[Pain therapy care in Germany-Do patients receiving day care differ from those receiving outpatient or inpatient care at the start of treatment? : A further evaluation based on the KEDOQ-pain data set]. / Schmerztherapeutische Versorgung in Deutschland ­ unterscheiden sich teilstationär versorgte Patienten von den ambulant oder stationär versorgten bei Behandlungsbeginn? : Eine weitere Auswertung auf Basis des KEDOQ-Schmerz-Datensatzes.

The direct comparison of day care pain patients with patients from other treatment sectors with respect to sociodemographic, pain-related and psychological characteristics has not yet been the subject of systematic analyses. The project core documentation and quality assurance in pain therapy (KEDOQ-pain) of the German Pain Society (Deutsche Schmerzgesellschaft e.V.) makes this comparison possible. This second analysis of the available KEDOQ data was intended to show how patients receiving day care treatment can be characterized using the core data set and whether and to what extent they differ from patients receiving outpatient or inpatient treatment. This is a continuation of the first publication, which showed remarkably small differences between outpatients and inpatients but did not include day care patients.The KEDOQ-pain data from 25 centers with a total of 8953 patients were evaluated. Patients had completed the German pain questionnaire (DSF) between January 2012 and March 2017 and received day care (n = 1264), outpatient (n = 4082) or inpatient (n = 3607) pain therapy treatment. Sociodemographic, pain-related and psychometric data of the DSF reported by patients were evaluated as well as physician information on the pain chronification stage and pain localization. The evaluation was descriptive and compared groups using univariate and multivariate procedures.Day care treated patients were significantly younger, had a higher level of education, were more frequently employed, reported higher impairment values and showed a higher severity index according to von Korff than inpatients and outpatients treated for pain. In addition, they described a shorter pain duration as well as worse habitual well-being (Marburg questionnaire on habitual well-being, MFHW). These predictors explained roughly half of the variance in the prediction of the day care treatment setting. The comparison of outpatients and inpatients showed significant group differences for some variables; however, the effects were very small.The evaluations suggest that pain therapy day care facilities treat a special group of pain patients that significantly differ from patients in other treatment sectors. Cautious conclusions are drawn regarding the systematic allocation of patients to care appropriate to their treatment needs.

Identification of single nucleotide polymorphisms (SNPs) in the 16S rRNA gene of foodborne Bacillus spp.

The main goal of this work was the identification of single nucleotide polymorphisms (SNPs) in the 16S rRNA gene of foodborne Bacillus spp. that may be useful for typing purposes. These species include, among others, Bacillus cereus, an important pathogenic species involved in food poisoning, and Bacillus licheniformis, Bacillus subtilis and Bacillus pumilus, which are causative agents of food spoilage described as responsible for foodborne disease outbreaks. With this purpose in mind, 52 Bacillus strains isolated from culture collections and fresh and processed food were considered. SNP type "Y" at sites 212 and 476 appeared in the majority of B. licheniformis studied strains. SNP type "R" at site 278 was detected in many strains of the B. subtilis/Bacillus amyloliquefaciens group, while polymorphism "Y" at site 173 was characteristic of the majority of strains of B. cereus/Bacillus thuringiensis group. The analysis of SNPs provided more intra-specific information than phylogenetic analysis in the cases of B. cereus and B. subtilis. Moreover, this study describes novel SNPs that should be considered when designing 16S rRNA-based primers and probes for multiplex-PCR, Real-Time PCR and microarray systems for foodborne Bacillus spp.

Genetic discrimination of foodborne pathogenic and spoilage Bacillus spp. based on three housekeeping genes.

