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Biomedical subjects

V Pipitone

Publications and source records attributed to V Pipitone.

At least 19 recordsLinked to original sources

[Rheumatoid arthritis. Recent findings and new pathogenic concepts].

The etiology of rheumatoid arthritis (RA) is still unknown, and many uncertainties regarding its pathogenetic mechanisms persist. During the past decade, various hypotheses have been advanced, yet none of these has been able to explain the complexity of the disease. In light of the most recent research, a sub-division of the pathogenesis of RA, in four phases, has been proposed. The first phase is that of tissue damage, induced by unknown infective or traumatic factors with the liberation of possible arthrogenic antigens that are presented to the immune system. In the second phase the immune and inflammatory mechanisms should begin to function and, if they are effective, they should determine the resolution of the process; the failure of these mechanisms would create a further amplification of the immuno-inflammation response (the third phase). The fourth phase would then be a chronic inflammatory with progressive articular destruction, as well as anatomical and functional damage. This evolution, in response to common pathogenic agents, is dependent upon a particular hereditary genetic asset (not only the HLA system) that is able to control the production of citokines and also upon the neuroendocrine system. The final outcome of the process is, therefore, determinated by multiple interference between the inflammatory/immune system and other systems that also interact with it (the integrated pathogenetic hypothesis). This hypothesis reflects the complexity of the immune/inflammatory system that must be considered to be an acting part of an integrated network of diverse systems. A better knowledge of these interactions needed for the discovery of potential new therapies for RA.

Arthritis, Rheumatoid↗

Evaluation of bone turnover and osteoclastic cytokines in early rheumatoid arthritis treated with alendronate.

OBJECTIVE: Osteoporosis is a frequent complication of rheumatoid arthritis (RA). We investigated the effect of oral alendronate (AL) therapy on bone turnover and osteoclast activating factors in early RA. METHODS: A 90 day randomized placebo controlled trial of 40 mg oral AL/day compared with placebo in 32 patients with early mild disease. Serum interleukin 1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), IL-6, beta2microglobulin (beta2m), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), osteocalcin/bone gla protein (BGP), urinary crosslinks, and urinary hydroxyproline (HP) measured at 30 and 90 day intervals were the variables measured. RESULTS: A significant decrease of IL-1, IL-6, TNF-alpha, and beta2m was observed after 30 days, persisting after 90 days in the AL group, but with no significant variation in the placebo group. A significant decrease of ESR and CRP was observed after 90 days in the AL group, but with no significant variation after 30 days in the AL group, and after both 30 and 90 days in the placebo group. A significant decrease of BGP, HP, and urinary crosslinks was observed after 30 days, persisting after 90 days in the AL group, but with no significant variation in the placebo group. CONCLUSION: Our study demonstrates that alendronate reduces bone turnover in early RA and may have a possible antiarthritic effect. Because of the mild early form of the disease in the study cohort, further evaluations are required to confirm this effect.

Adult↗

Markers of bone turnover: consideration on their clinical application in osteoporosis.

Osteoporosis is a condition in which an imbalance appears between bone resorption and formation, with bone resorption exceeding formation. However since the rate of bone loss varies significantly from one individual to another resulting in different degrees of osteoporosis, new biochemical techniques to measure products of bone resorption and bone formation have been used in the last years allowing us to evaluate the degree of bone turnover. Bone tissue is constituted of an inorganic component and an organic matrix of collagen and noncollagenous proteins. Suitable bone marker should report the formation and degradation of all these constituents. Today markers of bone formation and markers of bone resorption are available. According to recent literature and personal data assessment of bone metabolism by the specific biochemical markers is helpful to select osteoporotic patients with high or low bone turnover and these parameters should be used to evaluate whether bone remains sensitive to different therapies.

Biomarkers↗

Chondrocyte phenotyping in human osteoarthritis.

