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Biomedical subjects

R Krause

Publications and source records attributed to R Krause.

At least 55 records · Page 3Linked to original sources

Right lower prefronto-parietal cortical dysfunction in akinetic catatonia: a combined study of neuropsychology and regional cerebral blood flow.

BACKGROUND: Catatonia is a psychomotor syndrome that can be characterized by behavioural, affective and motor abnormalities. In order to reveal further underlying pathophysiological mechanisms of psychomotor disturbances in catatonia we investigated neuropsychological function and regional cerebral perfusion (r-CBF) in a combined study. METHODS: Ten catatonic patients were investigated with Tc-99mECD brain SPECT and compared with 10 psychiatric (similar age, sex, medication and underlying psychiatric diagnosis but without catatonic syndrome) and 20 healthy controls. Neuropsychological measures included tests for general intelligence, attention, executive functions and right parietal visual-spatial abilities. Correlational analyses were performed between neuropsychological measures, catatonic symptoms and r-CBF. RESULTS: Catatonic patients showed a significant decrease of r-CBF in right lower and middle prefrontal and parietal cortex compared with psychiatric and healthy controls as well as significantly poorer performance in visual-spatial abilities associated with right parietal function. Correlational analysis revealed significant correlations between visual-spatial abilities and right parietal r-CBF only in psychiatric and healthy controls but not in catatonic patients. In contrast, attentional measures correlated significantly with motor symptoms, visual-spatial abilities and right parietal r-CBF in catatonia only but not in psychiatric or in healthy controls. CONCLUSION: Findings are preliminary but suggest right lower prefronto-parietal cortical dysfunction in catatonia, which may be closely related to psychomotor disturbances.

Adult↗

Effect of preoperative prophylaxis with filgrastim in cancer neck dissection.

BACKGROUND: Cancer surgery is known to lead to a deterioration in host defence mechanisms and an increase in susceptibility to infection after operation. Filgrastim enhances important antimicrobial functions of neutrophils including chemotaxis, phagocytosis and oxidative killing mechanisms. METHODS: The effects of additional (all patients received perioperative 3 ' 25 mg kg-1 cefotiam and 1 ' 20 mg kg-1 metronidazole) preoperative prophylaxis with filgrastim (5 microg kg-1 12 h prior to surgery plus 5 microg kg-1 0 h prior to surgery) on neutrophil phagocytosis and reactive oxygen radical production and postoperative infections in 24 patients undergoing cancer neck dissection were studied. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labelled Escherichia coli and Staphylococcus aureus by flow cytometry. Reactive oxygen generation after phagocytosis was estimated by determining the amount of dihydrorhodamine 123 converted to rhodamine 123, intracellularly. RESULTS: In the filgrastim-treated patients a higher neutrophil phagocytic capacity was seen intraoperatively, and 1-5 days postoperative, but not prior to surgery. Reactive oxygen radical production was significantly higher in filgrastim-treated patients prior to surgery, intraoperative and postoperative (1-5 days). 2/12 (17%) patients had postoperative infections in the filgrastim group and 9/12 (75%) patients had infections in the placebo group (P < 0.001). In particular, wound infections were recorded more often in the placebo group (1/12 vs. 6/12; P = 0.004). CONCLUSION: We conclude that filgrastim enhances perioperative neutrophil function and could be useful in the prophylaxis of postoperative wound infections in patients undergoing cancer neck dissection.

Adult↗

[Not Available].

In this piece of work the primary affects, as rage, fear, sadness and lacking of joy (anhedonia) are defined and discussed as specific causes for the development and outbreak of depressive states. Then conflicting primary emotions and depressive mental states are depicted to be followed by a discussion about the significance of emotion and situation-centered coping. Cognitive attribution models covering the development of emotions on the one hand as well as the exacerbation of depression on the other, are discussed on this background in a critical fashion.

Attachmen↗

Evaluation of HbA1c determination methods in patients with hemoglobinopathies.

