Intraoperative tramadol reduces shivering but not pain after remifentanil-isoflurane general anaesthesia. A placebo-controlled, double-blind trial.

BACKGROUND AND OBJECTIVE: Postoperative shivering and pain are frequent problems in patients recovering from anaesthesia with particularly high incidences being observed after remifentanil-isoflurane-based general anaesthesia. The opioid tramadol is generally effective in preventing shivering and treating pain, but its effects are not characterized after remifentanil-based general anaesthesia. This randomized, placebo-controlled, double-blind study evaluated the effects of intraoperative intravenous tramadol on postoperative shivering and pain after remifentanil-based general anaesthesia. METHODS: After Ethics Committee approval, 60 patients scheduled for lumbar disc surgery were included. Surgery was performed under general anaesthesia (remifentanil, isoflurane). Patients were randomly assigned to receive 2 mg kg(-1) tramadol in 30 mL 0.9% saline infused intravenously (n = 30) or 30 mL saline (n = 30) 45-30 min before skin closure. The following parameters were assessed every 10 min for 2 h: shivering, pain, postoperative nausea and vomiting, sedation, heart rate, non-invasive blood pressure and peripheral oxygen saturation. The primary outcome variable was the incidence of shivering during the first 2 postoperative hours. Secondary variables were: shivering intensity, pain, postoperative nausea and vomiting, sedation, heart rate, non-invasive blood pressure and peripheral oxygen saturation. RESULTS: Shivering was less frequent in patients treated with tramadol (20% vs. 70%, P = 0.0009) and was of lower intensity (severe shivering: 10% vs. 46.7%, P = 0.003). Pain scores were similar between the groups and all other secondary outcome variables failed to reveal significant differences. CONCLUSIONS: Compared with placebo, intraoperative intravenous administration of 2 mg kg(-1) tramadol reduces the incidence and extent of postoperative shivering without alterations in pain perception after lumbar disc surgery under remifentanil-isoflurane-based general anaesthesia.

Noncollinear magnetic order in quasicrystals.

Based on Monte Carlo simulations, the stable magnetization configurations of an antiferromagnet on a quasiperiodic tiling are derived theoretically. The exchange coupling is assumed to decrease exponentially with the distance between magnetic moments. It is demonstrated that the superposition of geometric frustration with the quasiperiodic ordering leads to a three-dimensional noncollinear antiferromagnetic spin structure. The structure can be divided into several ordered interpenetrating magnetic supertilings of different energy and characteristic wave vector. The number and the symmetry of subtilings depend on the quasiperiodic ordering of atoms.

[Death by burning in open spaces. Death caused by suicide or homicide?]. / Verbrennen im Freien. Tod durch eigene oder fremde Hand?

The authors report on four cases of suicidal fire deaths in the open air. In three cases the proper cause of death was severe burning and in one case deep cuts of the neck. In all these events the concentrations of CO-Hb were < 30%. Kerosene was indicated in lipophile tissue or lung in two cases. There was no evidence of incapacitation preceding the exposition to fire. The autopsy findings and the scene allowed a reconstruction of the course of events. All victims had motives of suicide. The authors conclude that close cooperation between police, fire experts and forensic medicine is necessary to permit a correct classification of the mode of death in such cases.

[Methods of suicide in an autopsy sample of the Institute of Forensic Medicine of the Hannover Medical School]. / Suizidmethoden im Sektionsgut des Instituts für Rechtsmedizin der Medizinischen Hochschule Hannover.

Between 1978 and 1987 513 cases of suicide were examined at the Institute of Legal Medicine of the Medical School of Hannover (337 males (65.7%) and 176 females (34.3%). The greatest share of the suicides was found in the age group 18 to 30. 42.1% of the cases showed positive alcohol concentrations with men accounting for a relatively higher share. The most frequently used methods for committing suicide were intoxications (28.1%), hanging (25.3%), firearms (17.2%), falling from great height (9.7%) and drowning (7.6%). The incidence in terms of sex showed marked differences in distribution, however. Women mostly used the following methods for committing suicide: Intoxication (37.4%), falling (17.6%) and hanging (17%). With men we found the following order: Hanging (29.7%), firearms (24.3%) and intoxications (23.1%). Compared with other institutes of legal medicine the five most frequent suicide methods showed similar distributions, but with a higher rate of intoxications. On the other hand there were distinct differences as to the relative frequency of the individual suicide methods in the total population and the respective number of autopsies performed. Especially in cases of gunshot wounds the number of autopsies performed to rule out homicide was higher. Of 2390 case of suicide registered in Greater Hannover an autopsy was ordered by the court in only 6.7%. According to our experience the autopsy rate seems too low, because homicide in the form of pretended suicide is not too rare.

