[Inhibition of thrombocyte aggregation as a therapeutic principle. Review of the literature and currently approved thrombocyte aggregation inhibitors].
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Clinical Trials as Topic↗
Biomedical subjects
K Huber
Publications and source records attributed to K Huber.
Comparative studies on Na-dependent Pi transport in ovine, caprine and porcine renal cortex.
In contrast to monogastric species, renal excretion of inorganic phosphate (Pi) in ruminants is low and this could be attributed to an almost complete tubular Pi reabsorption. However, the functional and regulatory basis for this phenomenon has not yet been clarified. Therefore, it was the aim of the present study to characterize the kinetic parameters of the tubular Pi reabsorption system as affected by P or Ca depletion using preparations of renal cortex brush border membrane vesicles (BBMV) from goats and sheep and to compare the data with respective parameters of porcine preparations. Na-dependent Pi uptake into renal cortex BBMV as a function of Pi concentration showed typical Michaelis-Menten kinetic and respective Scatchard plot analysis of the specific Pi uptake revealed linearity indicating the predominant presence of a single type of Pi transporters in the preparations. Under control conditions Vmax values of Na-dependent Pi uptake into BBMV were highest in goats and sheep and lowest in pigs (1.98, 1.39 and 0.95 nmol x mg(-1) protein x 10s(-1), respectively). Km values were not different between goats and sheep under all feeding conditions and ranged from between 0.34 mmol x l(-1) and 0.55 mmol x l(-1) which was three- to five-times higher than that found in pigs (0.11 mmol x l(-1)). Oligonucleotides derived from rat kidney cortex type IIa Na/Pi cDNA were used for reverse transcriptase-polymerase chain reaction (RT-PCR) in goat, sheep and pig kidney cortex. The products isolated were 768 bp for sheep and pigs and 765 bp for goats, with the respective amino acids sequences, representing a segment of approximately 40% in length of the entire transporter, exhibiting an at least 92% sequence homology between different species. From the results, involvement of type IIa Na/Pi cotransport in tubular Pi reabsorption in small ruminants can be postulated. However, it should not be considered that a potential role of other Pi transport systems be completely be excluded. Interestingly, neither P nor Ca depletion caused significant effects on Na-dependent Pi transport capacities and affinities in goats and sheep. From this, parathyroid-hormone independent regulatory pathways of tubular Pi reabsorption can be assumed.
Animals↗
Effects of vitamin E on chronic and acute endothelial dysfunction in smokers.
OBJECTIVES: The aims of this study were to determine whether chronic or acute impairment of flow mediated vasodilation (FMD) in the brachial artery of smokers can be restored or preserved by the antioxidant vitamin E. BACKGROUND: Transient impairment of endothelial function after heavy cigarette smoking and chronic endothelial dysfunction in smokers result at least in part from increased oxidative stress. METHODS: We studied 22 healthy male smokers (mean +/- SD, 23 +/- 9 cigarettes per day) randomly assigned to receive either 600 IU vitamin E per day (n = 11, age 28 +/- 6 years) or placebo (n = 11, age 27 +/- 6 years) for four weeks and 11 age-matched healthy male nonsmokers. Flow mediated vasodilation and endothelium-independent, nitroglycerin-induced dilation were assessed in the brachial artery using high resolution ultrasound (7.5 MHz) at baseline and after therapy. Subjects stopped smoking 2 h before the ultrasound examinations. At the end of the treatment period, a third scan was obtained 20 min after smoking a cigarette (0.6 mg nicotine, 7 mg tar) to estimate transient impairment of FMD. RESULTS: Flow mediated vasodilation at baseline was abnormal in the vitamin E (5.3 +/- 3.8, p < 0.01) and in the placebo group (6.4 +/- 3.5, p < 0.05) compared with nonsmoking controls (11.6 +/- 4.7). Using a two-way repeated measures analysis of variance (ANOVA) to examine the effects of vitamin E on FMD, we found no effect for the grouping factor (p = 0.5834) in the ANOVA over time but a highly significant difference with respect to time (p = 0.0065). The interaction of the time factor and the grouping factor also proved to be significant (p = 0.0318). Flow mediated vasodilation values remained similar after treatment for four weeks in both groups but declined faster after smoking a cigarette in subjects taking placebo compared with those receiving vitamin E (p values from successive differences for the time/group factor: 0.0001/0.0017). The transient attenuation of FMD (calculated as the percent change in FMD) was related to the improvement of the antioxidant status, estimated as percent changes in thiobarbituric acid-reactive substances (r = -0.67, p = 0.0024). Nitroglycerin-induced dilation did not differ between study groups at baseline or after therapy. CONCLUSIONS: These results demonstrate that oral supplementation of vitamin E can attenuate transient impairment of endothelial function after heavy smoking due to an improvement of the oxidative status but cannot restore chronic endothelial dysfunction within four weeks in healthy male smokers.
