Traitement de l’hyperthyroïdie par l’iode 131 : à propos de 280 cas

We report through this work the experience of nuclear medicine department at Ibn-Sina hospital (Rabat), in the treatment of hyperthyroidism with iodine-131. We retrospectively studied a cohort of 280 patients with hyperthyroidism, from several regions of Morocco between January 2001 and January 2010. A clinical examination and a serum assessment of TSHus, FT4 and FT3 have been made at baseline and at 3, 6, 12 and 24 months after radioiodine therapy. The activity of iodine-131 administered ranged from 296 to 740 MBq and depended on the pathology being treated, age, thyroid volume, intensity of clinical and biological hyperthyroidism and socioeconomic situation. Radioiodine therapy has often been proposed as a treatment for second or third intention, 71 patients were initially treated with iodine-131, while 209 patients had received iodine-131 after failure of medical treatment and/or recurrence after surgical treatment. Graves’ disease was the most common etiology (60%), followed by toxic adenoma (20%), and multinodular toxic goiter (13%). The therapeutic efficacy of a single dose of radioiodine evaluated after a 6-months follow-up was 92% in Graves’ disease, 98% in toxic adenomas and 97% in toxic multinodular goiter. No acute complication was observed. Taking into account our socioeconomic context, radioiodine therapy remains the preferred treatment of hyperthyroidism in our country with good value vs. price and excellent tolerance.     

Mechanistic insights into mode of action of potent natural antagonists of BACE-1 for checking Alzheimer’s plaque pathology

Alzheimer’s is a neurodegenerative disorder resulting in memory loss and decline in cognitive abilities. Accumulation of extracellular beta amyloidal plaques is one of the major pathology associated with this disease. β-Secretase or BACE-1 performs the initial and rate limiting step of amyloidic pathway in which 37–43 amino acid long peptides are generated which aggregate to form plaques. Inhibition of this enzyme offers a viable prospect to check the growth of these plaques. Numerous efforts have been made in recent years for the generation of BACE-1 inhibitors but many of them failed during the preclinical or clinical trials due to drug related or drug induced toxicity. In the present work, we have used computational methods to screen a large dataset of natural compounds to search for small molecules having BACE-1 inhibitory activity with low toxicity to normal cells. Molecular dynamics simulations were performed to analyze molecular interactions between the screened compounds and the active residues of the enzyme. Herein, we report two natural compounds of inhibitory nature active against β-secretase enzyme of amyloidic pathway and are potent lead molecules against Alzheimer’s disease.     

Molecular analysis for mitochondrial DNA disorders

In this article, we review the current methodologies used for the molecular diagnosis of mitochondrial DNA defects. Definition of mitochondrial disorders at the molecular level has been difficult because of both clinical and genetic heterogeneity. Direct DNA analysis for common point mutations and large mtDNA deletions is readily performed and can be done routinely. However, a large number of patients who have the clinical manifestations and muscle pathology findings consistent with mitochondrial DNA disorders do not have detectable common mutations. Additional mutation screening methods are required for the detection of rare and previously undescribed mutations in the mitochondrial genome.     

Partie 2. Orthopedie – Traumatologie

Bone scintigraphy is a nuclear imaging scan using a radiopharmaceutical composed of a bisphosphonate coupled to a radionuclide (technetium 99 m). Radiopharmaceutical uptake is particularly important at the level of the bone structures having a strong osteoblastic activity. These uptakes can be due to a benign pathology (fracture, loosening of prosthesis, rheumatic pathologies, etc.) or to a malignant pathology (primary or secondary bone lesion). The high sensitivity of bone scintigraphy makes it particularly interesting at the initial stage of the pathology, especially when x-rays are normal. In addition, its specificity has clearly improved in recent years with the increasingly use of tomoscintigraphy coupled with X-ray scanning (SPECT/CT). We describe the operating principle of bone scintigraphy, normal uptakes with its variants as well as pathological uptake features in traumatic, rheumatic, prosthetic or cancerous pathologies.     

