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Biomedical subjects

A Fassolt

Publications and source records attributed to A Fassolt.

At least 19 recordsLinked to original sources

Measurement of extracellular fluid carboplatin kinetics in melanoma metastases with microdialysis.

Clinical anti-tumour efficacy of anti-cancer drugs is a function of dose intensity, i.e. the concentration--time profile in tumour tissue. Hence, information on drug concentration profiles in tumours is of critical importance but appropriate methods for measurement are lacking. The aim of the present study was to obtain, by microdialysis sampling, concentration--time profiles in a solid tumour (melanoma) of a model anti-cancer drug, carboplatin, and thereby to assess the scope of microdialysis for tumour pharmacokinetic studies in man. Six patients with cutaneous melanoma metastases at the extremities or body trunk, scheduled to receive carboplatin (400 mg m-2 i.v.) were studied. Carboplatin concentrations were monitored in serum, intratumoral and subcutaneous tissue. Calibration of the microdialysis probes was carried out in vitro and in vivo with use of the retrodialysis method. Complete carboplatin concentration vs time profiles in tumour and subcutaneous tissue were obtained. Major pharmacokinetic parameters (maximum concentration, time to maximum concentration, area under the curve, elimination half-life) were calculated for tissues and tumour/serum concentration ratios for carboplatin were derived. Mean free concentrations of carboplatin in cutaneous melanoma metastases reached only about 50-60% of total serum levels; maximal intratumoral concentrations were 7.6 (+/-2.0; s.e.m.) microgram/ml, mean concentrations in subcutaneous tissue were similar to those in tumour. The present study demonstrates that microdialysis is a novel tool for measuring drug concentrations in solid tumours in humans in vivo and appears to be a valuable addition for pharmacokinetic/pharmacodynamic studies in oncology.

Antineoplastic Agents↗

The effect of hyperoxia and hypercapnia on fundus pulsations in the macular and optic disc region in healthy young men.

The purpose of this study was to investigate the influence of hyperoxia and hypercapnia on fundus pulsations in the macular and optic disc region and determine a potential autoregulative capacity of the choroid under these conditions. In a randomized cross-over study 100% O2 and a mixture of 5% CO2 with air was inhaled for 10 min by ten healthy male volunteers on different study days. Fundus pulsations were measured with a recently described laser interferometer. These results were compared to changes in systemic haemodynamics and Doppler-sonographic measurements of the radial artery. The fundus pulsation amplitude significantly decreased during hyperoxia and significantly increased during hypercapnia. These effects on fundus pulsations were stronger in the optic disc region than in the macular region. The systemic parameters showed only minor changes. Hence the amplitudes of fundus pulsations measured during hyperoxia and hypercapnia are assumed to be a consequence of metabolic autoregulative mechanisms. This autoregulative capacity is greater in the optic disc region than in the macular region, implying that the fundus pulsation amplitude in the papilla is influenced by both the choroidal and the retinal circulation.

Adult↗

Key metabolite kinetics in human skeletal muscle during ischaemia and reperfusion: measurement by microdialysis.

The tissue kinetics of key metabolites of ischaemic and postischaemic tissue damage were studied in the intercellular space of human skeletal muscle by microdialysis. In vivo microdialysis calibration experiments (n = 5) yielded the basal intercellular concentration of glucose in human skeletal muscle (3.6 +/- 0.6 mM; mean +/- SD). The corresponding mean plasma glucose concentration was 4.3 +/- 0.2 mM which was significantly higher. The time vs. concentration profiles of intercellular glucose (n = 7), lactate (n = 5), TxB2 (n = 6) and urea (n = 8) were characterized during a 20 min period of leg constriction. TxB2 increased exclusively during reperfusion in comparison to baseline (n = 6). Administration of 500 mg acetylsalicylic acid, 5-10 min after onset of ischaemia blunted TxB2-response to reperfusion (n = 4). It is concluded that intercellular muscle glucose concentration is less than that in plasma. Glucose uptake in skeletal muscle is rapid even under ischaemic conditions. Synthesis and release of TxB2 is not evident during ischaemia. TxB2 mediated reperfusion injury might be reduced by acetylsalicylic acid, even if administered after onset of ischaemia.

Adult↗

Studies on the neutralizing effects of protamine on unfractionated and low molecular weight heparin (Fragmin) at the site of activation of the coagulation system in man.

