[Posttraumatic stress disorder : Risk factors, phenomenology, early recognition and management]. / Posttraumatische Belastungsstörung : Risikofaktoren, Phänomenologie, Früherkennung und Management.

Posttraumatic stress disorder is characterized by the symptom levels intrusion, avoidance and hyperarousal as a reaction to an exceptionally threatening event. It is a well-investigated and well-treatable mental condition; however, the frequently accompanying disturbances in sleep, cognition, affect and especially avoidance behavior represent substantial hurdles in the trauma surgery treatment as well in occupational reintegration. Basic knowledge about risk factors and the clinical phenomenology also enable early identification by the primary trauma surgeon or the accident insurance consultant (D-physician) and if necessary to initiate a qualified psychotraumatologically founded treatment.

[Psychological care in the intensive care unit : Task areas, responsibilities, requirements, and infrastructure]. / Psychologische Versorgung auf der Intensivstation : Tätigkeitsbereiche, Aufgaben, Anforderungen und Ausstattung.

The relatively high rates of mental stress among critically ill patients and their relatives implies the necessity of conceptually and financially embedded psychological care in intensive care units (ICUs). Professional associations also recommend the involvement of psychological professionals and screening of mental symptoms in critically ill patients. Intensive care medicine psychologists and psychotherapists take this as an opportunity to describe the content and goals of psychological care. Task areas are care for patients and relatives as well as staff support. Goals of psychological support in the ICU are detection of mental symptoms in patients and their treatment, psychological first aid for relatives in crisis situations, and support of the staff in terms of communication with patients and relatives as well as regarding development and maintenance of an adaptive coping style for dealing with emotionally challenging situations. Psychological care in the ICU is offered by psychologists, psychotherapists, or physicians with a psychotherapeutic qualification. The psychologist is integrated into the ICU team and has a proactive, resource-oriented, and supportive orientation. Psychological support can be an enrichment and a relief, both in the interdisciplinary treatment of patients as well as in the care of relatives, and also represent a resource for the team.

GSK-3-specific inhibitor-supplemented hESC medium prevents the epithelial-mesenchymal transition process and the up-regulation of matrix metalloproteinases in hESCs cultured in feeder-free conditions.

Feeder-free culture induces spontaneous differentiation of human embryonic stem cells (hESCs), identified as an epithelial to mesenchymal transition (EMT). The maintenance of pluripotency of hESCs in feeder-free cultures through the activation of the WNT pathway using a glycogen synthase kinase (GSK)-3-specific inhibitor (BIO) was reported. The aim of this study was to determine the effect of BIO on the EMT process. In contrast with those grown in feeder-free conditions with control medium, hESC colonies cultured with BIO-supplemented hESC medium did not show any fibroblast-like cells at the periphery. Transmission electron microscopy, relative quantitative real-time RT-PCR and immunostaining analyses showed the presence of epithelial features and a diminution of mesenchymal features in the BIO-treated hESCs such as a strong E-cadherin expression, the down-regulation of Vimentin, Snail and Slug expressions and a cytoplasmic beta-catenin expression. An up-regulation of matrix metalloproteinases (MMP) MMP-2, MMP-9, MT-1MMP (membrane-type 1 MMP) and EMMPRIN (extracellular MMP inducer) expression was also found associated with the EMT occurring in feeder-free hESCs cultures using mouse embryonic fibroblasts conditioned medium (MEF CM). The presence of BIO clearly down-regulated the expression of these MMPs. This study showed that BIO, a GSK-3-specific inhibitor, prevents the EMT process which is associated with the feeder-free hESC culture. Nevertheless, BIO was not sufficient to expand hESCs in a long-term culture system.

A new Coenzyme Q10 tablet-grade formulation (all-Q) is bioequivalent to Q-Gel and both have better bioavailability properties than Q-SorB.

