Association of hydroxyurea adherence with transcranial Doppler screenings in children with sickle cell disease.

BACKGROUND: National sickle cell disease (SCD) guidelines recommend oral hydroxyurea (HU) starting at 9 months of age, and annual transcranial Doppler (TCD) screenings to identify stroke risk in children aged 2-16 years. We examined prevalence and proportion of TCD screenings in North Carolina Medicaid enrollees to identify associations with sociodemographic factors and HU adherence over 3 years. STUDY DESIGN: We conducted a longitudinal study with children ages 2-16 years with SCD enrolled in NC Medicaid from years 2016-2019. Prevalence of TCD screening claims was calculated for 3 years, and proportion was calculated for 12, 24, and 36 months of Medicaid enrollment. Enrollee HU adherence was categorized using HU proportion of days covered. Multivariable Poisson regression assessed for TCD screening rates by HU adherence, controlling for age, sex, and rurality. RESULTS: The prevalence of annual TCD screening was between 39.5% and 40.1%. Of those with 12-month enrollment, 77.8% had no TCD claims, compared to 22.2% who had one or higher TCD claims. Inversely, in children with 36 months of enrollment, 36.7% had no TCD claims compared to 63.3% who had one or higher TCD claims. The proportion of children with two or higher TCD claims increased with longer enrollment (10.5% at 12 months, 33.7% at 24 months, and 52.6% at 36 months). Children with good HU adherence were 2.48 (p < .0001) times more likely to have TCD claims than children with poor HU adherence. CONCLUSION: While overall TCD screening prevalence was low, children with better HU adherence and longer Medicaid enrollment had more TCD screenings. Multilevel interventions are needed to engage healthcare providers and families to improve both evidence-based care and annual TCD screenings in children with SCD.

Pediatric Neurodevelopmental Delays in Children 0 to 5 Years of Age With Sickle Cell Disease: A Systematic Literature Review.

INTRODUCTION: Sickle cell disease (SCD) is the most common abnormal genetic blood disease that affects ∼100,000 Americans. Approximately 20% to 37% of children with sickle cell anemia have silent cerebral infarcts by the age of 14 years old. Neurocognitive deficits are identified in infants and preschool children with SCD. The purpose of this systematic literature review is to provide a comprehensive understanding of the prevalence, severity, and the associated risk factors for neurodevelopmental delays (NDDs) in children with SCD 5 years of age and younger. METHODS: Systematic search of 6 databases identified 2467 potentially relevant publications and 8 were identified through a manual search. Only 24 articles met the inclusion criteria. RESULTS: We identified an increased prevalence of NDDs (cognitive, motor, or both). Children experienced deficits with language, attention and behavior, executive functioning, school readiness and/or academic performance, and motor skills (fine and gross motor functioning). Risk factors include silent cerebral infarcts and strokes, SCD genotype (HbSS>HbSC), other biologic, and social factors. CONCLUSION: NDDs are common in children ages 0 to 5 years old with SCD. There is an opportunity to improve adherence to national guideline recommendations and early detection practices by pediatricians, hematologists, and other health care providers.

Natural course of mild Graves' orbitopathy: is it a chronic remitting or a transient disease?

BACKGROUND/AIMS: The natural course of Graves' orbitopathy (GO) has been poorly documented. The aim of this review is to provide current knowledge regarding the natural course of mild GO, trying to address the issue of whether and to what extent it constitutes a chronic remitting or transient disease. METHODS: We systematically searched PubMed for English language publications until August 2016 under the following terms: "Graves' orbitopathy" OR "Graves' ophthalmopathy" OR "thyroid eye disease" AND "natural course" OR "natural history". RESULTS: Few studies have investigated the course of mild orbital disease in patients with GO. Large controlled trials are lacking and data can be extracted mainly from small retrospective and some prospective studies, after excluding patients who had received radioiodine for thyrotoxicosis or surgical treatment for GO. In general, more than half of GO patients may show spontaneous improvement in their clinical features, whereas no safe conclusions can be drawn with regard to complete resolution, with percentages ranging from 6 to 58 %. CONCLUSIONS: The question whether mild GO is a remitting, albeit chronic disease, or even a transient event in the course of Graves' disease, remains currently unanswered.

Consequences of hyperthyroidism in male and female fertility: pathophysiology and current management.

