Prevalence of primary late-onset focal dystonia in the Belgrade population.

The aim of this cross-sectional study was to estimate the prevalence of different subtypes of idiopathic focal dystonia in the population of Belgrade (Serbia), Yugoslavia. On December 31, 2001, the crude prevalence of all studied types of dystonia (focal, segmental, and multifocal) in Belgrade was 13.6 per 100,000 population (11.8 per 100,000 for men and 15.2 per 100,000 for women). Type-specific prevalence for focal dystonia was 11.2 per 100,000. The prevalence for cervical dystonia, blepharospasm, writer's cramp and laryngeal dystonia were 5.9 per 100,000, 1.9 per 100,000, 1.9 per 100,000, and 1.1 per 100,000, respectively.     

A genetic study of idiopathic focal dystonias

The inheritance of focal dystonias was investigated in 43 families containing 43 index cases with torticollis (n = 21), blepharospasm (n = 18) and writer's cramp (n = 4). They generated a potential population of 235 first-degree relatives, and 168 out of 179 living first-degree relatives were examined. Ten relatives with dystonia were identified in ten families. Another two parents from two of the same group of ten families were affected according to the family history. The majority of the secondary cases (six patients, five siblings, and one child) were not aware of any dystonia. The tendency for affected relatives to have the same type of dystonia as index patients was observed only for torticollis. Overall, 23% of index patients had relatives with dystonia. Segregation analysis suggested the presence of an autosomal dominant gene or genes with reduced penetrante underlying focal dystonia.     

An evaluation of RVX-208 for the treatment of atherosclerosis

Introduction: RVX-208 is a first-in-class, orally active, novel small molecule in development by Resverlogix Corporation (Calgary, AB, Canada). It acts through an epigenetic mechanism by inhibiting the bromodomain and extraterminal (BET) family of proteins, increasing apolipoprotein A-I (apoA-I) and targeting high-density lipoprotein (HDL) metabolism, including generating of nascent HDL and increased larger HDL particles, resulting in the stimulation of reverse cholesterol transport. RVX-208 also has a beneficial effect on inflammatory factors known to be involved in atherosclerosis and plaque stability. New therapeutic strategies are needed for patients with atherosclerosis.

Areas covered: In this review, the authors evaluate the use of RVX-208 as an agent for the treatment of atherosclerosis. The article is based on a literature search considering both animal and human studies available on PubMed as well as Media Releases from the Resverlogix Corporation.

Expert opinion: The current evidence suggests promising beneficial effects of this novel drug in the prevention and treatment of atherosclerosis and other metabolic disorders. Its unique mechanism of action is encouraging; it affects several pathways and has a modest effect on HDL levels. There is also a shift in particle size to larger HDL particles, which may have potent atheroprotective effects. Future clinical development is needed, including safety assessment.     

Systemic humoral anti-Helicobacter pylori immune response in patients with gastric malignancies and benign gastroduodenal disease

BACKGROUND/AIMS: Helicobacter pylori elicits a strong local and systemic humoral immune response, but it is not able to eliminate bacteria. Immune response may be important for the course of infection that may lead to different gastroduodenal disease. In order to investigate differences in systemic humoral immune response between patients with different gastroduodenal diseases, we conducted clinical and serological studies. METHODOLOGY: From 1999 to 2001 we enrolled 80 patients with dyspeptic symptoms: 26 with gastritis, 12 with duodenal ulcer, 29 with gastric cancer and 13 with gastric lymphoma. In all patients during diagnostic work-up we performed ELISA test with Helicobacter pylori-specific IgG and IgA. We investigated difference in stimulation of different immunoglobulin classes in patients with different gastroduodenal diseases, particularly benign and malignant. We estimated significance of differences with Mann-Whitney and Fisher exact probability test. RESULTS: All patients enrolled in the study were seropositive. Patients with gastritis had statistically significant higher level of IgG than patients with gastric cancer (p=0.0001), and gastric lymphoma (p=0.006). Patients with duodenal ulcer had statistically significant higher level of IgG than patients with gastric cancer (p=0.02), and gastric lymphoma (p=0.046). IgA level was significantly higher in patients with gastritis than in patients with gastric cancer (p=0.03). IgA>IgG ratio was significantly more frequent in patients with gastric cancer and gastric lymphoma than in patients with gastritis and duodenal ulcer (p=0.0002). CONCLUSIONS: Result of our study suggested that Helicobacter pylori elicits different systemic humoral immune response in patients with gastritis and duodenal ulcer than in patients with gastric cancer and gastric lymphoma at least in intensity of stimulation of different immunoglobulin classes.     

Prevalence of FA-D2 Rare Complementation Group of Fanconi Anemia in Serbia

Objective

To investigate genetic subtypes of inherited bone marrow failure syndrome Fanconi anemia (FA) in Sebia. FA-D2 subtype was found to be the most frequent genetic subtype among investigated FA patients; specific observations of FA-D2 phenotype are pointed out.

Methods

Several biological endpoints of FA cells in vitro such as radiation-induced level of lymphocyte micronuclei (radiosensitivity), base line and radiation induced level of the DNA double strand breaks (DSBs), leukocyte apoptosis, and telomere capping function were assessed.

Results

The results indicate that all FA-D2 patients display radioresistant in vitro response, which is seen as significantly reduced yield of radiation-induced micronuclei. On the contrary, FA-A patients display radiosensitive in vitro response seen as increased number of radiation-induced micronuclei (MN). A massive elimination of irradiated cells via apoptosis is found in both FA-A and FA-D2 subtypes. In FA-A subtype apoptosis positively relates with the yield of radiation-induced MN, whereas in FA-D2 subtype apoptosis relates with a high percentage of cells carrying dysfunctional telomeres. The present results unequivocally demonstrate that cytokinesis-block micronucleus (CBMN) assay and analyses of telomere capping function can be used to distinguish FA-D2 and FA-A complementation groups.

Conclusions

Considering all biological endpoints were analyzed, it can be concluded that all FA patients are radiosensitive, regardless of their complementation group. Thus, using CBMN test and telomere capping function analysis can discriminate FA-A from FA-D2 complementation groups, which could be important for assessment the conditioning regimens prior to bone marrow transplantation.