Multiple symmetric lipomatosis - a reflection of new concepts about obesity.

Multiple symmetric lipomatosis (MSL) is characterized by subcutaneous accumulation of nonencapsulated adipose tissue. In type 2 MSL accumulation occurs on proximal limbs, upper back and hips. This sometimes unrecognized disease is similar to an exaggerated female fat distribution and can be confused with simple obesity. Obesity is a heterogeneous disorder and we suppose that type 2 MSL might have a place on the edge of the obesity spectrum. Several contemporary concepts about adipose tissue could be recognized in the model of MSL. Changes in fat distribution among different depots of adipose tissue in obesity have emerged as origin of its metabolic complications. Decreased insulin resistance and raised adiponectin have been found in MSL just as in some other conditions with accumulation of the subcutaneous adipose tissue (SAT). In that context, MSL may present as a model for possible favourable metabolic impact of SAT depots. Adipogenesis in MSL is not a consequence of energy excess but it is an active hyperplastic proliferation of SAT. This kind of behaviour of some adipocytes in several subcutaneous areas in MSL suggests that the energy unrelated adipogenesis could contribute to the expansion of at least a part of SAT depot in obesity in general. Contrary to current concept that the signals for adipogenesis are dependent only on the energy equation, allowing this additional mechanism would imply a new approach to issues of obesity, foremost to differentiate its particular types for which these concepts may be relevant.

IgH and TCRgamma gene rearrangements, cyclin A1 and HOXA9 gene expression in biphenotypic acute leukemias.

In this study we investigated IgH and TCRgamma gene rearrangements, cyclin A1 and HOXA9 gene expression as well as the in vitro growth of biphenotypic acute leukemia (BAL) blasts in relation to acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The aim of the study was to correlate BAL morphology and its biological parameters in order to get information that might be used for additional stratification of BAL. This rare form of AL was identified in a total of 10 patients, comprising 4.3% of adult and 3.0% of pediatric patients with de novo AL referred to our institution during the 1999-2003 period. Our results indicate that IgH and TCRgamma gene rearrangements correlated well with lymphoid BAL morphology, whereas the expression of cyclin A1 correlated with myeloid and undifferentiated BAL morphology. Surprisingly, HOXA9 expression, a marker associated with myeloid cell lineage, showed no strong correlation with BAL morphology. Finally, in vitro growth of blasts during a 7-day culture showed autonomous cell growth in 3/10 AML and 3/8 myeloid BAL samples tested, but not in any of the AL with lymphoid features. Further studies are needed to confirm these findings and to extend research to a broader spectrum of cell markers.

Expression of cyclooxygenase-2 in fine-needle aspirates from breast carcinoma and benign breast diseases.

Numerous studies have demonstrated that the levels of cyclooxygenase (COX), the enzyme that catalyzes the conversion of arachidonic acid to prostaglandin H(2), and of prostaglandins are higher in various tumors and cells during inflammation than in normal tissues. The aim of the present study was to analyze whether COX-2 isoform expression was noticeably higher in fine-needle aspirates (FNA) from breast carcinoma than in FNA from fibroadenoma and fibrocystic breast tissue. COX-2 expression was detected by immunocytochemical (IC) staining and was analyzed by microscopic scoring and computer gray-scale analysis. Evaluation of COX-2 IC positivity in FNA from three groups of patients (nine with breast carcinoma, nine with fibroadenoma, eight with fibrocystic breasts) revealed high COX-2 IC positivity in the majority of patients with breast carcinoma and low or absent COX-2 IC positivity in patients with fibrocystic breast changes. In addition, low or medium COX-2 IC positivity was found in the majority of patients with fibroadenoma, only three of these patients having high COX-2 IC positivity.

Treatment of autonomous and toxic thyroid adenomas by percutaneous ultrasound-guided ethanol injection.

