[History of anesthesia : "From narcosis to perioperative homeostasis"]. / Geschichte der Anästhesie : "Vom Narkotiseur zum perioperativen Homöostatiker".

In the western World 16 October 1846 is often called "Ether Day", marking the beginning of anesthesia. Before that date, for physicians there was only a struggle against pain. In the following 170 years all fields of general anesthesia as well as regional and local anesthesia were continuously developed. Pharmacological developments and technical innovations made this evolution possible. The complexity of this field of medicine requires a specialist: the anesthesiologist, whose selection of the most suitable form of anesthesia for the patient makes the surgical intervention painless. In addition, the history of anesthesia was characterized by personalities who were responsible for the progress of this medical field. Anesthesia is one part of the discipline of anesthesiology, which also includes resuscitation, intensive care medicine, emergency medicine and pain therapy.

[American influences on the development of anaesthesiology in the Federal Republic of Germany between 1949 and 1960]. / Angloamerikanische Einflüsse bei der Etablierung der Anästhesie in der Bundesrepublik Deutschland im Zeitraum von 1949 - 1960.

In anaesthesia, relations between the Federal Republic of Germany and the United States as well as Great Britain are traditionally good and long established. Political conditions have not interfered with the scientific exchange. In the years after World War II, these contacts helped to establish anaesthesia as a special field of medicine in Germany. Today, these contacts are mutual and indispensable. Important steps in establishing anaesthesiology in Germany were the support of the USA and Great Britain in reconstructing the field in general and enabling the education and advanced training of physicians. The participation of Sir Robert Macintosh in the German Surgeons' Congress in 1950 and his presentation there contributed decisively to the professionalization of anaesthesia. This was the starting point for the consolidation of anaesthesia as a special discipline of medicine in Germany in the 1960s.

Effect of bile acids on the proliferative activity and apoptosis of rat hepatocytes.

Bile acids are known to have damaging as well as protective effects on liver cells. A likely candidate for bile acid-mediated hepatocellular injury during cholestasis is glycochenodeoxycholic acid (GCDCA), a hydrophobic bile acid with a direct cytotoxic effect on hepatocytes. In contrast, ursodeoxycholic acid was shown to exhibit protective effects. Our aim was to determine the effect of GCDCA on proliferation, synthesis and secretion of proteins and death processes in cultured rat hepatocytes. Furthermore, it should be studied whether the hydrophilic bile acid tauroursodeoxycholic acid (TUDCA) might be able to protect cells from the damaging effect of GCDCA. Our results demonstrate that GCDCA decreased dose-dependently hepatocellular proliferation, synthesis and secretion of newly synthesized proteins and, at low concentration, induced apoptosis or, at high doses, cytolysis of cultured hepatocytes. TUDCA did not exert cytotoxic effects on the isolated hepatocytes at a wide range of concentrations. However, TUDCA coincubated with GCDCA protected the cells from the damaging effect of GCDCA at all measured parameters except the secretion of newly synthesized protein.

[Early contributions from Erlangen to the theory and practice of general anesthesia with ether and chloroform. 2. The animal experiments of Ernst von Bibra and Emil Harless]. / Frühe Erlanger Beiträge zur Theorie und Praxis der Ather- und Chloroformnarkose. Teil 2. Die tierexperimentellen Untersuchungen von Ernst von Bibra und Emil Harless.

Just three months after the first application of sulphuric ether to a patient in german-speaking countries the monography Die Wirkung des Schwefeläthers in chemischer und physiologischer Beziehung was published. In this book Ernst von Bibra and Emil Harless presented their experimental research on the effects of ether on humans and compared it to those on animals. The contents of the book are described. The authors "Theory on the action of ether" will be discussed in the context of contemporary criticism. Their hypothesis affected the discussion on the mechanisms of anaesthetic action up to the twentieth century.

Chronic liver injury alters basal and stimulated nitric oxide production and 3H-thymidine incorporation in cultured sinusoidal endothelial cells from rats.

