Integrative multidisciplinary approaches by the Integrative Medicine Research Group (IMRG): a new frontier in cancer setting.

This conference addresses the topic of integrative, multidisciplinary approaches to cancer settings according to evidence-based medicine. The multidisciplinary approach of the researchers involved characterizes this new and complex scenario. The Integrative Medicine Research Group (IMRG) has always been committed to the activities and dissemination of CAM in cancer patients, focusing on the safety and efficacy of these approaches. Thus, one of the main goals of IMRG is to demonstrate that CAM can support cancer patients during treatment and improve their quality of life and survival. In addition, IMRG's multidisciplinary network is ever vigilant in assessing the risks of interactions between cancer drugs and nutraceuticals. We hope that the integrative medicine approach can be transferred to the level of all chronic diseases, including oncology.

Biochemical analysis of cerebrospinal fluid in the laboratories of deployed medical treatment facilities: are Multistix 10 SG strip and iSTAT useful?

INTRODUCTION: During military deployment, the diagnosis and the management of acute bacterial meningitis can be problematic, as deployed Medical Treatment Facilities (MTFs) often have a limited laboratory diagnostic capability. However, French Role 2 and 3 MTFs have point-of-care (POC) testing to perform urinary (Multistix 10 SG strip) and blood (iSTAT handheld analyser) biochemical testing mentioned in AMedP8.5. The purpose of this study was to compare the accuracy of this urine test strip and of the iSTAT CHEM8 and CG4 cartridges with a standard hospital bench top analyser in order to determine if these POC devices have a potential role in the biochemical analysis of cerebrospinal fluid (CSF protein, CSF glucose and CSF lactate, respectively). METHODS: Agreement between the index methods and the reference methods (suitable kits on the Cobas 6 000 System) was evaluated by parallel testing of 30 CSF samples by both techniques. For CSF protein, agreement between the strip and the reference method was evaluated determining the κ coefficient. For CSF glucose and CSF lactate subgroups, least squares linear regressions were calculated and Bland-Altman analyses were performed. RESULTS: The Multistix 10 SG strip can be used to make a semiquantitative determination of CSF protein. A good agreement between the strip and the reference method was observed (κ coefficient: 0.93 (IC95 0.82 to 1)). This strip is thus well adapted to demonstrate an elevation of CSF protein level as observed in acute bacterial meningitis. The iSTAT CHEM8 and CG4+ cartridges correlated well with the reference methods for the determination of CSF glucose and CSF lactate, respectively (r2>0.98) but exhibited a negative bias (∼ -7% and ∼ -15%, respectively). CONCLUSIONS: The combined use of the Multistix 10 SG strip and of the iSTAT system appears to be an attractive solution for the biochemical investigation of CSF in medical treatment facilities with limited laboratory diagnostic capability.

[Prolonged neuromuscular block in a patient with butyrylcholinesterase deficiency]. / Curarisation prolongée liée à un déficit en butyrylcholinestérase.

Succinylcholine is a neuromuscular block whose duration of action depends on rapid hydrolysis by butyrylcholinesterase (BChE). In patients with common BChE activities, succinylcholine duration of action is short (10min). BChE deficiency induces a slower hydrolysis of the drug and consequently prolonged neuromuscular block, leading to apnea. We report a case of prolonged neuromuscular block after administration of succinylcholine in a 14-year-old boy. Biological investigations revealed a marked BChE deficiency (1099U/L) related to the presence of three point mutations in the BCHE gene in a compound heterozygous state: p.Asp70Gly (rs1799807), p.Ala539Tyr (rs1803274), and p.Phe118Valfs*12 (rs398124632). The diagnosis of genetic BChE deficiency (OMIM 177400) was retained. This case is intended to present the pathophysiology of genetic BChE deficiency, its management, and the diagnostic strategy to be implemented.

[The VR, the Russian version of the nerve agent VX]. / Le VR, version russe du neurotoxique organophosphoré VX.

