Relative calibration of a retarding field energy analyzer sensor array for spatially resolved measurements of the ion flux and ion energy in low temperature plasmas.

A calibration routine is presented for an array of retarding field energy analyzer (RFEA) sensors distributed across a planar electrode surface with a diameter of 450 mm that is exposed to a low temperature plasma. Such an array is used to measure the ion velocity distribution function at the electrode with radial and azimuthal resolutions as a basis for knowledge-based plasma process development. The presented calibration procedure is tested by exposing such an RFEA array to a large-area capacitively coupled argon plasma driven by two frequencies (13.56 and 27.12 MHz) at a gas pressure of 0.5 Pa. Up to 12 sensors are calibrated with respect to the 13th sensor, called the global reference sensor, by systematically varying the sensor positions across the array. The results show that the uncalibrated radial and azimuthal ion flux profiles are incorrect. The obtained profiles are different depending on the sensor arrangement and exhibit different radial and azimuthal behaviors. Based on the proposed calibration routine, the ion flux profiles can be corrected and a meaningful interpretation of the measured data is possible. The calibration factors are almost independent of the external process parameters, namely, input power, gas pressure, and gas mixture, investigated under large-area single-frequency capacitively coupled plasma conditions (27.12 MHz). Thus, mean calibration factors are determined based on 45 different process conditions and can be used independent of the plasma conditions. The temporal stability of the calibration factors is found to be limited, i.e., the calibration must be repeated periodically.

Teriflunomide in relapsing-remitting multiple sclerosis: outcomes by age and pre-treatment status.

BACKGROUND AND AIMS: To investigate effectiveness and safety of teriflunomide (14 mg once daily) in association with age and pre-treatment in unselected MS patients. METHODS: Prespecified analysis of a non-interventional, prospective, real-world study in Germany. RESULTS: A total of 558 (49.5%) patients were above 45 years old, and 593 patients (52.6%) had been pre-treated within 6 months prior to teriflunomide. Baseline Expanded Disability Status Scale (EDSS) was higher with older age, with lower number of relapses. Relapse rate decreased in all age groups, and in both treatment-naïve (0.82 ± 0.73 at baseline; 0.25 ± 0.55 under teriflunomide) and pre-treated (from 0.48 ± 0.76; 0.22 ± 0.50) patients after 12 months compared with the year before teriflunomide initiation. EDSS remained stable in patients of all age groups as well as in therapy-naïve and pre-treated patients over 24 months. The percentage of patients with adverse events (AEs) ranged between 29.2% (age group >25-35) and 38.9% (age group >55-65), with an increased discontinuation rate (most commonly due to diarrhoea, alopecia and nausea) in the higher age groups. AE rates were lower in pre-treated compared with treatment-naïve patients. CONCLUSION: Overall, patients of all age groups including older patients, and irrespective of pre-treatment, benefit from teriflunomide treatment in routine clinical practice. REGISTRATION: BfArM public study database number 2075.

Effects of the Ion to Growth Flux Ratio on the Constitution and Mechanical Properties of Cr1-x-Alx-N Thin Films.

Cr-Al-N thin film materials libraries were synthesized by combinatorial reactive high power impulse magnetron sputtering (HiPIMS). Different HiPIMS repetition frequencies and peak power densities were applied altering the ion to growth flux ratio. Moreover, time-resolved ion energy distribution functions were measured with a retarding field energy analyzer (RFEA). The plasma properties were measured during the growth of films with different compositions within the materials library and correlated to the resulting film properties such as phase, grain size, texture, indentation modulus, indentation hardness, and residual stress. The influence of the ion to growth flux ratio on the film properties was most significant for films with high Al-content (xAl = 50 at. %). X-ray diffraction with a 2D detector revealed hcp-AlN precipitation starting from Al-concentration xAl ≥ 50 at. %. This precipitation might be related to the kinetically enhanced adatom mobility for a high ratio of ions per deposited atoms, leading to strong intermixing of the deposited species. A structure zone transition, induced by composition and flux ratio JI/JG, from zone T to zone Ic structure was observed which hints toward the conclusion that the combination of increasing flux ratio and Al-concentration lead to opposing trends regarding the increase in homologous temperature.

