Evaluation of the value of p53 protein expression in the extra-capsular extension of prostate cancer.

INTRODUCTION AND OBJECTIVES: The objective of this study is to identify the nuclear expression of the p53 protein in prostate cancer and to determine its relationship with clinico-pathological variables. MATERIAL AND METHODS: The research included 83 patients, 43 of whom are patients with prostate cancer who underwent radical prostatectomy and a control group of 40 patients with benign hyperplasia of the prostate in whom a transurethral resection or a transvesical prostatectomy was undertaken. In all cases the nuclear expression of p53 protein was evaluated. A hystopatological evaluation of the tumour characteristics and the data of the local progression of the cancer were undertaken in the research group. RESULTS: The results show that the expression of the p53 protein does not have an important correlation with the preoperative PSA, but that it is in direct correlation with the malign potential of the cancer (Gleason score, Gleason sum, primary tumour) and with the features of the disease (metastatic lymph nodes, stage of the disease). CONCLUSION: p53 protein could be used as a valid biomarker in determining the malignant potential of the tumour and the prognosis of the disease. There is no practical use in predicting the extraprostatic extension.

Quantitative expediency assessment of the zeta sedimentation ratio and the plasma viscosity in arterial hypertension research.

Accepted methods of the ESR methodology (the Westergren mode and ZSR mode) and its alternative the plasma viscosity were tested for diagnostic utility in pregnancy induced hypertension and pre-eclampsia. The receiver-operating characteristic curve (ROC) analysis approved moderate diagnostic accuracy for the ESR methodology and supplied support for its preliminary estimated cutoff values but failed to indicate cogent discernment of pathology by values of plasma viscosity. Likely pathological whole blood alterations boost the erythrocyte aggregation while the concomitant depletion of macromolecules degrades plasma viscosity values.

Urinary diversion: 30 years experience of a single centre in Republic of Macedonia.

OBJECTIVES: The aim of this report is to present our 30 years experience with various types of urinary diversions, in particular the Bricker and Studer techniques for the management of muscle invasive bladder cancer at our institution. Perioperative, early and late complications are also evaluated. MATERIAL AND METHODS: Between 1977 and 2007, 186 male and 15 female patients underwent combined radical cystectomy, pelvic lymphadenectomy and urinary diversion. In two subgroups of patients we evaluated the complications, divided as early and late, and subdivided as those related or unrelated to the neobladder. Mean follow up time was 28 months (range 12-60 months). RESULTS: Two main types of urinary diversion were performed: the ileal conduit diversion using a technique previously described by Bricker and the ileal neobladder diversion using a technique previously described by a Studer. The ages at surgery ranged from 40 to 82 years with a mean age of 60 years. Histopathologically, transitional cell carcinoma was the most common tumor cell type (93,7%), followed by difuse papilomatosis (5.5%) and adenocarcinoma (0.7%). The pathological tumor stage was pT1 (4.7%), pT2 (31.4%), pT3 (50.3 %) and pT4a (13,3%). Histological evidence of regional lymph node involvement was seen in 25% of the cases. From 52 patients from the Studer subgroup perioperative complications were found in 16 patients (30.7%). Specific early complications directly related to the neobladder occurred in 14 (26.9%) patients. Prolonged ileus in 2 patient (3.8%), ureteral leakage in 9 patients (17.3%), mucous buildup within the diversion in 3 patients (5.7%). Late complications occurred in 10 patients (19.2%): retention of the urine in 4 patients (7.6%) (stricture of the urethra-pouch anastomosis in one 1 patient) and to big reservoir in 3 patients. One patient (1.9%) developed prolonged metabolic acidosis. Stone formation was observed in one patient, two years postoperatively. Unilateral hydroureteronephrosis was observed in 2 patients whereas bilateral hydroureteronephrosis was observed in one patients at one year postoperatively. Perioperative and late complications were similar in the 32 patients from the Bricker subgroup. CONCLUSION: We show that our results with urinary diversion are promising in patients requiring radical cystoprostatectomy. The two methods preferred in our institution offer a sufficient protection of the upper urinary tract with a low complication rate, good voiding function and continence.

Radical retropubic prostatectomy for prostate carcinoma; first results of the Clinic of Urology in Skopje.

