G. Kakuk

Effect of a Novel Free Radical Scavenger, Edaravone (MCI-186), on Acute Brain Infarction

Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. The present study was undertaken to verify its therapeutic efficacy following acute ischemic stroke. We performed a multicenter, randomized, placebo-controlled, double-blind study on acute ischemic stroke patients commencing within 72 h of onset. Edaravone was infused at a dose of 30 mg, twice a day, for 14 days. At discharge within 3 months or at 3 months after onset, the functional outcome was evaluated using the modified Rankin Scale. Two hundred and fifty-two patients were initially enrolled. Of these, 125 were allocated to the edaravone group and 125 to the placebo group for analysis. Two patients were excluded because of subarachnoid hemorrhage and disseminated intravascular coagulation. A significant improvement in functional outcome was observed in the edaravone group as evaluated by the modified Rankin Scale (p = 0.0382). Edaravone represents a neuroprotective agent which is potentially useful for treating acute ischemic stroke, since it can exert significant effects on functional outcome as compared with placebo.

The Serum Paraoxonase Activity in Patients with Chronic Renal Failure and Hyperlipidemia

Human serum paraoxonase is physically associated with an apolipoprotein (Apo-A1) and clusterin-containing high-density lipoprotein (HDL) and prevents low-density lipoprotein from lipid peroxidation. The aim of our study was to determine whether paraoxonase activity or phenotype is altered in patients with chronic renal failure and in hyperlipidemic subjects without renal insufficiency and to compare the values with those of healthy controls. We investigated the serum paraoxonase activity and polymorphism in 119 hemodialyzed uremic patients, 107 patients with primary hyperlipoproteinemia, and in 110 healthy control subjects. The serum paraoxonase activity was significantly decreased both in hyperlipidemic (p < 0.01) and uremic patients (p < 0.001) as compared with controls. On comparison, the serum paraoxonase activity was significantly lower (p < 0.001) in uremic than in hyperlipoproteinemic patients. The HDL and Apo-A1 levels were as follows: uremic < hyperlipidemic < control. To assess whether the observed reduction in paraoxonase activity was due to HDL and Apo-A1 level decreases, we standardized the enzyme activity for HDL and Apo-A1 concentrations. We found that the standardized paraoxonase activity (paraoxonase/HDL ratio) was also lower in the uremic patients (103.3 ± 69.5) as compared with hyperlipidemic patients (137.64 ± 81.0) and controls (194.45 ± 94.45). The standardized values for Apo-A1 showed a similar tendency: paraoxonase/Apo-A1 ratio in uremic patients 89.64 ± 47.8, in hyperlipidemic patients 128.12 ± 69.83, and in controls 161.40 ± 47.35. The phenotypic distribution of paraoxonase (AA, AB, BB) did not change significantly in the patient groups. These results suggest that HDL concentration and phenotypic distribution of paraoxonase may not be the only determining factors, but that other as yet undetermined factors could be involved in the enzyme activity changes.

Serum paraoxonase activity changes in uremic and kidney-transplanted patients

Serum paraoxonase (PON) is a high-density lipoprotein (HDL)-associated hydrolase, which inhibits low-density lipoprotein oxidation. Uremic and kidney-transplanted patients have an increased risk of atherosclerosis, to which an increased lipoprotein oxidation may contribute. The aim of our study was to determine whether the PON activity or phenotype is altered in uremic and kidney-transplanted patients, and to compare the values with those of healthy controls. 117 uremic patients on long-term hemodialysis treatment, 115 renal-transplanted patients, and 110 healthy controls were involved in the study. The PON activity was significantly reduced in the uremic patients compared to controls (PON 101.36±30.12 vs. control 188.05±58.96 U/ml; p < 0.001), while in kidney-transplanted patients the values were almost identical to those of controls (PON 161.5±35.39 U/ml). The different immunosuppressive drug combinations did not influence PON activity. To assess whether the altered PON activity was due to a decrease HDL level, we standardized the enzyme activity for the HDL concentration (PON/HDL ratio). We found that the standardized enzyme activity was lower in the uremic (102.7±54.8) and kidney-transplanted patients (144.5±32.7) when compared to controls (194.5±94.5; p < 0.001). The phenotypic distribution of PON in uremic, renal transplant and control patients are as follows: AA 66.67, 56.48 and 66.67%; AB 31.62, 33.3 and 26.67%; BB 1.71, 10.19 and 6.67%. We conclude that the decreased PON/HDL and PON/apoA-1 ratios may lead to a reduction in the antioxidant capacity of HDL, which might contribute to the accelerated development of atherosclerosis in uremic and kidney-transplanted patients.