A product of the arms race during the Cold War, the Russian VX, or VR, is an organophosphorus compound that is a structural isomer of the western VX compound (or A4), with which it shares a very high toxicity. It is much less studied and known than VX because the knowledge of its existence is relatively recent. A very low volatility and high resistance in the environment make it a persistent agent. Poisoning occurs mainly following penetration through skin and mucosa but vapour inhalation is a credible risk in some circumstances. The clinical presentation may be differed by several hours and despite the absence of signs and symptoms, the casualty should not be considered as contamination or intoxication-free. This agent has a long residence time in blood, a characteristics that clearly differentiates it from other compounds such as sarin. The protocols for antidote administration may thus have to be changed accordingly. The fact that VR poisoned individuals will less respond to the current oxime therapy used in France, the 2-PAM and that VR represents a higher threat than VX, being probably possessed by some proliferating states, justify the interest for this toxic product.

Management of a rifampicin-resistant meningococcal infection in a teenager.

We report a secondary case of rifampicin-resistant meningococcal disease and our experience in managing contact cases. Rifampicin resistance resulting from rpoB gene mutations is still uncommon enough that changing the current recommendations for chemoprophylaxis is unwarranted. However, ensuring limited but appropriate chemoprophylaxis may prevent the development of antimicrobial resistance. Thus, the definition of contact cases should be strictly respected. In the case of culture-positive Neisseria meningitidis, in vitro susceptibility testing to rifampicin must be systematically performed in order to detect rifampicin-resistant strains and, thus, institute appropriate prophylaxis in order to prevent secondary transmission.

Hereditary neuropathy with liability to pressure palsies occurring during military training.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant peripheral neuropathy characterized by recurrent isolated nerve palsies, which are precipitated by trivial compression and trauma. Although HNPP has been well-described in literature, it often goes unrecognized. We report a case of HNPP occurring during military training to promote recognition and proper management of this entity.

[The old man and the syrup]. / Le vieil homme et le sirop.

Intoxication by glycyrrhizin is a rare cause of hypokalemia. We describe a patient with severe hypokalemia caused by long-term consumption of syrup containing liquorice. The physiopathological mechanism of the intoxication and the differential diagnosis are presented.

[Value of assaying adenosine deaminase level in patients with neuromeningeal tuberculosis]. / Intérêt du dosage de l'adénosine désaminase dans les infections tuberculeuses neuro-méningées.

Neuromeningeal tuberculosis is a rare extrapulmonary location in France. Delayed diagnosis can lead to therapeutic failure and severe sequels. However early diagnosis is a major challenge that requires the proper epidemiological, clinical, radiological and biological resources. Problems related to diagnosis of mycobacteria infection and to shortcomings in certain healthcare systems can hinder early diagnosis. The purpose of this review was to describe the diagnostic value of assaying adenosine deaminase activity in cerebrospinal fluid from patients with neuromeningeal tuberculosis. Evidence from studies published over the last 25 years indicate that the sensitivity and specificity of measuring adenosine deaminase activity range from 36 to 92% and 71 to 100% respectively depending of cutoff values used. Before performing this assay, it is necessary to rule out obvious or frequent etiologies such as purulent bacterial meningitis or cryptococcosis in HIV patients. Taken together these studies show that this simple, inexpensive technique is a valuable tool for early diagnosis and management of tuberculosis patients and that it can be easily implemented in hospital labs regardless of technical or financial resources.

[HLA-B*5701 and abacavir hypersensitivity reaction]. / Génotype HLA-B*5701 et hypersensibilité à l'abacavir.

A potentially life-threatening hypersensitive reaction occurs in association with initiation of HIV nucleoside analogue abacavir therapy in 4 to 8% of patients. Preliminary studies appear to confirm the role of the immune system in abacavir hypersensitivity. The reaction is possibly the result of presentation of drug peptides onto HLA, that may induce a pathogenic T-cell response. Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele and prospective HLA-B*5701 genetic screening has now been instituted in clinical practice to reduce the risk of hypersensitivity reaction.