Cell-ECM (extracellular matrix) interactions are believed to play a key role in maintaining the normal structure of tissues such as cartilage. Cell surface adhesion molecules have been reported to mediate chondrocyte binding to ECM proteins in human normal cartilage but the behaviour of these molecules in human osteoarthritic cartilage is unknown. We studied receptor matrix proteins on freshly isolated chondrocytes obtained from 10 patients with osteoarthritis (OA). Chondrocytes were isolated by enzymatic digestion from three zones of the articular cartilage with a different degree of macroscopic and microscopic damage and chondrocyte phenotype was defined by flow cytometry. Chondrocytes strongly expressed beta1, integrin but not beta3 integrin. LFA-1 (CD18/CD11a) and ICAM-1 (CD54) antigens were almost undetectable. Interestingly, beta1 expression was significantly higher in the minimally damaged zone than in the zones with medium and maximum damage. These data show that beta1-integrin-mediated chondrocyte-ECM interactions decrease in osteoarthritic cartilage suggesting that perturbations of chondrocyte-matrix signalling occurs during OA.

Aged↗

Systemic sclerosis stimulates angiogenesis in the chick embryo chorioallantoic membrane.

Skin biopsies from patients with systemic sclerosis (SSc) were investigated for their angiogenic activity by using the chick embryo chorioallantoic membrane (CAM) assay. Ten samples of SSc and 10 of normal skin from age- and sex-matched subjects were grafted onto the CAM, and the angiogenic response in pathological and control implants was assessed on histological sections by a planimetric point-count method 4 days after grafting. The vascular counts in the area underlying the SSc were significantly higher than those of normal skin and a dense mononuclear cell infiltrate was detectable around the blood vessels in pathological specimens. These results suggest that SSc may promote angiogenesis, perhaps leading to the release of several angiogenic factors. Moreover, the role played in the angiogenic response by the inflammatory cells forming the cellular infiltrate is suggested by this study.

Adult↗

Recovery of erosive rheumatoid arthritis after human immunodeficiency virus-1 infection and hemiplegia.

The effects of human immunodeficiency virus type-1 (HIV-1) infection on rheumatoid arthritis (RA) are a matter of debate as there is no agreement on the influence of HIV-1 related immunodeficiency on this disease. We describe a patient with RA with symmetric joint erosions and positive rheumatoid factor (RF) who developed classic acquired immunodeficiency syndrome (AIDS) followed by left hemiplegia. RA improved with resolution of bony erosions and disappearance of RF, and reached complete clinical remission only in the paralytic limbs. Our observation suggests that, although essential, cell mediated immune response is not the sole mechanism involved in RA pathogenesis. Other factors such as the nervous system may play an important role.

Arthritis, Rheumatoid↗

Slow progression of joint damage in early rheumatoid arthritis treated with cyclosporin A.

OBJECTIVE: To evaluate the ability of low-dose cyclosporin A (CsA) to control radiologic disease progression, and to assess the clinical efficacy and tolerability of CsA, compared with conventional disease-modifying antirheumatic drugs (DMARDs), in patients with early active rheumatoid arthritis (RA). METHODS: In this long-term, multicenter, prospective, open, blinded end point, randomized trial, 361 consenting patients with early (<4 years since diagnosis) active RA were enrolled. Of the eligible patients, 167 were treated with CsA at 3 mg/kg/day, and 173 with DMARDs. The decision to use conventional antirheumatic drugs as controls was based on the fact that joint erosion could be expected to occur after 1 year regardless of the type of DMARD being used. The possibility of switching therapies in both groups was intended to keep the largest possible number of patients in the study. RESULTS: Blinded evaluation of hand and foot radiographs after 12 months of treatment showed that CsA led to a significant (P < 0.001) delay in the mean +/- SD progression in the eroded joint count (1.3 +/- 3.1 versus 2.4 +/- 3.0 for the control group) and in the joint damage score (3.6 +/- 8.9 versus 6.9 +/- 9.1 for the control group), both measured by the Larsen-Dale method. When only the patients without erosion at baseline were considered (37 in the CsA-treated group and 54 in the control group), erosion appeared in only 10.8% of the CsA-treated patients, but in 51.8% of the controls (P = 0.00005). Low-dose CsA was as effective as traditional DMARDs in controlling clinical symptoms. Maintenance on the initially prescribed treatment regimen ("survival on treatment") was also better at 12 months with CsA than with DMARDs (89.2% versus 77.5%; P = 0.002). The tolerability of CsA was acceptable. CONCLUSION: These 12-month results suggest that low-dose CsA decreases the rate of further joint damage in previously involved joints as well as the rate of new joint involvement in previously uninvolved joints, in patients with early RA.

