The clinical utility of bone turnover markers in the evaluation of bone disease in patients with haemophilia A and B.

Haemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, the utility of bone turnover markers (BTM) remains unknown. The aim of this study was to evaluate bone metabolism in men with haemophilia and to investigate associations between BTM and bone disease. Serum N- (NTX-I), C-terminal telopeptide of type I collagen (CTX-I) and tartrate-resistant acid phosphatase band-5b (TRAP-5b), as bone resorption markers, and osteocalcin (OC) and bone-specific alkaline phosphatase (b-ALP), as bone formation markers, were assessed. Seventy men with haemophilia A (n = 59) or B (n = 11) were studied. Patients with low BMD had significantly higher b-ALP concentrations compared with those with normal BMD (12.8 ± 1.60 vs. 9.72 ± 0.58 µg/L, P = 0.009), without any differences in the other BTM. NTX-I and CTX-I concentrations were negatively associated with oestradiol levels and hip BMD and positively with human immunodeficiency virus infection, number of affected joints and arthropathy scores. B-ALP and OC concentrations were negatively associated with hip BMD, severity of haemophilia and fracture history, and positively with the number of affected joints and testosterone concentrations. After multivariate analysis, NTX-I levels remained negatively associated with oestradiol levels, whereas b-ALP concentrations negatively correlated with the level of physical activity and positively with the number of affected joints. Increased bone metabolism exists in men with haemophilia and low BMD. Increased b-ALP levels may identify patients at high risk for fracture. Increased number of target joints, low physical activity and low oestradiol concentrations are independently associated with increased bone metabolism.

Long-term effects of thyroid fine-needle biopsy on the thyroid-related biochemical parameters.

AIMS: Thyroid fine-needle biopsy (FNB) is a simple, reliable, inexpensive and generally safe diagnostic procedure in the management of thyroid nodules. FNB may trigger biochemical alterations through destruction of thyroid follicles. We aimed to investigate long-term post-FNB alterations in serum thyroid-related parameters. METHODS: One hundred and ten consecutive patients with thyroid nodular disease were subjected to FNB. Thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3), thyroglobulin (Tg), thyroglobulin autoantibodies (anti-Tg), thyroid-peroxidase autoantibodies (anti-TPO) were measured in all subjects at baseline, 10 days, 2 and 6 months. Subsequently, patients were divided into subgroups according to the technique of FNB, the presence of disease characteristics as thyroid autoimmunity (Hashimoto's thyroiditis), goitre, singularity-maximum diameter-blood pattern of the nodule(-s), the number of passes and the administration of L-thyroxine (LT4). RESULTS: A significant increase in Tg, anti-Tg and FT3 levels was observed. These alterations were more prominent within patients with dominant nodule's maximum diameter ≥ 2 cm or without Hashimoto's thyroiditis. Tg and anti-Tg levels were significantly increased only in patients not being on LT4. On the other hand, FNB technique did not affect any of the measured parameters. CONCLUSION: Our data suggest that FNB results in statistically significant but clinically insignificant increases in Tg, anti-Tg and FT3 levels, implying a thyroid trauma of some level, more likely to happen in patients with larger nodules. The FNB technique used has no effect on the thyroid-related biochemical parameters.

