The effect of folic acid supplementation on carotid intima-media thickness in patients with cardiovascular risk: a randomized, placebo-controlled trial.

INTRODUCTION: Observational studies have suggested a causal relationship between hyperhomocysteinemia and cardiovascular complications such as stroke and ischemic heart disease. The Homocysteine Lowering Trialists' Collaboration has shown that daily administration of folic acid can significantly decrease homocysteine levels up to 25%. Aim of this study was to investigate the effect of daily supplementation of folic acid (5 mg) on IMT after 18 months of treatment in patients with at least one cardiovascular risk factor. METHODS: We enrolled 103 patients with at least one cardiovascular risk factor who were randomized to receive either a daily dose of 5 mg folic acid (group I, n=53) or placebo (group II, n=50) for 18 months. RESULTS: After 18 months of folic acid supplementation, homocysteine levels were significantly reduced in the active treatment group compared to a non-significant increase in the placebo group. Folic acid levels were markedly increased in the former group and non-significantly reduced in the latter. Significant regression of carotid IMT was observed (0.961+/-0.092 to 0.933+/-0.077 mm, p<0.001) compared to significant IMT progression in the placebo group (0.964+/-0.099 to 0.984+/-0.094 mm). CONCLUSION: Folic acid supplementation results in significant IMT reduction after 18 months in patients with at least one cardiovascular risk.

An audit of tumour marker utilization in Greece.

INTRODUCTION: Several international organizations have published guidelines for the correct use of tumour markers in clinical practice. However, there are reports that clinicians do not adhere to these guidelines in clinical practice. The present study constitutes an audit of TM use in a major hospital in Northern Greece. Purpose of our study is to quantify the magnitude of inappropriate TM requests as well as the corresponding financial cost. METHODS: We examined retrospectively all TM requests between 10/2006 and 07/2007 in the department of biochemistry of our hospital. The tumour markers included in our study were: CA 19-9, CA 125, CA 15-3, AFP, NSE, CYFRA 21-1 and CEA. RESULTS: We found 9782 inappropriate TM orders. For five of them - namely CA 125, AFP, CA 19-9, CYFRA 21-1 and NSE - the proper requests were below 10%. There were 5.6 TM requests per patient. The total cost for inappropriate TM reached 239,748 euro, which corresponds to a monthly cost of 23,974euro. CONCLUSIONS: There is considerable inappropriateness in the utilization of TM in Greece which corresponds to significant financial cost. Various measures should be applied in order to increase the cost-effectiveness of TM use.

Is there any association between high-density lipoprotein, insulin resistance and non-alcoholic fatty liver disease in obese children?

Non-alcoholic fatty liver disease (NAFLD) is estimated to occur in about 50% of obese children. The purpose of this study is to examine the association of anthropometric, biochemical and liver indexes in obese children with and without NAFLD and its relation with insulin resistance (IR). Forty-three obese children participated in the study. NAFLD was diagnosed by ultrasonography. Liver indices (SGOT, SGPT), lipid profile, glucose and insulin levels were performed in all patients. IR was measured by means of the homeostasis model assessment and oral glucose insulin sensitivity. Among the 43 obese patients, 18/43 (41.8%) had NAFLD based on ultrasonography. Fifty percent of them had mild steatosis and 50% had moderate/severe steatosis. In logistic regression analysis of factors associated with NAFLD, homeostasis model assessment IR (ExpB, 1.607; 95% confidence interval, 1.058-2.440; P <0.02) and high-density lipoprotein (0.952; 95% confidence interval, 0.814-1.075; P <0.03) were the most significant. IR, as has already been proved, is associated with NAFLD. Furthermore, high-density lipoprotein levels seem to play an additional role in predicting NAFLD in obese children.

Ceruloplasmin is a better predictor of the long-term prognosis compared with fibrinogen, CRP, and IL-6 in patients with severe unstable angina.

BACKGROUND: We investigated the time course and prognostic value of fibrinogen (Fib), C-reactive protein (CRP), interleukin-6 (IL-6), and ceruloplasmin (CP) in patients with severe unstable angina. METHODS: All 4 substances were measured on admission and after 6, 12, 24, 48, and 72 hours, and after 7 days and 6 months in 40 patients with Braunwald's classification class IIIB unstable angina. RESULTS: All recorded substances increased significantly; 15 patients had cardiovascular events during hospitalization and 11 patients during follow-up. The time course and the mean values of Fib, CRP, and IL-6 were similar in patients with and without complications both during hospitalization and follow-up. However, CP levels from 6 hours until 6 months were significantly higher in patients with complications during follow-up (P < .05). CONCLUSIONS: Fib, CRP, IL-6, and CP levels alter in patients with severe unstable angina. However, only CP levels were related to 12-month follow-up prognosis.