The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the differential diagnosis of cold thyroid nodules

Abstract. Various diagnostic techniques have been successfully used in the clinical management of cold nodules; however, the decision on whether to employ surgery or a conservative treatment is not always easy. This study was designed to appraise the diagnostic value of technetium-99m methoxyisobutylisonitrile (MIBI) scintigraphy in the assessment of cold nodules detected using 99mTc-pertechnetate. Fifty-two patients were included in the study. All had already been selected for surgery, based on their clinical and laboratory findings, including fine-needle aspiration biopsy. The total number of cold nodules on 99mTc-pertechnetate scans was 59. The thyroid scan was performed 20-40 min after i.v. injection of 400 MBq of 99mTc-MIBI. Uptake of MIBI in thyroid nodules was compared with that in the surrounding normal thyroid tissue, and a score of between 0 and 3 was assigned to each nodule as follows: 0, cold; 1, decreased; 2, equal; 3, hot. Definitive histology revealed nodular goitre in 24 cases, adenoma in 19, thyroiditis in 1, differentiated cancer in 12, medullary cancer in 2, and anaplastic cancer in 1. None of the degenerative nodules were hot on MIBI scan, while the adenomas showed a variety of MIBI imaging patterns, most frequently the score 3 pattern. In the diagnosis of differentiated thyroid cancer the sensitivities of score 3 and score 2+3 MIBI uptake patterns were 83% (10/12) and 100%, respectively. The score 3 MIBI uptake pattern had a specificity of 100% and a positive predictive value of 100% with respect to thyroid (benign and malignant) neoplastic diseases, whereas a specificity of 72% and a positive predictive value of 43% were observed in the detection of differentiated cancer. After a cold nodule had been detected using 99mTc-pertechnetate, a second scan with high MIBI uptake increased by 7.8 times the probability that this nodule would be a differentiated cancer. In conclusion, 99mTc-MIBI scintigraphy is a useful method in the differential diagnosis of cold thyroid nodules if the primary aim is to differentiate degenerative from neoplastic diseases rather than to differentiate benign from malignant nodules. High MIBI uptake considerably increases the probability of a differentiated thyroid cancer and facilitates immediate surgical removal, while decreased uptake actually excludes it. We suggest a combination of fine-needle aspiration biopsy and MIBI scan as a routine diagnostic approach to cold thyroid nodules.

Increased common carotid artery intima media thickness in adolescent hypertension: Results from the Debrecen Hypertension Study

Background: The aim of the present work was to investigate intima media thickness (IMT) in healthy and in hypertensive adolescents and its influencing factors. Methods: 103 hypertensive and 58 healthy adolescents were studied. IMT was measured in the common carotid artery using B-mode ultrasonography. Additionally, laboratory parameters (blood glucose, cholesterol, triglycerides, HDL- and LDL-cholesterols) and left ventricular mass indices were obtained. Results: IMT in the common carotid artery was higher in hypertensive adolescents (means ± SD: 0.55 ± 0.11 mm) than in healthy control subjects (0.48 ± 0.08 mm, p < 0.001). Similarly, a higher left ventricular mass index was measured in hypertensive (103.2 ± 30.6 g/m2) than in healthy teenagers (91.1 ± 25.2 g/m2, p < 0.001). In general, IMT in adolescents was associated with age, weight, body mass index, left ventricular mass index and average systolic and diastolic blood pressure values of the subjects. By assessing the multivariate association between IMT and other factors, intima-media thickness was only associated with age and left ventricular mass index of the hypertensive subjects and was independent from all the investigated factors in normotensive controls. Conclusions: Our data suggest an ongoing target-organ damage in adolescent hypertension. These patients need to be subjected to early diagnostic methods, treatment and a regular follow-up, in order to avoid severe clinical manifestations of secondary target-organ damage due to hypertension.