Adult↗
Grocery list for people on hemodialysis! (Food your patients CAN eat).
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Beverages↗
The decanucleotide polymorphism in the factor VII promoter predicts factor VII plasma levels but not the risk of acute coronary syndromes.
It is known from large epidemiological studies that the elevation of coagulation factor VII in plasma is an independent risk factor for acute coronary syndromes. The level of factor VII is influenced by polymorphic sites in the factor VII gene. However, data on the association of such polymorphisms with the risk of acute coronary syndromes are conflicting. A decanucleotide insertion/deletion polymorphic site has been described in the promoter of the factor VII gene that leads to a dramatic change in the plasma factor VII levels. We therefore analyzed the association of this polymorphism with the risk of acute coronary syndromes in a case-control study. Included in the study were 111 patients with angiographically documented acute coronary syndromes and 108 age- and sex-matched individuals from the same geographic area without signs or symptoms of coronary heart disease. The presence or absence of the decanucleotide stretch at position -323 in the promoter of factor VII was monitored using a polymerase chain reaction (PCR)-based restriction technique. The prevalence of the genotype with the homozygous deletion was similar in the patients with acute coronary syndromes (79.2%) and in the control patients (79.6%). There was a non-significant trend toward a higher prevalence of the homozygote deletion in patients with premature acute coronary syndromes (77.4%) compared with an age-matched subgroup of the control patients (67. 5%) (odds ratio [OR] 1.6, confidence interval [CI] 0.95, 0.61-3.93). Thus, we could not find a significant association of the occurrence of acute coronary events with the insertion/deletion polymorphism in factor VII.
Acute Disease↗
The TETAMI trial: the safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and of tirofiban versus placebo in the treatment of acute myocardial infarction for patients not thrombolyzed: methods and design.
Patients with acute myocardial infarction (AMI) who do not receive early reperfusion therapy are at high risk of reinfarction or death, and the efficacy and safety of antithrombotic therapy in this group of patients has not been evaluated. Enoxaparin is a low-molecular-weight heparin (LMWH) that has previously been shown to reduce the incidence of ischemic events in patients with unstable angina or non-Q-wave MI. The principal aims of the TETAMI study are to investigate the efficacy and safety of treatment with enoxaparin or tirofiban (a glycoprotein IIb/IIIa receptor antagonist) alone or in combination for 2 to 8 days in patients with AMI who are not eligible for early reperfusion therapy. In this 2 by 2 factorial design study approximately 900 patients will be randomly assigned, in a blinded manner, to one of four treatments: enoxaparin alone, enoxaparin plus tirofiban, unfractionated heparin (UFH), or UFH plus tirofiban, with appropriate matched placebos. The primary end point is the composite of death, recurrent AMI, and recurrent angina, analyzed at 30 days after AMI. The design and methods of the TETAMI study are described in this article.
Adult↗
Effects of the 5-HT3 antagonist cilansetron vs placebo on phasic sigmoid colonic motility in healthy man: a double-blind crossover trial.