[Lodged bullet or bullet penetration? Re-entry of a projectile and pseudo-shot]. / Steckschuss oder Durchschuss? Reentry eines Projektils bzw. Pseudoausschuss.

In an extended suicide an 11-year-old boy was killed by two shots into the back. In spite of corresponding entry and exit points one of the projectiles was found inside the body. By laying open the respective bullet track, examination of the deformations of the bullet, on which a total of three ricochet points were identified, and a second visit to the scene both the order in which the shots were fired and the reason why one of the projectiles was lodged inside the body, although there was an exit point, could be clarified: On firing the second shot the victim had been lying on the wooden threshold of a door, from which the projectile ricochetted. The terms "reentry" and "pseudo exit point" are discussed. The retention of the bullet in the depth of an alleged exit wound emphasizes the importance of post-mortal X-ray examinations.

Characterization of the prejunctional muscarinic receptors mediating inhibition of evoked release of endogenous noradrenaline in rabbit isolated vas deferens.

The aim of the present study was to characterize the prejunctional modulation of evoked release of endogenous noradrenaline in rabbit vas deferens by the use of muscarinic receptor agonists and subtype-preferring antagonists. Vasa deferentia of the rabbit were stimulated electrically by trains of 120 pulses delivered at 4 Hz or trains of 30 pulses at 1 Hz. The inhibition by muscarinic agonists of the stimulation-evoked overflow of endogenous noradrenaline in the absence and presence of antagonists was used to determine affinity constants for antagonists. These values were compared with those observed at putative M1 receptors inhibiting neurogenic twitch contractions in the rabbit vas deferens and with affinity data obtained at M1(m1)-M4(m5) receptors in functional studies and binding experiments. The evoked overflow of noradrenaline from sympathetic nerves was enhanced by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) and indomethacin, indicating a tonic inhibition by endogenous A1 and P2 purinoceptor agonists and prostanoids, respectively. The stimulation-evoked overflow at 4 Hz was not sensitive to inhibition by the muscarinic agonists methacholine or 4-(4-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium iodide (4-Cl-McN-A-343). In contrast, at a stimulation frequency of 1 Hz the evoked noradrenaline release was decreased by muscarinic agonists (EC50): arecaidine propargyl ester (0.062 microM), 4-Cl-McN-A-343 (0.32 microM), 4-(4-fluorophenylcarbamoyloxy)-2-butynyl-N-methyl-pyrrolidinium tosylate (4-F-PyMcN+; 0.48 microM) and methacholine (0.86 microM). The affinity constants of most of the muscarinic antagonists [atropine: pKB = 9.47; (R)-trihexyphenidyl: pKB = 9.18; pirenzepine: pA2 = 7.68; methoctramine: pKB = 6.90] are consistent with estimates of these antagonists at M1(m1) receptors determined in various functional and binding studies. The high antagonistic potency of pirenzepine and (R)-trihexyphenidyl and the agonistic activity of 4-F-PyMcN+ argue for the involvement of M1, and against that of M2 and M3 receptors in the inhibition of evoked noradrenaline overflow. However, the high apparent pKB of 8.30 for himbacine is not in accordance with an M1 receptor; by contrast, it would be compatible with the presence of M2 or M4 receptors. The potencies of the tested muscarinic agonists and antagonists largely agree with those obtained for the inhibition of neurogenic twitch responses (0.05 Hz) in the rabbit vas deferens.(ABSTRACT TRUNCATED AT 400 WORDS)

Results of selective screening for inborn errors of metabolism in the former East Germany.

Since the early 1970s selective screening for inherited metabolic disorders has been performed in larger children's hospitals or metabolic centres of the former East-Germany. As a rule the following methods were employed: initially paper chromatography, drop, dip and spot tests, later on thin-layer chromatography and more recently enzyme analysis, gas chromatography, mass spectrometry and HPLC. Normally urine, blood or leucocytes were investigated. The diagnoses were confirmed in metabolic centres in Greifswald, Berlin or Leipzig or in collaboration with specialized laboratories abroad. About 130,000 subjects from former East Germany as well as from different East European countries were investigated, of which 365 patients were diagnosed and classified into roughly 40 various metabolic diseases. The proportion of positive diagnoses was 1 in 400.