Bacillus genus includes foodborne pathogenic and spoilage-associated species, such as Bacillus cereus, Bacillus licheniformis, Bacillus subtilis and Bacillus pumilus. Bacillus is also a heterogeneous genus that includes closely related species that are difficult to discriminate among, especially when well-conserved genes such as 16S rRNA and 23S rRNA are considered. The main goal of the present work was to study the usefulness of three housekeeping genes, the TU elongation factor (tuf), the DNA gyrase ß subunit (gyrB) and the RNA polymerase ß subunit (rpoB) genes, for use in differentiating among the most important foodborne Bacillus spp. sequences from 20 foodborne isolated Bacillus strains, and sequences belonging to different Bacillus spp. retrieved from the GenBank were analysed. In general terms, gyrB, rpoB and tuf gene regions for the strains considered in this study exhibited interspecific similarities of 57.8%, 67.23% and 77.66% respectively. Novel tufGPF and tufGPR universal primers targeted to the tuf gene were designed and proved to be useful for the amplification of all Bacillus spp considered. In conclusion, the tuf gene can be considered to be a good target for the differential characterisation of foodborne Bacillus species, especially for differentiating B. subtilis and B. cereus from other closely related species.

Detection of food spoilage and pathogenic bacteria based on ligation detection reaction coupled to flow-through hybridization on membranes.

Traditional culturing methods are still commonly applied for bacterial identification in the food control sector, despite being time and labor intensive. Microarray technologies represent an interesting alternative. However, they require higher costs and technical expertise, making them still inappropriate for microbial routine analysis. The present study describes the development of an efficient method for bacterial identification based on flow-through reverse dot-blot (FT-RDB) hybridization on membranes, coupled to the high specific ligation detection reaction (LDR). First, the methodology was optimized by testing different types of ligase enzymes, labeling, and membranes. Furthermore, specific oligonucleotide probes were designed based on the 16S rRNA gene, using the bioinformatic tool Oligonucleotide Retrieving for Molecular Applications (ORMA). Four probes were selected and synthesized, being specific for Aeromonas spp., Pseudomonas spp., Shewanella spp., and Morganella morganii, respectively. For the validation of the probes, 16 reference strains from type culture collections were tested by LDR and FT-RDB hybridization using universal arrays spotted onto membranes. In conclusion, the described methodology could be applied for the rapid, accurate, and cost-effective identification of bacterial species, exhibiting special relevance in food safety and quality.

Characterisation and profiling of Bacillus subtilis, Bacillus cereus and Bacillus licheniformis by MALDI-TOF mass fingerprinting.

The Bacillus genus includes species such as Bacillus cereus, Bacillus licheniformis and Bacillus subtilis, some of which may be pathogenic or causative agents in the spoilage of food products. The main goal of this work was to apply matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) mass fingerprinting to the classification of these Bacillus species. Genetic analyses were also compared to phyloproteomic analyses. A collection of 57 Bacillus strains isolated from fresh and processed food and from culture collections were studied and their mass spectra compiled. The resulting mass fingerprints were compared and characteristic peaks at the strain and species levels were assigned. The results showed that MALDI-TOF was a good complementary approach to 16S rRNA sequencing and even a more powerful tool in the accurate classification of Bacillus species, especially for differentiating B. subtilis and B. cereus from Bacillus amyloliquefaciens and Bacillus thuringiensis, respectively. MALDI-TOF was also found to provide valuable information at both intra- and interspecies levels in the Bacillus species studied.

Isolation and characterization of Streptococcus parauberis from vacuum-packaging refrigerated seafood products.

Streptococcus parauberis is known as an etiological agent of mastitis in cows and for producing streptococcosis in farmed fish, although its presence in foods has seldom been reported. In this work, two bacterial isolates were recovered from a spoiled vacuum-packaged refrigerated seafood product. Both isolates were identified by 16S rRNA gene sequencing, exhibiting 99% homology with respect to S. parauberis. Both isolates were also characterized by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Genetic analysis revealed the clonal homogeneity of the isolates and their grouping together with other S. parauberis strains in a different cluster with respect to Streptococcus uberis strains. Proteomic analysis by MALDI-TOF MS allowed for the identification of five mass peaks in the range of 2200-6000 m/z that resulted to be specific to the species S. parauberis and allowed its rapid and direct identification with respect to other pathogenic and spoilage bacteria potentially present in seafood and other food products. This study represents, to our knowledge, the first report of S. parauberis in seafood in general and in vacuum-packed food products in particular. Moreover, it provides a rapid method based on MALDI-TOF MS for the identification of S. parauberis.

Characterisation of histamine-producing bacteria from farmed blackspot seabream (Pagellus bogaraveo) and turbot (Psetta maxima).

