Molecular survival strategies of Echinococcus multilocularis in the murine host

Larval infection with Echinococcus multilocularis starts with the intrahepatic postoncospheral development of a metacestode that-at its mature stage-consists of an inner germinal and an outer laminated layer (GL ; LL). In certain cases, an appropriate host immune response may inhibit parasite proliferation. Several lines of evidence obtained in vivo and in vitro indicate the important bio-protective role of the LL. For instance, the LL has been proposed to protect the GL from nitric oxide produced by periparasitic macrophages and dendritic cells, and also to prevent immune recognition by surrounding T cells. On the other hand, the high periparasitic NO production by peritoneal exsudate cells contributes to periparasitic immunosuppression, explaining why iNOS deficienct mice exhibit a significantly lower susceptibility towards experimental infection. The intense periparasitic granulomatous infiltration indicates a strong host-parasite interaction, and the involvement of cellular immunity in control of the metacestode growth kinetics is strongly suggested by experiments carried out in T cell deficient mouse strains. Carbohydrate components of the LL, such as Em2(G11) and Em492, as well as other parasite metabolites yield immunomodulatory effects that allow the parasite to survive in the host. I.e., the IgG response to the Em2(G11)-antigen takes place independently of alpha-beta+CD4+T cells, and in the absence of interactions between CD40 and CD40 ligand. Such parasite molecules also interfere with antigen presentation and cell activation, leading to a mixed Th1/Th2-type response at the later stage of infection. Furthermore, Em492 and other (not yet published) purified parasite metabolites suppress ConA and antigen-stimulated splenocyte proliferation. Infected mouse macrophages (AE-MØ) as antigen presenting cells (APC) exhibited a reduced ability to present a conventional antigen (chicken ovalbumin, C-Ova) to specific responder lymph node T cells when compared to normal MØ. As AE-MØ fully maintain their capacity to appropriately process antigens, a failure in T cell receptor occupancy by antigen-Ia complex or/and altered co-stimulatory signals can be excluded. Studying the status of accessory molecules implicated in T cell stimulation by MØ, it could be shown that B7-1 (CD80) and B7-2 (CD86) remained unchanged, whereas CD40 was down-regulated and CD54 (=ICAM-1) slightly up-regulated. FACS analysis of peritoneal cells revealed a decrease in the percentage of CD4+ and CD8+T cells in AE-infected mice. Taken together the obstructed presenting-activity of AE-MØ appeared to trigger an unresponsiveness of T cells leading to the suppression of their clonal expansion during the chronic phase of AE infection. Interesting information on the parasite survival strategy and potential can be obtained upon in vitro and in vivo treatment. Hence, we provided very innovative results by showing that nitazoxanide, and now also, respectively, new modified compounds may represent a useful alternative to albendazole. In the context of chemotherapeutical repression of parasite growth, we searched also for parasite molecules, whose expression levels correlate with the viability and growth activity of E. multilocularis metacestode. Expression levels of 14-3-3 and II/3-10, relatively quantified by realtime reverse transcription-PCR using a housekeeping gene beta-actin, were studied in permissive nu/nu and in low-permissive wild type BALB/c mice. At 2 months p.i., the transcription level of 14-3-3 was significantly higher in parasites actively proliferating in nu/nu mice compared to parasites moderately growing in wild type mice. Immunoblotting experiments confirmed at the protein level that 14-3-3 was over-expressed in parasites derived from nu/nu mice at 2 months p.i. In vitro-treatment of E. multilocularis with an anti-echinococcal drug nitazoxanide for a period of 8 days resulted in a significant decrease of both 14-3-3 and II/3-10 transcription levels,

Serum levels of mannose-binding lectin and the risk of fever in neutropenia pediatric cancer patients

