[Technique and results of percutaneous implantation of endovascular tantalum prostheses in iliac occlusive disease].
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Biomedical subjects
Publications and source records attributed to B Hagen.
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A total of 82 iliac artery lesions (62 stenoses and 20 occlusions) were treated with 3 different types of endovascular metallic stents (12 lesions with the Palmaz stent, 36 with the Wallstent, and 34 with the Strecker stent). The complication rate was 12%. Occlusion of 2 Wallstents occurred 4 and 12 weeks after stent placement, respectively. Both stents were recanalized by local fibrinolysis. One Strecker stent occluded after 8 months. The observation period was 3 to 26 months (mean 9.7 months). The patency rate with secondary intervention (fibrinolysis) was 100% after 3 and 6 months, and 98% after 9 months. All 3 stent designs turned out to be effective in the treatment of complicated iliac artery occlusive disease.
Precision-cut rat-liver slices were used to study the metabolism of the alkylating agent N,N',N''-triethylenethiophosphoramide (thio-TEPA). Exposure to high concentrations (1-10 mM) of thio-TEPA for 6 h did not prove to be toxic to the liver slices as indicated by insignificant leakage of potassium from the cells. The time course of the disappearance of thio-TEPA (initial concentration, 5.2 microM) from the buffer during incubation followed first-order kinetics. Formation of N,N'N''-triethylenephosphoramide (TEPA) apparently accounted for the elimination of thio-TEPA. Pretreatment of the rats with phenobarbital significantly increased the reaction rate. Conversely, pretreatment with the cytochrome P-450 inhibitor allylisopropylacetamide significantly reduced the metabolic rate. The elimination of thio-TEPA and formation of TEPA occurred independently of thio-TEPA concentration, which ranged from 5.2 to 104 microM. Thio-TEPA's oxo-analogue TEPA, which was not further metabolized, was the only metabolite identified. However, a significantly time-related increase in 4-(nitrobenzyl)-pyridine (NBP) alkylating activity was observed following incubation of liver slices with thio-TEPA but not after their incubation with TEPA. This may possibly indicate the formation of unknown active metabolites.
A total of 13 patients with ovarian cancer were studied during the initial two courses of i.v. thio-TEPA treatment they underwent after primary surgery. Following an increase in the dose from 60 to 80 mg for the second course, no sign of saturation of thio-TEPA elimination processes or of formation of the metabolite TEPA occurred, indicating dose-independent pharmacokinetics. Myelosuppression after courses was registered by serial measurements of platelets and leukocytes. The time to platelet nadir was quite uniformly 3 weeks and tended to be longer than that of leukocytes, which averaged 2 weeks but showed greater interindividual variation. Linear regression analyses of pharmacokinetic parameters versus myelosuppression revealed statistically significant correlations between thio-TEPA pharmacokinetics and the percentage of reductions in leukocytes and platelets at their mean nadirs. In contrast, no such correlation could be demonstrated for TEPA despite its greater exposure to the body in terms of AUC. We advocate further investigation of this pharmacokinetic-pharmacodynamic relationship so as to establish individualized dosing of thio-TEPA.
This study was performed to evaluate CA 125 in peritoneal fluid as an indicator of endometriosis. Peritoneal fluid from patients with mostly minimal and mild endometriosis (n = 43) and normal controls (n = 17) was collected at laparoscopy or laparotomy. The median concentration of CA 125 in peritoneal fluid did not differ significantly between patients and controls (79 IU/ml versus 76 IU/ml). In patients with endometriosis, a significantly increasing concentration of CA 125 in peritoneal fluid was seen from the early follicular to the late luteal phase; a similar change was not observed in the controls. In 14 patients, peritoneal fluid was sampled again after treatment with danazol and a significant reduction in median CA 125 concentration (76.5 IU/ml versus 57 IU/ml), peritoneal fluid volume (17.5 ml versus 10.5 ml) as well as reduced endometriosis scores (4 versus 2) were found. In controls, the concentration of CA 125 was about 10 times higher in peritoneal fluid than in serum. As the peritoneal levels of CA 125 did not differ significantly between patients with endometriosis and controls and as the reduction seen after danazol treatment did not correlate with the decrease of endometriotic implants, it is concluded that the monitoring of CA 125 in peritoneal fluid will not be useful in the diagnosis or control of endometriosis.
