[Virtual palliative care : Pilot study of an electronic tool to test cognitive, psychomotor and affective palliative medical and pain therapeutic learning contents during medical training]. / Virtuelle Palliativversorgung : Pilotierung eines elektronischen Tools zur Prüfung kognitiver, psychomotorischer und affektiver palliativmedizinischer und schmerztherapeutischer Lerninhalte während der ärztlichen Ausbildung.

BACKGROUND: This article describes a first use of an electronic case-based assessment tool in undergraduate palliative care education. It describes the development of the tool presenting strengths and shortcomings in order to contribute to an innovative design of assessment tools in medical education. DESIGN AND METHOD: An electronic (virtual) case-based assessment tool (the virtual palliative patient, vPp) was developed. Palliative care levels of knowledge, skills and attitude of students were tested at a computer workplace as a voluntary and non-performance-relevant pilot project at four faculties. RESULTS: On average the students achieved 80% of the points using the vPp tool, which is below the average score of 91% achieved in the regular examination. In particular, the free text task on reflection of dealing with the patient's death wish caused uncertainty, while multiple choice questions and an interactive conversation sequence were perceived as relatively easy. Technical problems were also identified in the evaluation but overall the concept was evaluated positively and establishment as a regular examination or e­learning tool was desired. CONCLUSION: The implementation of an innovative assessment tool in medical education is technically challenging. A coordination with contents of the individual faculties is necessary in order that students do not have a feeling of a lack of preparation. The development of the vPp describes an innovative assessment format. In the long term, all interested faculties could receive a form of toolbox containing the technical framework of the assessment tool, which can then be fed with new contents.

Influence of the NH2-terminal amino acid of the T cell receptor alpha chain on major histocompatibility complex (MHC) class II + peptide recognition.

The alpha/beta T cell receptor (TCR) recognizes peptide fragments bound in the groove of major histocompatibility complex (MHC) molecules. We modified the TCR alpha chain from a mouse T cell hybridoma and tested its ability to reconstitute TCR expression and function in an alpha chain-deficient variant of the hybridoma. The modified alpha chain differed from wild type only in its leader peptide and mature NH2-terminal amino acid. Reconstituted cell surface TCR complexes reacted normally with anti-TCR and anti-CD3 antibodies. Although cross-linking of this TCR with an antibody to the TCR idiotype elicited vigorous T cell hybridoma activation, stimulation with its natural MHC + peptide ligand did not. We demonstrated that this phenotype could be reproduced simply by substituting the glutamic acid (E) at the mature NH2 terminus of the wild type TCR alpha chain with aspartic acid (D). The substitution also dramatically reduced the affinity of soluble alpha/beta-TCR heterodimers for soluble MHC + peptide molecules in a cell-free system, suggesting that it did not exert its effect simply by disrupting TCR interactions with accessory molecules on the hybridoma. These results demonstrate for the first time that amino acids which are not in the canonical TCR complementarity determining regions can be critical in determining how the TCR engages MHC + peptide.

Analysis of the effects of oestrogen receptor alpha (ERalpha)- and ERbeta-selective ligands given in combination to ovariectomized rats.

