The Region of Difference Four is a Robust Genetic Marker for Subtyping Mycobacterium caprae Isolates and is Linked to Spatial Distribution of Three Subtypes.

Alpine Mycobacterium caprae isolates found in cattle and red deer display at least three genetic variations in the region of difference four (RD4) that can be used for further differentiation of the isolates into the subtypes 'Allgäu', 'Karwendel' and 'Lechtal'. Each genomic subtype is thereby characterized by a specific nucleotide deletion pattern in the 12.7-kb RD4 region. Even though M. caprae infections are frequently documented in cattle and red deer, little is known about the transmission routes. Hence, robust markers for M. caprae subtyping are needed to gain insight into the molecular epidemiology. For this reason, a rapid and robust multiplex PCR was developed for the simultaneous detection of three M. caprae RD4 subtypes and was used to subtype a total number of 241 M. caprae isolates from animals (145 cattle, 95 red deer and one fox) from Bavaria and Austria. All three subtypes occur spatially distributed and are found in cattle and in red deer suggesting transmission between the two species. As subtypes are genetically stable in both species it is hypothesized that the described genetic variations developed within the host due to 'within-host replication'. The results of this study recommend the genomic RD4 region as a reliable diagnostic marker for M. caprae subtype differentiation.

Toward knowledge-based liver surgery: holistic information processing for surgical decision support.

PURPOSE: Malignant neoplasms of the liver are among the most frequent cancers worldwide. Given the diversity of options for liver cancer therapy, the choice of treatment depends on various parameters including patient condition, tumor size and location, liver function, and previous interventions. To address this issue, we present the first approach to treatment strategy planning based on holistic processing of patient-individual data, practical knowledge (i.e., case knowledge), and factual knowledge (e.g., clinical guidelines and studies). METHODS: The contributions of this paper are as follows: (1) a formalized dynamic patient model that incorporates all the heterogeneous data acquired for a specific patient in the whole course of disease treatment; (2) a concept for formalizing factual knowledge; and (3) a technical infrastructure that enables storing, accessing, and processing of heterogeneous data to support clinical decision making. RESULTS: Our patient model, which currently covers 602 patient-individual parameters, was successfully instantiated for 184 patients. It was sufficiently comprehensive to serve as the basis for the formalization of a total of 72 rules extracted from studies on patients with colorectal liver metastases or hepatocellular carcinoma. For a subset of 70 patients with these diagnoses, the system derived an average of [Formula: see text] assertions per patient. CONCLUSION: The proposed concept paves the way for holistic treatment strategy planning by enabling joint storing and processing of heterogeneous data from various information sources.

Screening for carnitine palmitoyltransferase II deficiency by tandem mass spectrometry.

Mitochondrial carnitine palmitoyltransferase II (CPT II) deficiency is the most common inherited disorder of lipid metabolism in adults. Currently the routine diagnosis is based on the determination of CPT enzyme activity in muscle tissue. We have analysed the tandem mass spectra of serum acylcarnitines of nine CPT II-deficient patients. These spectra were compared to those of a cohort of 99 patients with other neuromuscular disorders and metabolic conditions supposed to cause alterations of the long-chain acylcarnitines. The spectra in CPT II deficiency showed characteristic elevations of C16:0 and C18:1 acylcarnitines while acetylcarnitine C2 was not elevated. In the present study, the ratio (C16:0+C18:1)/C2 has detected all CPT II deficiencies and discriminated them from unspecific alterations of serum acylcarnitines. The ratios of CPT II-deficient patients showed virtually no overlap with those observed in patients with other neuromuscular disorders. We suggest mass spectrometry of serum acylcarnitines as a rapid screening test that should be included early in the diagnostic work-up of patients with recurrent myoglobinuria, recurrent muscular weakness and myalgia.