[Multidrug intoxication]. / Intoxication polymédicamenteuse.

The authors report an suicide attempt by a 43 years old woman treated by Previscan, Effexor, Rivotril, and Stilnox for phlebitis anteriority and anxious-depressive disorders. On arrival to the emergency unit, the medical status and the patient history required a cardiovascular reanimation and gastric washing. The haemostasis analysis demonstrates an anticoagulant overdose and the prescription of vitamine K1 and PPSB was necessary. Later, the multidrug poisoning was demonstrated thanks to blood, urinary and gastric fluid high performance liquid chromatography toxicological analyses. This case report points out that biological and toxicological analyses are complementary. The first ones are useful to determine the emergency symptomatic cares, and to check the drugs' efficiency. The second ones, although longer, are necessary to identify with certainty incriminated drugs.

[Pharmacological and pharmacogenetic study of two immunomodulators: azathioprine and 6-mercaptopurine. Strategies for preventing complications]. / Etude pharmacologique et pharmacogénétique de deux immunomodulateurs: l'azathioprine et la 6-mercaptopurine. Stratégies de prévention des complications.

Thiopurines are frequently used in gastroenterology for Crohn's disease or hemorrhagic rectocolitis. Their metabolism is regulated by a particular enzyme, thiopurine S-methyltransferase or TPMT. There are three ways to evaluate the effectiveness and the risk of side effects associated with this treatment. TPMT activity measurement or genotyping are recommended to decide for treatment, while metabolites determination is a used as marker of monitoring. Phenotypic approach (TPMT activity measurement or metabolites determination) requires delicate techniques and interindividual variations make the interpretation difficult. Genotyping is easier to interpret but cannot exclude some risk of side effects.

[From gene to disease: copper-transporting P ATPases alteration]. / Du gène à la maladie : les anomalies des transporteurs du cuivre.

Copper is a trace metal, essential for many biological processes. Copper is also toxic if in excessive amounts; its homeostatic balance requires a delicate regulation. Several severe hereditary human disorders of copper regulatory mechanisms have been identified; they are related to mutations in gene ATP7A and ATP7B coding for copper-transporting proteins. Those mutations result in copper deficiency for ATP7A (Menkes disease) and copper overload for ATP7B (Wilson disease). Usually, clinical and biochemical phenotypes of these diseases are disparate. This article focuses on the molecular pathogenesis of Wilson and Menkes disease, and discusses how causing mutations are correlated with molecular defects and disease phenotypes.

[Automation and consolidation of clinical biology: the HIA Begin experiment]. / Automatisation et consolidation en biologie clinique: l'expérience de l'hôpital d'instruction des armées Bégin.

Reorganization of hospital or private sector labs is a strong trend. Such process implies consolidation of tests on a minimum of analyzers, harmonization of equipment (limitation of number of suppliers), posts number reduction, and development of powerful software. Increase of productivity needs set up of automation systems, specially at the level of pre-analytical phase, in a way to limit manual steps. At the same moment, quality improvement generates a decreasing TAT (Turn-Around-Time), a strong reduction of errors, a better protection against biological hazards, and standardization of sample management and validation process. After giving some notions about consolidation and integration, our choices for a brand new and innovative solution are explained.

[Obligate running and anorexia]. / Addiction au sport et anorexie.

The relationship between athletic participation and eating disorders is complex. We describe the case of a sportive man and examine the overall relationship between athletic participation and eating problems.

Should we have more definitions of metabolic syndrome or simply take waist measurement?

