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Biomedical subjects

J Muñoz-Gomez

Publications and source records attributed to J Muñoz-Gomez.

At least 19 recordsLinked to original sources

Serum osteoprotegerin and its ligand in Paget's disease of bone: relationship to disease activity and effect of treatment with bisphosphonates.

OBJECTIVE: To test the following hypotheses: 1) osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) serum levels in patients with Paget's disease are related to disease activity and are different from those in healthy individuals; 2) interleukin-6 (IL-6), a cytokine that has been shown to have higher levels in Paget's disease, modulates these factors; and 3) the antiresorptive effect of bisphosphonates in Paget's disease of bone may be mediated through these local factors. METHODS: The study group comprised 31 patients with Paget's disease who received 400 mg/day of oral tiludronate for 3 months. Serum levels of OPG, RANKL, IL-6, bone alkaline phosphatase (AP), N-terminal type I procollagen propeptide, urinary N-terminal crosslinking telopeptide of type I collagen, and urinary alpha-C-terminal crosslinking telopeptide of type I collagen were measured at baseline and 1 month after the end of therapy. In addition, the RANKL:OPG ratio was calculated, and disease activity was evaluated at baseline by quantitative bone scintigraphy. RESULTS: Mean baseline OPG values were higher in patients with Paget's disease than in healthy control subjects (P < 0.005), but RANKL and IL-6 values and RANKL:OPG ratios in the 2 groups were similar. OPG concentrations decreased significantly after treatment with tiludronate (P < 0.005), whereas no significant changes were observed in serum RANKL values. No correlation was found between either bone markers or quantitative scintigraphic indices and serum levels of OPG, RANKL, IL-6, and RANKL:OPG ratios. Serum OPG decreased significantly only in those patients with baseline OPG values >4.1 pM/liter. CONCLUSION: Serum OPG increases in Paget's disease and decreases after treatment with tiludronate, especially in patients with the highest OPG values. In contrast, RANKL serum levels and RANKL:OPG ratios are unmodified in patients with Paget's disease. Although serum OPG, RANKL, and IL-6 values were unrelated to disease activity, the increase in OPG may reflect a protective mechanism of the skeleton to compensate for increased bone resorption.

Adult↗

Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget's disease.

The aim of this study was to investigate the usefulness of biochemical markers of bone turnover for monitoring treatment efficacy of Paget's disease of bone, and also to evaluate the utility of biological variation data in choosing the best markers for assessment of biochemical response to therapy. Thirty-eight patients with Paget's disease were included in a prospective study. All received 400 mg/day of oral tiludronate for 3 months. In 31 patients that completed treatment, biochemical markers were measured at baseline and at 1 and 6 months after treatment ended. In serum we determined the levels of total alkaline phosphatase (tAP), bone alkaline phosphatase (bAP), procollagen type I N-terminal propeptide (PINP), and C-terminal telopeptide of type I collagen (sCTx). Urine samples were analyzed for hydroxyproline (Hyp) and for C- and N-terminal telopeptides of type I collagen (CTx and NTx, respectively). Quantitative bone scintigraphy was performed at baseline and at 6 months after discontinuation of therapy. A ratio for monitoring response to treatment was obtained for each marker. This ratio reflected the size of treatment response of the marker in relation to the value of its critical difference. Thus, ratio values of >1 indicated a significant decrease of the marker after therapy. In addition, response to therapy was evaluated according to disease activity. Mean values of all markers of bone turnover decreased significantly after therapy. Serum bAP and PINP and urinary NTx showed the highest percentage reduction (between 58% and 68%). Furthermore, serum bAP and PINP showed the highest ratios for monitoring changes induced by treatment, followed by serum tAP and urinary NTx. sCTx and urinary CTx as well as Hyp showed mean ratios for monitoring changes of <1, indicating a low sensitivity for monitoring treatment. Patients with polyostotic disease showed a continuous decrease in mean values for all markers at 6 months from the end of therapy, whereas, in monostotic patients, there was a trend toward increased levels at this timepoint. In conclusion, serum bAP and PINP were the most sensitive markers for monitoring treatment efficacy in Paget's disease, although serum tAP and urinary NTx were also sensitive markers for monitoring changes. Data on biological variation are useful for assessing actual changes induced by treatment.