Biochemical and immunological characterization of X-linked ichthyosis.

An immunoquantification protocol based on an enzyme-linked immunosorbent assay was developed to measure the abundance of the microsomal enzyme steroid sulphatase (STS). The two-step sandwich immunoassay is sufficiently sensitive to detect 100-200 pg purified steroid sulphatase in a 50-microliters sample. The steroid sulphatase content in fibroblast, leukocyte and placental extracts correlates with the steroid sulphatase activity in these extracts. No steroid sulphatase protein was found in approximately 350 micrograms plasma proteins from a normal person. In three of four X-linked ichthyosis patients a complete gene deletion was found by Southern hybridization with the full-length STS cDNA as probe. Neither steroid sulphatase protein nor enzymatic activity was found in fibroblast extracts of these three patients. In a fibroblast extract of another X-linked ichthyosis patient, which had a normal Southern blotting pattern, no immunoreactive protein was detected. Residual activity of steroid sulphatase was also not found after prolonged incubation of this fibroblast extract with the natural substrate oestrone sulphate.

New functionally selective muscarinic agonists.

The muscarinic pharmacology of two novel agonists related to McN-A-343, 4-F-PyMcN and 4-F-PyMcN+, has been studied by the use of pharmacological and radioligand binding techniques. Both compounds were potent agonists at M1 receptors in rabbit vas deferens (pEC50 = 6.24 and 6.96) and rat duodenum (pEC50 = 5.47 and 6.38), but very weak partial agonists or competitive antagonists at guinea-pig cardiac M2 and ileal M3 receptors. There was no receptor reserve for 4-F-PyMcN in rabbit vas deferens, for which the potency (pEC50 = 6.24) and apparent affinity (pKA = 5.99 and 6.21) were similar. 4-F-PyMcN+ showed only limited binding selectivity between four muscarinic receptor binding assays with apparent affinity constants (pKi) of 5.8, 5.2, 5.6 and 5.7 for M1, M2, M3 and M4 muscarinic receptor subtypes. The two novel functionally M1-selective agonists may provide useful tools with which to study muscarinic receptor mechanisms. The non-quaternary compound, 4-F-PyMcN, might become a starting point for the development of drugs that selectively affect M1 receptors involved in central cholinergic function.

PPADS, a novel functionally selective antagonist of P2 purinoceptor-mediated responses.

We have characterized PPADS (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid) as a novel antagonist which selectively blocks P2 purinoceptor-mediated responses in rabbit vas deferens at pre- and postjunctional sites. PPADS did not interact with alpha 1-adrenoceptors, muscarinic M2 and M3 receptors, histamine H1 and adenosine A1 receptors. Thus, PPADS is a novel and useful pharmacological tool to study co-transmission in tissues where ATP and co-existing neurotransmitters act in concert.

[Does the captopril test improve the diagnosis of primary hyperaldosteronism?]. / Verbessert der Captopril-Test die Diagnostik des primären Hyperaldosteronismus?

Plasma concentrations of renin and aldosterone were measured before and 60 min after taking 25 mg captopril in 242 patients with arterial hypertension (124 men, 118 women, aged 51.9 +/- 12.7 years; unilateral aldosterone-producing adrenal adenoma in 8, idiopathic hyperaldosteronism in 16 and essential hypertension in 189). Basal plasma aldosterone levels were twice as high in those with adenoma or hyperaldosteronism (216.9 +/- 99.1 pg/ml and 256 +/- 123 pg/ml, respectively) as in those with essential hypertension (117.7 +/- 115 pg/ml). Basal renin levels in adenoma and idiopathic hyperaldosteronism (1 +/- 0.8 microU/ml and 2.6 +/- 1.9 microU/ml, respectively) were decreased compared with those in essential hypertension (13.1 +/- 14.2 microU/ml). The basal aldosterone/renin ratio was higher in adenoma (436 +/- 370 pg/microU) and idiopathic hyperaldosteronism (615 +/- 950 pg/microU) than in essential hypertension (52.9 +/- 151.3 pg/microU). The sensitivity of this ratio in combination with the aldosterone concentration was 100% for recognizing an adrenal adenoma, its specificity 92.7%. The mean plasma aldosterone level after captopril administration did not change in adenoma patients, but fell to 162 +/- 85 pg/ml (P less than 0.001) in those with idiopathic hyperaldosteronism. These data indicate that the captopril test contributes to distinguishing primary from idiopathic hyperaldosteronism.