AIMS: 5-hydroxytryptamine3 receptor antagonists act antiemetically and slow colonic transit. This study evaluated effects of the high-affinity 5-HT3 antagonist, cilansetron, on fasting, meal-and anticholinesterase-stimulated phasic contractile activity of the human sigmoid colon as well as on bowel habits and stool consistency. METHODS: Five female and seven male healthy volunteers received, during three 7 day periods separated by 7 day wash-out periods, 4 mg cilansetron, 8 mg cilansetron or placebo three times daily orally under random, double-blind, crossover conditions. On day 8 of each treatment period, motility 20-40 cm from the anal verge was recorded using five pressure sensors spaced at 5 cm intervals. After a basal 30 min, subjects swallowed a further dose of the scheduled treatment; 60 min later, blood was taken for the determination of plasma cilansetron levels. Thereafter, subjects ingested a 4200 kJ meal and 250 ml sweetened mallow tea (166 kJ); 90 min after meal onset, 1 mg neostigmine was administered intramuscularly and motility recording was continued for 60 min RESULTS: Phasic contractile activity and intraluminal base-line pressure increased postprandially and more so after neostigmine. With cilansetron, the area under the pressure curve as the primary outcome variable and the number of contractions were significantly greater than with placebo (P = 0.005), amplitude and duration of contractions and base-line pressure were not affected. The effects of the two cilansetron dosages did not differ. With cilansetron, stool tended to become firmer. No adverse effects were observed. Plasma levels were highest with 8 mg cilansetron. CONCLUSIONS: Cilansetron slightly augments meal-stimulated and markedly neostigmine-stimulated phasic motility of the sigmoid colon. When administered over 7 days, it tends to increase stool consistency and is well tolerated.
Adult↗
The association between C-reactive protein on admission and mortality in patients with acute myocardial infarction.
OBJECTIVE: In patients presenting with acute myocardial infarction the pathophysiologic and prognostic value of serum C-reactive protein is not well defined. This study assessed the association between serum C-reactive protein levels on admission and mortality in patients admitted because of acute myocardial infarction. DESIGN: Retrospective cohort study. SETTING: Tertiary care centre. PATIENTS: A total of 729 patients with acute myocardial infarction admitted within a period of 3 years. MAIN OUTCOME MEASURES: C-reactive protein levels on admission, cardiovascular risk factors and survival within the observational period. RESULTS: Within the 3-year observational period, 118 patients died of a cardiovascular cause. With increasing serum C-reactive protein levels (<0.5, 0.5 to <2, 2 to <5, 5-10 and >10 mg dL-1) mortality also increased (14%, 19%, 20%, 39% and 28%, respectively). When controlling for the confounding effect of age, thrombolytic treatment, the time interval between onset of pain and admission, smoking, diabetes mellitus, hypercholesterolemia, hypertension, and elevated creatine kinase on admission in a multivariate Cox regression model, there was only a weak and nonsignificant association between increased serum C-reactive protein and the risk of death. CONCLUSIONS: Patients with elevated concentrations of serum C-reactive protein admitted to the hospital because of acute myocardial infarction are at an increased risk of dying. This association is however, largely explained by other baseline variables, in particular by an estimate of the duration of myocardial ischaemia. If C-reactive protein measured by means of an ultra-sensitive assay is more suitable for risk stratification of unselected patients with acute myocardial infarction, needs further study.
Aged↗
Plasma levels of C-reactive protein after coronary stent implantation.
AIMS: This study was designed to investigate the role of inflammation on the occurrence of angiographic restenosis 6 months after coronary stent implantation and the influence of different kinds of antithrombotic and antiplatelet strategies on inflammation. METHODS AND RESULTS: In an open randomized trial, 40 consecutive patients were treated with aspirin (100 mg. day(-1)) and either ticlopidine (2x250 mg. day(-1)) (n=17), or phenprocoumon (INR 2.0-3.0) and dipyridamole (3x160 mg. day(-1)) (n=23) after successful elective coronary stent implantation. Plasma levels of C-reactive protein were determined one day before stent implantation and serially thereafter twice daily up to 120 h. C-reactive protein plasma levels increased significantly (P<0.0001) after stent implantation. Phenprocoumon and dipyridamole or ticlopidine had no effect on C-reactive protein plasma levels (P=0.51) or the occurrence of angiographic restenosis (P=0.48). C-reactive protein plasma levels were significantly higher in patients with lesion type C compared to types A or B (P=0.035), respectively. C-reactive protein plasma levels were significantly higher and mean shoulder levels occurred 48 h later in patients with restenosis compared to patients without restenosis after 6 months (P=0.038). CONCLUSIONS: Elevated C-reactive protein plasma levels still persisting 96 h after stent implantation might reflect a prolonged inflammatory reaction to coronary stent implantation which might causally be involved in pathophysiological mechanisms leading to restenosis.