OBJECTIVES: The aim of this retrospective study is to present our experience and results in the management of prostate carcinoma, with radical retropubic prostatectomy, for a period of seven years. MATERIAL AND METHODS: From December 1997 to April 2005, 61 radical retropubic prostatectomies for prostate carcinoma were performed at the Clinic of Urology in Skopje. Mean age of the treated patients was 66.4 years. Mean serum PSA level was 32.75 ng/ml. None of the patients had distant or bone metastases. Mean operative time was 160 minutes and from 2 to 4 units of blood were transfused intra and postoperatively. Mean follow up time was 39 months. RESULTS: In all of 61 patients, the RRP was performed for adenocarcinoma of the prostate. The pathological findings postoperatively showed the following pTNM grade: pT2a in 8, pT2b in 10, pT3a in 10, pT3b in 27and pT4 in 6 patients. Positive lymph nodes were found in 14 cases. Intraoperative complications occurred in 6 patients. Early postoperative complications were seen in 12 patients. Urine leakage was seen in 2 patients, incontinence (day and night) in 8 and pulmonary embolia in 2 patients. Late postoperative complications occurred in 11 patients. Stenosis of the vesicourethral anasthomosis was seen in 3 patients and incontinence (during the night only) in 8 patients. The rate of potency was not evaluated but in the last 30 cases we insisted on preservation of the neurovascular bundles in the cases that it was possible. CONCLUSION: Radical retropubic prostatectomy is the method of choice and the golden standard for treatment of organ confined prostate carcinoma in patients with long life expectancy, no neither local nor distant metastases and good overall status. With this technique complication rates are minimal, the cure rate is very big and the patients have high quality of life. The experience of the surgeon is very important since the learning curve is crucial for diminishing operative time, postoperative complications and blood transfusions.

On the interrelationships between erythrocyte aggregation, plasma viscosity and the total peripheral resistance in arterial hypertension.

A probable conjunction of hemodynamic- and rheological variables was tested in hypertensive patients. Most pronounced correlation was fixed for some indices (sizable in value for plasma viscosity and small but distinct for blood pressure and ZSR) vs. total peripheral resistance. These results of a small scale elaboration are encouraging to get up a study extension.

Prevalence of factor V Leiden and prothrombin 20210 A variant in Bulgarian patients with pulmonary thromboembolism and deep venous thrombosis.

Factor V Leiden mutation and prothrombin variant 20210 A are well-known risk factors for venous thrombosis (DVT). Recent papers have reported a lower prevalence of factor V Leiden in patients with pulmonary thromboembolism (PTE) than in patients with deep venous thrombosis. The aim of the present study was to compare the prevalence of factor V Leiden and the prothrombin 20210 G <-- A mutation in patients with DVT and in patients with PTE. We studied 128 consecutive patients (45 with DVT, 40 with PTE, and 43 with DVT and PTE) for factor V Leiden and prothrombin 20210 A. One hundred healthy persons matched by age and sex were used as controls. Factor V Leiden was present in five of the patients with PTE [12.5%; 95% confidence interval (CI), 1.5-23.5%; not significant], 15 of the patients with DVT (33.3%; 95% CI, 9.6-38.7%; P < 0.001), and 12 of the patients with DVT and PTE (27.9%; 95% CI, 4.8-33%; P = 0.001). Results for the prothrombin 20210 A mutation were as follows: four of 40 patients with PTE (10%; 95% CI, 0-13.3%; P = 0.46), nine of 45 (20%) of the patients with DVT (95% CI, 0.5-25.5%; P < 0.05) and eight of 43 with DVT and PTE were heterozygous (18.6%; 95% CI, 0-23.9%; P = 0.02). In conclusion, there is a significantly higher frequency of factor V Leiden among patients with DVT than in patients with PTE. However, there is no significant difference of factor V Leiden or 20210 A prothrombin mutation in patients with DVT than in patients with combined DVT/PTE, therefore patients with DVT, carriers of the mutations, do not appear to be at lower risk for pulmonary embolism.

[Intermediate substrates in different stages of compensation of diabetes mellitus]. / Substrati ot intermediernata obmiana pri razlichna stepen na kompensatsiia na zakharniia diabet.

