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Biomedical subjects

A Frey

Publications and source records attributed to A Frey.

At least 55 records · Page 3Linked to original sources

Association between clinical presentation, biogroups and virulence attributes of Yersinia enterocolitica strains in human diarrhoeal disease.

Traditionally the enteric pathogen Yersinia enterocolitica has been differentiated into biogroups. Despite being considered as non-pathogenic, biogroup 1A isolates have constituted a sizeable fraction of strains from patients with gastroenteritis in many reports. To establish a potential clinical significance for biogroup 1A isolates of Y. enterocolitica, clinical disease in patients with gastroenteritis excreting such isolates was compared with symptoms among patients found infected with pathogenic biogroups. Clinical data and isolates of 66 patients from whom Y. enterocolitica had been isolated by direct plating were available for study. There was an association between patient age below 3 years and infection with 'pathogenic' Y. enterocolitica. The severity of gastroenteritis and other symptoms, however, did not depend on the biogroup, or the presence of the virulence plasmid in the yersinia strain isolated from the patients. Strains belonging to biogroup 1A of Y. enterocolitica showed two clusters of ribotypes, one of which encompassed most isolates recovered from humans, the other being associated with environmental isolates. This might indicate the existence of human-adapted and potentially pathogenic strains among biogroup 1A of Y. enterocolitica.

Adolescent↗

Spontaneous changes of heart rate, blood pressure, and ischemia-type ST-segment depressions in patients with hypertension without significant coronary artery disease: beneficial effects of beta-blockade.

In hypertensives, a reduced coronary flow reserve is observed and may contribute to angina pectoris and silent (painless) myocardial ischemia, which frequently occur in these patients even in the absence of coronary artery disease (CAD). To assess the frequency of ischemia-type ST-segment depressions in these patients and the influence of heart rate (HR) and blood pressure (BP) as major determinants of myocardial oxygen demand and to test the effects of beta-blocker therapy (10-20 mg betaxolol/day for 4 weeks) on these variables, simultaneous 24-h Holter and 24-h ambulatory BP monitoring was performed in 19 patients with hypertension (age, 43-71 years; nine women, 10 men) without CAD (stenosis < 50% in angiography). Before treatment, 25 periods of significant ST-segment depressions with a total duration of 470 min were observed in nine patients. ST-segment depressions were significantly correlated with preceding increases in HR and the rate-pressure product. The majority (79%) of episodes with ST-segment depression were clinically painless. In this open study, beta-blockade significantly decreased the number of episodes with ST-segment depressions to six in four of 15 patients and the total duration to 38 min (p < 0.05). The data demonstrate that HR seems to be associated with the development of ischemic ST-segment deviations in patients with hypertension without CAD. Antihypertensive therapy in these patients should target not only sufficient BP control, but also reduction of ischemic events.

Adrenergic beta-Antagonists↗

Moderate hypothermia in patients with severe head injury: cerebral and extracerebral effects.

Cerebral and extracerebral effects of moderate hypothermia (core temperature 32.5 degrees C-33.0 degrees C) were prospectively studied in 10 patients with severe closed head injury (Glasgow Coma Scale score < 7) in the intensive care unit of a university hospital. Hypothermia was induced by cooling the patient's body surface with water-circulating blankets. Before cooling, a conventional intracranial pressure (ICP) reduction therapy was applied, which remained unchanged throughout the study. Cerebral blood flow (CBF), cerebral metabolic rates for oxygen (CMRO2) and lactate (CMRL), and ICP were simultaneously measured prior to inducing hypothermia, after obtaining hypothermia, after 24 hours of hypothermia, and after rewarming. With respect to extracerebral effects, supplemental investigations were conducted 24 and 72 hours after rewarming. The median delay between injury and induction of hypothermia was 16 hours. Hypothermia reduced CMRO2 by 45% (p < 0.01), whereas CBF did not change significantly. Before cooling, six patients had elevated CMRL indicating cerebral ischemia. Cooling normalized CMRL in all patients (p < 0.01). The intracranial hypertension present prior to cooling declined markedly during hypothermia (p < 0.01) without significant rebound effects after rewarming. Cardiac index decreased by 18% after hypothermia was reached (p < 0.05), recovered at 24 hours of hypothermia, and surpassed baseline values after rewarming. Platelet counts dropped continuously up to 24 hours after rewarming (p < 0.01). Plasma coagulation tests did not show significant worsening. Creatinine clearance decreased during cooling (p < 0.01) and recovered by 24 hours after rewarming. Twenty-four hours after cooling had begun, eight patients had elevated serum lipase activity (p < 0.01) and four of them acquired pancreatitis. Rewarming normalized both pancreatic alterations. Seven patients made a good recovery; one survived severely disabled; and two patients died. Moderate hypothermia is effective in preventing secondary brain damage while reducing cerebral ischemia. However, there are potentially hazardous side effects that require additional monitoring.

