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Biomedical subjects

A Laffón

Publications and source records attributed to A Laffón.

16 recordsLinked to original sources

Primary solitary Echinococcosis in cervical spine. Postsurgical successful outcome after long-term albendazole treatment.

STUDY DESIGN: A case report of a young man with isolated cervical hydatidosis treated postoperatively with sustained cyclical albendazole therapy for 9 years of follow-up. OBJECTIVES: To communicate the efficacy and safety of prolonged albendazole treatment in the postoperative management of spinal hydatid disease, and recommend therapeutic regimes for preventing its recurrence. SUMMARY AND BACKGROUND DATA: Bone involvement in hydatid disease is uncommon and the cervical region of the spine is rarely affected. Surgical excision remains the treatment of choice but high rates of postoperative recurrence have highlighted the importance of adjuvant anthelmintic therapy. The selection of the drug(s) and the duration of the medical treatment is still controversial. METHODS: The patient described herein presented with isolated bone lesions, in an unusual cervical location, and without coincidental visceral involvement. Therefore, diagnosis was delayed and surgical debridement was carried out without any preoperative anthelmintic therapy. To prevent late recurrences, therapy with intermittent courses of albendazole has been maintained for nine years and is still ongoing. Response and toxicity related to therapy has been closely monitored by clinical, biochemical and radiological follow up. RESULTS: After surgery the patient has remained asymptomatic without sequelae or evidence of relapses. No clinically relevant side effects has been observed. CONCLUSION: Prolonged albendazole treatment appears to be safe and effective in the prevention of late recurrences after spine hydatidosis surgery. Long-term chemotherapeutic schedules should be considered after surgical excision of spine or bone lesions.

Adult↗

Aceclofenac, a new nonsteroidal antiinflammatory drug, decreases the expression and function of some adhesion molecules on human neutrophils.

OBJECTIVE: To study the effect of aceclofenac, a new nonsteroidal antiinflammatory drug (NSAID), on the expression and function of adhesion molecules in human neutrophils. METHODS: We used flow cytometry analysis to determine peripheral blood neutrophil expression of L-selectin, CD11a, CD11b, CD31, CD43, CD44, and intercellular adhesion molecule 2 (ICAM-3) surface adhesion molecules after treatment with aceclofenac, diclofenac, or dexamethasone. Granular enzyme activity was quantitated in extracellular medium of neutrophils treated with different NSAID: In vitro adhesion assays were developed to examine the effects of aceclofenac on both neutrophil adhesion to tumor necrosis factor alpha stimulated human umbilical vein endothelial cells under nonstatic conditions, and homotypic neutrophil aggregation induced by anti-ICAM-3 and anti-CD18 monoclonal antibodies (Mab). RESULTS: Aceclofenac induced a dramatic decrease of L-selectin expression, whereas a moderate and slight decrement of CD43 and ICAM-3 expression was also observed. In contrast, the expression of other adhesion molecules by neutrophils was unaffected (CD11a, CD31, CD44) or slightly increased (CD11b). Cell adhesion assays, performed under nonstatic conditions, revealed that aceclofenac significantly diminished the L-selectin dependent neutrophil adhesion to endothelial cells. Neutrophil aggregation induced with anti-CD43 Mab was also significantly inhibited by aceclofenac. CONCLUSION: Aceclofenac had a faster and more potent effect than the other NSAID studied, mainly on the expression of cell adhesion molecules. This new NSAID efficiently interferes with neutrophil adhesion to endothelium and this effect may represent an additional relevant mechanism in its antiinflammatory activity.

Anti-Inflammatory Agents↗

Expression of L-selectin, CD43, and CD44 in synovial fluid neutrophils from patients with inflammatory joint diseases. Evidence for a soluble form of L-selectin in synovial fluid.

