PubMed Health⌕ Search

Biomedical subjects

J Muñoz-Gómez

Publications and source records attributed to J Muñoz-Gómez.

At least 19 recordsLinked to original sources
PubMed2005

p53 expression in rheumatoid and psoriatic arthritis synovial tissue and association with joint damage.

BACKGROUND: Overexpression and functional mutations of p53 have been found in the synovial tissue (ST) of patients with rheumatoid arthritis (RA), but their clinical significance remains unclear. OBJECTIVE: To analyse p53 expression in the ST of patients with RA and psoriatic arthritis (PsA) and its association with joint damage. METHODS: Synovial biopsy specimens were obtained by arthroscopy in 45 patients (27 RA, 18 PsA). Radiographs of hands, feet, and the joint undergoing arthroscopy were obtained to evaluate the presence of erosive disease. Synovial cell populations were analysed using CD4, CD8, CD138, CD20, and CD68 monoclonal antibodies (mAbs). The p53 protein was determined by immunohistology using DO7 mAb in 34 patients (18 RA, 16 PsA). In 11 patients with early RA, the association between p53 and 1 year progression of radiographic damage was analysed using the Larsen-Scott method. RESULTS: The p53 protein was detected in 16/18 (89%) patients with RA and in 9/16 (56%) patients with PsA, but its expression in RA was significantly higher than in PsA. In RA, p53 expression was significantly associated with erosive disease, and its scores were higher in patients with radiological progression. CD68 expression was also associated with erosions and radiological progression in RA. No association was found between either p53 or CD68 and erosive disease in PsA. CONCLUSIONS: These results suggest that p53 ST overexpression and association with joint damage is characteristic of RA rather than PsA, and that p53 ST expression might be a prognostic marker of joint damage in RA.

Adult↗
PubMed2004

Long-term biochemical response after bisphosphonate therapy in Paget's disease of bone. Proposed intervals for monitoring treatment.

OBJECTIVES: To monitor the long-term evolution of Paget's disease activity after treatment with tiludronate by using serum total alkaline phosphatase (TAP) and more sensitive markers such as bone alkaline phosphatase (BAP), procollagen type I N propeptide (PINP) and urinary N-terminal cross-linking telopeptide of type I collagen (NTX); to analyse the predictors of long-term response to therapy; and to study the most appropriate intervals of time for monitoring the response to therapy. METHODS: Thirty-two patients with Paget's disease were included in the study. All received 400 mg of oral tiludronate daily for 3 months. A total of 21 patients completed the study. In these patients, serum TAP, BAP and PINP and urinary NTX were measured at baseline and at 1, 6, 12 and 24 months after discontinuation of therapy. Quantitative bone scintigraphy was performed at baseline and at 6 and 24 months after the end of treatment, obtaining a scintigraphic activity index (SAI). Patients were classified into two groups depending on the long-term response to treatment: Group 1, patients who presented a persistent and significant decrease in disease activity at this time, n = 12 (57%) and Group 2, patients who presented a relapse in the activity of the disease at 24 months after treatment, n = 9 (43%). The relapse of disease activity was defined as a significant increase of SAI (>13%) between 6 and 24 months after the end of treatment, whereas the response to therapy was defined as a significant reduction in SAI (>13%) at 6 months after the end of treatment. In addition, these results were compared with the biochemical evolution of bone markers. RESULTS: Biochemical markers and SAI decreased significantly after therapy and the nadir response was observed at 6 months. At this time 100% of patients responded to therapy. The persistent long-term response was associated with lower baseline indices of bone turnover (serum BAP<60 ng/ml or TAP<600 IU/l). The intervals of time for monitoring depended on the marker used: no patient from Group 1 presented a biochemical relapse in serum TAP at 1 and 2 yr after the end of treatment whereas 33 and 45% of these patients showed relapsed serum BAP at these time points. Moreover, all patients from Group 2 presented a biochemical relapse of serum BAP at 2 yr whereas in only 33% of these patients did serum TAP relapse at this time. CONCLUSION: Most of the Pagetic patients treated with tiludronate presented a long-term response, which persisted 2 yr after the end of treatment. The nadir response to treatment was observed 6 months after discontinuation of therapy whereas the relapse of disease activity was already observed 1 yr after the end of therapy and depended on both the baseline disease activity and the bone marker used in the evaluation.