Blood pressure distribution in a Hungarian adolescent population: comparison with normal values in the USA.

Objectives To describe the blood pressure characteristics and distribution of all adolescent high school students (aged 15–18 years) in Debrecen (total population 230 000), Hungary. To define threshold values for normal blood pressure by age-, sex- and height-specific groups. To compare our data with results from a USA meta-analysis, which forms the basis of current guidelines. Participants and methods All young people attending high school in Debrecen (final sample n = 10 359) participated in the study. After they had rested for 10 min, three blood pressure measurements were taken from the right upper arm, separated by 5 min intervals. All measurements were obtained by a validated, automated, digital Omron M4 device. Results The 50th, 90th and 95th percentile values of blood pressure were defined by dividing the adolescent population into age-, sex- and height-specific subgroups. In comparison with USA guidelines, in our sample the systolic blood pressure of boys in the different subgroups was 6–11 mmHg greater, whereas this difference was less marked for girls (1–5 mmHg). There were no marked differences in diastolic blood pressure, but our values were slightly lower. Conclusions Our findings demonstrate the influence of geographical and ethnic variations on blood pressure. Acceptance and use of non-population-specific blood pressure distributions may lead to under- or overdiagnosis of adolescent hypertension. The use of geographically more relevant data should be encouraged.

Relative Abundance of Some Free Fatty Acids in Plasma of Uremic Patients: Relationship between Fatty Acids, Lipid Parameters, and Diseases

The unesterified fatty acid patterns in plasma of predialytic (PHD) and hemodialysis (HD) patients were determined. The HD patients were divided into three groups: (1) HD without cardiovascular disease (HD-norm); (2) HD with cardiomyopathy (HD-CAD), and (3) HD with hyperlipidemia (HD-hyp). The relative abundance of saturated fatty acids (SFAs) was greater in the plasma of HD-norm and HD-CAD patients (73.3 and 70.0%, respectively) than that in controls (62.6%), and the relative abundance of monounsaturated fatty acids (MUFAs) was significantly greater in the plasma of HD-hyp patients than that in controls (38.9 vs. 21.6%, p < 0.01). In all HD patients the relative concentration of polyunsaturated fatty acids (PUFAs) was lower than in controls. There were no significant differences in the fatty acid patterns of PHD patients. In conclusion, the relative abundance of SFAs and MUFAs in plasma of HD patients is associated with their concomitant lipid disorders and cardiomyopathy, while the low relative abundance of PUFAs was common in all HD patients.

Study of cross-sectional and longitudinal distribution of some major and minor elements in the hair samples of haemodialysed patients with micro-PIXE

