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Biomedical subjects

Hasan Yazici

Publications and source records attributed to Hasan Yazici.

At least 19 recordsLinked to original sources
PubMed2006

EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis.

OBJECTIVES: To develop the European League Against Rheumatism (EULAR) recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis. METHODS: An expert consensus group was formed consisting of rheumatologists, nephrologists and specialists in internal medicine representing five European countries and the USA, a clinical epidemiologist and representatives from regulatory agencies. Using an evidence-based and expert opinion-based approach in accordance with the standardised EULAR operating procedures, the group identified nine topics for a systematic literature search through a modified Delphi technique. On the basis of research questions posed by the group, recommendations were derived for conducting clinical studies and/or clinical trials in systemic vasculitis. RESULTS: Based on the results of the literature research, the expert committee concluded that sufficient evidence to formulate guidelines on conducting clinical trials was available only for anti-neutrophil cytoplasm antibody-associated vasculitides (AAV). It was therefore decided to focus the recommendations on these diseases. Recommendations for conducting clinical trials in AAV were elaborated and are presented in this summary document. It was decided to consider vasculitis-specific issues rather than general issues of trial methodology. The recommendations deal with the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant end points, and biomarkers. A number of aspects of trial methodology were deemed important for future research. CONCLUSIONS: On the basis of expert opinion, recommendations for conducting clinical trials in AAV were formulated. Furthermore, the expert committee identified a strong need for well-designed research in non-AAV systemic vasculitides.

Antibodies↗
PubMed2006

Characterization of the divergent wound-healing responses occurring in the pathergy reaction and normal healthy volunteers.

Behçet's disease (BD) is a multisystem inflammatory disorder of unknown etiology characterized by recurrent oral and genital ulcerations and uveitis, with varying other manifestations associated with vascular inflammation. A unifying feature of BD inflammation is the skin pathergy reaction (SPR), a nonspecific tissue hyperreactivity to minor trauma involving epithelial disruption. This study compared skin responses to needle prick in BD patients and normal healthy volunteers. Two study groups, each consisting of 10 BD patients with SPR(+) and 6 controls, were evaluated using either immunohistochemistry or quantitative real-time PCR to measure inflammatory cell and cytokine levels in biopsy specimens obtained serially from independent sites at 0, 8, and 48 h after needle prick. We found similar cellular infiltration patterns in response to needle prick in BD patients and controls between 0 and 8 h. Further development of this immune response was limited in skin of normal control subjects, with stable or decreased inflammatory mediators observed at 48 h. In contrast, in BD-derived skin specimens, increased influxes of mature dendritic cells, monocytes, and lymphocytes, including T regulatory cells, were noted by 48 h. Similarly, increases in cytokines (IFN-gamma, IL-12 p40, IL-15), chemokines (MIP3-alpha, IP-10, Mig, and iTac), and adhesion molecules (ICAM-1, VCAM-1) were noted at 48 h in the skin of BD patients with SPR(+) but not in the skin of normal controls. These results suggest that, in contrast to the self-limited inflammation associated with epithelial disruption of normal skin, BD patients experience marked cellular influxes into the injury site, leading to an exaggerated lymphoid Th1-type response.

Antigens, CD↗
PubMed2006

The frequency of scarring after genital ulcers in Behçet's syndrome: a prospective study.