Guest Lecture 9.45–10.30 Wednesday 17 September 2003

The success of the Cervical Screening Programme (CSP) is due in part to its management being underpinned by Quality Assurance. These measures ensure uniform standards across the country. Since 1992 Colposcopy Guidelines have been in place; these were updated in 1997 and have just been redefined. It is entirely consistent with the National CSP that colposcopy is governed by Guidelines.
The aim of clinical practice guidelines is to raise the standard of care and improve outcomes. The objectives are, therefore:

The credibility of guidelines is crucial to their adoption and this depends far more on the demonstration of an evidence base than that the authors are 'experts'. Development by a professional group or body who are seen as having a legitimate role is very important as is involvement of all 'stakeholders' in ensuring acceptability.
In terms of their nature, guidelines should be valid i.e. they will achieve what they are intended to achieve, and they should be robust i.e. they will work when implemented by different individuals in different settings. Colposcopy lends itself well to guidelines because it is largely a routine practice, but substandard care can have serious consequences.
In previous years there has been a set of Guidelines for Practice ^{1, 2} and a set of Quality Standards ³ . On this occasion these two components have been put together in a simple publication.
It needs to be borne in mine that the new guidelines were being developed in the context of a number of potential changes which could interact with each other and impact on the Guidelines. These include:
 

     

Onychomycosis Due to <Emphasis Type="Italic">Aspergillus</Emphasis> spp.: a Current Review

Purpose of Review

The incidence of onychomycosis by Aspergillus has shown an increase in recent years, representing 34–60% of onychomycosis due to non-dermatophyte molds. At least 26 species of Aspergillus causing onychomycosis have been reported, some of which may be morphologically indistinguishable but genetically distinct, even in their susceptibility profile to antifungals. So in the diagnosis of this pathology, it is necessary to use both conventional and molecular methods to get to the identification of the fungus at the species level and thus establish the appropriate treatment.

Recent Findings

The current taxonomy of the genus Aspergillus includes sections that are made up of species whose morphology is almost identical but have different patterns of susceptibility to antifungals. Advances in the taxonomy of these fungi reveal the need to combine phenotypic methods (analysis of microscopic and macroscopic characteristics) with molecular ones (amplification and sequencing of fragments of the β-tubulin and calmodulin genes) to achieve their correct identification at the level of species.

Summary

From the demonstration of Aspergillus as the primary agent of onychomycosis, an increase in the incidence of this pathology worldwide has been reported, whose treatment is usually complicated. Various species of Aspergillus can cause nail infection but may respond differently to antifungal treatment, so it is important to know their epidemiology, clinical characteristics, etiologic agents, diagnostic methods, and treatment.

     

Molecular pathology in the diagnosis and treatment of non-Hodgkin's lymphomas

The non-Hodgkin's lymphomas encompass a wide spectrum of hematologic neoplasms that exhibit different clinical and biological features. Lymphomas classically have been initially assessed based on their cytologic and histologic features. Morphology alone is often inadequate as similar appearing neoplasms may be immunophenotypically and molecularly heterogeneous. Molecular diagnostic methods can provide an additional level of testing that not only helps refine diagnoses but can provide prognostic information. New methods are being refined that may provide information to establish precise diagnostic profiles, provide targets for therapy and provide more sensitive methods for monitoring the success of treatment. Molecular methods will be increasingly utilized and eventually required as the accepted method of diagnosis and for monitoring the disease. Understanding of the molecular abnormality and the pathogenesis of the neoplasm hopefully will lead to therapeutic intervention aimed at the specific molecular defect or its product. The molecular pathology of the non-Hodgkin's lymphomas is discussed.     

Molecular methods used in clinical laboratory: prospects and pitfalls

The role of molecular detection, identification and typing or fingerprinting of microorganisms has shifted gradually from the academic world to the routine diagnostic laboratory. Molecular methods have been used increasingly over the past decade to improve the sensitivity, specificity and turn-around time in the clinical laboratory. Molecular methods have also been used to identify new and nonculturable agents. Many high-throughput molecular tests are now available commercially, which impacts on the infrastructure in many of the diagnostic laboratories. In this paper, we take an overall look at the use of molecular methods (prospects vs. pitfalls) based on our clinical and public health experience, particularly as they related to Borrelia burgdorferi, a vector-borne pathogen, Treponema pallidum, a re-emerging sexually transmitted global pathogen, and West Nile virus, a newly recognized virus in North America.     

