Optimal sites for orthodontic mini-implant placement assessed by cone beam computed tomography

OBJECTIVES: To determine (1) the optimal sites for mini-implant placement in the maxilla and the mandible based on dimensional mapping of the interradicular spaces and cortical bone thickness and (2) The effect of age and sex on the studied anatomic measurements. MATERIAL AND METHODS: The cone beam computed tomography images of 100 patients (46 males, 54 females) divided into two age groups (13-18 years), and (19-27 years) were used. The following interradicular measurements were performed: (1) Buccolingual bone thickness; (2) Mesiodistal spaces both buccally and palatally/lingually; and (3) Buccal and palatal/lingual cortical thicknesses. RESULTS: In the maxilla, the highest buccolingual thickness existed between first and second molars; the highest mesiodistal buccal/palatal distances were between the second premolar and the first molar. The highest buccal cortical thickness was between the first and second premolars. The highest palatal cortical thickness was between central and lateral incisors. In the mandible, the highest buccolingual and buccal cortical thicknesses were between the first and second molars. The highest mesiodistal buccal distance was between the second premolar and the first molar. The highest mesiodistal lingual distance was between the first and second premolars. The highest lingual cortical thickness was between the canine and the first premolar. The males and the older age group had significantly higher buccolingual, buccal, and palatal cortical thicknesses at specific sites and levels in the maxilla and the mandible. CONCLUSIONS: A clinical guideline for optimal sites for mini-implant placement is suggested. Sex and age affected the anatomic measurements in certain areas in the maxilla and the mandible.

Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration

Background: With expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa. Methods: Pooled analysis of routine individual data from children who initiated ART in 7 South African treatment programs with 6-monthly viral load and CD4 monitoring produced Kaplan-Meier estimates of probability of virologic failure (2 consecutive unsuppressed viral loads with the second being >1000 copies/mL, after ≥24 weeks of therapy) and switch to second-line. Cox-proportional hazards models stratified by program were used to determine predictors of these outcomes. Results: The 3-year probability of virologic failure among 5485 children was 19.3% (95% confidence interval: 17.6 to 21.1). Use of nevirapine or ritonavir alone in the initial regimen (compared with efavirenz) and exposure to prevention of mother to child transmission regimens were independently associated with failure [adjusted hazard ratios (95% confidence interval): 1.77 (1.11 to 2.83), 2.39 (1.57 to 3.64) and 1.40 (1.02 to 1.92), respectively]. Among 252 children with ≥1 year follow-up after failure, 38% were switched to second-line. Median (interquartile range) months between failure and switch was 5.7 (2.9-11.0). Conclusions: Triple ART based on nevirapine or ritonavir as a single protease inhibitor seems to be associated with a higher risk of virologic failure. A low proportion of virologically failing children were switched.

Quantification of the carbonaceous matter origin in submicron marine aerosol by 13C and 14C isotope analysis

Dual carbon isotope anal. of marine aerosol samples has been performed for the first time demonstrating a potential in org. matter apportionment between three principal sources: marine, terrestrial (non-fossil) and fossil fuel due to unique isotopic signatures. The results presented here, utilizing combinations of dual carbon isotope anal., provides conclusive evidence of a dominant biogenic org. fraction to org. aerosol over biol. active oceans. In particular, the NE Atlantic, which is also subjected to notable anthropogenic influences via pollution transport processes, was found to contain 80 % org. aerosol matter of biogenic origin directly linked to plankton emissions. The remaining carbonaceous aerosol was of terrestrial origin. By contrast, for polluted air advected out from Europe into the NE Atlantic, the source apportionment is 30 % marine biogenic, 40 % fossil fuel, and 30 % continental non-fossil fuel. The dominant marine org. aerosol source in the atm. has significant implications for climate change feedback processes. [on SciFinder(R)]

Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients - A position paper endorsed by ESMINT and ESNR : Part II: methodology of future trials

Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines.

Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients: a position paper endorsed by ESMINT and ESNR : Part I: Current situation and major research questions

A new era of stroke treatment may have begun with mechanical thrombectomy (MT) by fully deployed closed-cell self-expanding stents (stent-triever). Multiple case series and the first randomised controlled trials (RCTs) have now been published. More studies are under way involving large numbers of patients, which in turn has resulted in less strict "pragmatic" study protocols. Problems with current trials include a lack of standardisation in the conduct of the recanalisation procedure, the definition of primary endpoints such as the grade of arterial recanalisation and tissue reperfusion, and the post-surgical care provided. In Part 1 of this two part series, we outline the current situation and the major research questions.

Capillary electrophoretic investigation of the enantioselective metabolism of propafenone by human cytochrome P-450 SUPERSOMES: Evidence for atypical kinetics by CYP2D6 and CYP3A4

An enantioselective CE method was used to identify the ability of CYP450 enzymes and their stereoselectivity in catalyzing the transformation of propafenone (PPF) to 5-hydroxy-propafenone (5OH-PPF) and N-despropyl-propafenone (NOR-PPF). Using in vitro incubations with single CYP450 enzymes (SUPERSOMES), 5OH-PPF is shown to be selectively produced by CYP2D6 and N-dealkylation is demonstrated to be mediated by CYP2D6, CYP3A4, CYP1A2, and CYP1A1. For the elucidation of kinetic aspects of the metabolism with CYP2D6 and CYP3A4, incubations with individual PPF enantiomers and racemic PPF were investigated. With the exception of the dealkylation in presence of R-PPF only, which can be described by the Michaelis-Menten model, all CYP2D6-induced reactions were found to follow autoactivation kinetics. For CYP3A4, all NOR-PPF enantiomer formation rates as function of PPF enantiomer concentration were determined to follow substrate inhibition kinetics. The formation of NOR-PPF by the different enzymes is stereoselective and is reduced significantly when racemic PPF is incubated. Clearance values obtained for CYP3A4 dealkylation are stereoselective whereas those of CYP2D6 hydroxylation are not. This paper reports the first investigation of the PPF hydroxylation and dealkylation kinetics by the CYP2D6 enzyme and represents the first report in which enantioselective CE data provide the complete in vitro kinetics of metabolic steps of a drug.

LH and IGF-1 release during oestrus and early luteal phase in lactating and non-lactating horse mares

The aim of the present study was to determine effects of lactation on basal LH and IGF-1 concentrations and on the LH response to a GnRH-analogue at different stages of the oestrous cycle in mares. A total of 17 cyclic Haflinger mares were included in the study. Experiments were performed on lactating mares in first postpartum oestrus, the subsequent early luteal phase, and second postpartum oestrus. Non-lactating mares were used in oestrus and early luteal phase. Blood samples were taken for 1 h at 15 min intervals. Mares were then injected with the GnRH-analogue buserelin (GnRHa; 5 microg i.v.) and blood samples were drawn every 15 min for further 2 h. LH in all samples and basal IGF-1-concentrations were determined by RIA. In lactating mares, basal LH concentrations during the early luteal phase tended to be lower (p = 0.07) and the LH response to GnRHa, calculated as area under the curve, was significantly less pronounced compared to non-lactating mares (p < 0.01). As well in lactating mares, the basal LH concentration between first early luteal phase and second oestrus differed significantly (p < 0.05) and the net response to GnRHa was significantly lower between first oestrus as well as second oestrus and first early luteal phase (p < 0.05) but not between first and second oestrous postpartum. Within the group of non-lactating mares, the LH response to GnRHa was as well significantly lower during oestrus than during early luteal phase (p < 0.01). IGF-1 concentrations differed neither between groups nor stages of the cycle within groups. In conclusion, basal and GnRHa-stimulated LH release in lactating mares is lower than in non-lactating mares. This difference, however, occurs only in the early luteal phase. In lactating mares, concentrations of LH appear adequate to allow ovulation to occur.

