Seroepidemiology of mumps in Europe (1996-2008): why do outbreaks occur in highly vaccinated populations?

Mumps outbreaks have recently been recorded in a number of highly vaccinated populations. We related seroprevalence, epidemiological and vaccination data from 18 European countries participating in The European Sero-Epidemiology Network (ESEN) to their risk of mumps outbreaks in order to inform vaccination strategies. Samples from national population serum banks were collected, tested for mumps IgG antibodies and standardized for international comparisons. A comparative analysis between countries was undertaken using age-specific mumps seroprevalence data and information on reported mumps incidence, vaccine strains, vaccination programmes and vaccine coverage 5-12 years after sera collection. Mean geometric mumps antibody titres were lower in mumps outbreak countries [odds ratio (OR) 0·09, 95% confidence interval (CI) 0·01-0·71)]. MMR1 vaccine coverage ⩾95% remained protective in a multivariable model (P < 0·001), as did an interval of 4-8 years between doses (OR 0·08, 95% CI 0·01-0·85). Preventing outbreaks and controlling mumps probably requires several elements, including high-coverage vaccination programmes with MMR vaccine with 4-8 years between doses.

Vascular remodelling of an arterio-venous blood vessel network during solid tumour growth.

We formulate a theoretical model to analyze the vascular remodelling process of an arterio-venous vessel network during solid tumour growth. The model incorporates a hierarchically organized initial vasculature comprising arteries, veins and capillaries, and involves sprouting angiogenesis, vessel cooption, dilation and regression as well as tumour cell proliferation and death. The emerging tumour vasculature is non-hierarchical, compartmentalized into well-characterized zones and transports efficiently an injected drug-bolus. It displays a complex geometry with necrotic zones and "hot spots" of increased vascular density and blood flow of varying size. The corresponding cluster size distribution is algebraic, reminiscent of a self-organized critical state. The intra-tumour vascular-density fluctuations correlate with pressure drops in the initial vasculature suggesting a physical mechanism underlying hot spot formation.

Emergent vascular network inhomogeneities and resulting blood flow patterns in a growing tumor.

Tumors acquire sufficient oxygen and nutrient supply by coopting host vessels and neovasculature created via angiogenesis, thereby transforming a highly ordered network into chaotic heterogeneous tumor specific vasculature. Vessel regression inside the tumor leads to large regions of necrotic tissue interspersed with isolated surviving vessels. We extend our recently introduced model to incorporate Fahraeus-Lindqvist- and phase separation effects, refined tissue oxygen level computation and drug flow computations. We find, unexpectedly, that collapse and regression accelerates rather than diminishes the perfusion and that a tracer substance flowing through the remodeled network reaches all parts of the tumor vasculature very well. The reason for decreased drug delivery well known in tumors should therefore be different from collapse and vessel regression. Implications for drug delivery in real tumors are discussed.

Identification of thrombin receptors in rat brain capillary endothelial cells.

Both thrombin and plasmin induce contraction of brain endothelial cells, which may increase capillary permeability thereby leading to disruption of the blood-brain barrier. Identification of thrombin receptors, as well as the influence of plasmin on their activation, in capillary endothelial cells and astrocytes are therefore essential for understanding injury-related actions of thrombin in the brain. Using the reverse transcriptase-polymerase chain reaction method, the present study shows that primary cultures of rat brain capillary endothelial (RBCE) cells and astrocytes derived from rat brain express two different thrombin receptors. The first is proteolytically activated receptor (PAR)-1, the receptor responsible for the vast majority of the thrombin's cellular activation functions; the second is PAR-3, a receptor described to be essential for normal responsiveness to thrombin in mouse platelets. In addition to these thrombin receptors, the mRNA (messenger RNA) for PAR-2, a possible trypsin receptor, was also identified. Functional significance of thrombin receptors was indicated by changes in [Ca2+]i in response to thrombin, as measured by FURA-2 fluorescence in RBCE cells. Thrombin as low as 4 nmol/L induced an abrupt increase in [Ca2+]i whereas, upon addition of active site-blocked thrombin or plasmin, [Ca2+]i remained unchanged. The [Ca2+]i signal attributable to thrombin was smaller in a low Ca2+-containing medium, indicating that an influx of Ca2+ from the extracellular medium makes a contribution to the overall [Ca2+]i rise. The amplitude of the transient [Ca2+]i signal was dependent on the concentration of thrombin, and repeated application of the enzyme caused an essentially complete and long-term desensitization of the receptor. The PAR-1 agonist peptide SFLLRN also elicited a transient increase in [Ca2+]i. After activation by SFLLRN, cells showed a diminished response to thrombin, but the response was not absent, indicating that PAR-3 might contribute to the generation of the [Ca2+]i signal. Pretreatment of RBCE cells with 100 nmol/L plasmin completely prevented [Ca2+]i rise attributable to thrombin. These data show that RBCE cells and astrocytes express at least two receptors for thrombin, PAR-1 and PAR-3, and probably both receptors are involved in thrombin-induced [Ca2+]i signals. Plasmin itself does not elevate [Ca2+]i but prevents the activation of receptors by thrombin.