OBJECTIVE: To study the expression of L-selectin, CD43, and CD44 on peripheral blood (PB) and synovial fluid (SF) neutrophils from patients with inflammatory joint diseases, and to investigate the presence of soluble L-selectin in both SF and plasma from patients with acute and chronic arthritis. METHODS: PB and SF neutrophils were isolated from 13 patients with rheumatoid arthritis (RA) and 17 patients with various inflammatory joint diseases other than RA. Expression of L-selectin, CD43, CD44, CD11a, and CD11b was determined in both unstimulated and in vitro-activated cells by immunofluorescence flow cytometry. Soluble L-selectin levels were estimated in SF and plasma by a semiquantitative radioimmunoassay. RESULTS: Neutrophils from SF showed diminished expression of L-selectin compared with PB neutrophils; CD43 expression and CD44 expression were decreased in SF neutrophils from most patients. In contrast, SF neutrophils exhibited significantly increased expression of CD11b, to an extent similar to that seen with in vitro-activated PB neutrophils. Soluble L-selectin was detected at similar levels in SF and PB. CONCLUSION: The phenotypic profile of SF neutrophils (low levels of L-selectin, CD43, and CD44, and high levels of CD11b) from most patients with RA or other inflammatory joint conditions resembles that observed in in vitro-activated neutrophils. Our results suggest that SF neutrophils are activated to a similar degree in inflammatory joint diseases with different pathogenic mechanisms.

Acute Disease↗

The role of adhesion molecules in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by infiltration of mononuclear cells, mainly T lymphocytes, into the synovial membrane (SM). The interaction of peripheral blood T cells with the different components of the rheumatoid synovium is mediated by cell surface proteins such as selectins, integrins, members of the immunoglobulin superfamily and homing receptors. T lymphocytes infiltrating the rheumatoid SM show an activated phenotype and display an increased avidity of their adhesion receptors that results in an enhanced interaction of these cells with both extracellular matrix proteins (ECM) and cellular ligands (VCAM-1, ICAMs). The interaction of T cell integrins with their ligands, besides an additional antigenic stimulus, could trigger a mitogenic response on these cells, a phenomenon that can contribute to increased cellularity observed into the rheumatoid SM. Moreover, cell attachment to ECM through integrins induces the secretion of several proteases that can contribute to the tissue damage observed in RA. The increased knowledge about the role of adhesion receptors in the pathogenesis of RA and other inflammatory diseases will allow the introduction of a new therapeutic approach by: the use of specific blocking reagents designed to interfere with the function of adhesion molecules.

Arthritis, Rheumatoid↗

VLA family in rheumatoid arthritis: evidence for in vivo regulated adhesion of synovial fluid T cells to fibronectin through VLA-5 integrin.

Adhesion of T cells to extracellular matrix (ECM) proteins through VLA integrin receptors is crucial for lymphocyte trafficking, tissue localization and inflammatory function. We have investigated the expression of different VLA integrins (VLA-1-5) on peripheral blood (PB) and synovial fluid (SF) T lymphocytes from patients with rheumatoid arthritis (RA). Their expression on different cell types from synovial membrane (SM) is also reported. The role of VLA-4 fibronectin (FN) receptors in the interaction of activated SF T cells from RA patients with a 38-kD fragment of FN has been previously demonstrated. Here we have focused functional studies on VLA-5 as an alternative FN receptor for RA T cells. A significant higher proportion of SF T cells were able to bind to an 80-kD fragment of FN, containing the Arg-Gly-Asp (RGD) cell binding site, compared with PB T cells. This attachment was almost completely inhibited by anti-VLA-5 MoAbs as well as by RGD peptides. This enhanced capability by SF T cells appears to be independent of the level of the surface expression of the receptor and correlates better with their activation state as determined by the expression of the activation molecule AIM (CD69). The evidence for the expression of VLA heterodimers on both SF and SM cells from RA patients suggests the possible implication of ECM proteins in mediating and perpetuating inflammation in vivo.

Adult↗

Activation markers on peripheral blood T cells from patients with active or inactive systemic lupus erythematosus. Correlation with proliferative responses and production of IL-2.

