Successful treatment with leflunomide of arthritis in systemic sclerosis patients.
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Biomedical subjects
Publications and source records attributed to M Sebastiani.
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We determined the minimum local anaesthetic dose (MLAD) of spinal levobupivacaine and ropivacaine for Caesarean section. Ninety women were randomly allocated to two groups and received 3 ml of study solution by a combined spinal/epidural technique. The initial dose was 12 mg for levobupivacaine and 17 mg for ropivacaine groups. To be considered effective, a test solution had to achieve a visual analogue pain score (VAPS) of 30 mm or less at skin incision, uterine incision, birth, peritoneal closure, and at the end of surgery. Effective or ineffective responses determined, respectively, a 0.3 mg decrease or increase of the same drug for the next patient in the same group, using up-down sequential allocation. The MLAD of levobupivacaine was 10.58 mg (CI 95%: 10.08-11.09) and the MLAD of ropivacaine 14.22 mg (CI 95%: 13.67-14.77), using the Dixon and Massey formula. The potency ratio between spinal levobupivacaine and spinal ropivacaine was 1.34.
OBJECTIVES: The pathogenesis of systemic sclerosis (SSc) includes complex alterations to the immune system, possibly responsible for diffuse microvasculature and fibroblast dysfunction. Previous anecdotal observations suggest a possible role for thymus alterations in some autoimmune rheumatic diseases, including SSc. This study aimed to investigate the prevalence of radiological thymus alterations in SSc patients. METHODS: Thirthy-four unselected patients [28 female and 6 male, mean age (+/- S.D.) 49.7 +/- 9.5 yr, range 33-67 yr] and 34 age- and sex-matched controls were included in the study. The presence of major radiological thymus alterations, i.e. an abnormally enlarged or nodular thymus, were blindly investigated by means of unenhanced multidetector computed tomography. RESULTS: Abnormally enlarged or nodular thymuses were detected in a statistically significant percentage of SSc patients compared with controls (21 vs 0%, P = 0.011). More interestingly, radiological thymus alterations were invariably observed in patients with shorter disease duration (< or =5 yr, 41% vs >5 yr, 0%; P = 0.007), frequently associated with serum anti-Scl70 antibodies (P = 0.017). Among patients with thymus alterations one developed myasthenia gravis while two others showed thymus hyperplasia at histopathological evaluation after thymectomy. CONCLUSIONS: The present study suggests a possible role of thymic disorders, mainly thymus hyperplasia, in a significant number of SSc patients. Due to the limitations of radiological evaluation, the actual relevance of such an association might be underestimated. The relationship of thymus alterations with shorter disease duration, as well as with serum anti-Scl70, suggests that thymic dysfunction could play a pathogenetic role mostly in the early phases of the disease, and possibly in specific SSc patient subsets.
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Scleroderma heart involvement (SHI) is often manifest, and virtually always present when accurately searched and holds a significant prognostic value. Myocardial involvement by patchy fibrosis (secondary to both repeated ischaemia and immunoinflammatory damage) leads to ventricular diastolic dysfunction, whereas right ventricle overload and failure may complicate pulmonary hypertension. Left ventricular systolic dysfunction is present in a minority of patients, namely those presenting atherosclerotic coronary artery disease and/or arterial hypertension, sometimes triggered by sclerodermic renal involvement. Dysrhythmias and conduction disturbances are considered an hallmark of SHI, facilitated by autonomic dysfunction. SHI is frequently linked to parenchimal and/or vascular lung disease; they determine symptom occurrence, particularly dyspnoea, fatigue, palpitations and chest pain when pericardium is affected. Accurate cardiologic baseline screening and subsequent follow-up are mandatory in all patients, initially consisting in some noninvasive diagnostic procedures: visit, electrocardiogram (EKG), chest X-ray, Doppler-echocardiography. When needed, these examinations should be integrated by EKG Holter-monitoring, cardiopulmonary stress tests, cardiac magnetic resonance imaging, nuclear studies of myocardial function and perfusion, cardiac catheterization to better estimate pulmonary hypertension, and cardiac natriuretic hormone evaluation. Several vasodilator approaches (prostacycline or NO/endothelin) may counteract the microvascular dysfunction at peripheral and cardiopulmonary level, and fight the sequelae of pulmonary hypertension.
