[Structured or protocol-based dispatching programs]. / Strukturierte bzw. standardisierte Notrufabfrage: Leisten die Systeme tatsächlich, was sie vorgeben zu leisten?

BACKGROUND: The increasing introduction of standardized emergency call systems in German-speaking countries follows the recommendations of the European Resuscitation Council (ERC) and German Resuscitation Council (GRC), according to which the emergency call shall be queried using specified protocols. Although there may be a need for improvement in terms of sensitivity and specificity with regard to the detection of special clinical pictures, standardized products are preferred for emergency call inquiries, which can enable constant call processing regardless of user, time and situation during the day. This increases both patient safety and the legal security of the control center staff and the company management. OBJECTIVES: Do such systems deliver what they are expected to perform? METHODS: Research of current literature. RESULTS: Emergency call interrogation systems are performing as expected. The compliance of the tele communicator has a significant impact on the quality of a call. CONCLUSION: There is a need for optimization of the establish standards for the use of the structured and protocol-based systems and in improving user training.

Potential detection of low-dose transdermal testosterone administration in blood, urine, and saliva.

Administration of low amounts of endogenous hormones - so-called micro-dosages - are supposed to represent a major challenge in doping analysis. To model such a situation, we have studied transdermal administrations of 2.4 mg/24 h testosterone patches and examined various steroid concentrations in blood, urine, and saliva of 11 volunteers. Multiple samples were collected at t = 0, 3, 6, 9, 24, 48, and 72 h in four different phases, i.e., all combinations with/without physical exercise and with/without testosterone. Testosterone was analyzed by enzyme-linked-immuno-assay as well as by mass spectrometry and validated in an accredited anti-doping laboratory. Circadian controls with and without exercise did not provoke prominent alterations of whole, free, and salivary testosterone. Testosterone application for 24 h led to a significant (all p < 0.001) mean increase above controls: total testosterone (median: 5.2 vs. 8.0 ng/mL), free testosterone (median: 11.3 vs. 15.6 pg/mL), and salivary testosterone (median: 62.4 vs. 99.9 pg/mL). Additionally, all three testosterone measurements indicated significant correlations to each other (all r > 0.538, all p < .001). Circadian-matching showed peaking testosterone values after 6 h and 9 h, reaching highest augmentation up to 252.6 ± 123.5% in saliva after 9 h. After removal of the testosterone patch, all testosterone levels in blood, saliva, and urine returned to baseline within 24 h. Different techniques of hormone detection (enzyme-linked immunosorbent assay (ELISA), gas chromatography-tandem mass spectrometry (GC-MS/MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS)) indicated significant correlations. Results indicate that saliva, blood, and urine exhibit comparable hormone augmentation during micro-dose testosterone application, indicating a possible consideration in future doping analysis. The inter-individual variability was high in all biofluids, requiring the use of an individual biological passport rather than statistical values. Copyright © 2016 John Wiley & Sons, Ltd.

Screening for Acromegaly in Patients with Carpal Tunnel Syndrome: A Prospective Study (ACROCARP).

Early diagnosis of acromegaly prevents irreversible comorbidities and facilitates surgical cure. Carpal tunnel syndrome (CTS) is common in acromegaly and patients have often undergone surgery for CTS prior to the diagnosis of acromegaly. We hypothesized that screening CTS-patients for acromegaly could facilitate active case-finding. We prospectively enrolled 196 patients [135 women, 56.9 (range 23-103) years] who presented with CTS for surgery. Patients were asked about 6 symptoms suggestive of acromegaly using a questionnaire calculating a symptom score (0-6 points), and insulin-like-growth factor 1 (IGF-1) was measured. If IGF-1 was increased, IGF-1 measurement was repeated, and random growth hormone (GH) and/or an oral glucose tolerance test (OGTT) with assessment of GH-suppression were performed. The mean symptom score was 1.7±1.3 points. Three patients reported the maximal symptom score of 6 points, but none of them had an increased IGF-1. There was no correlation between the symptom score and IGF-1-SDS (standard deviation score) (r=0.026; p=0.71). Four patients had an IGF-1>2 SDS. In 2 patients acromegaly was ruled out using random GH and OGTT. One patient had normal IGF-1 and random GH at follow-up. One patient refused further diagnostics. In this prospective cohort of patients with CTS, the observed frequency of acromegaly was at most 0.51% (95% CI 0.03 to 2.83%). In this prospective study, none of the 196 patients with CTS had proven acromegaly. Thus, we see no evidence to justify general screening of patients with CTS for acromegaly.

