Search PubMed⌕ Search

Biomedical subjects

X Bosch

Publications and source records attributed to X Bosch.

At least 181 records · Page 10Linked to original sources
PubMed1997

Circulating soluble adhesion molecules in patients with classical polyarteritis nodosa.

The objective was to evaluate whether changes in circulating soluble adhesion molecule levels reflect disease activity in patients with systemic polyarteritis nodosa (PAN). A sandwich ELISA was used to measure soluble (s) intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), E-selectin, L-selectin and P-selectin in sera and plasma from 22 patients with active PAN, in sera from 13 of these patients taken serially during follow-up, and in sera from 13 healthy controls. At the time of diagnosis, sICAM-1, sVCAM-1 and sE-selectin levels (488.5 +/- 201.3, 1176.5 +/- 514.1 and 60.6 +/- 27 ng/ml, respectively) were significantly higher in patients than in controls (P < 0.0001, P = 0.001 and P = 0.003, respectively). In contrast, sL-selectin levels tended to be lower in patients than in controls. Within the first 7 days after starting treatment, there was a significant increase in sICAM-1 concentrations, which fell thereafter, but did not completely reach normal levels when patients achieved clinical remission. sE-selectin also remained elevated during follow-up. Only sVCAM-1 decreased, tending to reach normal values in inactive disease. Increased levels of sICAM-1, sVCAM-1 and sE-selectin, and decreased levels of sL-selectin, in active PAN suggest immune and endothelial stimulation during disease activity. Abnormal levels of soluble adhesion molecules in clinically inactive patients might reflect persistence of immune activation and/or endothelial cell exposure to a remaining inflammatory microenvironment.

Adult↗
PubMed1997

Vitamin D metabolite-mediated hypercalcemia in Wegener's granulomatosis.

Hypercalcemia may occur during the course of various granuloma-forming diseases. Herein we describe a patient who had symptomatic hypercalcemia as a prominent sign of Wegener's granulomatosis. We observed a direct correlation between the serum levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] and both the serum and the urinary calcium levels. Administration of prednisone and cyclophosphamide led to a substantial decrease in the levels of calcium and serum 1,25(OH)2D, but the serum levels of 25-hydroxyvitamin D remained unchanged. Two months after admission of the patient, the levels of calcium and 1,25(OH)2D increased; after we increased the dose of cyclophosphamide, these levels decreased (the dose of corticosteroids was not changed). We suggest that the excessive synthesis of 1,25(OH)2D was inhibited by a direct or indirect action not only of prednisone but also of cyclophosphamide on the 1 alpha-hydroxylation of 25-hydroxyvitamin D in the activated macrophage of Wegener granulomas. Furthermore, in view of this case and two other recently reported cases, we believe that Wegener's granulomatosis must be definitively added to the list of granulomatous diseases that are responsible for 1,25(OH)2D-mediated hypercalcemia.

Calcium↗
PubMed1997

Ki-ras mutation modifies the protective effect of dietary monounsaturated fat and calcium on sporadic colorectal cancer.

The geographic differences in the incidence of colorectal cancer have been mostly attributed to variations in diet. The diversity of the Mediterranean diet and the heterogeneity of acquired genetic alterations in colorectal cancer sets the stage for investigating the possible association between dietary factors and mutations in tumor genes known to play a role in the pathogenesis of these neoplasms. With this purpose, we have studied the Ki-ras gene in 108 colorectal cancers using archival tissue and epidemiological data from our previous case-control study. Mutations in exon 1 of the Ki-ras gene were detected by a PCR-single strand conformation polymorphism approach. A polychotomous logistic regression model was used to assess the significance of observed differences between wild-type and mutated tumors with respect to population controls in the different categories of nutrient consumption. Multivariate density models were used to adjust the correlation between nutrients and total energy. Our studies show that high consumption of monounsaturated fats, mostly derived from olive oil, is associated with a statistically significant decrease in the risk of cancer with wild-type Ki-ras genotype but not of Ki-ras mutated cancers. Conversely, we find that high calcium intake is associated with a decreased risk of Ki-ras mutated tumors but not of wild-type tumors. Tumor genotyping can reveal epidemiological associations that are weak or unapparent when cases-control studies are not stratified by tumor genotype.

Aged↗
PubMed1996

Prediction of in-hospital cardiac events using dipyridamole-thallium scintigraphy performed very early after acute myocardial infarction.

