Traumatized pigs are unsuitable as organ donors for pancreatic islet isolation.
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Animals↗
Biomedical subjects
C Otto
Publications and source records attributed to C Otto.
Effect of selective immunosuppression with FK 506, anti-IL-2R, and anti-ICAM-1 MAb in rat small bowel transplantation.
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Animals↗
Noninvasive videomicroscopic monitoring of rat small bowel rejection.
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Animals↗
Effects of acipimox on haemorheology and plasma lipoproteins in patients with mixed hyperlipoproteinaemia.
AIMS: Epidemiological data have shown that haemorheological disorders are associated with an increased risk of atherosclerosis. We evaluated the effect of the nicotinic acid derivative acipimox on haemorheological and lipid parameters in 18 patients with mixed hyperlipoproteinaemia using a randomized, double-blind, placebo-controlled, cross-over study protocol. METHODS: Patients (7 women, 11 men, aged 49.3+/-3.0 years) were investigated with acipimox (dose adjusted to weight, 500 or 750 mg daily) compared with placebo treatment each for 12 weeks. Lipid parameters, whole blood viscosity, plasma viscosity, fibrinogen, and red cell aggregation at native and standardized (0.45) haematocrit as well as red cell filterability were measured at baseline, at week 12 (change of therapy), and at week 24. RESULTS: Total cholesterol concentration (8.30+/-0.32 vs 8.72+/-0.36 mmol/l(-1)) and apolipoprotein B (198.5+/-9.9 vs 217+/-9.9 mg dl(-1)) were significantly lower (P<0.05) during acipimox therapy compared with placebo, no significant changes were observed for triglycerides and low-density lipoprotein [LDL] cholesterol. However, total high-density lipoprotein [HDL] cholesterol (1.24+/-0.05 vs 1.10+/-0.05 mmol l(-1), P<0.001) as well as HDL2 and HDL3 cholesterol (P<0.05) were significantly higher during acipimox therapy. The LDL cholesterol to HDL cholesterol ratio significantly improved during acipimox therapy (4.63+/-0.25 vs 5.49+/-0.26, P<0.001). Red cell aggregation at native and standardized haematocrit were the only haemorheological parameters which improved during acipimox therapy in comparison with placebo (shear rate 3 s(-1):10.69+/-0.40 vs 11.50+/-0.44 U, P<0.05, for native red cell aggregation; 10.40+/-0.36 vs 11.28+/-0.39 U, P<0.05, for standardized red cell aggregation). CONCLUSIONS: We conclude, that the cardiovascular risk profile improves during acipimox therapy due to an elevation in HDL cholesterol and its subfractions as well as a decrease in red cell aggregation.
Blood Viscosity↗
[Role of apoptosis in induction of tolerance after liver and liver/small intestine transplantation].
Liver induced tolerance and the protecting effect towards a co-transplanted organ are well known effects after liver transplantation in rats. Isolated liver transplantation and combined liver/small bowel transplantation are used to investigate the cellular mechanisms of those two phenomenons. In both transplantation models a transient rejection process can be observed. During this response recipient derived graft infiltrating T-cells are subsequently inactivated. The initial peak of apoptotic cell death in the liver lobuli decreases and is followed by an increase in apoptosis of the infiltrating T-cells during the end of the rejection response. Donor specific tolerance occurs after LTx and LDDTx respectively, proofed by indicator heart transplantation.
Animals↗
[Selective immunosuppression with monoclonal antibodies against ICAM-1 and LFA-1 with FK 506 after experimental small intestine transplantation in the rat].