Adult↗

Early ultrastructural changes of articular cartilage and synovial membrane in experimental vitamin A-induced osteoarthritis.

OBJECTIVE: To evaluate the sequential ultrastructural changes of the articular cartilage and synovial membrane in the earliest phases of the vitamin A model of osteoarthritis (OA) in the rabbit. METHODS: The superficial layer of the weight bearing zone of the articular cartilage and the synovial membrane from femorotibial joints of 12 osteoarthritic rabbits were evaluated 3, 6, and 9 days after the triggering intraarticular injection of 100,000 i.u. of retinol palmitate. Four uninjected rabbits were used as controls. RESULTS: At 3 days, ultrastructural changes of chondrocytes could be seen (hypertrophic cells with increased lipid droplets, chondrocytes rich in microfilaments and glycogen, and some degenerating cells) with no evident lesions of the matrix. The synovium was similar to that of the control rabbits. At 6 days, chondrocyte changes seemed almost identical to those of 3 days, while the synovial membrane appeared markedly involved, substituted by a single layer of A-type cells lying on fibrous subsynovial tissue in which lymphocytes, mast cells, and blood vessels could be seen. Conspicuous alterations and necrobiosis of the cartilaginous cells characterized later stages (9 days). The intercellular matrix was mainly made up of amorphous material and bundles of collagen fibers. The synovial membrane was transformed into a thick fibrous tissue partially covered with scattered cells no longer distinguishable as A or B type. CONCLUSION: Our data suggest that in the vitamin A model of OA the initial metabolic changes of the chondrocytes have a pivotal role in determining the relentless cascade of events leading to the full expression of this disease. Moreover, although several studies have been carried out on the early changes in experimental OA, no complete morphological evaluations on the developmental aspect of this model have been available.

Animals↗

[Fast-dissolving sublingual tablets of piroxicam versus naproxen in the treatment of recurrent acute osteoarthrosis. Multicenter clinical trial].

An open comparative study was carried out to evaluate the efficacy and safety of piroxicam FDDF, for sublingual administration, versus naproxen in the treatment of osteoarthritis. Sixty-one patients with acute-phase osteoarthritis involving various joints are reported. They were treated with 20 mg/day piroxicam FDDF or with 1000 mg/day naproxen for a total of 4 weeks. Drug efficacy was evaluated on the base of the variation of spontaneous pain, pain on motion, functional limitation and capacity to perform a specific activity. The intensity of spontaneous pain on the first day showed a statistically significant improvement with both drugs, but the onset of analgesia was only after 15 minutes with piroxicam and after 1 hour with naproxen. The improvement in pain intensity increased on the first day and until the 7th day with both drugs, but the comparative analysis between the analgesic efficacy of the two treatments proved to be favourable to piroxicam. On the 7th day, pain on motion and the capacity to perform a specific activity showed a statistically significant improvement with both drugs, but the comparative analysis between the two treatments proved to be favourable to piroxicam. The two drugs showed the same efficacy in functional restriction. The local and systemic tolerability of piroxicam was good. Only 5 patients experienced 6 systemic side-effects, and 1 patients showed local side-effects, but 11 patients of the naproxen group showed 12 systemic side-effects. Thus piroxicam showed a better analgesic and anti-inflammatory efficacy than naproxen. Piroxicam proved to have a better systemic tolerability than naproxen. The local tolerability of piroxicam FDDF was good.

