The World Health Organization classification of lymphomas

The Revised European-American Classification of Lymphoid Neoplasms (REAL) classification has been validated by a multi-institutional study, and project data showed that it is both reproducible and clinically relevant. The new World Health Organization (WHO) Classification of Neoplastic Diseases of Hematopoietic and Lymphoid Tissues, as a joint project of the Society of Hematopathology and European Association of Hematopathologists, is an update of the REAL classification, with minor changes based on newly available information. We analyzed the incidence of different histological types of non-Hodgkin s lymphomas diagnosed in Zagreb University Hospital Center, which were reclassified according to the WHO classification. Furthermore, we present a conceptual grouping of lymphomas into four categories (indolent, aggressive, highly aggressive, and localized indolent).     

Epilepsy and serotonin (5HT): Variations of 5HT-related genes in temporal lobe epilepsy

Several lines of evidence point to the role of serotonin (5HT) neurotransmission in the epileptogenesis. The present preliminary study investigated possible association of the temporal lobe epilepsy (TLE) with the polymorphisms in several 5HT-related genes, including serotonin transporter (5HTT), monoamine oxidase A (MAO-A) and serotonin receptors 5HT-1A, 5HT-1B and 5HT-2C. All participants (101 TLE patients and 170 healthy controls) were unrelated individuals of Croatian origin. 5HT-1B allele 861G was found to be slightly overrepresented in the patient group (p = 0.0385). No significant differences between groups were observed for the other tested polymorphisms. Within the limitations imposed by the size of our sample, negative findings suggest that the respective loci do not make considerable contribution to the etiopathogenesis of TLE. Further examination of 5HT-1B gene, which yielded positive result at a trend level, is possibly warranted.     

Association of Nephrolithiasis and Gene for Glucose Transporter Type 9 (SLC2A9): Study of 145 Patients

Aim

To investigate the association of nephrolithiasis and solute carrier family 2, facilitated glucose transporter, member 9 (SLC2A9), also known as glucose transporter type 9, Glut9.

Methods

A total of 145 participants were recruited in the period April-October 2008 from the Department of Mineral Research of the Medical School Osijek, Osijek, Croatia; 58 (40%) had confirmed nephrolithiasis and 87 (60%) were asymptomatic. Four single nucleotide polymorphisms (SNP) from the SLC2A9 gene were genotyped in both groups (rs733175, rs6449213, rs1014290, and rs737267).

Results

There was a weak but significant association of all 4 SNPs and nephrolithiasis (P = 0.029 for rs733175; P = 0.006 for rs6449213; P = 0.020 for rs1014290, and P = 0.011 for rs737267). Logistic regression in an age- and sex-adjusted model suggested that genotype C/T for rs6449213 had odds ratio for nephrolithiasis of 2.89 (95% confidence interval 1.13-7.40). This SNP explained a total of 4.4% of nephrolithiasis variance.

Conclusion

Development of nephrolithiasis may be associated with SLC2A9 gene. Further studies are needed to clarify the role of SLC2A9 gene as a link between uric acid and nephrolithiasis.Renal stone formation (nephrolithiasis) is a disease characterized by the existence of solid deposits in the upper parts of the urinary tract (1). It is estimated to affect between 3%-9% of the population, with large differences between various populations (2,3). There is a number of causes that may lead to the renal stones formation, including diet and obesity status, some drugs, other diseases, climate changes, metabolic disorders, and genetic factors (2,4,5). The complexity of this disease caused researchers to consider nephrolithiasis as one feature of a broader systemic disease, rather than a local disease restricted to a single organic system (6). This is especially interesting in relation to gout and metabolic syndrome, which are both systemic disorders in close relation to nephrolithiasis (6-8). Even the cohort studies have confirmed the association of gout and kidney stones, suggesting that the history of gout increases the risk for kidney stones (9). Another study showed that, in the age-adjusted model, gout had an odds ratio of 1.97 for previous kidney stones (95% confidence interval [CI], 1.37-2.83) and that even after adjustment for sex, race, body mass index, and presence of hypertension the odds ratio remained significant (10).Genetic contribution to renal stones formation has been identified long time ago (2). In line with these suggestions, heritability of some of the traits associated with nephrolithiasis has been shown to be as high as 95% (11). Heritability of the urinary stones was reported to be lower (56%) (12), but still sufficiently high to be considered a substantial genetic proportion of variance and suggesting that it may be under genetic control. So far, a number of studies have established a link between predominantly oxalate kidney stones and several genes, including vitamin-D receptor gene (VDR) and calcitonin receptor (CTR) gene (13), heparan sulfate (HSPG2) gene (14), or fibronectin gene (FN1) (14).The quantitative trait associated with nephrolithiasis is the serum uric acid concentration, which is under strong genetic control by the gene for glucose transporter type 9 (SLC2A9 or Glut 9) (15). The gene was initially described in an isolated island community (16,17), where genetic properties of the population are expected to act in favor of facilitated gene mapping efforts (18). Subsequent meta-analysis of 14 populations confirmed the association of this gene with serum uric acid concentrations (19). This led to a number of clinical studies that have confirmed its involvement in the uric acid metabolism, including urate handling in the kidney and uptake in the liver (20,21). Based on the previous suggestions that gout and nephrolithiasis may share a common pathway (15), it might be interesting to see if SLC2A9 could explain the commonalities in patients with any of the following conditions. Therefore, the aim of this study was to investigate the association of nephrolithiasis and genetic variants of the SLC2A9.     