Prevention of allograft rejection remains a major problem after small bowel transplantation (SBT) and requires potent immunosuppressive regimens. In a variety of transplant models, e.g. liver or heart transplantation, the supplementary application of monoclonal antibodies (mabs) against adhesion molecules is effective in both prolonging graft survival and inducing long-term graft acceptance or tolerance in some cases. In this study anti ICAM-1 (1A29) and anti LFA-1 (WT1) mabs were used in combination with a subtherapeutic dose of FK 506 for 13 days after allogeneic SBT in the rat. The results of this study indicate that in contrast to the induction of allospecific tolerance after liver transplantation, the addition of anti ICAM-1 and/or of anti LFA-1 mabs after SBT reverses the FK 506 effect and results in early graft rejection. It has been shown that higher dosages of these mabs, given alone or in combination with CsA or FK 506, result in long-term survival of cardiac allografts in both, rats and mice [4-8]. Graft survival after pancreas transplantation is prolonged [6]. However, these negative therapeutic effects of the mabs 1A29 and WT1 after SBT have to be critically reevaluated and further analysed.
Animals↗
Multinational pharmaceutical companies gather in Berlin.
The 39th Annual General Meeting of the Pharma Documentation Ring (PDR) was held in Berlin, Germany, on September 26, 1997. Common themes reported on included the impact and widespread use of intranet technology; expansion in end-user searching; experience with electronic journals; and programs for the development of electronic archiving and document management systems. Other sessions discussed aspects of chemistry systems; copyright; drug information systems on development products; information management, in-house management of databases; Intranet/Internet activities; and patents. The core topic presented at the meeting involved an overview on document delivery/electronic journals. There is considerable activity in this area by primary and secondary publishers with real momentum seen in the area of electronic document delivery services on the Internet. The 40th anniversary of the PDR will be celebrated at the upcoming AGM, to be held in Montpellier, France, September 30 October 2, 1998.
Journal Article↗
Cholesterol, phospholipid, and protein changes in focal opacities in the human eye lens.
PURPOSE: Focal opacities are signs of early cataractogenesis in the human lens. They progress slowly over a lifetime and may be precursors of mature cataracts. The authors analyzed changes in proteins, phospholipids, and cholesterol in these opacities using in situ techniques: Raman microspectroscopy, filipin cytochemistry for cholesterol, and transmission electron microscopy (TEM). METHODS: Human lenses with verified focal opacities were fixed in 1% paraformaldehyde. Slabs with opacities were analyzed using confocal Raman spectroscopy, then filipin Raman analysis of cholesterol, and finally TEM. RESULTS: Compared with normal fibers, opacities consistently showed elevated levels of cholesterol and aliphatic chains, increased phospholipid acyl chain disorder, and changes in phospholipid lateral packing. Disulfide bridges of specific geometry (trans-gauche-trans) were found. Although protein content was unchanged, compared with normal fibers, aromatic amino acid content was significantly lower. The hydrophobicity of tyrosine residues showed a significant decrease, and a change in the tryptophan indole ring angle was found. The changes were abrupt and sharply delineated focal opacities. TEM confirmed this sharp boundary and showed that the opacities were densely packed with vesicles of varying size and electron density embedded in a homogenous matrix. CONCLUSIONS: The Raman and TEM analyses of opacities showed that early cataractogenic events led to disruption of fiber membranes, formation of vesicles from the membrane constituents, and protein changes. The aberrant morphology of the membranes enveloping the focal opacities may have segregated the affected fibers from the surrounding normal tissue, thus explaining the stationary or slowly progressing character of these opacities.
Adult↗
Evidence for Hoogsteen GC base pairs in the proton-induced transition from right-handed to left-handed poly(dG-dC).poly(dG-dC).