Acute Disease↗

Isolated sternoclavicular joint arthritis in heroin addicts and/or HIV positive patients: three cases.

The authors describe three patients in whom septic arthritis of the sternoclavicular joint (SCJ) occurred, drug addiction and human immunodeficiency virus (HIV) infection representing the predisposing conditions. Infectious arthritis is well known in intravenous drug users, but it is rare in HIV positive patients, who are prone to bacterial infections from usual or unusual microorganisms. In one case, staphylococcus aureus methicillin sensitive was responsible for septic arthritis. In another case, SCJ infection was associated with pneumonitis.

Adult↗

Mononuclear cells are not involved in BGP synthesis and secretion.

Osteocalcin or bone GLA protein (BGP) is found at high levels in only two tissues, the extracellular matrix of bone and dentine. Tissue culture experiments have demonstrated that BGP is synthesized by two osteoblastic osteosarcoma cell lines (ROS 2/3 and 17/2) and by normal osteoblastic cells in primary culture. BGP was not found in rat cartilage nor in liver, kidney, lung, spleen, brain, heart, thymus, skeletal muscle. In this study secretion of BGP was assayed by RIA in the supernatants of 48-hour cultures of peripheral blood lymphocytes or monocytes. Lymphocyte cultures were carried out using RPMI-1640 supplemented with L-glutamine and antibiotics at the concentration of 1 x 10(6) cells/ml and activated by PHA (10 ng/ml). Peripheral blood monocytes were purified by adherence to plastic Petri dishes and treated with cold PBS supplemented with EDTA. Monocytes were cultured as previously described and stimulated with LPS (50 micrograms/ml). Cell-free supernatants were obtained by centrifugation and stored at -20 degrees C, until the BGP assay was performed. The authors did not observe secretion of detectable amounts of BGP in the supernatants of short-term lymphocyte or monocyte cultures. These data indicate that circulating mononuclear cells are not involved in BGP synthesis and secretion.

Cells, Cultured↗

Iliolumbar ligament ossification as a radiologic feature of reactive arthritis.

We describe the case of a 21-year-old woman with the clinical picture of HLA-B27+ reactive arthritis (ReA) in whom the ossification of the left iliolumbar ligament was detected. Our case proves that ligament calcifications, which have so far been ascribed to diffuse idiopathic skeletal hyperostosis may also occur in young patients with ReA not primarily affected by metabolic osteoarticular diseases with negative family history.

Adult↗

[Linear bone densitometry by monochromatic photon absorptiometry. A study of a normal population in Apulia].

An epidemiological survey was conducted on a group of Apulian residents in order to compare the densitometric data obtained with those produced by other European and North American authors. The results confirm the need for personal data on our own population given the often significant differences in order to avoid errors in monitoring patients who may require even long-term treatment.

Absorptiometry, Photon↗

[Significance of anticardiolipin antibodies in connective tissue diseases].

