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Mean platelet volume (MPV) as an inflammatory marker in ankylosing spondylitis and rheumatoid arthritis

AIMSnThe aim of this retrospective study was to investigate the correlation between MPV and the clinical disease activity indices of rheumatoid arthritis and ankylosing spondylitis.nnnMETHODSnThe study consisted of 32 active RA patients (males/females: 7/25, mean age: 49+/-13) and 30 active AS patients (males/females: 15/15, mean age: 36+/-12) along with 26 osteoarthritis (OA) patients (males/females: 4/22, mean age: 52+/-8) and 29 age-matched healthy subjects (males/females: 5/24, mean age: 41+/-7) as control groups for RA and AS, respectively.nnnRESULTSnMPV was significantly lower in both AS patients and RA patients with active disease as compared to controls (RA vs OA p<0.001, AS vs healthy subjects p<0.001). After treatment MPV values significantly increased in AS and RA (p<0.001 for all). However, MPV values remained somewhat lower in RA patients than OA patients (p=0.019). There was a negative correlation between MPV values and BASDAI scores in AS patients after two months of treatment (r=-0.507; p=0.004).nnnCONCLUSIONnOur results suggest that assessment of MPV may provide additional information about inflammation in AS and RA.

Frequency of Lymphadenopathy in Rheumatoid Arthritis and Systemic Lupus Erythematosus

This study aimed to assess the frequency of all palpable lymph nodes during active disease and remission in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Hospital records of 100 SLE patients, 100 RA patients, 100 spondyloarthropathy patients, and 150 osteoarthritis patients, treated in our rheumatology department, were evaluated retrospectively. Overall frequencies of enlarged lymph nodes in patients with active RA and SLE were 82% and 69%, respectively. Enlarged lymph nodes associated with RA were mostly located in the axillary region, and in SLE the nodes were smaller and lymphadenopathy was more generalized compared with RA. Palpable lymph nodes disappeared in the majority of patients during remission. Lymphadenopathy was significantly less frequent in patients treated with steroids before admission. Lymph node enlargement is an important physical finding associated with RA and SLE disease activity. Atypical locations and unusually large lymph nodes should raise clinical suspicion of another underlying disease.

The efficacy of oral cyclophosphamide plus prednisolone in early diffuse systemic sclerosis

Pharmacological treatment of diffuse systemic sclerosis (SSc) directed at the tissue fibrosis has generally been ineffective. Many immunosuppressive drugs have been tried as therapy for SSc, regardless of the disease subtype and/or stage. The aim of this study was to show the efficacy and the toxicity of oral cyclophosphamide and prednisolone therapy on the prevention of fibrosis-based tissue damage in the early stages of the diffuse SSc. Twenty-seven patients with early diffuse SSc were treated with oral cyclophosphamide (1–2 mg/kg/day) plus oral prednisolone (40 mg/every other day) between the years 1995 and 1998. The results regarding the efficacy and toxicity of cyclophosphamide were compared with those of 22 early SSc patients who had been treated with oral D-penicillamine between 1992 and 1995. All the patients were evaluated using clinical and laboratory parameters every 6 months for 2 years. There was a significant improvement on the skin score, maximal oral opening, flexion index, predicted forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) in the cyclophosphamide group. The decrease in skin score in the cyclophosphamide group started earlier than in the D-penicillamine group. No life-threatening or irreversible adverse reaction was observed. This open study supports the use of oral cyclophosphamide plus prednisolone therapy to prevent fibrosis and its complications in the early stages of diffuse SSc.

Thrombopoietin inside the pulmonary vessels in patients with and without pulmonary hypertension.

