Klinička važnost VEGF-A i mikrožilne gustoće u difuznom limfomu velikih B-stanica i folikularnom limfomu niskog stupnja

Angiogenesis is essential for the development, growth and progression of tumors. Although vascular endothelial growth factor (VEGF) is a well-known proangiogenic factor, its impact on lymphoma has not yet been fully clarified. The aim of this study was to evaluate VEGF-A ­expression and microvessel density (MVD) in aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL), in indolent lymphomas such as low-grade follicular lymphoma (FL), and in lymph node reactive follicular hyperplasia (FH). In 80 prospective and retrospective cases (30 DLBCL, 30 FL and 20 FH), CD31 was analyzed by immunohistochemical staining assessing density of blood vessels, as well as the total number of CD31 positive endothelial cells. The results were compared with relevant clinical data. MVD was 85% in FH, followed by 60% in DLBCL and 43% in low-grade FL. VEGF-A was significantly higher in DLBCL than in low-grade FL and FH. A statistically significant association of MVD and VEGF-A with the International Prognostic Index (IPI) was found in DLBCL. High MVD and VEGF-A expression was observed in DLBCL patients with high IPI, while there was no statistically significant association between MVD and VEGF-A with the Follicular Lymphoma International Prognostic Index in low-grade FL. Our results suggested an important relationship between angiogenesis and high-grade lymphoma.Angiogeneza je bitna za razvoj, rast i progresiju tumora. Iako je vaskularni endotelni faktor rasta (VEGF) dobro poznati proangiogeni čimbenik, njegov utjecaj na limform nije u potpunosti razjašnjen. Cilj ovoga istraživanja bio je procijeniti izraženost VEGF-A i mikrožilnu gustoću (MVD) kod agresivnog limfoma kao što je difuzni limfom velikih B-stanica (DLBCL), kod indolentnih limfoma kao što je folikularni limfom niskog stupnja (FL) i kod reaktivne folikularne hiperplazije limfnih čvorova (FH). Analiza CD31 provedena je u 80 prospektivnih i retrospektivnih slučajeva (30 DLBCL, 30 FL i 20 FH) imunohistokemijskim bojenjem za procjenu gustoće krvnih žila, kao i ukupnog broja endotelnih stanica pozitivnih na CD31. Rezultati su uspoređeni s relevantnim kliničkim podacima. MVD je bila 85% kod FH, 60% kod DLBCL i 43% kod FL niskog stupnja. VEGF-A je bio značajno viši u DLBCL u odnosu na FL niskog stupnja i FH. Statistički značajna udruženost MVD i VEGF-A s Internacionalnim prognostičkim indeksom (IPI) utvrđena je kod DLBCL. Visoka izraženost MVD i VEGF-A zabilježena je u bolesnika s DLBCL s visokim IPI, dok nije bilo statistički značajne udruženosti MVD i VEGF-A s Internacionalnim prognostičkim indeksom za folikularni limfom kod FL niskog stupnja. Rezultati ovog istraživanja ukazuju na važan odnos između angiogeneze i limfoma visokog stupnja

Usporedba seronegativnog i seropozitivnog reumatoidnog artritisa u odnosu na izvjesne kliničke karakteristike