OBJECTIVE: To describe clinical and serological features of a large series of patients affected by primary Sjogren's syndrome (pSS), assessing the evolution of the disease in a long-term follow-up study. METHODS: Clinical and laboratory data of 250 patients with pSS attending our Unit for a mean follow-up period of 140 months were retrospectively collected and analysed. In all the cases the diagnosis was made according with the recent international criteria. RESULTS: Glandular involvement was almost universally present, typically as the first manifestation of the disease and a slow progression of the salivary and lachrymal dysfunction was seen during the observation period. Extraglandular involvement was mild, quite rare and delayed. The respective percentages for muscle-skeletal disease, urogenital, haematological, skin, pulmonary, gastrointestinal, neurological and renal involvement were 60%, 40%, 24%, 20%, 11%, 7%, 8% and 3%. Only 6 patients developed a lymphoma. The serological pattern of the majority of patients remained constant throughout the follow-up period. CONCLUSIONS: pSS is often a benign condition. Since some patients may develop lymphoid malignancies, clinical follow-up is recommended.
AIM: Using the statistic method of sequential allocation, we realized a prospective double-blind study in order to establish the minimum local anesthetic concentration (MLAC) of large intrathecal volume of levobupivacaine, during the first stage labour analgesia in spontaneous and induced laboring women. METHODS: Seventy-five nulliparous, at term, with cervical dilatation <5 cm parturients requesting combined spinal/epidural analgesia, were enrolled. The starting concentration was chosen according to recent literature. Total volume of study solution was 10 ml and efficacy was assessed with a visual analogue pain scale at the height of the uterine contraction. RESULTS: We established that MLAC of levobupivacaine, in 10 ml intrathecal volume, during the first stage of spontaneous and induced labour was 0.0134% and 0.0195%, respectively. No complications occurred during the study and the only side effect was shivering, which is common even in other anesthetic techniques. We produced a very selective sensitive block. Neither sympathetic nor motor block occurred. CONCLUSIONS: Low intrathecally concentration of local anesthetic allows the anesthetist to reduce the total amount of drug and improves not only the differential blockade between motor and sensitive but also between sympathetic and sensitive fibers.
OBJECTIVES: Mixed cryoglobulinaemia (MC) is a systemic vasculitis frequently associated with hepatitis C virus (HCV) infection. A possible link between HCV infection and type 2 diabetes has been suggested. This study evaluated the prevalence and clinical phenotype of diabetes in MC-HCV+ patients. METHODS: Two hundred and twenty-nine consecutively recruited MC-HCV+ patients were compared with 217 sex- and age-matched controls without HCV infection. RESULTS: The prevalence of type 2 diabetes was significantly higher in MC-HCV+ patients than in controls (14.4 vs 6.9%, P < 0.01). Diabetic MC-HCV+ patients were leaner than diabetic patients without MC-HCV (P < 0.0001), and showed significantly lower total and low-density lipoprotein cholesterol levels (P < 0.001) and lower systolic (P = 0.01) and diastolic blood pressure (P = 0.005). MC-HCV+ diabetic patients had non-organ-specific autoantibodies more frequently (34 vs 18%, P = 0.032) than non-diabetic MC-HCV+ patients. CONCLUSIONS: The prevalence of type 2 diabetes is higher in patients with MC-HCV than in controls. Diabetic MC-HCV+ patients show an attenuated diabetic phenotype and are more likely to carry non-organ-specific autoantibodies.
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For a long time now we have been putting forwards the hypothesis that, when two cells belonging to different tissues of the same organism fuse, the nucleous/nuclei of the resulting "fused" cell could lay into a cytoplasm possibly containing factors influencing the activation or deactivation of genes able to interfere with the differentiation "iter" proper of the parent cells. As a consequence, the fused cells could undergo neoplastic transformation. In order to give an experimental support to such an hypothesis, mononuclear cells and granulocytes were isolated from the white blood cells of the same individual, mixed (at 1/1 ratio) and fused, using polyethylen glycol (PEG). The fused cells were then cultured into a suitable medium, supplemented with phytohemoagglutinin (PHE), a lectin which is able to stimulate at least one of the nuclei. Samples from these cultures were withdrawn at progressive time-intervals and stained with May Grümwald-Giemsa. Microscopic examination showed the appearance of cells morphologically resembling Hodgkin's and Reed Sternberg cells, or leukemic cells. A crown of mononucleated cells was often surrounding such anomalous cells, as happens in the early stage of killer cells action against target cells. In two out of fifty cultures, cells grew without need for serum supply, suggesting the onset of an autocrine system.
