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Biomedical subjects

A Kleemann

Publications and source records attributed to A Kleemann.

9 recordsLinked to original sources

Effects of lovastatin on progression of non-dilated and dilated coronary segments and on restenosis in patients after PTCA. The cholesterol lowering atherosclerosis PTCA trial (CLAPT).

OBJECTIVES: The Cholesterol Lowering Atherosclerosis PTCA Trial (CLAPT) is a prospective, randomized trial with blinded angiographic end-points to assess the effect of 2-year's treatment with lovastatin initiated 4 weeks prior to PTCA, compared to usual care on non-dilated coronary segments and on dilated coronary lesions in male patients with total cholesterol between 200 and 300 mg. dl(-1)who underwent elective PTCA. METHODS AND RESULTS: Two hundred and twenty six patients were randomized 4 weeks prior to PTCA to special care (diet plus lovastatin n=112) or usual care (diet; n=114). One hundred and ninety-nine patients underwent PTCA at baseline and were finally included in the study. Quantitative coronary angiographic assessment was performed on blinded cinefilms at baseline (PTCA) and repeated after 4 and 24 months in 91% and 81% of the patients. The primary end-point was a change in the mean segment diameter of non-dilated segments. The mean lovastatin dose was 33 mg. day(-1). Total- and LDL-cholesterol decreased by 21% and 29% in the special care group and by 7% and 11% in the usual care patients. After 2 years, the mean segment diameter of non-dilated segments decreased by 0.03 mm in the usual care group and 0.004 mm in the special care group (P=0.27). The decrease in the mean segment diameter of dilated lesions was 0.17 mm (usual care) and 0.06 mm (special care) (P=0.04) after 4 months; 0.16 mm (usual care) and 0. 002 mm (special care) after 24 months, respectively (P=0.05). In both groups, the mean segment diameter of dilated lesions increased between 4 and 24 months after PTCA compared to a decrease in mean segment diameter of non-dilated segments (P<0.05). Restenosis (>50% diameter stenosis at follow-up) occurred in 28.4% of usual care and 22.2% of special care patients (P=0.17). CONCLUSIONS: Lovastatin reduced the progression of dilated lesions in men with elective PTCA. Independent of treatment allocation, the dilated lesions regressed and the non-dilated segments progressed during the study follow-up. Four weeks of pre-treatment with lovastatin did not influence the rate of restenosis. Lovastatin had no statistically significant effect on non-dilated segments.

Angioplasty, Balloon, Coronary↗

Failure to confirm ferritin and caeruloplasmin as risk factors for the angiographic extent of coronary arteriosclerosis.

BACKGROUND: It has been suggested that iron overload, as assessed by increased serum ferritin concentration, may be a risk factor for coronary artery disease (CAD). Recent studies have reported conflicting data on the role of ferritin and other parameters of oxidative metabolism in CAD. OBJECTIVE: The aim of this study was to assess the relation between the extent of CAD and parameters of oxidation. METHODS: We studied 275 patients (208 men aged 55.1 +/- 9.6 years and 67 women aged 54.6 +/- 10.0 years) who underwent coronary angiography or percutaneous transluminal coronary angioplasty for the first time. The parameters assessed were: iron, ferritin, transferrin, copper, caeruloplasmin and lipid. Cinefilms were assessed by the use of three scores: (1) Vessel score: 0-3 points; 1 point for each of the three main coronary arteries with a stenosis >70%. (2) Stenosis score: 0-32 points; the coronary artery tree was divided into eight segments that were scored 1-4 points per segment with respect to the maximal degree of stenosis. (3) Extent score: 0-100 points; extent of diffuse coronary lesions in each segment in relation to the length of the vessel. Multiple regression analyses were used to evaluate the results. RESULTS: Total cholesterol and low-density lipoprotein cholesterol (P < 0.001) in women, low-density lipoprotein cholesterol (P < 0.05) in men, and patient age showed a significant correlation with all three scores, but none of the parameters of oxidative metabolism (iron, transferrin, ferritin, copper, caeruloplasmin) correlated significantly with any of the three scores. CONCLUSION: This study demonstrated a correlation between lipoproteins and the angiographic extent of CAD, but did not confirm a role for serum ferritin and other oxidative parameters as risk factors for the extent of CAD.