BACKGROUND AND PURPOSE: Studies with oestrogen receptoralpha (ERalpha)- and ERbeta-selective compounds have already shown that the effects of 17beta-estradiol (E2) on body weight, movement drive and bone-protection are mediated via ERalpha. This study was based on the hypothesis that activation of ERbeta may antagonize ERalpha-mediated effects and designed to investigate potential effects of ERalpha/ERbeta heterodimers. EXPERIMENTAL APPROACH: Ovariectomized (OVX) female Wistar rats were treated with combinations of the ERalpha-specific agonist 16alpha-LE2 (ALPHA; 1 and 10 microg kg(-1) d(-1)), the ERbeta-specific agonist 8beta-VE2 (BETA; 100 microg kg(-1) d(-1)), the phytoestrogen, genistein (10 mg kg(-1) d(-1)) and with the anti-oestrogen compound, ICI 182,780 (3 mg kg(-1) d(-1)) for three weeks. The combined effects of the substances on body weight increase, tibial bone mineral density (BMD) and the influence on running wheel activity (RWA) were investigated. KEY RESULTS: OVX-induced body weight increase was reduced by co-administration of genistein and BETA. Co-application of BETA or genistein with ALPHA had no effect on ALPHA-mediated bone-protection. The RWA of OVX animals was significantly reduced by treatment with genistein but stimulated by application of ALPHA. The stimulatory effect of ALPHA on RWA could be antagonized by co-treatment with the pure antioestrogen ICI 182,780 but also by co-administration of genistein or BETA. CONCLUSIONS AND IMPLICATIONS: Our results indicate that activation of ERbeta may modulate ERalpha-mediated physiological effects in vivo. The observation that substances with selective affinity for ERbeta are able to antagonize distinct physiological functions, like RWA, may be of great relevance to the pharmaceutical use of such drugs.

Industrial carbohydrate biotransformations.

Nearly all major industrial processes which involve carbohydrates, include biotechnological transformations. This is due to the complex nature of carbohydrates where stereo- and regioselectivity are highly complex and difficult to control. Enzymes and microorganisms work highly selectively and efficiently in water solution, and provide high yield in general. The article focuses on different types of reactions, including large-scale processes. Topics are hydrolytic reactions, including starch processing, oxidation and reduction transformations including organic acids, such as gluconic and ketogluconic acids and vitamin C synthesis, and isomerization and transfer reactions, which are established on a very large scale to produce glucose/fructose syrups and sucrose isomers. The article will further discuss some mechanistic aspects which are relevant for technology and present selected details of industrial-scale processing. Finally an outlook outlines perspectives of future processes.

Dental pH Opti-Wand (DpOW): measuring oral acidity to guide enamel preservation.

Undetected caries can lead to painful cavities and surgical restorations. Lack of proper detection tools makes caries prevention dependent on dentist's expertise and presents obstacles in oral health monitoring. To overcome this problem, we have developed a new approach to predict early stages of enamel demineralization caused by oral bacteria. These bacteria metabolize sugars in our food and produce organic acids that lead to cavities. Measuring the acidity level can help predict early stages of tooth decay. pH paper or pH electrodes can be used to monitor acidity, but neither are able to track pH levels in all dental locations. Our device, DpOW, is a noncontact optics-based pH device that uses changes in the spectral fluorescence of FDA allowed fluorescein dye to measure acidity levels in difficult to access dental locations such as occlusal fissures. A prototype has been tested over a wide pH range (7.12 to 3.89) and shown to track the change in pH with 0.94 correlation coefficient.

The bone-protective effect of the phytoestrogen genistein is mediated via ER alpha-dependent mechanisms and strongly enhanced by physical activity.

