Abundant expression of the interleukin (IL)23 subunit p19, but low levels of bioactive IL23 in the rheumatoid synovium: differential expression and Toll-like receptor-(TLR) dependent regulation of the IL23 subunits, p19 and p40, in rheumatoid arthritis.

OBJECTIVE: Interleukin (IL)23, composed of a p19 and a p40 subunit, is suggested to play key roles in rheumatoid arthritis (RA), dependent on the promotion and proliferation of IL17-producing T helper (Th)17 cells. However, previous studies on IL23 expression in human tissues were based on the p19 subunit only. We aimed to study the expression and regulation of IL23 subunits p19 and p40 in RA compared to patients with osteoarthritis (OA). METHODS: The expression of p19 and p40 in synovial tissues was analysed by in situ hybridisation and immunohistochemistry. IL23 in RA and OA synovial fluids and sera was determined by ELISA. Toll-like receptor (TLR)-dependent induction of p19, p40 and bioactive IL23 was determined in RA synovial fibroblasts (RASF), monocytes and monocyte-derived dendritic cells (MDDCs) by real-time PCR and reverse transcriptase (RT)-PCR, Western blot and functional assays. RESULTS: The p19 subunit was abundantly expressed in RA but not in OA synovial tissues. p19 was most prominently expressed by RASF in the synovial lining layer and at the site of invasion, but no heterodimeric IL23 was detected at these sites. Correspondingly, soluble IL23 was not detectable or found at very low levels in synovial fluids and sera of patients with RA. By in vitro experiments, we confirmed that TLR-activated RASF expressed p19 but not p40, in contrast to monocytes, which produced IL23 following TLR stimulation. CONCLUSION: The TLR-dependent induction of p19 but not p40 in RASF and the abundant expression of p19 along with the low or undetectable levels of IL23 in patients with RA provides strong evidence that p19 does not necessarily indicate the presence of IL23, as has been proposed to date.

Distribution and clinical significance of blood dendritic cells in children with juvenile idiopathic arthritis.

BACKGROUND: A role for dendritic cells (DC) in the development of adult rheumatoid arthritis has been suggested. To date, this problem has been poorly explored in juvenile idiopathic arthritis (JIA). OBJECTIVE: To analyse distribution and maturation status of blood DC (BDC) in JIA. METHODS: Absolute BDC counts were assessed by the "single platform" method in peripheral blood (PB) of 47 untreated children with JIA and 32 healthy controls. Moreover, BDC were investigated in JIA synovial fluid (SF). When the panel of monoclonal antibodies against BDC antigens (BDCA) was used, three BDC subpopulations were determined: myeloid type 1 (mDC1; BDCA-1+/HLA-DR+/CD19-), myeloid type 2 (mDC2; BDCA-3+/HLA-DR+/CD14-) and plasmacytoid (pDC; BDCA-2+/HLA-DR+/CD123+). RESULTS: A considerable deficiency of all subtypes of BDC was found in the PB of children with JIA. BDC counts in JIA SF were significantly higher than in PB both from children with JIA (p<0.001) and healthy children (p<0.001). SF BDC, especially mDC1 and mDC2 subtypes, had significantly higher expression of maturation markers (CD40, CD80, CD86 or CD83 antigens) than those from PB. A smaller number of PB BDC at diagnosis correlated significantly with poor response to treatment. CONCLUSIONS: A deficiency of BDC in PB is accompanied by enrichment of SF with those cells. Probably, circulating BDC migrate to joints where they undergo maturation and help to mediate and maintain the local immune response. Interestingly, the level of PD BDC deficiency seems to influence the outcome in children with JIA.

Regulation of peripheral blood and synovial fluid lymphocyte apoptosis in juvenile idiopathic arthritis.