The structure of double-helical poly(dG-dC).poly(dG-dC) is investigated at various pH values with Raman spectroscopy, absorption spectroscopy, and circular dichroism. A comparison is made between the B-form with Watson-Crick base pairing at 1 mM [Na+] and pH 7.2, the Z-form with Watson-Crick base pairing at 4 M [Na+] and pH 7.2, and a different structure at 1 mM [Na+] and pH 4.5 as well as at 150 mM [Na+] and pH 3.1. The CD spectrum of poly(dG-dC). poly(dG-dC) under the latter conditions does not show a negative band at 290 nm. The structure is a double-helical structure different from the B-form and the Z-form according to circular dichroism, Raman, and absorption spectroscopic studies. The Raman spectra evidence that the structure contains Hoogsteen base pairing. This can be accommodated in the double helix when the cytosine group is protonated and the sugar-guanine conformer has adopted a C2'-endo/syn conformation. It is shown that this antiparallel-stranded Hoogsteen base paired structure can be maintained under varying conditions, balancing the decrease in pH with an increased salt concentration. It is further concluded that the proton-induced transition from a Watson-Crick to a Hoogsteen base pair is aided by a decrease of [Na+] at pH 4.5 and occurs prior to a conversion from a right-handed helix to a left-handed helix.
Base Composition↗
Absence of glucocorticoid receptor-beta in mice.
Two human glucocorticoid receptor (GR) isoforms, GRalpha and GRbeta, are derived from the same gene by alternative splicing involving exon 9 of the GR locus. The non-ligand binding isoform GRbeta was proposed to act as a transdominant negative inhibitor of GRalpha, thus modulating glucocorticoid responsiveness of target tissues. To study GRbeta in mice we characterized the genomic region around exon 9 of the murine GR gene. Sequence analysis revealed that the presumed exon 9beta contained an open reading frame of 59 amino acids. In contrast, human exon 9beta encoded only 15 amino acids. Using reverse transcriptase polymerase chain reaction the absence of GRbeta mRNA was demonstrated in all adult mouse tissues examined. To exclude the possibility that the polymerase chain reaction conditions employed were not suitable for the amplification of GRbeta mRNA, we synthesized an artificial template corresponding to the presumed GRbeta mRNA spanning exons 7, 8, and 9beta. Various amounts of this template were added to brain cDNA preparations and as little as 25 molecules were detectable under the polymerase chain reaction conditions chosen. Since GRbeta is not conserved across species its physiological significance in humans appears questionable.
Alternative Splicing↗
p55 Tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock. A randomized controlled multicenter trial. Ro 45-2081 Study Group.
OBJECTIVE: To evaluate the safety and efficacy of p55 tumor necrosis factor receptor fusion protein, a recombinant chimeric protein of human p55 (type I) tumor necrosis factor receptor (CD120a) extracellular domain and IgG1 sequences (referred to as p55-IgG), in the treatment of patients with severe sepsis or septic shock. DESIGN: Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial. SETTING: Forty-four community and university-affiliated hospitals in the United States and Europe. PATIENTS: There were 498 patients enrolled in this clinical trial. INTERVENTION: Patients prospectively stratified within each site into refractory shock or severe sepsis groups were randomized to receive a single infusion of p55-IgG, 0.083 mg/kg, 0.042 mg/kg, or 0.008 mg/kg, or placebo. Patients received standard aggressive medical/surgical care during the 28-day postinfusion period. OUTCOME MEASURE: Twenty-eight-day all-cause mortality. RESULTS: The distribution of variables describing demographics, organ system dysfunction or failure, infecting microorganisms, predicted mortality, plasma interleukin 6 levels, and plasma tumor necrosis factor alpha (TNF-alpha) levels were similar among patients in the p55-IgG and placebo treatment arms. A planned interim analysis was performed after 201 patients were enrolled. Because a statistically nonsignificant trend toward increased mortality was present in patients who had received 0.008 mg/kg, this treatment arm was discontinued, and the study continued with 3 arms. Among all infused patients, there was a statistically nonsignificant trend toward reduced 28-day all-cause mortality in those who received p55-IgG compared with placebo-treated patients (5% reduction, 0.042 mg/kg vs placebo; 15% reduction, 0.083 mg/kg vs placebo; P=.30). However, in patients with severe sepsis and early septic shock (n=247), therapy with p55-IgG, 