Adult↗
PubMed2003

Immunocytochemical evidence on the effects of glucocorticoids on type I collagen synthesis in human osteoblastic cells.

The effects of glucocorticoids on DNA synthesis and cellular function were assessed in cultures of human osteoblastic cells by using indirect immunoperoxidase staining with a type I antiprocollagen antibody and by measuring procollagen type I N and C propeptides (PINP, PICP) in the culture medium by radiometric methods. Likewise, we analyzed the correlation between intracellular immunostaining and procollagen propeptides released into the culture medium, as well as the correlation between PINP and PICP. Human osteoblasts were cultured with and without addition of dexamethasone (DEX) at two supraphysiological concentrations, 10(-6) M and 10(-7) M, for 24 and 48 h. Treatment with DEX at 10(-6) M was associated with a significant decrease in the percentage of cells showing intracellular type I procollagen immunoreactivity at 24 and 48 h ( P < 0.05). Similar effects were observed with 10(-7) M DEX. Dexamethasone 10(-6) M and 10(-7) M also induced significant decreases in PINP and PICP values after 24 and 48 h of treatment ( P < 0.05). The decrease in intracellular procollagen immunoreactivity and propeptide secretion was not associated with a reduction in DNA synthesis. A highly significant correlation was observed between the values of PINP and PICP in the culture medium as well as between the values of intracellular immunostaining and PINP and PICP ( P < 0.001). In conclusion, our results suggest that supraphysiological doses of glucocorticoids produce a direct inhibition on osteoblastic function through their effect on type I procollagen synthesis. Immunoperoxidase detection of type I intracellular procollagen as well as the quantification of PINP and PICP in the culture medium are reliable methods of assessing osteoblast function.

Alkaline Phosphatase↗
PubMed2003

Diagnostic usefulness of synovial vascular morphology in chronic arthritis. A systematic survey of 100 cases.

OBJECTIVES: To assess the diagnostic usefulness of the systematic analysis of synovial vascular morphology in various inflammatory, early, and longstanding arthropathies, and to examine the validity of the vascular patterns in predicting the evolution of a group of patients with undifferentiated arthritis (UA). METHODS: One hundred patients who underwent rheumatologic arthroscopy of a symptomatic joint (85 knees, 11 wrists, 3 elbows, 1 metacarpophalangeal joint) were evaluated. The same observer, blinded to patient diagnosis, analyzed the video recordings of the arthroscopies. Vascular morphology was classified into 3 patterns: straight, tortuous, and mixed. RESULTS: Eighty-one patients had inflammatory arthritis: 35 rheumatoid arthritis (RA), 16 psoriatic arthritis (PsA), 13 spondyloarthropathies (SpA), and 17 UA. Forty-nine percent of patients with RA had a straight pattern, 28% a mixed, and 23% a tortuous one. The sensitivity rate of the straight pattern for RA was 77% and the specificity rate was 70%. Seventy-six percent of RA patients with a straight pattern were rheumatoid factor positive (RF+) against 25% of RA patients with a tortuous pattern. The odds ratio for RA associated to straight compared with tortuous pattern was 57.3 (95% confidence interval, 6.6 to 499.5; P <.001). Patients with PsA and SpA shared the same pattern and were analyzed as 1 group. Ninety-three percent of patients with PsA/SpA had a tortuous pattern, 4% a straight pattern, and 3% a mixed pattern. The sensitivity rate of the tortuous pattern for PsA/SpA was 61% and the specificity rate was 95%. During 2 years of follow-up, 6 of 17 patients with UA were definitely diagnosed: 4 RA (2 RF+ and straight pattern; 2 with a tortuous pattern, 1 with RF+ and HLA-B27+); 1 SpA and 1 PsA, both with a tortuous pattern. No differences in vascular patterns were observed according to disease duration. Our results indicate that vascular patterns are not modified by disease modifying antirheumatic drug (DMARD) treatment. The other 19 patients had osteoarthritis (n = 8) and calcium pyrophosphate dihydrate crystal deposition disease (n = 11) and their predominant vascular pattern was tortuous-like. CONCLUSIONS: Arthroscopic assessment of synovial vascular changes in chronic arthritis may be of diagnostic and pathogenetic interest, although differences between published studies suggest a need for consensus in evaluating vascular patterns. A straight pattern is strongly associated with RF + RA whereas a tortuous pattern is generally associated with PsA or SpA; these associations are independent of disease duration. The vascular pattern likely does not change qualitatively with DMARD therapy. The application of this technique to the diagnosis or prognosis of patients with UA may be a complementary tool for the treatment of these patients, but larger, prospective studies are necessary to confirm this hypothesis.

