Clopidogrel versus Acetylsalicylsäure in der Sekundärprophylaxe vaskulärer Erkrankungen

Ohne Zusammenfassung     

13C-ethanol and 13C-acetate breath tests in normal and aldehyde dehydrogenase deficient individuals

Four normal and five aldehyde dehydrogenase (ALDH) isozyme I deficient individuals were subsequently loaded with (1-13C)ethanol and (1-13C)sodium acetate and the conversion of the label to 13CO2 was determined in expired air by isotope ratio mass spectrometry. In the 13C-acetate breath test, both groups showed virtually identical recovery of the label in expired air, namely 48.5 +/- 2.3% (mean +/- S.D.) for normal and 46.8 +/- 5.7% for deficient individuals. However, in the 13C-ethanol breath test, both the groups performed differently. On average, although a certain overlap of the single data was observed, the recovery of the label after four hours was 43.4 +/- 3.8% for the normal and 35.6 +/- 6.8% for the ALDH deficient subjects. These findings suggest a slower conversion of ethanol to carbon dioxide in aldehyde dehydrogenase deficient individuals, which may be another consequence of this deficiency besides the higher plasma acetaldehyde levels observed after ethanol loading in comparison to individuals with normal aldehyde dehydrogenase activity.     

Use of a computer-based health risk appraisal by older adults

BACKGROUND. A health risk appraisal (HRA) is a tool for health promotion. Conversational microcomputer-based HRAs may be more cost effective than other HRA formats. The acceptability of conversational HRAs, however, has not been demonstrated for older adults. METHODS. We studied the acceptability of a conversational microcomputer-based HRA in a sample of 247 adults at the Minnesota State Fair and the Senior Options Exposition. All users were offered the appraisal via mouse or keyboard interface. Acceptability was measured in terms of user-reported helpfulness, intent to change, time of use, and willingness to view HRA health recommendations. Data on completion time and willingness to view HRA recommendations were collected for Senior Exposition users only. Regression analyses were used to examine the combined impact of interface (mouse or keyboard), location (State Fair or Senior Exposition), age, and sex on user acceptability. Results. Interface and location had no effect on helpfulness or change ratings. Older users rated the appraisal more helpful (P less than .007). Both older and female users reported more intent to change behavior (P = .016, both). Time to use the appraisal was related to interface, age, and sex. Mouse users (P less than .0001), older users (P less than .0001) and female users (P less than .05) took significantly longer to use the appraisal. Significantly more mouse users declined to see recommendations (P less than .02). CONCLUSIONS. Older users can derive as much or more value from conversational health risk appraisals as younger users; however, a mouse interface may be less effective for this age group.     

Minimally Invasive Coronary Artery Bypass Grafting: A New Method Using an Anterior Mediastinotomy

The benefit of internal mammary artery (IMA) grafting as a long-lasting intervention for coronary artery disease is well recognized. However, largely because they are less invasive, catheter based alternatives are frequently chosen, particularly to treat single or double vessel disease. To retain the advantages of the IMA graft, and to offset the invasiveness of conventional coronary artery bypass grafting, we developed a new minimally invasive method using an anterior mediastinotomy for treating left anterior descending (LAD) or right coronary artery disease, or both. Feasibility studies using 16 pigs and a human cadaver led to approval by the Institutional Review Board for use of this procedure to treat six patients (four men, two women; mean age, 63.8 ± 13.6 [SD] yrs) who granted informed consent. Pedicle dissection of the IMA, using video assisted thoracoscopy if necessary, was made through a 2-to 3-inch horizontal anterior mediastinotomy. The underlying LAD artery was grafted during femoral vessel cardiopulmonary bypass, with cooling to 30°C, induced ventricular fibrillation, and left ventricular venting if required. Transesophageal echocardiography performed after bypass showed that two patients maintained normal wall motion and four had improvement from the original impairment. One patient suffered a recurrence of angina 4 weeks after the procedure; recatheterization showed an acutely angled IMA, subsequently corrected by balloon angioplasty. The results of follow-up dobutamine echocardiographic stress tests were negative in all patients. With this minimally invasive approach, the procedure should provide the benefits of IMA grafting with shorter hospital stay, more rapid recovery, and less overall cost.     

Laser placement in noncontact Nd:YAG cyclophotocoagulation

We treated 40 eyes of 40 patients by using noncontact transscleral Nd:YAG cyclophotocoagulation to determine whether treatment 1.5 or 3.0 mm posterior to the corneoscleral lumbus was preferable. Patients were randomly assigned to one of the treatment groups, and all other variables, including power, number, and distribution of laser applications, were kept constant. Six months postoperatively, those treated 1.5 mm posterior to the corneoscleral limbus had a lower intraocular pressure (P = .0047) than those treated 3.0 mm from the corneoscleral limbus. The 1.5-mm group also required fewer retreatment (P = .017) and had a slightly lower occurrence of visual acuity loss after this procedure. We believe it may be advantageous to locate the laser application approximately 1.5 mm posterior to the corneoscleral limbus, rather than further posteriorly, when performing noncontact transscleral Nd:YAG cyclophotocoagulation.     