BACKGROUND: Although genital ulceration with or without scar formation is an important manifestation of Behçet's syndrome, formal data on the rate of genital scarring are lacking. OBJECTIVE: To study prospectively the frequency of genital scar formation after genital ulcers in patients with Behçet's syndrome. Methods One hundred and two patients (72 males and 30 females) with fresh genital ulcers presenting at a dedicated Behçet's syndrome outpatient clinic were followed for 6 weeks. The ulcer location, size, and frequency of scar formation were noted. All patients were treated with similar topical therapy. RESULTS: Two hundred and ten genital ulcers were followed in both sexes. The rate of scar formation was 66.2% (102/154) in male patients and 60.7% (34/56) in female patients. When genital ulcers were stratified as a function of size, large genital ulcers (> or = 1 cm in diameter) developed scars more frequently than did smaller ulcers (< 1 cm). The rate of scar formation in male patients with large genital ulcers was 89.4% (59/66) and with small ulcers was 48.9% (43/88) (P < 0.001). In females, all 19 large ulcers healed with scarring, and the same was true for 40.5% (15/37) of the small ulcers (chi(2) = 18.61, P < 0.001). CONCLUSION About two-thirds of genital ulcers in Behçet's syndrome leave scars. The rate of scar formation depends on the ulcer size.

Adult↗
PubMed2005

Successful management of cryoglobulinemia-induced leukocytoclastic vasculitis with thalidomide in a patient with multiple myeloma.

Leukocytoclastic vasculitis (LV) is a systemic inflammatory disorder involving mostly the small vessels. It is characterised by segmental angiocentric neutrophilic inflammation, endothelial cell damage and fibrinoid necrosis. LV is related to a variety of clinical disorders including cryoglobulinemia and, very rarely, multiple myeloma (MM), among many others. The development of LV in patients with MM has been linked to cryoglobulinemia, infections, drugs and paraneoplasia. It has been speculated that myeloma patients with a poorer prognosis and progressive disease are more prone to develop LV. Thalidomide is a rediscovered old drug with anti-angiogenic, immunomodulatory and anti-inflammatory properties. It is highly effective in the treatment of MM and other clinical disorders such as leprosy, various cancers, graft-versus-host disease and autoimmune diseases. We report here a female patient with Durie-Salmon stage IIA MM who initially presented with cryoglobulinemia and LV. LV in this patient was primarily considered to be the result of progressive cryoglobulinemia, which was closely associated with MM. She was successfully managed with thalidomide and dexamethasone.

Cryoglobulinemia↗
PubMed2005

Short-term trial of etanercept in Behçet's disease: a double blind, placebo controlled study.

OBJECTIVE: To determine the effect of the tumor necrosis factor-alpha blocker etanercept on the pathergy and monosodium urate (MSU) status and on the mucocutaneous and articular manifestations of patients with Behçet's disease (BD). METHODS: Forty male patients with BD, all with positive pathergy and MSU tests and mucocutaneous disease and/or arthritis, were randomized (20 patients to each study arm) to receive either etanercept 25 mg twice a week or placebo for 4 weeks. The pathergy and MSU responses and the frequencies of mucocutaneous and articular manifestations were compared between the 2 groups. RESULTS: There were no decreases in the pathergy and MSU responses in the etanercept group compared to the placebo group at any time. The mean numbers of oral ulcers, nodular lesions, and papulopustular lesions were less in the etanercept group compared to the placebo group at all weekly evaluations, except for the second week for papulopustular lesions. The probability of being free of oral ulcers and nodular lesions was also significantly higher in the former group (log-rank chi-square = 9.83, p = 0.0017; log-rank chi-square = 14.17, p = 0.0002, respectively). CONCLUSION: Etanercept did not affect the pathergy reaction and the cutaneous response to MSU crystals. However, the drug was effective in suppressing most of the mucocutaneous manifestations of BD.

Adolescent↗
PubMed2004

Behçet syndrome.

PURPOSE OF REVIEW: Interest in Behçet syndrome (BS), although the condition is rare in many parts of the world, is increasing as judged by the growing number of related publications and scientific meetings. RECENT FINDINGS: Recent work reconfirmed the following without further insight into their meaning in pathogenesis: males have a more severe course; one third of the patients have a thrombophilia; papulopustular lesions and arthritis go together; gammadelta T are increased; and HLA B51 is still the main genetic association. Presence of increased levels of antibodies to Saccharomyces cerevisiae and the proposal of alpha-enolase as the target antigen of antiendothelial cell antibodies, known to be present also in BS, are observations that might help in delineating the unknown pathogenesis. For management, preliminary yet promising experience with the use of anti-tumor necrosis factor agents is being reported. SUMMARY When compared with 2 decades ago, we know considerably more and can do more about BS.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Behçet's syndrome: an update.