BACKGROUND: Fever in neutropenia (FN) is a frequent complication in pediatric oncology. Deficiency of mannose-binding lectin (MBL), an important component of innate immunity, is common due to genetic polymorphisms, but its impact on infections in oncologic patients is controversial. This study investigated whether MBL serum levels at cancer diagnosis are associated with the development of FN in pediatric cancer patients. PROCEDURE: Serum MBL was measured using ELISA. Frequency, duration, and cause of FN were assessed retrospectively. Association with MBL level was analyzed using uni- and multivariate Poisson regression taking into account both intensity and duration of chemotherapy. RESULTS: In 94 children, with a cumulative follow-up time of 81.7 years, 177 FN episodes were recorded. Patients with both very low MBL levels (<100 microg/L; risk ratio (RR), 1.93; 95% CI, 1.14-3.28; P = 0.014) and normal MBL levels (>/=1,000 microg/L; RR, P = 0.011) had significantly more frequent FN episodes than patients with low MBL levels (100-999 microg/L). Patients with very low MBL levels had significantly more episodes of FN with severe bacterial infection (bacteremia or pneumonia; RR, 4.49; 1.69 = 11.8; P = 0.003), while those with normal MBL levels had more FN episodes with no microbial etiology identified (RR, 1.85; 1.14 = 3.03; P = 0.014). CONCLUSIONS: Very low MBL levels are associated with more frequent FN episodes, mainly due to severe bacterial infections. The surprising finding that children with normal MBL levels had more frequent FN episodes than those with low MBL levels needs testing in prospective studies. Pediatr Blood Cancer (c) 2006 Wiley-Liss, Inc.

Changes in respiratory mechanics and gas exchange during the acute respiratory distress syndrome

BACKGROUND: The time course of impairment of respiratory mechanics and gas exchange in the acute respiratory distress syndrome (ARDS) remains poorly defined. We assessed the changes in respiratory mechanics and gas exchange during ARDS. We hypothesized that due to the changes in respiratory mechanics over time, ventilatory strategies based on rigid volume or pressure limits might fail to prevent overdistension throughout the disease process. METHODS: Seventeen severe ARDS patients {PaO2/FiO2 10.1 (9.2-14.3) kPa; 76 (69-107) mmHg [median (25th-75th percentiles)] and bilateral infiltrates} were studied during the acute, intermediate, and late stages of ARDS (at 1-3, 4-6 and 7 days after diagnosis). Severity of lung injury, gas exchange, and hemodynamics were assessed. Pressure-volume (PV) curves of the respiratory system were obtained, and upper and lower inflection points (UIP, LIP) and recruitment were estimated. RESULTS: (1) UIP decreased from early to established (intermediate and late) ARDS [30 (28-30) cmH2O, 27 (25-30) cmH2O and 25 (23-28) cmH2O (P=0.014)]; (2) oxygenation improved in survivors and in patients with non-pulmonary etiology in late ARDS, whereas all patients developed hypercapnia from early to established ARDS; and (3) dead-space ventilation and pulmonary shunt were larger in patients with pulmonary etiology during late ARDS. CONCLUSION: We found a decrease in UIP from acute to established ARDS. If applied to our data, the inspiratory pressure limit advocated by the ARDSnet (30 cmH2O) would produce ventilation over the UIP, with a consequent increased risk of overdistension in 12%, 43% and 65% of our patients during the acute, intermediate and late phases of ARDS, respectively. Lung protective strategies based on fixed tidal volume or pressure limits may thus not fully avoid the risk of lung overdistension throughout ARDS.

Tactile sensibility of single-tooth implants and natural teeth

AIM: The purpose of this randomized split-mouth clinical trial was to determine the active tactile sensibility between single-tooth implants and opposing natural teeth and to compare it with the tactile sensibility of pairs of natural teeth on the contralateral side in the same mouth (intraindividual comparison). MATERIAL AND METHODS: The hypothesis was that the active tactile sensibilities of the implant side and control side are equivalent. Sixty two subjects (n=36 from Bonn, n=26 from Bern) with single-tooth implants (22 anterior and 40 posterior dental implants) were asked to bite on narrow copper foil strips varying in thickness (5-200 microm) and to decide whether or not they were able to identify a foreign body between their teeth. Active tactile sensibility was defined as the 50% threshold of correct answers estimated by means of the Weibull distribution. RESULTS: The results obtained for the interocclusal perception sensibility differed between subjects far more than they differed between natural teeth and implants in the same individual [implant/natural tooth: 16.7+/-11.3 microm (0.6-53.1 microm); natural tooth/natural tooth: 14.3+/-10.6 microm (0.5-68.2 microm)]. The intraindividual differences only amounted to a mean value of 2.4+/-9.4 microm (-15.1 to 27.5 microm). The result of our statistical calculations showed that the active tactile sensibility of single-tooth implants, both in the anterior and posterior region of the mouth, in combination with a natural opposing tooth is similar to that of pairs of opposing natural teeth (double t-test, equivalence margin: +/-8 microm, P<0.001, power >80%). Hence, the implants could be integrated in the stomatognathic control circuit.

