Intérêt de la TEP/TDM au FDG dans l’investigation étiologique des syndromes paranéoplasiques

Paraneoplastic syndromes (PNS) represent a rare and heterogeneous group of entities whose clinical symptoms may sometimes antedate the diagnosis of the causative tumor. In the context, the identification of the underlying tumor becomes very important for the patient's functional and sometimes vital prognosis, by allowing an earliest treatment of the tumor. ¹⁸FDG PET/CT has become indispensable in the diagnosis and follow-up of numerous cancers but its role in etiological investigation of isolated paraneoplastic syndromes for the research of an occult tumor is not defined yet. Nevertheless, requests of PET/CT in this indication are frequent in nuclear medicine departments, with an uncertain diagnostic yield. We have listed retrospectively 64 patients, sent to nuclear medicine department of Nancy university hospital between 2004 and 2010 for the research of an occult tumor because of a clinically suspected paraneoplastic syndrome, in order to estimate its diagnostic contribution in this indication. According to our results, ¹⁸FDG PET-CT would be interesting by its negative predictive value concerning the tumoral risk, in keeping with its known sensitivity PET-CT may also present an interest for the diagnosis and the characterization of non-tumoral conditions generating symptoms initially wrongly suspected to be paraneoplastic.     

Parkinson's disease: from causes to mechanisms

Parkinson's disease (PD) is a common age-related, progressive neurodegenerative disease of unknown etiology. Environmental factors have long been suspected to participate in the pathogenesis of PD due to the existence of neurotoxins that preferentially damage the dopaminergic nigrostriatal pathway. In the past few years, novel insights into the degenerative process have been provided by the discovery of genes responsible for rare monogenic parkinsonian syndromes. Compelling evidence is accumulating, suggesting that the products of several of these genes can interact with environmental toxins and intervene in molecular pathways controlling the functional integrity of mitochondria.     

Fusarium mycotoxins: a review of global implications for animal health, welfare and productivity

Trichothecenes, zearalenone (ZEN) and fumonisins are the major Fusarium mycotoxins occurring on a worldwide basis in cereal grains, animal feeds and forages. Other important Fusarium mycotoxins include moniliformin and fusaric acid. Spontaneous outbreaks of Fusarium mycotoxicoses have been recorded in Europe, Asia, New Zealand and South America and, in addition, chronic exposure occurs on a regular and more widespread scale. The metabolism and adverse effects of the Fusarium mycotoxins are considered in this review with particular reference to recent data on specific and proposed syndromes and to interactions among co-occurring mycotoxins. Within the trichothecene group, deoxynivalenol (DON) is associated with emesis, feed refusal and depressed feed intake in pigs, while T-2 toxin and diacetoxyscirpenol (DAS) are now clearly linked with oral lesions in poultry. The gut microflora of farm livestock are able to transform DON to a de-epoxy derivative. In contrast, the ovine metabolism of ZEN results in the production of five metabolites and relatively high levels of these forms may be excreted in the urine as glucuronides. There is now undisputed evidence that ZEN and its metabolites possess estrogenic activity in pigs, cattle and sheep, but T-2 toxin has also been implicated in reproductive disorders in farm livestock. Fumonisins are positively linked with pulmonary edema in pigs, leukoencephalomalacia in equines and with deranged sphingolipid metabolism in these animals. Fusarium mycotoxins have also been provisionally implicated in ovine ill-thrift, acute mortality of poultry and in duodenitis/proximal jejunitis of horses. Several Fusarium mycotoxins may co-occur in a particular feed ingredient or in compound feedingstuffs. In general, combinations of Fusarium mycotoxins result in additive effects, but synergistic and/or potentiating interactions have been observed and are of greater concern in livestock health and productivity. Synergistic effects have been reported between DON and fusaric acid; DON and fumonisin B₁ (FB₁); and DAS and the Aspergillus-derived aflatoxins. Limited evidence of potentiation between FB₁ and DON or T-2 toxin has also emerged recently. Additive and synergistic effects between known and unidentified mycotoxins may account for enhanced adverse effects observed on feeding Fusarium-contaminated diets. The potential for transmission of DON into eggs and of ZEN into porcine kidney and liver has been demonstrated. However, lactational carry-over of FB₁ appears not to occur, at least in cows and sows. It is concluded that livestock health, welfare and productivity may be severely compromised by consumption of DON, T-2 toxin, DAS, ZEN and fumonisins and by interactions among these mycotoxins. Safety of some animal products may also be at risk. Furthermore, in view of the limited options available for remediation, it is concluded that exploitation of crops resistant to Fusarium infection offers the most viable strategy for reducing mycotoxin contamination of grain and animal feed.     