Comparison of oral glucose tolerance test (OGTT) 100 g with OGTT 75 g for evaluation of acromegalic patients and the impact of gender on test reproducibility.

CONTEXT: Growth hormone (GH) measurements during an oral glucose tolerance test (OGTT) are essential for the diagnosis and follow-up management of acromegaly. However, both 100 g glucose (OGTT(100) ) and 75 g glucose (OGTT(75) ) test variants are in clinical use. Whether the tests are interchangeable concerning GH nadir and test interpretation is unclear. Furthermore, information on test reproducibility and the impact of gender is scarce. OBJECTIVE: To compare both tests in acromegalic patients and to evaluate test reproducibility with respect to gender. DESIGN, SUBJECTS AND METHODS: OGTT(100) and OGTT(75) were performed on two consecutive days in 54 acromegalic patients (46·9 ± 1·8 years, 30 women). OGTT(75) was repeated on three different occasions in 11 healthy men and 13 healthy women at different phases of the menstrual cycle. RESULTS: GH nadirs were comparable between tests [2·40 ± 0·52 (OGTT(100) ) and 2·46 ± 0·54 µg/l (OGTT(75) ); P = 0·356]. There were no differences at any time point in the mean values of GH, serum glucose or insulin between the two test variants. Test interpretation was highly consistent between the OGTT(100) and OGTT(75) [area under the receiver operated curve (ROC) = 0·995]. In men, GH, insulin and glucose measurements during OGTT(75) were highly reproducible. In women, however, basal and GH nadirs were significantly higher midcycle (P < 0·05). CONCLUSIONS: In acromegalic patients, there is no difference in GH nadirs and test interpretation after the ingestion of 100 g or 75 g glucose. The OGTT(75) is highly reproducible in men, but in women, it should be performed preferably in the early follicular phase.

Successful jejunal nutrition therapy in a pregnant patient with apallic syndrome.

A 41-year-old woman was admitted in the 8th pregnancy week as a consequence of a left-sided media infarction. After alloprothetic aortic valve replacement, she had discontinued deliberately the mandatory anticoagulation treatment. Following an initial clinical stabilisation, a second insult with right-sided media total infarction occurred 3 weeks after admission. In the further course, she developed an apallic syndrome and required respirator therapy. The initial enteral nutrition therapy via naso-gastric tube, was continued via percutaneous endoscopic gastrostomy (PEG). Due to recurrent vomiting from the 24th pregnancy week, the PEG was changed into a PEG with jejunal position of the tube (JET-PEG). Via this access and simultaneous body impedance analysis (BIA) control, the further nutrition therapy could be continued uneventfully. In the 27th pregnancy week, the patient gave birth to a female newborn (birth weight: 820 g) by Caesarean section in pre-eclampsia. The foetal development was in accordance with the gestational period and uncomplicated in the further course. The mother could be released into ambulatory care where the above nutrition therapy was continued. Reports on a successful nutrition therapy of pregnant comatose patients are rare. To the best of our knowledge, this is the first case where JET-PEG and monitoring by repeated BIA measurement were used for the control of the enteral nutrition.

N-ras mutation in a canine lymphoma: short communication.