Angioplasty, Balloon, Coronary↗
Soluble selectins and the systemic inflammatory response syndrome after successful cardiopulmonary resuscitation.
OBJECTIVE: Elevated cytokine levels have been reported after ischemia/reperfusion injury and might cause a systemic inflammatory response syndrome (SIRS) after successful cardiopulmonary resuscitation (CPR). It is unknown whether patients with SIRS after CPR exhibit higher levels of soluble adhesion molecules than patients without SIRS and whether SIRS or elevation of adhesion molecules is associated with outcome after CPR. We analyzed the relationships among various CPR-related variables, plasma levels of E- and P-selectin, the occurrence of SIRS after CPR, and the development of sepsis and outcome. DESIGN: Prospective, controlled study. SETTING: Intensive care unit at a university hospital. PATIENTS: A total of 25 patients on the second day after successful CPR and 7 non-critically ill control patients. INTERVENTIONS: Blood sampling for determination of plasma levels of soluble (s) E- and P-selectin. MEASUREMENTS AND MAIN RESULTS: SIRS was a frequent finding after CPR (66% of all patients) unrelated to time until return of spontaneous circulation (SIRS, 17+/-13 mins; no SIRS, 19+/-16 mins; p = .761), epinephrine dose (SIRS, 4+/-5 mg; no SIRS, 5+/-6 mg; p = .906), or serum lactate level after CPR (SIRS, 8.6+/-2.6 mmol/L; no SIRS, 8.7+/-4.0 mmol/L; p = .174). sP-selectin levels were higher in patients with SIRS (291.7+/-227.4 ng/mL) compared with patients without SIRS (113.4+/-88.4 ng/mL; p = .018) or with non-critically ill patients (116.9+/-33.4 ng/mL; p = .031). Compared with non-critically ill control patients (42.8+/-19.4 ng/mL), sE-selectin levels were higher in patients with (96.2+/-47.3 ng/mL; p = .023) and without SIRS (99.5+/-65.7 ng/mL; p = .030). sP-selectin was higher in patients developing sepsis within 1 wk after CPR (n = 9) than in patients without sepsis (350.2+/-233.4 ng/mL vs. 158.5+/-157.8 ng/mL; p = .022) and sE-selectin levels were higher in nonsurvivors (n = 5) than in survivors (144.2+/-62.4 ng/mL vs. 85.7+/-45.3 ng/mL; p = .025) whereas SIRS was unrelated to the development of sepsis (p = .4) and unrelated to survival (p = .4). CONCLUSIONS: SIRS is an unspecific finding after CPR with only minor impact on outcome. Determination of sP- and sE-selectin early after CPR might help to identify patients at a high risk for sepsis or for an adverse outcome, respectively.
Adult↗
A modular software system for computer-aided surgery and its first application in oral implantology.
Development of complex software applications in image guided therapy (IGT) is often complicated by the fact that providing basic functionality for image processing and user interaction from a graphical user interfaces (GUI) requires considerable manpower for software development. We present a programming environment that combines the high-level image processing library AVW, in-house developed patient-to-image registration procedures, and an interface to position measurement hardware. A specific application can be developed by using Tcl/Tk, a simple platform-independent scripting language, for GUI development. This environment was applied to developing VISIT, a navigation system for computer-aided implant dentistry. VISIT is presented as a result of this paper. Parts of the development environment were made accessible to the public. Future work includes the implementation of video input for connecting ultrasound or fluoroscopy units. We conclude that our approach is well suited to accelerate the development of exploratory new applications of IGT.
Dental Implantation↗
Epithelial phosphate transporters in small ruminants.
