions and compulsions. Early-onset OCD is one of the most common mental illnesses of children and adolescents, with a prevalence of 1% to 3%. It is related to worse lifespan symptoms and prognosis. Therefore, the treatment of OCD in children and adolescent has gained importance. If it is not treated successfully, the compulsive behaviors may cause extreme stress for children and their parents. Although minor complications of OCD are commonly observed, major complications are considerably rare due to the nature of compulsive behaviors. Apparently, loss of vision, autocastration, rectal prolapse are examples of major complications secondary to OCD. As far as we know, it is the first case of tibia stress fracture secondary to OCD. In the present case report, we will discuss tibia stress fracture developing secondary to compulsive behavior due to OCD.

Persistent hiccups due to aripiprazole in an adolescent with obsessive compulsive disorder responding to dose reduction and rechallenge.

Our case involves persistent hiccup arising in an adolescent with obsessive compulsive disorder (OCD) who was using aripiprazole as an augmentation to fluoxetine and whose hiccups remitted with dose reduction and rechallenge. Treatment suggested that aripiprazole might lead to hiccups. Antipsychotics are also used for the treatment of hiccups, but recent case reports suggest that they cause hiccups as well. Within 12 h of taking 5 mg aripiprazole, the 13-year-old girl began having continuous hiccups, which lasted for 3-4 h. The hiccups resolved when the dose of aripiprazole was reduced to 2.5 mg. To achieve augmentation, aripiprazole was replaced with risperidone 0.5 mg/day for 1 month, but excess sedation was observed. As a result, aripiprazole was restarted at a dose of 2.5 mg/day, and 1 week later, it was increased to 5 mg/every other day. No hiccups were observed.

Self-concept in children and adolescents with epilepsy: The role of family functioning, mothers' emotional symptoms and ADHD.

PURPOSE: This study aimed to identify the associated factors of poor self-concept in children and adolescents with epilepsy. METHODS: Fifty-three patients with uncomplicated epilepsy (aged 7-18years) and 28 healthy controls were included. Study measures included the Piers-Harris 2 Self-Concept Scale, Family Assessment Device (FAD), Turgay DSM-IV based ADHD rating Scale (T-DSM-IV-S), Conners' Teacher Rating Scale (CTRS-R), Beck Depression Inventory and State-Trait Anxiety Inventory (STAI). Neurology clinic charts were reviewed for the epilepsy-related variables. RESULTS: While the Piers-Harris 2 total score was not significantly different between the groups, patients with epilepsy had lower (poorer) scores on freedom from anxiety and popularity subscales. Linear regression analysis revealed that the problem solving, affective responsiveness, general functioning and communication scores of FAD; total and inattentiveness scores of T-DSM-IV-S and mothers' Beck scores were associated with the total score of Piers-Harris 2. Epilepsy-related factors were not found to be associated with self-concept scores. CONCLUSION: Poor self-concept in children with epilepsy is associated with negative family functioning, mothers' emotional symptoms and ADHD, especially the symptoms of inattentiveness.

Dystonia in an adolescent on risperidone following the discontinuation of methylphenidate: a case report.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with common comorbidities that include oppositional defiant disorder, conduct disorder, anxiety disorder, and affective disorders. Because of these comorbidities, drug combination treatments and drug-drug interactions are becoming increasingly more frequent. The present case report describes an acute dystonic reaction following the abrupt discontinuation of methylphenidate from a drug regimen with risperidone. The patient experienced acute dystonic reactions on three separate occasions when he forgot to take his methylphenidate medication. The present report informs clinicians about the possible side effects, such as dystonia, when psychostimulant and antipsychotic drug combinations are altered and suggests that the abrupt cessation of stimulants may lead to the development of movement disorders. Therefore, appropriate care is necessary when changing the dose of a drug or abruptly discontinuing a drug from a combination of psychostimulants and antipsychotics.

Current Approaches in Hip and Knee Arthroplasty Anaesthesia.

Risk assesment, preoperative drug regulation, the anesthesia and analgesia techniques are very important and the effectivity on success of surgery is great. So, these topics in arthroplasty were reviewed under current knowledge.

Does dexmedetomidine provide cardioprotection in coronary artery bypass grafting with cardiopulmonary bypass? A pilot study.

OBJECTIVE: The purpose of this pilot study was to evaluate whether dexmedetomidine has a cardioprotective effect during coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). DESIGN: A prospective, double-blind, randomized controlled trial. SETTING: A university hospital. PARTICIPANTS: Thirty-eight patients undergoing coronary artery bypass graft surgery. INTERVENTIONS: Patients were randomized into 2 groups: dexmedetomidine and placebo groups. In the dexmedetomidine group, dexmedetomidine infusion was started by a loading dose of 0.5 µg/kg/10 min, followed by a continuous infusion of 0.5 µg/kg/h. The placebo group received the same volume of saline. Measurements of central venous pressure, mean pulmonary artery pressure (MPAP) and cardiac index were performed before and after dexmedetomidine loading dose and 2, 24 and 48 hours after CPB. Simultaneously, arterial blood was sampled for CK-MB, cardiac troponin T, and N-terminal probrain natriuretic peptide. MEASUREMENTS AND MAIN RESULTS: CK-MB, cardiac troponin T and N-terminal probrain natriuretic peptide values were elevated in the periods after CPB in both groups (p<0.05) and there were no statistically significant differences between groups. MPAP was decreased in the dexmedetomidine group at the 2nd, 24th and 48th hour after CPB (p<0.001, p<0.001, p = 0.002, respectively). Higher cardiac index values were seen earlier in the dexmedetomidine group than in the placebo group (p< 0.05). CONCLUSIONS: Myocardial damage was not reduced by administration of 0.5 µg/kg loading dose and 0.5 µg/kg/h infusion of dexmedetomidine. However MPAP tended to be lower in the dexmedetomidine group. Large-scale clinical outcome studies are indicated to confirm the effect of dexmedetomidine.