Reduced estrogen levels occurring during menopause in women are accompanied by a variety of disorders, e.g. hot flushes, depressions, osteoporosis, increase in body weight and reduced movement drive. The phytoestrogen genistein (GEN) has been demonstrated to have a significant bone-protective potency. In order to study the ER subtype-specific effects of this phytoestrogen on bone in an animal model, ovariectomized (OVX) female Wistar rats were either treated with 17beta-estradiol (E(2)) (4 microg/kg/day), the ER alpha-specific agonist (ALPHA) 16 alpha-LE(2) (10 microg/kg/day), the ER beta-specific agonist (BETA) 8 beta-VE(2) (100 microg/kg/day) or GEN (10 mg/kg/day) for 3 weeks. Vehicle-treated OVX animals served as controls. All animals had the opportunity of voluntary wheel running. Movement activity, changes of body weight and trabecular bone mineral density (BMD) in the tibia were analyzed. E(2) and ALPHA treatment, but not treatment with BETA, significantly increased the movement activity of OVX rats. Treatment with GEN resulted in a significant decrease of movement activity as compared to OVX animals. Bone mineral density in the trabecular area of the tibia and the expression of bone morphogenetic protein-2 (BMP-2) were significantly reduced in OVX- and BETA-treated rats as compared to rats substituted with E(2), ALPHA and GEN. The bone-protective effect of ALPHA was antagonized by co-treatment with the pure antiestrogen Faslodex (ICI). In order to distinguish hormone-dependent effects from those of exercise, we performed an additional experiment where the animals had no opportunity of wheel running. The results demonstrate that physically inactive rats have a stronger decrease of bone mineral density than physically active animals. Very surprisingly, our data demonstrate that GEN has no bone-protective activity in the absence of physical activity. In contrast, ALPHA and E(2) are bone-protective in the presence and absence of physical activity. In conclusion, our data provide evidence that the effects of E(2) on body weight, movement drive and protection of bone mineral density are mediated via ER alpha, whereas activation of ER beta has only a limited effect. Our data also indicate that the bone-protective effects of GEN may be mediated via ER alpha-dependent mechanisms and that physical activity has a strong impact on the bone-protective potency of this phytoestrogen.

Incorporation studies of clickable ceramides in Jurkat cell plasma membranes.

The incorporation properties of ceramide analogues for click chemistry in Jurkat T cells were investigated. The analogues varied in the acyl chain length and the position of the functional group for click chemistry. Fluorescence microscopy studies including anisotropy and quenching experiments showed significant differences in the accessibility of the functional group indicating different incorporation properties into the plasma membrane.

Synthesis of the rare disaccharide nigerose by structure-based design of a phosphorylase mutant with altered regioselectivity.

In the absence of the natural acceptor inorganic phosphate wild-type sucrose phosphorylase from Bifidobacterium adolescentis (BaSP) produces maltose (4-O-α-d-glucopyranosyl-d-glucose) and kojibiose (2-O-α-d-glucopyranosyl-d-glucose) as sole transfer products. A Q345F exchange switches the enzyme's regioselectivity from 2 to 3 exclusively, yielding the rare sugar nigerose (3-O-α-d-glucopyranosyl-d-glucose, sakebiose).

Incorporation and visualization of azido-functionalized N-oleoyl serinol in Jurkat cells, mouse brain astrocytes, 3T3 fibroblasts and human brain microvascular endothelial cells.

The synthesis and biological evaluation of azido-N-oleoyl serinol is reported. It mimicks biofunctional lipid ceramides and has shown to be capable of click reactions for cell membrane imaging in Jurkat and human brain microvascular endothelial cells.

Tissue-specific modulation of cyclooxygenase-2 (Cox-2) expression in the uterus and the v. cava by estrogens and phytoestrogens.

Cyclooxygenase 2 (Cox-2), an enzyme involved in prostaglandin production, is a key player in the development of pathologic changes, such as colorectal cancer, arteriosclerosis and thrombosis. In this study, we investigated the effects of estrogens, selective estrogen receptor modulators (SERMs), pure antiestrogens and phytoestrogens on the tissue-specific expression of Cox-2 in the uterus and the v. cava of ovariectomized female rats. Cox-2 expression could be detected in the uterine epithelium and in the endothelium of the v. cava. Cox-2 expression was time-dependently stimulated after administration of 17beta estradiol (E2) in the uterus. In the v. cava, E2 treatment resulted in a stimulated expression of the progesterone receptor (PR), a gene known to be regulated by E2, whereas Cox-2 was simultaneously down-regulated. Administration of the pure antiestrogen faslodex (Fas) had no effect on Cox-2 expression. In contrast, administration of tamoxifen (Tam) resulted in a decrease of Cox-2 expression in the v. cava but does not stimulate Cox-2 expression in the uterus. Interestingly, the same expression pattern of Cox-2 could be detected after dose-dependent administration of genistein (Gen). Here, down-regulation of Cox-2 could already be detected after administration of merely 0.5 mg/(kgBW) Gen, a dose where no effects on uterine weight were observed. In summary, our results demonstrate a reverse tissue-specific regulation of Cox-2 expression by estrogens in the v. cava and uterus indicating the existence of complex molecular mechanisms which have to be characterized in future studies. Remarkably, Tam and the phytoestrogen Gen, both share the ability to decrease the expression of Cox-2 in the v. cava without effecting its uterine expression. These observations may be of great importance with respect to potential beneficial or adverse effects of estrogens, SERMs and phytoestrogens on the cardiovascular tissue.

