[Sarcoid-like granulomatosis in patients treated with anti-TNFα]. / LE CAS CLINIQUE DU MOIS. Granulomatose sarcoïdose-like chez les patients traités par anti-TNFα.

Over recent years, anti-TNFα have been used to treat rheumatoid arthritis. The principal secondary effect of anti-TNFα is tuberculosis infections. Another paradoxical effect, previously less well understood, is the development of sarcoid-like granulomatous reactions. We report the case of a 36 year old woman who had been treated for 9 years with anti-TNF alpha. She developed a pulmonary sarcoid-like gra-nulomatosis, complication that is rare but not exceptional in patients treated with TNF-blockers. Discontinuation of anti TNF usually led to recovery. It has been suggested that these reactions mainly occur with etanercept, but this requires further confirmation.

Myasthenia in patients with dermatomyositis: clinical, electrophysiological and ultrastructural studies.

In 4 patients with clinical signs of dermatomyositis, confirmed by electromyography and muscle biopsy, a form of muscle fatigue was detected which was expressed clinically by predominantly proximal motor deficit, with phonation and deglutition disturbances, slightly influenced by prostigmine. In all patients, stimulation of the ulnar nerve at 3--10 Hz induced a decrement of muscle-evoked potentials in abductor digiti minimi and at 15--50 Hz an increment at the end of the trains (1.2 sec in duration) of repetitive stimulation (preceded in two cases by a decrement in the response to the fifth stimulus in the train). Stimulation at 30 Hz for 10 sec resulted in a transient facilitation, followed (at 3 Hz stimulation) by postactivation exhaustion which disappeared after 5--15 min. The post-tetanic facilitation, the incremental response and the myasthenic symptoms reverted to normal under treatment with corticosteroids, an immunosuppressor agent and guanidine hydrochloride. A mixed, pre- and postsynaptic mechanism is presumed to underlie the muscle fatigue in our patients. Electron microscopy of muscle biopsies disclosed zones of necrosis and, in incipient stages, large agglomerations of glycogen that had disorganized the structure of myofibrils. The end-plates in the biopsies were larger than normal and the cholinesterase reaction was hyperactive. Serum immunoelectrophoretic and electrophoretic data--increase of IgG and IgM, decrease of IgA and hypergammaglobulinaemia -- point to a possible autoimmune mechanism of the neuromuscular disorders in our patients.

Polyneuropathy with lipid deposits in Schwann cells and axonal degeneration in cerebrotendinous xanthomatosis.

The present paper is a histological, histochemical and electron microscopic study of biopsied specimens from both right and left Achilles tendon, sural nerve and gastrocnemius muscle in a case of peripheral neuropathy with decreased sensory conduction velocity within a cerebrotendinous xanthomatosis confirmed biochemically in a 29-year-old woman. The tendon specimens contained large deposits of complex, non-homogeneous lipids, distributed intra- and extracellularly. The right sural nerve specimen showed a very severe neuropathy with massive diffuse myelinated fiber loss, presence of foamy macrophages and lipid droplets in Schwann cells. Segmental de- and remyelination was noted in 17% of the teased myelinated fibers. No onion bulbs were observed. Two years later, the left sural nerve specimen revealed a mild diffuse myelinated fiber loss, a more active segmental de- and remyelination (23%) without onion bulbs, and an active regeneration. Lipid storage aspects were absent. The gastrocnemius muscle specimens exhibited slight alterations of neurogenic origin. The pathogenesis of this neuropathy is discussed.

Electron microscopic localization of silver binding proteins in the cytoplasmic granules of guinea pig eosinophil.

A new electron optic configuration is described in the specific granules of eosinophil leukocytes. Application of the ammonium silver nitrate impregnation after treatment of intact cells with formaldehyde-OsO4 solution reveals regular deposits of 50 A-electron-opaque particles which are localized in the axial region of the central core. They contain acid-extractable proteins that seem to include the eosinophil basic proteins which participate to the local immune response of the host.

Activation of guinea pig peritoneal macrophages by ribosomal extract of Salmonella typhi strain. Electron microscopy studies.