Specialisation and specialist education in prosthetic dentistry in Europe

This presentation reports on the results of a meeting of prosthodontists from selected European countries. The aim of the meeting was to analyse and promote specialisation and specialist education in Prosthetic Dentistry in Europe. Representatives for Europe were selected from the European Prosthodontic Association (EPA) board, the Education and Research Committee of International College of Prosthodontists (ICP), countries with a legally recognised speciality, countries without a recognised speciality but organised training programmes and countries with neither of these situations. Data about specialisation and specialist training in Prosthodontics in Europe was scrutinised and discussed. The programmes for countries with specialist training had relatively similar content, mostly of three years duration. There was strong agreement that a recognised speciality raises the level of care within the discipline for both specialists and non-specialists. In several of the countries where a speciality had been introduced it had been initiated by pressure from public health planning authorities. The conclusions are that from a professional viewpoint an advancement of the speciality over Europe would develop the discipline, improve oral health planning and quality of patient care. A working group for harmonisation was recommended.

Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results

All-trans retinoic acid (ATRA) plus anthracycline chemotherapy is the reference treatment of newly diagnosed acute promyelocytic leukemia (APL), whereas the role of cytosine arabinoside (AraC) remains disputed. We performed a joint analysis of patients younger than 65 years included in Programa para el Estudio de la Terapéutica en Hemopatía Maligna (PETHEMA) LPA 99 trial, where patients received no AraC in addition to ATRA, high cumulative dose idarubicin, and mitoxantrone, and APL 2000 trial, where patients received AraC in addition to ATRA and lower cumulative dose daunorubicin. In patients with white blood cell (WBC) count less than 10 x 10(9)/L, complete remission (CR) rates were similar, but 3-year cumulative incidence of relapse (CIR) was significantly lower in LPA 99 trial: 4.2% versus 14.3% (P = .03), although 3-year survival was similar in both trials. This suggested that AraC is not required in APL with WBC count less than 10 x 10(9)/L, at least in trials with high-dose anthracycline and maintenance treatment. In patients with WBC of 10 x 10(9)/L or more, however, the CR rate (95.1% vs 83.6% P = .018) and 3-year survival (91.5% vs 80.8%, P = .026) were significantly higher in APL 2000 trial, and there was a trend for lower 3-year CIR (9.9% vs 18.5%, P = .12), suggesting a beneficial role for AraC in those patients.

Post-surgical follow-up (by ELISA and immunoblotting) of cured versus non-cured cystic echinococcosis in young patients

The study was designed to determine comparatively the prognostic value of immunoblotting and ELISA in the serological follow-up of young cystic echinococcosis (CE) patients exhibiting either a cured or a progredient (non-cured) course of disease after treatment. A total of 54 patients (mean age 9 years, range from 3 to 15 years) with surgically, radiologically and/or histologically proven CE were studied for a period up to 60 months after surgery. Additionally, some of the patients underwent chemotherapy. Based on the clinical course and outcome, as well as on imaging findings, patients were clustered into 2 groups of either cured (CCE), or non-cured (NCCE) CE patients. ELISA showed a high rate of seropositivity 4 to 5 years post-surgery for both CCE (57.1%) and NCCE (100%) patients, the difference found between the two groups was statistically not significant. Immunoblotting based upon recognition of AgB subcomponents (8 and 16 kDa bands) showed a decrease of respective antibody reactivities after 4 years post-surgery. Only sera from 14.3% of CCE patients recognized the subcomponents of AgB after 4 years, while none (0%) of these sera was still reactive at 5 years post-surgery. At variance, immunoblotting remained positive for AgB subcomponents in 100% of the NCCE cases as tested between 4 and 5 years after surgical treatment. Immunoblotting therefore proved to be a useful approach for monitoring post-surgical follow-ups of human CCE and NCCE in young patients when based upon the recognition of AgB subcomponents.

