Autism severity is associated with child and maternal MAOA genotypes

Cohen IL, Liu X, Lewis MES, Chudley A, Forster‐Gibson C, Gonzalez M, Jenkins EC, Brown WT, Holden JJA. Autism severity is associated with child and maternal MAOA genotypes. We replicated and extended a previously reported association between autism severity and a functional polymorphism in the monoamine oxidase A (MAOA) promoter region, MAOA‐uVNTR, in a sample of 119 males, aged 2–13 years, with autism spectrum disorder from simplex families. We demonstrated that (i) boys with the low activity 3‐repeat MAOA allele had more severe sensory behaviors, arousal regulation problems, and aggression, and worse social communication skills than males with the high activity allele; and (ii) problems with aggression, as well as with fears and rituals, were modified by the mothers' genotype. Boys with the 4‐repeat high activity allele who had homozygous 4‐repeat mothers showed increased severity of these behaviors relative to those born to heterozygous mothers. These findings indicate the importance of considering maternal genotype in examining associations of MAOA and other genes with behavior in male offspring.     

BIOLOGIC CHARACTERISTICS OF CULTURED HUMAN VITILIGO MELANOCYTES

Background. Vitiligo is a pigmentary disorder of unknown cause characterized by depigmented patches due to destruction of melanocytes. Recently, the inherent cellular defect theory has been discussed. To investigate the biologic characteristics of cultured melanocytes from normal and vitiligo subjects, this study had the purpose to examine the functional and ultrastructural characteristics of these melanocytes and to observe the morphologic and functional changes of melanocytes in response to ultraviolet B irradiation. Methods. Melanocytes were isolated and cultured from foreskin and arm skin of normal and vitiligo subjects. The DNA synthesis, tyrosinase activity assay, transmission and scanning electron microscopic examination, and the effects of ultraviolet B(uvB)-irradiation on cultured melanocytes were studied. Results. Vitiligo melanocytes showed no significant differences in DNA synthesis and tyrosinase activity compared with normal melanocytes, but the vitiligo melanocytes contained dilated and/or circular rough endoplasmic reticulum (RER) on transmission electron microscopic examination. Exposure of the cultured melanocytes to UVB resulted in increased protein synthesis and tyrosinase activity. Morphologic alterations and changes in DNA synthesis were also noted. Compared with normal melanocytes, the responses of vitiligo melanocyte to UVB showed no significant difference. Conclusions. Normal and vitiligo melanocytes showed similar biologic characteristics except in the changes of RERS in the vitiligo melanocytes. The ultrastructural aberrations in vitiligo subjects do not seem to be directly related to the biologic characteristics and the responses to UVB irradiation in vitiligo melanocytes.     

PERIPHERAL BLOOD LYMPHOCYTE IMBALANCE IN KOREANS WITH ACTIVE VITILIGO

Background. An immune-mediated destruction of melanocytes is the most popular current theory of vitiligo. There have been a few published reports on the assessment of lymphocyte population in vitiligo, and they showed mixed results. The purpose of our investigation was to assess peripheral lymphocyte subpopulations in Koreans with actively spreading vitiligo. Methods. Fifty patients with actively spreading vitiligo and 30 normal persons were studied for peripheral blood lymphocyte imbalance using flow cytometry. The percentages of total T-lymphocytes, B-lymphocytes, helper T cells, suppressor T cells, and natural killer cells were evaluated with the use of CD3, CD19, CD4, CD8, and CD16 monoclonal antibodies, respectively. Results. The mean value of helper T cells showed a significant difference between the two groups with the value being 38.2% in patients and 43.5% in control subjects. Seventeen of the 50 patients showed reversed helper/suppressor T cell ratio, whereas only 1 of 30 control subjects showed reversed ratio. There was a statistically significant difference in the mean percentage of helper T cells and suppressor T cells between generalized vitiligo patients and control subjects. The percentage of B cells in patients with recent onset less than 1 year was higher than control subjects and patients with late onset. The mean percentage of natural killer cells was increased significantly in patients with negative autoantibody test. Conclusions. The present data show that immunologic abnormalities, both cellular and humoral, are involved in the pathogenesis of vitiligo.     

The direct cost of patients with multiple sclerosis: a survey from Italian MS centres

Multiple sclerosis (MS) is a chronic progressive disease of the CNS causing disability and neurological symptoms that carry a substantial burden. Previous Italian studies appear outdated, and investigation on the burden of recently marketed drug treatments should provide further economic evidence for policy makers. The objective of the study was to investigate patterns of care, resource consumption and direct medical cost of MS, in the perspective of the public health-care provider. Ten MS experts from public centres extracted and reported data of all MS patients seen during 2009, using a detailed questionnaire. The data of 8,326 MS patients were analysed: the course was relapsing?Cremitting in 5,376 (62%), secondary progressive in 1,798 (23%) and primary progressive in 691 (9%); 461 (6%) had a clinically isolated syndrome. The EDSS score was 0?C3.5 in 5,118 (61%) patients, 4?C6.5 in 2,408 (29%) and 7?C9.5 in 800 (10%). The average cost of diagnosis (N?=?694) was 1,236??/patient with large variations between centres due to the chosen diagnostic setting. The average direct medical cost for biological disease-modifying drugs (bio-DMD) was 10,444??/patient/year (cost/patient by primary drug: 9,501?? for interferon (IFN)-beta1a-im; 8,553?? for IFN-beta1b; 11,255?? for IFN-beta1a-sc44; 9,883?? for IFN-beta1a-sc22; 8,174?? for glatiramer acetate (GA); 21,817?? for natalizumab) and 3,151?? for non-bio-DMD. The cost of diagnosis is largely influenced by care setting, due to local health-care provision patterns. The annual medical cost/patient is largely driven by the cost of drugs (89.2% of total); GA represents the least expensive bio-DMD in the Italian health-care setting.     

