Macro-creatine kinase: a neglected cause of elevated creatine kinase.

Macro-creatine kinase (macro-CK) is a neglected cause of raised CK. Over a 10-year period, we observed five cases. Three patients had macro-CK type 1. One patient with fibromyalgia underwent several explorations to find a muscular pathology; another, who had elevated CK-MB (muscle-brain fraction) activity, was referred to a cardiologist, and statin therapy was erroneously discontinued in two patients. Two patients had macro-CK type 2: a man with a neuroendocrine carcinoma and a woman with rheumatoid arthritis. Diagnosis of type 1 obviates the need to carry out pointless and expensive investigations seeking a neuromuscular or cardiac pathology, and also, the unwarranted discontinuation of statin therapy. Type 2 must prompt investigations for a neoplasm.

[Differential diagnosis of status epilepticus in intensive care: about one case of sporadic Creutzfeldt-Jakob]. / Diagnostic différentiel d'un état de mal épileptique en réanimation: à propos d'un cas de Creutzfeldt-Jakob sporadique.

A 78-year-old man was admitted in the intensive care unit for epilepsy seizure (tonic-clonic seizure). Since three months, his wife reports motor dysfunction (weakness) and since two weeks, rapidly progressive changes in cognition (apraxia, akinetic mutism). The diagnosis of probable sporadic Creutzfeldt-Jakob on the basis of clinical, EEG and MRI lesions was made. Refining diagnostic criteria is probably needed, including the usefulness of repeated MRI with FLAIR and diffusion-weighted imaging.

Differences between women and men with recent-onset axial spondyloarthritis: results from a prospective multicenter French cohort.

OBJECTIVE: To clarify sex differences in early axial spondyloarthritis (SpA). METHODS: In total, 475 patients included in the Devenir des Spondylarthropathies Indifférenciées Récentes (Outcome of Recent Undifferentiated Spondylarthropathies) cohort, a prospective multicenter French cohort of patients with early inflammatory back pain suggestive of SpA, and fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA were studied. The clinical and imaging features were compared between sexes and according to the clinical or imaging arm of the ASAS criteria using univariate and multivariate analysis. RESULTS: Comparisons between the 239 men and 236 women showed that women had higher disease activity when measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Patient Global Score and higher fatigue and functional scores despite having less radiographic sacroiliitis and magnetic resonance imaging (MRI) inflammation of sacroiliac joints and the spine than men. Disease activity measured by the C-reactive protein (CRP)-based Ankylosing Spondylitis Disease Activity Score was not different between men and women. In contrast to patients classified with the clinical arm, disease activity and functional scores did not differ between women and men with sacroiliitis on imaging scans, except for fatigue and the Ankylosing Spondylitis Quality of Life questionnaire. Women with sacroiliitis had more peripheral involvement and more family history, whereas HLA-B27 positivity, elevated CRP, and MRI inflammation of the spine were associated with male sex. CONCLUSION: Women with early axial SpA according to the ASAS criteria had greater disease activity when measured by the BASDAI and worse functioning despite fewer radiologic abnormalities than men. The differences in disease expression may be confounding factors to establish the diagnosis of SpA and to assess disease activity in women, suggesting that the imaging arm is a pivotal measure in the ASAS criteria.

European League Against Rheumatism Sjögren's Syndrome Disease Activity Index and European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index: a complete picture of primary Sjögren's syndrome patients.