In a double-blind, randomized, cross-over study the neutralizing action of protamine towards unfractionated heparin (UFH, 150 U/kg i.v.) and a low molecular weight heparin (LMWH, Fragmin, 100 anti-Xa U/kg i.v.) was investigated in 15 healthy subjects in vitro by measuring activated partial thromboplastin time (APTT), thrombin time (TT) and anti factor Xa activity (anti-Xa) in venous blood and in vivo by determination of prothrombin fragment 1.2 (f1.2) and thrombin-antithrombin III complexes (TAT) in venous blood and in shed blood. UFH and LMWH caused a prolongation of APTT and TT, an increase in anti-Xa and significantly inhibited f1.2 and TAT formation in shed blood, whereas only a minimal effect on TAT and f1.2 formation in venous blood was noted. Administration of 1 mg protamine/100 U UFH resulted in a near complete reversal of APTT, TT and anti-Xa, whereas lower doses (0.25 and 0.5 mg) were less effective. The effects of UFH on f1.2 and TAT generation in shed blood were partially (60-70%) neutralized only by the high dose (1.0 mg). Application of 1 mg protamine/100 anti-Xa U LMWH caused a near complete reversal of both APTT and TT but had only a weak effect on anti-Xa. In shed blood, the effect of LMWH on TAT and f1.2 formation was reversed by protamine only by 14% and 23% respectively. Our data do not support the concept that to reduce the incidence of protamine's potential clinical side effects, the administration of a lower dose of protamine than 1 mg protamine/100 U UFH is justified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Concentration and memory impairment in the later postoperative phase].

Of the different psychic function disturbances which may occur during the postnarcotic phase, those showing symptom complexes with sensory, neurotic-emotional or psychotic reactions mostly diminish within some hours or a few days. On the other hand, a great many patients suffer from individual mental problems of which concentration and memory weaknesses are the main characteristics, sometimes outlasting the surgical operation by a number of weeks or even months. The results of a preliminary examination of 520 patients, recently released from surgical departments, confirmed that 30% suffered from prolonged memory disturbances. Of a control group of patients treated with local anesthesia only 6% of 69 persons questioned had been aware of such symptoms. In the consecutive analysis of 90 surgical patients, making use of psychometric test methods such as digit span, learn- and memory test (German abbreviation LGT1) and concentration test d2, no reduction of memory capacity could be ascertained. An additional questioning of these patients about subjectively experienced disturbances, in comparison with the preliminary examination, resulted in approximately identical statements. The aetiology of subjectively experienced impairment of memory and concentration during the later postoperative phase appears to be still insufficiently clarified, for which psychogenic factors must be taken in consideration.

Adult↗

[Blind nasotracheal intubation in the muscle-relaxed patient].

A modified method of blind nasal intubation, using a muscle relaxant, is described, which has been used in 100 patients with an efficacy of 96%. The risk of suboxygenation was overcome by withdrawing the tube to the epipharynx and ventilating the patient's lungs after each failure to insert the tube in the trachea. The blind nasotracheal intubation of a relaxed patient is to be considered, when orotracheal intubation will be difficult or impossible to achieve, because of anatomic abnormalities or pathologic conditions of the upper respiratory tract. The dangers and complications of the method are discussed.

Adult↗

Pharmacokinetics and bioavailability of suprofen injection solution after intravenous application versus capsules on six healthy male volunteers.

In a three-way cross-over study six healthy male volunteers received intravenously 50 mg and 100 mg suprofen as a bolus injection and orally 200 mg as one capsule. The plasma level curves could be fitted to a two-compartimental model by means of the computer program NONLIN. The pharmacokinetic parameter estimates did not show dose dependency. The absolute bioavailability of suprofen taken as one capsule was 92.2% based on AUC-values and did not indicate a first-pass effect. The plasma input curve was determined by point-area deconvolution. Assuming first order input a half-life of 23 min could be derived based on point-area deconvolution. Different dissolution models based on USP XX are discussed in relation to the kinetic data generated.

Adult↗

[Phlebitogenicity of venous catheters of Vialon].

During three days 132 surgical patients with postoperative infusion treatment were checked on the frequency of venous reactions in the arms when catheters/cannulas of 4 different materials were used and the outcome compared. A significant result was obtained in connection with the I-cath catheter made of vialon (a polyurethanelike resin polymer) and the L-cath of polyurethane. Phlebitis was decreased to 27.3% resp. 24.2% - approximately half of its usual frequency - when I-cath of polyvinyl-chloride and FEP-teflon vasofix cannulas were applied (both 51.5%). The different predisposing factors of infusion phlebitis are under discussion.

Catheters, Indwelling↗

[Treatment of postoperative wound pain with suprofen].