0.083 mg/kg, was associated with a 36% reduction in 28-day all-cause mortality compared with placebo (P=.07): 20 (23%) of 87 patients died among those treated with p55-IgG, 0.083 mg/kg; 30 (37%) of 82 among those treated with p55-IgG, 0.042 mg/kg; and 28 (36%) of 78 in the placebo group. A prospectively planned logistic regression analysis to assess treatment effect on 28-day all-cause mortality by means of predicted mortality and serum interleukin 6 levels as continuous covariates demonstrated a significant improvement in outcome for the patients with severe sepsis treated with p55-IgG, 0.083 mg/kg, compared with placebo (P=.01). Serious adverse events, including death and the development of new organ system dysfunction, were reported in 65% of patients infused with placebo, with no increased frequency (56%) present in the 2 p55-IgG treatment arms. There were no reports of immediate hypersensitivity reactions caused by p55-IgG. CONCLUSIONS: In this dose-finding study, there was no decrease in mortality between placebo and p55-IgG in all infused patients. In the prospectively defined population of patients with severe sepsis who received p55-IgG, 0.083 mg/kg, there was a trend toward reduced mortality at day 28 that became significant when predicted mortality and plasma interleukin 6 levels were included in a logistic regression analysis.
APACHE↗
[Hypoglycemia. Symptoms, differential diagnosis, therapy].
Hypoglycemia is often associated with typical, but not specific symptoms. A differentiation is made between neuroglucopenic symptoms (e.g., confusion, somnolence) on the one hand, and those that arise as a result of the counterregulatory response of the sympathetic nervous system (e.g., tremor, sweating), on the other. The diagnosis of hypoglycemia can cause considerable problems, in particular when only isolated single symptoms present (e.g., confusion, psychosis, seizures, coma). For the elective clarification of recurrent hypoglycemia, further diagnostic examinations (e.g., fasting with determination of hormones, measurement of insulin) are employed in addition to the patient's history. For differential diagnostic considerations not only organic causes, but also adverse drug reactions and a factitious genesis must be excluded. In the event of an emergency (e.g., hypoglycemic coma) the usual form of treatment is the administration of glucoses or glucagon.
Diagnosis, Differential↗
Postprandial hemorrheology and apolipoprotein B metabolism in patients with familial hypertriglyceridemia.
Impaired postprandial lipoprotein metabolism has been found to be related to the extent of coronary artery disease. Moreover, since dyslipoproteinemias are associated with impaired hemorrheology, we investigated the effect of postprandial hypertriglyceridemia on hemorrheological parameters before and after triglyceride-lowering therapy. Triglyceride-rich lipoproteins (TRLs) separated by ultracentrifugation (d < 1.006 g/dL) and chylomicrons and chylomicron remnants (quantified by apolipoprotein [apo] B-48 determination) were determined after a fat load in 10 patients with familial hypertriglyceridemia before and after therapy with gemfibrozil (900 mg daily). Lipid and hemorrheological parameters (plasma and whole-blood viscosity [PV and BV], red cell aggregation [RCA], hematocrit, and fibrinogen) were determined at baseline and every hour up to 6 hours postprandially. Fasting total triglycerides and TRL triglycerides significantly decreased with gemfibrozil therapy (P < .01). Total triglycerides postprandially increased from 9.53 +/- 1.72 to 14.47 +/- 2.07 mmol/L (TRL triglycerides by 61%) before therapy (P < .05) and from 4.61 +/- 1.28 to 7.17 +/- 0.99 mmol/L (TRL triglycerides by 57%) after therapy (P < .05). The postprandial TRL apo B increase was reduced with gemfibrozil (from 11.6 +/- 2.8 to 20.7 +/- 5.0 mg/dL with therapy v 19.0 +/- 7.6 to 33.0 +/- 12.5 mg/dL before therapy, P < .05, respectively) with a proportionally greater increase in apo B-48 (119% and 169%, respectively) compared with apo B-100 (64% and 64%, respectively). Fasting RCA was improved with lipid-lowering therapy (P < .05), but PV, BV, RCA, and fibrinogen did not show any statistically significant postprandial changes either before or after lipid-lowering therapy. In summary, we did not find any statistically significant changes in hemorrheological parameters, despite a strong postprandial increase of triglycerides. In particular, these findings were independent of fasting triglyceride levels. We conclude that triglyceride-lowering therapy by gemfibrozil had no substantial beneficial effects with respect to hemorrheology in patients with familial hypertriglyceridemia.