Adult↗

[Quality comparison of modified neurolept-, balanced and intravenous anesthesia. 1. Study design and patient analysis of the Krefelder study 1992].

The choice of appropriate anaesthesia in a more or less seriously ill patient requires detailed information on the risk and tolerance of each specific anaesthetic regimen. The objective of this prospective, randomised clinical trial was to test the hypothesis that three regimens of general anaesthesia--neurolept-(NLA), balanced (BAL), and intravenous propofol anaesthesia (IVA)--differ with regard to safety and comfort. The criteria for the intraoperative safety and postoperative comfort of the patients were the incidents, events and complications (IEC) that required medical treatment as well as the evaluation of postoperative complaints by the patients according to the IEC list and patient questionnaires of the German Society of Anaesthesia and Critical Care Medicine (DGAI). METHODS. The study duration was about 4 months, from January to April 1992. During this period the patients of all nine operative departments of the hospital received strictly randomised NLA, BAL, or IVA. Patients who had regional anaesthesia or were not capable of understanding the German language, were nonco-operative, or were seriously ill (ASA class IV to V) as well as children under 18 years of age did not participate in the study. All eligible patients provided their informed consent. ANAESTHESIA. For premedication 10 mg chlorazepate was administered the night before and on the day of surgery. Anaesthesia was conducted under normoventilation using a mixture of 70% nitrous oxide and 30% oxygen. NLA patients were induced intravenously with 0.2 mg/kg body weight etomidate and received 0.005 mg/kg fentanyl and 0.07 mg/kg droperidol before the start of surgery. The repetition dose was 0.2 mg fentanyl and 2.5 mg droperidol. In the BAL patients the dose of fentanyl and droperidol was reduced to 50% due to the addition of isoflurane up to 1 vol. %. IVA patients received 2 mg/kg propofol over 3 min followed by an infusion of 3-5 mg/kg per hour together with 0.2 mg fentanyl/h. Neuromuscular blockade was accomplished with vecuronium 0.1 mg/kg. If the blood pressure and heart rate increased by more than 20% of preoperative values, analgesia was reinforced by an additional fentanyl dose. Anaesthesia was subsequently enhanced by increasing the neurolept/propofol/isoflurane dose by up to 50%. DATA COLLECTION. The following parameters were registered: patients' personal data and physical condition according to ASA classification; the grade of risk according to the Munich risk checklist; the frequency of IEC during surgery; the patients' permanent medications; postanaesthetic vigilance and recovery; the acceptance of the assigned anaesthetic by the physician; the cost of the anaesthetic used; and pre- and post-operative complaints as well as the assessment of anaesthesia by the patient. The statistical evaluation was performed using the chi-square test. RESULTS. A total of 1,346 patients were enrolled in the study; 28 (2%) were excluded because the treatment protocol was changed by the anaesthesiologist. Seventy per cent were recruited from general, gynaecologic, or otorhinolaryngologic surgery. The three anaesthetic regimens (NLA, BAL, and IVA) were used in other departments with the same frequency with the exception of ophthalmology and urology (P > 0.1) (Fig. 1). Of the 1,318 eligible patients, 443 received NLA, 443 BAL, and 432 IVA (P = 0.8). The distribution of the various parameters was surprisingly similar among the three groups: the average age was 50 years (P = 0.91), body weight 71 kg (P = 0.33), reference or initial blood pressure 130/80 mm Hg (P = 0.36), average time of anaesthesia 103 min (P = 0.82), and all had the same risk score (P = 0.42). Sixty per cent were female. An average of 85% of the 18- to 89-year-old patients were considered to be healthy according to the ASA risk classification (P = 0.42). However, on applying the Munich risk checklist the average number of healthy individuals was 5% to 10% lower than that of the ASA risk classification.

Adolescent↗

[Qualitative comparison of modified neurolept-, balanced and intravenous anesthesia. 2. Results of a clinical study, 1992].

