Mycosis fungoides and Sézary syndrome: Current challenges in assessment,management and prognostic markers

Mycosis fungoides and Sézary syndrome are the most common variants of the cutaneous T‐cell lymphomas. Assessment of a patient with a suspected diagnosis requires thorough history taking and physical examination, in combination with skin biopsy. In some cases flow cytometry, molecular studies and imaging are also required in order to diagnose and stage the disease. Staging is derived from the tumour‐node‐metastasis‐blood classification and is currently our best attempt to stratify prognosis and hence guide management in this complex disease. Many other clinical, biological and pathological factors may help to distinguish groups at risk and predict prognosis more accurately. Management remains heavily guided by staging, such that patients with early‐stage disease generally begin treatment with skin‐directed or local therapies and those with advanced‐stage disease have many treatment options, including chemotherapy, the use of biological agents, local and total body radiotherapy, as well as haematopoietic stem cell transplantation. Besides staging, many other patient‐related factors influence the treatment strategy, particularly where symptom relief is paramount. There are many challenges remaining in the study of Mycosis fungoides and Sézary syndrome and, given the rarity of the disease, concerted worldwide efforts are required to conduct efficient and effective research.     

Does a reduced glucose intake prevent hyperglycemia in children early after cardiac surgery? a randomized controlled crossover study

Introduction

Hyperglycemia in children after cardiac surgery can be treated with intensive insulin therapy, but hypoglycemia is a potential serious side effect. The aim of this study was to investigate the effects of reducing glucose intake below standard intakes to prevent hyperglycemia, on blood glucose concentrations, glucose kinetics and protein catabolism in children after cardiac surgery with cardiopulmonary bypass (CPB).

Methods

Subjects received a 4-hour low glucose (LG; 2.5 mg/kg per minute) and a 4-hour standard glucose (SG; 5.0 mg/kg per minute) infusion in a randomized blinded crossover setting. Simultaneously, an 8-hour stable isotope tracer protocol was conducted to determine glucose and leucine kinetics. Data are presented as mean ± SD or median (IQR); comparison was made by paired samples t test.

Results

Eleven subjects (age 5.1 (20.2) months) were studied 9.5 ± 1.9 hours post-cardiac surgery. Blood glucose concentrations were lower during LG than SG (LG 7.3 ± 0.7 vs. SG 9.3 ± 1.8 mmol/L; P < 0.01), although the glycemic target (4.0-6.0 mmol/L) was not achieved. No hypoglycemic events occurred. Endogenous glucose production was higher during LG than SG (LG 2.9 ± 0.8 vs. SG 1.5 ± 1.1 mg/kg per minute; P = 0.02), due to increased glycogenolysis (LG 1.0 ± 0.6 vs. SG 0.0 ± 1.0 mg/kg per minute; P < 0.05). Leucine balance, indicating protein balance, was negative but not affected by glucose intake (LG -54.8 ± 14.6 vs. SG -58.8 ± 16.7 μmol/kg per hour; P = 0.57).

Conclusions

Currently recommended glucose intakes aggravated hyperglycemia in children early after cardiac surgery with CPB. Reduced glucose intake decreased blood glucose concentrations without causing hypoglycemia or affecting protein catabolism, but increased glycogenolysis.

Trial registration

Dutch trial register NTR2079.     

倾斜试验中真假阳性的血流动力学和神经激素的研究

目的探讨血管迷走性晕厥患者和正常人倾斜试验阳性时不同的触发机制.方法倾斜试验采用静息平卧10min和80°直立30min.心脏监测仪连续监测心率和血压.试验阳性标准为晕厥先兆伴收缩压＜90imHg(1mmHg=O.133kPa)和(或)心率＜60次/min.超声心动图于基础平卧,直立2min和每隔3min直至试验结束时连续记录左室内径及降低速率,左室短轴缩短分数(SF)和每分心输出量(CO).同时测量平卧和直立时儿茶酚胺血浆浓度.试验分组为正常自愿者且倾斜试验阴性者8例(组1),平均年龄(34±5)岁;正常自愿者伴倾斜试验阳性者8例(组2),平均年龄(31±6)岁;原因不明晕厥伴倾斜试验阳性者16例(组3),平均年龄(30±9)岁.结果三组间年龄、性别以及基础状态下心率,平均动脉压、左室内径、SF、CO和儿茶酚胺血浆浓度无明显差异.直立时各组发生改变为(1)组3出现阳性反应时间明显短于组2[(10±4)min比(17±8)min,P＜0.05];(2)组3平均动脉压有即刻和持续性降低;(3)组3左室舒张末期内径降低速率明显大于其他两组;(4)SF在组3显著增强;(5)肾上腺素浓度在组3升高显著,试验终止时组1为(65±35)pg/ml,组2为(78±29)pg/ml,组3为(126±80)pg/ml(P均＜0.05);去甲肾上腺素在三组均增高但组间比较差异无显著性.结论血管迷走性晕厥患者和部分正常人倾斜试验虽均呈阳性反应,但血流动力学反应和触发机制不同.前者可能与外周血管张力异常,回心血量及左室容量聚降,肾上腺素分泌增多,促使左室收缩力增强触发Bezold-Jarisch神经反射有关;而后者在发生假阳性反应时,其左室内径和SF及肾上腺素血浆浓度与阴性组无明显不同.倾斜试验时血管迷走性晕厥患者肾上腺素分泌异常在血管舒缩反应损害和左室收缩力异常方面可能起恶化作用.     