The 50 year evolution of in vitro systems to reveal salt transport functions of teleost fish gills

This short review traces the history of in vitro experimental methods that have been used to help elucidate the ion transport mechanisms of teleost fish gills. It begins with an isolated gill preparation published by Denis Bellamy in 1961 and progresses through many different approaches and concludes with current techniques. Among them are perfused gill arches, primary cultures of gill epithelia, isolated opercular skin preparations, whole embryos in vitro, the yolk-ball technique, dissociated gill epithelial cells, vibrating microprobe and scanning ion-selective microelectrodes; currently all are combined with molecular biological techniques. Each new approach brought new findings but is subject to certain limitations and each has contributed significantly to this important subfield of comparative physiology.     

Genetic disorders of the skeleton: a developmental approach

Although disorders of the skeleton are individually rare, they are of clinical relevance because of their overall frequency. Many attempts have been made in the past to identify disease groups in order to facilitate diagnosis and to draw conclusions about possible underlying pathomechanisms. Traditionally, skeletal disorders have been subdivided into dysostoses, defined as malformations of individual bones or groups of bones, and osteochondrodysplasias, defined as developmental disorders of chondro-osseous tissue. In light of the recent advances in molecular genetics, however, many phenotypically similar skeletal diseases comprising the classical categories turned out not to be based on defects in common genes or physiological pathways. In this article, we present a classification based on a combination of molecular pathology and embryology, taking into account the importance of development for the understanding of bone diseases.     

Insulin‐like growth factor axis targeting in cancer and tumour angiogenesis – the missing link

Numerous molecular players in the process of tumour angiogenesis have been shown to offer potential for therapeutic targeting. Initially denoted to be involved in malignant transformation and tumour progression, the insulin‐like growth factor (IGF) signalling axis has been subject to therapeutic interference, albeit with limited clinical success. More recently, IGFs and their receptors have received attention for their contribution to tumour angiogenesis, which offers novel therapeutic opportunities. Here we review the contribution of this signalling axis to tumour angiogenesis, the mechanisms of resistance to therapy and the interplay with other pro‐angiogenic pathways, to offer insight in the renewed interest in the application of IGF axis targeting agents in anti‐cancer combination therapies.     

Molecular imaging of autoimmune diseases and inflammation

Molecular imaging methods allow the noninvasive detection and localization of specific molecules. Agents that report on molecular disease biomarkers can be used to diagnose and monitor disease. Many inflammatory diseases have molecular signatures within altered tissues. Although tissue biopsy is still the gold standard for detecting these signatures, several molecular imaging markers have been developed. Pharmacologic agents that block specific immune molecules have recently entered the clinic, and these drugs have already transformed the way we care for patients with immune-mediated diseases. The use of immunomodulatory drugs is usually guided by clinical assessment of the patient's response. Unfortunately, clinical assessment may miss the signs of inflammation, and many of the serologic markers of immune-mediated diseases correlate poorly with the underlying inflammatory activity within target tissues. Molecular imaging methods have the potential to improve our ability to detect and characterize tissue inflammation. We discuss some of the molecular signatures of immune activation and review molecular imaging methods that have been developed to detect active tissue inflammation.     

100 years of Haldane's rule

Haldane's rule is one of the ‘two rules of speciation’. It states that if one sex is ‘absent, rare or sterile’ in a hybrid population, then that sex will be heterogametic. Since Haldane first made this observation, 100 years have passed and still questions arise over how many independent examples exist and what the underlying causes of Haldane's rule are. This review aims to examine research that has occurred over the last century. It seeks to do so by discussing possible causes of Haldane's rule, as well as gaps in the research of these causes that could be readily addressed today. After 100 years of research, it can be concluded that Haldane's rule is a complicated one, and much current knowledge has been accrued by studying the model organisms of speciation. This has led to the primacy of dominance theory and faster-male theory as explanations for Haldane's rule. However, some of the most interesting findings of the 21st century with regard to Haldane's rule have involved investigating a wider range of taxa emphasizing the need to continue using comparative methods, including ever more taxa as new cases are discovered.     