PURPOSE: To evaluate the feasibility and efficacy of US-guided percutaneous ethanol injection (PEI) in the treatment of autonomous and toxic thyroid adenomas. MATERIAL AND METHODS: PEI was performed in 42 patients with solitary, scintigraphically "hot" nodules (n=37) or toxic nodular goiter (n=5). The nodular volume ranged from 2.5 to 38 cm3 (mean volume, 20.7+/-14.1 cm3). Ethanol was injected using a free-hand technique, usually in multiple sessions, using color and power Doppler US guidance. Treatment success was evaluated following 3-4 months after PEI by scintigraphy, hormonal status, and US findings. RESULTS: The procedure was technically successful in 39 patients (93%). Three patients were lost to follow-up. Minor complications were pain (all patients), subcutaneous hematoma (n=6), and transitory dysphonia (n=1). A complete cure was achieved in 22 patients (52%), and a partial cure in 10 patients (24%). In 4 cases (9%), the result was unsatisfactory since only moderate hormonal remission was observed. A satisfactory results was thus achieved in 32/42 patients (76%). Significant nodular volume reduction was observed in all cases. Better results were observed in smaller nodules and in cases of autonomous adenomas. There were no cases of recurrent hyperthyreosis. CONCLUSION: US-guided PEI is an efficient and safe method in the treatment of autonomous thyroid nodules and it enables inactivation of nodules with minimal or transitory complications.

A novel missense mutation C127R (FH Zagreb) in the LDL-receptor gene.

We employed the analysis of single-strand conformation polymorphisms to identify mutations in exon 4 of the low density lipoprotein receptor gene causing familial hypercholesterolemia. Three familial hypercholesterolemia heterozygotes had abnormal single-strand conformation polymorphism patterns. DNA sequencing revealed that the abnormal pattern of exon 4A was due to heterozygosity (T/C) at nucleotide 442. Nucleotide 442 is the first base of codon 127, and the T-->C mutation (C127R) changes this codon from CysTGT to ArgCGT. Abnormal patterns of exon 4B were due to heterozygosity (A/G) at nucleotide 662: nucleotide 662 is the second base of codon 200, and the A-->G mutation (D200G) changes this codon from AspGAC to GlyGGC. Mutation D200G was previously described as FH Padova, but mutation C127R (FH Zagreb) has not been reported previously. This novel mutation was confirmed by restriction endonuclease analysis with Dsa I. The screening of 420 familial hypercholesterolemia heterozygotes suggests that C127R and D200G account for about 0.7% of mutations causing familial hypercholesterolemia in Croatia.

[In situ PCR in the diagnosis of acute leukemia]. / PCR in situ u dijagnostici akutnih leukemija.

Cytomorphologic and cytochemical bone marrow analysis is essential in the diagnosis of acute leukemia. Immunophenotyping and conventional cytogenetics, just as fluorescent in situ hybridization (FISH) are other diagnostic procedures, as well as genome analysis by PCR (polymerase chain reaction). PCR is inevitable in searching for minimal residual disease, because it may detect very small amount of malignant hematopoietic cells even when a patient is in complete remission (less than 5% malignant cells in bone marrow and disappearance from peripheral blood) which helps better monitoring of patients. By in situ hybridization (ISH) it is possible to associate specific cell type with genome alteration, but the method is not sensitive enough. By combining ISH and PCR a novel technique with increased sensitivity was developed, PCR in situ, which enables nucleic acid amplification in an intact cell. In this case report we present two patients whose bone marrow aspirates were analyzed also by PCR in situ.

Effects of a membrane-metallopeptidase blocking agent thiorphan in long-term cultures of human bone marrow.

Thiorphan [(DL-3-mercapto-2-benzylpropanoyl)-glycine], a drug blocking the activity of membrane metalloendopeptidase EC 3.4.24.11 (CD10, CALLA), was added to long-term cultures of human bone marrow. Progression of the cultures was assessed by cell counts, cytology and clonogenic (GM-CFU) ability of the non-adherent cells in the supernatant and by morphology of the adherent stromal layer. A stimulatory effect on hematopoiesis was noted.

Double immunoenzymatic APAAP staining for the detection of leukemia-associated immunophenotypes.