Adolescent↗

The usefulness of dietary medium-chain triglycerides in body weight control: fact or fancy?

Compared to long-chain triglycerides (LCT), medium-chain triglycerides (MCT) display some specific physico-chemical, and biological characteristics. Thus, MCT are currently used in clinical nutrition as energy-yielding substrates, and have been advocated for three decades as a useful mean for body weight reduction. This review encompasses most aspects of MCT metabolism arguing this slimming hypothesis pro and con. Findings in support of the opinion (lower energy density, control of satiety, rapid intrahepatic delivery and oxidation rates, poor adipose tissue incorporation) may be invalidated by counteracting data (stimulation of insulin secretion and of anabolic-related processes, increased de novo fatty acid synthesis, induced hypertriglyceridemia). The balance between these two opposing influences depends on the composition (energy intake, nature of ingredients, MCT/LCT ratio, octanoate/decanoate ratio) and duration of the regimen. Due to the high energy level (around 50%) of MCT necessary to achieve body weight loss, long-term compliance to such slimming regimens is unlikely in human nutrition.

Adipose Tissue↗

Sequence analysis by NMR spectroscopy of the peptide lantibiotic epilancin K7 from Staphylococcus epidermidis K7.

The amino acid sequence of the novel lantibiotic epilancin K7 from Staphylococcus epidermidis K7 was determined by NMR spectroscopy. NMR spectroscopy was used because sequencing by conventional Edman degradation techniques was prohibited by internal sequence blocks owing to the presence of modified residues. Epilancin K7 consists of 31 residues, including two alpha,beta-didehydroalanine (one-letter code U) and two alpha,beta-didehydrobutyrine (O) residues, one lanthionine (A-S-A), two beta-methyllanthionines (A*-S-A), and six lysines. Epilancin K7 has a molecular mass of 3032 +/- 1.5 Da. The amino acid sequence of epilancin K7 was derived from both through-space dipolar proton-proton interactions and through-bond scalar proton-carbon interactions as detected by two-dimensional 1H-NOESY, 1H-ROESY and three-dimensional 1H-TOCSY-NOESY, and by two-dimensional 1H,13C-heteronuclear multiple-bond correlation spectroscopy, respectively. The sequence is as follows: [sequence: see text] The N-terminal residue X partly resembles an alanine but its exact nature is unclear. The organization of the sulfide-bridge-containing (beta-methyl-)lanthionines was revealed by 1H-NMR and 1H,13C-NMR spectroscopy. Epilancin K7 has a linear structure and a high positive net charge, and therefore is classified as a type-A lantibiotic. NMR analysis of a degraded though still active form of epilancin K7 showed that two N-terminal residues of epilancin K7 were missing, owing to decomposition at the alpha,beta-didehydro alanine at position 3; it was called the epilancin K7-(3-31)-peptide (peptide fragment of epilancin K7 consisting of positions 3-31). The usefulness of three-dimensional 1H-TOCSY-NOESY, and two-dimensional 1H,13C-heteronuclear multiple-bond correlation spectroscopy at natural abundance for the study of (modified) polypeptides is demonstrated.

Amino Acid Sequence↗

gamma-Glutamyl transpeptidase-cellular expression in populations of normal human mononuclear cells and patients suffering from leukemias.

The expression of the ectoenzyme gamma-glutamyl transpeptidase (EC2.3.2.2., gamma GT) was investigated by flow cytometry on populations of peripheral blood mononuclear cells (PBMC) from healthy subjects and patients suffering from several types of leukemia before and under chemotherapy. In unstimulated PBMC, 28% of these cells were found to be gamma GT positive. The highest expression was measured on monocytes (CD14/gamma GT+ cells: 60%). Within the subsets of T lymphocytes (CD3/gamma GT+ cells: 18%) we saw no clear differences between CD4+ and CD8+ cells. B lymphocytes, NK cells, and activated cells showed low expressions (up to 10%). Treatment of PBMC with mitogens, alpha-IFN, IL-2, and GM-CSF did not affect the enzyme expression on normal mononuclear cells (MNC). However, a rapid increase of gamma GT+ cells was found in the presence of glutathione (GSH) and n-acetyl cysteine (nAC), particularly on monocytes, B cells, and NK cells. Comparing 40 healthy subjects and untreated patients suffering from leukemias, a significantly higher expression of gamma GT+ cells in the total MNC populations (B-CLL: 57%, CML: 62% gamma GT+ cells) was observed in B-chronic lymphocytic leukemia (B-CLL) and chronic myelogenous leukemia (CML), whereas other leukemias did not show clear differences. Most interestingly, the gamma GT expression was diminished in all populations of CML cells after 5 h of incubation in the presence of 10 units/ml IFN-alpha. These data suggest a possible protective role of gamma GT in MNC and a regulatory function of this enzyme in the development of CML.