Homocysteine and carotid intima-media thickness in ischemic stroke patients are not correlated.

INTRODUCTION: Hyperhomocysteinemia has been linked to cardiovascular morbidity and mortality by numerous authors. Whether this association is causal or not remains uncertain. The aim of the study was to investigate the association of hyperhomocysteinemia with the degree of carotid atherosclerosis in stroke patients. METHODS: We studied 97 Greek patients in our stroke unit who were hospitalized as a result of ischemic stroke between March 2006 and May 2007. The patients were divided into two groups: the first (52 patients) included stroke patients with serum levels of homocysteine below 15 mumol/L, but in the second group (45 patients) serum homocysteine exceeded this value. We measured carotid intima-media thickness (cIMT) in all patients and correlated it with serum homocysteine. RESULTS: The mean homocysteine concentration was 11.5 mumol/L in the first group and 21.5 mumol/L in the second group. Carotid IMT was 1.012 mm in the first group, and 1.015 mm in the second group, an insignificant difference. On the contrary, serum folate concentration was 21.3 nmol/L in the first group compared with 16.7 nmol/L in the second group (p < 0.001). VitB12 was 401 pmol/L in the first group and 340 pmol/L in the second group, a statistically significant difference (p < 0.001). CONCLUSIONS: Serum levels of homocysteine were not correlated with cIMT in ischemic stroke patients. Both folate and vitB12 were decreased in hyperhomocysteinemic ischemic stroke patients.

Are saturated fatty acids and insulin resistance associated with fatty liver in obese children?

BACKGROUND: Fatty liver (FL) is a common cause of liver disease in children. Obesity and insulin resistance (IR) play an important role in pathogenesis of FL. Diet has been reported to affect IR and possibly FL. The purpose of this study was to investigate certain parameters (anthropometric, biochemical, dietary intake) of obese Greek children with and without FL. METHODS: Forty-three obese children aged 9-14 (25 boys/18 girls) participated in the study. FL was diagnosed by ultrasonography (US). Liver indexes (ALT, AST, gamma-GT) were measured in all children. A 3-day dietary was recorded for all subjects. None of the subjects were positive for viral hepatitis or had a history of consuming alcohol. RESULTS: Eighteen out of 43 subjects (41.8%) had FL based on US. Intakes of carbohydrates and simple refined carbohydrates were significantly higher in subjects with FL compared to children without FL, while saturated fatty acids (SFA) were proportionally increased to the degree of hepatic steatosis. In multiple regression analysis of factors associated with FL, only HOMA-IR [Beta: 0.160, 95%CI (0.122-1.340), P<0.001] and SFA [Beta: 0.455, 95%CI (0.129-2.129), P<0.001] were the most significant one. CONCLUSIONS: Our results suggest that high intake of carbohydrates and simple refined carbohydrates as well as low intake of fiber may be correlated with the pathogenesis of FL. Moreover, IR and high intake of SFA are independently associated with FL in obese children.

The administration of estrogens, combined with anti-androgens, has beneficial effects on the hormonal features and asymmetric dimethyl-arginine levels, in women with the polycystic ovary syndrome.

The present study was designed in order to: (a) compare ET-1 and ADMA levels, between women with PCOS (n=106) and healthy controls (n=30); (b) determine the effects of treatment with estrogens and anti-androgens on the hormonal features of PCOS, insulin resistance, ET-1 and ADMA levels. Women with PCOS were randomized in five therapeutic protocols: (I) 17beta-estradiol+cyproterone acetate 50mg; (II) conjugated estrogen+CA 50 mg; (III) ethinyl estradiole+CA 2mg; (IV) EE+CA 52 mg; (V) EE+desogestrel. In all women, gonadotropin, PRL, androgen, SHBG, insulin, glucose, ET-1 and ADMA levels were determined; in women with PCOS, testosterone, SHBG, ET-1 and ADMA levels were measured again after 3, 6, 12 months of treatment and insulin and glucose levels after 12 months. ET-1 and ADMA concentrations were higher in women with PCOS, and they were positively correlated with each other. ADMA levels were decreased and IR was increased with treatment. Treatment with synthetic estrogens (EE) resulted in a more pronounced increase in SHBG and a more pronounced decrease in FAI, compared to natural estrogens. Conclusively, PCOS is associated with endothelial dysfunction, which is ameliorated by the administration of estrogens and anti-androgens, independent of IR.

Discrimination indices as screening tests for beta-thalassemic trait.

