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Biomedical subjects

D Mitrovic

Publications and source records attributed to D Mitrovic.

At least 19 recordsLinked to original sources

Standardization of transrectal ultrasound-guided biopsy.

Ultrasound-guided biopsy is more sensitive to biopsy performed under the digital control, because 29% of prostatic cancers are not palpable. On the other hand, at least 30% of cancers are isoechogenic, so they cannot be viewed by transrectal ultrasound examination. It means that target biopsy is not sufficient for diagnosis of localized prostatic cancer, i.e., randomized samples are needed as well. More than ten years ago, the technique of sampling the six specimens became a standard procedure to which previously harvested target specimens from suspected growths were added. Today, the expansion of biopsy protocol is recommended, by obtaining the additional specimens from peripheral lateral area, four plus two samples if the prostate has volume over 50 ml. Larger number of biopsies requires anesthesia. In order to reduce complication, the cleaning of rectal ampulla and prophylactic use of quinolone are suggested.

Biopsy, Needle↗

Correlation of high-molecular cytokeratin in tissue of prostatic cancer with Gleason score and PSA.

The absence of basal cell layer of prostatic acini containing high-molecular cytokeratin, which is immunohistochemically detected by monoclonal antibody 34betaE12, is an essential diagnostic characteristic of prostatic cancer. The absence of immunohistochemical reaction in 3 or more pseudoglandular structures of prostatic tissue indicates malignant process. The percentage of immunohistochemically completely negative glandular structures was determined by semiquantitative measurement in tissue specimens obtained by TRUS biopsy of the prostate, and it was correlated with serum PSA concentration and Gleason score. The increase of percentage of glandular prostatic formations completely negative to high-molecular cytokeratin detected by 34betaE12 led to simultaneous rise of mean value of Gleason prostatic cancer score (p < 0.001) as well as the average serum PSA concentration in subjects (p < 0.05).

Adenocarcinoma↗

The possibilities of age reference values of PSA density in prostatic cancer screening.

INTRODUCTION: The possibilities of PSA (prostate specific antigen) test in screening of prostatic cancer may be evaluated by measuring its sensitivity, specificity and positive predictive value. The majority of reference articles in this field has evaluated the possibility of detection of prostatic cancer by radioimmunoassay (RIA). MATERIAL AND METHODS: Prospective study included 2000 male patients over 50 years of age. The objective of the study was to examine the possibility of enzyme PSA test for differentiation of benign prostatic hyperplasia (BPH) and localized prostatic cancer (PC). The possibility of enzyme PSA assay for detection of prostatic cancer was compared with RIA method, by digital rectal examination and echotomography. The effect of PSA density and age reference values for differentiation of PC from BPH was also examined. DISCUSSION: The results of enzyme immunoassay test (EIA) were compatible with radioimmunoassay results (RIA). Diagnostic algorithm of prostatic cancer detection should be corrected with PSA density values according to aged-specific groups (49 years - 0.09 ng/ml/cm3; 59 years - 0.13 ng/ml/cm3; 69 years - 0.17 ng/ml/cm3; 79 years - 0.19 ng/ml/cm3) in order to reduce the number of false positive results in PSAD grey zone (0.10 - 0.20).

Aged↗

Age-related decrease in the responsiveness of rat articular chondrocytes to EGF is associated with diminished number and affinity for the ligand of cell surface binding sites.

The effect of age on the responsiveness of articular chondrocytes (AC) to epidermal growth factor (EGF) was examined. Cells were isolated by digesting cartilage fragments from the humeral and femoral heads of 21-day old, 8- and 14-month old rats with collagenase. The cells were cultured under standard conditions, as monolayers. DNA synthesis was measured by [3H]thymidine incorporation and cell proliferation by the DNA content of subconfluent cultures. [125I]EGF binding and the amounts of EGF and EGF-receptor mRNAs were determined using confluent cells. DNA synthesis was decreased with age of animals. EGF stimulated DNA synthesis in cultures in 1- and 8-month old rats at low serum concentrations (< 5%), and in cultures in 14-month old animals at high serum concentrations. It also increased 5-day DNA content of cultures compared to serum-treated controls but this effect was weak in cultures in 14-month old rats. The number of high affinity binding sites for [125I]EGF decreased from 37,800 in the 1-month old to 1950 in the 14-month old rat AC. The apparent dissociation constant (Kd) also decreased with age: 0.18 nmol/l in the 1-month old; 0.12 nmol/l in the 8-month old; and 0.07 nmol/l in the 14-month old cells. AC in older rats contained more EGF mRNA and less EGF-receptor mRNA. Incubation of the cells with EGF resulted in down regulation of the EGF- and upregulation of EGF-receptor mRNA expressions. These findings show the age-related quantitative and qualitative alterations in EGF and EGF-receptor which may account, at least in part, for the diminished responsiveness of senescent AC to EGF.