In this research there were studied the changes in the concentrations of pyruvate, lactic acid, maleate, beta-oxybutyric acid oxyacetyc acid, blood fats, triglycerides, cholesterol blood lipoproteins in patients in different stages of compensation of diabetes mellitus. Studied were 44 patients during ablatio retinae during latentive diabetes, 16 patients with decompensated, 12 with subcompensated, and 8 with compensated diabetes. The average age of the studied patients was 54 years. The control group of 35 healthy people was of average age 52 years. All the groups show decreasing of the blood maleat. In the group of decompensated diabetes decreasing of keto-bodies, piruvat acid and lipid fractions was present. These factors were normalized, when diabetes was compensated. In this study, the diagnostic value of the investigation metabolites for compensation of diabetes mellitus is discussed.

[Epidemiology of the major histocompatibility complex-human leukocyte antigen in the Madeconian population]. / Epidémiologie du complexe majeur d'histocompatibilité "human leucocyte antigens" dans la population macédonienne.

Human leukocyte antigens (HLA) at loci A (14 antigens) and loci B (29 antigens) were determined in 2,385 healthy Macedonians, using the microlymphocytotoxicity test. Results were compared with those obtained in Caucasians. The most common HLA antigens in the Macedonian population are: A2 (51.65%), A1 (25.87%), A3 (17.14%) and A24 (20.41%) for loci A and B51 (32.03%), B35 (23.98%), B8 (12.11%), B44 (12.11%), B7 (11.48%) and B18 (10.23%) for loci B. These frequencies are similar to those found in Caucasians. However, antigens B12, B44, B7, B8 and especially B15 are more common in Caucasians, while B51 and B35 antigens are more common in the Macedonian population. The most common haplotypes in the Macedonian population are: A2/B51 (15.68%), A2/B35 (10.35%), A2/B12 (7.79%), A9/B51 (7.50%) and A1/B8 (7.50%). The frequencies of HLA antigens were also determined in 348 patients with chronic renal disease and compared with those observed in the healthy population (2,385 subjects). No significant differences was observed between HLA frequencies depicted in patients and those described in healthy individuals. Results should therefore make easier the finding of compatible kidney transplants in the Macedonian population.

Study on long-term biological variability of erythrocyte sedimentation rate.

The aim of the study was the estimation of long-term within-subject variability of ESR. ESR was measured in 52 healthy persons of both sexes, aged 20-50 years, twice a month during 6 consecutive months, after the method of Westergren. The within-run imprecision, expressed as CV was 13.2% (mean value, x = 3.9 mm h-1) and 3.8% (x = 16.0 mm h-1) respectively. The analytical day-to-day imprecision, calculated by duplicate measurements during 23 consecutive days. was s = 0.6 mm h-1. The medians from within-subject variances were 0.9 for men and 8.6 for women, respectively. The 90th percentiles were 11.3 for men and 40.6 for women, respectively. The critical differences based on the median value (dk50) were 3.1 mm h-1 (men) and 8.3 mm h-1 (women). The critical differences based on the 90th percentile (dk90) are 9.5 mm h-1 (men) and 17.7 mm h-1 (women).

[Changes of laboratory hematologic indices in patients with chronic glomerulopathies following treatment with superhigh doses of cyclophosphamide]. / Promeni v niakoi khematologichni laboratorni pokazetali pri bolni s khronichni glomerulopatii sled lechenie sus svrukhvisoki dozi tsiklofosfamid.

41 patients with active glomerulopathies treated with super high doses of Cyclophosphamide were studied. The following indices were followed up dynamically: hemoglobin concentration, number and morphology of erythrocytes, number and morphology of leucocytes and differential count. Hemoglobin concentration and erythrocyte count remain in the reference ranges in most of the patients. They fall more considerably compared to the initial values between the 90-120 day after the treatment. This fall improves spontaneously and does not require discontinuance of the treatment. The single application of super high dose of Cyclophosphamide does not influence significantly the leucopoiesis. Because of the parallel application of glucocorticosteroids no fall of the leucocyte count is observed and they remain in their reference ranges.

[The limits of the reference range of serum enzymes]. / Granitsi na referentnata oblast na niakoi serumni enzimi.