Adult↗

Idiopathic hypoparathyroidism associated with adult rheumatoid arthritis.

A 48-year-old female patient with adult onset idiopathic hypoparathyroidism diagnosed at the age of 28 years developed a typical seropositive rheumatoid arthritis (RA) at 46 years of age after several years of evolution of a palindromic rheumatism. Only one case of an association between idiopathic hypoparathyroidism and RA has been described in the medical literature. Autoimmunity seems to play a pivotal role in the aetiopathogenesis of both diseases, and could explain the nature of this association; nevertheless, a chance association could not be excluded.

Absorptiometry, Photon↗

Spondyloarthropathy presenting as a polymyalgia rheumatica-like syndrome.

Two female patients, aged 57 and 58 year-old presented with pain and stiffness in shoulder and/or pelvic girdles and a high ESR, suggesting polymyalgia rheumatica (PMR). The lack of response to low dose of steroids prompted us to reconsider this diagnosis and, after a careful evaluation and taking into account past clinical history, a final diagnosis of spondyloarthropathy (SpA) was made. The clinical spectrum of late SpA is heterogeneous, and in some instances may present as a polymyalgia-like syndrome.

Anti-Inflammatory Agents, Non-Steroidal↗

Scintigraphic evaluation of the severity of inflammation of the joints with 99TCm-HIG in rheumatoid arthritis.

A prospective study was carried out to determine the usefulness of 99TCm-human immunoglobulin G (HIG) scintigraphy in the assessment of the severity of joint inflammation. Twenty-four patients with rheumatoid arthritis were studied. The presence or absence of pain and/or swelling was evaluated in 34 joints and a clinical index taking into account the surface area of each joint was calculated. We measured the following biological markers of inflammation activity: erythrocyte sedimentation rate, C-reactive protein, haemoglobin, platelet count, serum levels of IL-6, TNF-alpha and soluble receptors of IL-2. Scintigraphic was performed 4 h after the injection of 740 MBq 99Tcm-HIG. The scans were evaluated by visual and quantitative analysis and the scores in each joint were weighted for joint size. Pathological uptake of the radiopharmaceutical was noted in 46% (24/52) of joints evaluated as painful, 89% (146/164) of swollen joints and 94% (78/83) of both painful and swollen joints. Both the visual and the quantitative scintigraphic indices correlated significantly with the clinical index, the number of painful joints, the number of swollen joints and several biological markers of inflammation. A very high correlation was also found between the visual and the quantitative scintigraphic indices (r = 0.91, P < 0.0001). In conclusion, 99Tcm-HIG scintigraphy is an objective test to detect synovitis and to assess the severity of inflammation. A careful visual analysis of scans is good enough for routine evaluations and computer quantitative analysis should be used when more accurate intra-individual variation is required.

Adult↗

Reduced serum creatine kinase activity in inflammatory rheumatic diseases.

OBJECTIVE: To determine if serum CK activity is reduced in inflammatory rheumatic diseases and to evaluate whether this phenomenon is linked to disease activity or steroid therapy. METHODS: Serum CK activity was measured in patients with systemic lupus erythematosus (SLE, n = 52), rheumatoid arthritis (RA, n = 80), ankylosing spondylitis (AS, n = 82), spondyloarthropathies other than AS (SpA, n = 22), and a miscellaneous group (MI, n = 27), and in 103 control patients with noninflammatory arthropathies (NIA). Laboratory variables of inflammatory activity such as ESR, CRP, platelet count, and hemoglobin (and anti-DNA antibodies and complement levels in SLE) were measured at the same time. Daily dose of steroids was also evaluated. RESULTS: Serum CK activity was significantly reduced in SLE (mean +/- SD: 49 +/- 41 IU/l), RA (68 +/- 41 IU/l), SpA (88 +/- 53 IU/l), and MI (75 +/- 32 IU/l) compared to controls (111 +/- 38 IU/l) (p = 0.002 for SpA and p < 0.001 for the other groups). No differences in CK values were observed between AS and controls, although AS patients with peripheral arthritis had lower serum CK activity than those without (80 +/- 32 vs 121 +/- 62 IU/l, respectively, p < 0.05. ESR, CRP, and platelets correlated inversely with CK values in RA, AS, and MI. In the SpA group only ESR correlated inversely with CK. In SLE, a positive correlation was found between CK values and CH50 and a negative one with anti-DNA levels. Patients taking steroids had significantly lower CK activity than those without corticotherapy. However, multivariate analysis showed that only inflammatory activity and no steroids had an effect in reducing CK activity. CONCLUSION: Serum CK activity is significantly reduced in several inflammatory rheumatic diseases. Inflammatory activity seems to play the major role in this phenomenon.

