Circulating tumor cells in the peripheral blood and bone marrow of patients with ovarian carcinoma do not predict prognosis

BACKGROUND: Ovarian carcinoma is apparently restricted for a long time to the peritoneal cavity. However, about 50% of patients with a surgically documented complete intraabdominal response experience later recurrence. Occult hematogenous micrometastases are common to most epithelial malignancies and have recently been found in 30% of bone marrow samples of ovarian carcinoma patients, as examined by immunocytochemistry. Moreover, these findings were associated with poor progression-free and overall survival. The aim of the current study was to evaluate the possible prognostic significance of tumor cells detected in the peripheral blood and bone marrow of ovarian carcinoma patients by an immunomagnetic method. METHODS: In a total of 90 patients with histologically proven epithelial ovarian carcinoma, blood and (in 73 cases) bone marrow samples were taken. Tumor cells were identified by a microbead coated with the antibody MOC-31, which recognizes an epitope regularly expressed on ovarian carcinoma cells. RESULTS: The authors detected carcinoma cells in the bone marrow in 21% of ovarian carcinoma patients, and in the peripheral blood in 12% of patients. Mean overall survival was 25 and 28 months for patients with or without circulating tumor cells, respectively. CONCLUSIONS: Ovarian carcinoma cells seem to reach peripheral circulation more frequently than expected. However, in contrast to an earlier report, detection of tumor cells in the bone marrow and/or blood was not associated with poor prognosis in ovarian carcinoma patients. This discrepancy remains unexplained, but characterization of circulating ovarian carcinoma cells for their malignant and metastatic capacity is clearly warranted.     

Early and late effects of X-irradiation on submandibular gland: a morphological study in mice

BACKGROUND: Radiotherapy for head and neck cancers causes permanent salivary gland dysfunction and xerostomia. The aim of this study was to determine changes in mice submandibular glands after X-irradiation. METHODS: The submandibular glands of male C57BL/6 mice were locally X-irradiated in the head and neck region with a single dose of 7.5 or 15 Gy and analyzed morphologically and morphometrically at 1, 3, 6, 10, 40, and 90 days after irradiation. RESULTS: Two phases of gland reaction to irradiation have been noted. The first, early phase is observed up to 10 days after irradiation. The second, late phase was observed 90 days after irradiation. Also, a dose-related effect was noticed. The most prominent morphological changes were pyknotic nuclei, vacuolization of acinar cells and lysis of acini and granular convoluted tubules. Changes were detected at 3 and 6 days after irradiation followed by tissue regeneration. Ninety days after irradiation, prominent pathological changes (vacuolization and pyknotic nuclei of acinar cells, lysis of acini and granular convoluted tubules and edema) were detected, but the most remarkable change was disseminated mononuclear infiltration. Also, a statistically significant reduction in number of acinar cells was detected in both irradiated glands. CONCLUSIONS: Occurrence of disseminated mononuclear infiltration in gland during late post-irradiation phase makes the mouse model potentially better than the rat model for investigation of irradiation-induced salivary gland damage.     

Leptin receptor gene variation predicts weight change in subjects with impaired glucose tolerance

The leptin receptor (OB-R) gene is a promising candidate gene for type 2 diabetes, because leptin and its receptor play an important role in insulin secretion and the development of obesity. Therefore, we studied whether the pentanucleotide insertion polymorphism of the 3'-untranslated region (3'UTR) of the OB-R gene has an influence on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the STOP-Noninsulin-Dependent Diabetes Mellitus trial. The STOP trial was a longitudinal, double-blind, placebo-controlled randomized trial that included 1429 subjects with IGT from high-risk populations. Using the restriction fragment length polymorphism method, we genotyped 770 subjects whose DNA was available for the insertion/deletion polymorphism of the 3'UTR of the OB-R gene. We did not find a relationship between the OB-R polymorphism and the conversion from IGT to type 2 diabetes (p = 0.747). However, the insertion allele was associated with a significant reduction in weight (p = 0.016), BMI (p = 0.009), and waist circumference (p = 0.006) in all subjects. Women carrying the I allele had a larger waist circumference change (p = 0.036), whereas men lost more weight and had a greater decrease in BMI. The pentanucleotide insertion/deletion polymorphism in the 3'UTR of the OB-R gene did not influence the conversion to type 2 diabetes in obese patients with IGT. However, this polymorphism was associated with a significant weight change, suggesting that it may potentially modulate the risk for type 2 diabetes.     

Soluble CD30 and HLA antibodies as potential risk factors for kidney transplant rejection

Recent literary data suggest that high pre- and post-transplant serum levels of the soluble CD30 (sCD30) molecule may be a risk factor for acute rejection and worse prognosis of the transplanted kidney. The aim of our study was to correlate the concentrations of sCD30 and the presence of HLA antibodies as defined by flow cytometry and ELISA with the clinical course and graft prognosis after transplantation. One hundred and seventeen kidney transplant patients were included into the study. The incidence of rejection episodes, graft function and graft survival for up to 1 year post-transplant were evaluated. Soluble CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. In both patient groups, a significant decrease of sCD30 was detected 2 weeks after transplantation (104.4 U/ml before vs. 37.0 U/ml post-transplant, P < 0.001). However, there was a substantial difference in the level of decrease of sCD30 between rejecting and non-rejecting patients. Patients without rejection had lower sCD30 values (31.2 U/ml post-transplant) compared to patients who experienced rejection episodes (62.9 U/ml), P < 0.04. Multifactorial analysis showed that antibodies to HLA class II antigens and elevated concentrations of sCD30 shortly after transplantation were associated with increased risk for acute rejection in the first post-transplant year. Measurement of soluble CD30 after transplantation, taken into consideration with the presence of HLA class II antibodies, might be helpful for evaluating the potential risk for acute rejection.     

