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Biomedical subjects

M Piperno

Publications and source records attributed to M Piperno.

At least 19 recordsLinked to original sources

Cross sectional evaluation of biochemical markers of bone, cartilage, and synovial tissue metabolism in patients with knee osteoarthritis: relations with disease activity and joint damage.

OBJECTIVE: To analyse the relations between the urinary levels of type II collagen C-telopeptide (CTX-II) and glucosyl-galactosyl pyridinoline (Glc-Gal-PYD)-two newly developed biochemical markers of type II collagen and synovial tissue destruction respectively-disease activity and the severity of joint destruction in patients with knee osteoarthritis (OA). The clinical performance of these two new markers was compared with that of a panel of other established biochemical markers of connective tissue metabolism. METHODS: The following biochemical markers were measured in a group of 67 patients with knee OA (mean age 64 years, median disease duration eight years ) and in 67 healthy controls: for bone, serum osteocalcin, serum and urinary C-telopeptide of type I collagen (CTX-I); for cartilage, urinary CTX-II, serum cartilage oligomeric matrix protein (COMP), and serum human cartilage glycoprotein 39 (YKL-40); for synovium, urinary Glc-Gal-PYD, serum type III collagen N-propeptide (PIIINP), serum hyaluronic acid (HA); and for inflammation, serum C reactive protein. Biochemical markers were correlated with pain and physical function (WOMAC index) and with quantitative radiographic evaluation of the joint space using the posteroanterior view of the knees flexed at 30 degrees. RESULTS: All bone turnover markers were decreased in patients with knee OA compared with controls (-36%, -38%, and -52%, p<0.0001 for serum osteocalcin, serum CTX-I and urinary CTX-I, respectively). Serum COMP (+16%, p=0.0004), urinary CTX-II (+25%, p=0.0009), urinary Glc-Gal-PYD (+18%, p=0.028), serum PIIINP (+33%, p<0.0001), and serum HA (+ 233%, p<0.0001) were increased. By univariate analyses, increased urinary Glc-Gal-PYD (r=0.41, p=0.002) and decreased serum osteocalcin (r=-0.30, p=0.025) were associated with a higher total WOMAC index. Increased urinary CTX-II (r=-0.40, p=0.0002) and Glc-Gal-PYD (r=-0.30, p=0.0046) and serum PIIINP (r=-0.29, p=0.0034) were the only markers which correlated with joint surface area. By multivariate analyses, urinary Glc-Gal-PYD and CTX-II were the most important predictors of the WOMAC index and joint damage, respectively. CONCLUSION: Knee OA appears to be characterised by a systemic decrease of bone turnover and increased cartilage and synovial tissue turnover. CTX-II, Glc-Gal-PYD, and PIIINP may be useful markers of disease severity in patients with knee OA.

Aged↗

Glucosamine sulfate modulates dysregulated activities of human osteoarthritic chondrocytes in vitro.

OBJECTIVE: The efficacy of glucosamine sulfate (GS) in the symptomatic treatment of patients with osteoarthritis (OA) is suggested to be mediated by still unknown effects on the altered OA cartilage. DESIGN: Using human OA chondrocytes in culture, the effects of GS on protein synthesis, caseinase, collagenase, phospholipase A2 (PLA2) and protein kinase C (PKC) activities as well as production of nitric oxide and cyclic AMP were studied in both cells and culture medium. RESULTS: GS significantly reduced PLA2 activity, and more modestly collagenase activity, in the OA chondrocytes in a dose-dependent manner. By contrast, PLA2 and collagenase activity of the culture medium was not modified. No effects on caseinase activity was seen. GS significantly and dose-dependently increased protein synthesis. GS did not modify nitric oxide and cAMP production but significantly increased PKC production. CONCLUSION: GS modified cultured OA chondrocyte metabolism by acting on PKC, cellular PLA2, protein synthesis and possibly collagenase activation. Extrapolation of the effect to the in-vivo situation remains hypothetical but they might represent some possible mechanisms of action of the drug in human.

Caseins↗

[Primary nutritional and drug prevention of atherosclerosis].

