On fluoroquinolones treatment safety in children (clinical, morphological and catamnesis data)]

Results of prospective comparative investigation of monofluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin) arthropathy are presented. The trial was performed at 144 children with mucoviscidosis (aged 0.5-16) and at 37 children with aplastic anemia (aged 1.75-15). Two groups differ by necessary antibacterials regimes and hence by different abilities for arthropathy development: patients with mucoviscidosis were treated with fluoroquinolones followed by repeated short courses in combination with other antibacterials; patients with aplastic anemia--were treated permanently for a long time with low doses as monotherapy for autoinfection prophylaxis. Analysis was performed on the base of catamnesis, year growth rate, postmortal morphological investigation of the right knee joint. It was shown that quinolone arthropathy development didn't depend on treatment duration, as it developed during the first three weeks of the fluoroquinolone use, but depended on the drug, patient age and nosology. Arthropathy has favourable prognosis and was fully resolved at the period from 7 days to 3 month according to the arthropathy form (arthrologic, arthritic). Quinolones arthropathy at the children has specific features, the main one is absence of cartilage damage confirmed by morphological analysis.     

Fluorine level in the bone and cartilage in children treated with ciprofloxacin (data obtained from the femur distal part]

Comparative data on the content of fluorine in various sections of the left femur distal part, i.e. spongy bone, process zone and articular cartilage are presented. The examination was performed on postmortem sections from 10 pediatric cases (the average age of 9.5 years) with mucoviscidosis or aplastic anemia treated before the death for up to 12 months with ciprofloxacin in a dose of 20 to 40 mg/kg body weight. The control postmortem sections were from 10 practically healthy children (the average age of 10.4 years) killed in a car accident. The sections were subjected to 2-stage dry ashing with ionometric determination of the fluorine ions. The results were treated according to the V.Yu. Urbach procedure. It was shown that the content of fluorine in the sponge bone and process zone in both the groups did not significantly differ. A comparatively high content of fluorine was detected only in the postmortem sections of the articular cartilage from the children of the main group who however had no chondrotoxic symptoms while alive. That means that the difference is statistically and clinically insignificant.     

Evaluation of tolerance and efficacy of pefloxacin in the treatment and prevention of severe infections in children with mucoviscidosis and aplastic anemia]

Pefloxacin (Abaktal) efficacy and safety were investigated at 21 children (7-16 years old) randomized in 2 groups: children with mucoviscidosis and children with aplastic anemia. The drug was used at the dose 15-20 mg/kg per day bid for 14-28 days. Pefloxacin was used in combination with ceftazidime and amikacin. Combined therapy demonstrated good clinical efficacy. Bacteriological efficacy was not uniform: staphylococci were not isolated from sputum since the 7th day of treatment, but pseudomonads were cultured even on the 14th day of the treatment (the sensitivity to pefloxacin remained). The only but frequent side-effect was arthropathy. The background and some peculiarities of arthropathy development were analyzed. This phenomenon is called quinolone-induced synovitis. The risk group for quinolone-induced synovitis was estimated--children elder than 10 years with allergic anamnesis. Good clinical efficacy and tolerability of pefloxacin at the children with mucoviscidosis or aplastic anemia is a reason and base to cancel the limits to its use in pediatrics.     

Comparative yearly growth rate of children with mucoviscidosis treated and not treated with ciprofloxacin:clinicomorphological comparisons]

The results of the prospective and comparative investigation of the linear growth of children at the age of 4 to 16 years with mucoviscidosis treated with ciprofloxacin in combination with a cephalosporin or an aminoglycoside in the main group and a cephalosporin or an aminoglycoside alone in the control group are presented. The children were observed for 3 and 5 years. It was shown that in spite of the treatment term with ciprofloxacin the yearly growth rate in the children in the main and control groups did not significantly differ. The morphological investigation did not reveal any injury of the armicular cartilage and growth zone. The hyperplastic reaction in the tegmental cartilage was states and considered as a physiological one in response to the presence of ciprofloxacin and therefore reversible. No chondrotoxicity of the fluoroquinolones and ciprofloxacin, particularly in the children, is explained.     

Activities of dipeptidyl peptidase II, dipeptidyl peptidase IV, prolyl endopeptidase, and collagenase-like peptidase in synovial membrane from patients with rheumatoid arthritis and osteoarthritis.

We examined the activities of peptidases in the synovial membrane from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Dipeptidyl peptidase II (DPP II), prolyl endopeptidase (PEP), and collagenase-like peptidase (CLP) activities were higher in knee joint synovial membrane from patients with RA than in that from patients with OA. DPP II and PEP activities in knee joint synovial membrane of patients with RA increased in parallel with the increase in joint fluid volume, whereas DPP IV activity decreased in parallel with the increase in joint fluid volume. These results suggest that these peptidases in the synovial membrane may play some role in immunological disturbances in the joints of patients with RA. Measurement of these peptidases in synovial membrane may be useful in the diagnosis of the severity of local joint inflammation.     