Role of cyclic AMP in promoting the thromboresistance of human endothelial cells by enhancing thrombomodulin and decreasing tissue factor activities.

1. The effects of forskolin, prostaglandin E1 (PGE1), dibutyryl cyclic AMP (db cyclic AMP), dibutyryl cyclic GMP (db cyclic GMP) and 3-isobutyl-l-methyl-xanthine (IBMX) were investigated on the expression of tissue factor and thrombomodulin activities on the surface of human saphenous vein endothelial cells (HSVEC) in culture. 2. Forskolin (10(-6) to 10(-4) M), PGE1 (10(-7) to 10(-5) M) and db cyclic AMP (10(-4) to 10(-3) M) caused a concentration-dependent decrease of cytokine-induced tissue factor activity. 3. Similar concentrations of forskolin, PGE1 and db cyclic AMP enhanced significantly constitutive thrombomodulin activity and reversed the decrease of this activity caused by interleukin-1 (IL-1). 4. IBMX (10(-4) M) decreased tissue factor activity and enhanced the effect of forskolin on tissue factor and thrombomodulin activities. 5. Forskolin (10(-4) M) decreased the IL-1-induced tissue factor mRNA and increased the thrombomodulin mRNA level. IL-1 did not change the thrombomodulin mRNA level after 2 h of incubation with HSVEC in culture. 6. Dibutyryl cyclic GMP (10(-4) M to 10(-3) M) did not influence tissue factor or thrombomodulin activity. 7. Our data suggest that elevation of intracellular cyclic AMP levels may participate in the regulation of tissue factor and thrombomodulin expression, thus contributing to promote or restore antithrombotic properties of the endothelium.

Interaction of antithrombin III and thrombin-antithrombin III complex with cultured aortic endothelial cells.

The binding of antithrombin III, thrombin, thrombin-antithrombin III complex to endothelial cells was investigated. While the rate of the binding of thrombin to these cells was very rapid, that of antithrombin III was relatively slow and the thrombin-antithrombin III complex was intermediate. Binding kinetics indicated that antithrombin III, like thrombin, showed high affinity to endothelial cells; with a Kd of 3 X 10(-8) M and with 5 X 10(4) binding sites per cell. The dissociation of the inhibitor molecule was also rapid, i.e., approximately 70% bound antithrombin III was released in 2 minutes. Heparin, in a 100-fold molar excess to antithrombin III, or the modification of lysine residues of the inhibitor involved in the interaction with heparin, did not influence the association of antithrombin III with endothelial cells. In addition, antithrombin III did not compete with thrombin blocked in its active center for binding to endothelial cells. It is suggested that the binding sites of endothelial cells are different for thrombin and antithrombin III, and antithrombin III does not bind to these cells through its heparin binding domain.

[Significance and possibilities of removing the debris layer forming during root canal therapy (review of the literature)]. / A gyökérkezelés során kialakuló "törmelék réteg" jelentösége, és eltávolításának lehetöségei.

The clinical estimation of the "Debris Layer" forming in the course of expanding the root channel is not entirely uniform in the literature wherefore also the question of its removal is the subject of dispute. Also the variety of methods suggested for stopping the DL proves that, for the time being, there is no optimum method yet and further research is still necessary.

[Endodontic treatment of gangrenous teeth--literature review]. / A gangrénás fogak endodontial kezelése (lrodalmi összefoglaló).