Investigation of cytokine levels and their association with SCORAD index in adults with acute atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing frequency over the last decades, especially in adults. Cytokines orchestrate atopic skin inflammation. Objectives The aim of this study was to compare serum levels of cytokines in adult patients with acute AD (AD1) with other groups of AD patients and controls and investigate the possible association between such cytokines and disease severity. METHODS: We measured cytokine levels using flow cytometry in 21 adult patients with acute AD, 12 adults with chronic AD, 10 children with acute AD and 10 healthy adults. RESULTS: Flow cytometry analysis of cytokines revealed that interleukin 10 (IL-10), IL-6, interferon γ (IFN-γ) and IL-4 levels were significantly decreased in AD1 group compared with controls, whereas IL-2 and tumour necrosis factor (TNF) did not differ. Comparison of AD1 group with adults chronic phase group showed that IgE, eosinophil and IL-2 levels remained unaltered, whereas IL-10, IL-6, IFN-γ, IL-4 and TNF were significantly decreased. SCORAD and IgE levels were significantly increased, IL-10, IL-6 and IFN-γ were decreased and TNF, IL-2, IL-4 and eosinophil levels remained unchanged in AD1 group compared with children acute phase group. Within AD1 group correlation analysis revealed that IgE and TNF levels were significantly associated with AD severity. Coefficient of determination analysis revealed that TNF and IgE levels could explain 49.14% and 35.28% of the variance of SCORAD. CONCLUSIONS: These data indicate that serum IgE and TNF levels correlate with AD severity and that serum cytokines are downregulated in AD1 group. Further studies are clearly needed to elucidate cytokines' role in adults with AD.

Alterations of erythrocyte superoxide dismutase activity in patients suffering from asthma attacks.

BACKGROUND: Oxidant-antioxidant imbalance may play an important role in the development and progression of bronchial asthma. However, the role of blood antioxidants especially in asthma exacerbation has not been fully discussed. OBJECTIVE: This study examines a part of the intracellular antioxidant defense mechanism in asthmatic patients admitted to hospital due to severe exacerbation of their disease. METHODS: Peripheral blood Erythrocyte Superoxide Dismutase (SOD) activity was measured in 38 patients (33 men - 5 women, with a mean age of 56 +/- 2.8 yrs), using a colorimetric method. On the days of admission and discharge the Forced Expiratory Volume in 1 second (FEV1) and the Partial arterial Oxygen pressure (PaO2) were recorded and correlated with SOD activity at the same time. RESULTS: A statistically significant decrease of SOD activity was observed on the day of admission compared to SOD activity on the day of discharge (43.64 +/- 31.78 vs. 96.16 +/- 54.05 units/ml, p < 0.001), suggesting the presence of oxidative stress during an asthma attack. A statistically significant correlation was observed between FEV1 on admission and SOD activity at the same time (r = 0.57, p < 0.001). Furthermore, SOD activity on admission was correlated with PaO2 on discharge (r = 0.55, p < 0.001), as well as SOD on discharge with PaO2 on discharge (r = 0.53, p = 0.001). CONCLUSIONS: Decreased systemic erythrocyte SOD activity was observed during asthma attacks. This activity was correlated with severity criteria such as FEV1 and PaO2. Therefore, it seems that measurement of SOD activity could be a useful tool in the evaluation of an asthma attack. The supplementary administration of antioxidants in the future needs further clarification.

The effect of zoledronic acid on serum dickkopf-1, osteoprotegerin, and RANKL in patients with Paget's disease of bone.

Overexpression of dickkopf (DKK)-1 in pagetic osteoblast cultures resulted in stimulation of osteoclast proliferation and inhibition of osteoblast growth. The aim of this study was to evaluate for the first time in Paget's disease of bone (PDB): 1) the serum levels of DKK1; 2) the association of DKK-1 with receptor activator of nuclear factor kappa B (RANKL) and osteoprotegerin (OPG); and 3) the effect of zoledronic acid (ZOL) on serum DKK-1, RANKL, and OPG. The study was conducted as a prospective open-label cohort study. Eleven patients with PDB (median age 60 years) were recruited. Twelve age- gender- and body mass index (BMI)-matched healthy individuals were used as controls at baseline. Blood samples were obtained before treatment (baseline) and after 3, 6, 12, and 18 months following ZOL infusion in patients with PDB. Patients with PDB had significantly higher RANKL (p=0.002), OPG (p=0.001), and bone markers (total alkaline phosphatase and C-terminal cross-linking telopeptide of type I collagen) compared with controls at baseline. There was no difference between groups in DKK-1 at baseline. Bone markers were both significantly decreased after therapy. Serum OPG, RANKL, RANKL:OPG ratio, and DKK-1 remained unaffected throughout the study. No correlations were found between OPG, RANKL, RANKL:OPG ratio, and DKK-1 at baseline nor between their changes during the study. Although both OPG and RANKL were increased in patients with PDB, ZOL had no effect on their serum levels. Serum DKK-1 was neither increased in patients with PDB nor related to OPG and RANKL, and was unaffected by ZOL.