Commercial Coenzyme Q10 (CoQ10, ubiquinone) formulations are often of poor intestinal absorption. We investigated the bioavailability of DSM Nutritional Products Ltd. (Kaiseraugst, Switzerland) CoQ10 10% TG/P (all-Q), a new tablet-grade formulation, with CoQ10 Q-Gel Softsules based on the Bio-Solv technology (Tishcon Corp., Salisbury, MD; marketed by Epic4Health, Smithtown, NY) and Q-SorB (Nature's Bounty, Bohemia, NY). Twelve healthy male subjects participated in a randomized, three-period crossover bioequivalence study. Plasma CoQ10 was determined from pre-dose until +36 hours. To compare bioavailability, corrected maximum concentration (Cmax) and area under the curve from 0 to +14 hours [AUC(0-14 h)] were assessed and tested for bioequivalence. The bioequivalence ranges of 0.8-1.25 hour x microg/mL for AUC(0-14 h) and 0.75-1.33 microg/mL for Cmax were applied. In summary, the kinetic profiles of all CoQ10 preparations revealed a one-peak plasma concentration-time course. Highest Cmax values were seen after Q-Gel application, whereas time to Cmax was nearly identical across all treatments. The AUC(0-14 h) values were highest for Q-Gel, narrowly followed by all-Q. The tests for bioequivalence showed a bioequivalence between Q-Gel and all-Q, and both preparations were found to have better bioavailability properties than Q-SorB. Although all-Q and Q-Gel have equivalent bioavailability properties, all-Q can be directly used in tablets, while this is not the case for Q-Gel or other similar forms.

Influence of cefmenoxime, ceftriaxone, latamoxef, and ceftazidime on the lysis of Klebsiella pneumoniae: a light and electron microscopic study.

The influence of antibiotics on the morphologic alterations of the cell wall of Klebsiella pneumoniae serotype K 17 has been studied by electron microscopy as well as by phase-contrast microscopy. Ceftazidime, cefmenoxime, ceftriaxone, and latamoxef were the antibiotics used. The effect of each concentration between 0.03 and 1,024 mg/liter was investigated on 5 X 10(7) bacteria per milliliter. Two different reactions could be detected: ceftazidime and latamoxef produced at first long forms and suddenly lysis; cefmenoxime and ceftriaxone produced at first long forms, later spherical forms, and then gradually lysis.

Humoral immune response to Klebsiella capsular polysaccharides in HLA-B27-positive patients with acute anterior uveitis and ankylosing spondylitis.

Klebsiella is suggested to trigger ankylosing spondylitis (AS) and acute anterior uveitis (AAU) in HLA-B27-positive individuals. Previous investigations showed an increased antibody response to the Klebsiella capsular types K26, K36, and K50 in sera from HLA-B27-positive AS patients. In the present study the prevalence and titers of antibodies against Klebsiella capsular antigens were measured by means of an ELISA in 32 sera from HLA-B27-positive AAU patients either with (n = 10) or without AS (n = 22) and compared with sera from HLA-B27-negative AS-patients (n = 13). Sera from either HLA-B27-positive (n = 45) or negative (n = 40) healthy individuals served as control. Sera from HLA-B27-positive AAU with or without AS showed significantly higher antibody prevalence and IgG-titers against capsular antigens of the Klebsiella serotypes K26, K36, and K50 when compared with sera from HLA-B27-negative AS patients or with healthy controls. These results might be taken to indicate the predominance of these serotypes in the HLA-B27-associated AS and AAU.

Rapid detection by reverse hybridization of mutations in the UL97 gene of human cytomegalovirus conferring resistance to ganciclovir.

UNLABELLED: BACKGROUND OF STUDY: Diseases due to human cytomegalovirus (HCMV) infection constitute a major threat in marrow and solid organ transplant recipients. Ganciclovir (GCV) is widely used in prophylaxis and pre-emptive therapy of active HCMV infection. Resistance to ganciclovir (GCV) may arise at variable frequency under GCV therapy and is conferred by mutations (i) in the UL97 gene (codons 460, 520, and 591-607) encoding a phosphotransferase which is essential for monophosphorylation of GCV and, to a lesser extent, (ii) in the UL54 gene coding for the DNA polymerase of HCMV. OBJECTIVE: The purpose was to develop a rapid assay to screen for emerging GCV resistance mutations in the UL97 gene of HCMV whereby avoiding virus isolation and nucleotide sequencing procedures. STUDY DESIGN: A nested PCR (nPCR) amplifying UL97 codons 450-672 was developed. Nested amplicons were subsequently sequenced directly. Oligonucleotides for use in a reverse hybridization assay were designed to detect relevant non-synonymous mutations at codons UL97 460, 520, 603 and 607. Strain AD169 served as a wild-type control. RESULTS: UL97-specific nPCR amplicons were obtained from 18 EDTA blood samples of ten transplant recipients receiving GCV for more than 30 days. In three consecutive samples from a single patient a GCV resistance mutation at codon 603 (C-->W) was detected. In addition, two out of four cell culture-adapted HCMV isolates known to exhibit GCV resistance in vitro revealed mutations at codons 460 (M-->V) and 607 (C-->Y), respectively. By reverse hybridization a discrimination of single nucleotide changes at codons 460, 520, 603 and 607 was possible whereby matching exactly the results of the nucleotide sequence analysis for all 23 amplicons examined. CONCLUSIONS: Reverse hybridization appeared to be a rapid and convenient alternative to nucleotide sequencing when screening the UL97 gene of HCMV for selected markers of GCV resistance.