This overview was put together to update the endodontic knowledge of the general practitioners. Several treatment methods sometimes with contradicting principles are applied in Hungary using a wide range of endodontic medicines. The aim of the paper was not only to clarify the basic therapeutic principles but also to provide practical information about the relevant endodontic products for the everyday use.

[Cleansing effect of two micromotor-driven endodontic handpieces.II. Effect of various rinsing solutions on the cleansing effect of the handpieces]. / Két, mikromotorral meghajtott endodontiai kézidarab tisztítóhatásának vizsgálata. II. rész. Különbözó átöblítófolyadékok alkalmazásának befolyása az egyes kézidarabokkal végzett tisztítás eredményességére.

The cleansing effectivity of citric acid solution was significantly better than that of Neomagnol both with respect to the removal of the Smear Layer (SL) and to the number of visible dentinal tubular orifices, however a complete elimination of the SL could not be obtained. Neomagnol seemed to be more effective in the removal of superficial debris and tissue-remnants.

[Comparison of the cleansing effect of two micromotor-driven endodontic hand pieces. I. Comparison ot the cleansing effect of the two handpieces]. / Két mikromotorral meghajtott endodontiai kézidarab tisztitó hatásának vizsgálata. I. rész. A két kézidarab tisztitó hatásának összehasonlitása.

The aim of the study was to assess the cleansing-effect of two endodontic handpieces (Excalibur, W & H; MM 1400 Micro Méga) in root canals that were previously manually prepared, and treated with chlor-(Neomagnol) and citric acid containing solutions. The analyses were performed by scanning electron microscope (SEM). The elimination of the Smear Layer (SL) with Neomagnol was not successful with either of the two handpieces. The cleansing of the Superficial Debris (SD) with Neomagnol activated by MM 1400 was significantly more effective in the apical (p < 0.05) and in the middle (p < 0.01) third of the root-canal, than by Excalibur. In contrast, SL was better eliminated by Excalibur using citric acid, significant differences--when compared with MM 1400--could be seen in the middle third (p < 0.05) of the root-canal. The handpieces seem to have their own specific characteristics: thus MM 1400 was better in eliminating the SD (used with Neomagnol), while Excalibur was superior in eliminating the SL (used with citric acid).

[In vitro comparative study of instruments for root canal preparation. IV. Correlations between the original shape of the root canal and the asymmetry resulting from the preparation]. / Gyökércsatorna-preparáló müszerek in vitro összehasonlító vizsgálata. IV. rész. A gyökércsatorna eredeti formája és a preparálás során keletkezö aszimmetriák összefüggései.

Certain asymmetry of root canal preparation can be observed in the straight root canal group, as well. The modification of original root canal shape in this group usually is not substantial. Using hand instruments for shaping curved canals special tecniques are required to minimize the asymmetry. Though tendencies of different shaping characteristics can be observed on the mesiodistal and oro-vestibular views there are no statistically significant differences between the asymmetries measured on the oro-vestibular and mesio-distal views. The three dimensional form of canals usually exclude the possibility of forming the same asymmetry on both projections, but the difference between the two views is not striking, therefore the conventional clinical radiographs usually do not give complete information about the asymmetry of preparation.

[Comparative evaluation of different instruments for root canal preparation tested on extracted human teeth III. Study of sonic and ultrasonic instruments]. / A gyökércsatorna-tágító müszerek összehasonlító értékelése kihúzott emberi fogakon III. rész. A hangfrekvenciás és az ultrahangmüszerek vizsgálata.

A total of 460 roots of extracted human teeth were divided into three groups i.e. straight, apically curved and entirely curved groups. Each of the three groups were divided into seven subgroups according to instrumentation by conventional hand, K-Flex file, 3-LD, 3-LDSY, Excalibur. MM 1400 and Endo Sonic. Radiographs were taken both clinical and proximal views before and after the enlargement of canals. An assessment of shaping characteristic of instrumentation was made on the basis of overimposed radiographs including perforation, ledge formation smoothness of wall contour incidence of elbow and zip measurements at the elbow level and asymmetry measurements. The majority of enlarged root canals were asymmetrical in shape. High differences were found between the incidence of elbow and zip formation. Under laboratory conditions the K-Flex file produced minor canal aberrations and significantly less asymmetry than the conventional instruments. But both the above mentioned instruments caused perforations on curved canals, such as the instrumentation by Excalibur. The loss of working distance was significant in all canal forms prepared with 3-LD and 3-LDSY instruments, which could have occurred through the packing of debris towards the apical constriction. The Excalibur appeared to be superior to the conventional hand instrument in straight canals, but its shaping characteristic was similar to conventional hand instrument in curved canals. The MM 1400 handpiece and ultrasonic instruments resulted in less aberration and significantly less asymmetry than the other tested instruments.