The pathogenic mechanisms in Behçet's syndrome are largely unknown. An autoantigen role for human leukocyte antigen B51 has been proposed. The reasons behind the thrombophilia are also not clear. Endothelial pathology could be the main culprit. The recently proposed association between familial Mediterranean fever and Behçet's syndrome might not be well founded. The long-term prognosis is more guarded among the young and among males. However, the disease burns out in many cases. Clinicians are getting better at management, and have better understanding of the old drugs, such as colchicine, and have new and potent drugs like tumor necrosis factor-alpha inhibitors.

Behcet Syndrome↗
PubMed2003

The long-term mortality and morbidity of Behçet syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center.

We surveyed the 20-year outcome of a cohort of patients with Behçet syndrome with emphasis on both mortality and morbidity. During 1999 and 2000, we collected outcome information on 387/428 (90.4%) of a cohort of patients (262 male, 125 female) who had registered in a dedicated outpatient clinic between July 1977 and December 1983. In 245/345 (71.0%) patients, outcome information was based on a formal hospital reevaluation, and in the remaining patients, on detailed telephone interviews. Forty-two patients (9.8%) (39 male, 3 female) had died, mainly due to major vessel disease and neurologic involvement. Mortality, as measured by standardized mortality ratios (SMR), was specifically increased among young males, among whom morbidity was also the highest. However, the SMR tended to decrease significantly with the passage of time. The same was also true for all mucocutaneous and articular manifestations. Both the onset of eye disease and its greatest damage were also usually within the first few years of disease onset. These suggest that the "disease burden" of Behçet syndrome is usually confined to the early years of its course, and in many patients the syndrome "burns out." However, central nervous system involvement and major vessel disease are exceptions. They can have their onset late (5-10 yr) during the disease course. As reflected in the mortality figures, the disease was less severe among the females for almost each disease manifestation. There were no female patients with arterial aneurysms. Severely impaired vision did not always mean an eventual loss of useful vision, and those patients with a late onset of eye disease had a better visual prognosis.

Adult↗
PubMed2002

Target organ associations in Turkish patients with Behçet's disease: a cross sectional study by exploratory factor analysis.

OBJECTIVE: To look for target organ associations in Turkish patients with Behçet's disease (BD). METHODS: We studied target organ associations in 272 consecutive patients with BD. The occurrence of any of the clinical manifestations related to BD within the previous 3 months was sought by history questionnaire completed by a rheumatologist and by physical examination. Factor analysis was used to analyze the data. RESULTS: Four factors were identified by factor analysis of variables oral and genital ulcers, erythema nodosum, papulopustular skin lesions, uveitis, superficial and deep vein thrombosis, joint, arterial, neurological, and gastrointestinal involvement; the 4 identified factors explained 69% of the original information of the matrix. There was an association between oral ulcers, genital ulcers, and erythema nodosum (Factor 1); and between superficial and deep vein thrombosis (Factor 2). Uveitis was identified as a distinct feature, and was negatively associated with erythema nodosum (Factor 3) only among the females. There was also an association between papulopustular skin lesions and joint involvement (Factor 4). Factors 2 and 3 had higher scores in males (p = 0.001 and p = 0.009, respectively) versus females. CONCLUSION: We studied clinical features of BD in Turkish patients. The 4 factors we identified by factor analysis differ from a previous study from Israel, probably due to different methodologies used in the 2 studies. One factor described in our study, the association between papulopustular lesions and arthritis, supports findings of our recent study. A recognized association between superficial and deep vein thrombosis was also confirmed.

