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Biomedical subjects

E Böhm

Publications and source records attributed to E Böhm.

At least 37 records · Page 2Linked to original sources

[Decubitus ulcer in paraplegic patients--a comparative clinico-pathologic study].

331 pressure sores of 141 patients with paraplegia were investigated histologically, the results were partly correlated with the roentgenological features. The level of the spinal cord lesion was the segment Th12-L1 in 45%, the decubital ulcers were mostly localized above the os ischiadicum (64%). A pseudocancerosis was diagnosed in 14.2%, one time a cancer in a sacral decubitus has been found. The inflammation was limited to the soft tissue in 56.9%, in 28.5% a chronic osteomyelitis of different severity had developed. In 73.6% of the patients with a histologically proven osteomyelitis this osteomyelitis could be diagnosed roentgenologically too. The high amount and severity of the dermal and bony lesions justifies the radical surgical therapy of the pressure sores, which is practised today. Our investigations of chronic pressure sores did not point out new aspects of aetiology of pathogenesis--this is only possible by experimental models.

Adolescent↗

[Changes in lung function following administration of eyedrops containing timolol, metipranolol, pindolol and pilocarpine in healthy probands and patients with mild bronchial asthma].

Lung function was studied double blind and randomized in 5 patients with mild asthma bronchiale and 10 normal adults before and 30, 60 and 90 minutes after one drop of 0.5% Timolol, 0.6% Metipranolol or 0.9% NaCl in each eye. In the asthmatics bronchoconstriction was seen after both beta-receptor blocking agents, more pronounced after Timolol than after Metipranolol. There was a decrease in the forced expiratory volume in one second (FEV1.0) of 32, respectively 18%. No changes were observed in the normal subjects. In a separate study no significant changes were seen in the mean values of 10 other asthmatic subjects after 1% Pindolol, 3% Pilocarpin or 0.9% NaCl. However, in two patients FEV1.0 was reduced by 15% and 20% of the control values after applying Pindolol. In summary, not only beta-receptor-blocking agents without ISA produce a bronchoconstriction in asthmatic subjects, but also beta-blocker with ISA in individual cases.

Airway Resistance↗

The role of cytoplasmic (newly synthesized) dopamine for the spontaneous and electrically evoked release of dopamine and its metabolites from the isolated neurointermediate lobe of the rat pituitary gland in vitro.

Isolated rat NILs were incubated in Krebs-HEPES solution. The release of dopamine and its metabolites (DOPAC, HVA and MOPET) was determined by HPLC with electrochemical detection. The spontaneous release of the sum of metabolites was about 40 times that of dopamine. The spontaneous outflow of dopamine metabolites was unaffected after inhibition of dopamine uptake (by GBR 12921) or after pretreatment with reserpine (5 mg/kg, 12 h before the experiments), but it was reduced by 50% after preincubation with the irreversible DOPA decarboxylase inhibitor, (MFMD, 10 microM, for 10 min). The combination of pretreatment with reserpine and preincubation with MFMD resulted in an 80% inhibition of the spontaneous outflow of dopamine metabolites. Treatment with reserpine caused a 98% depletion of the dopamine tissue content, whereas 60 min after exposure to MFMD the dopamine tissue content was decreased by 40%. Electrical stimulation of the pituitary stalk (3-15 Hz, in the presence of GBR 12921) caused a frequency-dependent release of dopamine. Stimulation at 7 or 15 Hz caused also a significant release of dopamine metabolites. After pretreatment with reserpine, the release of dopamine evoked by stimulation at 15 Hz was abolished, whereas the evoked release of the metabolites was only reduced by about 55%. After MFMD, the evoked release of dopamine decreased by a percentage similar to that of dopamine tissue content, but the reduction of the evoked release of metabolites was more pronounced. In conclusion, the spontaneous release of dopamine metabolites from the dopaminergic nerve endings in the NIL largely reflects the catabolism of newly synthesized dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Pharmacokinetics of the thioether phospholipid analogue BM 41.440 in rats.

