[Gynecological Lemierre's syndrome: A case report and literature review]. / Syndrome de Lemierre inversé : à propos d'un cas et revue de la littérature.

INTRODUCTION: Lemierre's syndrome is defined as an oropharyngeal infection due to Fusobacterium necrophorum, associated with septic thrombophlebitis of the internal jugular vein. The uncommon pelvic variant of the syndrome is a rare condition, poorly described in literature. CASE REPORT: We report a case of gynecological Lemierre's syndrome in a 19-year-old woman after a first sexual intercourse, who presented acute respiratory failure, left internal iliac vein thrombosis with pulmonary embolism, in the setting of salpingitis and F. necrophorum bacteriemia. CONCLUSION: Gynecological Lemierre's syndrome is a rare and unrecognized condition, which could be lethal. Early recognition of the disorder enables initiation of appropriate antibiotic therapy for 4 to 6 weeks, and discussion of anticoagulant therapy which indications are not yet well defined.

Novel aspects on the contribution of T cells and dendritic cells in the pathogenesis of myositis.

This review focuses on recent advances and new hypothesis in the understanding of the T and dendritic cells contribution to the pathogenesis of idiopathic inflammatory myopathies (IIMs), especially polymyositis (PM) and dermatomyositis (DM). The new data show that non-specific amplification of muscle inflammation by T lymphocyte and dendritic cells may result from the local production of cytokines and chemokines. Synergistic interactions between these factors explain some of the clinical features. The potent role of these molecules suggests their potential for therapeutic manipulation using specific inhibitors.

Interleukin-17 increases the effects of IL-1 beta on muscle cells: arguments for the role of T cells in the pathogenesis of myositis.

We studied the production of interleukin (IL)-6 and CCL20/macrophage inflammatory protein-3 alpha (MIP-3 alpha) by human myoblasts and muscle samples in response to IL-17 alone or in combination with IL-1 beta. Both IL-17 and IL-1 beta induced IL-6 production by normal myoblasts and muscle samples. IL-17 had no effect on CCL20 production by myoblasts. Combination of IL-17 and IL-1 beta further increased IL-6 and CCL20 production by muscle samples but not that of CK. IL-17 induced also HLA class I, C-Fos, nuclear factor kappa B (NF-kappa B) and C-Jun expression by myoblasts but not that of HLA class II, CD40, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). Finally, immunostaining of dermatomyositis (DM) and polymyositis (PM) muscle biopsies showed IL-17 and CCL20 expression. Our study shows that low levels of cytokines produced by T cells (IL-17) and monocytes (IL-1 beta) can act in combination on skeletal myoblasts and muscle tissue.

Attenuation of the ischaemia-induced fall of electrical ventricular fibrillation threshold by a calcium antagonist, diltiazem.

Calcium antagonists have been reported to decrease the incidence of sudden death in postinfarction management and vulnerability to fibrillation secondary to experimental coronary occlusion. In order to confirm such beneficial results regarding ischaemic ventricular fibrillation, the threshold intensity for fibrillation electrically induced with impulses of 100 ms and 180 beats.min-1 was measured during the course of ischaemias obtained by total occlusion of the left anterior descending coronary artery near its origin in open-chest pigs. The variations of electrical fibrillation threshold with ischaemia duration (30, 60, 120, 180, 240, 360 s) were compared under control conditions and after i.v. diltiazem (0.50 mg.kg-1 plus 0.02 mg.kg-1.min-1 over 25 min). Electrical fibrillation threshold was not influenced by diltiazem before, but raised during ischaemia, particularly from the 60th s (1.7 to 4.0 mA), with delay in the triggering of fibrillation which occurs when the fibrillation threshold falls down to the pacing threshold (0.2 to 0.3 mA). In 6 pigs out of 8, fibrillation was even avoided in the longest of the ischaemic periods considered (360 s), for fibrillation threshold ceased falling before reaching the critical level. These experimental results obtained with diltiazem are consistent with the clinical effectiveness of calcium antagonists recently observed in the prevention of postinfarction sudden death, provided that myocardial contractility is not too much adversely affected. But, left ventricular dP/dtmax was not reduced by more than 6.8% in the present experiments.

Role of asynchronous activation of the ventricular fibres by an ectopic pacemaker in the accidents, especially fibrillation, caused by Ic antiarrhythmic drugs.