Adolescent↗
PubMed2001

[Efficiency of multidisciplinary treatment of chronic pain with locomotor disability].

BACKGROUND AND OBJECTIVE: Disabling chronic pain is especially devastating among working population and, in many cases, it does not respond to conventional therapies. In chronic pain, the importance of psychosocial and occupational factors, in addition to biological ones, has prompted the development of successful multidisciplinary treatment programmes in various countries. We assessed the outcome of a multidisciplinary therapeutic program for work-disabled selected patients with chronic pain refractory to conventional treatment. PATIENTS AND METHOD: The study included 70 patients (58 women, mean age [SD]: 42 [9]years) with chronic pain and sick leave (mean [SD]: 7 [4] months of work disability) diagnosed with fibromyalgia (51%), chronic low back pain (16%), regional myofascial pain (15%), cervicocraneal syndrome (3%), anquilosing spondylitis (3%), and other conditions(12%). All patients had received previous pharmacological treatment,physical therapy and/or other measures (surgery in 12% cases)without improvement. All patients underwent an intensive multidisciplinary treatment of 4 weeks' duration including medical techniques for pain control, cognitive-behavioural therapy, physical therapy,and occupational therapy. Average follow-up was 10 (4) months(1-24 months) post-discharge. RESULTS: Significant improvements were observed with regard to all relevant variables, as reflected in pre and post-discharge measures: pain(Visual-Analogue Scale 1-10 cm): 7.4 (1.5) versus 3.2 (2) (p <0.01); anxiety (HARS), 19 (7) versus 14 (8) (p < 0.01); depression(BDI), 16 (8) versus 10 (8) (p < 0.01); functional ability(HAQ), 1.6 (0.4) versus 0.6 (0.5) (p < 0.001). At discharge,73% of patients returned to work. In addition, 69% of treated patients maintained the acquired improvement and their employment status at the end of follow-up. CONCLUSION: Multidisciplinary treatment of chronic pain with special attention to work return is useful for selected patients with a disabling chronic pain syndrome refractory to conventional treatment.

Adult↗
PubMed2001

The clinical significance of amyloid fat deposits in rheumatoid arthritis: a systematic long-term followup study using abdominal fat aspiration.

OBJECTIVE: To analyze the prevalence of subclinical amyloid fat deposits in patients with rheumatoid arthritis (RA) and to evaluate its clinical significance. METHODS: A cohort of 313 adult RA patients were included in this prospective observational study. Systematic abdominal subcutaneous fat aspiration (ASFA) was performed on all patients at study entry. The prevalence of visceral amyloidosis at study entry and at the end of followup was analyzed for patients with a positive ASFA test result. Followup ranged from 1 to 14 years (mean +/- SD 6.7 +/- 4.1 years). Patients with clinical and subclinical amyloidosis were compared with regard to clinical characteristics and the degree of amyloid deposits in abdominal fat. RESULTS: The first ASFA test found amyloid in the abdominal fat of 51 patients (16.3%), and subsequent ASFA tests found amyloid in the abdominal fat of 10 additional patients. At the time of the ASFA test, amyloidosis was subclinical in 45 of these 61 patients, 41 of whom were followed up. During followup, 11 of these 41 patients developed renal involvement, 5 due to amyloid nephropathy. Thus, amyloidosis remained subclinical in at least 30 of 41 patients (73%) throughout followup. Marked amyloid fat deposits were found more frequently in patients with clinical amyloidosis than in those whose amyloidosis remained subclinical at the end of followup (57% versus 22%; P = 0.04). CONCLUSION: Amyloid fat deposits are not uncommon in adult RA. In the majority of patients, the deposits do not indicate clinically evident organic dysfunction, even after several years of followup. Patients with more extensive fat deposits may have a higher risk of developing clinical amyloidosis.

