Reuse of silver-palladium ceramic metal

The effect of various percentages of reused silver-palladium alloy on the bond strength of porcelain was considered. All-new metal and once-cast alloy with the addition of 50% new metal produced the highest bond values. Once-cast alloy with less than 50% new metal produced bond strength values that were significantly lower. When using this silver-palladium alloy, 50% new alloy should be added to each casting button, and buttons with questionable casting history should not be used.     

Evaluation of the MLH1 I219V alteration in DNA mismatch repair activity and ulcerative colitis

BACKGROUND: Inflammatory bowel diseases (IBDs; ulcerative colitis, UC, and Crohn's disease, CD) show familial clustering suggestive of a genetic background. A linkage susceptibility region for these diseases (IBD9) lies on chromosome 3p and includes the DNA mismatch repair gene MLH1. Loss of MLH1 confers the characteristic microsatellite instability (MSI) phenotype which is also frequently found in the mucosa of IBD patients. A common germline alteration of MLH1 (655A>G) results in the amino acid exchange MLH1 I219V. Conflicting data exist on its effect on the function of the protein and it has recently been reported to cosegregate with refractory UC, suggesting that this alteration may impair mismatch repair activity and thereby contribute to certain forms of UC. METHODS: We analyzed the MLH1 I219V alteration using in silico and biochemical analyses and assessed its appearance in 67 well-classified UC patients in comparison to 40 healthy individuals. RESULTS: The analyses showed that I219 is a conserved, buried hydrophobic residue, and that I219V is unlikely to abolish MLH1 function but may modulate it. Quantitative biochemical evaluation showed identical stability and activity of the protein. Furthermore, the alteration occurred equally frequently in analyzed patients and healthy volunteers. CONCLUSIONS: The MLH1 I219V alteration does not directly contribute to the etiology of UC through an impairment of mismatch repair. A putative linkage disequilibrium of MLH1 I219V with the causative gene(s) of the IBD9 locus is rather distant.     

Lysyl oxidase like‐4 monoclonal antibody demonstrates therapeutic effect against head and neck squamous cell carcinoma cells and xenografts

A new member of the lysyl oxidase (LOX) family, lysyl oxidase‐like 4 (LOXL4), is overexpressed in head and neck squamous cell carcinoma (HNSCC) compared to normal squamous epithelium. A monoclonal antibody (mAb) derived from fusion of Balb/c mouse splenocytes immunized with LOXL4 specific peptide was used to evaluate its therapeutic efficacy in 15 HNSCC cell lines associated with LOXL4 overexpression. For xenograft experiments 41 severe combined immunodeficient (SCID) mice were used to analyze LOXL4‐mAb mediated tumor regression. Cell viability was analyzed using cytotoxicity‐, and clonogenic‐assays. Significant suppression of tumor cell growth was observed in 12 out of 15 (80%) tumor cell lines after 48 hr exposure to the mAb (LD50 of 15 µg/ml to 45 µg/ml). The effect induced by the antibody could be blocked by pre‐incubation of the antibody with the peptide used for immunization of the mice and antibody generation, indicating that the effect of the antibody is specific. In mice inoculated with HNSCC cells, i.v. injections of the LOXL4‐mAb resulted within 70 days in extensive tumor destruction in all treated animals whereas no tumor regression occurred in control animals. In mice pre‐immunized i.v. with LOXL4‐mAb and subsequently injected with HNSCC cells, tumor development was considerably delayed in contrast to non LOXL4‐mAb pre‐immunized animals. These results demonstrate that the LOXL4‐mAb has potent antitumor activity and suggest its suitability as a therapeutic immune agent applicable to HNSCC exhibiting tumor specific upregulation of LOXL4.     

Suizidalität im klinischen Kontext hämatopoetischer Stammzelltransplantationen

Background

Allogeneic hematopoietic stem cell transplantation (HSCT) is nowadays implemented as a standard treatment in hematological oncology. In a few years there are expected to be 500,000 long-term survivors of HSCT worldwide and the numbers will show a clear increase. Little is known about suicidal ideation and suicide in the context of HSCT.

Objective

The current state of knowledge on suicide after HSCT was systematically reviewed. Specific and as yet unresolved issues are presented.

Material and methods

A systematic literature search on the topics of HSCT and suicide was carried out in the Medline and Embase databases. The results are discussed in detail.