The two most frequent microcytic anemias are beta-thalassemic trait (beta-TT) and iron deficiency anemia (IDA). Several discrimination indices have been proposed to distinguish between these two conditions. These indices are derived from several simple red blood cell indices, like red blood cell (RBC) count, mean cell volume, and RBC distribution width (RDW), as these are provided by electronic cell counters. The purpose of the study is to examine the diagnostic accuracy of six discrimination indices in the differentiation between IDA and beta-TT. The six discrimination indices that were examined were as follows: Mentzer Index (MI), Green & King Index (G&K), RDW Index (RDWI), England & Fraser Index (E&F), RDW, and RBC count. We calculated these indices on 373 patients (205 men, 168 women) with beta-TT and 120 patients (50 men, 70 women) with IDA, as well as their sensitivity, specificity, positive and negative prognostic value, efficiency, and Youden's index (YI). G&K shows the highest reliability, followed by E&F, RBC count, MI, and RDWI. On the contrary, RDW completely failed to differentiate between IDA and beta-TT. G&K proved to be the most reliable index as it had the highest sensitivity (75.06%), efficiency (80.12%), and YI (70.86%) for the detection of beta-TT. These six discrimination indices cannot be relied on for a safe differential diagnosis between beta-TT and IDA. They do have high specificity, but their sensitivity for the detection of beta-TT is not satisfactory. Consequently, they cannot be used neither as a screening tool for beta-TT because they could result in a significant number of false negative results.

Serum lipase after secretin stimulation detects mild pancreatic involvement in cystic fibrosis.

BACKGROUND: The assessment of severe pancreatic insufficiency in cystic fibrosis (CF) is not a diagnostic problem. However, identification of mild cases remains a challenge. The aim of this study was to assess the ability of serum lipase after secretin stimulation to identify mild pancreatic insufficiency in patients with CF. MATERIAL AND METHODS: Thirty patients with CF and pancreatic insufficiency (CF-PI) and 30 patients with CF and pancreatic sufficiency (CF-PS) were studied. Thirty healthy subjects with no known gastrointestinal disease served as controls. In all subjects, fecal fat excretion, fecal elastase-1 (E1) concentration and basal and secretin-stimulated serum lipase concentration were measured. RESULTS: All patients with CF-PI and 3 with CF-PS had abnormally low fecal E1 concentrations. The remaining 27 CF-PS patients and all controls had normal values. Basal and post-stimulation lipase levels were extremely low in patients with CF-PI. Mean basal and poststimulation serum lipase concentrations were significantly higher in CF-PS who had normal fecal E1 concentrations but were still below those of controls (P < 0.001). Among the 27 CF-PS patients with normal fecal elastase, high basal and poststimulation lipase values were found in 6 and 17 patients respectively. CONCLUSION: In patients with CF-PS who have normal fecal elastase-1 concentration, the measurement of basal or secretin-stimulated lipase levels might be helpful in identifying the progression of the destructive process in the pancreas.

The influence of continuous seven-day elevated intra-abdominal pressure in the renal perfusion in cirrhotic rats.

Since hepatorenal syndrome is a functional renal failure due to renal ischemia in cirrhotics with refractory ascites, we investigated whether increased intra-abdominal pressure (IAP) impairs the renal function and perfusion in cirrhotic portal hypertensive rats. Eight groups of 32 rats each were studied, including 4 control and 4 CCl(4) cirrhotic groups. These were subdivided into two groups each, with and without an increased IAP, and further subdivided into groups of rats with and without NO inhibition. IAP was increased to 20 mm Hg for 7 consecutive days by means of an intraperitoneally placed balloon filled with water. The animals were studied in normal conditions and after inhibition of NO synthesis. Changes in mean arterial pressure and renal microcirculation by means of femoral artery catheterization and laser-Doppler technique, respectively, were recorded. Venous samples for determination of plasma renin-aldosterone activity, biochemical parameters of liver and renal function, and plasma nitrite/nitrate levels as an index of NO synthesis were drawn. Cirrhotic rats showed decreased renal microcirculation (P = 0.05), while elevated IAP produced a further decrease (P = 0.01). Renin-aldosterone levels found increased (P = 0.001) in cirrhotics, and elevated IAP produced a further increase (P = 0.01] in both groups. Inhibition of NO synthesis resulted in a nonsignificant decrease in both renal microcirculation and renin-aldosterone levels in all experimental groups. Liver and renal function was found to be impaired in cirrhotics, but increased IAP had a nonsignificant further functional impairment in both organs. In conclusion, chronically elevated IAP in cirrhotic rats is associated with an increase in renin-aldosterone levels and significant impairment of renal perfusion.