The immunological evidence for a phenylalanine hydroxylase like immunoreactive protein in different human cells and tissues.

Phenylalanine hydroxylase (PAH) was purified 105-fold from human liver. The rel mol mass of the subunits in sodium dodecylsulfate-polyacrylamide gel electrophoresis was 54,000 Da and the isoelectric point was estimated to be between pH 5.0 and 5.2. The activity of purified PAH was inhibited by p-Cl-phenylalanine (p-Cl-Phe), 3-J-tyrosine (3-J-Tyr) and 6-F-tryptophane (6-F-Trp) by 73%, 26% and 10%, respectively. The Km value was 0.36 x 10(-3) mol/l for L-Phe and 5.88 x 10(-5) mol/l for the synthetic cofactor dimethyltetrahydrobiopterin (DMPH4). Polyclonal antibodies raised in rabbits against the active human enzyme showed only a slight cross-reaction with purified rat liver PAH. Using the rabbit antibodies an immunoreactive protein with the same mol mass and isoelectric point as purified human liver PAH and PAH from crude liver extract was detected in extracts from kidney, heart, spleen, brain, pancreas, lung, placenta, leucocytes, cultured skin fibroblasts and chorionic villus cells.

[The HLA and protease inhibitor (Pi) system in erythropoietic (hepatic) protoporphyria. Family studies]. / HLA- und Proteaseninhibitor (Pi-) System bei erythropoetischer (-hepatischer) Protoporphyrie. Familienstudien.

Relations between porphyrias (porphyria cutanea tarda, variegate porphyria) and HLA- or protease inhibitor (Pi-) system were repeatedly found or supposed. Corresponding investigations do not exist for erythropoietic protoporphyria (EP), for which an autosomal dominant mode of inheritance with highly varying expressiveness (additional genes?) is being discussed. Three families with five EP-patients were examined for possible relations between the manifestations of this disease (skin - and liver changes) and the above-mentioned genetic markers. It was remarkable that three of the patients had the HLA A 3, but nobody of the obvious gene-carriers of this disease without clinical manifestations. On the other hand, two ill couples of siblings were genetically different as to HLA A 3. One couple with liver morphological changes each were different as Pi M-carrier and Pi MS-carrier respectively. Thus, relations between the disease and the genetic markers examined could not be proved.

Tryptophan metabolic studies in patients with presenile cataracts.

In 43 patients with presenile cataracts an oral tryptophan loading test with 5 g L-tryptophan was performed and the 24-hour urinary excretion of kynurenine and xanthurenic acid was determined. 5 cases showed pathological deviations and an excretion pattern of tryptophan metabolites via kynurenine, similar as in vitamin B6-dependent xanthurenic aciduria.

[Studies of tryptophan metabolism in cancer of the urinary bladder]. / Tryptophanstoffwechseluntersuchungen beim Harnblasenkarzinom.

In 100 patients suffering from urinary bladder cancer (pTA-4, Nx, M0-1, G0-3) we created an oral tryptophan load administering 5 g of L-type tryptophan. Thereafter the amount of both xanthurenic acid and kynurenin was determined quantitatively in the 24-hour urine. 16 patients revealed pathological test results and excretion pattern of tryptophan metabolites via kynurenin were similar to vitamin B6-dependent xanthurenic aciduria both in its homocygotic and heterocygotic pattern. It has not been possible to prove a direct correlation between xanthurenic aciduria and urinary bladder cancer. However, xanthurenic aciduria may be of significance as a risk factor in the etiopathogenesis of urinary bladder cancer.

[The acetylator phenotype in patients with urinary bladder cancer]. / Zum Azetylierungsphänotyp bei Harnblasenkarzinompatienten.

In 53 patients suffering from bladder cancer the acelylization phenotype was examined. The frequency of slow acetylizers (70%) was significantly higher than in the control group. The more frequently occurrence of slow acetylizers in the group with professional pollutant exposition is an important reference to a higher bladder cancer morbidity in the case of carcinogen contact. A screening of the acetylization phenotype in professions with carcinogen contact may be important in the prophylaxis of bladder cancer.