Atherosclerosis results from a multifactorial process. For that reason, primary prevention of cardiovascular diseases requires several measures that should exhibit antiatherogenic, antithrombotic, antioxidative and antihypertensive properties. Two types of therapeutic strategies can be individualized. Nutritional interventions are the first line measures for population wide primary prevention in subjects at low risk of developing atheroscleric diseases. In high risk individuals who have either one major risk factor (LDL cholesterol above 190 mg/dL) or several additional risk factors, dietary measures must be frequently combined with drug treatments. However, the cost-effectiveness ratio should be weighed prior to any treatment especially with statins. Dietary measures consist to reduce caloric intakes in overweight subjects, or more generally to adopt eating patterns which correspond to the following recommendations: (i) proteins = 15% of total calories; (ii) saturated and polyunsatured fats = 10% each; (iii) carbohydrates plus monounsaturated fats = 65%. Such dietary instructions permit individual dietary changes, just by adjusting the carbohydrates/monounsaturates balance, the sum of both nutrients remaining in all cases equal to two-thirds to total calories. Drug treatments are only indicated after secondary dietary failure. They are generally based on the use of statins since the efficacy of these treatments has been clearly established by such preventive trials as the WOSCOP Study, provided that the therapeutic interventions result in significant reduction of LDL cholesterol levels over several years. Antiplatelet agents (aspirin), antihypertensive therapies, antioxidant supplementations with vitamins E or C are also recommended in some individuals for completing the beneficial effects of the above mentioned measures.

Anticholesteremic Agents↗

Evaluation of the 'Lequesne's false profile' of the hip in patients with hip osteoarthritis.

OBJECTIVES: To compare the value of Lequesne's false profile (LFP) radiograph of the hip and antero-posterior (AP) X-ray of the pelvis in the assessment of joint space narrowing (JSN) and osteophyte (Ost) in patients with hip osteoarthritis (OA). METHODS: AP and LFP radiographs of the hip were performed using a standardized method in 50 consecutive patients with hip OA. JSN and Ost were graded at different days by a single observer blinded for patients identity, using a six point scale (JSN:0-5) and a four point scale (Ost:0-3) from AP and LFP respectively. Scores obtained from AP and LFP were compared. RESULTS: Mean JSN grade was significantly higher for LFP (2. 7+/-1.0) than AP (2.4+/-1.2) (P=0.001). It was identical for AP and LFP in 28 patients (56%) while the highest grade was found on LFP in 16 (32%) and on AP in 6 (12%). No significant difference between LFP and AP was found for osteophyte grading. CONCLUSION: These data suggest that the combination AP+LFP provide more information than AP alone for the evaluation of joint space narrowing in about one third of patients. LFP may be helpful for the radiographic assessment of OA changes particularly in structure modifying drugs evaluation.

Aged↗

Radiographic assessment of hip and knee osteoarthritis. Recommendations: recommended guidelines.

Pathological lesions of osteoarthritis, demonstrated by conventional radiography, can be assessed by scoring systems and/or measurement with a quite acceptable reproducibility. Scores are recommended for a rough staging of osteoarthritis and of bone changes. Measurement is recommended for assessment of joint space narrowing progression. A good assessment of progression implicates a perfect reproducibility of the radiographic image of the joint. Accuracy of standard radiograph is improved by some views such as the hip profile and the schuss view.

Humans↗

Quantitative evaluation of joint space width in femorotibial osteoarthritis: comparison of three radiographic views.

OBJECTIVE: Quantitative evaluation of radiographic methods proposed to improve the detection of joint space narrowing (JSN) in femorotibial osteoarthritis (OA). METHODS: Thirty-two consecutive patients with knee OA and five normal controls had three different weight-bearing radiographs of the knee: (1) anteroposterior film of both knees in full extension (extended knees), (2) anteroposterior film of one knee in extension while the patient was standing on the homolateral foot (standing on homolateral foot), (3) posteroanterior film of both knees flexed at 30 degrees (schuss view). Joint space was analyzed blind using both an evaluation of JSN with a six-grade scale (JSN score) and an image analyser computer measurement of the mean joint space width (mean JSW). The medial compartment of medial femorotibial OA knees, the lateral compartment of lateral femorotibial OA knees, as well as both compartments of control knees, were measured. Extended knee and schuss views were made 1 year later in 10 patients for the evaluation of sensitivity to change. RESULTS: The JSN scores +/- S.D. in schuss, standing on the homolateral foot and extended knee views were 2.75 +/- 1.31, 1.95 +/- 1.3 and 1.66 +/- 1.27, respectively. The mean JSW +/- S.D. in schuss, standing on the homolateral foot, and extended knee views were 2.9 +/- 1.9 mm, 3.5 +/- 1.6 mm and 3.8 +/- 1.5 mm, respectively. Changes in JSN scores and mean JSW with schuss view increased with OA severity. In controls, JSW of the medial compartment did not vary in the three views. JSW of the lateral compartment of controls was significantly larger in the schuss view. The change in JSW after 1 year was -0.41 mm (P = 0.02) in the schuss view and -0.17 mm (P > 0.05) in the extended knee view. CONCLUSION: The schuss view is suggested as the most accurate method for the evaluation of JSW in femorotibial OA.