BACKGROUND AND HYPOTHESIS: Ischemic complications occur frequently during hospitalization after acute myocardial infarction. Dipyridamole-thallium scintigraphy performed early after admission can detect residual ischemia, may have additional prognostic value and be useful in the management of these patients. METHODS: Dipyridamole infusion and 201thallium imaging were performed on the third day of infarction in 114 consecutive patients. Coronary angiography was performed before hospital discharge in 90% of patients and exercise testing was performed at the time of discharge in patients without contraindications. RESULTS: Side effects occurred in 28 patients, but they were mild and transient or rapidly reversed with intravenous aminophylline. During hospitalization, three patients died and four had a nonfatal reinfarction. Patients with these major cardiac events had previously shown a higher prevalence of reversible perfusion defects during testing (71 vs. 31%, p < 0.05). In addition, 19 patients had early recurrent ischemia requiring early in-hospital revascularization. Overall, cardiac events defined as death, reinfarction, or early myocardial revascularization occurred in 22 patients. Of the patients with these events, 68% had thallium redistribution on initial myocardial scanning compared with 25% of patients without events (p = 0.0001). Patients with cardiac events also showed a higher number of myocardial segments with reversible perfusion defects (1.8 +/- 2.2 vs. 0.6 +/- 1.3, p = 0.001). Logistic regression analysis revealed that among all the other clinical, scintigraphic, and angiographic variables, the presence of thallium redistribution on the dipyridamole-thallium scan was the only independent predictor of cardiac events, increasing the risk by sixfold. Furthermore, during a 1-year follow-up, 14 other patients had ischemic events. Of these, 64% had previously shown thallium redistribution during early dipyridamole testing compared with 19% of patients without cardiac events (p < 0.001). CONCLUSIONS: Intravenous dipyridamole-thallium-scintigraphy performed very early after myocardial infarction is safe and useful to predict in-hospital ischemic events.

Aged↗
PubMed1995

Occurrence of antineutrophil cytoplasmic and antineutrophil (peri)nuclear antibodies in rheumatoid arthritis.

OBJECTIVE: To elucidate whether sera from patients with rheumatoid arthritis (RA) contain antineutrophil cytoplasmic antibodies (ANCA) or granulocyte specific antinuclear antibodies (GS ANA), or both, and to analyze possible correlations with different clinical and laboratory data. METHODS: Forty-seven consecutive outpatients with RA were included. Control sera were obtained from patients with well defined rheumatic diseases and from healthy individuals. Serum samples were examined by indirect immunofluorescence (IIF) on both ethanol and paraformaldehyde fixed neutrophils and by ELISA using as substrates myeloperoxidase (MPO), proteinase 3, and a purified extract of alpha-granules. ANA were detected by IIF using cultured HEp-2 cells. RESULTS: Twenty-three patients (49%) had a perinuclear pattern (p-ANCA) by ethanol fixation, of which only 2 became cytoplasmic on paraformaldehyde fixed cells. These 2 patients also had a positive myeloperoxidase ELISA, while none of the remaining 45 had a positive result from the 3 ELISA performed. All 21 patients (45%) with a p-ANCA pattern that was not modified by paraformaldehyde fixation had a specific immunostaining upon examination at high power magnification; we termed this GS ANA specific pattern. The specificity of this pattern was further confirmed by a doubled blind test performed by 2 independent observers. In our study, all GS ANA pattern positive sera fulfilled the previously known definition of these antibodies. We found no relationship between GS ANA and variables such as disease duration and activity, rheumatoid factor, and vasculitis. Notably, 2 RA patients with "true" ANCA (anti-MPO antibodies) had an associated pulmonary-renal syndrome (microscopic polyangiitis). CONCLUSION: Most p-ANCA in our series of patients with RA did not seem to correspond to "true" ANCA but to antibodies directed against nuclear or perinuclear antigenic constituents of the neutrophils (GS ANA). The observation of their distinctive and specific immunostaining pattern, when screening patients for the presence of ANCA by IIF, may alert us to the possible presence of RA.

Adult↗
PubMed1994

[Neutrophil anticytoplasmic antibodies: their diagnostic utility in vasculitis and glomerulonephritis].

BACKGROUND: The prevalence and diagnostic usefulness of antineutrophil cytoplasmic antibodies (ANCA) were analyzed in a series of patients with different types of vasculitis, connective tissue diseases, nephropathies and lung diseases. METHODS: Six hundred seventy-six consecutive patients with systemic vasculitis, connective tissue diseases, nephropathies and different lung disturbances were included in the study. The ANCA were determined by indirect immunofluorescence (IIF) on neutrophils fixed in ethanol. For the detection of antimyeloperoxidase (MPO) antibodies (Ab) a new technique was developed consisting in the performance of IIF on neutrophils with a deficiency in MPO. The serologic samples were also analyzed by enzyme-linked immunosorbent assays with MPO and purified proteinase 3 (PR3). RESULTS: ANCA were demonstrated in 95 patients. A cytoplasmic pattern (c-ANCA) was detected in 25 cases (26%) and in 70 (74%) a perinuclear pattern (p-ANCA) was observed. Twenty-one of the 25 cases (84%) of c-ANCA corresponded to anti-PR3 Ab and 61 of the 70 (87%) of p-ANCA corresponded to anti-MPO Ab. The anti-PR3 Ab identified Wegener's granulomatosis, with a sensitivity and specificity for the generalized and clinically active forms being 65 and 88%, respectively. The anti-MPO Ab were principally detected in patients with rapidly progressive glomerulonephritis (RPGN) and hemorrhagic alveolar capillaritis. The sensitivity and specificity of the anti-MPO Ab for the RPGN and alveolar capillaritis were 75% and 98%. CONCLUSIONS: Two principal subtypes of ANCA may be detected, which also recognize two fundamental clinicopathologic entities. The high diagnostic sensitivity and specificity of these antibodies for each of the processes to which they are associated can justify the adoption of therapeutic measures in determined cases.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Idiopathic pulmonary-renal syndrome with antiproteinase 3 antibodies.

