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Data regarding the incidence and outcome of renal involvement in patients with inflammatory myopathies (IM) remain scarce. We assessed the incidence and causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in 150 patients with dermatomyositis, polymyositis, and antisynthetase syndrome followed in 3 French referral centers. Renal involvement occurred in 35 (23.3%) patients: AKI in 16 (10.7%), and CKD in 31 (20.7%) patients. The main cause of AKI was drug or myoglobinuria-induced acute tubular necrosis. Male sex, cardiovascular risk factors, cardiac involvement, and initial proteinuria >0.3 g/d were associated with the occurrence of AKI. The outcome of patients with AKI was poor: 13 (81%) progressed to CKD and 2 (12.5%) reached end-stage renal disease. In multivariate survival analysis, age at IM onset, male sex, a history of cardiovascular events, and a previous episode of AKI were associated with the risk of CKD. We also identified 14 IM patients who underwent a kidney biopsy in 10 nephrology centers. Renal pathology disclosed a wide range of renal disorders, mainly immune-complex glomerulonephritis. We identified in 5 patients a peculiar pattern of severe acute renal vascular damage consisting mainly of edematous thickening of the intima of arterioles. We found that AKI and CKD are frequent in patients with IM. Prevention of AKI is crucial in these patients, as AKI is a major contributor to their relatively high risk of CKD. A peculiar pattern of acute vascular damage is part of the spectrum of renal diseases associated with IM.

We report three non-inbred patients with Val 107 transthyretin (TTR) amyloidosis. Clinical features were remarkable by the combination of peripheral polyneuropathy, carpal tunnel syndrome, cardiomyopathy, and epilepsy. Pathologic examination disclosed unusual striking systemic amyloid angiopathy in all studied tissues including nerve, muscle, gut, lung, salivary glands, and synovial membrane. It appears that the rare TTR Val 107 variant causes a peculiar familial amyloid syndrome characterized by both widespread systemic TTR amyloidosis and central nervous system deposition sufficient to cause seizures, pointing out the extent of TTR amyloidosis phenotypic heterogeneity.

Unlabelled: Experiments were performed on rabbits randomly assigned to intracisternally receive 0.3 mL of plain bupivacaine 5 mg/mL, liposomal bupivacaine 5 mg/mL, bupivacaine-free liposomes, or isotonic phosphate-buffered saline. Mechanical ventilation was initiated or intravenous dopamine was infused when respiratory depression or hypotension occurred. Seven days after the injection, the whole spinal cord was removed and histopathologic characteristics were studied on transverse sections. All preparations were devoid of phosphatidylcholine hydrolysis or oxidation compounds. Solutions without bupivacaine produced transient irritative signs that required sedation in most rabbits. Despite the similar duration of respiratory depression in groups receiving liposomal or plain bupivacaine, liposomes produced significantly prolonged motor blockade (126 vs 70 min). Correction of hypotension after plain bupivacaine required a longer dopamine infusion and larger doses than after liposomal bupivacaine (28 vs 18 min and 74 vs 47 mg). Necrosis was observed in the cervical area of two rabbits (one in the liposomal bupivacaine group and another in the phosphate buffer group). No demyelinated areas were noted in spinal cord examinations. We conclude that liposomal bupivacaine leads to a less severe sympathetic block and to a prolonged motor block, whereas histologic changes are not significantly different among groups., Implications: Multilamellar liposomes containing bupivacaine administered intracisternally to rabbits produce spinal cord histopathologic changes not significantly different from those observed with plain bupivacaine. Sustained release of bupivacaine from liposomes is suggested by the prolonged motor blockade and the reduced severity of arterial hypotension. Use of these liposomes could prolong the local anesthetic effects of bupivacaine.

Background: Graft-versus-host disease (GVHD) is a major complication after bone marrow transplantation, which may be refractory to immunosuppressive drugs. As preliminary case reports suggested that extracorporeal photochemotherapy (ECP) using a Therakos device might be beneficial, we conducted a pilot study to assess the efficacy and safety of a new ECP method that does not require administration of 8-methoxypsoralen (8-MOP) to the patient., Methods: ECP was performed three times a week for 3 weeks and then tapered according to the patient's course. Soluble 8-MOP was added ex vivo to an enriched mononuclear cell suspension obtained by a cell separator. This cellular suspension was then ultraviolet A irradiated and reinfused into the patient. Evaluation was performed using specific objective tests depending on clinical conditions., Results: The two patients in the study with acute GVHD and severe liver dysfunction resistant to steroid pulse showed no improvement with ECP treatment. The five patients with chronic GVHD (c-GVHD) had the following clinical features: three patients had myositis and two patients had severe cutaneous c-GVHD, including one patient with sclerodermoid lesions, one with bronchiolitis obliterans, one with bronchitis, and one with liver involvement. Immunosuppressive drugs were either prohibited or ineffective. The number of procedures for each patient ranged from 13 to 30. Cytapheresis required the use of a double-lumen catheter (4/5) or an arteriovenous fistula (1/5). No side effects were related to 8-MOP or ultraviolet A irradiation. Four of five patients improved after ECP; one patient with bronchiolitis obliterans, a fibrotic condition, remained stable., Conclusions: ECP treatment may be helpful for the treatment of severe c-GVHD and the avoidance of increased immunosuppression.