In vitro fracture strength and thermal shock resistance of metal-ceramic crowns with cast and machined AuTi frameworks

STATEMENT OF PROBLEM: AuTi alloys with 1.6% to 1.7% (wt%) Ti provide sufficient bond strength to veneering ceramics, but the strength of entire metal-ceramic restorations fabricated from these alloys is not known. However, this information is important to assess the clinical performance of such materials. PURPOSE: This in vitro study evaluated the fracture strength and thermal shock resistance of metal-ceramic crowns with AuTi frameworks produced by milling or casting. MATERIAL AND METHODS: Frameworks of the alloy Au-1.7Ti-0.1Ir (wt%) (Esteticor Vision) were produced by milling or casting (test groups). A high-gold alloy (Esteticor Special) was used as the control. The frameworks were veneered with ceramic (VMK 95). Specimens (n=7) were loaded until fracture. Loads at failure (N) were recorded and the mean values statistically evaluated using 1-way analysis of variance and a post hoc Dunnett test (alpha=.05). To assess the crazing resistance of the veneering ceramic, 6 additional crowns of each group were subjected to a thermal shock test. Fractured surfaces were documented by scanning electron microscopy. Coefficients of thermal expansion of the materials used were measured (n=2) to assess the thermal compatibility between alloys and ceramic. RESULTS: The mean fracture strength of the crowns with machined AuTi frameworks (1294 +/- 236 N) was significantly lower (P=.012) than that of the cast AuTi frameworks (1680 +/- 150 N), but statistically not different than the high-gold alloy (1449 +/- 159 N). Bonding failure to the AuTi alloy predominantly occurred at the alloy-oxide interface. For the high-gold alloy, more ceramic residues were observed. In the thermal shock test, crowns with milled AuTi frameworks showed significantly higher thermal shock resistance compared to the other groups. The coefficients of thermal expansion (Esteticor Vision cast: 14.5 microm/m.K; Esteticor Vision milled: 14.3 microm/m.K; Esteticor Special cast: 13.7 microm/m.K) did not correlate with the results of the thermal shock test. CONCLUSION: The in vitro fracture strength of crowns with milled AuTi frameworks is lower than that obtained with cast AuTi frameworks, but comparable to those crowns produced with a high-gold alloy.

Fibula free flap reconstruction of the mandible in cancer patients: Evaluation of a combined surgical and prosthodontic treatment concept

The final goal of mandibular reconstruction following ablative surgery for oral cancer is often considered to be dental implant-supported oral rehabilitation, for which bone grafts should ideally be placed in a suitable position taking subsequent prosthetic restoration into account. The aim of this study was to evaluate the efficacy of a standardized treatment strategy for mandibular reconstruction according to the size of the bony defect and planned subsequent dental prosthetic rehabilitation. Data of 56 patients, who had undergone such a systematic mandibular fibula free flap reconstruction, were retrospectively analyzed. Early complications were observed in 41.5% of the patients but only in those who had been irradiated. Late complications were found in 38.2%. Dental implant survival rate was 92%, and dental prosthetic treatment has been completed in all classes of bony defects with an overall success rate of 42.9%. The main reasons for failure of the complete dental reconstruction were patients' poor cooperation (30.4%) and tumour recurrence (14.3%) followed by surgery-related factors (10.8%) such as implant failure and an unfavourable intermaxillary relationship between the maxilla and the mandible. A comparison of our results with the literature findings revealed no marked differences in the complication rates and implant survival rates. However, a systematic concept for the reconstructive treatment like the method presented here, plays an important role in the successful completion of dental reconstruction. The success rate could still be improved by some technical progress in implant and bone graft positioning.

Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on circadian intraocular pressure

