Takayasu's arteritis on steroid therapy. Seven years follow-up.

The authors report a 7 year follow-up of Takayasu's arteritis (TA) type III, group 1, in a young Italian woman. At diagnosis, at the age of 25, the echotomographic and angiographic studies showed narrow subclavian arteries, narrow abdominal aorta (diameter of 0.6-0.8 cm) below the renal arteries, stenotic left common carotid and renal arteries, and occluded upper mesenteric artery. With steroid therapy, (prednisone 50 mg/day per os), the erythrocyte sedimentation rate (ESR) normalized within 12 days. With a maintenance dosage of 7.5 mg/day per os, the patient achieved remission as documented by the absence of symptoms, the persistent normalization of ESR, and the improving of the diameter of the abdominal aorta (1.3-1.4 cm). On steroid therapy, the patient had a normal pregnancy and delivered a healthy baby girl. The disease has been stable for seven years. Recently, diabetes mellitus occurred and it has been treated with insulin therapy. The rising of ESR after tapering of steroid therapy (prednisone 5 mg per os on alternate days) suggests an alternative treatment with a cytotoxic agent.

Tortuosity, kinking, and coiling of the carotid artery: expression of atherosclerosis or aging?

The etiology of carotid abnormalities is both congenital than acquired. The aim of this study was to clarify the role of aging and atherosclerosis in the acquired cases, and the role of these abnormalities in hemodynamic alterations and neurologic symptoms. Over a 1-year period the authors studied all the subjects undergoing carotid examination by continuous-wave and color-coded Doppler sonography at an Angiology Unit. They evaluated neurologic symptoms; risk factors for atherosclerosis; number, sites, and kinds of carotid abnormalities; atherosclerotic lesions; stenosis; hemodynamic alterations of the carotid; and other localizations of atherosclerotic diseases. There were 469 subjects: 272 (58%) with abnormalities (group 1) and 197 (42%) without abnormalities (group 2). The total number of abnormalities was 479 (104 tortuosities, 262 kinkings, and 113 coilings). The abnormalities were more prevalent in the elderly (P<0.001) and in women (P<0.001). In group 1 they found significant prevalences of hyperlipemia (P<0.001), hypertension (P<0.01), chronic cigarette smoking (P<0.01), and ischemic heart disease (P<0.05). Carotid atherosclerotic lesions were more prevalent in group 1 than in group 2 (P<0.001); among the patients with atherosclerotic carotid lesions, those in group 1 were older than those in group 2 (P<0.001). Tortuosity seemed to be associated with fewer hemodynamic alterations. The authors conclude that atherosclerosis, hypertension, and aging may play an important role in producing carotid abnormalities. The aging seemed more important than atherosclerosis. Only a prospective study of patients with carotid abnormalities and no atherosclerotic lesion will clarify the role of hemodynamics and neurologic symptomatology.

Putative liver progenitor cells: conditions for long-term survival in culture.

Oval cells proliferate extensively in the livers of animals exposed to oncogenic insults, are bipotent and are believed to be related to the so far unidentified liver stem cell. In normal liver, cells antigenically related to oval cells and expressing liver and epithelial markers are considered to be liver progenitor cells. We isolated, by fluorescence-activated cell sorting or magnetic bead sorting, cells expressing the oval cell antigens OC.2 or OC.3 from the liver of normal newborn or day 12 embryonal age rats. Magnetic bead sorting of positive cells was as efficient as fluorescence-activated cell sorting. A two-chamber culture system was devised in which cells were plated onto transwell filters coated with type IV collagen and cultured in a serum-free Ham's F12 medium supplemented with free fatty acids and bovine serum albumin. Under these conditions, cells remained viable for up to 6 weeks and their antigenic phenotype was unchanged throughout. Approximately 30% of sorted cells expressed epithelial and/or liver-specific markers. Growth factors mitogenic for epithelial cells and hepatocytes did not elicit cell proliferation. These results provide an important background for further studies designed to determine the biological significance of OC.2+ and OC.3+ cells in normal liver, to test the liver stem cell hypothesis and to develop protocols for the expansion in vitro of normal liver progenitors.

Flow cytometry and monoclonal antibodies identify normal liver cell populations antigenically related to oval cells.

Oval cells, a non-parenchymal cell population induced to rapidly proliferate in animals treated with carcinogens, are thought to be related to the hypothesized liver stem cells. In normal liver there are poorly defined cells antigenically related to oval cells. These oval cell antigen positive (OCAP) cells present in normal animals are thought to include hepatocyte and bile duct cell precursors. To isolate them, we modified the existing protocols designed for oval cells and used it on normal neonatal rat livers. Using flow cytometry, the percentage of normal liver OCAP-cells varied with the monoclonal antibody (MoAb) to the different oval cell membrane markers used: 12% (MoAb 18.2), 23% (MoAb 270.38), 27% (MoAb 18.11), 31% (MoAb 18.13), and 37% (MoAb 374.3). Macrophages consisted 10% of the cells (MoAb MCA 275); hepatocytes were essentially absent ( < 1%, MoAb 236.4). Our results demonstrate that is possible to obtain significant numbers of normal cells antigenically related to oval cells and that using different MoAbs, different cell populations can be sorted for use in experimental studies testing liver progenitor cell hypothesis.