Recent attention has focused on the possibility that the presence of Anticardiolipin Antibodies (ACA) in patients with connective tissue diseases, particularly with Systemic Lupus Erythematosus (SLE), may be associated with clinical and serological symptoms that identify a particular subset of patients. This group is characterized by recurrent arterial and/or venous thrombosis, multiple abortions and or intrauterine fetal death, presence of Lupus AntiCoagulant (LAC), false positive VDRL, thrombocytopenia and neuro-psychiatric diseases. These clinical features may identify the so-called "Anticardiolipin Syndrome". In this work, we have measured ACA, by ELISA test, in 194 serum samples: 97 SLE patients, 5 Mixed Connective Tissue Disease (MCTD), 8 Progressive Systemic Sclerosis (PSS), 7 Dermato/PolyMyositis (D PM), 3 Sjögren Syndrome (SS), 3 Unclassifiable Connective Tissue Disease (UCTD), 9 Rheumatoid Arthritis (RA), 1 Idiopathic Anticardiolipin Syndrome, 19 cases of Miscellanea, 42 healthy controls. The Optical Density (O.D.) was greater than 0 (higher than 0) in 89 serum samples (out of the 194): 43 SLE, 4 MCTD, 4 PSS, 3 D PM, 1 SS, 7 RA, 10 cases of Miscellanea, the Idiopathic Anticardiolipin Syndrome and 16 healthy controls. The O.D. was greater than m (greater than mean healthy controls level) + 3 Standard Deviations (S.D.) in a restricted number of cases (25 out of the 194): 14 SLE, 2 MCTD, 1 PSS, 1 D/PM, 1 SS, 1 RA, 3 cases of Miscellanea and 2 healthy controls. Therefore, we have noticed, first of all, the lack of specificity of positive results obtained: all the groups of patients, healthy controls included, had low as well as high levels of ACA. Moreover, we have examined the relationship between the presence of ACA and typical clinical features of the so-called. "Anticardiolipin Syndrome"; there was not difference of clinical symptoms between patients with low or high ACA levels. We have also clinically examined ACA negative patients; most of them had one or several clinical features of the "Syndrome", until almost complete clinical picture. Therefore, no correlation was found between clinical picture and immunological features of the so-called "Anti-cardiolipin Syndrome"; we would not exclude the existence of the "clinical" subset of patients, but of the "immunological" subset.

Autoantibodies↗

Early alteration of synovial membrane in osteoarthrosis.

Biopsy specimens of the synovial membrane were obtained during arthroscopy and surgical meniscectomy from the knees of 20 patients with meniscus lesions. The aim of this study was to identify the morphological and immunological changes which appear in the synovium during the earliest phase of osteoarthrosis. Interstitial deposits of IgG and, in some cases, C3 were found not only in patients with evident arthrotic degeneration (cartilaginous lesions and synovitis), but also in patients who showed no overt arthrotic changes. Furthermore, light and electron microscopy showed an increased number of mast-cells with peculiar semilunar or piecemeal aspects of their secretory granules. These ultrastructural modifications are characteristic of slow, chronic release of mediators in response to a constant, moderate degranulatory stimulus. Our findings suggest that synovial changes may occur before the advent of cartilage degeneration and that the latter may be directly influenced by early pathological changes in the synovial membrane.

Adolescent↗

[Tetracycline in the evaluation of bone turnover].

A new and easy technique for the fluorimetric evaluation of rolitetracycline calcium complex was studied. The study was carried out in 3 different groups of rats; an increase in power of fluorescence in the rats on a low calcium diet (LC) and on a low calcium diet plus vitamin D (LC + D) versus the group of rats on a normal calcium diet (NC) was found. Moreover, the amount of spongy bone showed a significant decrease in bone mass in the first two groups (LC and LC + D) versus control. These data indicated that the bone tie of tetracycline was only related to the high turnover of bone and there was no relationship with bone mass. This new technique, in comparison with the others, (double marking and evaluation of space between the two fluorescent bands) enables to evaluate the kind and the evolution of bone rarefaction by biopsy.

Animals↗

Evaluation of mineral metabolism and bone turnover in osteoporotic females treated with phosphorus and salmon calcitonin.

Twenty-five patients with radiological and clinical evidence of osteoporosis were studied. Nineteen patients received oral phosphorus at a dose of 1,000 mg/die for 10 days followed by salmon calcitonin (100 U MRC/die) for 20 days. Six patients received only oral calcium at a dose of 1,000 mg/die). In the first group, a significant increase in serum osteocalcin and parathyroid hormone, after administration of phosphorus and persisting after treatment with salmon calcitonin, was found. No variation in the controls was observed. In a later study, a significant increase in serum 1,25 dihydroxyvitamin D (1,25(OH)2D3), after receiving phosphorus and persisting after salmon calcitonin, was demonstrated. In accordance with the authors' results, phosphorus could be considered a useful activator of bone formation and this stimulus by parathyroid hormone was mediated. Finally, the positive effects of phosphorus on circulating 1,25(OH)2D3 must be considered for a good treatment protocol of osteoporosis.

Administration, Oral↗