Adult↗

Discriminative value of biochemical markers of bone turnover in assessing the activity of Paget's disease.

Clinical biochemical markers of bone turnover are usually increased in Paget's disease. However, the analysis of "new" markers, such as serum bone alkaline phosphatase (BAP), carboxy-terminal propeptide of type I procollagen (PICP), tartrate-resistant acid phosphatase (TRAP), telopeptide carboxy-terminal propeptide of type I collagen (ICTP), and urinary pyridinoline (PYR) and deoxipyridinoline (D-PYR), may improve the diagnostic efficacy and the evaluation of Paget's disease compared with conventional markers, such as serum total alkaline phosphatase (TAP) and urinary hydroxyproline (HYP). To evaluate the diagnostic accuracy and the changes of biochemical markers of bone turnover according to Paget's disease activity, we measured the levels of all these markers in three groups of pagetic patients classified according to their serum TAP activity: G-I, patients with serum TAP lower than 250 U/l (upper limit) (n = 15); G-II, patients with serum TAP between 251 and 500 U/l (n = 18); and G-III, patients with serum TAP greater than 501 U/l (n = 26). Serum TAP and BAP showed the highest diagnostic accuracy among the markers of bone formation with a sensitivity of 78% and 84%, respectively, when the specificity was 100%. Urinary PYR was the most sensitive marker of bone resorption. Also, urinary PYR showed the highest proportion of increased values in pagetic patients (73%) compared with urinary HYP (64%), urinary D-PYR (60%), serum ICTP (41%), or serum TRAP (39%). In pagetic patients with normal serum TAP activity (G-I), serum BAP concentration was increased in 60% of patients, and urinary PYR was increased in 40% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Aetiology and presenting symptoms in male osteoporosis.

In order to analyse the clinical characteristics and the principal causes of osteoporosis in men, 81 osteoporotic males from an out-patient rheumatology department were studied. Bone mass assessment, automated biochemical profile and biochemical markers of bone turnover were performed in all patients, and hormonal measurements were taken when a specific aetiology was not readily apparent. Sixty-three men (78%) had secondary osteoporosis and 18 (22%) primary osteoporosis. Secondary causes of osteoporosis included hypogonadism (12 patients), corticosteroid therapy (10 patients) and alcoholism (10 patients); the remaining patients had various causes of osteoporosis. Eighteen patients had primary osteoporosis, eight of them with associated hypercalciuria. Normocalciuric patients showed lower 25-hydroxyvitamin D and 1-25-hydroxyvitamin D levels than the control group, whereas hypercalciuric patients had lower parathyroid hormone and renal threshold for phosphate excretion. In 69 patients (85%), back pain was the chief complaint. Forty-five of these 69 patients (65%) had chronic back pain and 24 (35%) had subacute episodes. Fifty per cent of the patients with chronic back pain had vertebral fractures. Both patients with and without chronic back pain were found to have a similar number of vertebral fractures. In conclusion, male osteoporosis is frequently associated with major risk factors. Patients with primary osteoporosis may have associated hypercalciuria or decreased vitamin D levels. However, not all the patients for whom back pain was the chief complaint were found to have vertebral fractures.

Adult↗

The effect of systemic lupus erythematosus and long-term steroid therapy on bone mass in pre-menopausal women.

