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.

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.

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)

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.

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.

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.

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.

[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.

[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.

[Multicenter long-term study of gallopamil in patients with coronary heart disease]. / Multizentrische Gallopamil-Langzeitstudie bei Patienten mit koronarer Herzkrankheit.

Efficacy and tolerance of gallopamil (Procorum) were investigated over a period of 1 year under practice conditions in a total of 455 patients (254 male, 201 female), aged 62 years (male) and 66 (female) on an average, with electrocardiographically confirmed coronary heart disease. The most frequently applied dosage was 1 film-coated tablet of gallopamil 50 mg 2-3 times daily. Frequency of attacks and nitro consumption as criteria of efficacy decreased by an average of approx. 80% in comparison to the placebo period. Full effectiveness was usually reached 4 weeks after start of therapy. ST-depression under exercise diminished by approx. 50%. An improved exercise tolerance was likewise observed, especially in patients who only tolerated up to 100 Watt prior to therapy. Therapeutic success was defined as good in 73% of the cases, satisfactory in 17.3% and insufficient in 6.7% by the trial physicians - the patient's opinion also being taken into consideration. A decrease of effectiveness was not observed during the one-year therapy. No uniform influence on the laboratory parameters could be revealed. The most frequent side-effects were: gastric discomfort (13 patients), bradycardia (7 patients) and AV-prolongation (3 patients). A total of 77 patients (16.9%) had to discontinue therapy. 29 out of these discontinuations were not therapy-related (drop-outs); 12 were based on an insufficient therapeutic success, 13 on hospitalization, 11 on extracardiac, 4 on cardiac adverse reactions and 8 patients (1.8%) died during the study. In a global assessment the trial physicians described the tolerability as good in 92% of the patients, fair in 2.9% and poor in 2.4%.(ABSTRACT TRUNCATED AT 250 WORDS)