Deep phenotyping neuropathy: An underestimated complication in patients with pre-diabetes and type 2 diabetes associated with albuminuria.

AIMS: The aim of the study was to assess whether quantitative-sensory-testing could be used to evaluate prevalence and predictors of diabetic neuropathy (DPNP) in patients with pre-diabetes and type 2 diabetes. METHODS: Twenty-eight pre-diabetics and 108 patients with type 2 diabetes were evaluated using neuropathy-deficit-score (NDS), neuropathy-symptom-score (NSS), nerve-conduction-studies (NCS), short-QST-protocol to examine small fibers and the comprehensive QST-battery (long-QST) according to the German Research Network on Neuropathic Pain protocol. RESULTS: Long-QST revealed a DPNP-prevalence of 71% in pre-diabetics and 95% in patients with type 2 diabetes, while according to NDS it was only 11% and 63%, and NCS missed 58% of patients with DPNP. Small and medium fibers were similarly affected in both groups, while large fiber deficits were significantly more common in type 2 diabetes (p < 0.01). Complete loss of function in all fibers was significantly higher in patients with type 2 diabetes than in pre-diabetics (26% vs. 11%, p < 0.05). Hyperalgesia was slightly increased in pre-diabetes than in type 2 diabetes (57% vs. 43%, p = n.s.). However, NSS only showed significant associations with large fiber deficits. Logistic regression analyses revealed that age (OR 1.14[1.05/1.24]) and albuminuria (OR 12.8[1.52/107.3]) were independent predictors for the presence of DPNP. CONCLUSIONS: DPNP is much more prevalent in patients with pre-diabetes and type 2 diabetes and clinical routine tests may miss the majority of affected patients. Age and albuminuria, but not HbA1c, appear to be significantly associated with DPNP. CLINICAL TRIAL REGISTRATION: NCT03022721.

Prevention of hepatitis C virus infection and spread in human liver chimeric mice by an anti-CD81 monoclonal antibody.

UNLABELLED: CD81 is a required receptor for hepatitis C virus (HCV) infection of human hepatocytes in vitro. We generated several high-affinity anti-human CD81 monoclonal antibodies (mAbs) that demonstrated potent, specific, and cross-genotype inhibition of HCV entry. One of these mAbs, K04, was administered to human liver chimeric mice before or after HCV infection to determine its ability to prevent HCV infection or spread of HCV infection, respectively. All vehicle control mice established HCV infection, reaching steady-state levels of serum HCV RNA by day 21. Pretreatment of mice with K04 prevented HCV infection in all mice (n = 5). Treatment of mice with mAb K04 every 3 days for 21 days, starting at 6 hours postinfection, resulted in effective inhibition of virus spread. In 3 mice that were sacrificed on day 24, serum HCV levels remained detectable, below the limit of quantification (LOQ), indicating that infection was established, but virus spread was blocked, by the anti-CD81 mAb. In 5 additional mice that were followed for a longer time, virus remained detectable, below LOQ, until days 24 and 30 in 4 of 5 mice. In the fifth mouse, viral load was quantifiable, but reduced to 64-fold below the mean viral load in vehicle control at day 24. In addition, 2 of 5 mice cleared the infection by day 30 and 1 mouse had undetectable virus load from day 6 onward. CONCLUSION: These results demonstrate that CD81 is required for HCV infection and virus spread in vivo, and that anti-CD81 antibodies such as K04 may have potential as broad-spectrum antiviral agents for prevention and treatment of HCV infection.

A novel glycoengineered bispecific antibody format for targeted inhibition of epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor type I (IGF-1R) demonstrating unique molecular properties.