MAO-A inhibition in brain after dosing with esuprone, moclobemide and placebo in healthy volunteers: in vivo studies with positron emission tomography

Objective: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. Methods: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined␣with positron emission tomography (PET) with [¹¹C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide, and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7, one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning dose on day 7. Results: PET showed a high degree of binding of [¹¹C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point. In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about 4 h. Conclusion: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination of dosing intervals. Received: 21 August 1996 / Accepted in revised form: 22 November 1996     

Pre-clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic control in obese diabetic patients

OBJECTIVE Autonomous cortisol secretion without clinical stigmata of Cushing's syndrome (CS) has been recently recognized and termed pre-clinical or sub-clinical CS. The common assumption is that CS is an extremely rare cause of uncontrolled diabetes; however, the prevalence of this entity has not been studied. We assessed the prevalence of pre-clinical CS among obese patients with uncontrolled diabetes. PATIENTS AND DESIGN (1) In a retrospective analysis, the medical records of 63 patients with endogenous CS were reviewed. (2) In a cross-sectional study, 90 obese patients (BMI >25 kg/m²) followed in a University Hospital and the local Health Fund endocrine and diabetes clinics, with poorly controlled diabetes (glycosylated haemoglobin >9%), underwent an overnight 1 mg dexamethasone suppression. In patients with non-suppressible cortisol levels (>140 nmol/l), Liddle's 2 and 8 mg dexamethasone suppression tests and imaging studies were performed. MEASUREMENTS The prevalence of poorly controlled diabetes, the major presenting symptom of CS, was assessed in the retrospective analysis. The prevalence of ‘true’ CS and the false positive rate in the overnight dexamethasone suppression test were calculated. The endocrine evaluation of the patients with pre-clinical CS and the effects of surgical cure on glycaemic control are described. RESULTS In the retrospective analysis, 11 (17.5%) had diabetes and 2 (3.2%) lacked the classic physical characteristics of the syndrome. In the cross-sectional study, 4 patients failed to suppress plasma cortisol (<140 nmol/l). In one patient the diagnosis of CS was not confirmed by a standard Liddle’s test and was therefore considered false positive. In the other 3, the diagnosis of CS was confirmed (prevalence of 3.3%, 95% confidence interval 1–9%). In all other patients the overnight cortisol suppression test was normal (cortisol level 47.3 ± 2.5 nmol/l (mean ± SEM)). After surgical treatment of CS, glycaemic control was markedly improved in all 5 patients (2 from retrospective and 3 from cross-sectional studies). CONCLUSIONS The prevalence of pre-clinical Cushing's syndrome in obese patients with poorly controlled diabetes appears to be considerably higher than previously believed. The overnight dexamethasone suppression test proved to be a simple, sensitive and highly specific screening test for Cushing's syndrome despite the presence of obesity and hyperglycaemia.     

Evidence for nitric oxide participation in down-regulation of CYP2B1/2 gene expression at the pretranslational level

Septic or inflammatory stimuli suppress drug metabolism by cytochrome P-450 in the liver, presumably at the pretranslational level. We have shown previously that nitric oxide is responsible at least in part for the inhibition by bacterial lipopolysaccharide of phenobarbital-induced CYP2B1/2 activity in vivo. This was attributed to the interaction of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report that endogeneous nitric oxide also contributes to LPS-induced suppression of CYP2B1/2 in vivo by down-regulating the expression of CYP2B1/2 protein and mRNA.     

A novel technique of ab interno glaucoma surgery: follow-up results after 24 months

Purpose It was the aim of this study to investigate the efficacy, longevity, and safety of a new ab interno intervention for the treatment of primary open-angle glaucoma (POAG). Methods The previously described method of radiofrequency-mediated “sclerothalamotomy ab interno” was applied in 53 eyes of consecutive patients with POAG between April 2002 and July 2002. Average preoperative intraocular pressure (IOP) was 25.6±2.3 mmHg (range 18–48 mmHg). Sclerothalamotomies were carried out with a custom-made high-frequency dissection 19 G probe (tip 0.3×1 mm) applying bipolar current with a frequency of 500 kHz (tip temperature 130°C). Results After a follow-up period of 24 months, the average IOP was 15.0±1.6 mmHg (range 11–20 mmHg) (p<0.005). The average number of topical agents was 2.6±1.0 (range 1–5) preoperatively. Twenty-four months after surgery such agents were used in only five (9.6%) eyes and the average was 0.21±0.53 (range 0–2). Transient IOP elevation was observed in 12 of 53 eyes (22.6%) postoperatively. In all cases elevated IOP could efficiently be controlled with topical medication. In general, IOP dropped continuously over the course of the 6 months following surgery and then remained constant. Conclusions This study indicates that sclerothalamotomy ab interno is a safe and efficient surgical method for the treatment of POAG. Long-term results clearly demonstrate the longevity of IOP reduction.