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Animals↗
Thrombolytic therapy in acute myocardial infarction.
Early reperfusion of thrombotically occluded coronary arteries by thrombolytic therapy has become a routine option in initial therapy of acute myocardial infarction. Many efforts have been made to improve the biological properties of thrombolytic agents in terms of fibrin specificity, plasma half-life and resistance to natural plasma inhibitors, to improve adjuvant therapy and to shorten the 'pain to reperfusion' time. Numerous randomised, multicentre trials have analysed the benefit of the various thrombolytic agents and regimens, which has enabled the creation of a 'current standard of therapy'. This review presents an update on available thrombolytic agents, their biochemical and pharmacological properties and results from clinical trials.
Adjuvants, Pharmaceutic↗
[Rotavirus gastroenteritis in infants and children. Results of a prospective study in the area of Geneva and Basel 1997/1998 (RoMoS). RoMoS Study Group].
BACKGROUND: In Europe information is scarce about the impact of rotavirus, probably the most important cause of acute gastroenteritis in children up to the age of 4 years. The aim of this study was to collect data on the frequency and symptoms of community-acquired rotavirus-positive acute gastroenteritis in Switzerland. PATIENTS AND METHODS: In 6 paediatric practices, 3 each in the Geneva and Basle areas, every child up to the age of 48 months presenting with acute gastroenteritis between December 1997 and May 1998 was eligible for inclusion in the study. The symptoms, course of the disease and treatment were recorded in a standardized fashion after informed consent had been obtained. Stool specimens were screened for rotavirus by ELISA, and PCR was performed for serotyping in ELISA-positive samples. RESULTS: 294 of 6672 children under observation were taken to their paediatrician because of acute gastroenteritis during the study period. Informed consent was obtained in 256 cases (mean age 19.2 months). 234 stool specimens were available of which 96 (41%) were rotavirus-positive. The incidence of rotavirus-positive acute gastroenteritis was 1.6 per 100 children and winter season. Acute gastroenteritis due to rotavirus was more severe than rotavirus-negative acute gastroenteritis, with diarrhoea and vomiting in 84% versus 54%, and dehydration in 42% versus 28%, 5% of the acute gastroenteritis cases compared to 11% of the rotavirus-positive cases were hospitalized. In the Geneva and Basle areas the predominant rotavirus types, as identified by PCR in ELISA-positive stool specimens, were G4 P[8] and G1 P[8] respectively (67% each). CONCLUSION: Rotavirus infection was a relevant cause of acute gastroenteritis in our study population, resulting in more severe symptoms than rotavirus-negative acute gastroenteritis. All G-types identified in our study are included in the recently developed tetravalent vaccine. Cost-benefit analysis and ethical issues will need to be considered in evaluating the impact of the vaccine in Switzerland.
Child, Preschool↗
The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro.
Although erythropoietin (Epo) is essential for the production of mature red blood cells, the cooperation with other factors is required for a proper balance between progenitor proliferation and differentiation. In avian erythroid progenitors, steroid hormones cooperate with tyrosine kinase receptors to induce renewal of erythroid progenitors. We examined the role of corticosteroids in the in vitro expansion of primary human erythroid cells in liquid cultures and colony assays. Dexamethasone (Dex), a synthetic glucocorticoid hormone, cooperated with Epo and stem cell factor to induce erythroid progenitors to undergo 15 to 22 cell divisions, corresponding to a 10(5)- to 10(6)-fold amplification of erythroid cells. Dex acted directly on erythroid progenitors and maintained the colony-forming capacity of the progenitor cells expanded in liquid cultures. The hormone delayed terminal differentiation into erythrocytes, which was assayed by morphology, hemoglobin accumulation, and the expression of genes characteristic for immature cells. Sustained proliferation of erythroid progenitors could be induced equally well from purified erythroid burst-forming units (BFU-E), from CD34(+) blast cells, and from bone marrow depleted from CD34(+) cells.
Adult↗
Primary PTCA versus thrombolysis with tPA in acute myocardial infarction: a formal cost-effectiveness analysis.