OBJECTIVE: To evaluate commercially available determination methods for HbA1c in patients with hemoglobin variants. RESEARCH DESIGN AND METHODS: HbA1c values were determined with various commercially available methods, including ion-exchange high-performance liquid chromatography (HPLC), boronate affinity assay, and immunoagglutination in patients with the hemoglobin mutations Hb Graz, Hb Sherwood Forest, Hb O Padova, Hb D, and Hb S. RESULTS: The effect of hemoglobinopathies on glycohemoglobin measurements was highly method dependent. The HPLC methods for HbA1c determination lacked the resolution necessary to differentiate hemoglobin variants. They demonstrated additional peaks in the chromatograms and HbA1c results either too low or too high compared with the nondiabetic reference range. With all immunoassays, Hb Graz demonstrated falsely low values. The other hemoglobinopathies in our study caused falsely low and/or high HbA1c results in immunoagglutination methods. The boronate affinity method showed values in an acceptable range for all hemoglobin variants. CONCLUSIONS: Because of the local occurrence of Hb variants and the ethnic origin of a given population, every individual laboratory must establish and validate its own assay method. In managing diabetic patients, knowledge of hemoglobinopathies influencing HbA1c determination methods is essential because hemoglobin variants could cause mismanagement of diabetes resulting from false HbA1c determinations.

Biomarkers↗

In vitro activity of newer broad spectrum beta-lactam antibiotics against enterobacteriaceae and non-fermenters: a report from Austrian intensive care units. Austrian Carbapenem Susceptibility Surveillance Group.

We compared the in vitro activity of broad spectrum beta-lactam antibiotics against 573 gram-negative isolates (enterobacteriaceae and non-fermenters) collected between November 1996 and May 1997 from 9 laboratories serving intensive care units throughout Austria. MIC's (Minimal Inhibitory Concentration) were obtained with the E-test for meropenem, imipenem, ceftazidime, cefepime, cefpirome and piperacillin/tazobactam. Pseudomonas aeruginosa was the most frequently isolated organism (22%), followed by E. coli (19%), Klebsiella spp. (16%), and Enterobacter spp. (14%). Acinetobacter spp., Proteus spp., Serratia spp., Stenotrophomonas maltophilia, Citrobacter spp., Morganella morganii, Burkholderia cepacia and Salmonella enteritidis were isolated less frequently. Overall meropenem, imipenem and ceftazidime were the most active compounds in vitro, inhibiting 90%, 89%, and 87% of the isolates, respectively. Pseudomonas aeruginosa was inhibited by piperacillin/tazobactam in 89%, by cefepime in 87% and by ceftazidime in 85%. Imipenem, meropenem and cefpirome were less active (79%, 75% and 69% respectively). All E. coli strains were inhibited by meropenem, 99% were inhibited by imipenem, cefepime and cefpirome. Ceftazidime was active against 95% and piperacillin/tazobactam against 92% of E. coli. All Klebsiella spp. were inhibited by meropenem, cefepime and cefpirome. Imipenem inhibited 99% and ceftazidime 98% of the Klebsiella isolates. Piperacillin/tazobactam was active against 95% of Klebsiella spp. In vitro carbapenems are still the most active of all antibiotics tested. The relatively high resistance of Pseudomonas spp. and Acinetobacter spp. to carbapenems reflects the wide use of carbapenems during the last years. However, most bacterial isolates are still sensitive to the tested broad spectrum beta-lactams.

Acinetobacter↗

Identification and characterization of G90, a novel mouse RNA that lacks an extensive open reading frame.

We describe the cloning and characterization of the murine G90 gene, identified by subtractive hybridization based on the differential presence of its transcript in large and small intestine. The full-length cDNA and genomic sequences were cloned and found to produce a 1.5kb transcript that is polyadenylated but has no open reading frame larger than 249bp. The G90 gene was mapped to the proximal region of mouse chromosome 6. Expression analysis by Northern blotting showed that G90 is transcribed at very high levels in the small intestine and at lower levels in large intestine, testis and kidney of the mouse. In situ hybridization analysis on sections of small and large intestine and testis showed that G90 transcripts are present only in post-mitotic cells.

Amino Acid Sequence↗

Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of in vivo benzodiazepine receptor binding.