Thyroid hormone acts on the oocytes, sperm and embryo during fertilization, implantation and placentation. Both hypothyroidism and hyperthyroidism may influence fertility. However, evidence of the association of hyperthyroidism with infertility is scarce and sometimes conflicting. Thyroid hormone influences human reproduction via a variety of mechanisms at both the central and the peripheral level. Infertility may occur in hyperthyroid men and women, but it is usually reversible upon restoration of euthyroidism. This review aims to summarize the available data on the association of hyperthyroidism and infertility in both men and women and to provide practical suggestions for the management of these patients.

The effect of L-thyroxine substitution on lipid profile, glucose homeostasis, inflammation and coagulation in patients with subclinical hypothyroidism.

AIMS: Subclinical hypothyroidism (SH) is associated with increased risk for atherosclerosis, mainly attributable to dyslipidaemia and hypercoagulability. However, conflicting data exist regarding the effect of L-thyroxine substitution on these parameters. The purpose of this study was to assess the effect of L-thyroxine therapy on lipidaemic profile, coagulation markers, high-sensitivity C-reactive protein (hsCRP) and glucose homoeostasis in SH patients. METHODS: It was a prospective open-label study. The following parameters were measured before and 6 months after intervention: anthropometric data, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoproteins B (apoB) and A1 (apoA1), lipoprotein (a) [Lp(a)], fasting plasma glucose and insulin, homoeostasis model assessment-insulin resistance (HOMA-IR), hsCRP, antithrombin III (AT-III), protein C (PC), protein S (PS), fibrinogen and homocysteine. RESULTS: Thirty-two patients (30 women) aged 52.1 ± 13.9 years with SH completed the study. Baseline mean TSH levels were 6.79 ± 2.58 mIU/ml. Achievement of euthyroidism significantly reduced systolic blood pressure (BP) in patients with SH (from 135.2 ± 18.5 to 129.7 ± 15.8 mmHg, p = 0.03) and diastolic BP only in those with baseline TSH levels > 7 mIU/ml (from 79.5 ± 9.8 to 72.1 ± 7.3 mmHg, p = 0.03). No significant changes in body weight, TC, LDL-C, HDL-C, TG, apoB, glucose, insulin, HOMA-IR, hsCRP, AT-III, PC, PS, fibrinogen or homocysteine levels were noticed after restoration of euthyroidism, except for a decrease in apoA1 (p = 0.04) and an increase in Lp(a) levels (p = 0.02). CONCLUSIONS: Except for a reduction in systolic and diastolic BP, thyroid substitution therapy does not affect lipidaemic profile, systematic inflammation, glucose homoeostasis or coagulation in patients with SH.

Oxidative stress and reduced antioxidative status, along with endothelial dysfunction in acromegaly.

Acromegaly is characterized by high cardiovascular morbidity and mortality. Oxidative stress and endothelial dysfunction are underlying mechanisms of atherosclerosis.The aim of this study was to evaluate the blood redox status and endothelial function by means of nitric oxide (NO) levels in patients with acromegaly. Total antioxidant capacity (TAC), catalase activity and glutathione concentration (GSH), as measures of antioxidative capacity, total oxidized glutathione (GSSG) and thiobarbituric acid reactive substances (TBARS), as indices of oxidative stress, and NO levels were assessed in 15 patients with acromegaly (age 55.4±10.5 years; 6 males) and 15 age- and sex-matched controls (age 58.4±8.1 years; 7 males). Active disease was present in 12 patients: 11 on current pharmacotherapy and 1 newly diagnosed. Three acromegalics were in remission after successful treatment. Acromegalics as compared with controls had significantly lower levels of catalase activity (8.2±5.8 vs. 51.3±29.1 mmol/ml/min, p<0.001), GSH (0.97±0.54 vs. 1.41±0.35 mmol/l, p=0.006), GSSG (0.27±0.19 vs. 2.04±1.32 mmol/l, p=0.002) and NO levels (6.0±3.1 vs. 43.0±29.8 mmol/l, p<0.001), but higher TBARS (16.3±8.9 vs. 10.1±10.8, nmol/ml, p=0.019). After adjustment for confounders, differences in catalase activity, NO levels and TBARS remained significant (p=0.004, p<0.001 and p=0.025, respectively). No association between IGF-I/GH and oxidative stress markers was noticed, except for a positive correlation between nadir GH and GSSG (r²=0.563, p=0.036). Acromegaly is associated with increased levels of oxidative stress coupled by diminished antioxidant capacity and endothelial dysfunction indicated by the presence of decreased NO levels.

De novo autoimmune hepatitis associated with PTH(1-34) and PTH(1-84) administration for severe osteoporosis in a liver transplant patient.