Proteomic analysis of recurrent joint inflammation in juvenile idiopathic arthritis

The synovial fluid proteome in juvenile idiopathic arthritis was investigated to isolate joint-specific biomarkers that are expressed in patients displaying recurrent joint inflammation. To identify the synovial specific proteome, matched synovial fluid and plasma samples were subjected to protein separation by 2-dimension electrophoresis (2DE). Forty-three protein spots, overexpressed in the joint, were identified. Synovial fluids from children with single-event knee joint inflammation were then compared with a group with recurrent knee disease. Nine synovial specific proteins were significantly differentially expressed in the recurrent group. Proteolytic fragments of collagen X, fibrin beta-chain, and T-cell receptor alpha-region have been identified among this protein cluster. Putative biomarkers, overexpressed in the joint and differentially expressed in children with recurrent joint inflammation, have been identified. These proteins may play a significant role determining the pathological state within the chronically inflamed joint and influence disease progression in JIA. This is the first study of the synovial proteome in children.     

Preparation of rat synovial membrane for studies of cytokine secretion

The objective of this work was to devise an in vitro system for studies on cytokine secretion by synovial membrane treated as a whole organ with various synoviocyte populations. Synovial membrane from knee joints of WAG rats was dissected and incubated in culture medium without serum for 4 - 48 h. The level of IL-1alpha was determined in synovial lysates and IL-6 in culture medium. The synovial membrane from left and right knee joint of the same rat produced similar amount of cytokines both in lysates and in the medium. Synovial membrane stimulated by LPS for 4 or 24 h gave significantly stronger cytokine response than the membrane from the opposite (control) knee. After 48 h incubation of synovial membrane drastic drop in cytokine level was noted, which indicated on deterioration of the membranes. The test may be useful in studies on factors affecting cytokine secretion by synoviocytes.     

gamma-Aminobutyric acid in synovial membrane of rat knee joint

gamma-Aminobutyric acid (GABA) content was measured, and the release of GABA was studied in the synovial membrane of the rat knee joint. GABA content of the synovial membrane was 20.1 nmol/g tissue. Ten days after unilateral dissection of the sciatic nerve, femoral nerve or both nerves, the GABA contents of the ipsilateral membrane were 13.8, 14.6 and 7.8 nmol/g tissue, respectively. High K+ evoked the Ca2+-dependent release of [3H] GABA from the synovial membranes of intact rats preloaded with [3H] GABA, but did not evoke release from the membrane ipsilateral to the dissection of both sciatic and femoral nerves. Evoked release of [3H] GABA was obtained in the synovial membrane preloaded with [3H] GABA in the presence of beta-alanine, but not in the presence of 2,4-L-diaminobutyric acid. These results indicate that GABA is present in the neuronal elements of the synovial membrane of the rat knee joint.     

The efficacy and safety of ciprofloxacin in treating children with mucoviscidosis]

Ciprofloxacin clinical and bacteriological efficacies, as well as tolerability mainly with respect to chondrotoxicity were evaluated in the treatment of children with mucoviscidosis. The drug was shown to have high clinical and moderate bacteriological efficacies. As for its tolerability, adverse reactions chiefly associated with affection of the gastrointestinal tract, i.e. nausea, stomach pain, diarrhea, increased transaminase levels were recorded. The arthrotoxicity episode was single and transitory. The use of ciprofloxacin had no negative effect on the children growth. No chondrotoxic effect of ciprofloxacin in the treatment of children was observed which is explained in the paper. It is concluded that ciprofloxacin is in general an efficient and safe antibiotic useful for the treatment of children.     

Laboratory and sonographic findings in dialyzed patients with bilateral chronic knee pain versus dialyzed asymptomatic patients

The aim of this study is to evaluate connection of plasma level of beta2-microglobulin, C-reactive protein and uric acid as well as sonographic parameters like thickness of synovial membrane, thickness of femoral condylar cartilage and presence of joint effusion and Baker's cysts with bilateral knee pain in dialyzed patients, comparing them with parameters in asymptomatic dialyzed patients. Plasma levels of beta2-microglobulin and C-reactive protein were significantly higher in symptomatic patients while uric acid level showed no difference among the groups. In symptomatic patients synovial membrane was thicker and in those patients there were more knee effusions and Baker's cysts. Thickness of femoral condylar cartilage showed no difference between groups. That suggests that inflammatory mechanisms developing from beta2-microglobulin accumulation could be important factor in bilateral knee pain in dialyzed patients even in shorter duration dialysis.     