The reference ranges of some of the most frequently used in the clinical laboratory practice serum enzymes and isoenzymes are determined: aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), creatine kinase (CK) and its isoenzyme (CK-MB), lactate dehydrogenase (LDH) and its isoenzyme--HBDH, and alkaline phosphatase (APh). The reference ranges of the enzymes and isoenzymes studied are calculated from the results obtained in 182 clinically healthy persons, 20-50 years of age, by the "single test" method. All analyses are made with the flexible discrete analyzer "Technicon PA 1000". The influence of several factors is studied. The age of the patients does not exert any influence on the enzymes and isoenzymes studied. Statistically significant sex dependent differences are established for CK, ASAT, ALAT and APh. The statistical processing of the results for the determination of the reference ranges of the enzymes and isoenzymes studied is accomplished with a computer "Hewlett Packard 85".

[Gamma-glutamyltransferase activity in the serum and the mean-cell erythrocyte volume of patients with chronic ethylism and chronic liver diseases (preliminary report)]. / Prouchvaniia otnosno aktivnostta na gama-glutamiltransferazata v seruma i sredniia eritrotsiten obem pri bolni s khronichen etilizum i khronichni chernodrobni zaboliavaniia (predvaritelno suobshtenie).

The dynamics of the enzyme gamma-glutamyltransferase (gamma GT) was followed up in 34 patients: 17 patients with liver cirrhosis, 9 patients with chronic hepatitis and 8 patients with liver steatosis. In the patients with alcoholic cirrhosis the activity of gamma GT rapidly fell in hospital conditions which is related to the forced abstinence. In the cirrhotic patients with nonalcoholic etiology no changes in gamma GT activity were found. In the patients with chronic hepatitis and liver steatosis with alcoholic etiology the gamma GT activity resembled that of alcoholic cirrhotic patients. The gamma GT activity fell most sharply in the patients with liver steatosis which is explained by the mild and reversible liver lesions characteristic for this disease. The mean erythrocyte volume determined by electronic blood cell counter shows a tendency toward macrocytosis in all chronic alcoholic patients. Macrocytosis is also found by ordinary microscopic examination of the blood cells.

[Effect of body position on laboratory hematological indices]. / Vliianie na polozhenieto na tialoto vurkhu khematologichnite laboratorni pokazateli.

The influence which the position of the body (recumbent, sitting or erect) exerts on the hematologic laboratory indices was studied in 32 clinically healthy persons from both sexes, 19 to 48 years of age. Blood was taken by venepuncture in each of three positions. The analyses were carried out by a hematologic analyzer "H 1 Technicon". The differences of the results were processed by the pair analysis. The values of hemoglobin, hematocrit, erythrocytes, leucocytes and platelets increase with the change of the body position from recumbent to sitting and to erect and the differences are statistically significant. The changes are due to a reversible hemoconcentration and redistribution of the blood. The analysis of the differential count revealed that the greatest increase is of the neutrophils which is probably due to the mobilization of the pool of neutrophils which are nearest to the vascular wall, the process being parallel to the process of hemoconcentration.

[Effect of body position on substrates, enzymes and electrolytes in the serum of healthy subjects]. / Vliianie na polozhenieto na tialoto vurkhu niakoi substrati, enzimi i elektroliti v seruma na zdravi litsa.

32 healthy persons, 12 men and 20 women, 19 to 48 years of age, were examined in the three positions--recumbent, sitting and erect. Blood was taken by venepuncture after 15 minutes stay in the position. The analyses were carried out with the discrete analyzer "PA-1000", flame photometer, chlorine titrator "Radiometer" and osmometer "Knauer". The statistical assessment was performed by the pair analysis. The changing of the body position from recumbent to sitting and to erect leads to a significant increase of the concentrations of the total protein and albumin which cannot pass through the capillary endothelial barrier following the changes in the hydrostatic and filtration pressure. The capillary endothelial barrier is permeable for the low-molecular compounds whose concentrations change insignificantly. Cholesterol and triglycerides are an exception since they are bound to nonfilterable lipoprotein complexes. Reliable increase of creatinine is found only in the women examined. Calcium which in the serum is protein-bound also increases significantly. A significant increase is found also of the activity of the enzymes creatine kinase, alkaline phosphatase and gamma GTP. The changes of the activity of the enzymes AsAT, AlAT, LDH and hydroxybutyrate dehydrogenase are insignificant.