In the present study, we have developed a novel one-arm single chain Fab heterodimeric bispecific IgG (OAscFab-IgG) antibody format targeting the insulin-like growth factor receptor type I (IGF-1R) and the epidermal growth factor receptor (EGFR) with one binding site for each target antigen. The bispecific antibody XGFR is based on the "knob-into-hole" technology for heavy chain heterodimerization with one heavy chain consisting of a single chain Fab to prevent wrong pairing of light chains. XGFR was produced with high expression yields and showed simultaneous binding to IGF-1R and EGFR with high affinity. Due to monovalent binding of XGFR to IGF-1R, IGF-1R internalization was strongly reduced compared with the bivalent parental antibody, leading to enhanced Fc-mediated cellular cytotoxicity. To further increase immune effector functions triggered by XGFR, the Fc portion of the bispecific antibody was glycoengineered, which resulted in strong antibody-dependent cell-mediated cytotoxicity activity. XGFR-mediated inhibition of IGF-1R and EGFR phosphorylation as well as A549 tumor cell proliferation was highly effective and was comparable with a combined treatment with EGFR (GA201) and IGF-1R (R1507) antibodies. XGFR also demonstrated potent anti-tumor efficacy in multiple mouse xenograft tumor models with a complete growth inhibition of AsPC1 human pancreatic tumors and improved survival of SCID beige mice carrying A549 human lung tumors compared with treatment with antibodies targeting either IGF-1R or EGFR. In summary, we have applied rational antibody engineering technology to develop a heterodimeric OAscFab-IgG bispecific antibody, which combines potent signaling inhibition with antibody-dependent cell-mediated cytotoxicity induction and results in superior molecular properties over two established tetravalent bispecific formats.

Target-mediated drug disposition and prolonged liver accumulation of a novel humanized anti-CD81 monoclonal antibody in cynomolgus monkeys.

CD81 is an essential receptor for hepatitis C virus (HCV). K21 is a novel high affinity anti-CD81 antibody with potent broad spectrum anti-HCV activity in vitro. The pharmacokinetics (PK), pharmacodynamics and liver distribution of K21 were characterized in cynomolgus monkeys after intravenous (i.v.) administration of K21. Characteristic target-mediated drug disposition (TMDD) was shown based on the PK profile of K21 and a semi-mechanistic TMDD model was used to analyze the data. From the TMDD model, the estimated size of the total target pool at baseline (V(c) • R(base)) is 16 nmol/kg and the estimated apparent Michaelis-Menten constant (KM) is 4.01 nM. A simulation using estimated TMDD parameters indicated that the number of free receptors remains below 1% for at least 3 h after an i.v. bolus of 7 mg/kg. Experimentally, the availability of free CD81 on peripheral lymphocytes was measured by immunostaining with anti-CD81 antibody JS81. After K21 administration, a dose- and time-dependent reduction in free CD81 on peripheral lymphocytes was observed. Fewer than 3% of B cells could bind JS81 3 h after a 7 mg/kg dose. High concentrations of K21 were found in liver homogenates, and the liver/serum ratio of K21 increased time-dependently and reached ~160 at 168 h post-administration. The presence of K21 bound to hepatocytes was confirmed by immunohistochemistry. The fast serum clearance of K21 and accumulation in the liver are consistent with TMDD. The TMDD-driven liver accumulation of the anti-CD81 antibody K21 supports the further investigation of K21 as a therapeutic inhibitor of HCV entry.

A novel angiopoietin-2 selective fully human antibody with potent anti-tumoral and anti-angiogenic efficacy and superior side effect profile compared to Pan-Angiopoietin-1/-2 inhibitors.

