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 Previous Italian studies appear outdated, and investigation on the burden of recently marketed drug treatments should provide further economic evidence for policy makers.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.     

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.     

Hematopoietic stem cells are not direct cytotoxic targets of natural killer cells

Bone marrow (BM) transplants from one individual to an irradiated histoincompatible individual of the same species are rejected. In mice, the primary host barrier cells that recognize bone marrow grafts bearing hematopoietic histocompatibility antigens bear surface markers of natural killer (NK) lymphocytes. Because of the innate ability of NK cells to kill susceptible targets, it has been proposed that the cytotoxic bone marrow graft rejection. To test this hypothesis, we purified hematopoietic stem cells from mice and incubated them with purified populations of actively cytotoxic allogeneic and semisyngeneic NK cells, followed by analysis of the ability of the treated hematopoietic stem cells (HSCs) to rescue lethally irradiated syngeneic animals. Such rescue was unimpaired. Also, HSC allografts were transplanted into transgenic mice deficient in NK and killer T-cell cytotoxicity generated by expressing diphtheria toxin A chain under the control of granzyme A promoter. Allogeneic HSCs were susceptible to allogeneic restriction in these mice, implying that the effector functions of NK marker-positive cells do not require NK cell cytotoxicity.     

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.     

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.     

Utilization of retrieved oocytes as an index of the efficiency of superovulation strategies for in-vitro fertilization treatment

An analysis of 581 in-vitro fertilization treatment cycles was carried out to determine the pattern of utilization of retrieved oocytes. Patients were divided into five groups depending on the number of retrieved oocytes. The mean fertilization rate of 57% was broadly similar amongst the groups but the proportion of retrieved oocytes that produced embryos of a quality suitable for transfer or cryopreservation (the cycle efficiency index) fell significantly with increase in the retrieved oocyte number. However, the pregnancy rate increased with the number of retrieved oocytes (13-38%). It is important to determine the point at which advantages of multifollicular development are outweighed by the potential for complications. Increased utilization of retrieved oocytes will decrease the need for production of a large number of oocytes.      

Astrocytosis measured by 11C-deprenyl PET correlates with decrease in gray matter density in the parahippocampus of prodromal Alzheimer’s patients

Purpose

The Alzheimer’s disease (AD) pathology is characterized by fibrillar amyloid deposits and neurofibrillary tangles, as well as the activation of astrocytosis, microglia activation, atrophy, dysfunctional synapse, and cognitive impairments. The aim of this study was to test the hypothesis that astrocytosis is correlated with reduced gray matter density in prodromal AD.

Methods

Twenty patients with AD or mild cognitive impairment (MCI) underwent multi-tracer positron emission tomography (PET) studies with ¹¹C-Pittsburgh compound B (¹¹C-PIB), ¹⁸?F-Fluorodeoxyglucose (¹⁸?F-FDG), and ¹¹C-deuterium-L-deprenyl (¹¹C-DED) PET imaging, as well as magnetic resonance imaging (MRI) scanning, cerebrospinal fluid (CSF) biomarker analysis, and neuropsychological assessments. The parahippocampus was selected as a region of interest, and each value was calculated for four different imaging modalities. Correlation analysis was applied between DED slope values and gray matter (GM) densities by MRI. To further explore possible relationships, correlation analyses were performed between the different variables, including the CSF biomarker.

Results

A significant negative correlation was obtained between DED slope values and GM density in the parahippocampus in PIB-positive (PIB?+?ve) MCI patients (p?=?0.025) (prodromal AD). Furthermore, in exploratory analyses, a positive correlation was observed between PIB-PET retention and DED binding in AD patients (p?=?0.014), and a negative correlation was observed between PIB retention and CSF Aβ42 levels in MCI patients (p?=?0.021), while the GM density and CSF total tau levels were negatively correlated in both PIB?+?ve MCI (p?=?0.002) and MCI patients (p?=?0.001). No significant correlation was observed with FDG-PET and with any of the other PET, MRI, or CSF biomarkers.

Conclusions

High astrocytosis levels in the parahippocampus of PIB?+?ve MCI (prodromal AD) patients suggest an early preclinical influence on cellular tissue loss. The lack of correlation between astrocytosis and CSF tau levels, and a positive correlation between astrocytosis and fibrillar amyloid deposition in clinical demented AD together indicate that parahippocampal astrocytosis might have some causality within the amyloid pathology.