Class Ic antiarrhythmic drugs, which are known to slow down conduction in the ventricular muscle, are likely to impair synchrony in activity of the ventricular fibres. Asynchronous activation was first investigated between an ischaemic and a normal area by the simultaneous recording in anaesthetized, open-chest pigs of two left ventricular monophasic action potentials (MAPs) under ventricular pacing at a high rate of 180 beats.min-1. Asynchronous activation was then investigated in the intact myocardium according to the distance separating the recording from the pacing electrode. Furthermore, mechanical effects of left ventricular systole were observed by recording dP/dt(max) and mean arterial blood pressure during the pacing periods. Ischaemia was produced by transient complete occlusion of the left anterior descending coronary artery near its origin; as a result, activation time reached 85 ms in the ischaemic area under flecainide administered iv in a 2.5 mg.kg-1 dose instead of approximately 60 ms in the normal area for fibres equi-distant from the pacing electrode. Similar delays in activation were observed in the intact myocardium, depending on whether the explored region was close to or far from the pacing electrode. In the latter case, the difference in activation time may become markedly greater if the distance or the dose of flecainide are increased. This difference, which possibly exceeds one-third of the MAP duration (practically unchanged by flecainide), may account for the occurrence of fibrillation or the sudden loss of systole mechanical efficacy.

Osteogenesis imperfecta: lifelong management is imperative and feasible.

Osteogenesis imperfecta is a group of inherited diseases responsible for varying degrees of skeletal fragility. Minimal trauma is sufficient to cause fractures and bone deformities. The classification of osteogenesis imperfecta has recently been improved by the inclusion of additional clinical and histomorphometric data. The diagnosis is often readily made in infancy; some cases, however, go unrecognized until adulthood. Lifelong multidisciplinary management is imperative. Pamidronate therapy in childhood is the most extensively studied treatment and has been proved beneficial. Other bisphosphonates are being evaluated, particularly in adults. Prevention of vitamin D and calcium deficiency is essential throughout life. Pain is common and should be given adequate attention.

[Comparative study of different classes of anti-arrhythmia agents on the vulnerability of ischemic ventricular fibrillation]. / Etude comparative des diverses classes d'antiarythmiques sur la vulnérabilité à la fibrillation ventriculaire ischémique.

A comparative study of the various classes of antiarrhythmic drugs as agents protecting against ischaemia-induced ventricular fibrillation was undertaken in the pig in situ heart, in anaesthetized animals which were subjected to complete temporary occlusion of the left anterior descending coronary artery. This occlusion resulted in fibrillation after a time which varied in inverse ratio to vulnerability to fibrillation. However, as this time did not exceed a few minutes, time to onset of fibrillation could be repeatedly measured in the course of an experiment, in the absence or in the presence of an antiarrhythmic drug. Under ventricular pacing at a constant rate, 180 beats/min, all the class I antiarrhythmic drugs, flecainide, disopyramide and lidocaine, in clinical dose range, reduced time to fibrillation to a large extent (25 to 50%) at the maximum of their action, with gradual return to control values within less than one hour. The enhancement of vulnerability to fibrillation was accompanied by reduction in intraventricular conduction velocity and fibrillation rate. With the same ventricular pacing, no change was observed in time to fibrillation under the influence of propranolol or amiodarone. As for verapamil, it lengthened this time considerably, up to 600%. However, bradycardia produced in usual circumstances ensures a real protection against ischaemic fibrillation with propranolol and amiodarone and enhances protection directly exerted by verapamil.

[Pharmacokinetics of fluorine contained in the Royale Saint-Yorre mineral water]. / Pharmacocinétique du fluor apporté par l'eau de Saint-Yorre Royale.

The pharmacokinetics of oral fluoride supplied by one half liter of Royale Saint-Yorre water, which contains 8.50 mg fluoride per liter, were studied in ten healthy volunteers. Fluoride plasma kinetics and urinary excretion of fluoride were determined over 24 hours. After ingestion of one half liter Royale Saint Yorre mineral water, mean peak serum fluoride level was 159 +/- 22 micrograms/l. Time to peak serum level was 1 h (0.9 +/- 0.21 h) and area under the curve from 0 to 24 hours was 1,040 +/- 168 micrograms/l/h. Mean urinary fluoride was 2.57 +/- 0.4 mg (range 1.90 to 3.32 micrograms). The authors compared their findings with previously published data on fluoride pharmacokinetics after oral administration of an enteric-coated sodium fluoride tablet containing 11.35 mg elemental fluoride (12 healthy volunteers). Both peak serum level standardized for the dose of elemental fluoride and time to peak serum level were greater with the water than with the tablet. The authors cannot conclude as to which of the two types of fluoride exhibits the best bioavailability because their absorption coefficients have not been determined. This study demonstrates that Royale Saint Yorre mineral water is a valuable source of fluoride. Additional prospective studies are needed to determine whether it has therapeutic potential.

Contribution of tumour necrosis factor alpha and interleukin (IL) 1beta to IL6 production, NF-kappaB nuclear translocation, and class I MHC expression in muscle cells: in vitro regulation with specific cytokine inhibitors.