Detection of unusual or aberrant cell immunophenotype with flow cytometry is the basis for the immunologic recognition of minimal residual disease (MRD) in patients with acute leukemia (AL). In this study, we have shown that the double immunocytochemical alkaline phosphatase antialkaline phosphatase (APAAP) staining technique also makes possible the detection of leukemic cells with unusual (leukemic) combinations of antigens (ULCA) both at diagnosis and during follow-up of patients with ULCA+ AL. The applicability of double APAAP was analyzed on bone marrow (BM) samples obtained from 12 patients (8 with AML, 3 with ALL, and 1 with undifferentiated acute leukemia [AUL]) randomly chosen from a larger group of 22 ULCA+ patients treated at our center in a 3-year period (22% observed ULCA+ AL frequency). The percentages of ULCA+ BM cells before chemotherapy were in the range of 5%-60%, which dropped to 0%-7% in 10 patients who achieved remission (range 0%-7%, p < 0.01). However, these cells could also be found 60 days after the initiation of therapy, ranging from 0%-2% of all nucleated cells. In 2 of 10 patients who achieved remission, 2% ULCA+ BM cells were found on days 35 and 60 after initiation of chemotherapy, and this finding was followed by relapse on days 110 and 270. However, the other 8 patients remained in remission despite positive finding of ULCA+ BM cells ranging from 0.2%-2% on at least one occasion. In 2 patients with AML FAB-M3 and cytomorphologic remission, the finding of ULCA+ cells by double APAAP correlated with the molecular finding of PML/RARalpha junction. These results indicate that double APAAP staining can identify leukemic cells in samples with a cytomorphologic pattern consistent with remission, but its applicability in detection of MRD awaits additional studies on a larger number of patients with ULCA+ AL.

Analysis of clonality in T-lymphoproliferative diseases by multiplex PCR.

Distinction between benign and malignant T-cell lymphoproliferative diseases can be difficult using morphological criteria. Using multiplex polymerase chain reaction system we have tested a series of patients with various lymphoproliferative disorders to detect clonal T-lymphocyte populations. Results show that clonal amplification products were obtained from all 10 patients with T-cell lymphoproliferative disorders while the amplification of DNA samples from B-cell neoplasms and normal individuals revealed polyclonal amplification products. By splitting the multiplex primer mix, the patient specific T-cell receptor gamma rearrangement was determined: five out of ten patients showed the exclusive presence of a single T-cell receptor gamma gene rearrangement. Three patients exhibited two rearranged T-cell receptor gamma genes, while in two patients positive reactions were obtained with three pairs of primers for variable and joining segments. Molecular analysis of rearranged T-cell receptor genes by multiplex polymerase chain reaction represents a useful and rapid tool for confirming diagnosis, to determine the extent of disease and to monitor the response to therapy.

Relation between urinary cytology abnormalities and cyclosporine A therapy in bone marrow transplant recipients.

The aim of the study was to determine the relationship, if any, between abnormalities in urinary cytology and the administration of cyclosporine A in bone marrow transplant recipients. Specific attention was given to the presence of tubular cells with round inclusions (TCRI). Two bone marrow transplant recipient groups were studied: one with allogeneic bone marrow transplantation (BMT) (20 patients) who were treated with cyclosporine A, and the other with autologous BMT (12 patients) who did not receive cyclosporine A. Urinary cytology showed TCRI in 41.66% of the patients after autologous BMT and in 80% of the patients after allogeneic BMT. In the group of patients treated with allogeneic BMT, the occurrence of TCRI was associated with a high incidence of glycosuria and was followed by an increase in the blood level of cyclosporine A, an increase in the serum creatinine concentration and a decrease in the creatinine clearance. These results demonstrated that TCRI, although related to, were not found to be exclusively specific to the administration of cyclosporine A.

Lipoprotein (a) levels in thyroid dysfunction before and after treatment.

AIM: To investigate the possible effects of thyroid hormones on the lipoprotein (a) (Lp(a)) serum concentration. METHODS: Eleven patients with hyperthyroidism (Grave's disease), 18 patients with hypothyroidism and low Lp(a) (Hashimoto's disease), and 13 patients with hypothyroidism (Hashimoto's disease) and elevated Lp(a) were examined before and after thyroid hormone normalization. The measurements included total cholesterol, HDL cholesterol (including HDL2 and HDL3 subfractions), LDL cholesterol, VLDL cholesterol, triglycerides, apoproteins A1 and B, and Lp(a), thyrotropin (TSH) and thyroid hormones/total thyroxine (T4), triiodothyronine (T3), free thyroxine (FT4), and free triiodothyronine (FT3). RESULTS: In patients with hyperthyroidism, serum concentrations of total cholesterol, LDL cholesterol, and apo B significantly increased (p<0.05) after the treatment, whereas a moderate increase in HDL (HDL2 subfraction), triglyceride, and Lp(a) concentrations did not reach statistical significance. In both groups of patients with hypothyroidism, concentrations of total cholesterol, LDL cholesterol, apo B, and triglycerides significantly decreased after the treatment, whereas the changes in HDL (HDL2 and HDL3 subfractions), VLDL cholesterol, apo A1, and Lp(a) were not significant. CONCLUSION: Thyroid hormones had only a moderate effect on the metabolism of Lp(a).