OBJECTIVES: Catatonia is a psychomotor syndrome with concomittant akinesia and anxiety which both respond almost immediately to benzodiazepines such as lorazepam. The benzodiazepine receptor distribution was therefore investigated in akinetic catatonia with single photon emission tomography (SPECT) using iodine-123-iomazenil ((123) I Iomazenil). METHODS: Ten akinetic catatonic patients, 10 psychiatric controls (similar age, sex, medication, and underlying psychiatric diagnosis but without catatonic syndrome), and 20 healthy controls were investigated with SPECT 2 hours after injection of (123) I Iomazenil. To exclude potential effects of cerebral perfusion (r-CBF) r-CBF was additionally investigated with Tc-99mECD SPECT. RESULTS: Catatonic patients showed significantly lower iomazenil binding and altered right-left relations in the left sensorimotor cortex compared with psychiatric (p<0.001) and healthy (p<0.001) controls. In addition, there was significantly lower r-CBF in the right lower prefrontal and parietal cortex in catatonia whereas in the left sensorimotor cortex no differences in r-CBF between groups were found. Catatonic motor and affective symptoms showed significant correlations (p<0.05) with benzodiazepine binding in the left sensorimotor cortex as well as with right parietal r-CBF. CONCLUSIONS: Reduced iomazenil binding suggests decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia. In addition to reduced GABA-A receptor density in the left sensorimotor cortex the parietal cortex seems to be involved in pathophysiology of catatonic symptoms. It is concluded that, considering results from correlation analyses, both emotional and motor symptoms in catatonia seem to be closely related to left sensorimotor and right parietal alterations.

Adult↗

Decreased incidence of complications in parturients with the arrow (FlexTip Plus) epidural catheter.

PURPOSE: To compare the incidence of complications during placement of Arrow (FlexTip Plus) and Concord/Portex epidural catheters in parturients receiving continuous epidural analgesia. METHODS: Two hundred parturients requesting continuous epidural analgesia were prospectively and randomly assigned to receive either the Arrow (FlexTip Plus) or the Portex epidural catheter. The incidences of paresthesiae, inadvertent venous cannulation and inability to thread the catheter into the epidural space were recorded. RESULTS: A total of 222 attempts at epidural placement occurred in the parturients enrolled. The Arrow catheter displayed a lower incidence of paresthesiae (3/112 vs 39/110, P < 0.0001) and venous cannulation (0/112 vs 11/110, P = 0.0007) than did the Portex catheter. The Portex catheter demonstrated a tendency towards increased inability to be advanced into the epidural space (5/110 vs 0/112, P = 0.057) in comparison to the Arrow catheter. When a Portex catheter would not advance into the epidural space (n = 5), an Arrow catheter was threaded successfully in all five cases without the need to reposition the Tuohy needle. CONCLUSION: Compared with a less flexible catheter, the Arrow decreases the incidence of transient paresthesiae and inadvertent venous cannulation, while improving the ability to thread the catheter into the epidural space. Intravascular injection, transarachnoid migration, and the rare occurrence of epidural haematoma may be further reduced with the use of flexible, soft-tip catheters.

Adult↗

Analysis of Peg1/Mest imprinting in the mouse.

In the mouse, Peg1/Mest is widely expressed in mesoderm-derived tissues. In separate studies, it has been shown to be maternally imprinted, that is, only the paternally inherited allele is active in mice and in humans. Here, we provide evidence that Peg1/Mest is expressed at very low levels in all tissues of adult mice as assessed by RT-PCR. Moreover, by using species-specific polymorphisms in the Peg1/Mest sequence we can demonstrate that in adult mice the gene remains imprinted in all of these tissues.

Animals↗

H19 and Igf2 are expressed and differentially imprinted in neuroectoderm-derived cells in the mouse brain.

