Specialist training of Slovene family physicians

Family medicine in Europe started to develop in the 1960s with the introduction of obligatory specialist training. Slovenia is a country with a long tradition of family medicine specialist training, but up until 2002 this was neither elaborated on nor conducted by peers in general practice/family medicine. When the country's socialist system started to transform due to political reforms, Slovenia began to modify its system in order to meet the criteria of the European Union. One of the changes was the introduction of a new healthcare system with an influential Medical Chamber responsible for postgraduate training in all specialities. A new model for vocational training in family medicine was established in 2002, following the recommendations of the European Union of General Practitioners (UEMO). According to the new programme, which lasts 4 years, trainees spend half of their training in a hospital setting and half in general practice, where they are supervised by a trainer in practice. This article describes the legal process of introducing new forms of specialist training in Slovenia, and its content.

Conclusion: A comparison with UEMO countries shows that the new model is comparable to other countries.     

Dynamic monitoring of cytosolic glucose in single astrocytes

It is becoming increasingly clear that astrocytes are no longer playing a subservient role to neurons in the central nervous system (CNS), and that these cells are being considered as active communication integrators. They respond to neurotransmitters by the regulated release of gliotransmitters. The delay between neurotransmitter activation and the release of gliotransmitters from astrocytes is in the time-domain of subseconds, much slower than the submillisecond synaptic delay. Astrocytes also control microcirculation and provide metabolic support for neurons. However, the dynamics of their energy metabolic response to neurotransmitter application is not known. We here used a FRET glucose nanosensor to dynamically measure the cytosolic glucose concentration in single astrocytes. We show that following the adrenaline or noradrenaline stimulation the availability of cytosolic glucose is increased promptly after stimulation with a time-constant of 116.7 s and 115.9 s, respectively. A decline in cytosolic glucose concentration with a time-constant of 50.7 s was observed during glutamate and 16.7 s during lactate addition to astrocytes, when these were bathed in the presence of extracellular glucose-containing solution, likely reflecting predominant glucose engagement in glycogen synthesis. In contrast, in the glucose-free extracellular solution, glutamate application to astrocytes resulted in a slow increase in cytosolic glucose concentration, consistent with the view that glutamate may be an alternative energy source in hypoglycemic conditions. We conclude that astrocytic cytosolic glucose metabolism responds in the time-domain of tens of seconds, which is slower compared to the whole brain functional magnetic resonance imaging measurements of the local intravascular hemodynamic response.     

Pre-vaccination genomic diversity of human papillomavirus genotype 6 (HPV 6): A comparative analysis of 21 full-length genome sequences

Comparative analysis of 21 full-length genome sequences of human papillomavirus genotype 6 (HPV 6): 18 determined in this study and three sequences available in nucleotide sequence databases, revealed more than 98% nucleotide similarity to the HPV 6 prototype isolate. The minimum and maximum genomic distance between the full-length genomic variants and the prototype sequence was three nucleotide substitutions, and 122 nucleotide substitutions and three insertions, respectively. Detailed sequence analysis of early viral genes E7, E1, E2 and E4, late viral gene L2, and three non-classic non-coding genomic regions (NNCR) revealed the existence of at least four E7, twelve E1, eleven E2, six E4, eleven L2, two NNCR1, two NNCR2, and three NNCR3 genomic variants. In addition, several novel, potentially important amino acid mutations were identified. A phylogenetic tree calculated from viral genome sequences was dichotomic, separating all isolates into HPV 6b (prototypic) and HPV 6a/6vc (non-prototypic) genetic lineages. This study, which contributed the largest number of full-length HPV 6 genome sequences to date, confirmed that HPV 6 diversifies virtually equally across the entire genome by nucleotide (amino acid) exchanges in coding regions and additional nucleotide insertions/deletions in non-coding regions. However, this diversification trend was more evident in non-coding regions LCR and NNCR3 and early viral genes E4, E5a and E5b.     