OBJECTIVE: The European League Against Rheumatism (EULAR) Sjögren's Syndrome (SS) Disease Activity Index (ESSDAI) and the EULAR SS Patient-Reported Index (ESSPRI) were recently developed. We aimed to determine whether patients' symptoms differed between patients with and without systemic involvement and if the disease-specific indices correlated with each other in primary SS. METHODS: Fifteen French centers included 395 primary SS patients in the Assessment of Systemic Signs and Evolution in Sjögren's Syndrome Cohort. At enrollment, physicians completed the ESSDAI, the SS Disease Activity Index (SSDAI), and the Sjögren's Systemic Clinical Activity Index (SCAI), and patients completed the ESSPRI, the Sicca Symptoms Inventory, and the Profile of Fatigue and Discomfort. All scores were compared between patients with and without systemic involvement. Correlations between scores of systemic activity and patients' symptoms were obtained. RESULTS: At enrollment, 120 (30.4%) patients had never experienced systemic complication and 155 (39.2%) patients and 120 (30.4%) patients had, respectively, only past or current systemic manifestations. Past or current systemic patients had higher levels of symptoms, except dryness. The ESSDAI did not correlate with the patient-scored ESSPRI (rho = 0.06, P = 0.30), whereas the SSDAI and the SCAI, which include subjective items, did correlate (rho = 0.28 and 0.25, respectively; P < 0.0001 for both). CONCLUSION: Alterations of common patient-reported outcomes are present in all patients with primary SS, including those with systemic complications. However, patient symptoms and systemic complications are 2 different facets of primary SS. Therefore, the use of both systemic and patients' indices, such as the ESSDAI and ESSPRI, are useful. Since these 2 facets weakly overlap, one should identify which of both components is the main target of the treatment to test, when designing clinical trials in primary SS.

[Treatment of gout]. / Traitement de la goutte.

In France, colchicine remains the standard treatment for the acute flare of gout. The lowest dose currently used decreases digestive toxicity. Doses of colchicine should be adapted to renal function and age, and possible drug interactions should be considered. Non steroidal anti-inflammatory drugs are an alternative to colchicine, but their use is frequently limited by comorbidity. When these treatments are contraindicated, corticosteroid injections can be performed after excluding septic arthritis. Systemic corticosteroids could be used in severe polyarticular flares. Anti-IL1 should provide a therapeutic alternative for severe cortico dependant gout with tophus. To prevent acute flares and reduce tophus volume, uric acid serum level should be reduced and maintained below 60mg/L (360µmol/L). To achieve this objective, it is often necessary to increase the daily dose of allopurinol above 300mgs, but the need to adapt the dose to renal function is a frequent cause of therapeutic failure. In the absence of renal stone or renal colic and hyperuraturia, uricosuric drugs are the second-line treatment. Probenecid is effective when creatinine clearance is superior to 50mL/min Benzbromarone, which was withdrawn due to hepatotoxicity, can be obtained on an individualized patient basis in the case of failure of allopurinol and probenecid. Febuxostat, which was recently approved, is a therapeutic alternative. Diuretics should be discontinued if possible. Use of fenofibrate should be discussed in the presence of dyslipidemia and losartan in patient with high blood pressure. Uricolytic drugs (pegloticase), which are currently being investigated, may be useful for the treatment of serious gout with tophus, especially in the presence of renal failure. Education of patient, identification and correction of cardiovascular risk factors should not be forgotten.

[Severe bronchospasm using Diprivan® in a patient allergic to peanut and birch]. / Bronchospasme sévère au Diprivan® chez un enfant allergique à l'arachide et au pollen de bouleau.

Diprivan® is composed of propofol, refined soybean oil and purified egg phosphatide. One must eliminate any allergy to one of its components before use. We report the story of a child who underwent nevus surgery under general anesthesia which was associated with an hypersensitivity reaction. In fact, this child had asthma and allergy to peanuts, raising the problem of cross allergy between birch, peanut, soy and Diprivan®.

[Transversal fractures in spinal ankylosis: a case series of 17 patients]. / Fractures transversales du rachis ankylosé : une série de 17 cas.

PURPOSE: Transverse fractures of the spine are rare. They occur in ankylosed spine and may lead to neurological complications. We report a series of 18 cases observed in 17 patients with ankylosing spondylitis (AS). The objective of this study were to describe the clinical, diagnostic and therapeutic features of our series and to compare our results with those of the literature. METHODS: We conducted a retrospective study from 1975 to 2008 in the neurosurgery and rheumatology departments of the university hospital (CHU) of Clermont-Ferrand. RESULTS: Eighteen transverse spine fractures were documented in 17 patients (one female patient had two fractures of the lumbar vertebrae). The 13 male and four female patients included in this series had a mean age of 57.4 ± 17.2 years and AS for a mean time of 21.3 ± 12 years (5-40). All patients had spinal ankylosis with a "bamboo" spine appearance. The reasons for hospital admission were suspicion of AS flare (n=10) and suspected traumatic fracture (n=8). Trauma, in most cases minor, was noted in 15 patients. Fourteen patients presented with mechanical spinal pain and three had both mechanical and inflammatory pain. Three patients experienced severe pain on mobilization. Two patients had pyramidal syndrome. The mean time to diagnosis of the fracture was 6.8 ± 8.4 weeks (0-22). The fracture was located in cervical spine (n=2), dorsal spine (n=8) and lumbar spine (n=8). It was transdiscal and transcorporeal in nine cases each. Standard radiographs (n=18) identified the fracture in nine cases. The fracture was demonstrated in all CT-scan (n=13). Magnetic resonance imaging (MRI) (n=6) showed the fracture in five cases and epidural hematoma in one. Eleven patients had orthopedic treatment and six underwent surgery. Outcome was favorable in 16 patients. One paraplegic patient died of pulmonary embolism. CONCLUSION: Transverse fractures of the spine are rare and diagnosis should be considered in a patient with AS and ankylosed spine who presented mechanical spine pain following even minor trauma. If standard radiographs are normal, further investigations should be performed using MRI, CT-scan, or both.