Abdomen↗
PubMed2001

Bone mass and mineral metabolism in liver transplant patients treated with FK506 or cyclosporine A.

The purpose of this study was to compare the effects of Cyclosporine A (CyA) and FK506 on bone mass and mineral metabolism in liver transplantation (LT) patients. A prospective study was performed on 18 male patients who underwent LT treated with CyA, and 7 LT patients who received FK506. Bone mineral density (BMD) of the lumbar spine and proximal femur (DPX-L) was measured before and at 6, 12, and 24 months after transplantation. Moreover, intact parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) levels were determined at the same time. The cumulative dose of glucocorticoids was calculated in all patients. At 6 months, lumbar BMD decreased 5.2 +/- 1.2% (P = 0.0005) and 2.9 +/- 2.1% (p = ns) in CyA and FK506 groups, respectively. Lumbar BMD reached baseline values at 1 year in the FK506 group and 2 years after LT in the CyA group. Moreover, significant intergroup differences in femoral neck BMD changes after 2 years of transplant were observed (CyA: -5.2 +/- 1.97 versus FK506: +1.55 +/- 2.2%; P = 0.039). In the first year posttransplant both groups showed a marked increase in PTH and 25OHD levels. The mean cumulative dose of glucocorticoids was higher in the CyA group (CyA group 11.06 +/- 0.46 g versus FK 506 group 6.71 +/- 0.42 g; P < 0.001), and multiple linear regression analysis showed a negative correlation between BMD changes at the lumbar spine and mean cumulative dose of glucocorticoids (P = 0.022). In conclusion, our data suggest that after liver transplantation treatment with FK506 shows a more favorable long-term effect on bone mass evolution than CyA therapy. These differences seem to be associated with the lower dose of glucocorticoids used in the FK506 group.

Absorptiometry, Photon↗
PubMed2001

Bone disease after liver transplantation: a long-term prospective study of bone mass changes, hormonal status and histomorphometric characteristics.

After liver transplantation there is a high incidence of fractures, with important rates of bone loss during the first months. However, the long-term evolution of bone mass and metabolism parameters have been scarcely studied. In order to determine the incidence and risk factors involved in the development of skeletal fractures and to analyze the long-term evolution of bone mass, bone turnover and hormonal status after liver transplantation, a 3-year prospective study was performed in 45 patients following liver transplantation. Serum osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH D) and testosterone levels (men), and bone mass at the lumbar spine and femur were measured before and sequentially at different time points during 3 years. Spinal X-rays were obtained during the first year. Histomorphometric analysis of bone biopsies obtained in 24 patients within the first 12 hours after surgery and 6 months after transplantation was performed. Fifteen patients (33%) developed fractures after liver transplantation, and pre-transplant risk factors for fractures were age and low bone mass (odd's ratio for osteoporosis, 95% confidence interval: 5.69, 1.32-24.53). Serum PTH, osteocalcin, 25-OH D, testosterone and creatinine levels increased after transplantation. Moreover, PTH correlated with creatinine and osteocalcin values. Bone mass decreased during the first 6 months and reached baseline values at the lumbar spine the second year, with posterior significant recovery at the femoral neck. Long term evolution of femoral neck BMD correlated with PTH levels. Six months after transplantation bone histomorphometric data showed an increase in bone formation parameters. After liver transplantation there is a high incidence of fractures, specially in elderly patients and those with osteoporosis. Bone mass decreased in the short-term period and improved, initially at the lumbar spine and later at the femur, according to histomorphometric evidences of an increase in bone formation. The increase in creatinine values induces a secondary hyperparathyroidism that influences the changes in femoral bone mass. Treatment of osteoporosis shortly after liver transplantation may be important in the prevention of bone fractures, particularly in patients with low bone mass.