Klebsiella capsular type K7 in relation to toxicity, susceptibility to phagocytosis and resistance to serum.

Klebsiella strains possessing capsule type K7 are found predominantly in respiratory secretions. To investigate the importance of this K antigen in virulence, 13 K7 strains were compared with K2 capsulate isolates which are generally regarded as highly virulent. The toxicity of the strains was determined in a mouse peritonitis model. Generally, K7 isolates were significantly less toxic for mice than K2 strains. In the absence of serum, neither capsule type showed much stimulation of leucocytes, measured as the chemiluminescence (CL) response of human polymorphonuclear leucocytes (PMNL). However, in the presence of normal human serum, CL values with K7 strains increased considerably, whereas the CL response to K2 isolates was unaffected. Correspondingly, intracellular killing by PMNL was observed with K7 strains only, whereas K2 isolates proved to be relatively resistant to phagocytic destruction. No correlation was found between capsule type K7 and serum resistance. These data suggest that, in contrast to K2, capsule type K7 may not be a critical factor in the virulence of K7-capsulate Klebsiella strains nor does it seem to act as an antiphagocytic barrier.

Characterisation of Hafnia alvei isolates from human clinical extra-intestinal specimens: haemagglutinins, serum resistance and siderophore synthesis.

Extra-intestinal Hafnia alvei isolates are rarely considered to be pathogenic. To investigate whether such strains are able to produce virulence factors, a total of 70 clinical H. alvei isolates was compared with clinical extra-intestinal isolates of other members of the enterobacterial tribe Klebsiellae (Kiebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens). Whereas mannose-sensitive haemagglutination (MSHA) was less common in H. alvei (59%) than in K. pneumoniae (86%) and E. cloacae (89%) isolates, the incidences of mannose-resistant haemagglutination indicative of type 3 pili (MR/K-HA) and of serum resistance properties were not lower. All H. alvei strains secreted siderophores but, unlike the other enterobacterial species examined, the siderophore type was neither enterobactin nor aerobactin. Although the low pathogenicity of H. alvei isolates could not be attributed to any of the factors investigated, the mean number of factors expressed by each H. alvei isolate was significantly lower than that expressed by K. pneumoniae and E. cloacae isolates but did not differ significantly from that of S. marcescens. Based on these findings, the low pathogenicity of H. alvei appears to be due to its low frequency of expression of virulence factors as compared with clinically significant species such as K. pneumoniae and E. cloacae.

Results of a clinical and pharmacokinetic study of ceftazidime in patients with postoperative pneumonia on assisted ventilation.

Thirty-three patients who developed nosocomial pneumonia postoperatively were treated with ceftazidime, 4-6 g daily, over an average period of 7 days. Twenty-nine patients were evaluated; 13 (45%) patients were cured, five showed improvement, two relapsed, and one could not be assessed. X-rays of the chest showed no infiltrates in 17 out of the 29 cases (59%) after treatment. On the first day of treatment, ceftazidime concentrations in bronchial secretions of nine patients were estimated. The mean values of serum concentrations were: 15 min after infusion, 98 micrograms ml-1; 60 min, 63; 120 min, 44; 360 min, 20; 480 min, 13 micrograms ml-1. The mean values of the corresponding bronchial secretions were 2.9, 5.8, 10.2, 7.11 and 5.2 micrograms ml-1.

Relative bioavailability of imipramine (Tofranil) coated tablets in healthy volunteers.