Aging↗

Effect of reactive oxygen species on the biosynthesis and structure of newly synthesized proteoglycans.

The effect of reactive oxygen species (ROS) generated by a xanthine oxidase hypoxanthine system (mainly H2O2) on proteoglycan (PG) metabolism and structure was investigated in vitro, using cell monolayers of cultured rabbit articular chondrocytes and purified resident and newly synthesized proteoglycans. It was shown that ROS generated in this system frequently stimulate (at low concentrations), and consistently inhibit (at higher concentrations), the incorporation of 35SO4 and 3H-glucosamine into PG molecules synthesized by cultured chondrocytes. The inhibition of isotopes' incorporation at higher enzyme concentrations was suppressed completely by heating xanthine oxidase and allopurinol with superoxide dismutase (SOD) and catalase. ROS at high concentration also inhibited 3H-uridine incorporation but had no effect on 35SO4 and 3H-uridine uptake by the cells. They also alter hyaluronan (HA) and PG monomers by fragmenting the core protein moiety and destroying the hyaluronic acid binding region. Altered PG monomers do not interact with HA to form complexes, but fragmented HA still retain a significant PG monomer-binding capacity. PG-HA complexes are easily and irreversibly destroyed by ROS. These results suggest that ROS may at low fluxes stimulate PG-synthesis under physiological conditions and alter cartilage metabolism and structure in conditions where they are overproduced, such as in rheumatoid arthritis, and in hemochromatosis and other iron storage diseases.

Allopurinol↗

[Effect of oxaceprol on the structure of proteoglycans synthesized by articular chondrocytes from calves].

Calf articular cartilage fragments were incubated in vitro in the absence and presence of 170 micrograms N-acethyl-trans-4, hydroxyproline (oxaceprol) and 20 muCi [35S]-Na2SO4 per ml of culture medium. Newly synthesized 35S labeled proteoglycans (35S-PGs) were extracted with buffered 4M guanidinium chloride (GdmCl) solvent and then characterized with respect to their hydrodynamic sizes, capacity to interact and form aggregates with hyaluronic acid (AH) and the length and composition of their glycosaminoglycan (GAG) side chains. It was demonstrated that extracted 35S-PGs synthesized in the presence of the oxaceprol are not significantly different from the molecules synthesized in the absence of this compound.

Animals↗

[The aging of joints and osteo-arthrosis].

Although the frequency and severity of osteo-arthrosis regularly increase after the age of 50 years, individual's age does not seem to be a causal factor of this disorder. Indeed, osteoarthrosis does not affect all age individuals and not all joints are involved at the time. Various etiological factors (traumatisms, joint malformations and preexisting disorders, overuse of joints, etc.) are usually identified. Joint lesions in osteo-arthrosis are not those characteristic of senile involution, but rather represent proliferative reparative processes. Therefore, old age may act as one of the risk factors, which favors a development of osteo-arthrosis if others, more specific, etiological factors are present.

Aging↗

[Results of autopsy examination of the knee cartilage of 120 patients dying in the hospital. II. The femoro-tibial joint].

The authors have studied the autopsy results of both tibio-femoral joints in 120 patients: 57 women and 63 men, 112 of whom were over the age of 50. The condylar and tibial cartilages were classified into 5 categories: no lesion (0); slight fissure (I); severe fissure (II); slight deep ulceration (III); large ulceration (in more than 25 p. cent of the cartilage surface) exposing the sub-chondral bone (IV). In 120 patients, the 4 condyles in 58 patients (43.8 p. cent) and both tibio-femoral joints in 51 patients (42.5 p. cent) did not present any degenerative lesions beyond stage I. Stage III and IV cartilaginous lesions are rare before the age of 50. Their frequency suddenly increases after the ages of 70 in women and 80 in men. 44 p. cent of women and 31 p. cent of men presented tibio-femoral cartilaginous lesions of stages II or IV in at least one knee; 15.8 p. cent of women and 4.7 p. cent of men presented tibio-femoral lesions, stage IV, in at least one knee. In 58 p. cent of stage III and IV knee lesions, the menisci were abnormal: atrophic or torn. A menisco-chondrocalcinosis was found in 50 knees (20.8 p. cent of knees) of 28 patients (23.3 p. cent of patients). After the age of 60, the cartilaginous lesions were more severe and more extended in knees with menisco-chondrocalcinosis).