There is increasing experimental evidence for an important role of Angiopoietin-2 (Ang-2) in tumor angiogenesis and progression. In addition, Ang-2 is up-regulated in many cancer types and correlated with poor prognosis. To investigate the functional role of Ang-2 inhibition in tumor development and progression, we generated novel fully human antibodies that neutralize specifically the binding of Ang-2 to its receptor Tie2. The selected antibodies LC06 and LC08 recognize both rodent and human Ang-2 with high affinity, but LC06 shows a higher selectivity for Ang-2 over Ang-1 compared to LC08 which can be considered an Ang-2/Ang-1 cross-reactive antibody. Our data demonstrate that Ang-2 blockade results in potent tumor growth inhibition and pronounced tumor necrosis in subcutaneous and orthotopic tumor models. These effects are attended with a reduction of intratumoral microvessel density and tumor vessels characterized by fewer branches and increased pericyte coverage. Furthermore, anti-Ang-2 treatment strongly inhibits the dissemination of tumor cells to the lungs. Interestingly, in contrast to the Ang-2/Ang-1 cross-reactive antibody LC08 that leads to a regression of physiological vessels in the mouse trachea, the inhibition with the selective anti-Ang-2 antibody LC06 appears to be largely restricted to tumor vasculature without obvious effects on normal vasculature. Taken together, these data provide strong evidence for the selective Ang-2 antibody LC06 as promising new therapeutic agent for the treatment of various cancers.

Targeted delivery of interferon-α to hepatitis B virus-infected cells using T-cell receptor-like antibodies.

UNLABELLED: During antiviral therapy, specific delivery of interferon-α (IFNα) to infected cells may increase its antiviral efficacy, trigger a localized immune reaction, and reduce the side effects caused by systemic administration. Two T-cell receptor-like antibodies (TCR-L) able to selectively bind hepatitis B virus (HBV)-infected hepatocytes of chronic hepatitis B patients and recognize core (HBc18-27) and surface (HBs183-91) HBV epitopes associated with different human leukocyte antigen (HLA)-A*02 alleles (A*02:01, A*02:02, A*02:07, A*02:11) were generated. Each antibody was genetically linked to two IFNα molecules to produce TCR-L/IFNα fusion proteins. We demonstrate that the fusion proteins triggered an IFNα response preferentially on the hepatocytes presenting the correct HBV-peptide HLA-complex and that the mechanism of the targeted IFNα response was dependent on the specific binding of the fusion proteins to the HLA/HBV peptide complexes through the TCR-like variable regions of the antibodies. CONCLUSION: TCR-L antibodies can be used to target cytokines to HBV-infected hepatocytes in vitro. Fusion of IFNα to TCR-L decreased the intrinsic biological activity of IFNα but preserved the overall specificity of the protein for the cognate HBV peptide/HLA complexes. This induction of an effective IFNα response selectively in HBV-infected cells might have a therapeutic advantage in comparison to the currently used native or pegylated IFNα.

Allosteric antibody inhibition of human hepsin protease.

Hepsin is a type II transmembrane serine protease that is expressed in several human tissues. Overexpression of hepsin has been found to correlate with tumour progression and metastasis, which is so far best studied for prostate cancer, where more than 90% of such tumours show this characteristic. To enable improved future patient treatment, we have developed a monoclonal humanized antibody that selectively inhibits human hepsin and does not inhibit other related proteases. We found that our antibody, hH35, potently inhibits hepsin enzymatic activity at nanomolar concentrations. Kinetic characterization revealed non-linear, slow, tight-binding inhibition. This correlates with the crystal structure we obtained for the human hepsin-hH35 antibody Fab fragment complex, which showed that the antibody binds hepsin around α3-helix, located far from the active centre. The unique allosteric mode of inhibition of hH35 is distinct from the recently described HGFA (hepatocyte growth factor activator) allosteric antibody inhibition. We further explain how a small change in the antibody design induces dramatic structural rearrangements in the hepsin antigen upon binding, leading to complete enzyme inactivation.

Cationic liposomes target sites of acute neuroinflammation in experimental autoimmune encephalomyelitis.