Igf2 and H19 are reciprocally imprinted genes that are closely linked and coexpressed in tissues of mesodermal and endodermal origin. Here we report that coexpression of these genes is also found in specific fetal tissues of neuroectodermal origin, that is in the ventral midline region of both the hindbrain and spinal cord. For cells of neuroectodermal origin, complete absence of Igf2 and H19 transcription was previously described. Analysis of allele-specific expression of both Igf2 and H19 in the ventral midline region of the hindbrain shows that H19 is expressed monoallelically, with the paternal allele being silent, whereas Igf2 is expressed biallelically. Furthermore, we observed a strong influence of the parental species background, in that the Mus musculus allele was always expressed at higher levels than the M. spretus allele. This was observed when the M. spretus allele was contributed by the mother or by the father. An analysis of Igf2 methylation by bisulphite genomic sequencing provided no clear answer as to whether Igf2 expression and methylation are linked in a tissue of neuroectodermal origin. Taken together, our results provide novel information on H19 and Igf2 expression and imprinting patterns in the fetal mouse brain. In addition, they indicate that some aspects of Igf2 regulation in cells of neuroectodermal origin do not follow the pattern that exists in mesoderm- and endoderm-derived tissues. Apart from the ventral midline region, H19 and Igf2 were found to be coexpressed in the ectodermally derived Rathke's pouch and in some circumventricular organs of the brain, such as the organum vasculosum of the lamina terminalis (OVLT) and the pineal gland.

Animals↗

Molecular cloning and characterization of murine Mpgc60, a gene predominantly expressed in the intestinal tract.

We have isolated from mouse intestine a full-length cDNA clone that encodes an 86-amino acid precursor protein containing a 26-amino acid signal sequence. As deduced from its sequence, the mature 60-aa protein named MPGC60 belongs to the Kazal type of secreted trypsin inhibitors. The MPGC60 peptide has 58% homology with the PEC-60 peptide isolated from pig intestine. In the gut of adult mice, an increasing rostrocaudal gradient in MPGC60 mRNA levels was observed by Northern analysis. In situ hybridization analysis demonstrated strong Mpgc60 expression in Paneth cells and in a subset of goblet cells in the differentiated gut. During postnatal differentiation of the gut, a strong increase in Mpgc60 expression was detected in both small and large intestine. However, in small intestine activation of the Mpgc60 gene occurred earlier than in the large intestine. Apart from the intestinal tract, MPGC60 mRNA was also detectable in the mesenchyme surrounding the uterine epithelium and in endothelia of some blood vessels. However, in contrast to the situation observed in pig, no Mpgc60 expression was detectable by Northern, in situ and reverse transcriptase polymerase chain reaction (RT-PCR) analysis in cells of the immune system, that is, in monocytes, macrophages, peripheral blood and in spleen. Northern blot analysis on mRNA isolated from porcine and murine intestine showed a single transcript in mouse, but several transcripts in pig. Southern blot and fluorescent in situ hybridisation (FISH) analysis demonstrated the presence of a single gene situated in band A of chromosome 4. This region is syntenic with human chromosome regions 6q, 8q and 9p. The gene responsible for human hereditary mixed polyposis syndrome has been localized to human 6q. This raises the possibility that Mpgc60 is a candidate gene for this human disorder.

Amino Acid Sequence↗

Population biology, evolution, and immunology of vaccination and vaccination programs.

The purpose of prophylactic vaccination is to reduce morbidity and mortality in a population. Many questions related to the design of vaccines and vaccination programs require a population standpoint for their sharp formulation and laboratory and field studies to understand their immunologic background. Practical suggestions of the workshop included increased studies of age-specific immunity, better immunoepidemiologic surveillance, better design of efficacy studies, and more systematic sampling of parasite strains to study the evolutionary pressure exerted by vaccines. Theoretical immunology has much to contribute. One of the realizations of the workshop was the value of a strong interdisciplinary approach in vaccine development, utilizing relevant contributions from immunology, population biology, mathematical modeling, epidemiology, molecular biology, and virology.

Animals↗

Triple versus dual therapy for eradicating Helicobacter pylori and preventing ulcer recurrence: a randomized, double-blind, multicenter study of lansoprazole, clarithromycin, and/or amoxicillin in different dosing regimens.