[Surgical site infections in orthognathic surgery and risk factors associated]. / Les infections du site opératoire en chirurgie orthognathique et leurs facteurs de risque.

INTRODUCTION: Surgical site infections (SSI) in orthognathic surgery are considered infrequent and without any important consequence for the final operative result. A procedure of epidemiological surveillance was implemented to determine the frequency of SSI in orthognathic surgery and to better document their risk factors. MATERIAL AND METHOD: This prospective study included all interventions in our orthognathic surgery department between September 1(st) 2006 and August 31(st) 2007. SSI and their risk factors were documented for up to one year of follow-up. Risk factors were correlated to SSI using monovariate and multivariate analyses. RESULTS: Ten (7%) out of 143 consecutive interventions in orthognathic surgery were complicated by a SSI. All the SSI were secondary to a mandibular ramus sagittal split osteotomy. The two significantly correlated risk factors with the SSI in multivariate analysis were the length of surgery and the type of antibiotic prophylaxis. DISCUSSION: This rate of SSI correlates to published data. To decrease this rate, it would be necessary, in association with the usual precautionary measures, to limit the operating time and to recommend an antibioprophylaxis combining amoxicillin plus clavulanic acid (Augmentin).

Trend towards increased arterial stiffness or intima-media thickness in ankylosing spondylitis patients without clinically evident cardiovascular disease.

OBJECTIVES: Increased incidence of cardiovascular disease (CVD) has been observed in AS. The reasons of this increase are not fully understood (greater prevalence of traditional cardiovascular risks, consequences of treatment (NSAID) or biological inflammation). The objectives of this study are to assess intima-media thickness (IMT) and arterial stiffness (i.e augmentation index AIx), markers of sub-clinical atherosclerosis in AS patients and to examine the effects of TNF-alpha inhibitors on arterial stiffness in active AS patients. METHODS: Sixty AS patients were enrolled with 60 healthy controls. Their BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) scores, ESR and CRP levels were recorded. Subclinical atherosclerosis was assessed by measurement of AIx by pulse wave analysis and IMT by carotid echography. RESULTS: We found significantly increased IMT in the AS group compared with healthy controls. After adjustment for confounding factors, an underlying trend towards increased IMT was still present (P = 0.06). No difference was found in arterial stiffness between the two groups. AS patients, treated or not with anti-TNF-alpha at baseline, had significantly increased IMT and AIx or a trend towards increase. IMT was positively correlated with tobacco use, WHR and blood pressure but not correlated with CRP level. Despite improvement in markers of disease activity, arterial stiffness was unchanged after 14 weeks of treatment with TNF antagonists. CONCLUSION: This study shows a trend towards increased subclinical atherosclerosis in AS patients. TNF-alpha blockade does not seem to improve arterial stiffness in AS patients, but our results lack statistical power.

[Fractures of the ankylosed spine: MRI features]. / Fractures du rachis ankylosé: intérêt de l'IRM.

The diagnosis of transverse spinal fractures in patients with ankylosing spondylitis and Forestier's disease (DISH) may be difficult. The MRI features of 9 such fractures at the disk, vertebral body, spinal canal and posterior elements are presented. Fractures of the posterior elements (posterior arch fractures and/or rupture of interspinous or supraspinous ligaments and contiguous soft tissue structures) were present in all cases, underscoring the importance of MR signal abnormalities of posterior structures for diagnosis of these fractures. MR is advantageous due to its ability to demonstrate signal abnormalities of the posterior elements, which combined with disk and vertebral body abnormalities, play a major role for accurate diagnosis of this type of fracture.