Age Factors↗

[Results of autopsy examination of knee cartilage in 120 patients dying in the hospital. I. Femoro-patellar joint].

The authors have performed the pathological examination of the knees of 57 women and 63 men or 112 patients over the age of 50, who died in the hospital. The lesions of the patellar and trochlear cartilages were studied and classified according to four categories: stage I: non extended fissures; stage II: fissures extending over 25 p. cent of the articular surface; stage III: fissures associated with small deep ulcerations of the cartilage; stage IV: deeps and extended ulcerations of the articular cartilage exposing the sub-chondral bone. Cartilage alterations were found in 93.3 p. cent of the patellas; 26.2 p. cent of stage I; 22.5 p. cent of stage II, 27.1 p. cent of stage III; 17.5 p. cent of stage IV. These alterations are bilateral and symmetrical, most of the time. Their frequency and severity increase with age. Thus, deep and extended ulcerations (stage IV) of the patellar cartilage have a frequency of 1.9 p. cent before the age of 60.8 p. cent between 60 and 70 years, 13.6 p. cent between 70 and 80 years and 38.9 p. cent after 80 years. Alterations of the patellar cartilage are more frequent and more severe in women than in men. In 85.7 of the patellas they occupy both facets, overriding the patellar crest; more seldom, they are exclusively localized to the medial patellar facet (11.6 p. cent) or lateral facet (3.1 p. cent). Alterations of the trochlear cartilage, although more common are less frequent than that of the patellar cartilages. Patellar osteophytosis is very frequent.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Cartilage and collagenases].

The articular cartilage is frequently destroyed in rheumatic diseases. Among the various responsible factors, enzymes and especially collagenases play a leading role. Their action explains the collagen degradation linked with cartilage destruction. The author recalls the origin, mechanism of action of the articular collagenases and discusses their role in the articular cartilage degradation in rheumatic diseases.

Arthritis, Rheumatoid↗

Anti-inflammatory drugs, prostanoid and proteoglycan production by cultured bovine articular chondrocytes.

The effect of various anti-inflammatory drugs on the production of prostaglandins E2 and F2 alpha, 6 keto PGF1 alpha and thromboxane B2 by bovine articular chondrocytes was measured by radioimmunoassay. While indomethacin and meclofenamic acid caused a dose-dependent inhibition of all prostanoids measured, the effects of hydrocortisone and colchicine varied with respect to different prostanoids. Hydrocortisone (10(-7)M - 10(-13)M) both in the presence and absence of added arachidonic acid, resulted in an inhibition of prostaglandins E2 and F2 alpha, and to a lesser extent, 6 keto PGF 1 alpha, but TxB2 production was only slightly inhibited by the drug in the absence of arachidonic acid and markedly increased in its presence. Colchicine (10(-7)M-10(-3)M) had the opposite effect, causing an inhibition of TxB2 and stimulating PGE2 and 6 keto PGF1 alpha production. These findings suggest that certain anti-inflammatory drugs may, in addition to their action on phospholipase A2 and cyclo-oxygenases, exert potent effects at the level of the different synthetases. In order to see whether these alterations in relative prostanoid levels affected proteoglycan metabolism, the effect of anti-inflammatory drugs on proteoglycan synthesis by cultured chondrocytes was tested using 35SO4 labeling methodology. The results showed that at the concentrations tested (10(-5)M to 10(-7)M), indomethacin, dexamethasone, hydrocortisone and colchicine inhibited 35SO4 incorporation into newly synthesized proteoglycan molecules both in the presence (10(-6)M) and absence of exogenous arachidonic acid. In the same concentration range chloroquine had no effect. These results do not support the hypothesis of direct prostanoid involvement in the modulation of proteoglycan synthesis in articular cartilage.

6-Ketoprostaglandin F1 alpha↗