OBJECTIVE: The efficacy and safety of dual and triple therapies with a proton pump inhibitor and antibiotic(s) for therapy of Helicobacter pylori-associated duodenal ulcer disease have been compared using results from independent studies using different methods and regimens, making interpretation difficult. In a large, double-blind, multicenter study conducted in the United States, we compared a triple therapy regimen with four dual therapy and one monotherapy regimens in the eradication of H. pylori and the prevention of ulcer recurrence. METHODS: Patients with active duodenal ulcer disease or history of duodenal ulcer disease within the past year and H. pylori infection were randomized to receive one of six 14-day treatment regimens: lansoprazole 30 mg, clarithromycin 500 mg, and amoxicillin 1 gm b.i.d.; lansoprazole 30 mg b.id. and either clarithromycin 500 mg b.i.d. or t.i.d.; lansoprazole 30 mg b.i.d. or t.i.d. with amoxicillin 1 gm t.i.d.; or lansoprazole 30 mg t.i.d. alone. No additional acid suppression therapy followed eradication therapy. Primary efficacy endpoints were eradication of H. pylori and ulcer recurrence. RESULTS: Of 396 patients enrolled in the study, 352 met the entry criteria for duodenal ulcer status and H. pylori positivity. At 4-6 wk after the end of therapy, H. pylori was eradicated from 94% (44 of 47) of patients receiving lansoprazole, clarithromycin, and amoxicillin triple therapy, 77% (39 of 51) of those receiving lansoprazole t.i.d./amoxicillin t.i.d., 75% (36 of 48) of those receiving lansoprazole b.i.d./clarithromycin t.i.d., 57% (28 of 49) of those receiving lansoprazole b.i.d./clarithromycin b.i.d., 53% (26 of 49) of those receiving lansoprazole b.i.d./amoxicillin t.i.d., and 2% (1 of 53) of those receiving lansoprazole monotherapy (p < or = 0.05, triple therapy vs each dual therapy and each dual therapy vs monotherapy). Of those patients who were documented as free of ulcer at 4-6 wk after treatment, ulcers recurred within 6 months in 7% of patients receiving triple therapy, as compared with 13-23% of patients receiving dual therapy, and 69% of patients receiving lansoprazole monotherapy. Patients who were H. pylori negative at 4-6 wk after treatment were less likely to have an ulcer recurrence than were patients who were H. pylori positive (11% [10 of 95] vs 47% [20 of 43], respectively, across treatment groups). For triple therapy and dual therapy, a similar proportion of patients reported a drug-related adverse event (23% vs 17-33%, respectively). CONCLUSIONS: In patients with active or a recent history of duodenal ulcer, a 14-day course of lansoprazole-based triple therapy without additional acid suppression therapy is highly effective in the eradication of H. pylori and in preventing ulcer recurrence. Among the dual therapies, higher eradication rates occurred when lansoprazole (with amoxicillin) or clarithromycin (with lansoprazole) was administered t.i.d. vs b.i.d., but the rates were still significantly lower than with lansoprazole triple therapy with all three drugs administered b.i.d.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Discovery of ascomycin analogs with potent topical but weak systemic activity for treatment of inflammatory skin diseases.

Drug therapy for the major inflammatory skin diseases, which include atopic dermatitis, psoriasis and allergic contact dermatitis, is often inadequate due to poor efficacy, toxicity, or both. Much research has focused on the macrolactam T cell inhibitors as a promising new class of agents for immunotherapy, and medicinal chemistry efforts to design novel ascomycin analogs have produced clinically promising agents. A synthetic program to modify the ascomycin nucleus to alter its physicochemical properties and promote systemic clearance is described. A biologic screening strategy to identify analogs with reduced systemic activity and rapid pharmacokinetic elimination led to identification of the clinical candidate, ABT-281. A swine contact hypersensitivity model was used as a stringent indicator of skin penetration as human doses of topical corticosteroids produced inhibition only in the 50% range and ED50 values were 100-fold less potent than in rat. Also, cyclosporine was confirmed to be topically inactive in swine, as seen in human. ABT-281 had topical potency equal to tacrolimus (FK506) despite a severalfold lower potency for inhibiting swine T cells in vitro, consistent with superior skin penetration. ABT-281 was found to have a shorter duration of action after i.v. dosing in monkeys using an ex vivo whole blood IL-2 production assay. Systemic potency was reduced by 30-fold or more in rat popliteal lymph node hyperplasia and contact hypersensitivity assays. Following i.v. or i.p. administration in the swine contact hypersensitivity model, ABT-281 was 19- and 61-fold less potent, respectively, than FK506. Pharmacokinetic studies showed that ABT-281 had a shorter half life and higher rate of clearance than FK506 in all three species. The potent topical activity and reduced systemic exposure of ABT-281 may thus provide both efficacy and a greater margin of safety for topical therapy of skin diseases.

Administration, Topical↗