Hyperinsulinemia and sex hormones in healthy premenopausal women: relative contribution of obesity, obesity type, and duration of obesity.

Insulin secretion in response to an oral glucose tolerance test (OGTT) and sex hormone levels (free testosterone, androstenedione, dehydroepiandrosterone sulfate [DHEAS], estradiol, and sex hormone-binding globulin [SHBG]) were evaluated in 49 healthy obese premenopausal women (body mass index [BMI], 30 to 50.6 kg/m2) and 21 control subjects (BMI, 17.8 to 24.0 kg/m2) with normal glucose tolerance and without signs of hyperandrogenism. Obese women were divided into two groups according to waist to hip ratio (WHR): 27 subjects with upper-body obesity (WHR > 0.85) and 22 subjects with lower-body obesity (WHR < 0.8). Both fasting and glucose-induced insulin levels were higher in women with upper-body obesity than in controls (P < .001) and those with lower-body obesity (P < .001). Hyperandrogenism was observed in women with upper-body obesity, as evident by significantly elevated free testosterone (P < .05 v controls and subjects with lower-body obesity) and decreased SHBG (P < .001 v controls). The most important independent determinants of fasting insulin levels were BMI (P < .01) and the ratio of DHEAS to free testosterone (P < .01). The most important determinants of cumulative insulin response were WHR (P < .0005), duration of obesity (P < .01), and androstenedione levels (P < .01). In conclusion, in healthy obese premenopausal women without clinical signs of hyperandrogenism, a high BMI and more pronounced upper-body fat localization resulted in hyperinsulinemia and hyperandrogenism. The duration of obesity exaggerated the glucose-induced insulin level and cumulative insulin response independently of the degree of obesity and obesity type. The ratio of DHEAS to free testosterone was an independent determinant of fasting insulin concentration. Furthermore, the ratio of DHEAS to free testosterone rather than either of these androgens alone may be important in the regulation of insulin action in women.

Effect of dietary fish supplementation on lipoprotein levels in patients with hyperlipoproteinemia.

Effect of dietary fish was investigated in 51 study group patients and 50 age- and sex-matched control group patients, all with type II-b hyperlipoproteinemia. In the study and control group, 21 and 22 patients, respectively, had well regulated non-insulin dependent diabetes mellitus. Neither the study group nor control group patients smoked or consumed alcohol beverages. Blood pressure was within normal limits (16/11-20/12 kPa) in both groups. During a six-month study period, the study group took 0.5-1 kg breaded pilchard per week, whereas the control group patients were on their standard hypolipoproteinemic diet. The following parameters were determined in both study and control group patients before the study, every 3 months during the study, and 3 months after the completion of the study, total cholesterol, HDL cholesterol (HDL2 and HDL3), LDL cholesterol, VLDL cholesterol, triglycerides, blood glucose and uric acid. Fish intake was found to statistically significantly decrease the levels of total cholesterol (-10.7%), LDL cholesterol (-11.7%), VLDL cholesterol (-14.8%) and triglycerides (-12.3%) (p < 0.05), whereas a statistically significant increase was observed in the levels of HDL cholesterol (+5.3%) and HDL3 (+7.4%) (p < 0.05). Three months after the completion of the study, when the study group patients had resumed their standard hypolipoproteinemic diet without extra fish intake, the levels of lipoprotein fractions returned to those recorded before the study. There were no statistically significant changes in the levels of blood glucose, uric acid and HDL2. In the control group, no statistically significant changes in lipoprotein fractions were recorded. Our findings suggested that dietary intake of 0.5-1 kg fish containing a small amount of omega-3 fatty acids, along with the standard hypolipoproteinemic diet, may decrease the level of atherogenic lipoprotein fractions, and increase the level of lipoprotein protective fractions, thus reducing or at least delaying the development of atherosclerosis.

Serum total, LDL, HDL cholesterol and triglycerides related to age, gender and cigarette smoking in patients with first acute myocardial infarction.