There is substantial evidence that platelet production and release take place in the lungs. Thrombopoietin (Tpo) stimulation can cause platelet release in the pulmonary vasculature. On the other hand, myelofibrosis can occur in Tpo-overexpressing transgenic mice models, and there is unexplained pulmonary hypertension in chronic myeloproliferative disorders including primary myelofibrosis. In this study, we aimed to assess local Tpo concentrations inside the pulmonary artery and associated vessels in humans. We measured Tpo concentrations in plasma samples taken concurrently from the right ventricle, the pulmonary artery, and the left ventricle during cardiac catheterization in patients with and without pulmonary hypertension. The study group comprised 10 patients with normal pulmonary arterial pressure (Group A, male/female 4/6, mean age 48 +/- 19) and 14 patients with pulmonary hypertension (Group B, male/female 9/5, mean age 57 +/- 16). The Tpo levels inside the right ventricle, the pulmonary artery and the left ventricle were 33.3 +/- 15.6, 47.2 +/- 33.9, and 34.4 +/- 18.6 pg/ml, respectively, in Group A; and 85.0 +/- 39.8, 128.4 +/- 50.4, and 81.5 +/- 35.5 pg/ml, respectively, in Group B. Levels of the Tpo were significantly higher in all three localizations in Group B compared to Group A. Moreover, the Tpo concentration inside the pulmonary artery is significantly higher than the Tpo concentrations in the right and left ventricles in Group B patients. There were positive correlations between the Tpo levels and pulmonary artery systolic pressure over the whole patient group. In conclusion, there could be an association between pulmonary hypertension and Tpo level. Moreover, lung vasculature holding the major regulatory thrombopoietic hormone, Tpo, may be an important place for megakaryocytopoiesis.Platelets of patients with uremia develop a defective platelet function and have a decreased production of thromboxane B2 (TxB2). Activated platelets generate thromboxane from free arachidonate that is previously released from the membrane phospholipids (PLs) by phospholipases. Phospholipase A2 (PLA2) release up to 70% of the arachidonate in normal platelets, and to date, the activity of this enzyme in uremia is unknown. This work studied the PLA2 activity in the platelets of nine uremic patients and nine healthy volunteers. Washed platelets were labelled with [ 14 C]arachidonic acid and activated with calcium ionophore A-23187 (4 w gr/ml). Lipids were resolved by TLC and identified by autoradiography. The distribution of [ 14 C]arachidonic acid in the five major platelet phospholipids was found to be normal. Uremic platelets released more radioactivity than normal platelets (19.0 - 5.2% versus 11.3 - 1.6%, P = 0.001). The production of both, radioactive thromboxane B2 and hydroxyheptadecatrienoic acid was normal (2.6 - 1.2% and 3.5 - 1.6% of total radioactivity respectively), but the formation of the lipoxygenase metabolite hydroxyeicosatetraenoic acid was increased with respect to the controls (12.9 - 4.6% vs 7.0 - 1.3% of total radioactivity, P = 0002). In conclusion, platelets of patients with uremia have an increased activity of phospholipase A2 and produce increased amounts of hydroxyeicosatetraenoic acid, an inhibitor of the platelet function.

Bloodstream Thrombopoietin in Rheumatoid Arthritis with Thrombocytosis

Abstract: Thrombopoietin (TPO) is the major regulator of growth and differentiation of megakaryocytes. Recent studies have shown that TPO may also act as an acute-phase reactant, and it has been suggested as a component of inflammatory reactions. In this study our objective was to investigate serum TPO levels in patients with rheumatoid arthritis, a complex chronic inflammatory disorder not uncommonly associated with thrombocytosis. Bloodstream TPO concentrations were assessed in 13 RA patients with platelet counts between 450 and 650×109/l, 10 RA patients with platelet counts >650×109/l, 15 RA patients with normal platelet counts and 12 healthy controls. RA patients with normal platelet counts had TPO levels comparable with healthy controls. TPO concentrations in patients with mild thrombocytosis were significantly elevated, whereas patients with markedly increased thrombocyte counts had prominently decreased TPO levels. These results indicate that TPO seems to be associated with reactive thrombocytosis in RA patients with active disease. In patients with extremely increased thrombocytosis serum TPO levels might be regulated by increased platelet mass via receptor-mediated uptake and metabolism.