Investigations of the transfructosylation reaction by fructosyltransferase from B. subtilis NCIMB 11871 for the synthesis of the sucrose analogue galactosyl-fructoside.

The exo-fructosyltransferase produced from B. subtilis NCIMB 11871 strain transfers the fructose moiety from donor alpha12 linked saccharides such as sucrose, raffinose and stachyose to the acceptor d-galactose, leading to the sucrose analogue, galactosyl-fructoside. Here, we report detailed kinetic studies. The enzyme showed a remarkably high optimal temperature at 50 degrees C and was effectively immobilised on Eupergit C 250 L and Trisopor-Amino. This is also the first report about the equilibrium of the transfructosylation reaction, its activation energy determination, the structure of the product and its preparative scale isolation.

Comparison of haematology, coagulation and clinical chemistry parameters in blood samples from the sublingual vein and vena cava in Sprague-Dawley rats.

The investigation of clinical pathology parameters (haematology, clinical chemistry and coagulation) is an important part of the preclinical evaluation of drug safety. However, the blood sampling method employed should avoid or minimize stress and injury in laboratory animals. In the present study, we compared the clinical pathology results from blood samples collected terminally from the vena cava (VC) immediately before necropsy with samples taken from the sublingual vein (VS) also prior to necropsy in order to determine whether the sampling method has an influence on clinical pathology parameters. Forty-six 12-week-old male Sprague-Dawley rats were assigned to two groups (VC or VS; n = 23 each). All rats were anaesthetized with isoflurane prior to sampling. In the VC group, blood was withdrawn from the inferior VC. For VS sampling, the tongue was gently pulled out and the VS was punctured. The haematology, coagulation and clinical chemistry parameters were compared. Equivalence was established for 13 parameters, such as mean corpuscular volume, white blood cells and calcium. No equivalence was found for the remaining 26 parameters, although they were considered to be similar when compared with the historical data and normal ranges. The most conspicuous finding was that activated prothrombin time was 30.3% less in blood taken from the VC (16.6 ± 0.89 s) than that in the VS samples (23.8 ± 1.58 s). Summing up, blood sampling from the inferior VC prior to necropsy appears to be a suitable and reliable method for terminal blood sampling that reduces stress and injury to laboratory rats in preclinical drug safety studies.

Tuberculosis presenting as a perirectal mass: report of a case.

The epidemic of acquired immunodeficiency syndrome has caused a worldwide resurgence of tuberculosis. A case of acute tuberculosis with anorectal involvement presenting at an urban American hospital is discussed. Although anorectal involvement by tuberculosis is not uncommon, the diagnosis is usually initially missed.

Psychiatric manifestations of the post-thyroidectomy bilateral abductor vocal cord paralysis syndrome. Cases and theoretical issues.

Post-thyroidectomy bilateral abductor vocal cord paralysis (BAVCP) is a life-threatening syndrome characterized by serious psychiatric manifestations as well as by voice, airway, hypothyroid, and hypoparathyroid symptoms. Of the 128 patients with post-thyroidectomy BAVCP syndrome, 45 (35.2 per cent) had psychiatric complications: 21 of the 128 patients (16.4 per cent) had pre-existing psychiatric symptoms exacerbated by the post-thyroidectomy BAVCP syndrome, 16 (12.5 per cent) had psychiatric symptoms initiated by the syndrome, six (4.7 per cent) had psychiatric symptoms etiologically distinct from the syndrome, and two (1.6 per cent) were misdiagnosed. The role of psychiatric treatment is described. Theoretical aspects of laryngeal dysfunctions associated with psychiatric disorders and psychotropic medications are discussed.