BACKGROUND/AIM: Under pathological conditions the nitric oxide synthase (NOS)-mediated nitric oxide production of sinusoidal endothelial cells might be altered. Therefore, studies were performed to evaluate the nitrite formation by cultured sinusoidal endothelial cells from rat livers chronically injured by thioacetamide and the effect of endogenously or exogenously generated nitric oxide on their proliferative activity. METHODS: Basal and stimulated nitrite formation, expression of NOS and DNA synthesis were examined in sinusoidal endothelial cells isolated and cultivated from livers with incipient or advanced chemically-induced cirrhosis. RESULTS: Cultured sinusoidal endothelial cells from injured livers exhibited a reduced basal and an increased lipopolysaccharide-stimulated nitrite production when compared with controls. Western blot analysis revealed a markedly reduced protein expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in sinusoidal endothelial cells from both experimental groups when compared with controls. Lipopolysaccharide stimulated iNOS expression in sinusoidal endothelial cells from control livers only marginally, and from those with cirrhosis more strongly. There was no clear correlation between the amount of enzyme and nitrite formation. Cultured sinusoidal endothelial cells from livers with incipient cirrhosis showed a higher proliferative activity than controls. Endogenously-produced nitric oxide inhibited DNA synthesis in all groups in a cGMP-independent way. Exogenously-generated nitric oxide affected DNA synthesis differently in sinusoidal endothelial cells from controls and injured livers. CONCLUSION: The results provide evidence that cultured sinusoidal endothelial cells from controls and livers with incipient or advanced cirrhosis differ with respect to basal and lipopolysaccharide-stimulated nitrite production. The data can be taken as evidence that in sinusoidal endothelial cells from livers chronically injured by thioacetamide, eNOS and iNOS are aberrantly expressed and differently regulated.

Differential effects of exogenous and endogenously generated H2O2 on phagocytic activity and glucose release of normal and cirrhotic livers.

BACKGROUND/AIMS: Reactive oxygen species play an essential role in necro-inflammatory processes. Therefore, the aim of the present studies was to investigate the effect of exogenous and endogenously produced H2O2 on the phagocytic capacity and glucose release of perfused cirrhotic rat livers in comparison with that on the controls. METHODS: Complete septal cirrhosis was achieved by oral treatment of rats with thioacetamide for 6 months. The phagocytic capacity of the perfused livers was measured by the uptake of colloidal carbon. During the continuous perfusion with colloidal carbon, either H2O2 or benzylamine was added to the perfusion medium for a limited time period. The latter functioned as an endogenous H2O2 donor. RESULTS: In control rats exogenous and endogenously produced H2O2 caused a transient stimulation of the hepatic colloidal carbon uptake as well as of the glucose release. Inhibition of the catalase by aminotriazol doubled the changes evoked by H2O2, whereas blockade of the Kupffer cells by GdCl3 drastically reduced its stimulatory effect. Cirrhotic livers took up less colloidal carbon and released lower amounts of glucose than the controls when stimulated by exogenous H2O2. The inhibition of the nitric oxide synthetase augmented the H2O2-induced effect in controls as well as in the cirrhotic livers by 250% and 620% (colloidal carbon uptake) and 340% and 760% (glucose release), respectively. The blockade of the eicosanoid production by indomethacin and caffeic acid drastically increased the glucose release and the colloidal carbon uptake in controls and, in absolute terms, to a lesser extent in cirrhotic livers. Endogenous H2O2 produced by the addition of benzylamine stimulated the colloidal carbon uptake and glucose release in livers from both groups. The inhibition of the lipoxygenase increased both parameters, whereas different effects were elicited by the addition of superoxide dismutase in controls and cirrhotic livers. CONCLUSION: The maximum uptake of colloidal carbon and glucose release, measured after stimulation by H2O2, was lower in cirrhotic livers than in controls, thus indicating a lowered phagocytic capacity of Kupffer cells and altered glycogenolytic response of the hepatocytes in cirrhotic livers. The use of various effectors provided evidence that superoxide anions, nitric oxide and, possibly, arachidonic acid are involved in the signal transduction between Kupffer cells and hepatocytes when stimulated by exogenous or endogenously produced H2O2. This signalling mechanism seems to be impaired in cirrhotic livers.