Development and validation of a rapid HPLC method for the determination of oseltamivir phosphate in Tamiflu and generic versions.

Oseltamivir phosphate (OP) is an antiviral drug that is used in the treatment and prophylaxis of both influenza A and influenza B. It is effective against all known influenza viruses than can infect humans, including pandemic influenza viruses and may be the most appropriate antiviral option against avian influenza caused by H5N1 virus. Tamiflu, the registered trademark used under exclusive license by Roche laboratories with OP as active pharmaceutical ingredient, is considered the best treatment for the bird flu disease. A simple, selective, linear, accurate and precise HPLC method was developed and validated for rapid assay of OP aimed to the quality control of Tamiflu capsules and generic versions. Isocratic elution at a flow rate of 1.2 mL/min was employed on a Zorbax CN column (150 mm x 4.6mm; 5 microm) at ambient temperature. The mobile phase consisted of methanol and 0.04 M formic acid pH 3.0 (50:50, v/v). The UV detection wavelength was 226 nm and 20 microL of sample was injected. Sotalol hydrochloride was used as the internal standard (IS). The retention times for OP and IS were 3.40 and 2.25 min, respectively. The method was successfully applied to commercial pharmaceuticals, Tamiflu and generic versions. The proposed method could be applicable for routine analysis of OP and monitoring of the quality of marketed drugs as possibly counterfeit Tamiflu.

Direct determination of niflumic acid in a pharmaceutical gel by ATR/FTIR spectroscopy and PLS calibration.

A simple, rapid and convenient analytical method without sample handling procedure is proposed for the determination of niflumic acid in a pharmaceutical gel with attenuated total reflectance/Fourier transform infrared spectroscopy (ATR/FTIR). A partial least square (PLS) calibration model for the prediction of niflumic acid contents was developed using 81 and 27 spectra of standard gels as training and validation sets, respectively. The used spectral range of niflumic acid for the establishment of this model was 2300-1100 cm(-1). All spectra were obtained in the transmittance mode, then normalized and first derivative transformed. The model yielded a regression coefficient R2 equal to 1 for the training set and a root mean square error of prediction (RMSEP) equal to 0.2 for the validation set. The percentage recoveries of the method for the analysis of Niflugel ranged from 96.60 to 101.02%.

Septic arthritis as a late complication of carcinoma of the breast.

OBJECTIVES: To see if a past history of radiation therapy is a risk factor for septic arthritis. METHODS: We retrospectively searched our records of 282 patients with septic arthritis and found 10 cases of septic arthritis post-radiotherapy, all in females. We analysed our group, correlating them with the literature. We also compared our patients with a group of septic arthritis patients without radiation therapy. RESULTS: Nine had had radiation therapy for carcinoma of the breast. The shoulder joint was involved in six and the sternoclavicular joint in three. The tenth patient had had brachytherapy and radiation for carcinoma of the cervix and presented with septic arthritis of the hip. The mean age of the patients was 69 yr (49-82 yr). The mean time elapsed since radiation was 16 yr (3-34 yr). Twenty-three cases of shoulder septic arthritis in patients without past radiation therapy were selected for comparison. The five patients with past radiation therapy had fever less often and a longer time lapse before diagnosis. They required longer antibiotherapy. However, this prevented neither bone destruction nor relapse. CONCLUSIONS: In our study, a past history of radiation therapy was observed in 6/50 infections of the shoulder, 3/5 infections of the sternoclavicular joint, 6/23 cases of septic arthritis of the shoulder and all cases of septic arthritis of the sternoclavicular joint for females. Radiation therapy seems to be a risk factor for septic arthritis. Diagnosis would be aided by a greater awareness of the clinical and radiological features of this septic arthritis.

[Fluoroscopy guided L5-S1 transforaminal injection as a treatement for s1 radiculopathy]. / Infiltration foraminale L5-S1 radioguidée dans le traitement de la lombosciatique S1.