Vocal cord paralysis and psychopathology. Data and clinical issues.

The nature and cause of psychiatric symptoms associated with the posthyroidectomy bilateral abductor vocal cord paralysis (BAVCP) syndrome are analyzed. The postthyroidectomy BAVCP syndrome is characterized by normal voice, airway obstruction, hypothyroidism, hypoparathyroidism, and psychiatric manifestations. Forty-five (35.2%) of 128 patients with postthyroidectomy BAVCP syndrome had psychiatric manifestations of some kind. The following four categories of psychiatric problems were found: (1) preexisting psychiatric symptoms exacerbated by the postthyroidectomy BAVCP syndrome, (2) psychiatric symptoms initiated by the syndrome, (3) psychiatric symptoms that were etiologically distinct from the syndrome, and (4) misdiagnosis. The variety of psychiatric symptoms, as well as the difficulty in determining the cause of the symptoms, makes it essential that surgeons, internists, and psychiatrists cooperate in the treatment of patients with the postthyroidectomy.

Caffeine-derived N-nitroso compounds. V. Carcinogenicity of mononitrosocaffeidine and dinitrosocaffeidine in bd-ix rats.

Mononitrosocaffeidine (MNC) and dinitrosocaffeidine (DNC) are new N-nitroso compounds obtained from in vitro nitrosation of caffeidine, a hydrolysis product of caffeine present in a typically made and widely consumed tea from Kashmir (India), a high incidence area of esophageal and stomach cancer. The chemical synthesis, in vitro metabolic studies and mutagenicity of the compounds has been previously reported. DNC, a nitrosamide is highly mutagenic both with and without metabolic activation whereas MNC, like several other aromatic asymmetric nitrosamines, does not exhibit genotoxic or mutagenic properties. We now report the results of the first carcinogenicity experiments on chronic oral administration of these compounds in BD-IX rats. The acute LD50 of MNC and DNC were about 1300 and 230 mg/kg b.w., respectively. Lung oedema and gastrointestinal haemorrhages were the first symptoms of intoxication observed after 2 days for both the compounds. All three dose groups of MNC treated rats showed localization of tumours in nasal cavity (93.9-100% of all malignant tumours). The tumours were histologically diagnosed as neuroepitheliomas of the olfactory epithelium (neuroblastoma of the bulbus olfactorii) and squamous cell carcinoma of the nasal cavity in the ratio of 3:1. No tumours of the nasal cavity were observed in the untreated controls. DNC, in contrast, induced squamous cell carcinoma of forestomach in 100% animals at low and high doses, of which nearly half the tumours metastasized predominantly into the peritoneum. No forestomach tumours were seen in the untreated controls. The data presented here clearly show the potential for induction of malignant tumours and distinct organ-specificity by MNC and DNC in rats, and support the postulate that a chronic exposure to these compounds may provide a carcinogenic risk for high incidence of gastrointestinal cancers in Kashmir.

Endocarditis caused by Actinobacillus actinomycetemcomitans.

Actinobacillus actinomycetemcomitans, a small, gram-negative bacillus with fastidious growth requirements, is a rare cause of endocarditis. The clinical course of this disease is characterized by long duration of symptoms before diagnosis (average of three months), prolonged incubation before growth (average of six days), and a high embolic rate. The optimal antimicrobial regimen cannot be determined from available data, but the combination of ampicillin and an aminoglycoside may offer the best chance for cure. Two cases are presented, one successfully treated. Previously reported cases are reviewed.