De novo autoimmune hepatitis (AIH) is a rare graft dysfunction occurring in patients having undergone liver transplantation (LT) for causes other than AIH. We describe for the first time a case of de novo AIH associated with the administration of parathyroid hormone 1-34 [PTH(1-34)] and PTH(1-84) for severe osteoporosis. A 61-year-old woman was referred to our metabolic bone clinic due to severe osteoporosis, 3 years after LT for primary biliary cirrhosis. Initial treatment with PTH(1-34) led to asymptomatic hypertransaminasemia (two-fold the upper limit of normal), which normalized after drug discontinuation. A new flare of transaminases (three-fold the upper limit of normal) along with elevated alkaline phosphatase was observed after administration of PTH(1-84), which did not resolve after PTH(1-84) withdrawal. Subsequently, after exclusion of common causes of liver enzyme elevation, a liver biopsy was performed. Histological findings showed de novo AIH, which responded rapidly to treatment with methylprednisolone.

Zoledronic acid-induced transient hepatotoxicity in a patient effectively treated for Paget's disease of bone.

Bisphosphonate (BP)-induced hepatotoxicity is very rare. There are only a few reports of liver injury after BP treatment, including aledronate and risedronate in postmenopausal osteoporosis patients. We describe hereby the case of a patient with Paget's disease of bone accompanied by nonalcoholic fatty liver disease (NAFLD) who developed transient hepatotoxicity after zoledronic acid (ZOL) treatment. NAFLD had been diagnosed 1 year before presentation, based on liver ultrasonography (US). One day after infusion, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) were increased by 8.1, 6.7, and 6.7 times, respectively, compared with pretreatment values. Serum bilirubin remained normal. US revealed hepatic mild homogenous brightness without focal lesion of the liver or biliary ducts. Subsequent biochemical and serologic investigation did not reveal a specific liver or systematic disease. The patient remained asymptomatic, and ALT, AST, and GGT were normalized 7 days post-treatment. Although the mechanism by which ZOL may cause liver damage is elusive, physicians should be aware of this possible adverse effect and ZOL cautiously administered in NAFLD patients.

Glucagon-like peptide-1-based therapies and cardiovascular disease: looking beyond glycaemic control.

Type 2 diabetes mellitus is a well-established risk factor for cardiovascular disease (CVD). New therapeutic approaches have been developed recently based on the incretin phenomenon, such as the degradation-resistant incretin mimetic exenatide and the glucagon-like peptide-1 (GLP-1) analogue liraglutide, as well as the dipeptidyl dipeptidase (DPP)-4 inhibitors, such as sitagliptin, vildagliptin, saxagliptin, which increase the circulating bioactive GLP-1. GLP-1 exerts its glucose-regulatory action via stimulation of insulin secretion and glucagon suppression by a glucose-dependent way, as well as by weight loss via inhibition of gastric emptying and reduction of appetite and food intake. These actions are mediated through GLP-1 receptors (GLP-1Rs), although GLP-1R-independent pathways have been reported. Except for the pancreatic islets, GLP-1Rs are also present in several other tissues including central and peripheral nervous systems, gastrointestinal tract, heart and vasculature, suggesting a pleiotropic activity of GLP-1. Indeed, accumulating data from both animal and human studies suggest a beneficial effect of GLP-1 and its metabolites on myocardium, endothelium and vasculature, as well as potential anti-inflammatory and antiatherogenic actions. Growing lines of evidence have also confirmed these actions for exenatide and to a lesser extent for liraglutide and DPP-4 inhibitors compared with placebo or standard diabetes therapies. This suggests a potential cardioprotective effect beyond glucose control and weight loss. Whether these agents actually decrease CVD outcomes remains to be confirmed by large randomized placebo-controlled trials. This review discusses the role of GLP-1 on the cardiovascular system and addresses the impact of GLP-1-based therapies on CVD outcomes.

FDG PET/CT features of ovarian metastasis.