The binding selectivity of charged liposomes to the spinal cord of rats affected by experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, was investigated. Positively and negatively charged liposomes were injected into the tail vein of rats, and blood/brain barrier (BBB) targeting was determined by confocal microscopy as a function of the temporal evolution of the inflammatory response. Accumulation in spinal cord endoneural vessels was observed for cationic, but not for anionic, liposomes, and only in EAE but not in healthy rats. The overall binding efficacy paralleled the severity of the clinical score, but targeting was observed already before clinical manifestation of inflammation. Preferential binding of positively charged liposomes in the course of acute EAE can be ascribed to subtle changes of BBB morphology and charge distribution in a similar way as for the binding of cationic particles to proliferating vasculature in chronic inflammation and angiogenesis. Our findings suggest that vascular changes related to increased binding affinity for cationic particles are very early events within the inflammatory reaction in acute EAE. Investigation of cationic vascular targeting can help to shed further light on these occurrences, and, potentially, new diagnostic and therapeutic options may become available. In neuroinflammatory diseases, cationic colloidal carrier particles may enable intervention at affected BBB by an approach which is independent from permeability increase.

Fracture characteristics of anterior resin-bonded zirconia-fixed partial dentures.

Resin-bonded fixed partial dentures (RBFPD) are used as a minimal invasive, tooth-preventing alternative for replacing anterior teeth. Zirconia cantilever restorations were supposed to show sufficient strength for a clinical application. The aim of this investigation was to determine the fracture characteristics of cantilever and two-retainer RBFPD, which are fabricated by computer-manufactured high-strength zirconia. Human incisors and canines were used to form three groups of 14 RBFPDs with different types of preparation: group 1, an invasive cantilever; group 2, a minimal-invasive cantilever and group 3, a two-retainer RBFPD control. After thermal cycling and mechanical loading, which was performed to simulate oral service, all restorations were loaded to fracture in a universal testing machine. One half of the specimens were investigated as a control without simulated service. Mode of failure was determined for the three designs. Both cantilever groups showed comparable fracture resistance of 227 N (no. 1) and 210 N (no. 2) before thermal cycling and mechanical loading. The resistance after aging was reduced to 210 N for the invasive cantilever RBFPD and to 179 N for the minimal invasive group. Three-unit RBFPDs showed a significantly higher (p < 0.02) fracture resistance than cantilever bridges before (426 N) as well as after aging (360 N). Predominant failure was FPD and retainer fracture for the invasive cantilever design, debonding for the minimal cantilever design and RBFPD fracture for the two-retainer design. The present study revealed a significantly higher fracture resistance for two-retainer RBFPDs than for cantilever RBFPDs. The frequency of adhesive debonding increased for non-retentive prepared cantilever RBFPDs.

CD4-anchoring HIV-1 fusion inhibitor with enhanced potency and in vivo stability.

In this study, we describe a novel CD4-targeting bifunctional human immunodeficiency virus (HIV-1) fusion inhibitor (CD4-BFFI) that blocks HIV-1 entry by inhibiting both HIV-1 attachment and fusion and is highly potent against both R5 and X4 HIV-1 viruses in various antiviral assays, including peripheral blood mononuclear cell (PBMC) infection assays. Previously, we have reported a CCR5 antibody-based bifunctional HIV-1 fusion inhibitor (BFFI) that was highly active in blocking R5 HIV-1 infection but was ineffective against X4 viruses infecting human PBMCs (Kopetzki, E., Jekle, A., Ji, C., Rao, E., Zhang, J., Fischer, S., Cammack, N., Sankuratri, S., and Heilek, G. (2008) Virology J. 5, 56-65). CD4-BFFI, which consists of two HIV-1 fusion inhibitor (FI) T-651 variant peptides recombinantly fused to the Fc end of a humanized anti-CD4 monoclonal antibody, has demonstrated more than 100-fold greater antiviral activity than T-651 variant or the parental CD4 monoclonal antibody. Mechanistic studies revealed that CD4-BFFI primarily blocks the HIV-1-cell fusion step through its FI peptide moieties. The enhanced antiviral activity of CD4-BFFI is most likely due to avid binding of the bivalent FI peptides as well as the increased local concentration of CD4-BFFI via attachment to the target cell surface receptor CD4. In vivo pharmacokinetic studies demonstrated that CD4-BFFI was stable in monkey blood, and a dose of 10 mg/kg maintained serum concentrations greater than 2,000-fold over the IC(90) value for 7 days postdosing. This novel bifunctional inhibitor with improved potency and favorable pharmacokinetic properties may offer a novel approach for HIV-1 therapy.