The aim of this study was to examine relationships between total cholesterol, LDL, HDL cholesterol, triglycerides and age, gender, and cigarette smoking in 190 patients (132 men and 58 women) aged 34-87 years with first AMI. The control group included 103 patients (57 men and 46 women) aged 29-90 years without a history of angina pectoris or AMI. High total cholesterol (over 5.2 mmol/L) was observed in 75% of patients with AMI vs. 48% of patients in the control group (p < 0.001). Patients with AMI had significantly higher total cholesterol and LDL cholesterol levels than controls (p < 0.0001). HDL cholesterol levels were significantly lower among patients with AMI than among the control group patients (p < 0.0001). Serum total cholesterol and LDL cholesterol is higher in patients with AMI up to 60 years old, but lower in patients older than 60 years. Women aged less than 50 years had significantly higher HDL cholesterol (p < 0.001), lower LDL cholesterol (p < 0.001), and lower total cholesterol (p < 0.05) than those over 50 years. Smokers with AMI who smoked over 20 cigarettes per day had significantly higher total cholesterol, LDL cholesterol and triglycerides levels than the non-smokers (p < 0.05). These findings suggest important influences of hyperlipoproteinemia and cigarette smoking upon development of myocardial infarction, especially in younger patients.

Effect of kinesiologic recreation on plasma lipoproteins and apolipoproteins in fertile women.

The effect of physical exercise on lipid and apoprotein levels was studied in 31 healthy fertile women (mean age, 39.7 +/- 2.3 years) working as civil servants and leading a mostly sedentary way of life (group 1). A control group consisted of 31 age-matched women (mean age, 39.2 +/- 2.4 years) with a comparable life-style (group 2). Group 1 performed physical exercise for at least 30 minutes three times per week. They also climbed a 500-m hill at least once per week. The study lasted 6 months, ie, from May to November 1990. Changes in maximum oxygen consumption (Vo2max), body weight, body mass index (BMI), waist to hip ratio (WHR), and levels of lipids and apolipoproteins (apos) A-1 and B were compared between the two groups of subjects. During the May-November period, the control group showed an increase in body weight (P < .02), total cholesterol, high-density lipoprotein (HDL) cholesterol, HDL3, and low-density lipoprotein (LDL) cholesterol (P < .01) and a decrease in HDL2 (P < .05). In contrast, group 1 did not show any increase in total cholesterol, and their body weight decreased (P < .01). Very-low-density lipoprotein (VLDL) cholesterol and triglyceride levels decreased (P < .02), as did LDL cholesterol and HDL2 levels (P < .05), whereas HDL cholesterol and HDL3 levels increased (P < .01). There were no statistically significant changes in WHR and apo A-1 level. The findings indicated possible seasonal variations in lipoprotein levels in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum paraoxonase and cholinesterase activities in individuals with lipid and glucose metabolism disorders.

In patients with hyperlipaemia, serum paraoxonase activities were polymodally distributed with 75% individuals in the low activity mode. In the same patients the distribution of serum cholinesterase activities was unimodal, but asymmetrical. Patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus had slightly higher cholinesterase activities than patients with hyperlipaemia only.

Correlation of morphological FAB classification and immunophenotyping: value in recognition of morphological, cytochemical and immunological characteristics of mixed leukaemias.

Correlation between the FAB classification and immunophenotype was studied in 169 consecutive adult patients with acute leukaemia (AL). The lineage of leukaemic cells could be determined in the majority of cases, whereas 3 patients (1.8%) remained unclassified. In 22 out of 71 patients (31%) with acute myeloid leukaemia (AML) FAB M1 and M2 types, and in 5 out of 16 patients (31%) with chronic myeloid leukaemia (CML) in myeloid blast crisis, leukaemic cells did not express myeloid lineage-related markers, indicating asynchronous expression of cell markers in a substantial proportion of patients. Flow cytometric two-colour immunofluorescence revealed mixed AL immunophenotype in 6 out of 169 patients (3.4%). This group included five CD2+AML (5% of AML tested) and one undifferentiated AL expressing CD10(CALLA), CDw65(VIM-2). The former group included FAB M1, M2, M3 and M4 forms of AML with a single cell population, and an AML M2 patient with both cytochemically and immunologically two separate populations of leukaemic cells. This further illustrates the heterogeneity of the target cell(s) for leukaemogenesis and the level of differentiation of AML cells. However, there was no difference in the treatment response and the remission duration between AML patients and patients with mixed phenotype AML.