Using various monoclonal antibodies to T cell activation molecules it has been shown that purified T cells from patients with active systemic lupus erythematosus overexpress the 4F2, IL-2R (CD25), HLA-DR and T10 antigens. T cells from patients with inactive disease had increased expression of VLA-1 and HLA-DR. Increased T10 expression on T cells from patients with active disease correlated inversely with the production of IL-2, whereas expression of CD25 was slightly increased after 3-day culture with either PHA or anti-CD3. These results provide further evidence of the in vivo activation of T cells in SLE and suggest that such activation comes slowly to a halt upon disease remission.

ADP-ribosyl Cyclase↗

Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis.

The VLA-4 (CD49d/CD29) integrin is a cell surface receptor involved in the interaction of lymphoid cells with both extracellular matrix (ECM) and endothelial cells. We have investigated the expression and function of VLA-4 fibronectin (FN) receptors on T cells localized in the inflammed synovium of patients with rheumatoid arthritis (RA). A high proportion of T cells in both synovial membrane (SM) and synovial fluid (SF) expressed the activation antigens AIM (CD69) and gp95/85 (Ea2) as well as an increased number of VLA-4 alpha and beta 1 adhesion molecules, as compared with peripheral blood (PB) T cells from the same patients. Furthermore, the majority of these activated SF T cells were able to adhere to a 38-kD FN proteolytic fragment containing the connecting segment-1 (CS-1) specifically through VLA-4 receptors, whereas a significantly lower proportion of PB T cells displayed this capacity. Therefore, our results show that activated T cells selectively localize at sites of tissue injury in RA disease and provide evidence for the in vivo regulation of the expression and function of the VLA-4 integrin. This regulatory mechanism may enable T cells either to facilitate migration or to persist at sites of inflammation.

Adult↗

Hepatic sinusoidal dilatation in rheumatoid arthritis.

In a review of 100 consecutive patients with adult rheumatoid arthritis (RA), clinical evidence of liver disease was absent, whereas minor abnormalities of liver biochemistry, mainly a raised alkaline phosphatase, were present in 32 cases. Liver biopsies were obtained in eight patients; the most striking finding was the presence of sinusoidal dilation in all samples, with a normal central vein and preservation of hepatic architecture. The mechanism of this nonspecific histological change is not known, though it could be speculated to be secondary to a humoral factor related to RA. We conclude that hepatic involvement in adult RA is common but trivial and that routine liver biopsy is not indicated.

Adult↗

Systemic lupus erythematosus and tetrasomy-X.

An 18-year-old woman with tetrasomy-X (48,XXXX karyotype) who developed systemic lupus erythematosus is described. This is, to our knowledge, the first recorded case of this association. The occurrence of autoimmune disorders in patients with chromosomal aberrations is discussed.

Adolescent↗

Differences in the production of and/or the response to interleukin-2 by T lymphocytes from patients with the various connective tissue diseases.

We have studied the production of and the response to interleukin-2 (IL-2) by blood T lymphocytes from 83 untreated patients with six connective tissue diseases, each patient with a healthy age/sex matched control. SLE patients had markedly decreased production of IL-2, both when elicited with phytohemagglutinin (PHA) and when promoted by autologous mixed lymphocyte reaction (AMLR). They also had decreased response to IL-2. Conversely, patients with scleroderma had normal production of IL-2 with both stimuli and their lymphocytes responded to IL-2 similarly to, or even better than, controls. Patients with mixed connective tissue disease had decreased production of IL-2 upon PHA stimulation but it was normal in AMLR systems. Response to IL-2 was moderately diminished. Patients with rheumatoid arthritis showed moderately decreased production of Il-2 with both stimuli but a normal response to Il-2. Patients with Sjögren's syndrome had similar, but less marked defects than those of SLE. Patients with dermato-polymyositis showed decreased production of IL-2 in AMLR but normal production of IL-2 in response to PHA as well as normal response to IL-2. The differences found between the various connective tissue diseases support the notion that the T cell dysregulation that results from or leads to "autoimmunity" in them is peculiar to each disease.