Zirconia resin-bonded fixed partial dentures in the anterior maxilla.

OBJECTIVE: To determine the fracture resistance of resin-bonded fixed partial dentures (RBFPDs) by examining the influence of framework design and abutment mobility. METHOD AND MATERIALS: RBFPD frameworks were made of zirconia (Cercon Base, Degudent) or a nonprecious alloy (reference; Dentitan, Elephant Dental) and veneered with ceramic (Cercon Ceram S, Degudent). The zirconia framework design varied between a 2-retainer RBFPD with 3 different levels of tooth mobility (groups 1 to 3) and a 1-retainer cantilever version with 2 different grades of tooth mobility (groups 4 and 5). To achieve different mobility (rigid, medium, movable), the roots of the teeth were covered with a polyether material of different thicknesses. All RBFPDs were adhesively luted on prepared human teeth (Panavia 21 Ex, Kuraray). The specimens were mechanically (1.2 x 10(6); 25 N) and thermally (6,000 x 5 degrees C/55 degrees C; 2 minutes per cycle) cycled and finally loaded to failure (universal testing machine 1445, Zwick) at a speed of 1 mm/min. RESULTS: The fracture force of the reference RBFPD (541 N) was significantly higher than that of both cantilever RBFPDs (group 4 = 271 N, group 5 = 104 N) and one 2-retainer group with rigid abutments (group 3 = 150 N). With 2 movable abutments, the fracture force increased to 261 N (group 1) and with mixed movable/rigid teeth to 324 N (group 2). Zirconia RBFPDs showed improved survival with increased tooth mobility, but the framework design showed only a minor influence on loss rate and fracture resistance. CONCLUSIONS: Assuming chewing forces in anterior areas between 200 and 300 N, 1- and 2-retainer zirconia RBFPDs may be suitable as minimally invasive provisional alternatives to metal-supported RBFPDs.

Effect of design of all-ceramic resin-bonded fixed partial dentures on clinical survival rate.

In the treatment of single-tooth gaps, the resin-bonded fixed partial denture (FPD) has established itself as an alternative treatment modality. With the advent of high-strength ceramics, such as aluminum oxide ceramics, it appeared to be possible to fabricate all-ceramic resin-bonded FPDs without a metal reinforcement. However, fractures of the traditional two-retainer design of these restorations occurred quite frequently. It was proposed to change the two-retainer design to a single-retainer design with the hope that the survival rate could be improved. Nevertheless, the use of aluminum oxide ceramics can be problematic. The present study strongly suggests that the clinical performance of resin-bonded FPDs made of a high-strength glass-ceramic is in large measure dependent on their design.

Elucidation of the molecular mechanism underlying tumor-selective replication of the oncolytic adenovirus mutant ONYX-015.