The aim of this study is to establish a scientific comparative analysis between seronegative and seropositive rheumatoid arthritis (RA), with regard to some clinical characteristics. The studied group consisted of RA seronegative patients with titters lower then 1:64 defined by Rose-Waaler test, while the control group consisted of RA seropositive patients with titters of 1:64 or higher. Examinees all belonged to the 2nd and 3rd functional classes according to ARA criteria, were between 25-60 years of age (Xb=49.96), with disease duration between 1-27 years (Xbox=6.41). In the disease onset most frequently affected joints were metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joint of the hands, almost equally represented with regard to sero-status and sex. During the examination seropositive patients showed a higher presence of inflamation of peripheral joints of hand and foot, but only the presence of PIP of the hands was statistically significant (χ2=15.63, p<0.01). Knees, talocrural joints and elbows were more frequently affected in seropositive patients, whereas humeroscapular, coxofemoral and sacroiliacal joints were more frequently affected in seronegative patients, but without significant statistical difference with regard to sero-status. The presence of affected PIP of the hands (χ2=9.96, p<0.01) and knees (χ2=4.17, p<0.05) with regard to sex was statistically significant in seropositive female patients, as well as the presence of atacked PIP of the hands (χ2=6.08, p<0.05), and cervical vertebrae (χ2=6.00, p<0.05) in seropositive male patients. There were some differences between groups with regard to sex in metatarsophalangeal joints (MTP), PIP of the foot, and other joints, but without any statistical significance. In both subsets statistically significant domination was found in affected second (χ2=20.85, p<0.01) and third (χ2= 15.70, p<0.01) fingers of the PIP level of hands and third finger (χ2=6.52, p<0.05) of the MCP level. The mentioned parameters did not show a significant statistical difference with regard to sero-status and sex. Majority of patients had 1-4 deformities. Seropositive group had prevalent knee contractures, e.g. the eversion of the foot, while seronegative group had more “swan neck” deformities. The mentioned parameters did not show a significant statistical difference with regard to sero-status and sex. Longer duration of the disease resulted in an increased number of deformities, and this difference was statistically significant (t=5.92, p<0.01). Linear correlation between these two parameters resulted as high positive in general (r=0.49, p<0.01) and for groups separately, but without significant statistical difference with regard to sero-status. Duration of the disease with regard to the type of deformities was different in both subsets: in case of the longer duration of the disease “buttonhole” was prevalent with statistically significant difference in seropositive patients (t=2.10, p<0.05), whereas “fibular deviation” was prevalent in seronegative patients (t=2.64, p<0.01).U našem istraživanju uspoređena je skupina seronegativnog i seropozitivnog reumatoidnog artritisa (RA) u odnosu na neke kliničke karakteristike. Ispitivana skupina je obuhvatila seronegativne bolesnike s titrom manjim od 1:64 određenim pomoću Waaler-Roseova testa, dok su kontrolnu činili seropozitivni bolesnici s titrom 1:64 ili višim. Svi ispitanici su pripadali II. i III. funkcionalnom razredu (ARA), bili životne dobi u rasponu 25-60 godina (Xb=49,96) s trajanjem bolesti 1-27 godina (Xb=6,41). U početku bolesti, najčešće zahvaćeni zglobovi su bili metakarpofalangealni (MCP) i proksimalni interfalangealni (PIP) zglobovi ruku, približno jednako zahvaćeni u odnosu na serološki status i spol. Tokom ispitivanja, seropozitivni bolesnici imali su znatno zahvaćenije periferne zglobove ruku i nogu, ali statistički značajno samo u slučaju rasprostranjenosti PIP ruku (χ2=15,63 p<0,01). Koljena, talokruralni zglobovi i laktovi su bili znatno više zahvaćeni u seropozitvnih bolesnika, dok humeroskapularni, koksofemoralni, sakroilijakalni i radiokarpalni zglobovi u seronegativnih, bez znatne statističke razlike u odnosu na serološki status. U odnosu na spol, relevantna statistička razlika je nađena u zahvaćenosti PIP ruku (χ2=9,96, p<0,01) i koljena (χ2=4,17, p<0,05) u seropozitivnih ženskih bolesnika, kao i kod zahvaćenosti PIP ruku (χ2=6,08, p<0,05) i cervikalnog dijela kralježnice (χ2=6,00, p<0,05) u seropozitivnih muških bolesnika. Kod metatarzofalangealnih (MTP) zglobova, PIP nogu, kao i kod drugih zglobova, nađene su određene razlike između skupina u pogledu spola, ali statistički neznačajne. U obje ispitivane skupine statistički značajno je bila zahvaćenost drugih (χ2=20,85, p<0,01) i trećih (χ2= 15,70, p<0,01) prstiju u razini PIP ruku, kao i trećeg prsta (χ2=6,52, p<0,05) u razini MCP, ali statistički neznačajno u odnosu na serološki status i spol. Veliki broj bolesnika je imao 1-4 deformiteta. U seropozitivnih bolesnika su dominirale kontrakture koljena, laktova, kao i everzija stopala, a u seronegativnih bolesnika deformiteti u obliku labuđeg vrata. Nisu nađene statistički relevantne razlike u odnosu na serološki status i spol. Broj deformiteta se povećao s povećanjem prosječnog trajanja bolesti i ova razlika je izražena sa znatnom statističkom razlikom (t=5,92, p<0,01). Izračunavanjem linearne korelacije između ovih dviju pojava, nađena je pozitivna i visoka korelacija (r=0,49, p<0,01) u cjelini i po skupinama, ali bez znatne statističke razlike u odnosu na serološki status. Trajanje bolesti u odnosu na vrstu deformiteta između skupina bilo je različito. Znatne statističke razlike su nađene za deformitet “bottonhole” s dužim trajanjem bolesti u seropozitvnih bolesnika (t=2,10, p<0,05), i za fibularnu devijaciju u seronegativnih bolesnika (t=2,64, p<0,01)