Adult↗
Remote, mobile telemedicine: the satellite transmission of medical data from Mount Logan.
The purpose of this investigation was to demonstrate the potential of remote, mobile telemedicine during a four-week, high-altitude mountaineering expedition to Mount Logan, Canada's highest summit. Using a mobile satellite terminal and a laptop computer (both powered by a photovoltaic solar panel), ECG tracings and blood pressure measurements, in addition to colour images, short-segment video and audio clips were transmitted during the course of the ascent. The data were transmitted via a mobile communications satellite to a ground station in Ottawa, a distance of over 4000 km. The data were then transferred to the public switched data network and delivered to the University of Ottawa Heart Institute for analysis. Similarly, data were transmitted from the ground station to the expedition team on Mount Logan throughout the ascent. Using this technique, medical diagnosis and emergency care can be facilitated in extreme and isolated locations lacking a telecommunications infrastructure. Such technology has applications in developing countries, disaster response efforts, remote civilian and military operations, and in space operations.
Canada↗
Seasonal variations of hemorheological and lipid parameters in middle-aged healthy subjects.
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Adult↗
Dipeptide uptake: a novel marker for testicular and ovarian macrophages.
BACKGROUND: Testicular and ovarian macrophages seem to be involved in paracrine regulation of steroidogenesis. Markers suitable for the identification of these cells under viable conditions would allow new experimental approaches in the study of biological interactions between hormone-producing cells and tissue macrophages. METHODS AND RESULTS: Dipeptide uptake was studied in primary cultures from rat testis and ovaries with the fluorescent dipeptide derivative beta-Ala-Lys-N epsilon-aminomethylcoumarin acetic acid (AMCA). Fluorescence microscopic studies revealed that the reporter peptide accumulated specifically in testicular macrophages, which were identified by subsequent immunostaining with the OX-42 antibody. In the ovarian cultures, however, transport of the fluorescence-labeled dipeptide was observed in cells that exhibited the morphological characteristics of macrophages but did not show positive immunoreactivity against the antibody employed. In both cases, dipeptide accumulation was blocked by the addition of Tyr-Gly, thus indicating that transport was not due to endocytosis. Competition studies performed with primary cultures from testis have shown that di-and tripeptides effectively reduce uptake of the tracer peptide, whereas compounds without an alpha- or beta-amino group, such as captopril and benzylpenicillin, do not. CONCLUSIONS: These results indicate that the testicular and ovarian macrophages are equipped with a dipeptide transport system. The selective accumulation of the fluorescent dipeptide derivative beta-Ala-Lys-N epsilon-AMCA in testicular and ovarian macrophages permits the identification of these cell types under viable conditions.
Amino Acids↗
Future directions for resuscitation research. II. External cardiopulmonary resuscitation basic life support.