AIMS: Information concerning the cost-effectiveness of primary percutaneous transluminal coronary angioplasty (PTCA) compared to thrombolytic treatment with tissue plasminogen activator (tPA) for the management of acute myocardial infarction (AMI) is limited. The existing data are derived from studies using a wide range of intervention, re-intervention and a high rate of mortality. The present study examined the cost-effectiveness of primary PTCA compared to thrombolytic treatment with tPA in the setting of AMI by applying data from published prospective randomised studies. METHODS AND RESULTS: We performed a formal cost-effectiveness analysis. As estimates for "cost" of therapy we applied the reimbursement paid by the public health insurance organisations in Austria. Coronary intervention rates and re-intervention rates were extracted from published studies. Assuming a moderately reduced in-hospital mortality for patients treated with primary PTCA (4.8%) compared to tPA (6.6%) on the basis of AMI in a 60-year-old male, the estimated additional cost per life saved was 274.-ECU (95% confidence interval 231.- to 318.-ECU). However, the cost per life saved was sensitive to the given range of intervention and re-intervention rates (range 2,518.-ECU gain to 9,560.-ECU additional cost). CONCLUSIONS: Assuming a moderate in-hospital survival benefit from treatment with primary PTCA in patients with AMI, PTCA seems to be cost effective in comparison to treatment with tPA--at least from the perspective of cost reimbursement by public health insurance organisations.
Angioplasty, Balloon, Coronary↗
Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphism in coronary disease and malignant ventricular arrhythmias.
OBJECTIVES: It has been reported that patients carrying the angiotensin-converting enzyme (ACE) deletion DD genotype with the angiotensin II type 1 (AT1) C allele are at increased risk for myocardial infarction. The frequency distribution of the ACE and AT1 receptor gene polymorphism and their possible relation regarding malignant ventricular arrhythmias in patients with coronary artery disease (CAD) and left ventricular dysfunction was determined. METHODS: The ACE I/D and AT1 A/C polymorphisms (using polymerase chain reaction) in 100 Caucasian patients suffering from CAD with a history of malignant ventricular arrhythmias treated with an implantable cardioverter defibrillator (ICD group) was compared to 127 age-matched Caucasian patients with CAD and no history of malignant ventricular arrhythmias (control group). All patients had reduced left ventricular ejection fraction of < 40% and were comparable regarding sex distribution, body mass index, ACE-inhibitor treatment, lipid status and duration of CAD. RESULTS: The prevalence of DD/CC in the ICD group was significantly higher (19% versus 10%, p < 0.0001). The risk for malignant ventricular arrhythmias was associated with the combination of ACE D and AT1 C alleles (odds-ratio: 2.4, 95% confidence interval 1.41 to 3.94, p < 0.001). The distribution of ACE and AT1 genotypes was not different between the two group. CONCLUSIONS: Patients with coronary artery disease and left ventricular dysfunction carrying ACE D and AT1 C alleles are at increased risk for development of malignant ventricular arrhythmias. Because of available pharmacological inhibitors, these results may have clinical implications for the prevention of sudden cardiac death.
Aged↗
Positioning of dental implants using computer-aided navigation and an optical tracking system: case report and presentation of a new method.
A navigation system for computer-aided surgery (Virtual Patient System, VPS) has been described in previous studies for different indications in oral and maxillofacial surgery. The aim of the system is the intraoperative transfer of preoperative planning on radiographs or CT scans on the patient, in real-time, and independent of the position of the patient's head. Until now an electromagnetic tracking system has been used for intra-operative position measurement. For placement of dental implants, the electromagnetic tracking system is not suitable since the motor of the implant drill leads to a considerable distortion of the magnetic field, thus direct visualization of drilling the implant socket was not possible. To overcome this problem, an optical tracking system which is not disturbed by conductive materials was integrated in the VPS system. The first patient operated on with this system had a posttraumatic loss of the upper incisors; three implants have been placed according to the prosthetic axis previously planned on radiographs and CT scans. The experience gained in this intervention led to the conclusion that computer-aided surgery provides a valuable tool in implant dentistry.
Adult↗