Factor XIII activation peptide is released into plasma upon cleavage by thrombin and shows a different structure compared to its bound form

The first step of coagulation factor XIII (FXIII) activation involves cleavage of the FXIII activation peptide (FXIII-AP) by thrombin. However, it is not known whether the FXIII-AP is released into plasma upon cleavage or remains attached to activated FXIII. The aim of the present work was to study the structure of free FXIII-AP, develop an assay for FXIII-AP determination in human plasma, and to answer the question whether FXIII-AP is released into plasma. We used ab-initio modeling and molecular dynamics simulations to study the structure of free FXIII-AP. We raised monoclonal and polyclonal antibodies against FXIII-AP and developed a highly sensitive and specific ELISA method for direct detection of FXIII-AP in human plasma. Structural analysis showed a putative different conformation of the free FXIII-AP compared to FXIII-AP bound to the FXIII protein. We concluded that it might be feasible to develop specific antibodies against the free FXIII-AP. Using our new FXIII-AP ELISA, we found high levels of FXIII-AP in in-vitro activated plasma samples and serum. We showed for the first time that FXIIIAP is detached from activated FXIII and is released into plasma, where it can be directly measured. Our findings may be of major clinical interest in regard to a possible new marker in thrombotic disease.

Novel sst5-selective somatostatin dicarba-analogues: synthesis and conformation-affinity relationships

We describe synthesis, conformational studies, and binding to the five somatostatin receptors (sst 1-5) of a few analogues of the cyclic octapeptide octreotide (1), where the disulfide bridge was replaced by a dicarba group. These analogues were prepared by on-resin RCM of linear hepta-peptides containing two allylglycine residues; first- and second-generation Grubbs catalyst efficiencies were compared. The C=C bridge was hydrogenated via two different methods. Binding experiments showed that two analogues had good affinity and high selectivity for the sst5 receptor. Three-dimensional structures of the active analogues were determined by (1)H NMR spectroscopy. Conformation-affinity relationships confirmed the importance of D-Phe(2) orientation for sst2 affinity. Moreover, helical propensities well correlates with the peptide sst5 affinity. The presence of the bulky aromatic side chain of Tyr(Bzl)(10) favored the formation of a 3(10)-helix and enhanced the sst5 selectivity suppressing the sst2 affinity. Finally, a new pharmacophore model for the sst5 was developed.

Maxillary sinus floor elevation using the (transalveolar) osteotome technique with or without grafting material. Part I: Implant survival and patients' perception

OBJECTIVES: To analyze the survival and success rates of implants installed utilizing the (transalveolar) osteotome technique, to compare peri-implant soft tissue parameters and marginal bone levels of osteotome-installed implants with implants placed using standard surgical procedures, and to evaluate patient-centered outcomes. MATERIAL AND METHODS: During 2000 to 2005, 252 Straumann dental implants were inserted in 181 patients. The surgical technique was a modification of the original osteotome technique presented by Summers. In addition to the clinical examination, the patients were asked to give their perception of the surgical procedure, utilizing a visual analogue scale. RESULTS: The cumulative survival rate of the osteotome-installed implants after a mean follow-up time of 3.2 years, was 97.4% (95% confidence intervals: 94.4-98.8%). From the 252 implants inserted, three were lost before loading and another three were lost in the first and second year. According to residual bone height the survival was 91.3% for implant sites with < or =4 mm residual bone height, and 90% for sites with 4 mm and 5 mm, when compared with that of 100% in sites with bone height of above 5 mm. According to implant length the survival rates were 100% for 12 mm, 98.7% for 10 mm, 98.7% for 8 mm and only 47.6% for 6 mm implants. Soft tissue parameters (pocket probing depth, probing attachment level, bleeding on probing and marginal bone levels) did not yield any differences between the osteotome-installed and the conventionally placed implants. More than 90% of the patients were satisfied with the implant therapy and would undergo similar therapy again if necessary. The cost associated with implant therapy was considered to be justified. CONCLUSION: In conclusion, the osteotome technique was a reliable method for implant insertion in the posterior maxilla, especially at sites with 5 mm or more of preoperative residual bone height and a relatively flat sinus floor.