Effect of response quality and line of treatment with rituximab on overall and disease-free survival of patients with B-cell lymphoma

Background

The introduction of rituximab into the treatment of patients with non-Hodgkin’s lymphomas has improved the overall response rate, as well as the response duration and the overall survival of patients with B-cell lymphomas. But only a few studies have addressed the question whether the better response (complete response) and the early introduction of rituximab into the treatment translate into the better survival. The aim of this retrospective study was to assess the potential relationship between either the quality of the response or the line of the rituximab treatment and the overall survival (OS) as well as the disease-free survival (DFS) of patients with B-cell lymphomas.

Patients and methods.

In the study, we analysed treatment outcomes in patients with different histological types of B-cell lymphomas who were treated at the Institute of Oncology between 2003 and 2007 with rituximab and chemotherapy. We included only patients who had the level of CD20 expression assessed prior to the introduction of the treatment with quantitative flow-cytometric measurements. The OS and DFS were evaluated by Kaplan-Meier survival curves.

Results

One hundred and fourteen patients were enrolled in the study. Patients who achieved a complete response after the rituximab containing treatment had a significantly longer OS than those reaching a partial response (hazard ratio [HR], 0.34; 95% CI, 0.05 to 0.91, P = 0.0375) and than patients with stable (hazard ratio [HR], 0.11; 95% CI, 0.0002 to 0.033, P < 0.0001) or progressive disease (hazard ratio [HR], 0.09; 95% CI, 0.003 to 0.03, P < 0.0001). Patients who achieved a complete response (CR; n = 70; 61.4%) had also a significantly longer DFS (hazard ratio [HR], 0.26; 95% CI, 0.021 to 0.538, P = 0.0068) than those reaching only a partial response (PR; n = 17; 14.9%). Patients treated with rituximab as the first-line treatment (n = 50; 43.9%) had a significantly longer OS than those treated with rituximab for the first (hazard ratio [HR], 0.27; 95% CI, 0.106 to 0.645, P = 0.0036) or second relapse (hazard ratio [HR], 0.22; 95% CI, 0.078 to 0.5, P = 0.0006). Also the DFS of patients treated with rituximab as the first-line treatment (n = 46; 52.9%) was significantly longer (hazard ratio [HR], 0.32; 95% CI, 0.088 to 0.9, P = 0.0325) than in patients treated with rituximab for their first relapse (n = 25; 28.7%).

Conclusions

These data indicate that a better response to rituximab therapy presumably translates into an improved OS and DFS for patients with B-cell lymphomas. The early introduction of rituximab into the treatment (i.e. first-line treatment) might improve OS. Therefore, the response adapted first-line therapy with rituximab should be considered when the treatment decision is taken in B-cell lymphoma patients.     

Insufficient Recanalization of Thrombotic Venous Occlusion—Risk for Postthrombotic Syndrome

Purpose

To investigate the relationship between recanalization rate of occluded veins after deep venous thrombosis (DVT) and development of postthrombotic syndrome (PTS).

Prevention of microvesiculation by adhesion of buds to the mother cell membrane--a possible anticoagulant effect of healthy donor plasma

Microvesicles (MVs) found in peripheral blood are derived from the budding of cell membranes and are associated with a higher risk of thrombosis. Recently, a hypothesis has been suggested that certain plasma proteins could suppress microvesiculation by mediating adhesion of the buds to the mother cell membrane. In a pilot study, we have tested this hypothesis by considering the relation between the amount of MVs in peripheral blood and the ability of plasma to induce adhesion between giant phospholipid vesicles (GPVs). MVs were isolated from human plasma and counted by flow cytometry. The adhesion between GPVs was measured by assessing the average angle of contact between the adhered vesicles. It was found that greater ability of plasma to induce adhesion relates to smaller concentration of MVs in plasma. The ratio between the concentration of MVs and the concentration of platelets proved the most efficient parameter to predict the propensity of the membrane to shed vesicles. Our results indicate that a stronger attractive interaction between GPVs mediated by plasma is associated with a smaller amount of MVs per platelets. Plasma that mediates stronger attractive interaction between GPVs might potentially be associated with a smaller risk of thrombosis.