Adult↗

Osteoarthritic cartilage fibrillation is associated with a decrease in chondrocyte adhesion to fibronectin.

OBJECTIVE: Cartilage destruction in osteoarthritis (OA) is generally accepted as a failed repair process. Cell adhesion is implicated in tissue repair. Therefore, adhesion of OA chondrocytes to extracellular matrix proteins was investigated. DESIGN: Using chondrocytes from human OA femoral head cartilage, adhesion to fibronectin and type II collagen of cells from distinct areas showing an intact cartilage surface or a fibrillated cartilage surface was studied. Modulation of chondrocyte adhesion by both protein kinase C (PKC) inhibitors and glucosamine sulfate (GS) was also investigated. RESULTS: A significant (P < 0.05) decrease in adhesion to fibronectin of chondrocytes from fibrillated cartilage, relative to those from grossly normal OA cartilage, was demonstrated. Adhesion to type II collagen was not modified by the chondrocyte origins (either from normal or fibrillated OA cartilage). Adhesion to fibronectin of cells from grossly intact cartilage was decreased by the addition of PKC and calmodulin-dependent kinase inhibitors, W7 and sphingosine, to the cell culture. Adhesion to fibronectin of chondrocytes from fibrillated cartilage was significantly (P < 0.05) increased after glucosamine sulfate treatment. CONCLUSION: Fibrillation of cartilage from OA femoral head is associated with a defective adhesion of chondrocytes to fibronectin. The process is suggested to be dependent of PKC and/or calmodulin-dependent kinases and potentially reversible. Conceivably, it could play a role in OA cartilage destruction.

Aged↗

Phospholipase A2 activity in herniated lumbar discs. Clinical correlations and inhibition by piroxicam.

STUDY DESIGN: Prospective study of phospholipase A2 activity in the serum and intervertebral discs of patients undergoing surgery for sciatica due to disc herniation. OBJECTIVES: To determine correlations between herniated disc phospholipase A2 and clinical, radiographic, and anatomic signs of common sciatica; to evaluate serum phospholipase A2 activity as a marker of disc phospholipase A2; and to investigate the in vivo effect of piroxicam on disc phospholipase A2. SUMMARY OF BACKGROUND DATA: Several studies suggest disc inflammation as a mechanism of sciatica due to disc herniation, and phospholipase A2 emerges as a key enzyme of cartilage and disc tissues. METHODS: Phospholipase A2 activity was determined, using the degradation of a specific substrate, in the serum and discs of 31 patients (14 treated with acetaminophen and 17 treated with piroxicam) undergoing surgery for sciatica due to lumbar disc herniation. Visual analog scale for pain, Dallas Pain Questionnaire, Lasègue's sign, radiographic stage of degeneration of the herniated disc, volume of disc herniation shown by computed tomography, and surgical findings were recorded. RESULTS: Disc phospholipase A2 activity was independent of the patient's age or sex, the radiologic stage of disc degeneration, and the volume of the herniation, and showed no significant correlation with Lasègue's sign or pain measured on a visual analog scale. The correlation between disc phospholipase A2 and the Dallas category of items measuring the impact of pain on daily activities approached the level of significance (P = 0.07). Disc phospholipase A2 activity was significantly higher in cases of sequestrated discs than in other herniations. Disc phospholipase A2 was significantly correlated with serum phospholipase A2, and was significantly lower in patients treated with piroxicam than in those treated with acetaminophen. CONCLUSIONS: Disc phospholipase A2 is thought to participate in the physiopathology of sciatica and to bemodulated by nonsteroidal anti-inflammatory drug therapy. Serum phospholipase A2 is suggested as a biologic marker of disc inflammation in patients with sciatica.

Acetaminophen↗

[Primary AL-type amyloidosis disclosed by Horton disease].

Primary systemic amyloidosis rarely affects the walls of small and medium-sized vessels. We report a case of primary AL amyloidosis masquerading as giant cell arteritis at the onset of the disease, revealed by the temporal arteritis biopsy, and successfully treated by corticotherapy for three years. Histology of temporal arteritis confirms the diagnosis of amyloidosis (characteristic birefringence with Congo red). We discuss in this case the diagnosis of primary amyloidosis revealed by Horton disease, or the coincidental association of these two diseases.

Aged↗

Progression of digital osteoarthritis: a sequential scintigraphic and radiographic study.