The disorder now known as metabolic syndrome has been recognized for 50 years, but its multiple definitions have led to some confusion and even doubt about its very nature. Metabolic syndrome is directly linked to the presence of android obesity, which indicates insulin resistance and lies at the root of all risk factors and early indications of type 2 diabetes. It is diagnosed by systematic measurements of waist size and its direct interpretation taking ethnic origin into account. This pragmatic approach avoids the uncertainties generated by differing definitions and is subtler than the presence or absence of metabolic syndrome in a given patient. Drug-free treatment of an android obese patient is inexpensive and effective, but this apparently simple approach masks difficulties of application. However, these are sociological problems.

[Role of pharmacogenetics in chemotherapy of colorectal cancers]. / Implication de la pharmacogénétique dans les traitements des cancers colorectaux.

SCOPE: Clinical implications associated with polymorphisms in drug-metabolizing genes involved in the chemotherapy of colorectal cancers (5-flurorouracil, oxaliplatin and irinotecan) are reviewed. CURRENT SITUATION AND SALIENT POINTS: Treatments of colorectal cancers have been greatly improved last years but patients respond differently to identical medication. Genetic polymorphisms are one of the major causes of these individual responses to drugs associated with sometimes severe adverse effects. Pharmacogenetics is based on all polymorphisms that determine genetic human diversity associated with variable response to anticancer drugs. PERSPECTIVES: Morbidity and mortality related to toxicity or inefficacy of these drugs could be reduced by analyzing the pharmacogenetic profile of patients before treatment. Results should be integrated in protocols for monitoring and assessment the dosage of drugs.

[Nelson's syndrome management: current knowledge]. / Prise en charge du syndrome de Nelson: données actuelles.

PURPOSE: Nelson's syndrome is a severe complication of bilateral adrenalectomy performed in the treatment of some Cushing's diseases, and its management remains difficult. Trough the observation of a patient suffering from a severe form of Nelson's syndrome for more than 10 years, the authors review the literature and discuss the main current therapeutic possibilities. CURRENT KNOWLEDGE AND KEY POINTS: Many molecules have been used with variable results. In our observation cabergoline at 2 mg per week seems to be efficient after a 3 and a half years follow-up, in accordance with some recent publications. More than bromocriptine, this dopamine agonist provides interesting prospects for this disease's management. Moreover, if the conventional treatments as valproic acid or cyproheptadine are not very efficient, somatostatin analogs seem to be of some therapeutic interest. FUTURE PROSPECTS AND PROJECTS: New molecules are currently evaluated, but studies are difficult to conduct because of the low disease prevalence. Tumour receptors analysis undoubtedly constitutes an attractive way to find new therapeutic targets.

[Inappropriate ADH secretion-induced hyponatremia and associated with paroxetine use]. / Hyponatrémie par sécrétion inappropriée d'ADH associée à la prise de paroxétine.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressants prescribed for elderly people. Although they are generally better tolerated than other antidepressant treatment classes, they can be responsible for potentially life-threatening hyponatremia, related to syndrome of inappropriate antidiuretic hormone secretion (SIADH). OBSERVATION: A 64 years-old woman was hospitalized for cognitive function alteration and vomiting after introduction of paroxetine for depressive symptoms. Serum investigations revealed hyponatremia (121 mmol/l) with low plasma osmolarity and normal natriuria consistent with diagnosis of SIADH. Hyponatremia was reversible after paroxetine withdrawal. DISCUSSION: Hyponatremia induced by SIADH is a serious but underestimated complication of SSRI treatment. This complication occurs in the elderly people within the first month of treatment. Monitoring of the serum sodium concentration during the first month of treatment is recommended for older patients.

[A case of acquired angioedema]. / Un cas d'oedème angioneurotique acquis.

We report the case of a 46 year-old woman presenting an acquired angioedema. Angioedema is an C1 inhibitor deficiency. Patients present recurrent non inflammatory swelling of the head and extremities and recurrent attacks of severe abdominal pain. This clinical presentation is non specific : investigation of complement is useful for diagnosis. Laboratory testing show low serum levels of C4 with normal levels of C3. Low C1 esterase inhibitor confirm the diagnosis. If acquired angioedema, a cause must be searched.