D-penicillamine and gold salt treatments were complicated by myasthenia and pemphigus, respectively, in the same patient with rheumatoid arthritis.

A 53-year-old woman with rheumatoid arthritis developed myasthenia gravis after 6 months of therapy with D-penicillamine. Nineteen months after D-penicillamine was discontinued and 12 months after the beginning of gold therapy, she developed pemphigus vulgaris. This is the first reported case of gold-induced pemphigus in rheumatoid arthritis. This study further underlines the complex interactions between the effects of treatment with sulfhydryl-disulfide exchange drugs and the altered immunological system of patients affected by rheumatoid arthritis.

[Falls and fractures in the elderly. Causes and consequences]. / Cadute e fratture nell'anziano. Cause e consequenze.

OBJECTIVE: To evaluate the causes of non-pathologic traumatic fractures in the elderly and their consequences on quality of life. DESIGN: A prospective trial. FOLLOW-UP: 12 months for the inpatients and 3 months for the outpatients. SETTING: Basal assessment in orthopaedic hospital; follow-up in geriatric unit. PATIENTS: Both inpatients and outpatients, 65 years and over, both sexes, both living in a nursing home and in their own home, admitted to an orthopaedic hospital because of a fall, with diagnosis of a subsequent fracture. Criteria of exclusion: patients with pathologic fracture. 121 patients were enrolled, 108 had a complete follow-up. SURVEYS: Health and functional status prior to the fracture, causes and concomitant causes of the fall, site of the fracture, complications and functional disabilities. RESULTS: The most frequent cause of fracture is an accidental fall, especially in younger elderly, other causes being acute cardiovascular and neurological diseases. Fractures occur more frequently in females. The most serious injuries affect frailer subjects, with advanced age, neurologic and multiple chronic diseases. Fracture of femur is the most frequent fracture and it has the highest risk complications, functional disabilities and death. CONCLUSIONS: Because of the high frequency of accidental falls, the authors emphasize the necessity of primary prevention, especially the removal of architectural barriers both at home and in public environment.

Synthesis of biologically active fibroblast-activating factor (FAF) by xenopus oocytes injected with T lymphocyte mRNA.

Activation of human peripheral blood T lymphocytes results in the production of fibroblast-activating factor (FAF), a mediator which stimulates fibroblast proliferation. This lymphokine, which may provide a molecular link between cell-mediated immune reactions and fibroplasia, has been identified as a T-cell product both in vitro and in vivo. In order to study the mechanisms of synthesis and activity of FAF, poly(A) RNA was isolated from concanavalin A-stimulated T lymphocytes and injected into Xenopus oocytes. The injected oocytes translated the messenger RNA and produced a material with the biological and biochemical properties of human FAF. The oocyte product induced proliferation in serum-free quiescent fibroblast monolayers and exhibited the same molecular weight and charge as the T-cell-derived factor. Oocytes injected with poly(A)-RNA from unstimulated T lymphocytes produced little, if any, FAF activity. We conclude that activation of T lymphocytes enhances transcription of FAF mRNA as detected in the oocyte translation assay. This translated material has biological activity and biochemical characteristics consistent with FAF and is suitable for further studies on the expression and synthesis of FAF (poly)peptides.

Cytokines and fibrosis.

Inflammation is frequently associated with changes in the surrounding connective tissue. Inflammatory mononuclear cells (MNC) produce biologically active molecules, cytokines (CK), which may regulate the growth and function of connective tissue fibroblasts. In this article, we review the characteristics of lymphocyte and monocyte CK which appear to be involved in regulating fibroblast recruitment, proliferation, and matrix synthesis. Whereas these MNC products are important in normal physiologic wound healing, an imbalance of these CK may lead to pathophysiologic fibrosis and/or destruction of connective tissue components. Clinical states associated with MNC-mediated connective tissue pathology include scleroderma, rheumatoid arthritis, diffuse pulmonary idiopathic fibrosis, sarcoidosis and atherosclerosis. Characterization of the molecular pathways linking inflammatory mononuclear cells and fibrosis may provide avenues for therapeutic intervention.

Detection of anti-extractable nuclear antigens in connective tissue diseases: comparison between passive hemagglutination, counterimmunoelectrophoresis and double immunodiffusion.

Antibodies to the three major components of the complex called soluble extractable nuclear antigen (ENA) were detected by passive hemagglutination (HA), counterimmunoelectrophoresis (CIE) and double immunodiffusion (DI) in 256 patients with connective tissue diseases. Anti-ENA antibodies were demonstrated by all the three employed methods in only 44.9% of the cases. These methods were not able to detect all antibodies to these antigens or any single specificity; CIE was however the most sensitive method for anti-RNP and HA for anti-Sm antibodies, while DI was the most suitable technique for serum samples with multiple anti-ENA specificities. Only in less than 50% of the cases the specificity detected by HA was comparable with that given by CIE or DI. Hence, for detecting anti-ENA antibodies a combination of these methods should be maintained, at least until more precise and reliable methods will become available.