Lymphomas of dogs were investigated by molecular genetic methods. Regions of exon 1 and 2 of the N-ras gene, which harbours the mutation hot spots (codons 12, 13 and 61) were screened. A GGT [symbol: see text] GAT (glycine [symbol: see text] aspartic acid) mutation in codon 13 was present in a multicentric-type lymphoma of a 1-year-old male dog.

Secretion of free and protein-bound leptin from subcutaneous adipose tissue of lean and obese women.

Leptin circulates as a free (FL) and a protein-bound (BL) form, with the soluble leptin receptor (LR) as an important binding compound. Here we measured these components of leptin in serum and in the incubation medium of sc adipose tissue in healthy lean (n = 10) and obese (n = 13) female subjects using recently developed specific RIA systems. In addition, immunostaining for FL, BL, and LR in adipose tissue was performed. Serum FL levels were increased in the obese subjects (P < 0.0001), whereas BL and LR concentrations in serum of lean and obese subjects were similar. Both FL and BL were secreted from human preadipocytes and increased in parallel to the differentiation of the cells. In sc fat cell explants LR antibodies predominantly stained the fat cell membrane, whereas FL and BL antibodies revealed intracytoplasmatic adipocyte staining. The release of FL, BL, and LR from adipose tissue was increased in obese compared with lean subjects (P < 0.005 for FL; P < 0.02 for BL, and P < 0.01 for LR). In summary, fat cells are capable of releasing not only FL, but also BL and LR.

Tumour suppressor gene p53 mutation in a case of haemangiosarcoma of a dog.

Haemangiosarcomas of dogs were analysed by molecular genetic techniques. Regions of the tumour suppressor gene p53, including the well-known tumour hot spots (codons 175, 245, 248, 249, 273 and 282) were screened. A 24 bp deletion was detected in exon 5 of the gene.

Canine tumour suppressor gene p53 mutation in a case of anaplastic carcinoma of the intestine.

Tumours localised in the large bowel of dogs were subjected to molecular genetic studies. Highly conserved regions of the tumour suppressor gene p53, including typical tumour hot spots (codons 175, 245, 248, 249, 273 and 282), were analysed. A mutation CGG-->TGG (arginine-->tryptophan) was present in codon 249 in an anaplastic carcinoma in the caecum.

Distinct effects of cAMP and mitogenic signals on CREB-binding protein recruitment impart specificity to target gene activation via CREB.

Ser-133 phosphorylation of the cAMP-responsive element-binding protein (CREB) is sufficient to induce cellular gene expression in response to cAMP, but additional promoter-bound factors are required for target gene activation by CREB in response to mitogen/stress signals. To compare the relative effects of different signals on recruitment of the coactivator CREB-binding protein (CBP) to CREB in living cells, we developed a fluorescence resonance energy transfer (FRET) assay. cAMP promoted the interaction of CREB with CBP in a phosphorylation-dependent manner by FRET analysis, but mitogen/stress signals were far less effective in stimulating complex formation even though they induced comparable levels of Ser-133 phosphorylation. cAMP and non-cAMP stimuli were comparably active in promoting this interaction in the cytosol; the formation of CREB x CBP complexes in response to non-cAMP signals was specifically inhibited in the nucleus. Non-cAMP signals had no effect on intrinsic CREB- or CBP-binding activities by Far Western blot assay, thereby supporting the presence of a distinct CREB x CBP antagonist. Our studies indicate that the relative effects of cAMP and mitogen/stress signals on CREB x CBP complex formation impart selectivity to gene activation through CREB phosphorylated at Ser-133.

Metathesis-based monoliths: influence of polymerization conditions on the separation of biomolecules.