Modified ESHAP as Salvage Chemotherapy for Recurrent or Refractory Non-Hodgkin’s Lymphoma: Results of a Single-Center Study of 32 Patients

Background: We have evaluated the clinical efficacy and toxicity of a modified etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) chemotherapy regimen that has been used by the Hacettepe University Department of Medical Oncology (Ankara, Turkey) since 1993. Methods: Thirty-two patients (18 men and 14 women) with refractory or recurrent non-Hodgkin’s lymphoma (NHL) were treated with this protocol. The median age of the patients was 39 years (range 21–66 years). Patients were hospitalized during therapy. On the first day, 2 g/m2 cytarabine was given, followed on days 2–5 by 60 mg/m2 etoposide, 500 mg of methylprednisolone and 25 mg/m2 cisplatin. After two cycles of chemotherapy, clinical efficacy was assessed by clinical examination, chest radiography, ultrasonography and/or computed tomography. The complications were assessed on the basis of the World Health Organization criteria. Results: Nine patients (28%) had a complete response and 8 patients (25%) had a partial response. In responders, the median duration of remission was 6 months. By the end of the first year, 27% of the patients were still disease free and 66% were alive. High serum levels of lactate dehydrogenase had an adverse effect on disease-free survival, but no effect on overall survival (OS). The only unfavorable prognostic factor for OS was the presence of bulky disease. Neutropenia developed in 59% of patients, and febrile neutropenia developed in 74% of these patients, requiring hospitalization for an average of 8 days. Three patients died of neutropenia-associated sepsis despite broad-spectrum antibacterial and antifungal treatment. Thrombocytopenia was detected in 10 patients and anemia in 3 patients; among these, 7 patients with thrombocytopenia and 1 patient with anemia required transfusions. Conclusions: The modified ESHAP regimen induced remission in more than half of the patients with refractory or recurrent NHL. However, the duration of remission was brief. Moreover, significant myelotoxicity was common, and the risk of treatment-related death was 9%.

Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected liver metastases from colorectal cancer.

Background: We aimed to investigate the impact of adjuvant systemic therapy with modern chemotherapy combinations on survival outcomes in patients with resected liver-confined metastases from colorectal carcinomas, and whether addition of bevacizumab (BEV) provides further benefit. Methods: A total of 229 consecutive patients who underwent resection for liver-confined colorectal liver metastases were retrospectively analyzed. Results: Of 229 patients, 204 who received chemotherapy with fluoropyrimidine-based (n = 27), irinotecan-based (n = 84) and oxaliplatin-based (n = 93) combinations were analyzed. Among these, 87 patients received BEV while 117 did not (NoBEV). With a median follow-up of 27 months after metastasectomy, the median recurrence-free survival (RFS) and overall survival (OS) were 17 and 53 months, respectively. OS rates at 3 and 5 years were 71% and 40%, respectively. No significant differences were found in the median RFS (p = 0.744) and OS (p = 0.440) among different chemotherapy regimens. The median RFS (p = 0.375) and OS (p = 0.251) were similar in BEV and NoBEV arms. In multivariate analysis, having 4 liver metastases was the only negative independent factor on both RFS and OS, while positive surgical margin was another negative independent factor for RFS. Conclusion: Chemotherapy type and addition of BEV have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal liver metastases.

The relation between pathological complete response and clinical outcome in patients with rectal cancer.

BACKGROUND/AIMS: Preoperative chemoradiotherapy (CRT) is the standard treatment modality in locally advanced rectal cancer. The primary aim was to correlate pathological complete response (pCR) with patient outcome, and the secondary objective was to identify predictive factors of pCR. METHODOLOGY: Patients with clinical stage II/III rectal cancer who received preoperative CRT between 2002 and 2010 were retrospectively studied.The median radiotherapy dose was 54 Gy (range, 45 to 64 Gy), and all patients received concurrent infusional 5-fluorouracil-based chemotherapy. RESULTS: Median follow-up time was 48.3 months (range, 24 to 96 months) and 51 months (range, 44 to 110 months) for no-pCR and pCR groups, respectively. Eighteen patients (18.6%) had pCR. The 5-year overall survival was 95% for patients with pCR and 74.8% in patients without pCR (p=0.009). The 5-year local relapse free survival was 87.5% and 95% for the no-pCR and pCR groups, respectively (p=0.09). The 5-year distant relapse free survival was 93% in pCR group and 79.8% in no-pCR group (p=0.02). The 5-year distant free survival was 94% and 66% in patients with and without pCR, respectively (p=0.017). The clinical T4 (p=0.043) and pretreatment carcinoembryonic antigen level (CEA) >5ng/mL (p=0.012) were significantly associated with a lower pCR rate. In the multivariate logistic regression analysis, pretreatment CEA level >5ng/mL (p=0.008) was the only independent factor associated with a lower pCR rate. CONCLUSIONS: Patients with pCR after preoperative CRT had a significantly improved outcome. Furthermore, the pretreatment CEA level was independently associated with pCR.