Tumor-selective replicating viruses offer appealing advantages over conventional cancer therapy. ONYX-015 (dl1520) is the prototype for oncolytic adenoviral therapy. It has undergone extensive clinical testing with proven safety and evidence of promising clinical efficacy. The strategy underlying its tumor-selective cell killing is based on deletion of the viral E1B-55K gene, which is crucial for efficient viral replication in normal cells but dispensable in tumor cells. Originally, the successful replication of ONYX-015 was thought to strictly depend on deregulated p53 signaling in tumor cells. However, recent preclinical as well as clinical evidence questions this mechanism. The study by O'Shea and colleagues is of immense importance as it sheds new light into the molecular mechanism underlying the tumor-selective replication of ONYX-015. Based on these findings, modulation of the proposed molecular mechanism by pharmacologic agents or hyperthermia may largely enhance the therapeutic index of ONYX-015 for tumor cells versus normal tissue and improve clinical efficacy. Finally, new strategies to allow successful patient stratification for future clinical trials appear to be in reach, based on the reported results.

Oncolytic viruses for the treatment of cancer: current strategies and clinical trials.

Tumor-selective replicating viruses offer appealing advantages over conventional cancer therapy and are a promising new approach for the treatment of human cancer. The development of virotherapeutics is based on several strategies that each provides a different foundation for tumor-selective targeting and replication. Results emerging from clinical trials with oncolytic viruses demonstrate the safety and feasibility of a virotherapeutic approach and provide early indications of efficacy. Strategies to overcome potential obstacles and challenges to virotherapy are currently being explored and are discussed here. Importantly, the successful development of systemic administration of oncolytic viruses will extend the range of tumors that can be treated using this novel treatment modality.

Hearing threshold in sport divers: is diving really a hazard for inner ear function?

OBJECTIVE: To investigate the effect of scuba diving on the hearing threshold of sport divers who have no history of excessive noise exposure or of diving-related inner ear damage. DESIGN: Cross-sectional controlled comparison study. SETTING: General sports diving community. PARTICIPANTS: Sixty sport divers with an average of 650 dives each and at least 4 years of diving experience (mean, 10 years) were compared with a control group of 63 nondivers from our hospital staff or patients referred for rhinologic problems or benign tumors of the salivary gland. MAIN OUTCOME MEASURE: After microscopic otoscopy and tympanometry, we used pure-tone audiometry to measure the hearing threshold for air and bone conduction. The participants were divided into 3 age groups, and the hearing test results for both ears combined were statistically compared. RESULTS: There were no statistically significant differences in the hearing thresholds between sport divers and nondivers. CONCLUSIONS: The reduced hearing levels of professional divers found in other studies are probably due to the high noise levels that they have to deal with or may be a result of inner ear accidents.

[Frontal dysfunctions in Huntington's disease -- neuropsychology and therapy]. / Frontale Dysfunktion bei Chorea Huntington -- Neuropsychologische und therapeutische Aspekte.

Huntington's disease is a hereditary and progressive disease of the central nervous system. Sudden and irregular hyperkinesias are prominent. Psychopathological findings are very frequent and often proceed the decline of motor functions for years. Almost all the patients develop a dementia in later stages of the illness. This case study shows the treatment of a patient with Huntington's disease, verified by genetic analysis, with the atypical antipsychotic drug amisulpride. In this case the psychiatric disturbances and cognitive impairments were the only signs of the disease. The treatment showed an impressive improvement. Neuropsychological aspects of the disease are discussed.

Treatment of a juvenile patient with a maxillary all-ceramic resin-bonded fixed partial denture: a case report.

Treatment of juvenile patients with a missing maxillary incisor is difficult, because an implant cannot be placed until growth is completed. The other minimally invasive alternatives are also problematic: Removable dentures are rarely accepted by juvenile patients, and the conventional resin-bonded fixed partial denture often provides a poor esthetic result because the metal retainer causes the abutment teeth to lose their natural translucency and to become grayish. Moreover, the alveolar ridge defect makes it easy to identify the prosthesis in the pontic area. The present case report describes the prosthetic treatment of a juvenile patient who had lost a maxillary incisor to trauma. To avoid the disadvantages of conventional therapies, subepithelial connective tissue was grafted to reshape the alveolar ridge. The space was closed with an all-ceramic resin-bonded fixed partial denture.