Plasma drug and antiplatelet profiles of the original acetylsalicylic acid preparations used in the AMIS,PARIS and German-Austrian trials for secondary prevention of myocardial infarction

Summary In a cross-over study 6 healthy male subjects were given for 9 days the acetylsalicylic acid (ASA) preparations used in the Aspirin Myocardial Infarction Study (AMIS), Persantine-Aspirin Reinfarction Study (PARIS) and German-Austrian secondary heart attack prevention trials, exactly according to the original study protocols. Plasma concentrations of ASA and its main metabolites salicylic acid (SA) and salicyluric acid (SUA), as well as platelet function (collagen-induced platelet aggregation; tissue extract-induced change in platelet shape) were studied repeatedly on the first day of each medication period and were again examined on the sixth and ninth days. Differences in the plasma concentrations of ASA and its metabolites were found only on the first day, probably as a result of different absorption rates. Collagen-induced platelet aggregation was more rapidly inhibited the faster the preparation was absorbed. Each ASA preparation inhibited tissue extract-induced platelet shape change from the first dose, although statistically significant inhibition was seen only with the AMIS preparation. It is concluded that differences in the antithrombotic efficiency of ASA cannot be explained by differences in the pharmacokinetic and antiplatelet profiles of the various ASA preparations tested.     

HPLC determination of azapropazone in human plasma

Determination of Azapropazone in Human Plasma by HPLC A HPLC method is described to determine azapropazone in human plasma. Azapropazone is extracted from acidified plasma samples (pH 4) with dichloroethane and reextracted into an alkaline methanol solution. Concentrations down to 0.1 μg per milliliter plasma can be determined. The procedure is suitable for pharmacokinetic routine analyses.     

Validation of 133Xe clearance as a cerebral blood flow measurement technique during cardiopulmonary bypass.

133Xe clearance to measure cerebral blood flow (CBF) was examined in 10 dogs during cardiopulmonary bypass. As a reference method, a continuous Kety-Schmidt technique (CBFKS) with 133Xe as indicator was used. Extracranial tissue was removed to directly place the 133Xe detectors on the skull, and the head was covered with a 3 mm lead shield to minimize contamination of the 133Xe clearance curve with extracranial radiation. 133Xe detectors for the Kety-Schmidt technique were embedded in a shielded brass block to minimize interference with radiation from the animal's body. 133Xe clearance data were analyzed using stochastic (CBF10, CBF15, and CBFINF) and initial slope methods (CBFIS), and the results were compared with CBFKS using linear regression. CBF15 and CBFINF yielded similar CBF values as CBFKS (CBFKS = 0.97.CBF15-2.08, r = 0.92, p less than 0.01; CBFKS = 1.13.CBFINF-1.21, r = 0.92, p less than 0.01). CBF10 slightly overestimated CBFKS but still showed a close correlation to CBFKS (CBFKS = 0.89.CBF10-2.58, r = 0.92, p less than 0.01) and CBFIS considerably overestimated CBFKS (CBFKS = 0.60.CBFIS-1.27, r = 0.87, p less than 0.01). With extracranial contamination of the 133Xe clearance curve minimized, all 133Xe clearance techniques used to measure CBF were consistently related to CBFKS in a constant, significant manner. 133Xe clearance therefore is a valid method to assess CBF during cardiopulmonary bypass.     

Impact of the C2/C6 Ratio of High-molecular-weight Hydroxyethyl Starch on Pharmacokinetics and Blood Coagulation in Pigs

Background: High-molecular-weight, low-substituted hydroxyethyl starch (HES) may not affect blood coagulation more than low-molecular-weight, low-substituted HES. The authors assessed in vivo the effect of a lowered C2/C6 ratio on pharmacokinetic characteristics and the impact on blood coagulation of high-molecular-weight, low-substituted HES.

Methods: A prospective, randomized, parallel study in 30 pigs compared HES 650/0.42/2.8 with HES 650/0.42/5.6. Before, during, and after infusion of 30 ml/kg body weight HES, blood samples were collected over 630 min to measure HES concentrations and plasmatic coagulation and to assess blood coagulation in whole blood by Thrombelastography(R) (TEG(R); Haemoscope Corporation, Niles, IL). Pharmacokinetic parameters were estimated using a two-compartment model.

Results: The elimination constant was 0.009 +/- 0.001 min-1 for HES 650/0.42/2.8 and 0.007 +/- 0.001 min-1 for HES 650/0.42/5.6 (P < 0.001); the area under the plasma concentration-time curve was 1,374 +/- 340 min [middle dot] g/l for HES 650/0.42/2.8 and 1,697 +/- 411 min [middle dot] g/l for HES 650/0.42/5.6 (P = 0.026). The measured plasma HES concentrations were not different between HES 650/0.42/2.8 and HES 650/0.42/5.6. Both HES solutions equally affected blood coagulation: Thrombelastographic coagulation index decreased similarly at the end of infusion of HES 650/0.42/2.8 and at the end of infusion of HES 650/0.42/5.6 (P = 0.293). Also, activated partial thromboplastin and prothrombin times increased similarly for HES 650/0.42/2.8 and HES 650/0.42/5.6 (P = 0.831).     