Septal Dyskinesia and Global Left Ventricular Dysfunction in Pediatric Wolff‐Parkinson‐White Syndrome with Septal Accessory Pathway

LV Dysfunction in WPW Syndrome. Introduction: Echocardiographic studies have shown that some patients with Wolff‐Parkinson‐White (WPW) syndrome have myocardial dyskinesia in the segments precociously activated by an accessory pathway (AP). The aim of the present study was to determine the extent to which the AP contributes to global left ventricular (LV) dysfunction. Methods: Electrophysiological and echocardiographic data from 62 children with WPW (age at diagnosis = 5.9 ± 4.2 years) were retrospectively analyzed. Results: The left ventricular ejection fraction (LVEF) of patients with septal APs (53 ± 11%) was significantly lower than that of patients with right (62 ± 5%) or left (61 ± 4%) APs (P = 0.001). Compared to patients with normal septal motion (n = 56), patients with septal dyskinesia (n = 6) had a reduced LVEF (61 ± 4% and 42 ± 5%, respectively) and an increased LV end diastolic dimension (P < 0.001 for both comparisons). Multivariate analysis identified septal dyskinesia as the only significant risk factor for reduced LVEF. All 6 patients with septal dyskinesia had right septal APs, and a preexcited QRS duration that was longer than that of patients with normal septal motion (140 ± 18 ms and 113 ± 32 ms, respectively; P = 0.045). After RFA there were improvements in both intraventricular dyssynchrony (septal‐to‐posterior wall motion delay, from 154 ± 91 ms to 33 ± 17 ms) and interventricular septal thinning (from 3.0 ± 0.5 mm to 5.3 ± 2.6 mm), and a significant increase in LVEF (from 42 ± 5% to 67 ± 8%; P = 0.001). Conclusion: The dyskinetic segment activated by a right septal AP in WPW syndrome may lead to ventricular dilation and dysfunction. RFA produced mechanical resynchronization, reverse remodeling, and improvements in LV function. (J Cardiovasc Electrophysiol, Vol. 21, pp. 290–295, March 2010)     

Coagulation Effect of Sugammadex as Determined by Thromboelastography in a Randomized Controlled Study of Surgical Patients

Introduction: Sugammadex has been shown to be associated with prolongation of prothrombin time and activated partial thromboplastin time. However, it is not known whether it could be associated with enhancing postoperative hypocoagulation. The objective of this study was to analyze the effect of 4 mg/kg of sugammadex on thromboelastography (TEG) parameters in surgical patients.Methods: After Institutional Review Board approval, a prospective double-blinded randomized controlled study was conducted between September 2016 and April 2017. Sixty adult patients scheduled for laparoscopic abdominal surgery were randomly allocated to receive either sugammadex 4 mg/kg (sugammadex group) or pyridostigmine 0.15 mg/kg in combination with glycopyrrolate 0.4 mg (control group) to reverse rocuronium-induced neuromuscular blockade at the completion of surgery. Blood samples were collected three time points; After the final suture of surgery (baseline) (T1), and at 10 min (T2) and 1 h (T3) after administration of the study drug. Whole blood was analyzed by TEG using TEG 5000 (Hemonetics Corp, Braintree, MA, USA). The primary endpoints were comparison of coagulation time (K, time to 20 mm clot amplitude), R (reaction time), alpha angle, and maximal amplitude (MA) between two groups.Results: Coagulation time was significantly prolonged in sugammadex group after 10 min of the study drug administration compared to control group (mean value 1.3 ± 0.4 vs. 1.5 ± 0.4, P = 0.03). However, R, alpha angle and MA value were not different between two groups.Conclusions: Sugammadex 4 mg/kg showed an increase in coagulation time in surgical patients. Physician should aware the potential enhancement of hypocoagulation by sugammadex in the setting of high risk of postoperative bleeding.     

Improvement of Dementia Screening Accuracy of Mini-Mental State Examination by Education-Adjustment and Supplementation of Frontal Assessment Battery Performance

This study aimed to investigate whether the demographic variable-adjustment and supplementation of Frontal Assessment Battery (FAB) score can improve the screening ability of Mini-Mental State Examination (MMSE) for dementia and its subtypes. Five hundred forty-one non-demented comparison (NC) and 474 dementia (320 Alzheimer''s disease [AD]; 139 non-Alzheimer''s disease dementia [NAD]; and 15 mixed AD-NAD dementia) individuals living in the community were included. Education-adjusted MMSE (MMSE-edu) score showed significantly better screening accuracy for overall dementia, AD, and NAD than MMSE raw score. FAB-supplemented MMSE (MMSE-FAB) score had significantly better screening ability for NAD, but not for overall dementia and AD, than MMSE raw score alone. Additional supplementation of FAB to MMSE-edu further increased the ability for overall dementia or NAD screening, but not for AD screening. Further education adjustment of MMSE-FAB also improved its ability for overall dementia, AD, and NAD screening. These results strongly support the usefulness of education-adjustment and supplementation of frontal function assessment to improve screening performance of MMSE for dementia and its subtypes, NAD in particular.     

Superimposition of nutcracker syndrome in a hematuric child with idiopathic hypercalciuria and urolithiasis

We report a 5-year-old girl with idiopathic hypercalciuria who developed gross hematuria and left flank pain despite normalization of calciuria, a renal stone, and microscopic hematuria. She was found to have nutcracker syndrome by renal Doppler ultrasound, which revealed the significant differences of the peak blood flow velocities in the two portions of the left renal vein.