Adult↗
PubMed2000

[Chronic low back pain: multispecialty assessment of 100 patients].

OBJECTIVES: Chronic lower-back pain (CLP) is a common pathology and has a high social and economic impact, especially in primary care where its treatment is changing at present. The results of the multi-disciplinary assessment of 100 patients with chronic lower-back pain are given. DESIGN: Cross-sectional, observational and prospective study. SETTING: Out-patient clinics of the rheumatology service of a tertiary-level hospital (referral from base districts where there is no primary care rheumatologist). PATIENTS: 100 consecutive patients seen for back pain lasting for more than 6 months were analysed. INTERVENTIONS: There was no therapeutic intervention. MEASUREMENTS AND MAIN RESULTS: The personal, work, clinical, examination, x-ray, functional and psychological features of 100 patients with CLP were analysed. There were 38 men and 62 women, with average age of 45 +/- 10 years and low social, cultural and job levels. Pain had lasted 82 +/- 7 months and 52% had had time off work. Mean intensity of pain was 6.5 +/- 2.3 (scale of zero to 10). There was vertebral restriction in 16%, and conduct expressing pain on examination in 47%. The x-ray showed disorder in 51%. Functional incapacity was nil or light in 46% and severe in 16%. 74.5% of the patients were depressed; 57% had features of anxiety; and 44% were anxious at the time of the interview. CONCLUSIONS: Patients with CLP are middle-aged, with long-standing pain and frequent time off work. Pain intensity is high, but vertebral restriction, disorders on x-rays and functional incapacity are scant. However, anxiety and depression levels are high. This could suggest a change in how we treat CLP towards a multi-disciplinary approach and psycho-affective, social and labour assessment, both at the time of assessment and in later treatment of patients.

Adult↗
PubMed2000

Collagen type Ialpha1 gene polymorphism in idiopathic osteoporosis in men.

OBJECTIVE: To analyse the distribution of polymorphism of the collagen type Ialpha1 gene (COL1A1) and its relationship with bone metabolism and bone turnover in men with idiopathic osteoporosis. METHODS: A total of 35 male patients with idiopathic osteoporosis, aged 50.4 +/- 10.3 yr, and 60 healthy males (controls), aged 47 +/- 17 yr, were included in the study. Serum osteocalcin, 25-hydroxyvitamin D and parathyroid hormone were determined in all patients. The COL1A1 Sp1 genotypes (SS, SS:, ss) were assessed by restriction enzyme digestion (BAL:1) of DNA amplified by the polymerase chain reaction. RESULTS: Patients with idiopathic osteoporosis had a higher frequency of the s allele than men in the control group (29 vs 11%, P: = 0.003) and a higher frequency of the SS: genotype (patients, 48% SS, 46% SS:, 6% ss; controls, 80% SS, 18% SS:, 2% ss; P: = 0.003). No significant differences between genotypes were observed in serum concentrations of osteocalcin, vitamin D or parathyroid hormone among either the patients or the controls. CONCLUSION: This study suggests that, in men with idiopathic osteoporosis, there is a high prevalence of the s allele and the SS: genotype that is unrelated to other parameters of bone metabolism.

Adult↗
PubMed2000

Differential Th1/Th2 cytokine patterns in chronic arthritis: interferon gamma is highly expressed in synovium of rheumatoid arthritis compared with seronegative spondyloarthropathies.