Transthoracic bronchial intubation in a case of main bronchus disruption.

We report on a case of blunt thoracic trauma that resulted in complete disruption of the right main bronchus. Due to massive loss of respiratory volume during thoracotomy, sufficient ventilation could not be maintained via the orotracheal tube. Transthoracic intubation of the left main bronchus via the right bronchial defect was the ultima ratio procedure that allowed reanastomosis of the disrupted right main bronchus.

Oxygen radical formation, proliferative activity and phagocytic capacity of cultivated macrophages from cirrhotic rat livers.

A method to isolate and cultivate macrophages from Macronodular-cirrhotic rat livers was developed in order to characterize them biochemically, by comparing various functional parameters in macrophage cell cultures from controls and cirrhotic livers. Cells were prepared from female Wistar rats, made cirrhotic by treatment with thioacetamide, by means of a pronase-collagenase digestion method followed by a nycodenz gradient and elutriation. The yield of macrophages was 8.9 x 10(6) cells/g for controls and 10.6 x 10(6) cells/g for cirrhotic livers. The vitality of the cells was > 95%. Forty-eight hours after cultivation, the purity of the cell fractions amounted to 94% and 91% in controls and in the experimental group, respectively. Nitric oxide synthesis was more markedly stimulated by lipopolysaccharide (LPS) in cultures from cirrhotic livers than in those from controls (25 +/- 4 vs 5.8 +/- 1 nmol/10(6) cells/72 hours). Interferon-gamma (IFN-gamma) induced the nitric oxide synthase more rapidly in macrophage cultures from cirrhotic livers than in controls. The production of superoxide anions by macrophages from cirrhotic livers stimulated by zymosan was significantly lower by about 40% when compared with the controls. Incorporation of 3H-thymidine was increased to 250% in cultivated macrophages from thioacetamide-treated rats in comparison with macrophages from untreated animals. The stimulated phagocytic activity of cultivated macrophages from cirrhotic livers did not differ significantly from that of the controls. The data presented provide evidence that it is possible to isolate and to cultivate macrophages from macronodular-cirrhotic livers with high yield and vitality. They are characterized by enhanced proliferation, reduced formation of superoxide anions, and increased production of nitric oxide.

Phagocytic function and metabolite production in thioacetamide-induced liver cirrhosis: a comparative study in perfused livers and cultured Kupffer cells.

BACKGROUND/AIMS: The aim of the study presented here was to evaluate the basal and stimulated phagocytic activities and the metabolite production of isolated perfused livers, and also the phagocytic capacity of cultured Kupffer cells from rats with macronodular cirrhosis. METHODS: Rats were made cirrhotic by oral administration of thioacetamide. The phagocytic activity was assessed by the rate of removal of colloidal carbon. The Kupffer cells were prepared by a pronase/collagenase digestion method followed by elutriation. RESULTS: The phagocytic activity and production of glucose, lactate and pyruvate were reduced in cirrhotic livers when calculated per g liver. Due to hyperplastic-regenerative processes the mass of the cirrhotic livers was markedly augmented so that the colloidal carbon uptake calculated per cirrhotic liver was not significantly different from the controls. Colloidal carbon-induced glucose release increased more markedly in the controls than in cirrhotic livers. Isoproterenol considerably stimulated phagocytosis and glucose production in controls, whereas the response was clearly reduced in cirrhotic livers when calculated either per g liver or per total liver weight. The cyclic AMP analogue elicited a marked glycogenolytic response in the controls, whereas there was only a slight increase in glucose production in cirrhotic livers. Phagocytosis of cirrhotic livers was only moderately stimulated by opsonized zymosan when compared with the controls. Freshly isolated Kupffer cells exhibited a reduced phagocytic activity. Stimulation by zymosan was observed only in cell suspensions of the controls. In contrast, Kupffer cells from cirrhotic livers did not differ from controls with respect to basal or zymosan-stimulated phagocytic activity after 48-h cultivation. CONCLUSION: The stimulated phagocytic function was disturbed in perfused macronodular-cirrhotic livers as compared to controls. In contrast, 48-h cultured Kupffer cells from cirrhotic livers exhibited the same basal and stimulated phagocytic capacity as controls. The glucose release from perfused livers, initiated by stimulation of Kupffer cells or hepatocytes, was significantly reduced in cirrhotic livers. Therefore, we postulate an impaired intra- and/or intercellular signalling in macronodular-cirrhotic livers.

