Exercise testing-based algorithms to diagnose McArdle disease and MAD defects.

OBJECTIVE: As exercise intolerance and exercise-induced myalgia are commonly encountered in metabolic myopathies, functional screening tests are commonly used during the diagnostic work-up. Our objective was to evaluate the accuracy of isometric handgrip test (IHT) and progressive cycle ergometer test (PCET) to identify McArdle disease and myoadenylate deaminase (MAD) deficiency and to propose diagnostic algorithms using exercise-induced lactate and ammonia variations. METHODS: A prospective sample of 46 patients underwent an IHT and a PCET as part of their exercise-induced myalgia and intolerance evaluation. The two diagnostics tests were compared against the results of muscle biopsy and/or the presence of mutations in PYGM. A total of 6 patients had McArdle disease, 5 a complete MAD deficiency (MAD absent), 12 a partial MAD deficiency, and 23 patients had normal muscle biopsy and acylcarnitine profile (disease control). RESULTS: The two functional tests could diagnose all McArdle patients with statistical significance, combining a low lactate variation (IHT: <1 mmol/L, AUC = 0.963, P < .0001; PCET: <1 mmol/L, AUC = 0.990, P < .0001) and a large ammonia variation (IHT: >100 µmol/L, AUC = 0.944, P = .0005; PCET: >20 µmol/L, AUC = 1). PCET was superior to IHT for MAD absent diagnosis, combining very low ammonia variation (<10 µmol/L, AUC = 0.910, P < .0001) and moderate lactate variation (>1 mmol/L). CONCLUSIONS: PCET-based decision tree was more accurate than IHT, with respective generalized squared correlations of 0.796 vs 0.668. IHT and PCET are both interesting diagnostic tools to identify McArdle disease, whereas cycle ergometer exercise is more efficient to diagnose complete MAD deficiency.

[Monitoring vancomycin in an intensive care unit: A retrospective survey on 66 patients]. / Monitorage de la vancomycine en réanimation : étude rétrospective de 66 patients.

OBJECTIVES: The study objectives were to check whether recommended vancomycin doses were related to pharmacological objectives for intensive care patients: steady-state plasma concentration (SSc) and ratio SSc/MIC (Minimal Inhibiting Concentration). The authors tried to identify variability factors for vancomycin plasmatic concentrations at peak. PATIENTS AND METHODS: This monocentric, observational, and retrospective survey was performed on 66 intensive care patients treated by antibiotics including vancomycin, alone or in combination, as a curative treatment for a severe infection with Gram-positive bacteria. Vancomycin was dosed at 15mg/kg during the first hour, then 40 to 60mg/kg per 24hour. Vancomycin SSc and bacteria MIC were recorded. The SSc/MIC ratio was determined and was considered efficient when superior to 8. RESULTS: Forty-two percent of vancomycin SSc were within the effectiveness rate. Twenty-three percent of SSc/MIC ratios were superior to 8. The rate of clinical recovery was 71 %. The length of antibiotherapy was identified as positively interacting with biological effectiveness, unlike severe sepsis, a factor of negative interaction on vancomycin SSc in this study. CONCLUSION: Less than half of the SSc and less than a quarter of the SSc/MIC ratios were at effective rates in our study. Therefore, adequacy between dosage, administration, and monitoring should be reviewed.

[Guidelines for the order process of medical laboratory tests]. / Outils pour l'élaboration et la gestion des formulaires de demande d'examens de biologie médicale.

This document presents the requirements enumerated in the ISO 15189 standard to make reliable the formulation of a medical laboratory test order. The contents and the filling conditions of the request laboratory tests form are described, to clarify the interest of the information required. The purpose is to help to construct a specific formulation allowing the adequate realization of the laboratory tests but also to collect the needed clinical information essential to allow a relevant interpretation of the results with a goal of improvement of patient care. We present also the main forms required for special laboratory tests, particularly concerning the human genome. Finally, the criteria to be reviewed at the entry of the laboratory (contract review) during the request acceptation before its registration are enumerated.

[Guidelines relative to the collection and handling management of biological samples]. / Recommandations pour la maîtrise de l'étape de prélèvement des échantillons biologiques.

Guidelines relative to the management of samples collection and handling for common tests are proposed with a list of websites to improve knowledge concerning the practices of biological sampling. Then, methodology is given for the creation of an electronic primary sample collection manual for medical laboratory tests. A list containing the medical laboratory tests for which the information and/or particular documents are needed either for the request or interpretation is presented. Another list for some specific laboratory tests with special individual requirements is proposed. We give also items allowing a standardized description of laboratory tests to help to create a personalized list of the available examinations, facilitating the information of professionals.

[Management of pre-analytical nonconformities]. / Outils pour la gestion et la maîtrise des non-conformités pré-analytiques.

The main nonconformities enumerated to facilitate consensual codification. In each case, an action is defined: refusal to realize the examination with request of a new sample, request of information or correction, results cancellation, nurse or physician information. A traceability of the curative, corrective and preventive actions is needed. Then, methodology and indicators are proposed to assess nonconformity and to follow the quality improvements. The laboratory information system can be used instead of dedicated software. Tools for the follow-up of nonconformities scores are proposed. Finally, we propose an organization and some tools allowing the management and control of the nonconformities occurring during the pre-examination phase.

[Monitoring aminoglycosides in an Intensive Care Unit]. / Monitorage des aminosides en réanimation.