OBJECTIVE: Complex regulatory mechanisms are involved in the induction of apoptosis. Their impairment may play a role in the pathogenesis of several autoimmune diseases. Recently, we have described higher incidences of spontaneous apoptosis of peripheral blood (PB) lymphocytes in children with juvenile idiopathic arthritis (JIA). This study aimed to evaluate the regulatory mechanisms that may be responsible for this phenomenon. METHODS: Thirty-four JIA children were examined and compared with 20 healthy children of similar ages. Expression of regulatory proteins p53, Bax and Bcl-2 in lymphocytes isolated from PB and synovial fluid (SF) was assessed. Serum and SF levels of interleukin-15 (IL-15) were also evaluated. RESULTS: The study showed significantly decreased Bcl-2 expression in JIA PB lymphocytes, compared to both healthy control (p = 0.03) and JIA SF lymphocytes (p = 0.005). There were no significant differences found in Bax expression between groups or compartments examined. However, the Bax/Bcl-2 ratio was nearly two-fold higher in PB lymphocytes than in SF of JIA patients (p = 0.001). p53 expression in PB lymphocytes from both JIA and control children did not statistically differ. In JIA, however, p53 was significantly higher in PB than SF lymphocytes (p = 0.016). IL-15 levels were about 20-fold higher in JIA SF than in serum from either JIA or healthy children (p < 0.0001). CONCLUSION: The results suggest that a higher incidence of apoptosis of PB lymphocytes observed in JIA may be associated with down-regulation of Bcl-2, rather than with changes in expression of Bax and p53. In contrast, the low p53 expression and elevated IL-15 appear to provide mechanisms responsible for suppression of apoptosis in SF cells from JIA patients.

Apoptosis of peripheral blood lymphocytes in patients with juvenile idiopathic arthritis.

BACKGROUND: Recent data suggested that abnormalities in mechanisms regulating apoptosis may have a role in the development of the rheumatoid process. OBJECTIVE: To evaluate different aspects of apoptosis in children with juvenile idiopathic arthritis (JIA). METHODS: The frequency of TUNEL positive peripheral blood (PB) lymphocytes (apoptotic index (AI)), as well as serum CD95 (APO1/Fas) antigen expression and serum levels of sFas and interleukin 15 (IL15), were examined in 44 cases of JIA. Results were correlated with type of onset, activity of JIA, and acute phase indicators. RESULTS: The AI of lymphocytes was significantly higher in patients with JIA than in controls (p=0.020). The mean AI of lymphocytes was increased in JIA with systemic type of onset and high activity (p=0.001). Moreover, IL15 levels in systemic disease were higher than in controls (p=0.012). An increased AI correlated with raised IL15 (p=0.046), erythrocyte sedimentation rate (p=0.005) and C reactive protein (CRP; p=0.017). Additionally, correlation was found between IL15 and CRP levels (p=0.039). CD95 and sFas levels were unchanged compared with controls. CONCLUSION: PB lymphocytes of children with JIA have an increased tendency to undergo apoptosis. The degree of apoptosis depends on the type of onset and activity of JIA and correlates with serum levels of IL15. Further studies are needed to explain whether this is an epiphenomenon of the disease activity or is related to the pathogenesis of JIA.

[Use of pedicled radial forearm flaps for covering of extensive soft tissue defects in the upper extremity]. / Zastosowanie uszypulowanych platów promieniowych w pokrywaniu rozleglych ubytków tkanek miekkich konczyn górnych.

Results of treatment of 13 patients with extensive defects of soft tissues in the upper extremities treated with pedicled radial forearm flaps are presented (11 fascio-cutaneous flaps and 2 adiposo-cutaneous). The group included 5 females and 8 males aged 9-85 years (mean age: 37 years). The defects followed trauma in 12 cases and in one case it was the result of oncological resection. The flap was used as a primary procedure in 4 cases after amputation of the finger or degloving of the hand. The flap appeared very useful in delayed reconstructions in older patients with extensive defects of soft tissues and bones, especially in the elbow region. Complete survival of all flaps with very good late results were obtained. Donor sites were covered with skin grafts and healed correctly in 11 patients. In two patients healing of the donor site prolonged in time for over 6 weeks. No other complications were observed using this method.

Activation of circulating platelets and platelet response to activating agents in children with cyanotic congenital heart disease: their relevance to palliative systemic-pulmonary shunt.