BM 41.440 (1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine) is a cytotoxic thioether phospholipid analogue that recently has entered phase I trials in cancer patients. The objective of this study was to evaluate the pharmacokinetics of this compound in female rats after administration of a single oral dose (15 mg/kg body weight [bw] ). Furthermore, BM 41.440 serum concentrations were determined under a daily oral treatment of up to 13 weeks. Blood samples were obtained via permanent catheters from the femoral arteries before and after drug administration for a total of 120 hr. Urine was collected in 24 hr-intervals for 120 hr; the volume was measured, and aliquots were stored at -20 C until analytical determination of the thioether derivative. BM 41.440 was assayed in serum and urine by means of a specific, newly developed reverse-phase high pressure liquid chromatography technique. Mean maximum serum concentrations (1.7 micrograms/ml, n = 4 animals) were attained after seven hr. A terminal half-life of ca. 27 hr was calculated from the rate constant for the terminal elimination phase (lambda z approximately 0.026/hr). The mean serum BM 41.440 concentration-time-area-under-the-curve was 52.9 mg X hr/l. The ratio of total body clearance to absorption fraction was 4.7 ml/min X kg bw. Only a small amount of the drug was found in the urine. The quantity excreted in the urine during a 24 hr-interval never exceeded 1.5% of the administered dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[Structural principles of hemostatic processes].

The formation of the hemostatic plug on areas of skin injury is characterized as a sequence of structure-forming processes ending in the formation of an impenetrable barrier. The morphology of this barrier is further elucidated by means of scanning- and transmission electron microscopy. Especially the fibrin coating of the injury shows a completely different formation than is deducible from the solely hemostaseologically orientated view of the formation of the hemostatic plug. These structure-forming processes are: activation of the intrinsic clotting system by means of explosion-like destruction of thrombocytes with an immediate formation of a fibrin clot within seconds after the injury. Later during the process the fibrin clot is then condensed and as a function of thrombocyte dependent retraction receives its final fibrin stabilisation and modellation towards an occluding plug. The very narrow net formation of fibrin fibers is interpreted as dependent on the destruction of thrombocyte pseudopodia using their round shape as a rail for fibrin fiber formation. Disturbances of clot formation of postmortal clots compared to vital clots are interpreted as functional thrombocytic distortions, especially of the thrombocytic energy metabolism. Extracorporal clotting of blood drops after extreme ischemia resemble fibrin structures and fibrin structure formation distortions of postmortal origin.

Animals↗

Pharmacological profile of carvedilol as a beta-blocking agent with vasodilating and hypotensive properties.

Carvedilol is a new beta-receptor blocking and vasodilating drug that is presently undergoing clinical trials in hypertension and coronary heart disease. In this article, the pharmacodynamic properties of carvedilol are compared with those of standard drugs. The beta-blocking activity was characterized in isolated organs and in conscious rats, rabbits, and dogs. For the beta 1-blockade in guinea pig atria, the pA10 values were 7.44 +/- 0.16 for carvedilol and 6.77 +/- 0.08 for propranolol. Carvedilol is a noncardioselective beta-blocker. The i.v. doses that inhibited the tachycardia by 50% induced by 1 microgram/kg isoprenaline were 62 micrograms/kg in dogs, 138 micrograms/kg in rabbits and 841 micrograms/kg in rats. In rabbits carvedilol was slightly more active and in rats less active than propranolol. In all models, carvedilol was much more active than labetalol or prizidilol. In contrast to propranolol, carvedilol relaxed rat aortic strips. A dose-dependent decrease in arterial blood pressure was seen in different in vivo models. The total peripheral and coronary resistance were decreased in conscious dogs. The doses required for both beta-blockade and decrease in blood pressure were in the same range. The drug was also active after oral administration. There is no hint for development of tolerance.

Adrenergic beta-Antagonists↗

Evaluation of the risk for drug-induced postural hypotension in an experimental model: investigations with carvedilol, prazosin, labetalol, and guanethidine.