Regulation of MYCN expression in human neuroblastoma cells

Background  

Amplification of the MYCN gene in neuroblastoma (NB) is associated with a poor prognosis. However, MYCN -amplification does not automatically result in higher expression of MYCN in children with NB. We hypothesized that the discrepancy between MYCN gene expression and prognosis in these children might be explained by the expression of either MYCN-opposite strand (MYCNOS) or the shortened MYCN-isoform (ΔMYCN) that was recently identified in fetal tissues. Both MYCNOS and ΔMYCN are potential inhibitors of MYCN either at the mRNA or at the protein level.     

Detection of human sperm acrosome reaction: comparison between methods using double staining, Pisum sativum agglutinin, concanavalin A and transmission electron microscopy

The acrosome reaction is an important marker for human sperm function. Since different laboratory techniques may be used for the detection of this exocytotic process, the purpose of the present study was to compare three common markers [Pisum sativum agglutinin (PSA), concanavalin A (ConA), double staining] and transmission electron microscopy for identification of acrosomal changes. Preliminary findings had demonstrated that similar results were achieved with Trypan Blue and Hoechst 33258 staining. Therefore, supravital stainings were omitted. In various experiments, human spermatozoa were treated with two concentrations (10 and 3.3 microM) of calcium ionophore A23187 for 15, 30 and 60 min after capacitation for 3 and 6 h at 37 degrees C. The percentages of spermatozoa with acrosomal loss detected by fluorescein isothiocyanate (FITC)-ConA were consistently lower than those obtained by double staining or FITC-PSA, which showed comparable results. Following 6 h of capacitation and incubation with 10 microM ionophore for 1 h at 37 degrees C, 25.9 +/- 15.7% of all spermatozoa showed almost complete loss of the acrosomal content. Binding of FITC- ConA to the acrosomal region was observed in 27.0 +/- 13.2% of spermatozoa obtained from the same sample. FITC-ConA and double staining or FITC-PSA detect different stages of the acrosome reaction and may be helpful for a differentiated evaluation of this sperm function.      

Peripheral neuropathy as initial sign of mitochondrial disorder

Charcot‐Marie‐Tooth disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory peripheral neuropathies. On the basis of electrophysiologic properties and histopathology, CMT has been divided into demyelinating (type 1) and axonal (type 2) neuropathies. The form of Charcot‐Marie‐Tooth neuropathy that maps to Xq13 may present mild electrophysiological changes (NCV > 40 M/s), mixed neuropathy (NCV: Intermediate (30–40 M/s), or demyelinating neuropathy (NCV: Slow (<37 M/s). On molecular grounds, CMTX is caused by mutations in GJB1 gene, coding for Connexin 32 protein. A 42‐year‐old man, with no other affected family members, was clinically evaluated for CMT. Three years ago he noticed thumb abductor atrophy and then leg muscle atrophy. He presented with hand and leg muscle atrophy, bilateral pes cavus, areflexia, and apallesthesia. The median and ulnar motor NVC were 35–38 m/s, and the median sensory NVC was 35 m/s. Both motor and sensory nerve action potentials were markedly reduced. After exclusion of CMT1A and 1B, analysis for CMTX was performed. The mutation screening of GJB1 gene showed a 9bp insertion upstream the 194ATG codon (Met194) with preservation of the downstream sequence. The three new amino acids (Thr‐Val‐Phe) inserted are localized between the end of the second extracellular domain and the beginning of the fourth transmembrane domain. This is the first 9bp insertion found in GJB1 gene; a genotype‐phenotype correlation may be deduced.