Superoxide dismutase activity in colostrum, transitional and mature human milk

Colostrum and mature human milk are rich sources of nutrients and contain biologically active molecules that are essential for specific antioxidant functions. The aim of the present study was to determine the activity of copper, zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) activity in different phases of lactation. Specific enzyme activity was determined in colostral milk (3rd-5th days after delivery), and in mature milk in the third week (15-20 days), and the fourth and seventh months of lactation. In the third week of lactation, the activity of CuZnSOD and MnSOD was significantly higher in comparison to the colostral phase. In the fourth month of lactation, the activity of both enzymes was suppressed, while in the seventh month of lactation the MnSOD activity was increased, and the CuZnSOD activity was not significantly changed. These findings show that the activities of superoxide dismutases significantly change during different phases of lactation.     

Comparison of two therapeutic protocols in patients with antiphospholipid antibodies and recurrent miscarriages

AIM: To compare the effects of two therapeutic protocols for the patients with recurrent miscarriages associated with the presence of antiphospholipid (anticardiolipin) antibodies. METHODS: A prospective observational study included 20 patients with antiphospholipid antibodies in the first group who received low-molecular heparin and aspirin. The second group of 20 patients, in addition to this therapy, received immunotherapy (intravenous immunoglobulin). Aspirin was administered at the time of a positive pregnancy test, and low-molecular heparin not before the fetal heart activity registration by ultrasound. Intravenous immunoglobulin was given prior to the conception or at the beginning of the pregnancy. We compared these groups according to the pregnancy outcomes and the occurrence of complications during pregnancy, using standard statistical tests. RESULTS: The rate of positive gestational outcome in the patients treated with aspirin and low-molecular heparin was 85% (17/20), and in the second group it was 90% (18/20). There was no significant difference in pregnancy outcomes between these groups (p > 0.05), except for the occurence of preeclampsia and thrombocytopenia, which were recorded only in the aspirin and low-molecular heparin group, but with no statistical significance (p > 0.05) compared to the second group, which received immunoglobulin additionally. CONCLUSION: There was no significant difference (p > 0.05) in pregnancy outcomes between the two studied therapeutic protocols, but the therapy with aspirin and low-molecular heparin was cheaper and easier to apply than the therapy with immunoglobulins. The results of our study confirmed that the final pathogenic mechanisms in recurrent fetal miscarriages were inflammation and thrombosis of the uteroplacental blood vessels.     

Epidemiology of myotonic dystrophy type 1 in the population of central Serbia

The objective of this epidemiological survey was to estimate the frequency and distribution of Myotonic dystrophy type 1 (MD1) (Steinert's disease) in central Serbia, during the period 1983-2002. The data on the number of diagnosed MD1 patients were obtained using the analysis of hospital records, which were examined in all the relevant neurological institutions in central Serbia in the mentioned period. Incidence rate and prevalence were used for the data analysis. In the study period in central Serbia, 154 patients (78 males and 76 females) with MD1 were identified. The average annual incidence rate of MD1 was 1.3 (95% CI-confidence interval 0.1-7.2) per 1,000,000 population, 1.4/1,000,000 (95% CI 0.1-7.2) for males, 1.3/1,000,000 (95% CI 0.1-7.2) for females. The trend of MD1 incidence rates in the observed period in central Serbia had a tendency of the statistically significant decrease, according to the linear model, in both male (y = 0.205 - 0.0066x, p = 0.021) and female populations (y = 0.1788 - 0.0048x, p = 0.032). The prevalence of MD1 on December 31, 2002 in central Serbia was 3.8/100,000 (95% IP 3.2-4.6), 3.7/100,000 (95% IP 3.3 - 4.8) for males, 3.3/100,000 (95% IP 3.0 - 4.4) for females.     

Emery-Dreiffus muscular dystrophy: MR imaging and spectroscopy in the brain and skeletal muscle

Emery-Dreifuss muscular dystrophy is a rare disorder characterized by childhood onset of contractures, humeroperoneal muscle atrophy, and cardiac conduction abnormalities. This report presents the cases of two brothers with this dystrophy in whom bilateral hypomyelination of the deep periatrial white matter was noted. In the hypomyelinated regions, a prominent peak centered at 1.5 parts per million was present on short-TE MR spectra likely representing prominence of proteolipids in the macromolecular region. Major peaks (N-acetyl-aspartate, creatine, choline, and myoinositol) were normal. With respect to muscle changes, atrophy of the medial head of the gastrocnemius muscle was noted at MR imaging, and phosphorus spectroscopy of this muscle revealed decreased phosphocreatine and inorganic phosphate peaks.