Usporedna analiza seronegativnog i seropozitivnog reumatoidnog artritisa u odnosu na neke epidemiološke i anamnestičke značajke

Classifying patients into two subsets of the disease - seronegative RA and seropositive RA - has been the subject of many studies which aim to clarify this phenomenon - without any conclusive or acceptable answer so far. The aim of this prospective study was to establish a scientific comparative analysis between seronegative and seropositive rheumatoid arthritis (RA) regarding some epidemiological and anamnestic characteristics. The studied group consisted of seronegative patients with titers lower than 1:64 as defined by Rose-Waaler test, while the control group consisted of seropositive patients with titers of 1:64 or higher. All patients belonged to 2nd and 3rd functional class according to the ARA criteria, were between 25-60 years of age (Xb=49,96), with disease duration between 1-27 years (Xb=6,41). Education, residence, economic and living conditions did not show any significant statistical difference regarding sero-status. Familial clustering of RA confirmed higher susceptibility in the seropositive group (χ2=7,02; p<0,01). In both subsets banal diseases, psychic and physical trauma, weakness, and numbness of hands and legs dominated, without any statistical difference regarding sero-status. Some differences between groups regarding sex were noticed, but were not statistically significant, except regarding physical trauma, which was more pre­sent in seronegative females (χ2=8,05; p<0,01).Klasifikacija bolesnika s reumatoidnim artritisom (RA) u dvije skupine - seronegativni RA i seropozitivni RA - predmet je mnogih dosadašnjih istraživanja. U ovome prospektivnom istraživanju provedena je usporedna analiza seronegativnog i seropozitivnog reu­matoidnog artritisa u odnosu na neke epidemiološke i anamnestičke karakteristike. Ispitivanu skupinu činili su bolesnici sa seronegativnim RA s titrom manjim od 1:64 određenim pomoću Waaler-Roseova testa, dok su kontrolnu skupinu činili bolesnici sa seropozitivnim RA s titrom 1:64 ili višim. Svi ispitanici su pripadali II. I III. funkcijskom razredu (ARA), bili su životne dobi između 25-60 godina (Xb=49,96) s trajanjem bolesti 1-27 godina (Xb=6,41). Edukacija, mjesto boravka, ekonomski i životni uvjeti nisu pokazali znatnu statističku razliku u odnosu na serološki status. U bliskih rođaka RA je bio češće prisutan u seropozitivnoj skupini (χ2=7,02; p<0,01). U obje skupine dominirale su tzv. banalne bolesti, psihičke i fizičke traume, malaksalost, ali bez istaknute statističke razlike u odnosu na serološki status. Nađene su određene razlike između skupina u pogledu spola, ali nisu bile statistički značajne, osim kod fizičkih trauma koje su bile češće prisutne u seronegativnih žena (χ2=8,05; p<0,01)