The serum pharmacokinetics of unchanged thio-TEPA and the active metabolite TEPA and the urinary excretion of thio-TEPA, TEPA and total alkylating activity were studied after a single i.v. bolus injection of thio-TEPA in six ovarian cancer patients. TEPA was present in serum as of 5 min after drug administration, and its concentration rapidly reached a plateau in the range of 50-100 ng/ml. After about 3 h the serum concentration of TEPA exceeded that of thio-TEPA, and in five of the six patients the metabolite persisted longer than the parent drug in serum. AUCs of thio-TEPA and TEPA were 822 +/- 83 and 1,084 +/- 234 ng h/ml, respectively. The great interindividual variation encountered in the serum pharmacokinetics of TEPA may be of clinical importance and represents a further indication that pharmacokinetically guided dosing of thio-TEPA could be valuable. Urinary recoveries of both thio-TEPA and TEPA were low, together constituting less than 2% of the delivered dose. A substantial gap existed between this and the total urinary alkylating activity, which averaged 13% of the dose in terms of thio-TEPA equivalents. This gap strongly indicates the presence of other unknown metabolites.
Of 91 women who underwent Burch colposuspension, 86 were available for clinical, urodynamic and isotope renographic follow-up examinations 5 years after surgery for evaluation of late complications and long-term effectiveness in urinary stress incontinence. A repeat urodynamic examination was accepted by 76 patients. Stress incontinence was cured in 71% of the patients with a stable bladder preoperatively, and in 57% with stress incontinence and detrusor instability (non-significant difference). Cure rate was not significantly related to age, hormonal status or previous anterior vaginal repair. The urodynamic measurements at follow-up showed a significant increase in the functional urethral length in the cured group, as compared with the improved group. The mean maximum urethral closure pressure was reduced in both groups. Symptomatic detrusor instability was found in 18% of the preoperative stable bladders, while 67% of the unstable bladders had become stable. Only 29% of the patients with a preoperative unstable bladder had a normal lower urinary tract function at follow-up. Late voiding difficulties were observed in 3% of the study group; enterocele, requiring surgical repair, developed in 7%. One patient suffered a damaged kidney due to undetected ureteral obstruction after surgery. Irritative bladder symptoms such as urgency, frequency, stranguria and nocturia represent a long-term problem after colposuspension. At the 5-year follow-up, only 52% of the study group were completely dry and free of complications, and about 30% needed further incontinence therapy. This may be due to some neurogenic factor which is not corrected by surgery.
The method of automated microscopic image analysis was tested in intention to support the taxonomy of Fusarium. The catalogue of morphometric object features of the software system AMBA provides size and shape parameters which can be utilize to discriminate populations of macroconidia of different Fusarium species and varieties. The applied colouring of macroconidia (methylene blue) has no significant effect on these features. The results of statistical analysis show fitness of chosen technique.
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The algesic effects of intravascularly injected solutions of sorbitol and ionic and nonionic contrast media (CM) with high and low osmolality were tested in the perfused isolated rabbit ear connected to the body by the great auricular nerve. The threshold for the pain reflex effect was found to be at an osmolality of between 600 and 700 mosm/kg H2O, that is, at about twice the osmolality of blood. This result is consistent with results obtained to date in investigations in the non-anesthetized rat and in diagnostic examinations with CM in humans. The effects of both sorbitol and the ionic CM at a given osmolality were dose dependent only after low doses and not after a high dose. There were no pain reactions after injection of ionic and nonionic CM with a low osmolality. Release of prostacyclin was observed in preliminary tests after injection of ionic substances with high osmolality, but not after injection of CM with low osmolality.