Hand radiographs and scintigraphy were obtained initially and at the 4-year follow-up in 15 patients with symptomatic osteoarthritis (OA) of distal and/or proximal interphalangeal joints. For each joint, a 0-15 score was obtained for the OA radiographic lesions read blind by the same observer. An abnormal isotope retention over a bone reference area was assessed and quantified. The predictive value of scintigraphy for the OA radiographic progression was confirmed and shown to be improved by a second investigation. During the study period, the percentage of radiographic OA joints increased from 66.3 to 76.6%, but joints showing an abnormal scan decreased from 40 to 22.5%. Progression of the OA radiographic score was closely related to scintigraphic changes. The mean difference between the final and initial OA score was -0.08 in joints with two normal scans (N = 115), +0.73 in joints showing a first abnormal and a second normal scan (N = 94) and +1.8 in joints with two abnormal scans (N = 14) or a scan becoming abnormal (N = 47). An abnormal scan appears to represent a transient event, and this event is associated with a period of progression of digital OA. Potentially, anti-OA therapies that suppress joint isotope retention might slow down OA progression. The magnitude of joint isotope retention was positively correlated with the OA radiographic score established at the same time (R = 0.61 and P < 0.001), but showed no predictive value for progression of the latter.

Adult↗

[Serum phospholipase A2 activity in osteoarthritis].

Serum phospholipase A2 activity in 67 osteoarthritis patients and 17 controls was determined using a radiolabeled specific substrate. Serum phospholipase A2 activity was significantly higher in osteoarthritis patients (115 +/- 73.6 dpm/h/ml) than in controls (45 +/- 25 dpm/h/ml) (p = 0.002). In 41 osteoarthritis patients, serum phospholipase A2 activity was unrelated to age, time since onset of osteoarthritis symptoms, duration of morning stiffness, Lequesne's index, roentgenographic stage of osteoarthritis, number of joints with osteoarthritis, erythrocyte sedimentation rate, or serum C-reactive protein levels. In 12 osteoarthritis patients who were evaluated twice at a mean interval of 46 days, changes in serum phospholipase A2 activity were unrelated to changes in Lequesne's index. Blind evaluation of long-term joint space loss was performed in 14 patients; serum phospholipase A2 activity increased only in those patients with progressive joint space loss, but the difference was not statistically significant as compared with the controls. These data suggest that serum phospholipase A2 activity is not useful in practice as a marker for osteoarthritis.

Adult↗

[Measurement of the hip joint space using automatic digital image analysis].

Joint surface area (JSA) and mean joint space width (MJSW) at the hip were measured using a ICMS-Techline computer program to analyze digitalised frontal weight-bearing roentgenograms of the pelvis. With this technique, the portion of joint space studied is always the same in a given patient and is enclosed within an acute ECS angle whose apex C is the center of the head of the femur and whose ends E and S are the lateral rim of the acetabulum and the highest point of the homolateral sacral wing respectively. ECS varies across individuals but remains constant in a given hip. Twenty hips were included in the first part of the study. For each hip, three roentgenograms were taken at five-minute intervals by three different radiologists who used their own constants (settings, position of the subject). JSA and MJSW are determined five times on each film by two different observers who had no information on the films under study. The interobserver coefficient of variation (CV) was 4.7% for JSA and 3.3% for MJSW. Intra-observer CVs were 2.97 and 3.54% for MJSW and 4.32% and 5.13% for JSA. There was a very close correlation between MJSW and JSA (r = 0.87, p < 0.0001). MJSW was then determined for roentgenograms of 30 hips with osteoarthritis. Results were compared with the values obtained using Lequesne's method of joint space measurement at the site of maximum narrowing. Measurements were performed in a double-blind fashion by two observers. The correlation coefficient was r = 0.89 (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Serum hyaluronic acid in osteoarthritis].

In this prospective study, serum hyaluronate (SH) was assayed using a radiometric method (Pharmacia) in 73 osteoarthritis patients and 39 controls. All assays were performed between 8 h 00 and 9 h 00 a.m. because SH levels exhibit circadian variations. SH levels were significantly higher in patients with osteoarthritis than in controls (92 +/- 66 micrograms/l and 39 +/- 21 micrograms/l, respectively, p = 0.0001). Among 50 patients with osteoarthritis, including 29 with knee involvement and 21 with hip involvement, SH levels were not correlated with morning stiffness, duration of symptoms, Lequesne's algofunctional index, erythrocyte sedimentation rate, C-reactive protein, severity of roentgenographic changes in the affected knee or hip, disease extension, or severity. The lack of any relationship between changes in SH levels and Lequesne's is index values in 25 patients or between SH levels and joint space narrowing evaluated retrospectively in 16 patients, as well as the prompt return to high SH levels after arthroplasty and synovectomy in 14 patients with hip joint osteoarthritis, suggest that this potential marker is not useful for monitoring osteoarthritis in a single joint.

Adult↗