谈《伤寒论》中的欲愈候

欲愈候是预示疾病将愈的一类证候。文章列举《伤寒论》中6种典型欲愈候，并结合后世医家评述，分别探讨其临床指征、作解机理、现代临床意义，这对于临床把握疾病的发展规律以及指导临床用药等，均具有一定的积极意义。     

骨髓增生异常综合征中相关微小RNA的研究进展

骨髓增生异常综合征(MDS)是一组异质性后天性克隆性恶性疾病,其基本临床特征是骨髓中造血细胞有发育异常的形态学表现和外周血中三系血细胞减少,以及转变为急性髓细胞性白血病(AML)的危险性很高。其鉴别诊断、评估预后对治疗决策有重要意义。近年来认为表观遗传途径参与了MDS病因和发病机制。尤其微小RNA(miRNA)在MDS的发生、发展及疾病转归中起了重要作用。本文通过miRNA的临床可监测性、与血液疾病的联系这两个方面阐述了相关miRNA研究的意义和地位;重点对MDS的诊断和临床进展中可能发挥重要作用的miRNA以及5q-综合征中miR145和miR146a等表达具有特殊性的miRNA进行了综述。以期能够在此基础上进行更深入的研究探索,使miRNA在骨髓异常增生综合征的临床诊疗中发挥更大的潜力。     

Neurodegeneration with brain iron accumulation — Clinical syndromes and neuroimaging

Iron participates in a wide array of cellular functions and is essential for normal neural development and physiology. However, if inappropriately managed, the transition metal is capable of generating neurotoxic reactive oxygen species. A number of hereditary conditions perturb body iron homeostasis and some, collectively referred to as neurodegeneration with brain iron accumulation (NBIA), promote pathological deposition of the metal predominantly or exclusively within the central nervous system (CNS). In this article, we discuss seven NBIA disorders with emphasis on the clinical syndromes and neuroimaging. The latter primarily entails magnetic resonance scanning using iron-sensitive sequences. The conditions considered are Friedreich ataxia (FA), pantothenate kinase 2-associated neurodegeneration (PKAN), PLA2G6-associated neurodegeneration (PLAN), FA2H-associated neurodegeneration (FAHN), Kufor-Rakeb disease (KRD), aceruloplasminemia, and neuroferritinopathy. An approach to differential diagnosis and the status of iron chelation therapy for several of these entities are presented. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Brown-band syndrome on feeding scars of the crown-of-thorn starfish Acanthaster?planci

Despite the growing impact of coral diseases on reef ecosystems, little is known about the role of coral predation in disease transmission. An experiment on the coral reefs of Derawan Island, Indonesia, revealed brown-band syndrome on Acropora cytherea coral colonies following predation by the crown-of-thorn starfish Acanthaster planci. To experimentally exclude predation, living coral tissue adjacent to feeding scars was enclosed using cages and monitored for 15 days. Compared with similarly caged but uninjured colonies, which showed no sign of disease or tissue loss, preyed upon colonies showed a higher incidence of the disease, coupled with further tissue mortality. This study provides preliminary evidence that A. planci might promote the transmission of some coral diseases.     

Deoxyribonucleotide metabolism in cycling and resting human fibroblasts with a missense mutation in p53R2, a subunit of ribonucleotide reductase

Ribonucleotide reduction provides deoxynucleotides for nuclear and mitochondrial (mt) DNA replication and DNA repair. In cycling mammalian cells the reaction is catalyzed by two proteins, R1 and R2. A third protein, p53R2, with the same function as R2, occurs in minute amounts. In quiescent cells, p53R2 replaces the absent R2. In humans, genetic inactivation of p53R2 causes early death with mtDNA depletion, especially in muscle. We found that cycling fibroblasts from a patient with a lethal mutation in p53R2 contained a normal amount of mtDNA and showed normal growth, ribonucleotide reduction, and deoxynucleoside triphosphate (dNTP) pools. However, when made quiescent by prolonged serum starvation the mutant cells strongly down-regulated ribonucleotide reduction, decreased their dCTP and dGTP pools, and virtually abolished the catabolism of dCTP in substrate cycles. mtDNA was not affected. Also, nuclear DNA synthesis and the cell cycle-regulated enzymes R2 and thymidine kinase 1 decreased strongly, but the mutant cell populations retained unexpectedly larger amounts of the two enzymes than the controls. This difference was probably due to their slightly larger fraction of S phase cells and therefore not induced by the absence of p53R2 activity. We conclude that loss of p53R2 affects ribonucleotide reduction only in resting cells and leads to a decrease of dNTP catabolism by substrate cycles that counterweigh the loss of anabolic activity. We speculate that this compensatory mechanism suffices to maintain mtDNA in fibroblasts but not in muscle cells with a larger content of mtDNA necessary for their high energy requirements.