Fructose 2,6-bisphosphate metabolism in Ehrlich ascites tumour cells.

Cancer cell energy metabolism is characterized by a high glycolytic rate, which is maintained under aerobic conditions. In Ehrlich ascites tumour cells, the concentration of fructose 2,6-bisphosphate (Fru-2,6-P2), the powerful activator of 6-phosphofructo-1-kinase, is tenfold increased. The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), synthesizing and degrading Fru-2,6-P2, was characterized. The molecular mass is 120 kDa. The dependence of PFK-2 activity on the substrate concentrations is hyperbolic (Km for Fru-6-P = 0.09 mM; Km for ATP = 0.7 mM), while the dependence of the FBPase-2 activity on the concentrations of Fru-2,6-P2 is sigmoidal (K0.5 for Fru-2,6-P2 = 4 microM). The PFK-2/FBPase-2 activity ratio is 1. PFK-2 activity is inhibited by citrate (I0.5 = 0.17 mM) and phosphoenolpyruvate (I0.5 = 0.08 mM) but only weakly by glycerol 3-phosphate (I0.5 = 1.57 mM). In contrast to the liver enzyme, the activity of tumour PFK-2/FBPase-2 is not influenced by the action of cAMP-dependent protein kinase. The kinetic properties as well as ion-exchange chromatography pattern differ from their normal counterparts in liver and muscle. The properties are likely to contribute to the maintenance of the high glycolytic rate in these tumour cells.

[The effect of halothane, enflurane and isoflurane on resistance and compliance in patients with asthma or chronic obstructive lung diseases]. / Die Wirkung von Halothan, Enfluran und Isofluran auf Resistance und Compliance bei Patienten mit Asthma oder chronisch-obstruktiven Lungenerkrankungen.

In order to test the hypothesis that halothane is more effective and safer than enflurane and isoflurane in patients with reactive airway disease, a clinical trial was performed to compare these three agents in patients with asthma or chronic obstructive pulmonary disease (COPD). METHODS. After obtaining institutional approval and informed consent, 31 patients with bronchial asthma or COPD were studied (FEV1 less than 65% of FVC); all patients underwent extensive surgery of the paranasal sinuses. Premedication consisted of i.m. atropine and promethazine; anesthesia was induced with diazepam, fentanyl, etomidate, and succinylcholine and maintained with pancuronium and 50% N2O in O2 together with one of the volatile agents, halothane, enflurane, or isoflurane, selected at random. Patients were mechanically ventilated. On the basis of respiratory pressures, volumes, and flows, inspiratory (Rin) and expiratory (Rex) resistance and compliance (C) were calculated after induction (control), 15 min after the addition of the volatile agent (1.25 MAC), every 15 min during the surgical procedure, and at the end of the operation. RESULTS. In 1 case, airway resistance increased markedly a few minutes after administration of isoflurane. The results obtained in this patient were not included in the evaluation of the data. There were no statistically significant differences in the preoperative data or control values of Rin, Rex, and C among the three groups (n = 10 each). With the respective inhalational agents, Rin increased maximally between 3% (halothane) or 8% (enflurane) and 21% (isoflurane), Rex between 16% (halothane, enflurane) and 29% (isoflurane). For the most part, however, these changes were not statistically significant as compared with controls. Intergroup comparisons failed to reveal any statistically significant differences either. In all groups C decreased continuously to about 90% of control. DISCUSSION. The results show that in patients with asthma or COPD, airway resistance remains virtually unchanged during surgery and anesthesia under halothane or enflurane anesthesia. With isoflurane, however, the resistance may rise by a slight but not statistically significant extent. Furthermore, marked bronchospastic reactions occurred in 2 patients in the isoflurane group. Thus, the three volatile anesthetics studied were not found to be unequivocally safe and effective in preventing increases in bronchomotor tone. However, pharmacodynamic effects other than those on respiration (e.g., cardiovascular actions, arrhythmogenic threshold, metabolism, toxicity) must additionally be taken into consideration.