OBJECTIVES: Imipramine is a tricyclic antidepressant drug with a considerable hepatic first-pass metabolism resulting in highly variable pharmacokinetic characteristics and desipramine as active major metabolite. This study describes the bioavailability of 3 formulations of imipramine. METHODS: In a randomized, three-period crossover study, 18 healthy male Caucasian subjects received single oral doses of Tofranil 25, Tofranil mite (10 mg) and an aqueous solution containing 25 mg imipramine-HCl. Serum concentrations of imipramine-HCl and its main metabolite desipramine were measured. The pharmacokinetic characteristics, Cmax, AUC, t1/2 and tmax were determined and the relative bioavailability of the two coated tablet formulations was calculated with the aqueous solution as reference. Safety and tolerability were assessed using vital signs, ECG, clinical laboratory and adverse event recording. RESULTS: The relative bioavailabilities of Tofranil 25 and Tofranil mite were 97% and 81%, respectively. The study medication was well tolerated. CONCLUSIONS: A sufficiently high extent of absorption was found for the test formulations ensuring therapeutic efficacy.

Plasma-kinetic characteristics of purified and isolated green tea catechin epigallocatechin gallate (EGCG) after 10 days repeated dosing in healthy volunteers.

This randomized, double-blind, placebo-controlled study assessed the safety, tolerability, and plasma-kinetic behavior of 94% pure crystalline epigallocatechin gallate (EGCG) after ten days' repeated dosing in 36 healthy male volunteers. Each of the three treatment groups consisted of 12 subjects; nine of them received oral EGCG in one dose of 200, 400, or 800 mg daily, and three received a placebo. Blood samples for plasma-kinetic EGCG characterization were taken on day 1 and day 10. Kinetic parameters for rate and extent, elimination half-lives, and accumulation factor (R) were determined and compared between day 1 and day 10 for each dosage group. Orally administered EGCG is rapidly absorbed from the gut. Dose linearity was applied for single-dose application (day 1). After repeated dosing (day 10) dose linearity was applied between the 200 mg and 400 mg group. Dose escalation to 800 mg was more than dose-proportional in rate and extent, and statistically different from the 200 mg and 400 mg group. An increase in elimination half-life (t1/2.z) and in the accumulation factor (R) in the 800 mg dosage group indicates dose-dependent saturation of capacity-limited excretion routes or an increase of hepato-duodenal re-circulation. Ten days' repeated administration of oral doses of EGCG of up to 800 mg per day were found to be safe and very well tolerated.

A single ascending dose study of epigallocatechin gallate in healthy volunteers.

This randomized, double-blind, placebo-controlled study assessed the safety, tolerability and plasma kinetic behaviour of single oral doses of 94% pure crystalline bulk epigallocatechin gallate (EGCG) under fasting conditions in 60 healthy male volunteers. In each group of 10 subjects, eight received oral EGCG in single doses of 50 mg, 100 mg, 200 mg, 400 mg, 800 mg or 1600 mg, and two received placebo. Blood samples were taken at intervals until 26 h later. The area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)), the maximum plasma concentration (Cmax) of EGCG, the time taken to reach the maximum concentration (Tmax), and the terminal elimination half-life (t1/2z) of EGCG were determined. Safety and tolerability were assessed. In each dosage group, the kinetic profile revealed rapid absorption with a one-peak plasma concentration versus time course, followed by a multiphasic decrease consisting of a distribution phase and an elimination phase. The mean AUC(0-infinity) of total EGCG varied between 442 and 10,368 ng.h/ml. The according mean Cmax values ranged from 130 to 3392 ng/ml and were observed after 1.3-2.2 h. The mean t1/2z values were seen between 1.9 and 4.6 h. Single oral doses of EGCG up to 1600 mg were safe and very well tolerated.

[Effectiveness of tetrachlorodecaoxide (TCDO) in the treatment of complicated disorders of wound healing. A controlled study: TCDO versus PVP-iodine complex]. / Die Wirksamkeit von Tetrachlordecaoxid (TCDO) zur Behandlung komplizierter Wundheilungsstörungen. Eine kontrollierte Studie: TCDO versus PVP-Jod-Komplex.