Exploiting drug-disease relationships for computational drug repositioning

Finding new uses for existing drugs, or drug repositioning, has been used as a strategy for decades to get drugs to more patients. As the ability to measure molecules in high-throughput ways has improved over the past decade, it is logical that such data might be useful for enabling drug repositioning through computational methods. Many computational predictions for new indications have been borne out in cellular model systems, though extensive animal model and clinical trial-based validation are still pending. In this review, we show that computational methods for drug repositioning can be classified in two axes: drug based, where discovery initiates from the chemical perspective, or disease based, where discovery initiates from the clinical perspective of disease or its pathology. Newer algorithms for computational drug repositioning will likely span these two axes, will take advantage of newer types of molecular measurements, and will certainly play a role in reducing the global burden of disease.     

Clinical applications of molecular biology for infectious diseases

Molecular biological methods for the detection and characterisation of microorganisms have revolutionised diagnostic microbiology and are now part of routine specimen processing. Polymerase chain reaction (PCR) techniques have led the way into this new era by allowing rapid detection of microorganisms that were previously difficult or impossible to detect by traditional microbiological methods. In addition to detection of fastidious microorganisms, more rapid detection by molecular methods is now possible for pathogens of public health importance. Molecular methods have now progressed beyond identification to detect antimicrobial resistance genes and provide public health information such as strain characterisation by genotyping. Treatment of certain microorganisms has been improved by viral resistance detection and viral load testing for the monitoring of responses to antiviral therapies. With the advent of multiplex PCR, real-time PCR and improvements in efficiency through automation, the costs of molecular methods are decreasing such that the role of molecular methods will further increase. This review will focus on the clinical utility of molecular methods performed in the clinical microbiology laboratory, illustrated with the many examples of how they have changed laboratory diagnosis and therefore the management of infectious diseases.     

食管鳞癌相关基因与预后及临床病理关系的研究进展

食管鳞癌是一种多因素的疾病,除了环境因素可以影响食管癌发生和发展,分子水平的基因改变是近年研究的热点。近年基因芯片技术的发展,已发现众多基因,如β-catenin、wnt1、p53、cyclinD1以及EGFR等基因表达的改变与食管鳞癌的发生、发展或预后相关,从而可更好地寻找判断预后的分子指标,具有广阔的应用前景,但其与影响食管鳞癌预后的众多因素之间的关系及其与临床病理的关系以及应用,仍需进一步研究。     

Spontaneous development of Alzheimer's disease‐associated brain pathology in a Shugoshin‐1 mouse cohesinopathy model

Spontaneous late‐onset Alzheimer's disease (LOAD) accounts for more than 95% of all human AD. As mice do not normally develop AD and as understanding on molecular processes leading to spontaneous LOAD has been insufficient to successfully model LOAD in mouse, no mouse model for LOAD has been available. Existing mouse AD models are all early‐onset AD (EOAD) models that rely on forcible expression of AD‐associated protein(s), which may not recapitulate prerequisites for spontaneous LOAD. This limitation in AD modeling may contribute to the high failure rate of AD drugs in clinical trials. In this study, we hypothesized that genomic instability facilitates development of LOAD and tested two genomic instability mice models in the brain pathology at the old age. Shugoshin‐1 (Sgo1) haploinsufficient (?) mice, a model of chromosome instability (CIN) with chromosomal and centrosomal cohesinopathy, spontaneously exhibited a major feature of AD pathology; amyloid beta accumulation that colocalized with phosphorylated Tau, beta‐secretase 1 (BACE), and mitotic marker phospho‐Histone H3 (p‐H3) in the brain. Another CIN model, spindle checkpoint‐defective BubR1^?/+ haploinsufficient mice, did not exhibit the pathology at the same age, suggesting the prolonged mitosis‐origin of the AD pathology. RNA‐seq identified ten differentially expressed genes, among which seven genes have indicated association with AD pathology or neuronal functions (e.g., ARC, EBF3). Thus, the model represents a novel model that recapitulates spontaneous LOAD pathology in mouse. The Sgo1^?/+ mouse may serve as a novel tool for investigating mechanisms of spontaneous progression of LOAD pathology, for early diagnosis markers, and for drug development.