OBJECTIVE: To investigate possible differences in Th1 and Th2 cytokine mRNA expression in the synovial tissue (ST) of patients with rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA) with diagnostic and/or pathogenic interest. METHODS: Eleven RA patients and 14 SpA patients (10 with undifferentiated spondyloarthropathy (USpA), two with ankylosing spondylitis (AS) and two with psoriatic arthritis (PsA)) were included. Th1 (interferon gamma, interleukin 2) and Th2 (interleukin 4, interleukin 5 and interleukin 10) cytokine mRNA levels from arthritic knee ST were quantified by using an optimised polymerase chain reaction method with a computerised analysis system. Protein levels of proinflammatory cytokines (interleukin 1, tumour necrosis factor alpha and interleukin 6) in synovial fluid were quantified with a specific ELISA test. RESULTS: Th1 cytokines were detected in all of RA ST samples in contrast with 58% (interferon gamma) and 71% (interleukin 2) of SpA samples. Th2 cytokines were expressed in 90% of RA ST samples, but the findings in SpA were interleukin 10 in 90%, interleukin 4 in 60% and interleukin 5 in 40% of ST samples. However, when the mRNA levels of each cytokine were quantified and corrected for T cell mRNA levels, only interferon gamma levels were significantly higher in RA than in SpA (p<0.003). Thus, the Th1/Th2 cytokine ratio in RA was fivefold that of SpA. Synovial fluid interleukin 1beta concentrations were higher in RA than in SpA (p<0. 05); there were also higher synovial fluid levels of tumour necrosis factor alpha in RA than in SpA, but without statistical significance. CONCLUSION: This study has detected both Th1 and Th2 cytokine gene expression in ST from RA and SpA patients. Synovium interferon gamma mRNA levels and SF interleukin 1beta protein levels were significantly higher in RA than in SpA, so reflecting the known proinflammatory activity of interferon gamma through macrophage activation. Thus, the Th1 (interferon gamma)/Th2 (interleukin 4) ratio is significantly higher in RA than in SpA ST. These data confirm previous studies on ST Th1/Th2 balance in RA and extend previous work in comparing ST RA with subgroups of SpA distinct of ReA.

Adult↗
PubMed1999

Calcitriol-mediated hypercalcaemia and increased interleukins in a patient with sarcoid myopathy.

In this report we describe a patient with Sjögren's syndrome (SS) and calcitriol-mediated hypercalcaemia. Initially, there was no clinical evidence of sarcoidosis. The patient had hypercalcaemia associated with increased calcitriol serum levels; circulating interleukin-6 and tumour necrosis factor alpha levels were also elevated. At the beginning, therapy with clodronate was effective in decreasing the serum calcium levels. However, the serum calcitriol decreased only after chloroquine treatment was added. After 2 years of therapy, the patient developed progressive and extensive muscle weakness. A muscle biopsy revealed a very prominent non-caseating granulomatous myopathy. Corticosteroid therapy was then instituted. Although both chloroquine and corticosteroid therapy were associated with decreased serum interleukin and calcitriol levels, only corticosteroid therapy was effective in treating the sarcoid myopathy. The role of cytokines in calcitriol mediated hypercalcaemia is discussed.

Antirheumatic Agents↗
PubMed1999

Biochemical markers of bone turnover after surgical menopause and hormone replacement therapy.

The objective of this study was to evaluate the effect of surgical menopause and hormone replacement therapy (HRT) on the new biochemical markers of bone turnover. Fourteen women who had undergone surgical menopause and began HRT 3 months after surgery were recruited for a 1-year study. Results were compared with a control group of 31 healthy premenopausal women of similar age. Serum samples were obtained to determine total alkaline phosphatase, bone alkaline phosphatase, propeptides carboxy- and amino-terminal of type I procollagen (PICP, PINP), osteocalcin, tartrate-resistant acid phosphatase, and carboxy-terminal telopeptides of type I collagen (ICTP and serum CTX). Urine samples were analyzed for hydroxyproline, pyridinoline, deoxypyridinoline, alpha- and beta-carboxy-terminal telopeptides of type I collagen (alpha-CTX and beta-CTX), and amino-terminal telopeptide of type I collagen (NTX). Determinations were performed after 3 months of surgical menopause and after 3 and 9 months of HRT. All biochemical markers increased after menopause, and most of them normalized after 9 months of HRT. Serum PINP showed the highest proportion of increased values after surgery among bone formation markers (62%), as well as the highest mean percent increase (101%). Among bone resorption markers in postmenopausal women, urinary beta-CTX, alpha-CTX, NTX, and serum CTX showed the highest proportion of increased values (100%, 67%, 58%, 58%, respectively) as well as the greatest mean percent increase. They were also the markers with the most marked response to HRT. In conclusion, serum PINP is the most sensitive marker of bone formation, whereas beta-CTX is the most sensitive marker of bone resorption after surgical menopause. In addition, both markers showed the highest response after HRT.