Adult↗

[Comparison of APACHE-II AND APACHE-III for classification of disease severity of intensive care patients].

The Acute Physiology and Chronic Health Evaluation model (APACHE II, APACHE III) is used to describe the severity of illness and predict the outcome in critically ill patients. APACHE III, introduced in 1991, has not yet been validated in Europe. We calculated APACHE II and APACHE III scores in patients after admission to the intensive care unit (ICU) and compared the prognostic value on hospital mortality. METHOD. One hundred fifty patients with stay of over 24 h were enrolled in the study and prospectively and consecutively investigated. APACHE II and III scores were calculated as described by the authors. The mean and median values of the survivors were compared with the non-surviving group (Mann-Whitney U test). Receiver operating characteristics (ROC analysis) and the areas under the ROC curves were plotted. RESULTS. Of the 150 patients, 34 died during their hospital stay (22.7%). The mean and median APACHE II and III scores were significantly higher (P < 0.001) in the non-surviving group. The area under the ROC curve was higher for APACHE III (0.899) compared to APACHE II (0.847). CONCLUSIONS. APACHE II and APACHE III were both found to have good prognostic value in general ICU patients. Our results suggest that the APACHE III version includes a more precise prediction of hospital mortality than APACHE II. A new aspect of APACHE III is an expanded modification of the Glasgow Coma Scale to assess neurologic derangements.

APACHE↗

Prevalence and clinical significance of vero-cytotoxin-producing Escherichia coli (VTEC) isolated from cattle in herds with and without calf diarrhoea.

To determine the clinical significance and prevalence of Vero cytotoxin (VT)-producing E. coli (VTEC) in Swiss cattle, faecal swabs and milk samples of 93 cattle from two farms with calf diarrhoea, and of 54 cattle from two similar farms without clinical problems, were screened for VTEC by PCR and colony-blot hybridization. On average, 21% of all cows were positive for VTEC by PCR, without differences between farms with and without diarrhoea problems. By contrast, VTEC were detected by PCR in 60% of animals younger than 2 years from farms with diarrhoea problems, whereas only 32% of comparable control animals from farms without clinical problems had VTEC. No VTEC were detected in the milk samples. A variety of toxin types, antimicrobial-susceptibility patterns and serotypes were found by colony-blot hybridization, among the VTEC in individual herds. However, there was a significant relationship between the VT1-only toxin type and the presence of antimicrobial resistance and clinical disease in calves. No association could be found between levels of VTEC excretion and the presence of diarrhoea. This is the first study to report systematic quantitative data on numbers of VTEC in faecal samples of cattle positive for VT genes by PCR.

Animals↗

Is the transfusion requirement predictable in critically ill patients after admission to the intensive care unit?

OBJECTIVE: In intensive care medicine the clinical decision to order and transfuse red blood cells (RBC) is usually based on hematocrit or hemoglobin levels. The intention of this study was to investigate whether clinical or laboratory variables, taken after the admission of patients to the intensive care unit (ICU), are able to predict the transfusion requirement of the following 72 h. DESIGN: The values of initially measured systolic blood pressure, hematocrit level, and the values of 2 scores of severity of disease (Acute Physiology And Chronic Health Evaluation [APACHE-II], Mortality Prediction Model [MPM]) were calculated after the admission of patients to the ICU. The decision for transfusion was based on specific criteria. The median values of the scores, those of the variables, and the median number of transfused RBC units of the surviving group were compared to the values of the group of patients who died during hospital stay. The quantity of RBC transfusions was compared to the variables and score values by linear regression analysis. Additionally, the values of the patients who did not receive blood transfusion were compared to those of patients who required RBC. Furthermore, the patient group with neurosurgical diseases was compared to the group without neurosurgical diseases. PATIENTS: 117 patients were prospectively and consecutively investigated in an 8-bed ICU of a university hospital. RESULTS: Nonsurvivors required significantly more units of RBC during the first 72 h (p < 0.05). Patients who did not require transfusion had a higher hematocrit and a lower APACHE-II value at admission (p < 0.001). In the MPM values no differences were found. Patients with neurosurgical diseases had a higher initial hematocrit value, and they required less units of RBC in comparison to patients without neurosurgical diseases. In the analysis of linear regression neither in the initially measured systolic blood pressure nor in the APACHE-II and MPM we found a strong linear correlation to the quantity of blood transfusion. CONCLUSIONS: A hematocrit value < or = 20% and a APACHE-II score > or = 20 at the time of admission to the ICU referred to a demand for blood transfusion. We believe that these parameters are useful as predictive instruments. The initially measured systolic blood pressure had no prognostic capacity. In the individual patient a number of factors should be taken into account to decide whether to transfuse or not.

