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.

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.

Vascular network remodeling via vessel cooption, regression and growth in tumors.

The transformation of the regular vasculature in normal tissue into a highly inhomogeneous tumor specific capillary network is described by a theoretical model incorporating tumor growth, vessel cooption, neo-vascularization, vessel collapse and cell death. Compartmentalization of the tumor into several regions differing in vessel density, diameter and in necrosis is observed for a wide range of parameters in agreement with the vessel morphology found in human melanoma. In accord with data for human melanoma the model predicts that microvascular density (MVD), regarded as an important diagnostic tool in cancer treatment, does not necessarily determine the tempo of tumor progression. Instead it is suggested that the MVD of the original tissue as well as the metabolic demand of the individual tumor cell plays the major role in the initial stages of tumor growth.

Flow correlated percolation during vascular remodeling in growing tumors.

A theoretical model based on the molecular interactions between a growing tumor and a dynamically evolving blood vessel network describes the transformation of the regular vasculature in normal tissues into a highly inhomogeneous tumor specific capillary network. The emerging morphology, characterized by the compartmentalization of the tumor into several regions differing in vessel density, diameter, and necrosis, is in accordance with experimental data for human melanoma. Vessel collapse due to a combination of severely reduced blood flow and solid stress exerted by the tumor leads to a correlated percolation process that is driven towards criticality by the mechanism of hydrodynamic vessel stabilization.

[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.

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.

A comparative study of seven instruments in shaping the root canal in vitro.

The objective of this study was to evaluate the shaping characteristics of various root canal instruments using human teeth. A total of 420 extracted human roots were embedded in resin blocks. The embedded roots were divided into three groups, i.e. roots with (i) straight, (ii) apically curved, and (iii) whole-length curved canals according to the Schneider's angle and the length of the radius of arc fitting the curvature of root canals. Each of the three groups containing 140 roots were randomly divided into seven subgroups prior to preparation. The canals were prepared manually with traditional and flexible instruments, engine driven Racer-type, Giro-type, randomly vibrating instruments and with sonic and ultrasonic instruments. The shortcomings of the seven preparation methods were assessed by the superimposition of projected radiographs taken in bucco-lingual and mesio-distal views before and after the preparation. The prepared straight canals showed a high percentage (75.7%) of apical asymmetry. Coronal transposition of the apical stop was graded with higher scores in all canal forms prepared with Racer-type and Giro-type instruments, which could have occurred through packing of debris towards the apical constriction. The majority of the prepared curved canals were asymmetrical in shape. The location of the aberrations depended on the original shape of the canal but the method of shaping also had a decisive effect on the post-operative form of the canal. Large differences were found between the incidence of elbow (11.7-40.0%) and zip (75.7-80.0%). K-Flex files produced minor canal aberrations and significantly less asymmetry (P < 0.05) than the conventional hand instruments. The MM 1400 handpiece and ultrasonic instruments were associated with less aberration and significantly less asymmetry than the other instruments tested. The Excalibur appeared to be superior to the conventional hand instruments in straight canals, but its shaping characteristics were similar to conventional instruments in curved canals. Under the conditions of this study, canal shaping with Cavi Endo, MM 1400 and K-Flex files appeared to be superior to that achieved with conventional hand instruments Excalibur, Intra Lux Endo Kopf 3LDSY, and 3LD instruments.

The effect of root canal morphology on canal shape following instrumentation using different techniques.

The objective of this study was to evaluate the shaping characteristics of different root canal instruments in teeth with different root canal forms. A total of 420 extracted human roots were embedded in resin blocks. The embedded roots were divided into three groups, i.e., roots with (i) straight (I form), (ii) apically curved (J form), and (iii) entirely curved canals (C form) with reference to the Schneider's angle and the length of the radius of arc of the curvature of the root canals. Each of the three groups containing 140 roots were randomly divided into seven subgroups prior to preparation. The canals were enlarged manually with traditional and flexible hand instruments, three different engine driven instruments and sonically and ultrasonically powered instruments. The shortcomings of the seven preparation methods were assessed by superimposition of projected radiographs taken in bucco-lingual and mesio-distal views before and after preparation. Results showed that observation of perforation, incidence of elbow and of asymmetrical preparation of the root canals depended on root canal configuration. It was striking that the coronal transposition of the apical stop, uneven wall contour, ledge formation and incidence of zip were independent of root canal morphology. Evaluation of data of asymmetry of preparation (canal transposition) revealed significant differences (p < 0.05). Asymmetry of preparation was the most frequent aberration of the prepared root canals and it was possible to study it with precision. It was concluded that this measurement should be a priority for future instrument testing. The shaping characteristics of hand and engine driven instruments was modified by root canal morphology, but that of sonic and ultrasonic instruments was less dependent on the original anatomical form of root canals.

[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 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.

[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.

[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.

[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.

[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.

Hypotensive action of aggregated IgG in rats. Study of the unresponsiveness to a second dose following restoration of the blood pressure.

Human IgG preparations containing aggregates have been reported to induce hypotension in rats. Animals surviving a hypotensive dose of such a preparation were found unresponsive to a second dose given the next day. Unresponsiveness was induced by an isolated fraction of aggregated IgG, but not by purified monomers. Preparations containing aggregated and monomeric IgG appeared more efficient in inducing unresponsiveness than aggregates alone. The phagocyte function in vivo was assessed in unresponsive animals. No significant difference was found in the carbon clearance and in the human erythrocyte clearance test suggesting that a general impairment of the phagocyte function is not necessary for unresponsiveness. Previous studies indicated the involvement of PAF in hypotension by aggregated IgG. Hypotension was elicited by the injection of PAF in rats made "refractory" to aggregated IgG like in controls.

[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.