The present randomized double-blind study was performed to investigate the analgesic effects of single doses of suprofen (alpha-methyl-4-(2-thienylcarbonyl)benzene acetic acid; Suprol) 200 mg, suprofen 400 mg paracetamol (APAP, acetaminophen) 650 mg, and combination suprofen 100 mg + APAP 650 mg versus placebo. The five treatment groups were homogeneous as to their demographic features and comprised 28--32 subjects each. Data for a total of 146 patients were evaluated. There were statistically significant differences between the therapeutic effect of the test preparations containing active substance on the one hand and placebo and the other hand. Of the active substances, the best results were obtained with the combination suprofen 100 mg + APAP 650 mg, followed by suprofen 400 mg and APAP 650 mg; there were hardly any differences in the results obtained with the two latter substances. Suprofen 200 mg ranked third. Statistical significance was only seen for the parameter pain intensity (SPID) on comparison of suprofen 100 mg + APAP 650 mg versus suprofen 200 mg. Side effects, homogeneously distributed over the treatment groups, were observed in four cases.

Acetaminophen↗

Suprofen kinetics in healthy male volunteers after intramuscular injection of increasing dosages.

Kinetics of alpha-methyl-4-(2-thienyl-carbonyl)-phenylacetic acid (suprofen, Suprol) a non-narcotic antiphlogistic analgesic, were studied in two clinical experiments. In a bioavailability study (study A) suprofen, given as intramuscular injection was absorbed more rapidly (mean peak plasma time 20.0 min) than from the capsule formulation (mean peak plasma time 57.5 min). With respect to the amount systemically absorbed, measured as area under the plasma concentration-time curve, both dosage forms were equivalent. Individual plasma concentration profiles (study B) were described by a 2-compartmental model with a mean first order absorption rate of 0.095 min-1, a rapid mean disposition rate alpha of 0.025 min-1 and an apparent terminal plasma elimination rate beta of 0.004 min-1. There was dose-independent kinetics and a linear correlation between peak plasma concentration versus dose and area under the curve (AUC) versus dose after intramuscular injection of suprofen up to 200 mg, leading to dose proportional bioavailability data.

Adult↗

[Central venous catheterization via the internal jugular vein (Rao's method) (author's transl)].

Central venous catheterization via the internal jugular vein was performed in 208 patients. The clavicle-orientated approach, as described by Rao in 1977, was employed. Apart from a higher incidence of failures, arterial punctures and misplacement of the catheter, as compared with other techniques, there were also 3 cases of pneumothorax (1.4 per cent) which were attributable to the proximity of the puncture site to the pleura. In 3 patients with considerable hypovolaemia venipuncture was successful at the first attempt. In view of these observations the technique cannot be regarded as suitable for routine purposes.

Catheterization↗

[Lung function after thoracic trauma. A contribution to the assessment of late functional lesions (author's transl)].

Respiratory function was investigated in 32 patients not later then 5 years after thoracic trauma. Forced expiration curves (volume/time and flow/volume mode) and nitrogen washout methods (single breath, multiple breath) were used including blood gas analyzes and thorax-X-rays. The typical effect of chest injury is mild to moderate restriction, which was found in 72% of the patients. Usually all volumes (FVC, FRC, TC) are reduced. 5 patients had slight to moderate obstruction, which we do not consider to be immediate consequence of trauma. 12 patients had signs of ventilatory maldistribution, which can be explained by reduced FRC in more or less all cases and obstruction in the above mentioned 5 patients. Observation of two cases leads us to conclude that chest injury may initiate development of chronic respiratory disease and that such a disease may be aggravated by thoracic injury. Motivation, young age, quality of rehabilitation, dorsal location of fractured ribs may help to improve the pulmonary status of the patient, existing or developing chronic lung disease, smoking, old age, lateral localisation of fractured ribs with dislocation will hinder improvement.

Adult↗

[Antithrombotic agents for the prevention of thromboses during infraclavicular vena cava catheterizaiton].

To study the suppressibility of thrombosis due to central venous catheter phlebographically, groups of 25 patients were given low-dose-heparin, dextran 70 or salicylate (initial application preoperatively). The catheter was inserted for 6 to 8 days. As a control group 25 patients received no antithrombotic medication whatsoever. Of these cases 35% showed evidence of thrombus formation. In comparison only the patients with salicylate showed a significant reduction of catheter-induced thrombosis by 67%. By comparing the heparin to the control group the total of thrombotic formations when planimetrically assessed results in a ration of 1:12, which is superior to dextran and salicylate.

Adolescent↗