Folic acid and vitamin B12 supplementation lowers plasma homocysteine but has no effect on serum bone turnover markers in elderly women: a randomized,double-blind,placebo-controlled trial

An elevated homocysteine level is a newly recognized risk factor for osteoporosis. Older individuals may have elevated homocysteine levels due to inadequate folate intake and/or lower absorption of vitamin B₁₂. The aim of this study was to determine whether there is an impact of folic acid and vitamin B₁₂ supplementation on homocysteine levels and, subsequently, on bone turnover markers in older women with mildly to moderately elevated homocysteine levels. It is hypothesized that supplementation with folic acid and vitamin B₁₂ will improve homocysteine levels and, in turn, positively modify bone turnover markers in this population. This randomized, double-blind, placebo-controlled trial included 31 women (65 to 93 years) with homocysteine levels greater than 10 μmol/L. Participants were randomly assigned to receive either a daily folic acid (800 μg) and vitamin B₁₂ (1000 μg) (n = 17) or a matching placebo (n = 14) for 4 months. The results showed significantly lower homocysteine concentrations in the vitamin group compared to the placebo group (10.6 vs 18.5 μmol/L, P = .007). No significant difference in serum alkaline phosphatase or C-terminal cross-linking telopeptide of type I collagen was found between the vitamin and placebo groups before or after supplementation. The use of folic acid and vitamin B₁₂ as a dietary supplement to improve homocysteine levels could be beneficial for older women, but additional research must be conducted in a larger population and for a longer period to determine if there is an impact of supplementation on bone turnover markers or other indicators of bone health.     

Vascular endothelial growth factor in children with neuroblastoma: a retrospective analysis

Background

Despite aggressive therapy, advanced stage neuroblastoma patients have poor survival rates. Although angiogenesis correlates with advanced tumour stage and plays an important role in determining the tumour response to treatment in general, clinical data are still insufficient, and more clinical evaluations are needed to draw conclusions. The aim of this study was to evaluate vascular endothelial growth factor (VEGF) expression in patients with neuroblastoma, determine whether it correlates with other prognostic factors and/or therapeutic response, and to assess should VEGF be considered in a routine diagnostic workup.

Materials and methods

VEGF expression was determined by immunohistochemistry using anti-VEGF antibody in paraffin embedded primary tumour tissue from 56 neuroblastoma patients. Semiquantitative expression of VEGF was estimated and compared with gender, age, histology, disease stage, therapy, and survival. Statistical analyses, including multivariate analysis, were performed.

Results

VEGF expression correlated with disease stage and survival in neuroblastoma patients. Combination of VEGF expression and disease stage as a single prognostic value for survival (P-value = 0.0034; odds ratio (OR) (95%CI) = 26.17 (2.97-230.27) exhibited greater correlation with survival than individually. Hematopoietic stem cell transplantation significantly improved survival of the advanced stage patients with high VEGF expression.

Conclusion

VEGF expression should be considered in a routine diagnostic workup of children with neuroblastoma, especially in those more than 18 months old and with advanced disease stage. High VEGF expression at the time of disease diagnosis is a bad risk prognostic factor, and can be used to characterize subsets of patients with an unfavourable outcome.     

Nm23‐H1 promotes adhesion of CAL 27 cells in vitro

nm23‐H1 was found to diminish metastatic potential of carcinoma cell lines and therefore was placed in the group of metastatic suppressor genes. Its protein product has a function of a nucleoside diphosphate kinase (NDPK) as well as protein kinase and nuclease. Though it was found that Nm23‐H1 is involved in many cellular processes, it is still not known how it promotes metastatic suppressor activity. Since the process of metastasis is dependent on adhesion properties of cells, the goal of our work was to describe the adhesion properties of CAL 27 cells (oral squamous cell carcinoma of the tongue) overexpressing FLAG/nm23‐H1. In our experiments, cells overexpressing nm23‐H1 show reduced migratory and invasive potential. Additionally, cells overexpressing nm23‐H1 adhere stronger on substrates (collagen IV and fibronectin) and show more spread morphology than the control cells. Results obtained by EGF induction of migration revealed that the adhesion strength predetermined cell response to chemoattractant and that Nm23‐H1, in this cell type, does not interfere with, EGF induced, Ras signaling pathway. These data contribute to the overall knowledge about nm23‐H1 and its role in cell adhesion, migration, and invasion, especially in oral squamous cell carcinoma. © 2009 Wiley‐Liss, Inc.     

Vaginal hysterectomy by means of morcellation

There were 1365 vaginal hysterectomies performed at the Department of Obstetrics and Gynaecology at Novi Sad. Morcellation was applied in 162 (11.9%) patients. It was most often applied in the group of patients from 40 to 49 years of age and in the sixth decade of life (27.2%; 44 cases). Uterine size was the basic indication for morcellation, but some other factors were of importance as well, such as: moveability, descensus, adhesions, fibroma location, depth and width of the vagina. The largest uterus in our study was 700 g in weight, while in most cases the uterus weighed approx. 250 g. There were no other complications during morcellation application. Postoperative morbidity was 24.7% and it followed the usual morbidity rate in V.H. Inflammations were the most frequent complications.