AIM: To assess the characteristics of [(18)F]-fluoro-2-deoxy-d-glucose (FDG) uptake in cases of ovarian metastasis using positron-emission tomography/computed tomography (PET/CT). MATERIALS AND METHODS: Twelve patients with 16 ovarian metastases arising from colon cancer (n=6), breast cancer (n=4), gastric cancer (n=3), and pancreatic cancer (n=3) who underwent FDG-PET/CT examination were included in this study. The effect of lesion size and morphological pattern (predominantly solid or cystic) on FDG uptake was evaluated using the quantitative standardized uptake value (SUV). RESULTS: The mean maximum SUV for the 16 lesions was 4.6±2.4 (range 1.8∼9.9). The Pearson correlation coefficient test showed no significant correlation between maximum SUV and lesion size (r=0.21, p=0.42). The maximum SUV of solid (n=5) and cystic (n=11) lesions was 5.5±2.7 and 4.3±2.2, respectively, and the difference was not significant (p=0.43). Breast cancer showed the highest maximum SUV (6.4±3.6), followed by colon cancer (5.3±1.4), gastric cancer (3.3±0.5), and pancreatic cancer (2.2±0.6). CONCLUSION: Ovarian metastases show a variable maximum SUV with mild to intense FDG uptake.

Effects of mechanical stress on cytokine production in mandible-derived osteoblasts.

OBJECTIVE: Mechanical stress is known to be an important factor in the regulation of bone remodeling, and mandibular bone is continuously exposed to mechanical stressors such as occlusal force. Therefore, in this study, we investigated the effects of mechanical stress approaching occlusal force, to which mandible-derived osteoblasts (MDOB) are exposed, on cytokine expression and production using an original hydrostatic pressure apparatus. MATERIALS AND METHODS: The levels of cytokine in MDOB were examined by real-time RT-PCR, ELISA, and western blotting. In addition, mitogen-activated protein kinase inhibitor for ERK1/2, JNK, and p-38 pathways was used to identify the signal transduction pathway. RESULTS: Hydrostatic pressure increased the expression of IL-6 and TNF-α mRNA in a magnitude- and time-dependent manner and also enhanced IL-6 and TNF-α protein production. Furthermore, hydrostatic pressure changed the RANKL/OPG ratio in favor of RANKL for both mRNA and protein levels. Specific inhibitor of p-38 pathway but not that of the ERK1/2 and JNK pathways suppressed the up-regulation of RANKL production induced by hydrostatic pressure loading. CONCLUSION: These results suggest that MDOB play a role in cytokine production in response to mechanical stress and that occlusal force may support the maintenance of mandible bone homeostasis by activating bone remodeling through osteoclastogenesis.

Pituitary incidentalomas: a single-centre experience.

AIM: Pituitary incidentalomas (PIs) are diagnosed in about 10% of the patients undergoing radiological investigation for non-pituitary disorders. The aim of this study was to describe the morphological and hormonal characteristics of PIs in a cohort of patients, followed up in a single centre from 1982-2009. METHODS: Retrospective analysis of electronic medical records of patients with PIs was carried out. All patients underwent basal and dynamic evaluation of the hypothalamus-pituitary axis. Mass size was assessed at yearly intervals. RESULTS: Sixty-one patients (38 men/23 women, aged 53±2 years) were studied. The mean follow-up time was 48±8 months, and mean size of PIs was 20±2 mm. Twelve PIs (20%) were microadenomas, 48 (78%) were macroadenomas and one (2%) was a Rathke's cyst. The most common reasons that led to their discovery were headaches, dizziness, syncope, stroke and head injury. Forty-seven of the 61 PIs (77%) were non-functioning, 11 (18%) prolactinomas, and two (3%) GH-secreting adenomas. Hypopituitarism was present in 12% at diagnosis. Forty-eight per cent of the patients were submitted to surgery with conventional radiotherapy in 8%. Relapse in size was observed in 48% of the surgically treated patients. Of the PIs followed conservatively, 78% remained stable, 11% showed decrease and 11% increase in size during follow up. Hypopituitarism rose to 57% postoperatively. CONCLUSIONS: Majority of PIs are non-functioning adenomas that remain stable in size. Relapse in size and hypopituitarism postoperatively are common. PIs, for which conservative management was initially considered appropriate, did not progress in size.

Acromegaly: presentation, morbidity and treatment outcomes at a single centre.