Squamous Cell Carcinoma of the Skin Associated with Systemic Sclerosis

background. The coexistence of systemic sclerosis and cancer has been recognized with increasing frequency. However, squamous cell carcinoma of the skin associated with systemic sclerosis is relatively rare. objective. The mechanisms of malignancy in systemic sclerosis are discussed. methods. An 18‐year‐old girl with progressive systemic sclerosis is described. results. The patient had developed squamous cell carcinoma of the skin on the sclerosed skin of her left leg requiring amputation. The tumor recurred on the distal end of the stump. Local radiotherapy was unsuccessful. conclusion. This report suggests that sclerosis of the skin may manifest a greater risk of developing skin cancers unrelated to chronic injury or scarring of the skin.© 1998 by the American Society for Dermatologic Surgery, Inc.

Rheumatic diseases as causes of fever of unknown origin: an update of classic data

Rheumatic diseases commonly present with fever, and in such cases, it may be a diagnostic challenge to the physician in spite of the advances made in the fields of medical diagnosis and technology in recent decades. In most previous series, rheumatic diseases were reported to be the third most common cause of fever of unknown origin (FUO), ranging between 10% and 20% of all FUO cases [1, 2]. As recent advances in diagnostic techniques might have changed the spectrum of diseases causing FUO, we intended to make an update of our knowledge regarding the causes of FUO in our hospital, and a more detailed analysis of collagen vascular and granulomatous disorders presenting with FUO. We retrospectively evaluated the hospital records of patients who were admitted to our Infectious Diseases Department with the diagnosis of FUO from January 1990 to September 2000. Immunosuppressed, neutropenic and HIV-positive patients were excluded from the study. One hundred and forty-five patients (63 females, 82 males, mean age 38.5 years, min–max: 16–80) who met the classic criteria for FUO were included in the study [2]. The statistical package Epistat was used to analyze the data. Statistical analyses were performed using the vtest. P values <0.05 were considered statistically significant. Infections, rheumatic diseases and neoplastic disorders were diagnosed in 93 (64.1%), 24 (16.6%) and 8 patients (5.5%), respectively. Neoplastic diseases were diagnosed in 2.7% (3/113) of patients under the age of 50, compared to 15.6% (5/32) of patients over 50. Miscellaneous conditions were found in 2 patients (one case of acute pancreatitis and one case of subacute thyroiditis) (1.4%). In spite of detailed evaluation, 18 patients (12.4%) remained undiagnosed. Rheumatic diseases were the second most common cause of FUO (Table 1). To establish the diagnoses of those rheumatic disorders, invasive procedures (biopsy or angiography) were necessary in 8 patients; noninvasive tests (seroimmunologic, bacteriologic, conventional radiological tests, tomography, clinical course and treatment response) were sufficient in the remaining 16. Six of 32 (18.8%) patients over the age of 50 were diagnosed to have rheumatic diseases as the cause of FUO, compared to 18 of 113 cases (15.9%) under the age of 50 (p>0.05). The ratio of rheumatic diseases as cause of FUO was similar in both sexes (10/66 (15.2%) in females vs 14/79 (17.7%) in males, p>0.05). Infection, malignancy and collagen vascular disease are classically known as the three most important causes of FUO. However, the relative importance of these major categories may change in time because of improvements in serodiagnosis, culture techniques and radiological imaging modalities. In addition, the spectrum of diseases causing FUO also appears to be determined by geographical factors and sanitary conditions. Although the proportion of infectious diseases has decreased and that of rheumatic disorders increased in recent decades in the developed countries [2, 3, 4, 5, 6, 7], infectious diseases