Absorption↗

Early proliferative response in the human autologous mixed lymphocyte reaction in scleroderma.

Autologous mixed lymphocyte reaction (AMLR) studied at 7 days with cells from 20 scleroderma patients appeared decreased as compared to healthy matched controls. In kinetic AMLR studies with cells from 16 patients, this was found to result from the decline after an early proliferative response occurring on Day 4 (9 patients) or 5 (4 patients), whereas the other 2 had low responses throughout. As this early response may be anamnestic, kinetic studies lasting 12 days revealed a second proliferative response on the 9th or 10th day and the responses in allogeneic mixed lymphocyte cultures did not differ from those found in normal controls. These findings suggest either that autoreactivity between T and non T cells might have occurred in vivo in scleroderma patients and is recalled in the AMLR or that alterations of immunoregulatory cells permit this earlier activation in the system.

Adult↗

Probable depiction of juvenile arthritis by Sandro Botticelli.

There is a question whether rheumatoid arthritis is a disease of recent or ancient onset since it was only first described in 1800. In support of its earlier appearance are depictions of rheumatoid hands in Flemish paintings of the fifteenth through eighteenth centuries. The first description of juvenile arthritis is attributed to Cornil in 1864, making the question of its antiquity also pertinent. We show here that the "Portrait of a Youth," painted in 1483 by the Florentine artist Sandro Botticelli, has features of rheumatoid arthritis in the hand of the subject, who would be young enough to be considered as having juvenile arthritis. A review of all of Botticelli's paintings revealed that these changes could not be attributed to stylistic traits. Neither could they be attributed to lack of technique, for he has been considered a superb artist. If the "Portrait of a Youth" does indeed represent juvenile arthritis, it would mean that this disease is older than its initial description would indicate.

Adolescent↗

Differences in the kinetics of the autologous mixed lymphocyte reaction between the various connective tissue diseases.

Kinetic studies of autologous mixed lymphocyte reaction (AMLR) over 7 days were made in 86 patients with various connective tissue diseases. None was receiving any treatment and each disease group was controlled with age-sex matched healthy controls. There were exceptions, but, as a rule, SLE patients (n = 22) had decreased responses on days 6-7. This was more apparent in patients with active disease than in those with inactive disease. Patients with scleroderma (n = 21) had early (day 4) proliferative responses. Half of the patients with RA (n = 14) had early (day 3) proliferation, but as a group they had normal increase in 3HtdR uptake on day 7. Patients with primary Sjögren's syndrome showed flat curves throughout and no significant proliferation on days 6-7 of culture. The pattern found in patients with mixed connective tissue disease (n = 11) was also peculiar in that they had peak proliferative responses on day 3 and normal 3HtdR uptake on days 6 and 7 of the AMLR. The number of patients with dermatomyositis or polymyositis was small (n = 6), but they showed a significant mean decrease in uptake on days 6-7. Studies using subpopulations of stimulatory cells further indicate that these patterns reflect immunoregulatory disturbances peculiar to each disease.

Adult↗

The autologous mixed lymphocyte reaction is not primarily due to xenoantigenic stimulation.

Autologous mixed lymphocyte reaction (AMLR) is an interesting in vitro system in which T lymphocytes proliferate when cultured with non-T cells from the same individual. Because this system has both memory and specificity and elicits help, suppression, cytotoxicity, and soluble mediators, it has been proposed that it reflects in vitro the complex interactions of the immunologic network as it operates in vivo. A recent study, however, has cast doubt on the significance of this reaction by implicating xenoantigens, present during separation and/or culture procedures (e.g., sheep red blood cells or fetal calf serum), in the proliferative response of T cells. This question is analyzed by performing AMLR studies with cells (from eight normal subjects) that were separated with and without the use of sheep erythrocytes, and incubated with either fetal calf serum on normal human AB serum. Results were similar in all circumstances and negate a primary role of xenoantigens in AMLR.

Animals↗