Objective: To define the factors associated with diagnosis of toxoplasmic encephalitis (TE) in AIDS patients; and to establish a rational procedure for the clinician faced with a decision concerning empiric antitoxoplasma therapy., Design: A 15-month prospective multicentre cohort study in France., Methods: One hundred and eighty-six consecutive HIV-positive inpatients undergoing empiric antitoxoplasma therapy for a first episode of presumed TE were monitored. The clinician's initial estimation of the probability of response to antitoxoplasma therapy was recorded. In addition, a validation committee classified cases as TE or non-TE., Results: Among the 186 patients, the following variables were significantly more frequent in TE (n = 113) than non-TE (n = 73) patients: fever (59% versus 40%). headache (55% versus 33%), seizures (22% versus 11%), suggestive lesions on the brain scan (98% versus 76%), positive Toxoplasma serology (97% versus 71%). Median CD4+ lymphocyte count was significantly higher in TE than in non-TE (27 x 10(6)/l versus 11 x 10(6)/l). The rate of TE in patients on systemic antiprotozoal prophylaxis at entry was 43% as compared with 75% in patients without previous prophylaxis. Pre-therapy estimation of response to empiric therapy was highly correlated with final diagnosis. Multivariate logistic regression analysis showed that the following variables contributed independently to the diagnosis of TE: clinician's estimation of response to treatment at entry > 75%; absence of systemic antiprotozoal prophylaxis; seizures; headache; suggestive lesions on CT or MRI brain scan; and positive Toxoplasma serology., Conclusions: A linear logistic model is proposed which uses significant variables, which are readily available. This model gives good accuracy to classify suspected cases of TE.

Background: Although ketamine has been administered spinally in humans, previous neurotoxicity studies have shown that it can induce spinal cord lesions in various animal models. The aim of this work was to evaluate by histologic and blood-brain barrier studies whether different components of the commercial ketamine solution might be responsible for the microscopic lesions observed., Methods: Forty white New Zealand rabbits were randomly assigned to four groups of 10. One-percent preservative-free ketamine (0.3 ml), 1% d-ketamine, 0.05% chlorobutanol, and 1% lidocaine were intrathecally injected through the atlantooccipital membrane. Laminectomy was performed on day 8, and the dura was preserved using paraformaldehyde-glutaraldehyde fixative. Light and fluorescence microscopy were performed on transverse spinal cord sections by a neuropathologist unaware of injected agents used. Specimens were then graded as normal or abnormal as compared with a control group receiving lidocaine., Results: Isomers of ketamine did not induce spinal cord lesions in either study, but chlorobutanol (the preservative used in the ketamine solution) induced significant severe spinal cord lesions in both studies., Conclusions: The appearance of spinal cord lesions after intrathecal chlorobutanol strongly suggests that this preservative is responsible for apparent toxicity of ketamine and therefore should not be used in any solution intrathecally injected into humans.

Ketamine and midazolam can produce analgesia following intrathecal administration in rabbits. However, neurotoxicity studies are required before these agents can be considered safe for clinical use. The aim of this study was to evaluate by histologic and blood-brain barrier (BBB) studies whether ketamine or midazolam could be used as an alternative to local anesthetics or opioids to produce spinal analgesia. Forty white New Zealand rabbits were randomly assigned to four groups of 10. In the conscious animal, 0.3 ml 0.9% saline solution, 1% lidocaine, 1% ketamine, or 0.1% midazolam was intrathecally injected intracisternally using a modification of the technique of Yaksh et al. Light and fluorescence microscopy were performed on transverse spinal cord sections by a neuropathologist unaware of the administered agents. All spinal cord section slides were scored within four zones: upper cervical, lower cervical, median thoracic, and lumbar segments. Spinal cord homogeneous lesions with higher scores than those of lidocaine-treated animals were considered abnormal. The BBB study showed evidence of neurotoxicity for ketamine, whereas light microscopy indicated no significant differences in comparison with saline and lidocaine. Midazolam-treated rabbits showed significant changes in both BBB and light microscopy studies. In view of these results, the intrathecal use of midazolam should be avoided in humans. Lesions observed following ketamine suggest the need for further experimental studies of the solvent and different ketamine enantiomers to establish definitively the safety of intrathecal free ketamine in humans.

We studied 2 unrelated adult patients under neuroleptic treatment who met all phenotypic and biochemical criteria for Niemann-Pick disease type B. In addition, they had chronic psychiatric disorders and low blood levels of HDL cholesterol. The marked and persistent deficiency of acid sphingomyelinase and the disturbance of sphingomyelin metabolism in skin fibroblast subcultures ruled out a pure drug-induced lipidosis. The association of Niemann-Pick disease type B with psychiatric disorders and with low levels of HDL cholesterol could be a chance association of 2 diseases, a new phenotype of Niemann-Pick type B, or the revelation by the neuroleptic treatment of a subclinical inborn sphingomyelinase deficiency.