Gross cystic breast disease (GCBD) is the most common benign disease of the human female breast, and patients with GCBD have an increased risk of breast cancer. The aim of this study was to evaluate the distribution inside apocrine cells and in breast cyst fluids aspirated from gross cysts of prostate-specific antigen (PSA) molecular forms, and to correlate the different intracystic PSA profiles to the subpopulations of gross cysts. Type I cysts showed a median value of 0.71 microg/L of total PSA and 0.32 g/L of ACT, significantly different to that of Type II cysts (Wilcoxon P < 0.001). Although large excesses of ACT were detected in all samples, BCF samples and apocrine cells from Type I gross cysts contained about 70% of free PSA, compared to the higher amounts of complexed PSA found in Type II gross cysts. We demonstrate that in apocrine/secretive Type I breast gross cysts the serine protease PSA was mainly present in its free form, in contrast to a major proportion of complexed PSA found in flattened/transudative Type II cysts. Our results are consistent with the notion that a prolonged exposure of apocrine breast cells lining the Type I gross cysts to the proteolytic activity of PSA could be involved in the etiopathogenesis of GCBD.
Breast duct epithelium produces, secretes, and metabolises several biologically important compounds, which are found in breast secretions obtained in physiologic and pathologic conditions (milk and nipple aspirate fluids, respectively). In order to preliminarily evaluate the ultrastructural morphology of the cells found in Type II nipple aspirate fluids (NAF) and correlate it with the biochemical profile of the extracellular fluid present in these breast secretions and in human milk, we analyzed 72 NAFs from nonlactating premenopausal women affected by various breast diseases and 10 normal milk samples. Although several constitutive proteins were detected in all samples examined, the preliminary biochemical analyses and electrophoretic profiles revealed characteristic behaviours for several biologic constituents, suggesting a possible basic mechanism of production by breast epithelial cells during both physiologic and pathologic conditions. The ultrastructural analysis of milk cellular components give preliminary evidence of the apocrine secretion mechanism peculiar of breast gland, whereas Type II NAF cells appeared as biosynthetically active cells, showing a possible modified secretion mechanism. Our multidisciplinary approach seems to support the hypothesis that cellular and biochemical behaviour of Type II NAF may be an useful tool to identify aberrated breast epithelial cells in nonlactating women that might be prone to premalignant transformation.
PURPOSE: We report on the importance of the integration of data obtained from digital coronary angiography and stress/rest 99mTc sestamibi myocardial perfusion single photon emission tomography in evaluating the hemodynamic significance of coronary arteriovenous fistulae. MATERIAL AND METHODS: Coronary fistulae were detected with coronary angiography in 9 patients. All patients underwent clinical examination, transthoracic echocardiography, stress electrocardiogram and stress/rest 99mTc sestamibi myocardial perfusion single photon emission tomography. RESULTS: Stress/rest 99mTc sestamibi myocardial perfusion single photon emission tomography and stress electrocardiogram showed stress-induced myocardial ischemia in 2 patients. The first patient with familial predisposition and risk factors for ischemic heart disease presented a mesocardic heart murmur on clinical examination. At stress ECG (125 Watt, 153 b/m' max frequency 93%, arterial pressure 230 mmHg, max frequency pressure product 35,200) ischemic alterations were recorded at the first minute of the second stage of the Bruce protocol. Coronary angiography detected a circumflex artery fistula in the coronary sinus. Stress/rest 99mTc sestamibi myocardial perfusion single photon emission tomography for the evaluation of stress/rest perfusion detected a reversible perfusion defect of the proximal portion of the posterolateral and lateral walls, thus confirming the hemodynamic importance of the flow through the fistula during stress cycloergometric testing. In the second patient familial predisposition to ischemic heart disease and previous inferior wall myocardial infarction and non-significant stress ECG, coronary angiography identified a subocclusive stenosis of the right coronary artery and an anomaly between the anterior interventricular artery and the left pulmonary artery. The presence of the contrast medium in the left pulmonary artery identified a flow from the left ventricle to the left pulmonary artery. Good angiographic results were