Results

Only seven articles were found that address the topic of suicide and suicidal ideations after HSCT. In two publications the topic is only mentioned without any further analysis. In one case report important indications of specific risk factors within the HSCT setting are presented.

Conclusion

There is an alarming paucity of investigations on suicide after HSCT. The existing publications indicate a twofold increase of the risk of suicide for patients who had to undergo a HSCT. Younger men with somatic and/or psychological stress are particularly at risk The suicide risk is elevated for many years after therapy; therefore, an ongoing screening of long-term survivors is recommended. There is a substantial lack of specialized knowledge on suicide after HSCT. Furthermore, case reports suggest a deleterious impairment of communication in the context of HSCT. Practical advice as part of a proactive suicide prevention is discussed in this article.

     

Hydraulic integration and shrub growth form linked across continental aridity gradients

Both engineered hydraulic systems and plant hydraulic systems are protected against failure by resistance, reparability, and redundancy. A basic rule of reliability engineering is that the level of independent redundancy should increase with increasing risk of fatal system failure. Here we show that hydraulic systems of plants function as predicted by this engineering rule. Hydraulic systems of shrubs sampled along two transcontinental aridity gradients changed with increasing aridity from highly integrated to independently redundant modular designs. Shrubs in humid environments tend to be hydraulically integrated, with single, round basal stems, whereas dryland shrubs typically have modular hydraulic systems and multiple, segmented basal stems. Modularity is achieved anatomically at the vessel-network scale or developmentally at the whole-plant scale through asymmetric secondary growth, which results in a semiclonal or clonal shrub growth form that appears to be ubiquitous in global deserts.     

Neurological complications after intrathecal liposomal cytarabine application in patients after allogeneic haematopoietic stem cell transplantation

Liposomal cytarabine has been proven to be useful for the prevention and intrathecal treatment of neoplastic meningitis. It has no demonstrable myelosuppressive effects and may therefore be an attractive alternative for prophylaxis and treatment of the central nervous system (CNS) relapse after allogeneic haematopoietic stem cell transplantation (HSCT). The use of liposomal cytarabine had not been reported in HSCT recipients. We retrospectively reviewed the feasibility of liposomal cytarabine in the prophylaxis (n = 2) and treatment (n = 4) of neoplastic meningitis in a cohort of patients after allogeneic HSCT. This report focusses on neurological complications after intrathecal application of liposomal cytarabine. Mild headache was the most commonly reported adverse event. Two patients experienced sacral radiculopathy with irreversible cauda equina syndrome in one patient. Another patient progressed with pre-existing leukencephalopathy. Intrathecal liposomal cytarabine should be used very cautiously in allogeneic HSCT recipients with a history of CNS complications potentially involving cerebral-spinal fluid circulation, since significant neurotoxicity was observed in patients with extensive CNS-directed pre-treatment. The feasibility and safety of liposomal cytarabine in HSCT recipients has to be evaluated in a prospective study.     

Corticosteroid-resistant nephrotic syndrome with focal and segmental glomerulosclerosis : an update of treatment options for children

Corticosteroid-resistant nephrotic syndrome (CRNS) with focal and segmental glomerulosclerosis (FSGS) is a heterogeneous disorder and the most severe and frequent type of all glomerulopathies in children leading to end-stage renal failure. The podocyte is at the center of development and progress of FSGS; this unique cell type plays a major role in the integrity of glomerular structure and permeability. The rate of complete remission of CRNS after induction therapy using different immunosuppressant agents is reported to range between 30% and 84%, depending on the treatment schedule and on the underlying defects of FSGS. Children with genetic types of FSGS barely respond to immunosuppressant therapies and over-treatment prior to transplantation should be avoided. The response of children with an idiopathic type of FSGS to immunosuppressants is superior to those with genetic FSGS. However, many children with idiopathic FSGS do not enter complete remission if they are under-treated, for example, with short-term immunosuppressant monotherapies. If immunosuppressant treatment fails, these patients will have to undergo renal transplantation. However, as unknown pathogenetic mechanisms may persist, more than one-third of these patients with idiopathic FSGS develop a rapid recurrence of CRNS that responds poorly to further long-term therapeutic attempts. In contrast with previously published data, this review takes into account recently identified genetic etiologies of CRNS, and superior results with long-term combination therapy in idiopathic forms to avoid over- and under-treatment.