In sudden cardiac deaths outside hospitals, the present performance of external cardiopulmonary resuscitation-basic life support (CPR-BLS), as a bridge to advanced life support (ALS) attempts for restoration of spontaneous circulation (ROSC), still yields suboptimal results. Therefore, future education research should develop more effective, simpler and quicker ways to enable everyone to acquire the necessary BLS skills. Individualized self-training by lay persons is being revived. Although airway control and direct mouth-to-mouth ventilation skills are difficult to acquire, they must continue to be taught to the lay public and health professionals, primarily for use on relatives and friends where infection risk is not a problem. In children and trauma victims, steps A and B alone may be lifesavers. The best way to ventilate and oxygenate during the initiation of brief external CPR-BLS should be re-evaluated. There is a great difference between animals and humans in the behavior of the airway and thorax during coma, and thus in the need for added positive pressure ventilation. During chest compressions in humans, steps A and B are needed. Details deserve re-evaluation. The low perfusion pressures (borderline blood flows) produced by standard external CPR remain the most serious limitation of this method. In spite of extensive efforts so far, novel laboratory research to remedy this limitation is important for the development of more effective emergency artificial circulation. The results of such studies are greatly influenced by different details in animal models. Active compression-decompression (ACD) external CPR, also called 'push-pull' CPR, with a plunger-type device used by hand or a machine, and intermittent abdominal compression (IAC) external CPR are both promising modifications of standard external CPR. Both need further experimental and clinical clarification. For BLS, developing a more effective purely manual CPR-BLS method for help in rapid ROSC should be given high priority. Portable external CPR machines need improvements. They will serve for bridging ROSC-resistant cases through transport and ALS attempts, primarily by freeing the hands of health professionals for more effective sophisticated ALS measures.
Cardiopulmonary Resuscitation↗
Effects of n-3 fatty acids and fenofibrate on lipid and hemorrheological parameters in familial dysbetalipoproteinemia and familial hypertriglyceridemia.
There is increasing evidence that hemorrheological abnormalities are associated with an enhanced risk of atherosclerosis. The n-3 fatty acids (n-3-FA) have been shown to have beneficial effects on atherosclerosis in patients with dyslipoproteinemias. We studied 23 patients with elevated plasma triglycerides to evaluate the influence of fish oil and fenofibrate therapy on hemorrheological parameters (15 patients with familial hypertriglyceridemia [FHTG] and eight with familial dysbetalipoproteinemia [FDL]). The patients (one woman and 22 men aged 45.7 +/- 2.0 years) were treated with increasing doses of n-3-FA (1.8 to 3.6 g/d: 0.9 to 1.8 g eicosapentaenoic acid and 0.6 to 1.2 g docosahexaenoic acid) for 8 weeks. Lipid parameters, whole-blood viscosity at different shear rates, plasma viscosity, fibrinogen concentration, and red blood cell aggregation (RCA) were measured at baseline and at weeks 2, 4, 8 (end of n-3-FA therapy), and 12. Compliance was ensured by measuring plasma concentrations of eicosapentaenoic acid and docosahexaenoic acid. After 12 weeks, patients began treatment with fenofibrate (250 mg daily); investigations were performed again at week 20. Total triglycerides (from 6.90 +/- 1.70 to 3.61 +/- 0.78 mmol/L in FDL and 7.44 +/- 1.50 to 4.15 +/- 0.55 in FHTG), very-low-density lipoprotein (VLDL) triglycerides, and VLDL cholesterol were significantly decreased with n-3-FA therapy in both groups (P < .05). In FHTG, low-density lipoprotein (LDL) cholesterol increased significantly (from 2.75 +/- 0.28 to 3.97 +/- 0.35 mmol/L, P < .01); in FDL, total cholesterol decreased (from 9.76 +/- 1.32 to 7.34 +/- 1.07 mmol/L, P < .05). No significant changes were observed in hemorrheological parameters, except for reduced RCA with 3.6 g n-3-FA in FHTG. However, with fenofibrate therapy, in addition to comparable lipoprotein changes seen with fish oil, fibrinogen levels and plasma and blood viscosity decreased in patients with FDL. We conclude that n-3-FA and fenofibrate have comparable effects on lipid parameters in patients with FDL and FHTG. Because of additional beneficial effects on hemorrheological parameters, fenofibrate may be preferred for the treatment of FDL.
Adult↗