Adult↗
PubMed2002

Interferon alfa combined with azathioprine for the uveitis of Behçet's disease: an open study.

BACKGROUND: Eye involvement is the main cause of morbidity in Behçet's syndrome. The efficacy of the combined use of azathioprine and interferon alfa in treating this condition has not been studied. METHODS: Ten male BD patients with retinal involvement but no irreversible structural changes were treated with azathioprine 2.5 mg/kg/day and IFN alpha 2b three times weekly for 24 weeks in an open trial. At week 24, IFN alpha was stopped and the patients continued to use azathioprine or received other immunosuppressives as indicated. Clinical response was assessed by visual acuity changes of either eye under the combination treatment and during the follow-up after stopping interferon. RESULTS: As compared to the study entry, the mean visual acuities of either eye increased significantly at the end of the combination treatment (right eye 5.8 +/- 1.26 vs. 8.3 1.14; P = 0.043; left eye 6.3 1.15 SEM vs. 9.1 +/- 0.9 SEM; P = 0.027). The improvement in visual acuity persisted in the nine patients who were followed for 7.2 +/- 1.6 SEM months after stopping interferon. Reversible hematologic toxicity, mostly in the form of leukopenia, was detected in six patients during the combination treatment. CONCLUSIONS: The combination of IFN alpha and azathioprine appears to be effective for eye involvement of BD. However, the frequent occurrence of myelosuppression mandates close monitoring.

Adult↗
PubMedDate not supplied

Headache in Behçet's syndrome.

OBJECTIVE: To study the frequencies and characteristics of different headache types seen in patients with Behçet's syndrome (BS) in a large cohort of patients. BACKGROUND: Patients with BS may present with different neurological problems, related either directly or indirectly to the disease, with headache being the most common neurological symptom seen in this syndrome, as well as independent from neurologic involvement. METHOD: This study was carried out at the multidisciplinary Behçet outpatient clinic of the Behçet's Syndrome Research Center. Every fifth admitted patient who had fulfilled the International Study Group for Behçet's Disease classification criteria was recruited for this study. Each patient was interviewed by one of the examining neurologists through a semistructured questionnaire. In case of the presence of more than one headache type, the best defined one was diagnosed and evaluated. All patients received a complete neurological and physical examination. A chi(2) test was used to evaluate the differences between frequencies. One sample t-test was used to compare means. The prevalence rates of primary headaches were compared with results of the Turkish Headache Epidemiology study by using goodness-of-fit test. RESULTS: Two hundred and twenty-eight patients were studied. Headache was reported in 66.2% (151/228) of the study cohort. Primary headaches were seen in 38.6% of the patient population, which corresponds to 58% of BS patients with any type of headache. Tension-type headache (TTHA) and migraine were seen in 23.6% and 14.9% of the whole study cohort, respectively. In 5.2% of the study cohort, the headache was associated with neurological involvement and in 3.9% to uveal inflammation. A predominantly frontal, bilateral paroxysmal throbbing pain of moderate severity was reported in 18.4% of the study cohort who did not fulfill the criteria of the International Headache Society (IHS) for any of the primary headaches. It was commonly associated with exacerbations of the mucocutaneous symptoms of the syndrome. The neurological examination was normal in all of these patients. This type of headache was categorized as the nonstructural headache of Behçet. CONCLUSION: Headache is the most common neurological symptom seen in BS, both in patients with and without neurological involvement. The results of our study reveal that headache is seen in a majority of patients with neurological involvement due to BS and in a minority with uveal inflammation. The prevalence of migraine and TTHA are close to the population in general, but a nonstructural migrainous headache, which is commonly associated with exacerbations with some of the systemic symptoms of the syndrome, is noteworthy in patients with BS. This form of headache is not specific for this disorder, but may be explained by a vascular headache triggered by the immunomediated disease activity in susceptible individuals.

Adult↗