Postural hypotension is a common side effect observed in the treatment of hypertension with various drugs. Carvedilol, a vasodilating beta-blocker, was compared with prazosin, labetalol, and guanethidine for its ability to induce orthostatic hypotension. The comparison was carried out using doses of the drugs required to lower baroreceptor reflex hypertension in anesthetized rabbits by 30 mm Hg (ED -30 mm Hg). The following doses were found in independent investigations to be equipotent in this rabbit model: ED -30 mm Hg (mg/kg i.v.): prazosin = 0.03; labetalol = 1.8; guanethidine = 0.12; carvedilol = 0.12. These doses did not markedly inhibit the orthostatic reaction in rabbits after tilting stress, so 10-fold higher doses were used and clear discrimination between the drugs was found. The orthostatic index was reduced after prazosin and labetalol by about 24%, after guanethidine by about 30%, and after carvedilol by about 13%. The 50-fold dose of carvedilol (6 mg/kg i.v.) does not lead to any greater inhibition of the orthostatic index. From these results it is concluded that a relatively lower risk of postural hypotension is to be expected after carvedilol treatment than with the other drugs presented here. Furthermore, these results do not provide any indication that carvedilol exerts its vasodilator properties via alpha-blockade.

Animals↗

Endogenous opioids inhibit the in vitro release of endogenous dopamine preferentially in the neural lobe of the rat neurointermediate lobe.

The release of endogenous dopamine (DA) from the in vitro incubated combined neurointermediate lobe (NIL) or isolated neural lobe (NL) was studied. In the presence of the DA uptake inhibitor GBR 12921 (200 nM), electrical stimulation of the pituitary stalk caused an increase of the outflow of DA from the NIL in a frequency-dependent manner. Naloxone (1 microM) enhanced the DA release from the NIL evoked by electrical stimulation at 7 or 15 Hz by about 40%, but had no effect on DA release evoked by stimulation at 3 Hz. When the electrical stimulation was carried out at 15 Hz, the evoked DA release (expressed as fraction of the DA tissue content) from the NL amounted to only 15% of that from the combined NIL. Naloxone (1 microM) increased the evoked DA release from the isolated NL by 242%. Thus, the effect of naloxone on DA release from the combined NIL may be confined mainly to the NL. In conclusion, DA release from the NL is under inhibitory control of endogenous opioids released from the NL during stimulation at 7 or 15 Hz. Beta-Endorphin, known to be released spontaneously at a high rate from in vitro incubated NILs, appears to lack inhibitory effects on DA release from the NIL.

3,4-Dihydroxyphenylacetic Acid↗

[Studies on the angioarchitecture of polypoid colonic processes].

Portions of the colon removed at operation were studied angiographically after arterial or venous injection with a barium-gelatin mixture. The aims of the investigation were: To study the differences between tumour and inflammatory angiographic appearances and the clinical value of in vivo angiography of the mesenteric arteries. A comparison of the micro-angiographic appearances of benign and malignant polypoid lesions of the colon. Adenomas and carcinomas showed patterns which are easy to distinguish and permit classification in uncertain lesions. Pseudopolyps in Crohn's disease resemble adenomas in the early stages, but later assume features characteristic of tumours.

Adenocarcinoma↗

Hydroxyl radical-induced strand break formation of poly(U) in the presence of oxygen: comparison of the rates as determined by conductivity, e.s.r. and rapid-mix experiments with a thiol.

The rate of OH radical-induced strand break formation of single-stranded poly(U) in N2O/O2-saturated aqueous solution was studied by measuring the time-dependence of the electrical conductivity following pulse radiolysis. The first half-life of the total conductivity increase depends slightly on pH and the molecular weight and on the dose per pulse. The activation parameters for strand break formation were found to be EA = 52 kJ mol-1 and A = 5 X 10(8) s-1. Similar first half-lives were observed when the decay of peroxyl radicals of poly(U) was measured by e.s.r. under various conditions. This indicates that poly(U)-peroxyl radicals are involved in the rate-determining step of strand break formation. After pulse radiolysis, strand break formation can be inhibited by the addition of dithiothreitol (DTT) in a rapid-mix apparatus. It is postulated that peroxyl radicals of poly(U) react with DTT by formation of hydroperoxides, thereby preventing strand breakage.

Dithiothreitol↗