obtained after percutaneous coronary angiography of the right coronary artery stenosis. Due to the onset of angina stress/rest 99mTc sestamibi myocardial perfusion single photon emission tomography was performed to evaluate stress/rest perfusion (75 Watt, 125 b/m', 88% max frequency, arterial pressure 200 mmHg, double max product 25,000 with ST depression of 1.5 mm in V1-V4) and identified an irreversible perfusion defect due to infarction and a reversible perfusion defect of the anterior wall and apex due to ischemia caused by the anomalous flow through the coronary fistula. The correspondence between the site of the coronary artery where the fistula originates, identified by coronary angiography, and the reversible perfusion defects, identified by stress/rest 99mTc sestamibi myocardial perfusion single photon emission tomography, indicates that the anomalous flow through the fistula may cause myocardial ischemia. The irreversible perfusion defects of the inferior wall are the result of right coronary artery subocclusive stenosis. CONCLUSIONS: Coronary fistulae cause myocardial ischemia only in a small number of patients. Data obtained from single photon emission tomography in evaluating stress/rest myocardial perfusion, correlated with data from coronary angiography, have shown that changes in patients with terminal coronary anomalies may be due to different coronary diseases: ischemia to anomalous flow through the fistula and myocardial infarction to subocclusive right coronary artery stenosis. Stress/rest 99mTc sestamibi single photon emission tomography for the evaluation of myocardial perfusion is a reliable means of assessing the functional importance of the terminal coronary anomalies detected by coronary angiography. Evaluation of the hemodynamic importance of the coronary fistulae is indispensable in programming corrective surgery.
Prostate-specific antigen (PSA), a serine protease thought to be exclusively produced by the prostate epithelial cells, has been recently found in human breast tissues and fluids. PSA in breast cancer is associated with the presence of steroid-hormones and receptors, and its presence seems to be a favourable prognostic indicator. In order to clarify whether the cells lining breast cysts may represent the source of PSA found in human breast cyst fluid, we performed an ultrastructural immunolocalization of PSA in the cells surrounding Type I breast cysts, obtained from breast cyst fluids of women affected by breast gross cystic disease, the most commonly occurring benign breast lesions associated with increased cancer risk. These apocrine cells show morphological features typical of actively synthesizing and secreting cells, and a PSA labelling distributed on free ribosomes, RER cisternae, and secretory granules, indicating that the metabolically active apocrine cells lining the Type I cysts are responsible for the production and secretion of PSA in Type I breast cyst fluids. The synthesis and intracystic accumulation of this serine protease in biosynthetically active apocrine Type I cysts can play an important role in the natural history of breast gross cystic disease as well as in the mechanism of cyst evolution.
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Human gross cystic breast disease is a benign condition affecting about 7-10% of adult women occurring with the highest incidence in the premenopausal decade. Although breast cysts do not represent a preneoplastic condition per se, several studies indicate an increased breast cancer risk in women affected by this pathology. In this report we study 115 breast cystic fluid samples obtained by needle-aspiration from women with gross cystic breast disease. The samples were analysed biochemically and the cells contained therein were observed at the electron microscope. According to their biochemical profiles, the cysts were subdivided into three types: Type I, showing a Na/K ratio < 0.5 and a typical protein content; Type II, showing a Na/K ratio >10 and a protein content quite similar to plasma; Type III, showing a Na/K ratio between 1 and 7 and an intermediate protein content. The electron microscopic examination demonstrated that Type I cystic fluid cells exhibit morphological features typical of actively synthesising and secreting cells, while the characteristics of Type II cells indicate a low metabolic activity. Type III cells have characteristics typical of both Type I and Type II cells, thereby confirming the intermediate nature of this cyst type. We hypothesise that these cyst types could represent different developmental stages of a structural evolution pathway, during which the biosynthetically active 'apocrine stage' would be the key step to cell neoplastic transformation.