Leishmaniases in Northern Greece: seroprevalence of the infection and incidence of the disease during the period 2001-2006.

Increasing risk factors are making leishmaniases a growing public health concern for many countries around the world. The aim of this study was to assess the seroprevalence of Leishmania infantum infection in the general population and in HIV infected subjects of Northern Greece, bordering the Mediterranean basin where leishmaniasis is endemic. The clinical cases of the disease during the last 6 years (2001-2006) are also presented. A low frequency of L. infantum antibodies was found by IFA and ELISA in 1,525 healthy individuals (2.8%), aged 18-80 years, living in the 16 prefectures of Northern Greece (Macedonia and Thrace regions), and in 167 HIV positive subjects (0.6%). Fifty-seven clinical cases were diagnosed in the same area and an approximate annual incidence of 0.34/100,000 was estimated. No endemic foci were identified and the cases of the disease were sporadic. Most presented with the visceral form (VL), few with the cutaneous, and one with VL-HIV co-infection. A significant shift in the age of people at risk was observed, with children less affected than adults (children/adults ratio: 0.36). No relevant data from previous studies are available to demonstrate a possible change of the infection in Northern Greece. The results of this study could be used as a reference for leishmaniasis surveillance in the area.

Head-to-head comparison of risedronate vs. teriparatide on bone turnover markers in women with postmenopausal osteoporosis: a randomised trial.

AIMS: We aimed to compare the effect of risedronate (RIS) and teriparatide (TPTD) (recombinant human parathyroid hormone 1-34) on bone turnover markers in women with postmenopausal osteoporosis. METHODS: Forty-four Caucasian women (age 65.1 +/- 1.6 years) with postmenopausal osteoporosis were randomly assigned to receive either RIS 35 mg once weekly (n = 22) or TPTD 20 microg once daily (n = 22) for 12 months. Serum N-terminal propeptide of type 1 collagen (P1NP), C-terminal telopeptide of type 1 collagen (CTx), total alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) were obtained from all women before, 3 and 6 months after treatment initiation. Lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry before and 12 months after treatment initiation. RESULTS: P1NP, CTx and total ALP levels decreased in RIS group (p < 0.001) and increased in TPTD group (p < 0.001) throughout the treatment. iPTH increased significantly in RIS group (p < 0.05) and decreased in TPTD group (p < 0.001). Finally, lumbar spine BMD increased significantly in both RIS (p = 0.003) and TPTD groups (p < 0.001) without significant differences between them. CONCLUSIONS: Our data suggest that both serum P1NP and CTx are reliable markers of RIS and TPTD action in women with postmenopausal osteoporosis. In a similar way, serum total ALP can be used as an alternative marker for monitoring both RIS and TPTD action, while iPTH can be used only for TPTD-treated women. The increase in P1NP and CTx after 3 months of treatment with RIS or TPTD can predict the increase in BMD after 12 months of treatment.

Anti-Mullerian Hormone (AMH) levels in serum and follicular fluid as predictors of ovarian response in stimulated (IVF and ICSI) cycles.