The aim of our study was to assess bone mineral density (BMD) in pre-menopausal women with systemic lupus erythematosus (SLE) and the influence of disease activity and use of corticosteroids. Lumbar and femoral BMD were measured in 43 patients with SLE (28 on regular steroid therapy, 15 with recent onset, non-treated) and compared with 43 healthy women matched for age. In addition, 21 SLE patients treated with corticosteroids were followed-up with a mean of 36.6 +/- 12.7 months. BMD was significantly lower in SLE patients with prednisone doses > or = 7.5 mg/day than those of recent onset (lumbar: 1.07 +/- 0.11 vs 1.15 +/- 0.13, P = 0.039; femur: 0.85 +/- 0.13 vs 0.98 +/- 0.21, P = 0.034) and the control group (lumbar: 1.07 +/- 0.11 vs 1.13 +/- 0.10, P = 0.040; femur: 0.85 +/- 0.13 vs 0.93 +/- 0.10, P = 0.028). In addition, 18% of SLE steroid users had osteoporosis. Lumbar and femoral BMD were inversely correlated with the time of treatment and the cumulative doses of prednisone. There were no significant BMD changes during the 3-yr follow-up period. In conclusion, in SLE pre-menopausal patients lumbar and femoral BMD is decreased and related to long-term corticosteroid therapy.

Adult↗

When does amyloidosis complicate systemic lupus erythematosus?

Secondary amyloidosis is a well recognised complication of rheumatic diseases, but the association with systemic lupus erythematosus is very unusual. We report the case of a patient with systemic lupus erythematosus who developed proteinuria due to renal amyloidosis. We also review the cases previously reported and the hypothesis on the pathogenic mechanisms.

Adult↗

Reduced activity of serum creatine kinase in rheumatoid arthritis: a phenomenon linked to the inflammatory response.

In a case-controlled study, serum creatinine kinase (CK) activity was significantly lower in 40 patients with RA than in 40 age- and sex-matched patients with non-inflammatory arthropathies [mean 37.6 (S.D. 29.2) vs 77.7 (S.D. 45.3) IU/l respectively P < 0.0001]. In contrast, serum levels of aldolase and myosin were not significantly lower in RA patients. A significant inverse correlation between CK activity and ESR, CRP and platelet count was observed in RA. There was also a positive correlation between haemoglobin levels and CK values. No correlation was found between CK activity and a meager mass index, disease duration and radiological erosion. No inhibitor of CK activity in the sera of RA patients was found. CK serum activity was markedly reduced in RA, and is related to the inflammatory activity of the disease. This finding may stimulate further exploration on the effect of inflammatory response in muscle metabolism.

Adult↗

Serum IgA anti-Klebsiella antibodies in ankylosing spondylitis patients from Catalonia.

IgA antibodies against Klebsiella pneumoniae were measured by immunofluorescence in 84 Catalan patients with ankylosing spondylitis (AS), 41 patients with non-inflammatory arthropathies (NIA) and 22 patients with rheumatoid arthritis (RA). Patients with AS showed higher levels of anti-klebsiella IgA antibodies (IgA-Kp) than NIA and RA patients (4.7 +/- 1.6 U vs 3.7 +/- 1.5 U and 3.1 +/- 1.4 U respectively, p = 0.001). In AS patients a significant correlation between IgA-Kp and levels of C-reactive protein was observed. Although no clear correlation was found between IgA anti-klebsiella and total serum IgA levels, a significant correlation between IgA anti-klebsiella and serum levels of secretory IgA was detected (r: 0.43, p = 0.003). In conclusion, some patients with AS disclosed raised levels of Klebsiella antibodies in sera and this is related to an increase of secretory IgA level. Analysis about the relationship between response to klebsiella and the presence of gut inflammation in AS patients could be of interest.

Adolescent↗

Coincidental amyloid nephropathy and IgA glomerulonephritis in a patient with ankylosing spondylitis.

A 43-year-old man with ankylosing spondylitis (AS) was admitted with proteinuria and renal insufficiency. Coincidental IgA nephropathy and secondary renal amyloidosis were diagnosed on renal biopsy. This is the first case reported of coincidental IgA nephropathy and renal amyloidosis as a cause of renal insufficiency in a patient with AS. Both entities should be considered in the diagnosis in a patient with AS and renal impairment. A careful study of the renal tissue including, Congo red stain and immunofluorescence studies is necessary to establish a correct diagnosis in these patients.

