Combining diagnosis and treatment using ASBRU

Traditionally, diagnosis and treatment have been seen as two distinct tasks. Consequently, most approaches to computer supported health care focus on one of the two-mostly on diagnosis or rather on the interpretation of measurements which is much better understood and formalised. However, in practice diagnosis and treatment overlap and influence each other in many ways. Combinations range from repeatedly going through the diagnosis-treatment loop over a period of time to permanent monitoring of the patients' health condition as it is done in intensive care units. In this article we describe how to model these combinations using the clinical protocol-representation language ASBRU. It implements treatment steps in a hierarchy of skeletal, time-oriented plans. Diagnosis can either be described in a declarative way in the conditions, under which treatment steps are taken or it can be modelled explicitly as plans of their own right. We demonstrate our approach using examples taken from the American Association of Paediatricians' guideline for the treatment of hyperbilirubinemia in the new-born.     

Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6

Pseudoxanthoma elasticum (PXE) is a systemic heritable disorder that affects the elastic tissue in the skin, eye, and cardiovascular system. Mutations in the ABCC6 gene cause PXE. We performed a mutation screen in ABCC6 using haplotype analysis in conjunction with direct sequencing to achieve a mutation detection rate of 97%. This screen consisted of 170 PXE chromosomes in 81 families, and detected 59 distinct mutations (32 missense, eight nonsense, and six likely splice-site point mutations; one small insertion; and seven small and five large deletions). Forty-three of these mutations are novel variants, which increases the total number of PXE mutations to 121. While most mutations are rare, three nonsense mutations, a splice donor site mutation, and the large deletion comprising exons 23-29 (c.2996_4208del) were identified as relatively frequent PXE mutations at 26%, 5%, 3.5%, 3%, and 11%, respectively. Chromosomal haplotyping with two proximal and two distal polymorphic markers flanking ABCC6 demonstrated that most chromosomes that carry these relatively frequent PXE mutations have related haplotypes specific for these mutations, which suggests that these chromosomes originate from single founder mutations. The types of mutations found support loss-of-function as the molecular mechanism for the PXE phenotype. In 76 of the 81 families, the affected individuals were either homozygous for the same mutation or compound heterozygous for two mutations. In the remaining five families with one uncovered mutation, affected showed allelic compound heterozygosity for the cosegregating PXE haplotype. This demonstrates pseudo-dominance as the relevant inheritance mechanism, since disease transmission to the next generation always requires one mutant allelic variant from each parent. In contrast to other previous clinical and molecular claims, our results show evidence only for recessive PXE. This has profound consequences for the genetic counseling of families with PXE.     

Interobserver variability,detection rate,and lesion patterns of 68Ga-PSMA-11-PET/CT in early-stage biochemical recurrence of prostate cancer after radical prostatectomy

European Journal of Nuclear Medicine and Molecular Imaging - 68Ga-PSMA-11-PET/CT is increasingly used in early-stage biochemical recurrence of prostate cancer to detect potential lesions for an...     

Expression and stability of a Rhizobium leguminosarum bv. trifolii Sym plasmid in R. meliloti and Agrobacterium tumefaciens and its effect on clover-bacterium symbiosis

The Rhizobium leguminosarum bv. trifolii Sym plasmid pRtr5a was transferred by conjugation to R. meliloti strains deleted or mutated in the nod and fix genes, and also to a plasmid-less strain of Agrobacterium tumefaciens. The plasmid transfer led to the elimination of the resident cryptic plasmid of the R. meliloti recipients. The Sym plasmid of the recipients was only eliminated in the case of a deletion. In some cases the transferred plasmid was instable. The nod and nif/fix genes of R. leguminosarum bv. trifolii were expressed in R. meliloti and somewhat delayed in A. tumefaciens. A high level of nitrogen fixation on clover was only found in R. meliloti containing pRtr5a. However, this occurred only if the nif/fix genes of the recipient had been deleted before. Inoculation of clover with this R. meliloti strain resulted in a higher dry matter production in comparison to clover inoculated with the donor strain.     

Effectiveness and efficiency of primary care based case management for chronic diseases: rationale and design of a systematic review and meta-analysis of randomized and non-randomized trials [CRD32009100316]

Background  

Case management is an important component of structured and evidence-based primary care for chronically ill patients. Its effectiveness and efficiency has been evaluated in numerous clinical trials. This protocol describes aims and methods of a systematic review of research on the effectiveness and efficiency of case management in primary care.     

Microleakage of a consolidated silver direct filling material.

Microleakage of an experimental direct filling material comprised of a chemically precipitated silver powder that had been surface treated with a dilute acid to promote cold welding upon consolidation was evaluated. Microleakage was compared to both dispersed-phase and spherical amalgam by use of an in vitro gas-diffusion method and in class 5 restorations placed in extracted human teeth. The effect of two cavity varnishes and two dentin adhesives as cavity liners on microleakage was also evaluated using extracted teeth. Microleakage of silver powder consolidated with dental instruments was less than that found with dental amalgam. The use of copal or polyamide cavity varnish resulted in the lowest combination of microleakage on dentin and enamel margins.     

Inhibition of IL-6-dependent growth of myeloma cells by an acidic peptide repressing the gp130-mediated activation of Src family kinases

An acidic domain (AD) of gp130 was previously found to interact with the Src family kinase (SFK) Hck. Here, the influence of myristoylated peptides derived from this AD was assessed in the mouse myeloma cell line, 7TD1. The IL-6-dependent growth of 7TD1 cells was reduced by approximately 75%, if 100 microM of myristoylated 18mer peptide (18AD) was included in the growth medium, but was unaffected by a control peptide with scrambled sequence (18sc). A similar differential inhibition by peptides 18AD and 18sc was observed for the erythropoietin-dependent growth of BaF-EH cells expressing chimeric erythropoietin receptor-gp130 and human Hck and for the human myeloma cell line INA-6. While the peptide 18AD concentration inhibiting 50% was approximately 30 microM in 7TD1 and BaF-EH cells, peptide 18AD did not significantly inhibit growth of IL-6-independent MM1.S myeloma and OKT1 hybridoma cells or of BaF-EH cells supplied with IL-3. Treatment with 100 microM peptide 18AD caused the same degree or 60% of apoptosis induction as IL-6 deprivation in 7TD1 or INA-6 cells, respectively. Co-immunoprecipitation experiments revealed that peptide 18AD interfered with the association of Hck and gp130 in 7TD1 lysates in a concentration-dependent manner. IL-6-treatment of INA-6 cells induced the kinase activities of Fyn, Lyn and Hck, but not Src, and the IL-6-induced SFK activities were inhibited by peptide 18AD. Expression in 7TD1 cells of a kinase-inactive Hck mutant (K269R) elicited a dominant-negative effect on cell number increases providing further evidence that SFKs are required for gp130 signalling in myeloma cells.