Abnormal platelet function has been hypothesised to play a role in the haemostatic abnormalities in cyanotic congenital heart disease (CCHD) patients. Using whole blood flow cytometry we found that platelets from cyanotic patients were hyperreactive and we related such hyperreactivity directly to young age, unoperated state, high haematocrit, reduced saturation with oxygen and low platelet count. Circulating platelets from CCHD children showed significantly enhanced P-selectin expression (P<0.004) and remained more reactive to 0.2 IU/ml thrombin, 1-8 microM TRAP and 2-4 microM ADP (P<0.04), especially in younger (0-3-year-olds) patients. Such a platelet 'priming' largely concerned CCHD children who were not subjected to modified Blalock-Taussig shunts in the past (non-MBTS). Only non-MBTS cyanotic children, but not MBTS-operated patients, showed significantly higher platelet reactivity compared to controls in response to ADP or 1 microM TRAP with respect to P-selectin expression (p<0.05) and in response to all examined agonists with respect to GPIb expression (P<0.045). The enhanced P-selection expression in MBTS-operated CCHD children and reduced GPIb expression in non-MBTS patients, especially in younger patients, were positively associated with the occurrence of the polymorphic variant Pl(A2) of platelet membrane glycoprotein IIIa gene. Altered blood morphology parameters (elevated RBC, Hb, Hct and MCHC, for all P<0.0005) in CCHD children correlated with the enhanced degranulation of circulating blood platelets and their hyperreactivity in response to some agonists (P<0.05). Overall, our data encourage the reasoning that circulating platelets are remarkably hyperreactive in non-MBTS cyanotic children, which are at higher risk to often encounter platelets activation in circulation. It seems unlikely that the apparently unchanged platelet reactivity in MBTS-operated children is due to the advantageous effects of the shunt, since these patients showed neither altered haematological parameters nor improved oxygen carrying capacity. Otherwise, it may rather result from more frequent episodes of platelet degranulation and preactivation in the past, and/or post-operative enhanced platelet consumption.

[The role of cyclooxygenase and prostaglandins in the pathogenesis of rheumatoid arthritis]. / Rola cyklooksygenaz oraz prostaglandyn w patogenezie reumatoidalnego zapalenia stawów.

Rheumatoid arthritis (RA) is a systemic inflammatory disease with polyarticular synovitis leading to formation of rheumatoid pannus and subsequent erosion of articular cartilage and bone. Prostaglandins (PGs)--a group of arachidonic acid metabolites found at elevated levels in synovial fluid and synovial membrane are considered to play a pivotal role in development of vasodilatation, fluid extravasation and pain in synovial tissues. Moreover, there is increasing evidence that PGs (especially prostaglandin E2) are mediators involved in complex interactions leading to development of erosions of articular cartilage and juxta-articular bone. Cyclooxygenase is an enzyme playing crucial role in PGs production. It is known that two forms of cyclooxygenase exist: cyclooxygenase-1 (COX-1) playing house-keeping functions and cyclooxygenase-2 (COX-2) involved in inflammatory responses. Synovial tissues from patients with RA are shown to contain COX-2 and to a less extent COX-1. COX-2 expression in rheumatoid synovium is induced by proinflammatory cytokines, mainly IL-1, while corticosteroids are capable of inhibiting COX-2 expression. The understanding of crucial role of COX-2 in synovial inflammation led to development of new group of anti-inflammatory agents--selective COX-2 inhibitors, that inhibit specifically COX-2, providing effective anti-inflammatory action without the side effects associated with inhibition of COX-1. In the context of widespread use of selective COX-2 inhibitors hypothetical role of COX-1 in RA pathology should be elucidated.

[Use of pedicled cutaneous groin flaps in distal reconstruction of the upper extremity]. / Zastosowanie uszypulowanego skórno-tluszczowego plata pachwinowego w rekonstrukcjach obwodowej czesci konczyny górnej.