OBJECTIVE: Analysis of patients with acromegaly followed-up at a single centre, focusing on baseline characteristics, morbidity and efficacy of treatment. DESIGN AND METHODS: Retrospective review of electronic medical records of acromegalics from 1987 to 2009. RESULTS: One hundred and fifteen patients (45 men), aged 47 ± 14 years, with a mean follow-up of 8.8 ± 0.8 years were studied. Twenty-five per cent had micro- and 75% macroadenomas. Forty-three per cent presented with visual field defects, 49% had hypertension, 25% diabetes mellitus and 35% dyslipidaemia. At follow-up, 50% had myocardial hypertrophy, 55% colon polypodiasis, 74% nodular thyroid disease and 18% adrenal masses. Surgery was performed in 79% (8% twice), followed by conventional radiotherapy in 27%. Fifty-two per cent of the patients achieved remission. Disease control was reported in 65% of microadenomas and 41% of macroadenomas. Remission rates with surgery alone were 41%. Improvement of remission rates was achieved with subsequent treatment with somatostatin analogues (SSA) (53%), or conventional radiotherapy (63%). Nevertheless, pituitary reserve was compromised with the latter. SSA significantly improved outcomes in microadenomas, even as a monotherapy (remission in 89%), in contrast to macroadenomas (0%), although these agents were associated with impaired glucose metabolism and cholelithiasis in half of the patients. CONCLUSIONS: Acromegaly is associated with an increased morbidity. About half of the treated patients achieved remission (2/3 of microadenomas). The best outcomes were reported for the combination of surgery with radiotherapy, in spite of a higher risk of hypopituitarism. SSA led to remission in a significant percentage of microadenomas, but was associated with increased rates of cholelithiasis and impaired glucose homeostasis.

Comparative effects of rosuvastatin and atorvastatin on glucose metabolism and adipokine levels in non-diabetic patients with dyslipidaemia: a prospective randomised open-label study.

AIMS: The impact of statins on glucose metabolism and adipokines remains controversial. We compared the effects of rosuvastatin and atorvastatin on glucose homeostasis, insulin sensitivity (IS), adiponectin and leptin levels as well as systemic inflammation in non-diabetic patients with dyslipidaemia. METHODS: Thirty-six patients were randomly assigned to 10 mg/day of rosuvastatin (n = 18) or 20 mg/day of atorvastatin (n = 18) for 12 weeks. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), quantitative IS check index (QUICKI), adiponectin, leptin and high-sensitivity C-reactive protein (hsCRP) were measured at baseline and after 4 and 12 weeks. RESULTS: Both statins significantly lowered TC, LDL-C, non-HDL-C and TG compared with baseline. Only rosuvastatin caused a significant reduction in insulin and HOMA-IR levels (-35%, p = 0.005 and -33%, p = 0.011 respectively) and a significant increase in QUICKI (+11%, p = 0.003) at 12 weeks. In terms of adipokines and hsCRP, no difference was observed after 4 and 12 weeks of treatment with either statin. CONCLUSIONS: Rosuvastatin compared with atorvastatin resulted in significant improvements in IS indices. No significant changes in adiponectin, leptin or hsCRP levels were observed at 4 and 12 weeks of treatment with either statin.

Detection of human coronavirus RNA in surgical smoke generated by surgical devices.

BACKGROUND: Gaseous by-products generated by surgical devices - collectively referred to as 'surgical smoke' - present the hazard of transmitting infective viruses from patients to surgical teams. However, insufficient evidence exists to evaluate and mitigate the risks of SARS-CoV-2 transmission via surgical smoke. AIM: To demonstrate the existence and infectivity of human coronavirus RNA in surgical smoke using a model experiment and to evaluate the possibility of lowering transmission risk by filtration through a surgical mask. METHODS: Pelleted HeLa-ACE2-TMPRSS2 cells infected with human coronavirus were incised by electric scalpel and ultrasonic scalpel, separately. A vacuum system was used to obtain surgical smoke in the form of hydrosol. Reverse transcription-quantitative polymerase chain reaction was used to analyse samples for the presence of viral RNA, and infectivity was determined through plaque assay. Furthermore, a surgical mask was placed centrally in the vacuum line to evaluate its ability to filter viral RNA present in the surgical smoke. FINDINGS: In this model, 1/106 to 1/105 of the viral RNA contained in the incision target was detected in the collected surgical smoke. The virus present in the smoke was unable to induce plaque formation in cultured cells. In addition, filtration of surgical smoke through a surgical mask effectively reduced the amount of viral RNA by at least 99.80%. CONCLUSION: This study demonstrated that surgical smoke may carry human coronavirus, though viral infectivity was considerably reduced. In clinical settings, surgical mask filtration should provide sufficient additional protection against potential coronavirus, including SARS-CoV-2, infection facilitated by surgical smoke.

Eradication of the commensal intestinal microflora by oral antimicrobials interferes with the host response to lipopolysaccharide.