OBJECTIVE: To compare the effect of bimatoprost and the fixed combination of latanoprost and timolol (LTFC) on 24-hour mean intraocular pressure (IOP) after patients are switched from a nonfixed combination of latanoprost and timolol. DESIGN: Randomized, double-masked, multicenter clinical trial. PARTICIPANTS: Two hundred patients with glaucoma or ocular hypertension. METHODS: Included were patients who were controlled (IOP < 21 mmHg) on the nonfixed combination of latanoprost and timolol for at least 3 months before the baseline visit or patients on monotherapy with either latanoprost or timolol who were eligible for dual therapy not being fully controlled on monotherapy. The latter group of patients underwent a 6-week wash-in phase with the nonfixed combination of latanoprost and timolol before baseline IOP determination and study inclusion. Supine and sitting position IOPs were recorded at 8 pm, midnight, 5 am, 8 am, noon, and 4 pm at baseline, week 6, and week 12 visits. MAIN OUTCOME MEASURE: An analysis of covariance model was used for a noninferiority test of the primary efficacy variable, with mean area under the 24-hour IOP curve after 12 weeks of treatment as response variable and treatment, center, and baseline IOP as factors. A secondary analysis was performed on the within-treatment change from baseline. RESULTS: Mean baseline IOPs were 16.3+/-3.3 mmHg and 15.5+/-2.9.mmHg in the bimatoprost and LTFC groups, respectively. At week 12, mean IOPs were 16.1+/-2.5 mmHg for the bimatoprost group and 16.3+/-3.7 mmHg for the LTFC group, and no significant difference between the 2 treatment groups could be found. As compared with baseline, mean IOP increased by 0.3+/-3.6 mmHg during the day and decreased by 0.8+/-3.8 mmHg during the night in the bimatoprost group, whereas there were increases of 1.43+/-2.6 mmHg and 0.14+/-3.2 mmHg in the LTFC group, respectively. CONCLUSIONS: Bimatoprost is not inferior to the LTFC in maintaining IOP at a controlled level during a 24-hour period in patients switched from the nonfixed combination of latanoprost and timolol.

Periprocedural embolic events related to carotid artery stenting detected by diffusion-weighted MRI: comparison between proximal and distal embolus protection devices

PURPOSE: To evaluate and compare the efficacy of proximal versus distal embolus protection devices (EPD) during carotid artery angioplasty/stenting (CAS) based on diffusion-weighted magnetic resonance imaging (DW-MRI). METHODS: Forty-four patients (31 men; mean age 68 years, range 48-85) underwent protected CAS and had DW-MRI before and after the intervention. The cohort was analyzed according to the type of EPD used: a proximal EPD was deployed in 25 (56.8%) patients (17 men; mean age 66 years, range 48-85) and a distal filter in 19 (14 men; mean age 70 years, range 58-79). Fifteen (60.0%) patients with proximal protection were symptomatic of the target lesion; in the distal protection group, 10 (52.6%) were symptomatic. RESULTS: New lesions were seen on the postinterventional DW-MRI in 28.0% (7/25) of the proximal EPD group versus 32.6% (6/19) of those with a distal filter (p = NS). The majority were clinically silent. The new lesions in the vascular territory of the stented carotid artery in the group as a whole and per patient were fewer in the proximal EPD group (p = NS). No significant differences were noted in the T(2) appearance of the new lesions or the number of new lesions observed away from the vascular territory of the stented artery. CONCLUSION: Proximal embolus protection devices show a nonsignificant trend toward fewer embolic events, which warrants large-scale studies. Furthermore, proximal protection devices can be useful to control and treat acute in-stent thrombosis.

Bodenerosions-Gefährdungskarte der Schweiz

Die Bodenerosions-Gefährdungskarte gibt einen nationalen Überblick über das Abtragsrisiko der Schweizer Böden und vor allem für die Ackerböden. Mit Hilfe einer angepassten Version des empirischen Erosionsmodells «Universal Soil Loss Equation» (USLE) wurde die langfristige Bodenerosionsgefährdung flächendeckend im Hektarraster berechnet. Die Bodenerosions-Gefährdungskarte soll den Kantonen als Grundlage dienen, detaillierte Karten zu erstellen oder besonders gefährdete Gebiete vertieft zu untersuchen. Unter der Annahme, dass alle Ackerflächen mit dem Pflug bearbeitet und keine Zwischenfrüchte angebaut werden, weisen bei heutiger Fruchtfolgegestaltung 61 % aller Ackerflächen einen langjährigen mittleren Bodenabtrag von unter zwei Tonnen pro Hektare und Jahr auf und sind damit als wenig erosionsgefährdet einzustufen. 22 % liegen im kritischen Bereich zwischen zwei und vier Tonnen pro Hektare und Jahr, 17 % sind mit mehr als vier Tonnen pro Hektare und Jahr als stark erosionsgefährdet zu bezeichnen. Die räumliche Verteilung der Abtragswerte zeigt ein sehr heterogenes Muster innerhalb der Hauptackerbau-Regionen ohne räumlich konzentrierte Schwerpunktregionen. In einer Szenario-Berechnung, bei der die Bodenbearbeitung mit dem Pflug durch Direktsaat sowie Winterbrache durch Zwischenkulturanbau flächendeckend ersetzt werden, reduziert sich das Bodenerosionsrisiko im Durchschnitt um rund zwei Drittel.