OBJECTIVES: This monocentric, observational and retrospective survey was performed to check the appropriateness between aminoglycoside prescriptions and inhibitor quotient to be reached, in Intensive Care Unit (ICU) patients. We identified variability factors for aminoglycoside plasmatic concentrations at peak such as standardized index of gravity (IGS2 scale), age, sex, weight, and severity of sepsis. PATIENTS AND METHOD: Eighty-seven ICU patients received an antibiotic combination mandatorily including an aminoglycoside (amikacin or gentamicin) as curative treatment for a severe infection. Prescribed dosages were 15mg/kg for amikacin and 5mg/kg for gentamicin. The maximal concentration (Cmax) and minimal inhibiting concentration (MIC) of involved bacteria were recorded. The aminoglycoside ratio Cmax/MIC, called inhibitor quotient, was determined. The inhibitor quotient was considered efficient when superior to 10. The Cmax for aminoglycoside first peak was also compared with the theoretical Cmax to be reached. RESULTS: In the aminoglycoside Cmax, 50.3% were efficient (59.6% for amikacin Cmax and 38.9% for gentamicin Cmax). In 46% of the cases, the inhibitor quotient was efficient; 12.6% of Cmax reached the theoretical Cmax. Factors identified as negatively interacting with biological efficiency were: Gram-positive bacteria or anaerobic bacteria infections and planned surgery. CONCLUSION: In the inhibitor quotients, 49.7% were at inefficient rates, even when the recommended aminoglycoside dosage for was given. Therefore, dose and administration should be updated.

[Biological signifiance of 410 microcytosis]. / Signification biologique de 410 microcytoses de découverte fortuite chez des adultes jeunes.

We have detected 410 microcytosis among biological tests of military people. These microcytosis are principally coumpounded by haemoglobin's abnormalities (minor thalassemia, sickle cell diseases, E haemoglobin cases and cases of C haemoglobin) and cases of iron deficiency, usually among women.

[Imported mycosis: a review of paracoccidioidomycosis]. / Mycoses d'importation: le point sur la paracoccidioïdomycose.

Population migration is increasing the number of systemic mycosis cases, a condition little or not present in Metropolitan France, thus often weakly documented for medical teams. Paracoccidioidomycosis is a systemic mycosis geographically confined to Latin America. The causative agent is Paracoccidioides brasiliensis, a dimorphic fungus present at ground level. Discovering that the armadillo was a new host allowed documenting the ideal conditions for this fungus development. The mortality rate is currently 1.45 for one million people and the disease affects mainly farmers. The mode of infection is respiratory and all organs and mucous membranes can be affected by lymphatic dissemination. The chronic form with pulmonary, cutaneous and oral lesions is the most important. The diagnosis can be carried out by direct examination of samples revealing the presence of budding yeasts, as well as culture at 25 and 37 degrees C. Antifungals like the sulfamethoxazole-trimethoprime combination, amphotericin B, but especially azole derivatives are use in the therapeutic management of patients. Detection and gp 43 antigen assay is useful for the patient's follow-up.

[Nefopam by continuous intravenous injection and adverse drug reactions: which causality assessment?]. / Néfopam en perfusion continue et effets secondaires indésirables: quelle imputabilité ?

We report the case of a 77-year-old man, with nefopam postoperative analgesia, who developed subacute neurological symptoms, whereas he had profound hypoprotidemia and acute renal failure. Chronological, semiological and bibliographical criteria are in favour of causality assessment. The plasma nefopam concentration (135 ng/ml) during the neurological symptoms is another argument.

[Convulsions induced by ropivacaine after midhumeral block]. / Convulsions induites par la ropivacaïne lors d'un bloc au canal huméral.

We report a case of central nervous system toxicity induced by ropivacaine following a brachial block at the humeral canal. Forty millilitres 0.75% ropivacaine (4.28 mg.kg-1) were used uneventfully, with slow injections and negative intermittent aspirations. Fifteen minutes later, the patient presented two episodes of generalised convulsions treated by diazepam, 20 mg. The total venous ropivacaine concentration measured two hours after the block was 2.3 mg.l-1.

[Chance discovery of methanol poisoning during a state of inebriation]. / Découverte fortuite d'une intoxication au méthanol lors d'un état d'ébriété.

We report a case of wood alcohol (methylated spirits) poisoning in a 40-year-old chronic alcoholic. The initial diagnosis of state of drunkenness was supported by the increased plasma level of ethanol (4.66 g.L-1) obtained with enzymatic method. The confirmation, using gas chromatography (GC), showed an unexpected peak with a retention time at 1.19 min, characteristic of methanol (0.41 g.L-1). The GC analysis of the absorbed beverage revealed a 5% methanol content. The osmolal gap was 115 mOsm.kg-1, with 13 mOsm.kg-1 due to methanol and 90 mOsm.kg-1 to ethanol. Seven hours after the ingestion, the anion gap was at 13 mmol-1. This result reflected the inhibition of methanol oxidation by alcohol-dehydrogenase, when the plasma ethanol concentration was above 1 g.L-1. This concentration was maintained by continuous intravenous administration of (Curéthyl-A) a 95% ethanol containing solution, until methanol concentration decreased below 0.2 g.L-1. The outcome was favourable without neurological and ophthalmological sequelae.

[Blood levels of homocysteine by high pressure liquid chromatography and comparison with two other techniques]. / Dosage de l'homocysteéine plasmatique par chromatographie liquide haute performance et comparaison à deux autres techniques.

Cardio-vascular diseases are the most common cause of death in industrialized countries. A new marker has emerged among offending risk factors in the past few years: homocysteine. This sulphured amino-acid is an important intermediate in transsulphuration and remethylation reactions of methionine's metabolism. We proposed to evaluate a home made method of determination for this parameter by high performance liquid chromatography (HPLC) and to compare it to fluorescence polarization immunoassay technique (FPIA) and to gaz phase chromatography (CG-SM). This method associated with good sensibility and precision remain much less expensive than FPIA technique.