Significance of proliferative epithelial changes in breast fine-needle aspiration.

The authors analyzed 6439 fine-needle aspirations (FNA). The total number of FNA performed per year at the authors' institution was found to be increasing. The authors analyzed the numbers of carcinomas and proliferative breast alterations separately. A statistically significant increase was recorded in the group of aspirate specimens that had epithelial proliferation; the increase was greater than that seen in aspirate specimens with normal epithelium (P less than 0.001). Biopsy was recommended in 151 of 6439 (2.3%) FNA and performed for 67 of the 151 (1.0%) recommendations. Cytologic findings were compared with pathohistologic findings. A histologic carcinoma was found in 14 of 67 (20.8%) patients who had biopsy performed. The authors concluded that clinicians should give particular attention to atypia in cytologic aspirate specimens.

Accuracy of routine flow-cytometric bitmap selection for three leukocyte populations.

A double-blind study was performed with peripheral blood of 41 human subjects to check the accuracy of determination of lymphocyte, monocyte, and granulocyte windows with which every flow cytometric analysis of leukocyte markers starts. White blood cell suspensions were prepared according to the whole blood method and analyzed on an EPICS-C flow cytometer using the two-parameter 90 degrees light scatter vs. forward angle light scatter (granularity vs. cell size) data distribution. Windows (bitmaps) for lymphocytes, monocytes, and granulocytes were drawn and numbers of cells determined in each. The proportions of lymphocytes, monocytes, and granulocytes were calculated in relation to total cell number, counted and in relation to the sum of cells in three bitmaps, and then compared with proportions determined by microscopic whole blood cell (WBC) differential and a WBC differential determined in an automated hematology analyzer. Average proportions of lymphocytes obtained by the flow cytometer were significantly lower than those obtained by either microscopic or automated differential, suggesting that some of the relevant cells were not included in the bitmaps. Granulocyte proportion related to total cell number was lower and that related to bitmap cell number higher than that obtained by microscopic and automatic differentials, suggesting that nongranulocytic cells were included in the granulocyte bitmaps. Proportions of lymphocytes and granulocytes obtained by the flow cytometer correlated well with those obtained by both microscopic and automatic differential. In contrast, the proportions of monocytes showed a poor correlation, which is probably due to their low number and delicate position in the distribution, and which makes them difficult to delineate.

[The effect of fenofibrate in various types of hyperlipoproteinemias]. / Djelovanje fenofibrata u razlicitim tipovima hiperlipoproteinemija.

Hyperlipoproteinaemia may represent a high risk factor in the pathogenesis of atherosclerosis, especially for the coronary heart disease. This metabolic disorder should therefore be treated. Strict diet is the basis of the treatment. In case the lipoprotein level does not normalize by means of diet, medicamentous therapy ought to be applied in addition. A total of 269 individuals suffering from hyperlipoproteinaemia have been treated in this study. According to Fredrickson there were 35 with Type IIa, 134 with Type IIb, 32 with Type IV and 68 with Type V. All of them had been previously treated with diet for at least three months. Afterwards, they were treated with fenofibrate (Katalip) in a dosage of 100 mg, 2 capsules in the morning and 1 in the evening. Biochemical parameters were checked a month after start of therapy. Cholesterol (-20%, -17%, -114%, -224%), triglycerides (-31%, -37%, -47%, -704), LDL cholesterol (-23%, -19%, -11% no significant, -31%), VLDL cholesterol (-25%, -29%, -32%, -59%), atherosclerosis index (-27%, -28%, -28%, -55%), urea (-5% no significant, -21%, -22%, -28%), gamma GT (-23%, -25%, -15% no significant, -39%) of patients with Type IIa, IIb, IV and V have decreased significantly (P less than 0.05), whereas the value of HDL cholesterol increased (0% no significant, +20%, +12%, +29%). No statistically significant changes during the therapy were observed in alkaline phosphatase (-8%, -9%, -11%, -10%), SGOT (-3%, -8%, +5%, -15%), SGPT (-22%, +4%, -18%, -15%) and glucose (-17% significant, -5%, -7%, -10%). Fenofibrate decreases the risk of the development of atherosclerosis by lowering lipoproteins and uric acid level.