[In vitro comparison of instruments for root canal preparation. III. Study of the instruments from the viewpoint of shaping asymmetry]. / Gyökércsatorna-preparáló müszerek in vitro összehasonlító vizsgálata. III. rész. A preparálóeszközök vizsgálata a tágítás aszimmetriájának szempontjából.

The shape of the prepared root canals is not consistent with the original anatomical shape in the majority of curved canals. The discrepancy is dependent of the type of instrument, the original anatomical form of the root canal and the location of the measurement. The original shape of the root canal has to be taken into consideration in the selection of preparatory instruments because their application is limited by the above mentioned factor. The sonic and ultrasonic preparatory instruments form an exception in this respect due to their non aggressive way of shaping. These instruments cannot be disregarded in the preparation of curved root canals.

[Comparison of the planimetric and gravimetric methods in the study of the efficiency of endodontic instruments]. / Az endodontiai eszközök hatékonyságának vizsgálatára szolgáló plani- és a gravimetriás módszer összehasonlítása.

Both gravimetry (measurement of weight loss of roots after root canal preparation) and planimetry (measurement of surface area corresponding to the removed dentin layer of canal walls on oro-vestibular and mesio-distal X-ray views of roots before and after the preparation) were used on the same samples for determination of the efficacy of root canal shaping instruments. There were no statistically significant differences between the results obtained using either the gravimetry or the planimetry indicating the evidence of reliability of results obtained using only the planimetry as a single method.

[In vitro comparison of instruments for root canal preparation. I. Pilot study of the homogeneity of study groups]. / Gyökércsatorna-preparáló müszerek in vitro összehasonlító vizsgálata. I. Rész. Elökísérlet a kísérleti csoportok homogenitásának vizsgálatára.

If extracted human teeth are used for comparative study of root canal preparatory instruments the selection of roots into homogeneous test groups is decisive step of the experiment. On the basis our pilot USDA it is necessary not only to consider the Schneider angle and the length of root canal curvature but the surface area of root canals on the mesio-distal and oro-vestibular radiographs showing the projected view of the canals.

[In vitro comparison of instruments used for root canal preparation. II. Effectiveness of the instruments]. / Gyökércsatorna-preparáló müszerek in vitro összehasonlító vizsgálata. II. rész. A müszerek hatékonyságának vizsgálata.

According to our examination, the anatomical shape of the root canal can influence the function of the examined instrument, therefore it's advisable to pay attention to the canal's curve at the selection of the root canal cutting instrument. Concerning the examined instruments, the least effective was the ultrasonic instrument.

Standardization of measles, mumps and rubella assays to enable comparisons of seroprevalence data across 21 European countries and Australia.

The aim of the European Sero-Epidemiology Network is to establish comparability of the serological surveillance of vaccine-preventable diseases in Europe. The designated reference laboratory (RL) for measles, mumps, rubella (MMR) prepared and tested a panel of 151 sera by the reference enzyme immunoassay (rEIA). Laboratories in 21 countries tested the panel for antibodies against MMR using their usual assay (a total of 16 different EIAs) and the results were plotted against the reference results in order to obtain equations for the standardization of national serum surveys. The RL also tested the panel by the plaque neutralization test (PNT). Large differences in qualitative results were found compared to the RL. Well-fitting standardization equations with R2> or =0.8 were obtained for almost all laboratories through regression of the quantitative results against those of the RL. When compared to PNT, the rEIA had a sensitivity of 95.3%, 92.8% and 100% and a specificity of 100%, 87.1% and 92.8% for measles, mumps and rubella, respectively. The need for standardization was highlighted by substantial inter-country differences. Standardization was successful and the selected standardization equations allowed the conversion of local serological results into common units and enabled direct comparison of seroprevalence data of the participating countries.