OBJECTIVE: To evaluate the effect of tumour necrosis factor alpha (TNFalpha), interleukin (IL) 1beta, and their respective inhibitors the p75 TNFalpha soluble receptor (sTNFR) and the type II sIL1betaR (sIL1RII) on whole muscle and isolated myoblast activation. METHODS: Normal muscle samples were stimulated for 7 days with TNFalpha alone or in combination with IL1beta, and myoblasts from these samples for 48 hours. IL6 production was measured by ELISA. Nuclear translocation of NF-kappaB was analysed by immunofluorescent staining and class I MHC expression by FACS. RESULTS: TNFalpha and IL1beta induced IL6 production by normal muscle samples and myoblasts, the action of TNFalpha being more potent on muscle samples. Their soluble receptors (1 microg/ml) decreased this production. Suboptimal concentrations of TNFalpha and IL1beta induced NF-kappaB translocation. sTNFR markedly down regulated TNFalpha-induced translocation while sIL1RII was less potent on IL1beta-induced activation. NF-kappaB translocation induced by the combination of optimal concentrations of TNFalpha and IL1beta was completely inhibited by their soluble receptors. TNFalpha and to a lesser extent IL1beta induced class I MHC expression by myoblasts and this effect was completely inhibited by their respective soluble receptors. CONCLUSION: These results suggest that TNFalpha and IL1beta should be targeted for myositis treatment.

Addition of interleukin 1 (IL1) and IL17 soluble receptors to a tumour necrosis factor alpha soluble receptor more effectively reduces the production of IL6 and macrophage inhibitory protein-3alpha and increases that of collagen in an in vitro model of rheumatoid synoviocyte activation.

OBJECTIVES: To evaluate the usefulness of combination treatment with cytokine inhibitors. METHODS: A simplified model was set up to evaluate the effect of tumour necrosis factor alpha (TNFalpha) soluble receptors (sTNFR) used alone and in combination with soluble interleukin 1 receptor (sIL1R) and sIL17R on the production of markers of inflammation (IL6), of migration of dendritic cells (macrophage inhibitory protein-3alpha (MIP-3alpha)), and of matrix synthesis (C-propeptide of type 1 collagen (P1CP)). Synoviocytes were stimulated with supernatants of activated peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA). Soluble receptors (sR) were preincubated at 1 gammag/ml alone or in combination with the supernatants before addition to RA synoviocytes. IL6, MIP-3alpha, and P1CP production was measured by enzyme linked immunosorbent assay (ELISA) in 48 hour synoviocyte supernatants. RESULTS: IL6 production decreased by 16% with sTNFR alone compared with no sTNFR (p<0.001) and by 41% with the combination of the three sR (p<0.001). MIP-3alpha production decreased by 77% with sTNFR alone compared with no sTNFR (p<0.001) and by 98% with the combination of the three sR (p<0.001). In the presence of sTNFR alone, P1CP production increased by 25% compared with no sR (p<0.01). The combination of the three sR increased P1CP production by 48% (p<0.01). CONCLUSION: The effect of sTNFR on IL6, MIP-3alpha, and P1CP production by RA synoviocytes stimulated by activated PBMC supernatants was further enhanced when combined with sIL1R and sIL17R.

Renal type AA amyloidosis associated with rheumatoid arthritis: a cohort study showing improved survival on treatment with pulse cyclophosphamide.

OBJECTIVE: To determine the incidence of renal AA amyloidosis and its association with rheumatoid arthritis (RA) in a cohort of all renal biopsies at one referral hospital and to measure the effect of a monthly pulse of cyclophosphamide on renal function and survival in these RA patients. METHOD: All renal biopsies with proven AA amyloidosis from a single pathology unit linked to a major nephrology referral unit in a university hospital were selected retrospectively and RA patients were identified. We studied 6931 renal biopsies. The effect of treatment with and without pulse cyclophosphamide on renal function and survival was studied in these patients. RESULTS: From March 1977 to February 1999, the incidence of AA amyloidosis was 2.4 cases/yr. The incidence and prevalence of the association of AA amyloidosis with RA were 0.68 cases/yr and 0.22% (15/6931) respectively. RA patients treated with cyclophosphamide (n=6) had a lower rate of renal function loss (P=0.013) and a higher median survival (P=0.026) than untreated patients (n=9). During the follow-up period, two out of six treated patients (33%) and all nine untreated patients (100%) died. CONCLUSIONS: AA amyloidosis is a rare complication of RA and complicates the evaluation of treatment. This retrospective study suggests that treatment with cyclophosphamide is able to reduce the incidence of end-stage renal failure and to increase survival. Prospective studies are needed to clarify this issue.