Adult↗

Non-association between 9.2 KB PvuII RFLP and seronegative spondyloarthropathies in Spain.

Several studies of DNA restriction fragment length polymorphism (RFLP) in ankylosing spondylitis (AS) have been carried out. The association between a recently identified class I HLA 9.2 kb PvuII RFLP and AS remain controversial. In order to evaluate this possible association in an Euro-Caucasian population, the genomic DNA of 42 AS patients and 18 patients with Reiter's syndrome (RS) and 42 healthy controls was analysed. Non-association between 9.2 kb PvuII RFLP and AS or RS was observed. As described previously, a strong association between this fragment and HLA-A3 and/or HLA-A9 antigens was demonstrated. A study of two families showed that this RFLP segregates with HLA-A3 and/or HLA-A9 and independently of the HLA-B27. Our findings support the view that the 9.2 kb PvuII fragment is not universally associated with AS.

Arthritis, Reactive↗

In vitro spontaneous synthesis of beta 2-microglobulin amyloid fibrils in peripheral blood mononuclear cell culture.

beta 2-microglobulin-related amyloidosis (A beta 2M), in long-term dialysis patients, is a new and frequent complication for which the pathogenesis remains unknown. The authors documented, by light and high resolution electron microscopy, the spontaneous polymerization of beta 2-microglobulin to amyloid fibrils in mononuclear cell culture supernatants from dialysis patients. These data provide significant information about the pathogenesis of dialysis-amyloidosis, revealing an unusual and different fibrillogenic mechanism for beta 2-microglobulin and dialysis-amyloidosis than for other forms of amyloidosis. beta 2-microglobulin does not appear to require a proteolytic process before polymerization into amyloid fibrils and deposits. This study represents the first cell culture system in which beta 2-microglobulin amyloid fibrils have been spontaneously created.

Amyloid↗

Reflex sympathetic dystrophy syndrome of the lower limbs in renal transplant patients treated with cyclosporin A.

In a 36-month period, 240 patients at our institution received kidney transplants from cadaver donors. Cyclosporin A (CsA) was used as the initial immunosuppressive therapy. Seven patients (5 men and 2 women) developed severe pain, periarticular soft tissue swelling with no effusion, and vasomotor changes in affected areas. Although articular mobility was conserved, most of the patients had great difficulty in walking. A patchy osteoporotic pattern was seen radiographically and increased uptake of 99mtechnetium with a periarticular distribution in the clinically affected areas were found. All of these symptoms and radiographic and scintigraphic signs are compatible with definite reflex sympathetic dystrophy syndrome (RSDS). Articular symptoms began within 3 months after kidney transplantation in all patients; all but 1 patient had plasma CsA levels greater than 200 ng/ml at that time. When the dosage of CsA was reduced, there was concomitant improvement in the RSDS, which appeared when the plasma CsA levels declined to less than 200 ng/ml. The mean duration of the clinical symptoms of RSDS was 8 months. We believe RSDS should be added to the list of complications that may appear in kidney transplant patients who receive CsA treatment.

Adult↗

Septic arthritis in heroin addicts.

Over a 6-year period (1982 to 1988), 36 episodes of septic arthritis were diagnosed in 35 heroin addicts from Barcelona, Spain. Thirty (86%) were men and five (14%) were women, with a mean age of 24 years (range, 14 to 39). Twenty-nine episodes (80%) were monoarticular and seven (20%) were oligoarticular. The sacroiliac (16 cases), sternoclavicular (8), hip (5), and shoulder (4) joints were most frequently infected. Staphylococcus aureus and Pseudomonas aeruginosa were the etiological agents in 75% and 11% of episodes, respectively. Response to antibiotic treatment was good in 32 cases (90%), eight patients needed surgical drainage, and none died. We conclude that septic arthritis in heroin addicts localizes predominantly in axial joints. In our geographic area, infection with S aureus is more frequent than with gram-negative rods such as P aeruginosa or Serratia marcescens, which are most frequently found in reports from the United States.

Adolescent↗