Turbot (Psetta maxima) and blackspot seabream (Pagellus bogaraveo) represent two of the most important emerging farmed fish species in European countries. However, no information of the presence and development of histamine-producing bacteria on them has been reported so far. Accordingly, the aim of this study was to isolate and identify the main histamine-producing bacteria in farmed turbot and blackspot seabream. For this study, 24 isolates (12 from turbot and 12 from blackspot seabream) were preliminarily selected on Niven medium. Two of these isolates were confirmed as prolific histamine producers by HPLC. Thus, Pseudomonas fragi (isolated from turbot) and Pseudomonas syringae (isolated from blackspot seabream) were able to produce 272±69ppm and 173±45ppm of histamine in vitro, respectively, after incubation at 30°C/24h. While turbot fillets proved to be quite resistant to histamine formation at temperatures below 10°C, blackspot seabream fillets inoculated with P. syringae and the prolific histamine former Morganella morganii accumulated 696±84 and 760±59ppm histamine, respectively, under such conditions. Genetic identification based on 16S rRNA sequencing was performed in parallel with the investigation of characteristic mass spectral profiles of the isolates by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). The MALDI-TOF MS analyses provided species-specific fingerprints, which allow rapid identification and classification of the isolates. Six genus-specific mass peaks in the range of 2218-4434 m/z were shared by both strains. Bacterial identification was achieved by the identification of six species-specific mass peaks in the ranges of 2534-7183 m/z and 2536-9113 m/z for P. fragi and P. syringae, respectively.

[Application of a seven-day buprenorphine transdermal patch in multimorbid patients on long-term ibuprofen or diclofenac]. / 7-Tage-Buprenorphinpflaster bei multimorbiden Patienten mit Ibuprofen- bzw. Diclofenac-Dauertherapie. Ergebnisse einer nicht interventionellen Studie.

The objective of this study was to evaluate the benefit of a seven-day buprenorphine transdermal patch for patients with chronic musculoskeletal pain previously receiving long-term treatment with ibuprofen or diclofenac alone. Data of a subgroup of 703 patients were analysed which were part of a multicenter observational study with 3,295 patients. These patients had previously received ibuprofen or diclofenac and were characterized by older age,the presence of gastrointestinal, cardiovascular, and renal risk factors and the existence of chronic musculoskeletal pain. The switch to the seven-day buprenorphine patch resulted in a clinically significant decrease of the mean pain intensity at rest during the day from 5.3 to 2.9, on physical effort during the day from 7.1 to 3.3, and at night from 4.9 to 1.9 at the end of the study (11-point NRS scale, p

Detection and quantification of spoilage and pathogenic Bacillus cereus, Bacillus subtilis and Bacillus licheniformis by real-time PCR.

A new primer-probe set for the detection and quantification of Bacillus cereus, Bacillus licheniformis and Bacillus subtilis by real-time PCR (Rti-PCR) was developed. For it, forty-eight strains belonging to these species were considered. The DNA of these strains was isolated and a fragment of the 16S rRNA gene amplified. The amplicons were sequenced and the obtained sequences were aligned with reference sequences from the GenBank. For the development of the Real-Time PCR (RTi-PCR) methodology based on TaqMan probes, a primer pair and probe, specific for the studied Bacillus spp., were designed. To establish the quantification method, two RTi-PCR standard curves were constructed; one with DNA extracted from a serially-diluted B. cereus culture and a second curve with DNA extracted from a sterilised food product inoculated with serial dilutions of B. cereus. The curves exhibited R(2) values of 0.9969 and 0.9958 respectively. Linear correlations between the log(10) input DNA concentration and the threshold cycle (Ct) values were observed with a magnitude of linearity in the range of 1.65 × 10(1) CFU/mL to 1.65 × 10(6) CFU/mL for both standard curves. The specificity of the designed primers and probe was tested with DNA extracted from B. cereus, B. licheniformis and B. subtilis strains, which gave Ct values between 14 and 15, whereas non-specific amplifications of the DNA from other microbial species of food interest exhibited a Ct value above 28.5. To our knowledge, this method represents the first study about the quantification of spoilage and/or pathogenic B. cereus, B. licheniformis and B. subtilis in food products, with the aim to prevent the presence of these undesirable species in the food chain.