Monolithic materials were prepared by transition metal-catalyzed ring-opening metathesis copolymerization of norborn-2-ene and 1,4,4a,5,8,8a-hexahydro-1,4,5,8-exo,endo-dimethanonaphthalene within the confines of surface-derivatized borosilicate columns in the presence of the porogenic solvents toluene and 2-propanol using Cl2(PCy3)2Ru(=CHPh) (1) as initiator. Relevant physicochemical data of the porous structure (specific surface area (sigma), pore volume (Vp), volume fraction of pores (epsilon(p)), and intermicroglobule volume (epsilon(z))) of the monolithic columns were determined by inverse size exclusion chromatography in tetrahydrofuran. Mean particle diameters were determined via electron microscopy. The influence of variations in polymerization conditions in terms of stoichiometry of the monomers and porogenic solvents on the chromatographic separation of the oligodeoxynucleotides dT12-dT18 and eight model proteins (ribonuclease A, insulin, cytochrome c, lysocyme, alpha-lactalbumin, alpha-chymotrypsinogen, beta-lactoglobulin B, catalase) were studied. Also, the role of additional phosphine on the entire polymerization setup and the associated chromatographic separations was elucidated. Relevant chromatographic data as well as differences between the separation of oligodeoxynucleotides and proteins may directly be attributed to the above-mentioned physicochemical properties of the metathesis-based monoliths. Finally, DSC-TGA-MS investigations on various monoliths of different composition and age were carried out in order to provide information on stability and oxidation behavior.

Lack of sequence variation in sporadic bovine leucosis in regions of tumour suppressor genes p53 and p16.

Regions of the promoter and exons 5-8 of the tumour suppressor gene p53 were analysed in 25 cases of sporadic bovine leucosis. The study included 17 cases of juvenile leucosis, five cases of adult leucosis and three cases of skin leucosis. Exon 2 of tumour suppressor gene p16 was also investigated in the same samples. No sequence variations were present in the analysed areas of the genes. In p53, this fact represents a clear difference in comparison with enzootic bovine leucosis. In p16, no comparative data are available.

Transcriptional regulation by the phosphorylation-dependent factor CREB.

The transcription factor CREB -- for 'cyclic AMP response element-binding protein' -- functions in glucose homeostasis, growth-factor-dependent cell survival, and has been implicated in learning and memory. CREB is phosphorylated in response to various signals, but how is specificity achieved in these signalling pathways?

Familial isolated parathyroid adenoma in a consanguineous family.

The 23-year-old Caucasian male propositus presented with symptomatic hypercalcemia, hypophosphatemia and normocalciuria for 2 months. His 29-year-old brother had undergone an operation for recurrent parathyroid adenoma at age 26 and 28. No other member of the family was affected. His father and mother were second-degree relatives. Laboratory studies showed primary hyperparathyroidism (pHPT), while the remaining endocrine studies and genetic testing for multiple endocrine neoplasia 1 and 2A were normal. Technetium-cardiolite scintigraphy and ultrasound scans revealed a parathyroid mass at the left lower neck. Apart from bilateral hearing loss due to gentamicin treatment as a pre-term child, the patient was in of good health. Signs or symptoms of other endocrinopathies were absent. The patient was referred for parathyroidectomy with subsequent autotransplantation of the remaining glands into his sternocleidomastoid muscle. Histological examination revealed an adenoma with oncocytic differentiation, similar to that seen in his brother. The disease may follow a recessive mode of inheritance or may be due to a dominant germ-cell mutation in one of the parents. The presented case may ultimately help in elucidating the molecular genetic basis of this rare form of pHPT.

Comparative analysis of ras proto-oncogene mutations in selected mammalian tumors.