In the years 1981-1997 at the Department of Plastic Surgery Medical Centre for Postsgraduate Education in Warsaw 116 patients were treated surgically using groin flaps and 97 patients using a pedicled cutaneous groin flap. This paper reports the results of the later technique. Reconstructions were performed in 10 female patients aged 18-58 (mean age 37.5 years) and 87 male patients aged 15-67 (mean age 33.8 years). The tissue defects or acquired deformations were caused by: crush injuries (26 cases), scalping injuries (23 cases), rugged injuries (18 cases), avulsion trauma (15 cases), explosion injuries (8 cases) and electric burns (7 cases). Flap size depended upon extent of the tissue defect and the from flaps were 7-26 cm long and 4-12 cm wide. Flap area ranged from 35 to 260 square centimetres. Emergency procedures were performed in 59 patients (61%). Secondary reconstructions were carried out in 38 cases (39%). Operative technique was based on the rules described by McGregor and Jackson. The donor site was sutured primarily tubulizing its basis--as in tube flap. The flap pedicle was cut off during a one stage procedure in 41 patients 21-30 days (mean 23 days) after surgery or during a two-stage procedure in 56 cases. The two-stage procedure consisted of an incision of part of the pedicle after 15-45 days post-op (mean 21 days) followed by a complete dissection after a few days (mean 4 days). In 44 cases the flap required modelling i.e. excision of excessives kin and/or thinning of subcutaneous tissue. The flap healed in 96 patients (99%). Complications at different stages of the treatment were observed in 40 patients (41%). In 3 cases wound ischemia was observed because of too tight suturing. Removal of skin sutures lead to normalization of blood supply. In 7 patients cyanotic skin of the distal part with no significant consequences was observed. In 27 patients (28%) necrosis of the marginal tissues surrounding the operation wound after cutting of the pedicle was noted. Besides supported necrectomy a conservative treatment was also applied by putting dressings soaked with antiseptics and 0.5% neomycine solution on a daily basis. This prolonged treatment by further several weeks. No significant complications were observed at the donor site.

[Evaluation of donor site morbidity after radial flap harvesting]. / Ocena miejsca dawczego po pobraniu plata promieniowego.

Donor sites of 58 radial forearm flaps in 56 patients were analysed and evaluated on the basis of documentation and follow-up examination. In 2 patients 2 radial flaps were harvested. There were 25 females and 31 males aged 9-85 (mean age: 35 years). 35 free flaps (31 on to feet, 2 on to tibial stumps and 2 on to contralateral forearm) and 4 pedicled flaps (on to the head) were transferred to distal body regions. Two of them included a part of the vascularized radius. The same upper extremity was covered with 19 pedicled radial forearm flaps (13 with retrograde blood flow). Six of them were osteo-fascio-cutaneous flaps. After harvesting 52 flaps (in 50 patients), the donor sites were covered with full or split thickness skin grafts. In 5 cases the donor sites were sutured, and in one case local V-Y plasty was used. In 11 cases the following complications were observed at the donor sites: delayed healing of the wound for more than 6 weeks in 4 cases;--chronic vascular insufficiency in 1 case;--dysesthesias on the dorsal part of the hand in 3 cases;--periodical pain and oedema of the hand in 2 cases;--unacceptable hypertrophic scar in 1 case. No acute ischemia of the hand, no fracture of the radial bone, and no neuroma of the sensory branch of the radial nerve were observed at the donor site.

Prenatal diagnosis of a fetal left atrial diverticulum.

Fetal echocardiography, performed on a 22-year-old woman at 31 weeks' gestation, revealed a diverticulum of the left atrium. The size of the diverticulum was similar to the size of the fetal heart in a four-chamber view. No evidence of congestive heart failure or changes in size of the diverticulum were observed on subsequent ultrasound examinations. The echocardiographic image suggested presence of a thrombus within the diverticulum. Echocardiography of the newborn confirmed the diagnosis, and surgical correction followed five days after the birth. Our approach to this problem is discussed here.

[Preliminary evaluation of the results of thumb replantation in the material of Plastic Surgery Clinic CMKP in Warsaw in 1983-1996]. / Ocena wczesnych wyników replantacji kciuków w materiale Kliniki Chirurgii Plastycznej CMKP w Warszawie w latach 1983-1996.

Forty-four patients underwent thumb replantation (after complete amputation) at Department of Plastic Surgery, Medical Center for Postgraduate Education at Warsaw between 1983 and 1996. There were 41 males and 3 females aged 13-58 years (mean 29 years). In 16 patients other fingers were also amputated. Circular saw wounds prevailed (27 patients--61%). Replantation time ranged from 3 hours to almost 12 hours (mean 6.5 h). In 38 cases (86%) the replanted thumb survived. Half of the failures occurred before 1988. In all types of amputation including avulsion good results were achieved with reversed vein grafts and vessels rerouting from the index finger (from among 7 avulsed thumbs 6 survived). Surgical technique modification according to the injury type has been discussed.