Molecular and probiotic characterization of bacteriocin-producing Enterococcus faecium strains isolated from nonfermented animal foods.

AIMS: The characterization of four novel bacteriocin-producing enterococcal strains, isolated from nonfermented animal foods, was carried out with a view to evaluate their potential application as probiotics in raw and processed foodstuffs. METHODS AND RESULTS: 16S rRNA sequencing and random amplification of polymorphic DNA-polymerase chain reaction (RAPD-PCR) analysis allowed the identification and intra-specific grouping of Enterococcus faecium strains, which inhibited the growth of four relevant food-borne pathogenic and spoilage species. Enterococcus faecium strains exhibited remarkable probiotic profiles, being able to survive to pH 3.0 and to the presence of bile salts, pancreatin and pepsin. Enterococcus faecium strains evaluated did not exhibit bile salt hydrolase or haemolytic activity, but showed good adhesion properties, also exhibiting sensitivity to clinically relevant antimicrobial agents. CONCLUSIONS: In our study, DNA sequencing of the 16S rRNA gene and RAPD-PCR analysis were equally discriminatory for typing E. faecium strains. This study also confirmed the potential tolerance and survival of E. faecium strains isolated from nonfermented animal foods to the gastrointestinal tract. SIGNIFICANCE AND IMPACT OF THE STUDY: This study represents the first report on potential probiotic E. faecium strains isolated from nonfermented meat and fish. Their moderate heat resistance opens the way to their potential use as probiotics in minimally processed foods subjected to moderate heat processing.

Buprenorphine in a transdermal therapeutic system--a new option.

Advanced patch technology has yielded a novel transdermal therapeutic system (TDS) for the rate-controlled systemic delivery of buprenorphine. Buprenorphine TDS is available in three strengths with release rates of 35, 52.5 and 70 microg/h over 72 h, corresponding to daily doses of 0.8, 1.2 and 1.6 mg, respectively. In total, 445 patients with chronic pain of malignant or non-malignant origin requiring long-term treatment with potent opioid analgesics were enrolled in the clinical trial programme. The patients were treated with buprenorphine TDS in one of three dosage strengths or with placebo TDS in a randomised double-blind setting. Greater pain relief was documented in patients treated with buprenorphine TDS than in those treated with placebo. The benefit of buprenorphine TDS was further reflected in the larger number of patients who slept for longer than 6 h per night. Patients switching from Step 2 or Step 3 opioids to buprenorphine TDS encountered no problems with the conversion. Typical opioid-related adverse events were reported with a low incidence and mild intensity. In an open follow-up study 239 patients elected to continue treatment with buprenorphine TDS. The confirmation of clinical benefit, coupled with a high level of patient compliance and improved quality of life, substantiate the usefulness of buprenorphine TDS in a practical setting.

Practicability and acceptance of subcutaneous self-administration of the selective serotonin agonist sumatriptan.

To cater to the special situation of much reduced oral bioavailability which occurs in severe migraine attacks with pronounced nausea and vomiting, sumatriptan can also be used in a subcutaneous form that can be self-administered. The aim of this study was to analyze the practicability and acceptance of a method of self-administration ("Glaxo-Pen") for treatment of severe migraine attacks by subcutaneous injection of sumatriptan. The Glaxo-Pen was compared with the conventional autoinjector for subcutaneous administration of sumatriptan. The multicenter study was conducted under practical conditions by 150 office-based physicians in Germany. Patients who commonly suffered from severe migraine attacks were given a careful explanation of how to use the device ("Glaxo-Pen") for self-administration of subcutaneous sumatriptan and were able to practice using it under guidance. They were given a Glaxo-Pen with two sumatriptan refills to take with them for treating their own migraine attacks. The patients used a headache diary to document administration outside the practice session. A total of 376 patients were included in the study. The major findings were that 80% of the patients rated the Glaxo-Pen "very easy" or "easy" to use, and only 6.4% rated it "difficult" or "very difficult." Compared with the conventional autoinjector, the Glaxo-Pen was rated "much better" or "better" by 77.9% of patients. Only 8.5% considered the Glaxo-Pen "worse" or "much worse" than the conventional autoinjector. The figures show that the great majority of patients found it easy to use sumatriptan for treating severe migraine attacks by self-administration under practical conditions. Thus, especially for patients who suffer from severe nausea, vomiting, or diarrhea during migraine attacks, this method of delivery is an easily used means of arresting migraine attacks.