APACHE↗

Lipid composition and structure of commercial parenteral emulsions.

In order to study the influence of the phospholipid/triacylglycerol (PL/TG) ratio of parenteral emulsions on the distribution and the physico-chemical properties of their fat particles, commercial 10, 20 or 30% fat formulas were fractionated by centrifugation into an upper lipid cake (resuspended in aqueous glycerol) and a subnatant or mesophase, from which a PL-rich subfraction (d = 1.010-1.030 g/l) was purified by density gradient ultracentrifugation. Chemical and 31P-NMR analyses of these fractions indicated that at least two types of fat particles coexist in parenteral emulsions: (i) TG-rich particles (mean diameter: 330, 400, 470 nm in the 10, 20, 30% emulsion) which contain practically all the TG and esterified phytosterols of native emulsions, but only a fraction of their PL, unesterified cholesterol and phytosterols, and other minor lipids; (ii) PL-bilayer particles or liposomes (mean diameter: 80-100 nm) which are constituted with the remaining PL and relatively very small amounts of TG and other lipids. The higher the oil content of the emulsion, the lower the amount of these PL-rich particles, which represent the major particle population of the mesophase. Indeed, minute amounts of TG-rich particles (probably the smallest ones) are also present in the mesophase, even in the PL-rich subfraction which contains the bulk of liposomal PL. Since the PL-rich particles of the infused emulsion generate lipoprotein X-like particles, only the large TG-rich particles can be considered as true chylomicron counterparts.

Centrifugation, Density Gradient↗

Hypoxaemia and myocardial ischaemia on the night before coronary bypass surgery.

Using pulse oximetry and Holter ECG monitoring on the night before coronary bypass surgery, we studied 30 male patients with coronary artery disease to determine the relationship between nocturnal hypoxaemia and myocardial ischaemia. The patients received intensive anti-angina medication and were sedated with clorazepate. Ten patients developed a total of 42 ischaemic episodes, 24 of which occurred between 22:00 and 06:00. Mean heart rate was significantly higher in patients with ischaemia than in those without ischaemia. In 60% of all patients, heart rate increased > or = 20% at the onset of the ischaemic episode. The patients spent a median of 2 (range 0.02-40.6)% of the night with oxygen saturation (SpO2) < 90% (the minimum SpO2 value recorded was 84 (69-88) %). Only five ischaemic episodes were associated with respiratory events. These were not associated with either extraordinary oxygen desaturation or marked increases in heart rate. Comparing patients with and without ischaemia, there were no significant differences in the extent of nocturnal hypoxaemia or the pattern of desaturation episodes (cyclic variations in saturation characteristic of periodical breathing vs non-cyclic desaturation episodes). Despite marked nocturnal hypoxaemia, simultaneous occurrence of desaturation episodes and myocardial ischaemia was a rare event in our study.

Aged↗

Blood-brain barrier: a molecular approach to its structural and functional characterization.

Our approach to analyze molecular components of the blood-brain barrier led to the identification of additional transcripts which can be regarded as "BBB markers". Other candidates are presently analyzed in order to find hitherto unknown cell type-specific transcripts. We investigated the expression of these marker-genes in cell culture and found all genes still being transcribed after 10 days in primary cultures, although at a lower level. This is surprising, since other authors report the disappearance of BBB characteristics under such conditions. Moreover, the BBB marker gamma-GT is found to be not only expressed in BMEC, but also in the closely associated pericytes. The hitherto unknown physiological function of the enzyme, especially the abundance in pericytes is still under investigation. Since the method of subtractive cloning has been proven as a fruitful approach, we consider to establish further subtractive cDNA libraries, using different subtraction parameters. The PCR method is applicable for amplification of subtracted cDNA (Timblin et al., 1990) and we expect to find additional clones, mainly of lower abundance which are of functional importance for the BBB phenomenon. The described characterization of cultured BMEC now allows to proceed to study BBB-specific gene expression with special regard to regulatory elements. We will perform these experiments by use of enhancer trap vectors transfected into BMEC. The isolation of the corresponding genomic DNA fragments of the BBB markers is in progress.