[Automatic and manual methods for counting the thrombocytes in the blood]. / Avtomatichen i manualen metod za izbroiavane na trombotsitite v kruvta.

The results are compared from the platelet count in blood via chamber method with phase contrast and via electronic method with "Thrombocounter C". The reproducibility was studied in a series in the low, referent and high region. The electronic-automatic method gives a better reproducibility than the chamber method in all three regions. The poorest is the reproducibility in the low region where VC of both methods were the closest. The results from the two methods are in a high positive correlation (r = 0.9145, n = 61), the arithmetical mean from the electronic method being insignificantly higher than the mean of the chamber method, p greater than 0.05. In the low region, with platelets under 80 X 10(9)/l, the reliability of the electronic-automatic method is decreased. The results from the chamber and electronic-automatic method have a normal distribution. The electronic-automatic method is several times faster and less tiresome than the chamber one.

[Comparative studies of the analytical reliability of the results of various hematologic tests]. / Sravnitelni prouchvaniia vurkhu analitichnata nadezhnost na rezultatite ot niakoi khematologichni izsledvaniia.

In connection with the implementation of new methods and apparatuses for the determination of hemoglobin, hematocrit, erythrocytes, MCV, MCH, MCHC and leukocytes, the reproducibility was studied in series, compared with the arithmetical means and standard deviations and correlation analysis of the results was performed. Manual and automated, to various degrees, investigation methods were used. The reproducibility in hemoglobin determination was very good, with no significant differences between the means of the different methodical variants. The microhematocrit method provided a very good reproducibility for hematocrit, with significant differences in the means of the three methods used. The reproducibility of erythrocytes was between 1,09% and 2,34%. VK of leukocytes ranged from 2,0% to 5,73%. The differences between the means of the different methods for erythrocyte count and, in the majority of the cases, for leukocytes, allow the statistically significant comparability of the results. The best reproducibility from the mathematical indices of erythrocytes was obtained for MCHC. The correlation analysis showed a positive correlation between the methods compared in all parameters studied.

[Methemoglobinemia and hemolytic anemia induced by Disulon]. / Méthémoglobinémie et anémie hémolytique induites par la Disulone.

Seven patients ingested (2.5 mg/kg) daily dapsone. Their serum samples were analyzed daily during the first week by spectrophotometry for methaemoglobinemia and weekly blood samples for red blood cells, reticulocytes count and haptoglobin level. The acetylator phenotype of each patient was estimated on the capacity to acetylate isoniazid. Methaemoglobinemia was always observed within the 48 hours after drug intake. The dapsone induced anemia was moderate being maximum between day 25 and 40 after the beginning of treatment. Reticulocytemia appeared in the second week and haptoglobin levels decreased between day 5 and 8 of therapy in 5 patients and at day 15 for the two others. The seven patients are divided in 4 rapid acetylator and 3 slow acetylator. The acetylator phenotype was not correlated with methaemoglobin, haptoglobin levels or RBC counts.

[Late postoperative results of anti-reflux ureterocystoneostomy]. / Kasni postoperativni rezultati antirefluksnih ureterocistoneostomija.

Presented are the postoperative results of 13 of the 15 operations on the urethrovesicular junction. Most (8) were treated by the Politano-Leadbetter method; three (3) by Cohen, and two (2) by the Swinney-Avata modification of the Politano-Leadbetter method which is described and shown schematically. Reasons for applying these treatments were stenosis of various origins localized in the terminal part of the urethra, gynecological damages to the urethra ("iatrogenic" injuries), displacement of the urethra, vesicular-urethral reflux, and megaurethra. At check-ups from 3 months to 6 years after the operation, 84.6% of the operations proved successful. In comparison with 18 operations for the same reasons in which an ordinary reimplantation of the urethra was performed, the former is 12.3% better. The Cohen operations achieved good results. However, should the need arise later, it is impossible to perform retrograde manipulations of the urethra with a probe in the usual way. Thus the authors ascribe the advantages to those operations that can develop naturally with the reimplantation of the submucous membrane of the urethra.