[Paraspinal opioids and pump systems]. / Rückenmarksnahe Opioide und Pumpensysteme.

The regional application of opioids close to the spinal cord by using pumps induces a pain reduction comparable to the systemic medication of the WHO analgesic ladder. However, this method does not reduce the side effects of these drugs, e.g. nausea, vomiting, dysfunctional bladder emptying, and obstipation. Problems and complications leading to revision surgery and system explantation, respectively, are of more severe importance. Pump explantation occurs in a frequency of 7.3% and revision surgery in a frequency of 6.2%. Catheters and port systems have to be revised in 15% of all cases. Therefore, the indication for this method has to be considered carefully and includes the following criteria: pain of somatic origin, exclusion of mental diseases and psychogenic causes of pain, causal therapy is exhausted, insufficient effects of peripheral analgesics and co-analgesics, oral or transdermal opioids are insufficient despite dosages resulting in side-effects, pain is sensible to opioids, regional application of opioids has been tested effective before implantation.

[Quality assurance in roentgen diagnosis. 1996 results and problems from the viewpoint of the Medical Section in accordance with ordinance 16 of the roentgen regulation of the Saxony Regional Medical Group]. / Qualitätssicherung in der Röntgendiagnostik. Ergebnisse und Probleme 1996 aus der Sicht der Arztlichen Stelle gemäss section 16 Röntgenverordnung der Sächsischen Landesärztekammer.

The "Arztliche Stelle gemäss RöV" was established in Saxony in 1992. Structure and results of quality assurance in radiological diagnostics are described briefly. Quality checks delivered acceptable results for the majority of X-ray devices. Typical errors are shown and explained by using some X-ray pictures.

Renal transplantation from donors aged < 6 years into children yields equal graft survival when compared to older donors.

Several articles have shown inferior renal allograft survival in patients receiving kidneys from young cadaver donors. We therefore assessed the survival and function of the first cadaveric graft from donors aged under 6 years of age, transplanted after 1983. The results were compared with the outcome of children receiving kidneys from older donors. Graft survival and serum creatinine were analyzed retrospectively at various time intervals after first cadaveric transplantation in 35 pediatric recipients of renal transplants grafted between 1983 and 1996 from donors < 6 years of age. Their data were compared with those of 167 pediatric recipients of renal transplants grafted from older donors. The proportion of young donors remained constant throughout the observation period. Mean recipient age was 10.4 years (range 3.2-17.5 years) in the patients grafted from donors < 6 years of age, not much different from the mean age of the donors in the 6+ years group (12.5 years, range 2.3-18.6 years). Five-year patient survival did not differ between the two groups (89 vs. 90%). In 1983-1996, graft survival rate of kidneys from donors aged < 6 years after one year was 77% (donors aged 6+ years=76%), after 2 years 66% (donors aged 6+ years=68%), after 3 years 62% (donors aged 6+ years=66%), and after 5 years 55% (donors aged 6+ years=60%, n.s., Log-rank test). In 1994-1996, 2-year graft survival was 88% (controls 91%, n.s.). In children receiving a cadaveric graft from a donor aged < 6 years, mean serum creatinine fell from 132+/-101 (SD) micromol/l after 3 months to 101+/-66 micromol/l after 12 months, and was 110+/-52 micromol/l after 5 years. This compared with a serum creatinine of 131+/-108 micromol/l after 3 months, 132+/-97 micromol/l after 12 months and 143+/-81 micromol/l after 5 years in children receiving grafts from older donors. When transplanting renal allografts from young donors into children, there was no significant difference in graft survival between donors aged < 6 years and older donors or in graft function. We conclude that good results from young donors can be obtained in a specialized center, and therefore the restriction of kidney selection to donors aged > 6 years may not be justified.