Point mutations within ras proto-oncogenes are frequently detected in human malignancies and in different types of experimentally induced tumors in animals. In contrast to findings in experimental animal models of carcinogenesis, little is known about the incidence of ras mutations in naturally occurring animal tumors. In the present study, we investigated whether point mutations, particularly within the mutational hot-spot codons 12, 13, and 61, occur at comparable frequencies in human malignancies and spontaneously occurring tumors in other mammalian species. Two hundred seventy-nine of the most frequent canine and feline neoplasms were analyzed for changes in mutational hot-spot regions of the N-, Ki-, and Ha-ras genes. DNA fragments from exons 1 and 2 of all three ras genes were amplified by polymerase chain reaction, and the presence of point mutations was assessed by single-strand conformation polymorphism analysis and direct sequencing of amplified products. Only one sample, a case of canine melanoma, exhibited an Ha-ras mutation. Thus, our data strongly suggested that ras mutations at the hot-spot loci are apparently very rare and do not play a major role in the pathogenesis of the spontaneously occurring canine and feline tumors investigated. These observations were in marked contrast to those in experimental rodent models of carcinogen-induced mammary and skin tumors that described a consistent association with Ha- or Ki-ras activation. The role of ras oncogene activation in related human malignancies therefore cannot be readily inferred from studies of experimental carcinogenesis in animal models.

Chiral beta-cyclodextrin-based polymer supports prepared via ring-opening metathesis graft-polymerization.

A series of norborn-2-ene-derivatized beta-cyclodextrins (beta-CDs), 6-O-(norborn-2-ene-5-carboxyl)-beta-CD (1), tetrakis(6-O-norborn-2-ene-5-carboxyl)-beta-CD (2), (3), 6-O-(6-norborn-2-ene-5-car-6-O-(7-oxanorborn-2-ene-5-carboxyl)-beta-CD bonylaminohexoyl)-beta-CD (4), 6-O-(norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (5), tris(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (6), tetrakis(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (7) and hexakis(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (8), have been synthesized. Compounds 1-3 were prepared via reaction of beta-CD with norborn-2-ene-5-carboxylic chloride and 7-oxanorborn-2-ene-5-carboxylic chloride, respectively; compounds 5-8 were synthesized from norborn-2-ene-5-yl-methyldichlorosilane and beta-CD, respectively. Compound 4 was accessible by reaction of norbom-2-ene-5-carboxylaminohexoyl chloride with beta-CD. Compounds 1-8 were surface grafted onto norborn-2-ene-derivatized silica-based supports using ring-opening metathesis polymerization employing the ruthenium-based initiator bis(tricyclohexylphosphino)benzylideneruthenium dichloride [Cl2Ru(CHC6H5)(PCy3)2, Cy=cyclohexyl, 9]. Generally speaking, the resulting chiral stationary phases (CSPs) I-VIII may be prepared with high reproducibility and may be used within a pH of 2-10. Thus, relative standard deviations (sigman-1) of the mean resolution (Rs) are <7%. The CSPs were used for the enantioselective separation of beta-blockers, N-dansyl-, N-3,5-dinitrobenzoyl- and Fmoc-protected amino acids and were characterized in terms of chemical stability, selectivity (alpha') and resolution (Rs). Additionally, the role of the spacer as well as influences of capacity and the degree of substitution of the beta-CD moiety on the separation characteristics were determined.

Influences of surface chemistry on the separation behavior of stationary phases for reversed-phase and ion-exchange chromatography: a comparison of coated and grafted supports prepared by ring-opening metathesis polymerization.

A series of poly(norborn-2-ene) (poly-NBE), poly(7-oxanorborne-2-ene-5,6-dicarboxylic acid) (poly-ONDCA), as well as poly(norborn-2-ene-co-7-oxanorborne-2-ene-5,6-dicarboxylic acid) (poly-NBE-co-ONDCA) based silica supports were prepared via ring-opening metathesis polymerization (ROMP) using both coating and grafting techniques. Poly-NBE-grafted and poly-NBE-coated supports were used for the reversed-phase separation of phenols; poly-NBE, poly-ONDCA as well as poly-NBE-co-ONDCA-grafted supports were used for comparative studies on the separation of a series of anilines and lutidines. As expected, grafted supports possess superior separation capabilities compared to their coated analogues. Compared to pure poly-NBE- and poly-ONDCA-grafted stationary phases, supports consisting of poly-NBE-co-ONDCA block-copolymers possess both hydrophobic and ion-exchange sites and represent optimum stationary phases for the separation of isomeric basic analytes.