Lack of evidence for a direct involvement of muscle infection by parvovirus B19 in the pathogenesis of inflammatory myopathies: a follow-up study.

OBJECTIVE: To clarify the association between parvovirus B19 and myositis. METHODS: Biopsy samples of muscle from eight patients with inflammatory myopathies were studied for the presence of B19 DNA by polymerase chain reaction. Expression of VP1 and VP2 capsid proteins was evaluated by immunohistochemistry. Interleukin 6 (IL-6) production was measured in the supernatant of myoblasts following incubation with parvovirus B19. RESULTS: In seven samples, detection of B19 DNA was negative. The expression of VP1 and VP2 capsid proteins was not observed by immunohistochemistry. In one patient, detection was transiently positive but became negative despite a flare-up of muscle disease. In vitro, parvovirus B19 was not able to induce IL-6 production by myoblasts. CONCLUSION: Our results do not support the direct implication of parvovirus B19 in the pathogenesis of myositis.

Dermatomyositis associated with the presence of parvovirus B19 DNA in muscle.

We report a case of dermatomyositis associated with molecular evidence of parvovirus B19 DNA in two muscle biopsies collected 5 months apart. IgG- but not IgM-specific antibodies were detected in serum. None of four serum samples was positive for parvovirus B19 DNA. The two biopsies contained B19 VP1 sequences and the second one was also positive for NS1. This is the first report of viral parvovirus B19 DNA in muscle of a patient with dermatomyositis. Latent muscle infection may contribute to the clinical picture.

Bone metastases from bronchial carcinoid tumors. Two case-reports.

Two case-reports of metastatic bone disease in patients with bronchial carcinoid tumors illustrate the diagnostic challenges raised by these slowly-growing malignancies of which the primary frequently escapes early identification. The first patient had the typical picture of a primary with a single bone metastasis. Unusual features in the second patient were the large number of bone metastases, involvement of distal skeletal sites, and elevation of serotonin and 5-hydroxyindoleacetic acid levels.

Hodgkin's disease and B cell lymphoproliferation in rheumatoid arthritis patients treated with methotrexate: a kinetic study of lymph node changes.

We describe 2 patients with seropositive rheumatoid arthritis treated with methotrexate (MTX) who developed Hodgkin's disease (HD) and non-Hodgkin's lymphoma. Followup allowed a lymph node biopsy at 4 different time points in 1 patient and at 2 in the other. In the first patient, the steps included a long history of benign follicle hyperplasia, a polymorphic diffuse B cell lymphoproliferation, and finally HD unassociated with Epstein-Barr virus (EBV). In the second patient, a polymorphic diffuse lymphoproliferation was followed by a monomorphic large B cell lymphoproliferation associated with EBV. The cytogenetic analysis showed a monoclonal proliferation associated with the same chromosomal abnormalities found in 1 of the clones observed in the initial biopsy. These 2 cases illustrate the complexity of the role of MTX in the outbreak of such manifestations.

Vulnerability to ventricular fibrillation related to ischaemia: comparison of the acute effects of beta-blockers and calcium antagonists.

A comparative evaluation of beta-blockers and calcium antagonists as protective agents against ventricular fibrillation related to myocardial ischaemia, was attempted in the pig heart in situ of anaesthetized, open-chest animals, subjected to a temporary complete occlusion of the left anterior descending coronary artery near its origin. This occlusion resulted in fibrillation occurring after a time depending on the vulnerability to the fibrillatory process. As this time to onset of fibrillation does normally not exceed a few minutes, its determination could be achieved repeatedly in the course of an experiment, in the absence and presence of drugs such as beta-blockers and calcium antagonists. When propranolol (0.05 mg/kg, i.v.) and verapamil (0.05 mg/kg, i.v.) abolished tachycardia produced by isoproterenol (0.25 micrograms/kg/min), the triggering of fibrillation was delayed in either case: in animals under atrial pacing at a rate close to the sinus rate on each determination, time to fibrillation was prolonged from about 160 to 400 sec by propranolol and from 160 to 640 sec by verapamil, with a return to control values within 60 min. Under ventricular pacing at a constant high rate (180 beats/min), no change was observed in time to fibrillation after propranolol (0.025 or 0.050 mg/kg), whereas verapamil, in the same conditions and in the same doses, multiplied this time by about 4 and 6, respectively. Consequently, propranolol and verapamil are likely to protect against fibrillation immediately after i.v. injection, but the protection due to propranolol is only indirect and a consequence of bradycardia which tends to increase the polarization of the muscular fibres, whereas verapamil adds to the same influence a direct preventive action by avoiding a cellular calcium overload in these fibres, which is responsible for the depolarization and fluctuations of their membrane potential.