Normal macrophages and Salmonella typhi ribosomal antigen-activated (immune) ones were studied by electron microscopy. Examination of fine sections from samples incubated between 30 and 120 minutes at 37 degrees C, emphasized phagocytic ability of activated macrophages (29-69% activated macrophages phagocytized 3.7-5.6 bacteria/cell, in contrast to 23-43% with 2.6-4.4 bacteria/phagocytized by non-immune cells). The ultrastructural studies of activated macrophages, performed by electron microscopy, showed the following aspects: a) macrophages with pseudopodiform prolongations, presenting the tendency of bacterial sequestration: b) phagosomes with ingested virulent germs; c). bacteria presenting various degrees of wall and cytoplasm alterations; d). mitochondria with multiple cristae; e). cells with well developed Golgi apparatus and the presence of lysosomes in great numbers; f). existence of a space between the phagosome membrane and the bacterial wall. Experimental results demonstrated: I. an increased phagocytic activity of Salmonella typhi ribosomal antigen-activated macrophages and II. activation expressed as ultrastructural modifications at the level of immune macrophages and also of the bacteria phagocytized by them.

Characterization of colonization factor antigen CFA/I from an enterotoxigenic Escherichia coli strain (0128:H12).

CFA/I antigen was isolated and purified from E. coli, mutant 279 B-1-14, serotype 0128:H12, and had the following biochemical and biological features: a) amino-acid content was similar to that of purified antigen prepared from strain H10407; b) latex particles sensitization with purified CFA/I antigen produced bovine and human erythrocytes group A/II hemagglutination in carbohydrates presence; c) purified anti-CFA/I specific antibodies agglutinated CFA/I-positive enterotoxigenic E. coli strains; d) 3H-leucine-labelled CFA/I antigen adhered to rabbits intestinal mucosa at significant values; e) intestinal mucosa pretreating with purified CFA/I antigen, followed by 3H-leucine labelled enterotoxigenic bacteria infection, had a least 3 local effects: 1) intestinal mucosa protection against parental enterotoxigenic bacteria; 2) inhibition of CFA/I-positive bacteria adherence to intestinal mucosa; 3) release of approximately 96% intraluminally inoculated bacteria.

Immunoprotection of guinea pigs against experimental acute pyelonephritis after the administration of Escherichia coli purified fimbriae.

Experimental results of the present study evidenced the following aspects: a) the antigen, prepared from type I Escherichia coli purified fimbriae (H. 2946 strain), induced immunity at urinary tract level; b) the immunoprotection induced by oral vaccination with multiple doses of fimbriated antigen produced a significant decrease of acute pyelonephritis in newborn guinea pigs and at the same time, a local protection of the urinary tract; c) the immunoprophylaxis by vaccine prepared from fimbriae represents a preferential solution for urinary tract infections prevention in general and especially in children; d) the frequency distribution differences between "protected" and "non-protected" animals were evaluated by chi-square--test with YATES correction and proved to be statistically significant at probability levels.

Sensorimotor neuropathy in a patient with Marinesco-Sjögren syndrome.

A case of Marinesco-Sjögren syndrome, displaying the characteristic signs (ataxia, congenital cataract and mental retardation) is presented. Electrophysiological examination pointed to the presence of a sensorimotor peripheral neuropathy with an underlying mixed process of segmental demyelination and axonal degeneration (probably secondary). The sural nerve and gastrocnemius biopsy confirmed these data, showing that in this case the segmental demyelination process was accompanied by axonal degeneration.

Atypical juvenile neurolipidosis. Ultrastructural study of a cerebral biopsy.

The description is given of a structural and ultrastructural aspect of a cerebral biopsy specimen collected from a 17-year-old patient, with very frequent convulsive seizures, dementia, motor aphasia and spastic tetraparesis. The disease started at the age of 9 years and evolved very slowly. The morphologic diagnosis was neurolopidosis, the ultrastructural one was atypical juvenile lipofuscinosis, the electron microscopic aspect being identical to that of another 3 cases published in the literature: highly polymorphous membranogranulovesicular cytosomes.

Laboratory diagnosis in a case of fatal progressive vaccinia due to manifest immunologic deficiencies.

A case of progressive vaccinia is described, in a 21 years old man, diagnosed after 8 months of vaccinial lesion's evolution. The area of vaccination developed progressive necrosis and metastatic lesions evolved on various regions of the body. The vaccinia virus was isolated on the chorioallantoic membrane of embryonated eggs, from the cutaneous lesions, blood, internal organs and even from the apparently intact skin.--The serological tests indicated hypogammaglobulinemia with absence of neutralizing antibodies.--The death occured after 366 days. The progressive vaccinia described above represents the case with the most prolonged evolution known until now.