In this report, we describe a patient who developed acute renal failure and fatal pulmonary hemorrhage. Autopsy examination revealed pauci-immune necrotizing glomerulonephritis and pauci-immune hemorrhagic alveolar capillaritis. No evidence of granulomatous inflammation or vasculitis other than capillaritis was found in either lungs or kidneys. In addition, histopathologic examination of the upper respiratory tract, liver, spleen, digestive tract, and skeletal muscle was completely normal. The patient's serum sample disclosed antiproteinase 3 antibodies with an immunofluorescence titer of 1:1,600. Although there have been reports of patients with pulmonary-renal syndrome in association with antiproteinase 3 antibodies in the absence of a well-known vasculitic disease, we have not so far seen a case documented by a detailed autopsy study such as is presented here. In view of our findings and those of some other reports on this clinicopathologic condition, we suggest that this might represent a distinct form of vasculitis with exclusive capillary involvement.

Aged↗
PubMed1994

Antineutrophil cytoplasmic autoantibody-associated alveolar capillaritis in patients presenting with pulmonary hemorrhage.

The objective of this study was to determine the significance of the antineutrophil cytoplasmic autoantibodies (ANCAs) from the clinicopathologic viewpoint of pulmonary hemorrhage occurring as a prominent event of disease. Forty-three consecutive patients with both pulmonary hemorrhage as a prominent clinical manifestation and a positive test for antineutrophil cytoplasmic autoantibodies were studied. Thirty-six patients underwent open lung biopsy, including histologic, tissue immunofluorescence, and microbiologic studies. Immunoassays were performed to investigate the antigenic specificities of antineutrophil cytoplasmic autoantibodies in the patients studied. All patients with lung biopsy confirmation had pauci-immune hemorrhagic alveolar capillaritis as the main morphologic substrate. In addition, renal involvement in the form of pauci-immune crescentic glomerulonephritis was a common finding. Serum samples from the 43 study patients contained antibodies that were monospecific for proteinase 3 (n = 13) or myeloperoxidase (n = 30). In our study, whereas anti-proteinase 3 antibodies were mainly detected in patients with alveolar capillaritis and a well-established diagnosis of Wegener's granulomatosis, antimyeloperoxidase antibodies were principally found in those patients who had alveolar capillaritis and polyarteritis nodosa not only as a primary finding but also accompanying other diseases. However, a significant number of patients with alveolar capillaritis and antimyeloperoxidase antibodies showed no evidence of polyarteritis nodosa (idiopathic pulmonary-renal syndrome and isolated forms of pulmonary hemorrhage). We conclude that in patients presenting with pulmonary hemorrhage as a prominent event of disease, antineutrophil cytoplasmic autoantibodies are a new clue strongly supportive of a pulmonary capillary vasculitis, irrespective of the primary underlying disease. Moreover, the antigenic subtype of antineutrophil cytoplasmic autoantibodies helps in recognizing the type of vasculitic disorder involved.

Antibodies↗
PubMed1993

Anti-neutrophil cytoplasmic autoantibodies (ANCA): antigenic specificities and clinical associations.

We have conducted a prospective study of 372 patients with well-defined forms of systemic vasculitis and connective tissue diseases to determine the prevalence, the antigenic specificities and the clinical associations of ANCA in such cases. These antibodies were detected by indirect immunofluorescence on ethanol-fixed neutrophils and also by enzyme-linked immunosorbent assay using myeloperoxidase (MPO) as a substrate. In our study, ANCA with a cytoplasmic immunostaining pattern were mainly found in patients with biopsy-proven Wegener's granulomatosis with or without renal involvement and pulmonary hemorrhage. Furthermore, MPO-ANCA strongly correlated with necrotizing glomerular and alveolar capillaritis, mostly in patients having a well-established diagnosis of polyarteritis nodosa.

Antibodies, Antineutrophil Cytoplasmic↗