INTRODUCTION: Anti-Mullerian Hormone (AMH) was recently introduced as a marker of ovarian reserve in assisted reproduction. The cutoff values of AMH for prediction of poor response have not yet been determined. MATERIAL AND METHODS: Ninety women undergoing their first IVF/ICSI cycle were prospectively included in this clinical, non-interventional study. Baseline AMH, follicle stimulating hormone (FSH) and antral follicle count (AFC) were measured before starting ovarian stimulation. AMH was also measured on day 5 of stimulation and in the follicular fluid of the first aspirated follicle. The predictive value of baseline AMH, day 5 AMH and follicular fluid AMH were assessed comparatively to FSH and AFC for ovarian response. Ovarian response was defined as poor (<4 oocytes), high (>12 oocytes) or normal (≥4 oocytes and ≤12 oocytes). However, only 3 patients met the criterion for high ovarian response and thus analysis was focused on the prediction of poor response. RESULTS: Significant differences were present between poor responders and non-poor responders regarding FSH (p = 0.019), baseline AMH (p = 0.002), AFC (p < 0.001), day 5 AMH (p = 0.005) but not for follicular AMH (p = 0.183). The largest AUC (area under the curve) for poor ovarian response was obtained by AFC (AUC = 0.81) followed by baseline AMH (AUC = 0.70). At a level below 2.74 ng/mL, the sensitivity of the test is 69% and specificity is 70.5%. CONCLUSION: Baseline AMH is almost as good a predictor for poor ovarian response as AFC.

Bronchoalveolar lavage fluid alteration in antioxidant and inflammatory status in lung cancer patients.

BACKGROUND: Increased oxidative and inflammatory markers have been reported in lung cancer patients, but relatively few studies have investigated the presence of antioxidants both in the local lung environment and in the systemic circulation. Furthermore, it is hypothesized that the immune system activation in vivo is regulated by the redox environment. OBJECTIVES: To investigate local and systemically circulating antioxidant and inflammatory mediators in lung cancer patients and potential correlations between them. METHODS: Forty two male patients (mean age 65±8years) with primary lung cancer were studied. Sixteen age and smoking history matched male subjects without any evidence of malignancy served as controls. Total antioxidant status (TAS) and glutathione (GSH), as well as interleukin-1a (IL-1a), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured in bronchoalveolar lavage fluid (BALF) and serum samples. RESULTS: A statistically significant increase of TAS and GSH in BALF was observed in lung cancer patients compared to healthy subjects (0.27±0.24 vs. 0.12±0.02mmol/L, p=0.02 and 7.56±4.29 vs. 4.62±2.23µmol/L, p=0.01 respectively). Statistically significant correlations in cancer patients were observed in BALF between TAS and a. IL-1α (r=0.87, p<0.001), b. IL-6 (r=0.52, p=0.001) and c. TNF-α (r=0.67, p<0.001). CONCLUSIONS: Alteration in antioxidant and inflammatory mediator status was found in lung cancer patients both in serum and in BALF compared to healthy subjects matched for smoking history. Moreover, a positive correlation was observed between antioxidants and pro-inflammatory cytokines, but only locally and not systematically.

Serum osteoprotegerin and RANKL are not specifically altered in women with postmenopausal osteoporosis treated with teriparatide or risedronate: a randomized, controlled trial.

Risedronate and teriparatide have opposite actions on the osteoblast-osteoclast dipole and are expected to influence the RANK/RANKL/osteoprotegerin (OPG) system. We aimed to evaluate changes in serum OPG and RANKL after risedronate or teriparatide administration in postmenopausal osteoporotic women. Seventy-four postmenopausal Caucasian women (age 64.1+/-1.0 years) were studied. Women with osteopenia served as controls (group 1, n=30). Women with osteoporosis were randomly assigned to either risedronate 35 mg once weekly (group 2, n=21) or teriparatide 20 microg once daily (group 3, n=23) for six months. Blood samples for serum RANKL, OPG, N-terminal propeptide of type 1 collagen (P1NP), and C-terminal telopeptide of type 1 collagen (CTx) were obtained before treatment and three and six months after treatment. P1NP and CTx levels remained unchanged in group 1, decreased in group 2 (p<0.001), and increased in group 3 women (p<0.001) throughout the treatment. OPG levels remained unchanged while RANKL decreased gradually in all groups (p<0.001). There was no correlation between OPG or RANKL and P1NP or CTx. Our data suggest that neither antiresorptive nor osteoanabolic therapy causes specific alterations of serum OPG/RANKL levels; therefore, these cytokines cannot substitute for the established markers of bone turnover in the monitoring of response to osteoporosis treatment.