Acid Phosphatase↗
PubMed1997

Relationship between biochemical markers of bone turnover and bone scintigraphic indices in assessment of Paget's disease activity.

OBJECTIVE: To evaluate the relationship between biochemical markers of bone turnover and bone scan indices of disease activity, as well as to analyze their variations based on skeletal involvement, in Paget's disease. METHODS: Serum samples were obtained from 51 patients with Paget's disease to determine the levels of total alkaline phosphatase (total AP), bone alkaline phosphatase (bone AP), propeptide carboxyterminal of type I procollagen (PICP), propeptide aminoterminal of type I procollagen (PINP), osteocalcin, tartrate-resistant acid phosphatase, and telopeptide carboxyterminal of type I collagen. Urine samples were analyzed for levels of hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), C-terminal telopeptide of type I collagen (CTx), and N-terminal telopeptide of type I collagen (NTx). In addition, 2 semiquantitative scintigraphic indices, disease activity (AI) and disease extent (EI), were obtained. Pagetic skeletal locations were evaluated individually, with special attention to skull involvement. RESULTS: All biochemical markers correlated with the AI and the EI. Serum PINP, bone AP, and total AP showed the highest proportions of increased values among the bone formation markers (94%, 82%, and 76%, respectively). Among the bone resorption markers, urinary NTx showed the highest proportion of increased values in patients with Paget's disease (96%), compared with PYR (69%), DPYR (71%), CTx (65%), and HYP (64%). In patients with mild disease activity, serum PINP was the marker with the highest proportion of increased values (71%). In contrast, serum PICP and urinary CTx were the most discriminative markers for skull involvement. Except for higher values for most of the biochemical markers of bone turnover in flat bones, no major differences in other skeletal locations were observed. CONCLUSION: The determination of serum PINP as a marker of bone formation and urinary NTx as a marker of bone resorption provided the best biochemical profile to ascertain the extent and activity of Paget's disease. In patients with skull involvement, serum PICP and urinary CTx were shown to be the most discriminative markers.

Acid Phosphatase↗
PubMed1997

Osteoporosis and bone mineral metabolism disorders in cirrhotic patients referred for orthotopic liver transplantation.

The purpose of this study was to determine the prevalence of osteoporosis, to estimate the bone turnover and hormonal status, and to identify the factors associated with bone disease in patients with end-stage liver disease who were referred for orthotopic liver transplantation. A prospective study was performed on 58 cirrhotic patients (6 with primary biliary cirrhosis, 14 with alcoholic cirrhosis, and 38 with posthepatitic cirrhosis), who were referred for orthotopic liver transplantation. Patients, excluding those with primary biliary cirrhosis, were classified in Child-Pugh groups according to the severity of liver disease (class B [28 patients], class C [24 patients]). Biochemical parameters of bone mineral metabolism and standard liver function tests were measured in all patients. Additionally, serum osteocalcin, urinary hydroxyproline/creatinine ratio, serum intact parathyroid hormone, serum 25-hydroxyvitamin D, serum 1,25-dihydroxyvitamin D, follicle-stimulating hormone, and luteinizing hormone levels were determined in patients and controls within the same age range. Plasma testosterone, sex hormone-binding globulin levels, and free testosterone index were obtained for all men included in the study. Bone mass of the lumbar spine and femur were measured by dual X-ray absorptiometry (DPX-L), and were expressed as a standard deviation of mean values (Z-score) from a sex and age-matched control group. Spinal X-rays were obtained to assess vertebral fractures. Osteoporosis was considered as a factor in spinal bone mineral density with a Z-score below 2 or at least one vertebral fracture. Twenty-five patients (43%) had osteoporosis, with lower bone mass measurements in the lumbar spine than in the femoral neck (P < 0.005). Alcoholic and Child-Pugh C patients showed the lowest femoral bone mineral density values. Cirrhotic patients showed lower osteocalcin levels than controls (14.3 +/- 5.9 vs. 18.2 +/- 8.1 ng/ml; P < 0.05) and showed increased urinary hydroxyproline (125.1 +/- 51.5 vs. 107.9 +/- 26.6 nM/mg creatinine; P < 0.05). Serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone levels were significantly lower in cirrhotic patients than in controls (10.3 +/- 9.1 vs. 23.1 +/- 26.6 ng/ml; P = 0.000), (12.9 +/- 9.1 vs. 48.3 +/- 11.5 pg/ml; P = 0.000), (16.6 +/- 9.2 vs. 27.9 +/- 8.2 pg/ml; P = 0.000), with no differences between Child-Pugh groups. Alcoholic Child-Pugh C patients showed the lowest 25-hydroxyvitamin D serum values (4.5 +/- 2.2 ng/ml; P < 0.05). Male patients had lower testosterone levels than controls (302.5 +/- 229.4 vs. 556.7 +/- 146.5 ng/dl; P = 0.000), with increased sex hormone-binding globulin values. Levels of testosterone and gonadotropin were related to Child-Pugh classification. No correlation was found between bone mass and hormonal values. A significant decrease in bone mass, particularly in the lumbar spine, is seen in end-stage cirrhotic patients. Reduced bone formation and significant disorders of bone mineral metabolism, such as vitamin D deficiency, reduced parathyroid hormone levels, and hypogonadism are involved. Moreover, severity and etiology of the liver disease are the main risk factors for developing bone loss and mineral metabolism disorders in patients referred for orthotopic liver transplantation.