Immunosuppressive treatment for acquired haemophilia: current practice and future directions in Germany, Austria and Switzerland

Acquired haemophilia is an autoimmune disorder characterised by autoantibody formation against coagulation factor VIII. Immunosuppressive treatments including steroids, cytotoxic drugs, rituximab or combinations thereof have been used to eradicate autoantibodies. Very few prospective studies exist evaluating the use of these treatments. Here, we performed a survey among 73 physicians from 57 haemophilia treatment centres in order to describe current practice patterns and critical issues for future research in acquired haemophilia. The results demonstrate a high diversity of first- and second-line treatments. Factors influencing treatment decision were underlying disorder, severity of bleeding and inhibitor titre. Frequently used first-line treatments were steroids plus cyclophosphamide (44%) and steroids alone (11%). Second-line treatment was most often rituximab (30%), with or without steroids and/or cyclophosphamide. Most participants indicated to change from first- to second-line treatment after 4 weeks in case of failure to obtain partial remission (31%), continued bleeding (40%) or continued severe bleeding requiring bypass treatment (59%). Immunoadsorption was preferred for first- and second-line treatment by 10% and 9% of participants, respectively. These results highlight critical issues in the field. Open questions and directions for future research are discussed.

Measuring finger joint cartilage by ultrasound as a promising alternative to conventional radiograph imaging

OBJECTIVE: To evaluate the reliability and validity of a novel ultrasound (US) imaging method to measure metacarpophalangeal (MCP) and proximal interphalangeal (PIP) finger joint cartilage. METHODS: We examined 48 patients with rheumatoid arthritis (RA), 18 patients with osteoarthritis (OA), 24 patients with unclassified arthritis of the finger joints, and 34 healthy volunteers. The proximal cartilage layer of MCP and PIP joints for fingers 2-5 was bilaterally visualized from a posterior view, with joints in approximately 90 degrees flexion. Cartilage thickness was measured with integrated tools on static images. External validity was assessed by measuring radiologic joint space width (JSW) and a numeric joint space narrowing (JSN) score in patients with RA. RESULTS: Precise measurement was possible for 97.5% of MCP and 94.2% of PIP joints. Intraclass correlation coefficients for bilateral total joint US scores were 0.844 (95% confidence interval [95% CI] 0.648-0.935) for interobserver comparisons and 0.928 (95% CI 0.826-0.971) for intraobserver comparisons (using different US devices). The US score correlated with JSN for both hands (adjusted R(2) = 0.513, P < 0.001) and JSW of the same finger joints (adjusted R(2) = 0.635, P < 0.001). Reduced cartilage shown by US allowed discrimination of early symptomatic OA versus early RA and healthy joints. In patients with RA, US scores correlated with duration of treatment-resistant, progressive RA. CONCLUSION: The US method of direct visualization and quantification of cartilage in MCP and PIP joints is objective, reliable, valid, and can be useful for diagnostic purposes in patients with arthritis.

Event-related electric microstates of the brain differ between words with visual and abstract meaning

The present study shows that different neural activity during mental imagery and abstract mentation can be assigned to well-defined steps of the brain's information-processing. During randomized visual presentation of single, imagery-type and abstract-type words, 27 channel event-related potential (ERP) field maps were obtained from 25 subjects (sequence-divided into a first and second group for statistics). The brain field map series showed a sequence of typical map configurations that were quasi-stable for brief time periods (microstates). The microstates were concatenated by rapid map changes. As different map configurations must result from different spatial patterns of neural activity, each microstate represents different active neural networks. Accordingly, microstates are assumed to correspond to discrete steps of information-processing. Comparing microstate topographies (using centroids) between imagery- and abstract-type words, significantly different microstates were found in both subject groups at 286–354 ms where imagery-type words were more right-lateralized than abstract-type words, and at 550–606 ms and 606–666 ms where anterior-posterior differences occurred. We conclude that language-processing consists of several, well-defined steps and that the brain-states incorporating those steps are altered by the stimuli's capacities to generate mental imagery or abstract mentation in a state-dependent manner.