[Use of psychological pain-control technics in psychiatry]. / Zum Einsatz psychologischer Schmerzkontrolltechniken in der Psychiatrie.

In recent years the initial attempts at algotherapy employing the predominating forms, such as medicinal treatment, electrotherapy, and operative treatment, have greatly improved the care of patients suffering pain. Psychological pain control techniques are a further feasible means of treatment. They include cognitive and behavioral intervention techniques in part already well known that can accompany and enhance traditional forms of anodyne therapy. By way of example, the concept of "pain inoculation" (Bullinger & Turk, 1982) is described in its sequence of phases. Methods of application in clinical practice are referred to.

[Effect of isoflurane on respiratory mechanics]. / Der Einfluss von Isofluran auf die Atemmechanik.

The effects of the inhalational anaesthetic, isoflurane, on two major parameters of respiratory mechanics--resistance and compliance--were studied in a total of 30 patients. With increasing inspiratory concentrations of isoflurane, resistance was measured in 5 spontaneously breathing patients using the oscillation method. In 16 mechanically ventilated patients resistance and compliance were calculated from airway pressure, gas flow, and tidal volume. In 9 patients with asthma or COPD the course of resistance and compliance was recorded intraoperatively. An increase in resistance of up to 117% of the initial volume occurred during spontaneous respiration, and was caused by a decrease in tidal volume. During mechanical ventilation with constant tidal volume, no definite changes in resistance or compliance were seen with increasing isoflurane concentrations. In the patients with elevated airway resistance there were only minor, statistically non-significant changes in resistance and compliance. The results show that the effects of isoflurane on respiratory mechanics do not differ from those of halothane or enflurane. Therefore, isoflurane may be considered appropriate for use in patients with impaired airway resistance.

Sulfonyliminoimidazolidines, a new class of oral hypoglycemic agents. 4. Toxicity and general pharmacology of 1-[p-[2-(crotonylamino)-ethyl]-phenylsulfonyl]-3-cyclohexy l-2-imino- imidazolidine (CGP 11 112).

Results of a first segment of toxicity tests and general pharmacological investigations with 1-[p-[2-(crotonylamino)-ethyl]-phenylsulfonyl]-3-cyclohexyl- 2- iminoimidazolidine (CGP 11 112), a potent new oral hypoglycemic agent, are reported. The acute LD50 in rats was 600 mg/kg p.o. and 25 mg/kg i.v. In a range finding study doses of 60 mg/kg p.o. and 10 mg/kg i.p., administered daily for 10 days, were tolerated without symptoms in rats, and 30 mg/kg p.o. produced no unequivocal toxic effects in dogs. Slight and transient increases of blood pressure were observed in anaesthetized cats at doses of 0.3 mg/kg i.v. and above. 3 mg/kg i.v. (1/10 LD) caused a transient blood pressure decrease. Heart rate, tidal volume and blood pressure effects of epinephrine (adrenaline), norepinephrine (noradrenaline) and acetylcholine were not significantly influenced in a dose range from 0.01 to 1.0 mg/kg i.v. In isolated organ segments, CGP 11 112 produced only unspecific effects at high concentrations. No intrinsic activity, but antagonism against BaCl2-induced contractions were observed in isolated guinea-pig ileum (one third papaverine hydrochloride). Rate and force of contraction of isolated guinea-pig atria were not affected up to 2.4 mumol/l; higher concentrations were cardiodepressant. In rats, CGP 11 112 increased the excretion of urine, sodium and chloride, but not potassium, dose-dependently (range 10-100 mg/kg). Similar effects observed in dogs suggest that the compound may affect fluid and electrolyte balance at high doses. Moderate antiphlogistic activity (ED40 10-40 mg/kg) was observed in the carrageenin-induced rat paw oedema.(ABSTRACT TRUNCATED AT 250 WORDS)