In a controlled study on the treatment of wound-healing impairments 29 patients underwent local treatment with TCDO (Oxoferin) while Beta-isodona was used in 31 cases. Regarding the criterion of reducing the wound area, i.e. epithelization, a highly significant superiority of Oxoferin could be demonstrated in the treatment of complicated wounds. The evaluation of the state of granulation, that was documented by a semiquantitative procedure, indicated that Oxoferin tends to be slightly superior. However, the following observations have to be emphasized: Oxoferin induces a development of granulation tissue on exposed tendons, bones, and fasciae and the granular tissue is of much better quality than after treatment with Betaisodona. Concerning its effect on the degree of contamination, Oxoferin proved to be at least as efficacious as the established and effective antiseptic Betaisodona. Both substances are tolerated well and the application is simple, they do not differ here.

[Serotonin syndrome]. / Le syndrome sérotoninergique.

The serotonin syndrome is a hyperserotoninergic state resulting from an excess of intrasynaptic 5-hydroxytryptamine, induced by multiple psychotropic agents, but also non psychiatric drugs. It is a potentially dangerous and sometimes lethal condition. The clinical manifestations usually include cognitive, neuromuscular and autonomic features and are mediated by the action of serotonin on various subtypes of receptors. The main differential diagnosis is the neuroleptic malignant syndrome. Treatment is mainly supportive. No pharmacological agent has been definitely demonstrated really effective. However, reports of cases treated with the 5-HT2 blockers, including cyproheptadine or chlorpromazine have suggested that these agents could have some efficacy. Serotonin syndrome is a toxic condition which requires heightened clinical awareness among physicians in order to prevent, recognize, and treat the condition promptly.

Epithelial-mesenchymal transition process in human embryonic stem cells cultured in feeder-free conditions.

Feeder-free human embryonic stem cell (hESC) culture is associated with the presence of mesenchymal-like cells appearing at the periphery of the colonies. The aim of this study was to identify this early differentiation process. Long-term feeder-free hESC cultures using matrigel and conditioned medium from mouse and from human origin revealed that the appearance of mesenchymal-like cells was similar regardless of the conditioned medium used. Standard characterization confirmed the preservation of hESC properties, but the feeder-free cultures could not be maintained longer than 37 passages. The early differentiation process was characterized in the short term after switching hESCs cultured on feeders to feeder-free conditions. Transmission electron microscopy showed an epithelium-like structure inside the hESC colonies, whereas the peripheral cells revealed the acquisition of a rather mesenchymal-like phenotype. Immunochemistry analysis showed that cells at the periphery of the colonies had a negative E-cadherin expression and a positive Vimentin expression, suggesting an epithelial-mesenchymal transition (EMT). Nuclear staining of beta-catenin, positive N-cadherin and negative Connexin 43 expression were also found in the mesenchymal-like cell population. After RT-PCR analysis, Slug and Snail, both EMT-related transcription factors, were detected as up-regulated in the mesenchymal-like cell population. Taken together, our data suggest that culturing hESCs in feeder-free conditions enhances an early differentiation process identified as an EMT.

Derivation of human embryonic stem cell lines from embryos obtained after IVF and after PGD for monogenic disorders.

BACKGROUND: Human embryonic stem (hES) cells are pluripotent cells usually derived from the inner cell mass (ICM) of blastocysts. Because of their ability to differentiate into all three embryonic germ layers, hES cells represent an important material for studying developmental biology and cell replacement therapy. hES cell lines derived from blastocysts diagnosed as carrying a genetic disorder after PGD represent in vitro disease models. METHODS: ICMs isolated by immunosurgery from human blastocysts donated for research after IVF cycles and after PGD were plated in serum-free medium (except VUB01) on mouse feeder layers. RESULTS: Five hES cell lines were isolated, two from IVF embryos and three from PGD embryos. All lines behave similarly in culture and present a normal karyotype. The lines express all the markers considered characteristic of undifferentiated hES cells and were proven to be pluripotent both in vitro and in vivo (ongoing for VUB05_HD). CONCLUSIONS: We report here on the derivation of two hES cell lines presumed to be genetically normal (VUB01 and VUB02) and three hES cell lines carrying mutations for myotonic dystrophy type 1 (VUB03_DM1), cystic fibrosis (VUB04_CF) and Huntington disease (VUB05_HD).