The host components and commensal microorganisms of the intestinal microenvironment play roles in the development and maintenance of the host defence. Recent observations have suggested that toll-like receptors (TLRs) are involved in the recognition of innate immunity against intestinal microbes. However, little is known regarding the role of TLR in the maintenance of systemic host defence by intestinal microorganisms. We studied the expression and function of TLR4 and TLR2 on alveolar and peritoneal macrophages in mice after 3 weeks of oral administration of streptomycin and cefotaxime. After active treatment, the intestinal microorganisms were nearly completely eradicated, and the surface expression of TLR4 and TLR2 on the peritoneal macrophages was prominently downregulated. When the actively treated mice were challenged with lipopolysaccharide (LPS), a TLR4 ligand, the host response was markedly impaired. Our results suggest that the oral administration of antimicrobials downregulates the expression of surface TLR on the peritoneal macrophages and modulates the host immune responses against LPS by modifying the intestinal environment.

The incidence, treatment and prognosis of cervical carcinoma in young women: a retrospective analysis of 4,975 cases in Japan.

OBJECTIVE: To determine the clinical characteristics of patients (young women) with cervical carcinoma aged less than 35 years. METHODS: Data from patients who were treated for cervical carcinomas from 1990 to 2000 in the Kinki District were retrospectively investigated for clinical stage, histologic type, treatment procedure and prognosis. RESULTS: Of a total of 4,975 cases, 441 patients were aged less than 35 years old. The incidence of cervical carcinoma in these women was 7.9% from 1990 to 1995, 9.1% from 1996 to 2000, and 9.5% from 2001 to 2005. FIGO Stage I included 374 cases, followed by, 49 in Stage II, 11 in Stage III, and seven in Stage IV. Squamous cell carcinoma incidence was 80.7% and non-squamous cell carcinoma incidence was 19.3%. Several types of surgery were performed in patients with Stage I and II, while patients with Stage III and IV were treated with radiotherapy and/or chemotherapy without any type of surgery. In patients who underwent lymphadenectomy, 21.1% cases had nodal involvement. The 5-year survival rate was 95% for Stage I disease, 73% for Stage II, 68% for Stage III, and 19% for Stage IV. CONCLUSION: The incidence of cervical carcinoma in young women slightly increased from 1990 to 2005. The prognosis of cervical carcinoma tends to be better in young women than in older patients, especially in Stage III disease.

Associations of obesity with modifiable risk factors for the development of cardiovascular disease in patients with rheumatoid arthritis.

OBJECTIVES: To assess the association of body mass index (BMI) with modifiable cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA). METHODS: BMI, disease activity, selected CVD risk factors and CVD medication were assessed in 378 (276 women) patients with RA. Patients exceeding accepted thresholds in >or=3 CVD risk factors were classified as having the metabolic syndrome (MetS). RESULTS: BMI independently associated with hypertension (OR = 1.28 (95% CI = 1.22 to 1.34); p = 0.001), high-density lipoprotein (OR = 1.10 (95% CI = 1.06 to 1.15); p = 0.025), insulin resistance (OR = 1.13 (95% CI = 1.08 to 1.18); p = 0.000) and MetS (OR = 1.15 (95% CI = 1.08 to 1.21); p = 0.000). In multivariable analyses, BMI had the strongest associations with CVD risk factors (F(1-354) = 8.663, p = 0.000), and this was followed by lipid-lowering treatment (F(1-354) = 7.651, p = 0.000), age (F(1-354) = 7.541, p = 0.000), antihypertensive treatment (F(1-354) = 4.997, p = 0.000) and gender (F(1-354) = 4.707, p = 0.000). Prevalence of hypertension (p = 0.004), insulin resistance (p = 0.005) and MetS (p = 0.000) was significantly different between patients with RA who were normal, overweight and obese, and BMI differed significantly according to the number of risk factors present (p = 0.000). CONCLUSIONS: Increasing BMI associates with increased CVD risk independently of many confounders. RA-specific BMI cut-off points better identify patients with RA at increased CVD risk. Weight-loss regimens should be developed and applied in order to reduce CVD in patients with RA.

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.

HIGH BACKGROUND AREA FOR RADIATION EDUCATION.

This paper describes our trial experience of the use of high radiation area for radiation education. We used environmental samples collected from the high radiation area in Fukushima prefecture and India, for the practice of radiation measurement and health risk assessment in Nagasaki University Medical School. We also carried out the field monitoring seminar for students in the existing exposure areas in Tottori prefecture and the Yamakiya observatory in Fukushima. Although the evaluation of educational effectiveness is still underway, both types of education appeared attractive for the students mostly due to the exposure from natural environment in our real life which was not achieved by using an artificial radiation source in a classroom.