Primary structure of the long and short splice variants of mouse collagen XII and their tissue-specific expression during embryonic development.

Type XII collagen, a member of the FACIT group of extracellular matrix proteins, consists of molecules that are trimers of alpha 1(XII) chains. The three chains in each molecule form a cross-shaped structure with a central globule from which a triple-helical tail and three finger-like regions (containing von Willebrand factor A-like regions (containing von Willebrand factor A-like domains and fibronectin type III repeats) extend. cDNA cloning/sequencing of chicken alpha 1(XII) collagen and protein studies with mouse, bovine, and human material suggest that the alpha 1(XII) collagen gene gives rise to two molecular variants, differing in the length of the finger-like regions, by alternative splicing of the primary transcript. To provide a basis for studies of the function of the two variants in an organism that can be genetically manipulated, we have isolated and sequenced mouse cDNAs encoding both splice variants. The sequence provides the first complete nucleotide and amino acid sequence of mammalian type XII collagen. From these cDNAs we have generated digoxigenin-labeled RNA probes for in situ hybridization of developing mouse embryos to find out whether the splicing mechanism responsible for generation of the two forms is developmentally regulated. The results, combined with Northern blot and RT-PCR analysis of RNA from embryos at various developmental stages, demonstrate that the long form of collagen XII, XIIA, is the predominant form at early stages (ED7 and 11); at later stages of development (ED15 and 17) the short form, XIIB, becomes the major form. As the short form becomes the major product, the long splice variant continues to be expressed in several tissues, even after birth. An exception is dermis, which is positive for the long form up to embryonic day 15, but negative at day 18, when only the short form RNA can be detected.

Terminal differentiation of chondrocytes in culture is a spontaneous process and is arrested by transforming growth factor-beta 2 and basic fibroblast growth factor in synergy.

At Day 17 of in ovo development, chondrocyte hypertrophy including synthesis of collagen X takes place in a limited region within the cranial part of chick embryo sternum. Here we analyze in suspension culture the differences in response to single growth factors of chondrocytes derived from the cranial part versus cells derived from the caudal part. Cells from either part were cultured separately without serum in the presence of insulin-like growth factor-1, transforming growth factor beta 2, basic fibroblast growth factor, or thyroid hormones. In culture, chondrocytes derived from the cranial part of sterna from 14- to 18-day-old chicken embryos become hypertrophic and initiated the synthesis of collagen X and alkaline phosphatase. These processes were enhanced by anabolic diffusible signals, such as those contained in fetal bovine serum, insulin-like growth factor-1, or thyroxine. Cells derived from the caudal part lack this capacity and, instead, prevented hypertrophy of cranial cells in cocultures, presumably by secreting diffusible signals. As candidate molecules, we have identified transforming growth factor beta 2 and basic fibroblast growth factor, which both were released by chondrocytes. Synergistic action of transforming growth factor beta 2 and basic fibroblast growth factor was required to suppress insulin-like growth factor-1-stimulated maturation of cranial chondrocytes in culture.

[The premedication of PTA. A double-blind and randomized comparison of midazolam/tramadol versus placebo/tramadol]. / Prämedikation der PTA. Doppelblinder und randomisierter Vergleich von Midazolam/Tramadol versus Placebo/Tramadol.

A prospective, randomised and double blind comparative study of Midazolam/Tramadol or placebo/Tramadol for premedication before PTA was carried out on 40 patients (12 female and 28 male, average age 66.1 +/- 12). The anxiolytic, analgesic and general findings were quantified by means of a visual analogue score. Pre- and peri-interventional blood gas, blood pressure and pulse rates were determined. The complications of the two schemes were compared. 19 patients received Midazolam/Tramadol and 21 placebo/Tramadol. Patient anxiety was reduced significantly from 25.8 +/- 25 to 4.3 +/- 6 by premedication. Significant increase in the pain score during PTA was observed only in the placebo group (4.3 +/- 12.6 to 27.4 +/- 20.9). There was no difference in the incidence of complications and respiratory depression due to the Midazolam/Tramadol combination was not observed.