[Meigs syndrome--diagnostic difficulties]. / Zespól meigsa--trudnosci diagnostyczne.

Meigs' syndrome in 68 years woman with pleural effusion and ovarian tumour was described. The cause of the pleural liquid in Meigs' syndrome is still not clear. New views on the pathogenesis and diagnostic methods of pleural liquids causes were presented.

[Acute and subacute autonomic neuropathy]. / Ostra i podostra neuropatia autonomiczna.

Acute and subacute autonomic neuropathies are rarely observed disease syndromes. Their symptoms result from the involvement of autonomic cholinergic fibres (cholinergic dys-autonomy) as well as cholinergic and noradrenergic ones (pan-dys-autonomy). The paper presents symptoms of both forms of the disease and methods of their diagnostics. Up-to-date trials of the treatment of orthostatic hypotonia a leading symptom of pan-dys-autonomy, have also been discussed.

[Effect of adrenergic drugs and exploitation on sexual reflexes and semen properties in Polish large white boars aged 2-3 years]. / Wplyw leków ukladu adrenargicznego i eksploatacji na odruchy plciowe i wlasciwosci nasienia knurów rasy wbp w wieku 2-3 lat.

The effect of exploitation and adrenergic system drugs on sexual reflexes and properties of the semen in somatically mature Polish Large White boars has been presented. At the first stage 8 males were exploited twice a week. Then, previous to semen collection, the animals were given beta-adrenolytic (Propranolol--Polfa), after 30 minutes followed by the preparation Levonor--Polfa (alpha-adrenomimetic). 15 minutes after last injection the semen was collected, this procedure having been repeated twice a week. At the second stage of the experiment the same males were exploited once a week. Like in the first stage, the animals were given the same doses of the drugs in the same sequence. 15 minutes after last injection the semen was collected once a week. At the third stage of the experiment the boars were exploited every day. Again, like in the previous stages, the animals were given the above mentioned beta-adrenolytic and alpha-adrenomimetic to collect the semen 15 minutes after last injection. In all the stages of the experiment 6-8 ejaculates were collected from each boar. Apart from preliminary assessment of concentration and morphology of spermatozoons there was determined the level of protein and activity of selected enzymes in the semen. The sexual drive as well as the time of searching reflex and ejaculation were observed. The drugs applied have been proved to be able to prolong the time of ejaculation reflex. Simultaneous application of beta-adrenolytic and alpha-adrenomimetic to animals exploited twice a week appeared to increase the number of spermatozoons in the whole ejaculate, the percentage of spermatozoons with proper movement and the activity of GGT and fucosidase. Intensive exploitation of a boar with parallel application of the preparations described bring about a gradual decrease in spermatozoons and protein in the ejaculate as well as in the activity of hyaluronidase in its plasma and in conversion to mg protein of semen plasma.

The effect of the cingulate cortex on the development of the frontal lobe in the human.

In the study, measurements of cortical structures of the medial surfaces of cerebral hemispheres of adults were taken. Its aim was to test whether the examined values were correlated with one another, and if so, then to what degree. Studies were conducted on 100 brains of adult people. It was assumed that the span of the corpus callosum (the genual retrosplenial length) of the left and the right hemisphere of the given brain was constant. The results of measurements and their statistical analysis prove that in both hemispheres the parameters concerning the cingulate gyrus, mainly of its paragenual width, are situated within the limits of significance. The mean values of the length of this gyrus were bigger on the left hemisphere. Differences in size of the hemispheres appeared to be statistically insignificant. The mean arithmetic values of the fronto-occipital distance of the hemispheres were greater for the right hemisphere. The results suggest that certain changes in the values of the frontal lobes depend on changes in values concerning the cingulate gyrus. This fact may confirm suggestions of certain authors that limbic structures of man, encompassing also the cortex of the cingulate gyrus, are not retarded and that their effect on the development of the frontal lobes may be as considerable as the one of the gyri.