IMPACT OF MORNING STIFFNESS, EDUCATION, AND AGE ON THE FUNCTIONAL STATUS OF PATIENTS WITH RHEUMATOID ARTHRITIS

Svrha istraživanja bila je proučiti i usporediti odnos izmeđ funkcionalnog statusa i trajanja jutarnje zakočenosti u šakama s obzirom na dob, razinu obrazovanja i spol u bolesnika s reumatoidnim artritisom (RA). Istražena je povezanost tih čimbenika u odnosu na postojanje reumatoidnog faktora, odnosno serološki status. Ova retrospektivna studija provedena je u 250 bolesnika s klasičnim oblikom RA (186 žena, 64 muškarca). Ispitanici su bili u dobi između 25 i 60 godina, (x=49.96) s trajanjem bolesti od jedne do 27 godina (x =6.41) i nisu ispunjavali revidirane dijagnostičke kriterije ACR-a (American College of Rheumatology – 1987). Svi ispitanici pripadali su II. i III. funkcionalnom razredu prema Steinbrockerovoj klasifi kaciji. Odnos između funkcionalnih razreda i odabranih varijabli (trajanje jutarnje ukočenosti u rukama, spol, dob i stupanj obrazovanja) u odnosu na serostatus mjeren je point-biserijalnim koefi cijentom korelacije. Nađena je pozitivna, iako niska korelacija između trajanja jutarnje ukočenosti i funkcionalnih klasa [(r=0.10, y=0.00x 2.37, p> 0.05) seronegativni, (r=0.12, y=0.00x 2.30, p>0.05) seropozitivni]. Visoke pozitivne vrijednosti dobivene su pri određivanju koefi cijenta linearne korelacije između trajanja bolesti i funkcionalnih klasa (p<0.01). Također su visoke vrijednosti dobivene za koefi cijent korelacije između dobi i funkcionalnih klasa [(r=0.29, p<0.01) seronegativni, (r=0.47, p<0.01) seropozitivni]. Slabije obrazovani bolesnici bili su znatno više zastupljeni u III. funkcionalnom razredu [23 (50%) seronegativni, 19 (42.2%) seropozitivni] nego u II. funkcionalnom razredu [16 (20.3%) seronegativni, 22 (27.5%) seropozitivni]. Zaključno, prema ovoj studiji bolesnika s reumatoidnim artritisom dulje trajanje jutarnje zakočenosti bilo je povezano sa stupnjem funkcionalne nesposobnosti. Funkcionalna nesposobnost bila je povećana s trajanjem bolesti, ovisna o dobi i obrazovnoj razini te je izraženija u starijoj dobi, bez obzira na RA serološki status. U odnosu na serološki status i spol, razlike nisu znatne.Th e purpose of this study was to explore the relationship between disability status and duration of morning stiff ness in hands with regard to age, level of education, and gender in patients with rheumatoid arthritis (RA). Also, the authors wanted to investigate this relationship with regard to the presence of rheumatoid factor, i.e., the serological status. A retrospective study was conducted in 250 patients with the classic form of RA (186 females, 64 males, mean age Xb = 49.96 years, range 25-60 years, disease duration 1-27 years, Xb = 6.41) previously diagnosed with RA according to the ACR (American College of Rheumatology 1987 criteria). All patients were in Steinbrocker functional classes II and III. Th e probability level was expressed by p < 0.01 and p < 0.05. Th e relationship between the variables was measured by point-biserial correlation. Th e correlation between duration of morning stiff ness and functional class was positive but low [(r = 0.10, y = 0.00x + 2.37, p > 0.05) seronegative, (r = 0.12, y = 0.00x + 2.30, p > 0.05) seropositive]. High positive values were obtained for the linear correlation coeffi cient between duration of the disease and functional class (p < 0.01). Also, high values were obtained regarding the coeffi cient of correlation between age and functional class [(r = 0.29, p < 0.01) seronegative, (r = 0.47, p < 0.01) seropositive]. Uneducated patients were signifi cantly more represented in functional class III [23 (50%) seronegative, 19 (42.2%) seropositive] than in functional class II [16 (20.3%) seronegative, 22 (27.5%) seropositive]. In conclusion, in this study of patients with rheumatoid arthritis, increased duration of morning stiff ness was associated with functional disability. Functional disability increased with the duration of the disease, depended on age and educational level, and was more pronounced in older age, regardless of RA serological status. With regard to serological status and sex, the diff erences were non-signifi cant

Tijek i prognoza seropozitivnog i seronegativnog reumatoidnog artritisa

Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis (RA), diagnosed with negative rheumatoid factor (RF) tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis. The aim of the study was to establish a scientific comparative analysis between RA seronegative and seropositive, regarding course and prognoses of the disease. Two hundred fifty patients with rheumatoid arthritis according to the (American College of Rheumatology) criteria were retrospectively studied by analysis the course and prognoses of disease. All examinees were between 25-60 years of age (Xb=49.9, SD=10.3) with disease duration between 1-27 years (Xbox=6.41, SD=6.47). Course of the disease with “remissions and exacerbations”, progressive continual course and bad prognoses, were more presented in seropositive group of patients. Partial remission was more common in seronegative patients but according to serostatus and gender has not shown statistically significant difference. Duration of the disease was a specific prognostic sign for both subsets [(r=0.32, p0.05) seronegative, (r=0.18, p0,05) seronegativni, (r=0,18, p<0,05) seropozitivni]. Seropozitivni i seronegativni RA se razlikuju po pitanju karakteristika tijeka i prognoze, ali ne dovoljno da bi ih razlikovali kao dvije različite vrste iste bolesti. U odnosu na spol, osim izvjesnih izuzetaka, razlike nisu značajne