Adult↗
PubMed1997

Biochemical markers of bone turnover in Camurati-Engelmann disease: a report on four cases in one family.

Moderate increases in "classical" biochemical markers of bone turnover have been described only in some patients with Camurati-Engelmann disease. However, the determination of the following "new" markers has not been previously performed: serum osteocalcin (BGP), bone alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), aminoterminal propeptide of type I procollagen (PINP), tartrate-resistant acid phosphatase (TRAP), telopeptide carboxyterminal of type I collagen (ICTP), urinary pyridinoline (PYR), crosslinked N-telopeptides of type I collagen (NTX), and Crosslaps (CL). Such a determination may improve the evaluation of the disease activity. To evaluate the usefulness of biochemical markers of bone turnover reflecting Camurati-Engelmann disease activity we measured the levels of all these markers in four affected patients. The results were compared with bone scintigraphic indices of disease activity. Except for PICP and TRAP, bone formation and resorption markers were abnormal in all patients and were related to bone scan indices of disease activity. Among the markers of bone formation PINP, BAP, and BGP showed the highest values, whereas NTX and CL were the most sensitive markers of bone resorption. These results suggest that the determination of NTX or CL, and PINP or either BAP and BGP, associated with bone scan evaluation, provides the best assessment of Camurati-Engelmann disease activity.

Acid Phosphatase↗
PubMed1997

Comparative cytokine gene expression in synovial tissue of early rheumatoid arthritis and seronegative spondyloarthropathies.

Interleukin 1-beta (IL-1 beta), IL-2, IL-4, IL-5, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression was determined in knee synovium of 16 patients with rheumatoid arthritis (RA) and 16 patients with seronegative spondyloarthropathies (SSP), by using polymerase chain reaction (PCR) amplification. The pattern of cytokines observed in RA synovium is of the macrophage-fibroblast type, with the highest expression of IL-1 beta and TGF-beta. GM-CSF and IL-2 bands were visualized in a minority of patients. Neither IL-4 nor IL-5 could be detected. No significant differences were observed in the cytokine profile between patients with early (< 12 months) and more advanced disease. No differences were observed according to gender, age, rheumatoid factor status and the duration of knee synovitis. The pattern of cytokines in the synovium of SSP patients is similar to that observed in RA patients and does not change in relation to disease duration. IL-2 was the only T-cell cytokine observed. These data provide evidence that the macrophage-fibroblast cells have an important role in early and more advanced rheumatoid synovitis, and show that this is also true for SSP peripheral synovitis.

Adult↗