Unstable Stifles without Clinical or Radiographic Osteoarthritis in Young Goats: An Experimental Study

Thirteen young, castrated male goats had instability of one stifle (knee joint) created by surgical transection of the cranial cruciate ligament, but did not develop any signs of osteoarthritis (OA) in treated joints when confined in limited space for 8 months. At the end of the experiment, the instability in the stifles had not improved, the joints were normal at radiographic examination, there were no signs of inflammation in the synovial membrane or joint capsule, and fibrosis in these tissues was not evident. The articular cartilage was normal both visually and histologically. This may indicate that the young age of the goats and the restricted physical activity on soft floor had prevented the expected development of OA in the experimantally operated joints. Synovial fluid volumes and proteoglycan concentration were measured in the treated and control joints in 6 of the goats. There seemed to be increased quantity of the proteoglycan aggrecan in the synovial fluid from the treated joints compared to the contralateral joints throughout the course of this study. It was concluded that the turnover of aggrecan in the articular cartilage of the treated joints may have been increased.     

Development and morphology of rat synovial membrane

The development of the knee joint and synovial membrane in Wistar rats was studied from the 13th fetal day until adulthood by means of light microscopy, transmission electron microscopy and scanning electron microscopy. Using acid phosphatase and peroxidase methods, the different cell types of synovial membrane could be identified.     

Ultrastructural changes in the synovial membrane in experimentally-induced osteoarthritis of rabbit knee joint.

Rabbit knee joint osteoarthritis was induced by intraarticular injections of a 10% sterile NaCl solution. Within 30 days the synovial membrane had undergone hyperplasia resulting in activated synovial fibroblasts. Transitional forms of synoviocytes as well as activated synovial macrophages were a very common finding. At 60 days a thickening of the synovial intima was perceptible. Most of the synoviocytes were of the fibroblast type. Transitional cell forms abounded. An increase in collagen fibres and capillaries of the fenestrated type occurred in the intercellular spaces. In the deep layer collagen bundles had formed between which activated fibroblasts and macrophages were noticed. The described changes point to an active participation of the synovial membrane in the destruction of articular cartilage in osteoarthritis.     

Arteriolo-venular anastomoses in the synovial membrane of the knee joint

The arteriolo-venular anastomoses (AVA) in the synovial membrane of the knee joint of fetuses (40), corpses of persons at various age (120) and dogs (30) have been studied by means of the impregnation method after V. V. Kupriyanov. In the synovial membrane shunts and semishunts are revealed. The AVA localize in composition of the deep vascular network of the synovial membrane. They are dynamic structures. The occurrence of their disclosure and their structure depend on the age factor.     

膝骨关节炎患者关节液和滑膜中IL-6、MMP-13、VEGF的表达及与病情进展的关系

目的:研究膝骨关节炎(KOA)患者关节液和滑膜中白细胞介素-6(IL-6)、基质金属蛋白酶-13(MMP-13)、血管内皮生长因子(VEGF)的表达及与病情进展的关系。方法:选择自2017年1月到2017年6月在我院就诊的KOA患者30例进行研究,其中维吾尔族和汉族各15例,分别记为维吾尔族组和汉族组。另选同期在我院接受骨折修复和截肢等手术治疗的10例无骨关节炎的患者作为对照组。对比各组IL-6、MMP-13及VEGF水平以及关节软骨中水通道蛋白3(AQP3)阳性表达率,对比维吾尔族组和汉族组软骨不同区域内AQP3阳性表达,分析KOA患者关节液和滑膜中IL-6、MMP-13、VEGF及关节软骨中AQP3的阳性表达与病情进展的相关性。结果:维吾尔族组和汉族组关节液和滑膜中IL-6、MMP-13及VEGF水平均分别高于对照组,差异均有统计学意义(均P0.05)。维吾尔族组和汉族组关节软骨中AQP3阳性表达率均分别明显高于对照组,且维吾尔族组明显高于汉族组,差异均有统计学意义(均P0.05)。维吾尔族组和汉族组浅层软骨磨损严重区的AQP3阳性表达率明显高于软骨深层区和软骨下骨区,差异均有统计学意义(均P0.05)。Spearman相关性分析显示,KOA患者关节液和滑膜中IL-6、MMP-13、VEGF及关节软骨中AQP3的阳性表达与病情进展均呈正相关(均P0.05)。结论:KOA患者关节液和滑膜中IL-6、MMP-13、VEGF水平及关节软骨中AQP3阳性表达均异常升高,以上指标参与了病情的进展,且AQP3阳性表达高低还与民族有关,临床上可考虑将这些指标作为监测KOA患者病情的靶点。     

Bone marrow transplantation for leukemia and aplastic anemia: management of ABO incompatibility.