Monitoring of Oxygen Delivery in Cardiac and Vascular Surgery

Monitoring the adequacy of oxygen (02) delivery is of paramount significance in the perioperative period of surgical patients undergoing cardiac and major vascular surgery. These patients are at considerable risk for ischemic perioperative complications due to a high incidence of coronary artery disease. Monitoring the adequacy of global 02 delivery is based on observing stability of haemodynamics, absence of elevated lactate levels and preservation of 02 consumption. Monitoring the adequacy of regional 02 delivery focuses on the coronary, cerebral, splanchnic and renal circulation. Myocardial ischemia can be detected relatively easily by continuous ECG monitoring of leads II and V5 and in selected cases by transesophageal echocardiography. There are relatively few monitoring modalities clinically available at the present time to reliably assess adequacy of 02 delivery in the cerebral, splanchnic and renal circulation. Expecting relatively low intra- and postoperative haemoglobin levels per se does not necessarily mandate greatly exaggerated monitoring. However, continuous ECG monitoring of leads II and V5, invasive blood pressure measurement, determination of hourly urine production may be indicated in most patients. In high risk patients extended monitoring with a pulmonary artery catheter and transesophageal echocardiography may be indicated. Most important, however, is the clinical surveillance by an experienced physician integrating the information of all applied monitoring modalities who realises early alterations indicating (potentially) compromised 02 delivery.     

Vascular surgery, implantation surgery, and vacuum erection aids. Review-overview-aspects of three therapy options in erectile dysfunction

Summary Vascular surgery or penile prosthesis implantation are the main surgical options for erectile dysfunction. In this category, penile revascularization is the only causal therapy for selected patients: males younger than 50 years of age at time of surgery, maximum of two risk factors, exclusion of diabetes mellitus. Long-term success decreased to 53 % to 55 % in comparison to first encouraging reports of 80 % success. Venous surgery resulted in an even more distinct decline of success the longer the elapse of time after surgery. Long-term success dropped under 40 %, leaving only a few indications for penile venous ligation. In contrast, penile prosthesis implantation results in high satisfaction rates. Despite this, it is not generally recommended as first choice surgical management as it is linked to irreversible damage of the cavernosal bodies. Among numerous types of penile implants, preference is nowadays mostly given to the three-piece hydraulic models. However, such complications as defective or perforated cylinders in up to 35 % after 5 years have arisen, depending on the type of implant. In a selected patient group, vacuum constriction devices with a mean patient acceptance of 75 % (50 % to 90 %) seldom result in complications and are thus considered to be a well-established therapeutical option.      

Resonant amplification and flow/pressure characteristics in high-frequency ventilation

In an in vitro study, the influence of different basic characteristics of high-frequency oscillation (HFO) circuits upon pressure and flow patterns was investigated for a wide variety of lung surrogates. A distinct resonant amplification was observed: the delivered oscillatory volume was found to exceed the piston displacement up to a factor of 1.6. In the whole frequency range of 0–70 Hz the delivered oscillatory volume and its resonance characteristics were entirely determined by the HFO circuit and independent of the properties of the lung surrogates investigated. Accordingly, it appears to be possible to determine the delivered oscillatory volume in vitro and to calibrate the HFO circuit also for use under physiological conditions. in the formation of mean pressure, contributions were found which emerged outside the lung surrogate. They were highly dependent on the HFO circuit arrangement and were superimposed to the local mean pressure components in the lung.     

Practical and technical considerations in establishing an intraoperative radiation therapy program in the community practice

The Radiation Oncology Center in Sacramento, California, has developed a procedure for establishing an intraoperative radiation therapy facility in a community practice. The logistics pertaining to personnel, equipment, physical measurements, and quality assurance are presented. Particular emphasis is given to the most effective means of acquiring the large quantity of data needed to ensure a program of acceptable quality.     

Radial artery tonometry: moderately accurate but unpredictable technique of continuous non-invasive arterial pressure measurement

Radial artery tonometry provides continuous measurement of non-invasive arterial pressure (CNAP) by a sensor positioned above the radial artery. An inflatable upper arm cuff enables intermittent oscillometric calibration. CNAP was compared with invasive radial artery pressure recordings from the opposite wrist in 22 high-risk surgical patients with an inter-arm oscillometric mean arterial pressure difference < or = 10 mm Hg. Oscillometric, tonometric and invasive digital pressure values, and invasive and CNAP waveforms were obtained by the same instrument (Colin BP-508). Correlation coefficients (r) of invasive vs oscillometric values (n = 481 pairs) were 0.83, 0.90 and 0.92, and mean absolute errors of oscillometry were 7.6, 4.7, and 2.6 mm Hg for systolic, diastolic and mean arterial pressures, respectively. Correlation was poor for systolic (r = 0.80), diastolic (r = 0.77) and mean (r = 0.84) invasive vs CNAP values (n = 1375). Compared with oscillometry, mean absolute errors of 15.2, 10.9 and 9.4 mm Hg for systolic, diastolic and mean CNAP, respectively, were significantly (P < 0.001) higher. Mean prediction errors of CNAP, compared with invasive values, were -5.8 (SD 14.2) mm Hg for systolic, +7.2 (8.3) mm Hg for diastolic and +3.9 (8.8) mm Hg for mean arterial pressure. Individual patient accuracy of CNAP was assessed as good (individual prediction error < or = 5 (8) mm Hg and individual absolute error < or = 10 mm Hg) in seven patients, as acceptable (< or = 10 (12) and < or = 15 mm Hg) in 11 patients, and as inadequate in four of 22 patients. Individual accuracy of oscillometry was good or acceptable in all 22 patients. The trend in CNAP changes (difference between consecutive measurements) was sufficiently accurate during induction of anaesthesia, as only 47 (7.6%), 14 (2.3%) and 27 (4.4%) of 616 systolic, diastolic and mean CNAP values differed by more than 10 mm Hg of invasive pressure trends. We conclude that: intermittent oscillometry provides accurate arterial pressure monitoring; CNAP measurements offer a reliable trend indicator of pressure changes during induction of anaesthesia and may be considered an alternative to invasive pressure measurements, should arterial cannulation be difficult in an awake patient; and accuracy of absolute CNAP values is only moderate and unpredictable, thus radial artery tonometry should not replace invasive monitoring in high-risk patients during major surgical procedures.