OBJECTIVE: To assess the efficacy of fluoroscopy guided L5-S1 transforaminal steroid injections for the treatment of S1 radiculopathy secondary to intervertebral disk disorder. METHOD: 41 patients were included: prospective study (20 patients) and retrospective study (21 patients). All patients suffered from S1 radiculopathy secondary to nerve root compression by intervertebral disk material, as demonstrated by lumbar spine CT. The patients underwent 2 fluoroscopy guided L5-S1 transforaminal injections of steroid (Hydrocotancyl 125 mg), at 8 days interval. RESULTS: 60% of patients showed significant improvement of their painful radiculopathy at day 8 (n:41), 60-67% at day 30 (n:41) and 67% at day 90 (n:18). CONCLUSION: Fluoroscopy guided L5-S1 transforaminal injection showed good efficacy in the treatment of S1 radiculopathy.

Determination of pKa values of 2-amino-2-oxazolines by capillary electrophoresis.

The dissociation constants of new 2-amino-2-oxazolines were determined by capillary electrophoresis (CE) as a new technique. A method based on a linear model has been used in the CE determination. A series of eight 2-amino-2-oxazolines are investigated to determine their ionization constant. Among them, three new oxazolines synthesized are presented. The Ka values were obtained from the plots of reciprocal effective mobility against inverse concentrations of protons. The potentiometric method (PM) was performed as a comparative method. No significant differences were observed between the determined dissociation constants using both methods. Thus, the pKa values have been found to vary between 8.55 and 8.68.

Separation of new antidepressants and their metabolites by micellar electrokinetic capillary chromatography.

Selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenergic reuptake inhibitors (SNaRIs) and noradrenergic and specific serotoninergic antidepressant (NaSSA) are widely used in the treatment of depression. An increase in antidepressant intoxications led to the development of reliable analytical methods for their analysis. A new determination procedure for these compounds (milnacipran, venlafaxine, desmethylvenlafaxine, mirtazapine, desmethylmirtazapine, citalopram, desmethylcitalopram, fluvoxamine, paroxetine, sertraline and fluoxetine) was developed by micellar electrokinetic capillary chromatography (MEKC) with diode array detection (DAD). Separation and determination were optimised on an uncoated fused-silica capillary (600 mm, 75 microm I.D.). The migration buffer consisted of 20 mM sodium borate, pH 8.55, with 20 mM SDS and 15% isopropanol, at an operating voltage of 25 kV. The column temperature was maintained at 40 degrees C. Injection in the capillary was performed in the hydrodynamic mode (0.5 p.s.i., 15 s). In these conditions, the migration time of the antidepressants was less than 11 min. In most cases, calibration curves were established for 30 - 2000 ng/ml (r > 0.995). The limit of detection and the limit of quantification were ranged between 10 and 20 and between 20 and 30 ng/ml, respectively, for all the molecules. This method allowed the determination of some of these compounds in biological fluids (blood, urine) in post-mortem cases. Samples (1 ml) were extracted with diethyl ether (5 ml) at pH 9.6 and reconstituted in diluted migration buffer. Similar results were obtained by a HPLC-DAD determination, performed as a reference method. These results suggest that this MEKC method can be useful for the determination of new antidepressants in post-mortem cases.

Spectrophotometric, spectrofluorimetric, HPLC and CZE determination of mirtazapine in pharmaceutical tablets.

Four analytical methods have been developed for the quality control of tablets containing mirtazapine: spectrophotometry, spectrofluorimetry, high performance liquid chromatography (HPLC) and capillary zone electrophoresis (CZE). All the methods only require a simple extraction procedure of mirtazapine from the tablets before analysis. The concentration of mirtazapine in solutions was determined in the linearity range of 5-25 microg/ml at lambda=315 nm for spectrophotometry and at lambda=220 nm for HPLC and CZE. Spectrofluorimetric determinations were achieved at lambda(excitation)=328 nm and lambda(emission)=415 nm in the linearity range of 2-25 ng/ml. All the methods gave similar results and were validated for selectivity, linearity, precision and sensitivity. Spectrometric methods gave slightly higher RSD values (up to 2.54%). The four methods were directly and easily applied to the pharmaceutical preparation with accuracy, resulting from recovery experiments between 99.72% in HPLC and 101.47% in spectrofluorimetry.