The new isotonic contrast medium iotrolan has been compared with iopromide in aortofemoral arteriography, selective femoral arteriography, and intravenous digital substraction angiography (DSA). In each case a crossover study design has been chosen with special emphasis on patient comfort. Despite problems in the interpretation of results due to a "hangover" effect in selective peripheral arteriography, it may be concluded: (1) Iotrolan causes significantly less discomfort, such as the feeling of heat and most likely also pain, than iopromide. However, one patient reported slight pain after the injection of iotrolan even when no previous injection of iopromide had been performed; (2) in intravenous DSA contrast appeared 1 to 2 seconds later in the region of interest after the injection of iotrolan compared with iopromide, probably due to the slightly higher viscosity of the former agent; (3) otherwise, no differences between the two agents have been observed. No cardiovascular or other kind of side effects occurred with the exception of one slight allergy-like reaction in 60 patients.
We present a comparative study report of the properties of the hypoosmolal contrast media iotrolan (isotonic to blood) and iopromide and ioxaglate (having twice the osmolality of blood) in selective peripheral angiography. Pain sensations were felt much more with the later media. Psychological effects could be responsible for the mild painful reactions in case of iotrolan. Opacification of peripheral zones of interest was delayed with the highly viscous iotrolan. No systemic or anaphylactoid reaction was noted. We believe that these side effects could significantly reduced both quantitatively and qualitatively in comparison with iopromide and ioxaglate but the high cost and viscosity of iotrolan will play an important role in its selection.
Thio-TEPA pharmacokinetics were studied at doses of 20 mg and 30 mg in six patients treated for ovarian cancer. Considerable interindividual variation was encountered in its pharmacokinetics, which were dose-independent within the dose range studied and similar to those reported at far higher doses. Interindividual dosing of thio-TEPA based on an initial AUC estimation is suggested.
A case of scimitar syndrome is reported in which the diagnosis was first suggested on chest radiograph. The diagnosis was confirmed by computed tomography (CT) and intravenous digital subtraction angiography (DSA). CT and DSA seem to be able to evaluate the structure and distortion of the lung and the vessels.
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Triethylenethiophosphoramide (thio-TEPA) pharmacokinetics were studied in 15 patients being treated for epithelial ovarian carcinoma. Unchanged thio-TEPA was assayed in serum and urine by means of a gas chromatographic procedure. No accumulation or alteration of the pharmacokinetics occurred during therapy, which was continued for up to 7 months with biweekly administrations of 20 mg, after two initial loading courses with 20 mg daily for 3 consecutive days 2 weeks apart. No significant difference in the pharmacokinetics between i.m. and i.v. administration was demonstrated. However, three patients showed a reduced absorption ability from the i.m. injection site to the systemic circulation and an apparent increase in the elimination half-life (3.86 +/- 0.97 h), which could be of clinical relevance. A first-order elimination process with a short elimination half-life (approximately 1.5 h) was demonstrated for thio-TEPA in all patients after i.v. administration. The apparent volume of distribution averaged 50 1. The renal clearance was below 1% of the total-body clearance, which averaged 412 ml/min. The urinary excretion of unchanged thio-TEPA was complete within 8 h after administration, with an average urinary recovery of 0.14% of the dose. Calculation of the area under the serum concentration vs time curve revealed wide variation between patients (range 517-1480 ng/h ml-1), indicating the need for drug monitoring during therapy.
Binding of triethylenethiophosphoramide (thio-TEPA) in serum from healthy individuals and from cancer patients and its binding to isolated serum protein fractions were studied by equilibrium dialysis. A drug-protein binding in the order of 10% was demonstrated in serum, with little interindividual variation. The protein binding of thio-TEPA seemed to be restricted to albumin and lipoproteins, with the greatest affinity to albumin. The previously reported selective binding of thio-TEPA to gamma globulin was contrary to our findings. The almost insignificant degree of serum protein binding of thio-TEPA indicates that the drug is well suited for use in cancer drug combinations.