Between February 1971 and October 1980, 34 patients with leukemia or aplastic anemia received bone marrow transplants from HLA-identical siblings whose lymphocytes did not react in a mixed leukocyte culture. The donors of 10 patients were ABO-incompatible, and for five pairs the ABO incompatibility was major. Plasma exchanges followed by a red blood cell exchange transfusion reduced the anti-A titres to 1:4 or less in these patients. The ABO incompatibility had no adverse effect on the results of marrow transplantation. Twenty-two patients, including 16 of the 20 who received their transplant after Jan. 1, 1980, are still living. Seven of the 15 patients with acute leukemia have survived 89 to 466 days, and 4 of the 6 with chronic myelogenous leukemia (CML) have survived 117 to 545 days. Of the 13 patients with aplastic anemia, 11 are alive up to 8 years after transplantation. Marrow transplantation, when possible, is the treatment of choice for young patients with acute leukemia in remission and for patients with aplastic anemia. Marrow transplantation may also prove to be effective in patients with CML.     

Comparative assessment of articular cartilage and synovial membrane in experimental haemarthrosis

The changes in articular cartilage and synovial membrane of the knee joints were studied in two groups of rabbits and Wistar rats with experimental haemarthrosis, electron microscopically. Hamarthrosis was produced in group 1 by a single autologous blood injection, in group 2 by intraarticular fracture of the femoral condyles. Samples were taken from the intact articular cartilage, the menisci and the infrapatellar portion of the synovial membrane 12 h to 20 days after intervention. Blood resorption occurs only in the synovial membrane. Fragmentation of erythrocytes and erythrocytophagy by synovial macrophages is documented. The different stages of intracellular digestion of erythrocyte fragments are traced down. Synovial fibroblasts do not participate in erythrocytophagy, although they disclose morphological signs of enhanced functional activity. The findings show changes in the matrix and chondrocytes within the articular cartilage and menisci, and presence of free erythrocytes and lipoprotein complexes amidst the collagen fibres of the matrix. The chondrocytes are poor in cell organelles, while the intracytoplasmic filaments, lipid droplets and glycogen granules are augmented in number. There is no evidence of erythrocytophagy by cartilage cells. On single blood injection in the joint, the ensuing changes are reversible, and the normal synovial membrane structure is restored much quicker than the articular cartilage.     

T-lymphocyte subpopulations in the peripheral blood and bone marrow of patients with aplastic anemia

A decrease in the absolute number of total lymphocytes, OKT3+ and OKT4+ lymphocytes, and a normal number of OKT8+ lymphocytes were found in the peripheral blood of patients with aplastic anemia. The OKT4:OKT8 ratio was decreased in patients due to a reduction in the percentage of OKT4+ cells and 3 out of 18 patients had a ratio less than 1. The values of the OKT4:OKT8 ratio were not associated either with the severity of the disease or with treatment with androgens. There was no correlation between the OKT4:OKT8 ratio and the number of transfusions received by patients. On the other hand, studies performed with bone marrow lymphocytes showed that the OKT4:OKT8 ratio for both patients and controls was lower than that of the peripheral blood. Since the ratio of OKT4:OKT8 cells in aplastic and control bone marrow was similar no direct pathogenic role can be assigned to the marrow for the imbalance detected in the peripheral blood.     

Rational use of antibiotics in mucoviscidosis pediatric cases with an account of local microbiological monitoring]

The results of local microbiological monitoring of bronchial secretion in 482 children with mucoviscidosis observed within 2000-2004 in the Republican Centre of Mucoviscidosis are presented. The results provided development of recommendations for rational use of antibiotics in the treatment of infectious processes in pediatric patients with mucoviscidosis. Since the emergence of MRSA in such patients is low, it is recommended to use antistaphylococcal betalactams (oxacillin, cefazolin, amoxycillin/clavulanate) for the treatment of infections due to S. aureus. For the treatment of infections due to some other pathogens, except S. maltophilia, the most active betalactams were carbapenems (imipenem and meropenem). Ciprofloxacin was active against numerous etiological agents causing low respiratory tract infections in children with mucoviscidosis except S. maltophila and A. xylosoxidans subsp. xylosoxidans. For the treatment of infections due to P. aeruginosa, P. aeruginosa muc. and K. pneumoniae the most active aminoglycosides were amikacin and tobramycin (for P. aeruginosa and P. aeruginosa muc.), while gentamicin was not active in such cases. As for antibiotics of other groups, high activity against S. aureus in the treatment of children with mucoviscidosis was recarded with the use of vancomycin, fusidic acid and rifampicin. Azithromycin and co-trimoxazole were active against H. influenzae. Chloramphenicol was active against S. maltophilia, B. cepacia and H. influenzae in the treatment of such patients.