The safety and tolerance of neuroleptanaesthesia (NLA), balanced anaesthesia (BAL), and intravenous anaesthesia with propofol (IVA) were analysed for the first time in a prospective, randomised clinical trial. METHODS. In all, 1318 surgical patients received either NLA, BAL, or IVA. Patients who had regional anaesthesia, were aged under 18 years, or were non-cooperative or vitally threatened (ASA class i.v. to V) did not participate in the study. Premedication and anaesthetic course were set up at a standard of 30% oxygen and 70% nitrous oxide. Incidents, events, and complications due to anaesthesia were obtained (IEC key of the German Society of Anaesthesia and Critical Care Medicine, DGAI). Furthermore, postanaesthetic alertness based on specific recovery tests and the quality of anaesthesia from the patient's viewpoint, rated by patient questionnaires from the DGAI were evaluated. All parameters were calculated and checked for statistical significance using the chi-square test. RESULTS AND DISCUSSION. The groups were broadly comparable with respect to age (P = 0.91), ASA class (P = 0.42), preoperative blood pressure (P = 0.36), and length of anaesthesia (P = 0.82). The anaesthesia, which averaged 103 min, comprised the following regimens: (1) NLA: 7.1 mg droperidol and 0.008 mg/kg body weight fentanyl, (2) IVA: 493.4 mg propofol and 0.004 mg/kg body weight fentanyl, and (3) BAL: 2.6 mg droperidol and 0.004 mg/kg body weight fentanyl with 0.4 vol.% isoflurane. With respect to anaesthetic risk, the following reactions were observed: the use of NLA led to a high incidence of tachycardia (P = 0.001), arrhythmias (P = 0.05), and hypertensive reactions (P = 0.001), whereas in the IVA group only hypotension (P = 0.0001) occurred. However, after the use of BAL none of the aforementioned complications were detectable to any considerable degree. Similarly, patients who had cardiac disease showed greater IEC changes after the use of NLA than after BAL or IVA (P = 0.02) (Tables 1 and 2). The heart rates and blood pressures during BAL and IVA were extremely stable, and therefore, vasoactive therapy was required considerably less in comparison to NLA (P = 0.001) (Table 4). Recovery after the use of IVA was strikingly rapid: the patient's responsiveness, orientation, and ability to concentrate was significantly better than after the other anaesthetic regimen (P = 0.01) (Table 5). With regard to the typical discomforts after anaesthesia, IVA was highly superior to BAL and NLA: nausea (P = 0.0003) and retching (P = 0.03) hardly ever occurred (Table 6). Due to the tolerable manner of waking up and rapid return of orientation and the ability to concentrate, IVA was highly favoured by the patients (P = < 0.01) (Table 7). CONCLUSION. The present results show clear clinical advantages of BAL and IVA in contrast to neuroleptanaesthesia. Due to the very low incidence of side effects such as nausea and vomiting IVA was highly recommended by the patients, at least in part because of the rapid recovery time.

Adult↗

Synthesis and antitumor activity of two ifosfamide analogs with a five-membered ring.

Two ifosfamide (CAS 3778-73-2) analogs with a five-membered ring, i.e. the oxazaphospholidine derivatives 6 and 7, were synthesized and their cytotoxic activity in vitro, acute toxicity and antitumor activity in vivo determined in comparison with the oxazaphorinane ifosfamide 1. The observed low biological activity gives evidence that both, the six-membered oxazaphosphorinane ring and the two N-2-chloroethyl-side chains are necessary for the generation of the ultimate alkylator, i.e. the ifosfamide mustard 5.

Animals↗

Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.

In the course of studies on tranquilizers, new non-benzodiazepine-like compounds were synthesized. These are 1-(3,4,5-trimethoxyphenoxy)-3-[4-(2-methoxyphenyl)piperazinyl]prop an-2-ol (INN: enciprazine) and derivatives thereof which were screened pharmacologically in order to evaluate their central nervous system activity. Compounds with marked antiaggressive and anxiolytic properties but without dependence potential could be detected. Enciprazine was selected for clinical investigations.

Aggression↗

[Synthesis of germinal 3,3-dithienyl compounds (author's transl)].

A new synthetic approach to the cerebroactive compound (+)-(R)-alpha-[(S)-1-[(3,3-di-3-thienylallyl)amino]ethyl]benzyl alcohol(1) (tinofedrine), its stereoisomers and related derivatives is reported. Several compounds increased blood flow in the arteriae vertebralis and femoralis of anesthesized dog.

Animals↗