The concentration of Zn, K, Ca, Fe and Cl was determined in the hair samples of haemodialysed patients and healthy controls. Cross-sectional and longitudinal measurements were performed using the micro-PIXE method. The concentration changes of the above mentioned elements along the length of the hair and their cross-sectional distribution were studied. The effect of the washing procedure on the concentration of these elements has also been determined. The ability of the PIXE method was examined using Human Hair certified reference material (NCS DC 73347), and the results show that this method can be used to determine the concentration of the selected elements in the hair samples. We compared the results of the PIXE method with the results obtained from microwave digested reference material with the ICP-OES method. The concentration ranges of Ca, Fe and Zn were similar in the patients and controls while the concentration ranges of Cl and K were different (controls: Ca, 135-1598; Cl, 394-2382; Fe, 6-51; K, 54-1055; Zn, 102-183 µg g –1 ; versus patients: Ca, 298-559; Cl, 2476-7821; Fe, 15-58; K, 327-2031; Zn, 96-163 µg g –1 ). The washing procedure highly affected the concentration of K and Cl (unwashed: K, 1164±846; Cl, 6107±1714 µg g –1 ; versus washed: K, 497±552; Cl, 3470±1446 µg g –1 ). There were no differences between controls and patients in the cross-sectional distribution of the selected elements; the distribution of Cl was homogeneous, the Ca was concentrated in the outer layer of the hair while the distribution of K was nearly homogeneous with a slight increase at the outer layer.

Fever of unknown origin with seronegative spondyloarthropathy: an atypical manifestation of Whipple's disease

Many authors emphasise the diagnostic difficulties and point out the multifaceted nature of Whipples disease.1,2 Joint symptoms are present in 90% of all cases and may precede other disease manifestations by decades.3 We report here a case with fever of unknown origin accompanied by seronegative spondyloarthropathy with no typical gastrointestinal symptoms and initially negative upper panendoscopy. To confirm the diagnosis, the bacterial 16S ribosomal RNA sequence of Tropheryma whippelii was determined by polymerase chain reaction (PCR). A 58 year old white man had a 12 year history of intermittent arthralgias and seronegative polyarthritis. In 1993, monolateral stage II sacroiliitis was disclosed with no definite cause. Low dose methylprednisolone treatment was started, but there was no clinical improvement. In 1998 the patient became febrile, lost 10 kg of weight but had no gastrointestinal symptoms. He underwent an extensive examination, including radiological examinations of the chest and paranasal sinuses, abdominal sonography, echocardiography, abdominal computed tomography, upper panendoscopy, bone marrow biopsies, whole body gallium-67 citrate scan, multiple blood, stool, and urine cultures, as well as serological investigations for known …

Comparison of the Lipid-Lowering Effects of Fluvastatin, Lovastatin and Simvastatin in Patients with Hyperlipoproteinaemia

AbstractObjective: The pathogenesis of coronary artery disease is influenced by several risk factors, of which one of the most prominent is hypercholesterolaemia. The aim of this study was to compare the effect of fluvastatin, lovastatin and simvastatin on lipid levels in the same patients following a standard lipid-lowering diet. Patients: This was a comparative study in 25 patients with primary hypercholesterolaemia Fredrickson type IIb, 18 of whom completed the study. Design: After a 6-week washout period, patients were treated for 1 month with fluvastatin 20 mg/day, after which the dosage was increased to 40 mg/day. Lipid parameters were measured at baseline and after 1 and 2 months. The study drug was then continued for a further 8.5 months until the beginning of the next washout period. At that time (i.e. 1 year after the first study) the same pattern was followed using lovastatin 20 and 40 mg/day; finally, the treatment pattern was repeated in the third year with simvastatin 10 and 20 mg/day. Results: All three agents significantly decreased low density lipoprotein and total cholesterol levels (p < 0.001). Simvastatin had the most pronounced cholesterol-lowering effect. Lovastatin and fluvastatin caused no significant change in the level of high density lipoprotein (p = 0.74 and p = 0.19), whereas simvastatin increased it significantly by 8% (p = 0.029). In contrast with fluvastatin, lovastatin and simvastatin significantly decreased apolipoprotein B-100 (p = 0.81 vs 0.039 and <0.001, respectively). Apolipoprotein A was not changed significantly by any drug (p = 0.06, 0.59 and 0.28, respectively). Conclusions: Simvastatin was a more effective lipid-lowering drug than fluvastatin or lovastatin in this study of the sequential administration of the three drugs to the same group of patients over a 3-year period. This internally controlled study supports the results of previous parallel-group studies showing simvastatin to be the most effective of these three drugs.