Animals↗

[ST-segment depressions and spontaneous changes in blood pressure and heart rate in simultaneous 24-hour recording in hypertensive patients].

In 15 patients with essential hypertension (but without coronary heart disease) simultaneous 24-h monitoring of the ST-segment and blood pressure was performed. Twenty-six periods with significant ST-segment depressions were recorded. In 10/26 periods with ST-segment depressions blood pressure was elevated, heart rate was increased in 20/26 ST-segment depressions. During nine periods with ST-segment depressions angina pectoris was reported, and 27 anginal attacks without ST-segment depressions were observed. These data show ischemic episodes in hypertensive patients without coronary heart disease being associated with spontaneous increases of blood pressure and/or heart rate.

Angina Pectoris↗

Pericytes of the brain microvasculature express gamma-glutamyl transpeptidase.

The expression of gamma-glutamyl transpeptidase (GGT) is a specific property of the brain capillary endothelium that constitutes the blood-brain barrier. We report here the detection of GGT, not only in endothelial cells, but also in pericytes, demonstrating that a brain capillary-specific pericyte population exists. We raised antibodies to GGT using a porcine brain microvessel GGT-protein-A (staphylococcal protein A) fusion protein as antigen which was expressed in Escherichia coli. The immunohistochemical analysis of the subcapillary distribution of GGT in porcine brain cortex and cerebellum sections by both light and electron microscopy revealed the expression of GGT in the capillary-adjacent pericytes in addition to the GGT-positive endothelial layer. We confirmed these data for cultured porcine brain microvascular endothelial cells and pericytes. GGT immunofluorescence could be detected in both cell types in culture. Endothelial cells exhibited a weak staining, whereas pericytes were strongly positive for GGT. Due to the high phagocytotic activity of pericytes and their location on the abluminal surface of the microvessels, we propose a possible protective or detoxifying function of GGT in cerebrovascular pericytes.

Animals↗

Regulated replication of an episomal simian virus 40 origin plasmid in COS7 cells.

The replication of a simian virus 40 (SV40) origin-containing plasmid, pSLneo, stably transfected COS7 cells has been studied. pSLneo contains the SV40 origin of replication and encodes the positive selectable marker for G418 resistance. In transient replication assays, pSLneo replicates to a high copy number in COS7 cells. Uncontrolled SV40 plasmid replication has been reported to be lethal to such transfected cells. Thus, it was anticipated that extensive plasmid replication would preclude isolation of permanent cell lines containing pSLneo. However, significant number of G418-resistant colonies arose after transfection of COS7 cells with pSLneo. Cell lines established from these drug-resistant colonies contained between 100 and 1,000 extrachromosomal pSLneo copies per cell. Episomal plasmid DNA in pSLneo/COS7 lines was stably maintained after 2 months of continuous culture in selective medium. Bromodeoxyuridine labeling and density shift experiments demonstrated that replication of pSLneo closely paralleled that of cellular DNA. On average, plasmid DNA did not replicate more than once during a single cell generation period. Regulation of pSLneo replication appeared to be negatively controlled by a cis-acting mechanism. Endogenous copies of episomal pSLneo remained at a stable low copy number during the simultaneous, high-level replication of a newly transfected plasmid encoding SV40 large T antigen in the same cells. These results indicate that regulated replication of an SV40 origin plasmid can be acquired in a cell and does not require the presence of additional genetic elements. The molecular mechanism by which cells enforce this regulation on extrachromosomal SV40 plasmids remains to be defined.

Animals↗

[Thrombocyte aggregation and fibrinolysis in healthy probands treated with molsidomine, isosorbide-5-mononitrate and placebo].

Twelve healthy volunteers received either a single oral dose of molsidomine (4 mg), isosorbide-5-mononitrate (ISMN, 20 mg), or placebo in a randomized, double-blind fashion. Blood was drawn prior to, as well as 30 and 60 min after intake of the respective drug. Platelet aggregation and the plasma levels/activity of plasminogen activator (tPA) and its inhibitor (PAI-1) were determined. In contrast to ISMN and placebo, molsidomine provoked a significant reduction in platelet aggregability. No alteration in plasma tPA concentrations was observed independent of whether molsidomine, ISMN, or placebo was applied. However, plasma PAI-1 activity was considerably reduced following molsidomine, but not altered following ISMN or placebo. We conclude that a single oral dose of molsidomine, but not of ISMN inhibits platelet aggregation and increases the fibrinolytic potential in healthy volunteers.

Adult↗