Intravenous dexmedetomidine for treatment of intraoperative penile erection.

BACKGROUND: Intraoperative penile erections following the initiation of either regional or general anaesthesia is rare; however, when it occurs in patients undergoing urologic procedures it may delay, or even cancel the planned surgery. The aetiology is unclear. Various treatments proposed for producing detumescence are not always effective. Use of intracavernous alpha-adrenergic agonists is an efficient and rapid but short-lasting treatment. Furthermore, repeated intracavernous injections of vasoactive drugs may be harmful. Dexmedetomidine is a potent, selective α(2)-adrenoreceptor agonist. In our study, we evaluated the effect of dexmedetomidine on intraoperative penile erection. METHODS: Penile erection developed during an endoscopic procedure in 12 more than 7,800 patients. Anaesthesia used was general in 3 patients, epidural in 1 patient and spinal in 8 patients. The erection rigidity was evaluated by the operating urologist. Dexmedetomidine was diluted in normal saline to a concentration of 4 µg/ml. In all of the cases, 0.5 µg/kg dexmedetomidine was injected intravenously. RESULTS: The incidence of intraoperative penile erection was 0.34% for general anaesthesia, 0.11% spinal anaesthesia and 1.72% epidural anaesthesia at our institution. Detumescence was achieved in 9 patients during the first 5 min and in one patient at the 9th minute after a single intravenous dexmedetomidine (83%). There was no detumescence in two patients after 15 min (17%). CONCLUSION: This study demonstrated that 0.5 µg/kg intravenous injection of dexmedetomidine is a simple, effective and safe method for immediate relief of intraoperative penile erection with high success rate.

The comparison of the effects of dexmedetomidine and midazolam sedation on electroencephalography in pediatric patients with febrile convulsion.

BACKGROUND: When electroencephalogram (EEG) activity is recorded for diagnostic purposes, the effects of sedative drugs on EEG activity should be minimal. This study compares the sedative efficacy and EEG effects of dexmedetomidine and midazolam. SUBJECTS AND METHODS: EEG recordings of 60 pediatric subjects with a history of simple febrile convulsions were performed during physiologic sleep. All of these patients required sedation to obtain follow-up (control) EEGs. Subjects in Group D received 0.5 µg·kg(-1) of dexmedetomidine, and those in Group M received 0.1 mg·kg(-1) of midazolam. For rescue sedation, the same doses were repeated to maintain a Ramsey sedation score level of between 4 and 6. RESULTS: The mean doses that were required for sedation were 0.76 µg·kg(-1) of dexmedetomidine and 0.38 mg·kg(-1) of midazolam. Diastolic blood pressure and HR were lower in Group D than in Group M (P < 0.05). Hypoxia was observed in 11 (36.7%) subjects in Group M and none in Group D; this was statistically significant (P < 0.001). Frontal and parieto-occipital (PO) EEG frequencies were similar during physiologic sleep and dexmedetomidine sedation. However, EEG frequencies in these areas (P < 0.001) and PO EEG amplitude (P = 0.030) were greater during midazolam sedation than during physiologic sleep. CONCLUSIONS: Dexmedetomidine is a suitable agent to provide sedation for EEG recording in children. There is less change in EEG peak frequency and amplitude after dexmedetomidine than after midazolam sedation.

The efficiency of pulsed radiofrequency application on L5 and l6 dorsal roots in rabbits developing neuropathic pain.

BACKGROUND: Injury of a peripheral nerve may lead to neuropathic pain, a form of chronic pain that does not respond to traditional pain therapies. The aim of this study was to investigate the effect of pulsed radiofrequency (PRF) applied to the L5 and L6 dorsal roots on the neuropathic pain that develops after sciatic nerve injury in rabbits. METHODS: In this study, 18 New Zealand rabbits were used. These were divided into 3 groups. In groups 1 and 2, the left sciatic nerve was tightly ligated as a partial ligation model with 4-0 silk sutures. Group 3 was a sham group. Pulsed radiofrequency was applied to group 1 rabbits on both dorsal roots at 42 degrees C for 8 mins. The responses of all the groups to thermal and mechanical stimuli were measured for a period of 4 weeks after this process. RESULTS: Ten days after ligation of the left sciatic nerve and before PRF application, neuropathic pain occurred; the responses of groups 1 and 2 to the hot plate test and to the mechanical stimulus were lower (P < 0.005) when compared with the baseline values. There were no statistically significant differences between baseline values and group 1 rabbits' responses to the hot plate test 2 weeks after the application of PRF or to the mechanical stimulus 3 weeks after RF application. The decrease seen in group 2 persisted after 4 weeks (P < 0.001). CONCLUSIONS: The hyperalgesia that develops as a result of neuropathic pain in rabbits was observed to be reduced by PRF application.