Embryotoxic/teratogenic potential of halothane

Summary The embryotoxic/teratogenic potential of halothane was evaluated on the basis of available data obtained in an extensive literature search. It was found that halothane induced ultrastructural visible changes in the offspring of rats exposed to concentrations of 10 ppm during gestation. These consisted of degenerative changes in the cerebral cortex and, in particular, the weakening of cell membranes and the vacuolisation of the Golgi-complex. Macroscopically visible morphological changes were seen in rats only after exposure to concentrations equivalent to 320-fold (1600 ppm) the MAK value (maximum concentration value at the workplace). Furthermore, behavioural disorders were seen when exposure to concentrations 10 ppm occurred during gestation and after parturition. In mice, only macroscopical investigations were performed. The first disturbances scored were only visible as retardation in the offspring, and occurred after exposure to concentrations of halothane 200-fold (1000 ppm) the MAK-value. In the rabbit, anaesthetic concentrations of 22 000 ppm. halothane did not result in an embryotoxic/teratogenic effect.The individual epidemiological findings in humans were discussed controversially. The studies are inconclusive in establishing an embryotoxic/teratogenic risk following sole exposure to halothane at the MAK level, since mixed exposures occurred and data on the concentrations of halothane in the inhaled air were missing. Therefore, the decision on whether halothane can impair intrauterine development is primarily based on the animal experimental findings. As long as a threshold value has not been established for the observed lesions, halothane should not be inhaled during pregnancy.     

Activation of benzylic alcohols to mutagens by human hepatic sulphotransferases

Four primary and five secondary benzylic alcohols derived frompolycyclic aromatic hydrocarbons were tested for mutagenicityin Salmonella typhimurium TA98 in the presence of 3'-phosphoadenosine-5'-phosphosulphate,the cofactor for sulphotransferases, and varying amounts ofhepatic cytosol from three or four different human subjects,a 3-year-old child, an adult female, an adult male and one unknown.All compounds except one, 4H-cyclopenta[def] phenanthren-4-ol,were activated to mutagens. The interindividual variation inthe activities was at most 3-fold and the individual activitiestowards the different substrates were correlated with each other.The same compounds had previously been tested in the presenceof hepatic cytosol from rats and all compounds activated inone species were also activated in the other species. However,there were marked quantitative differences, which were furthercomplicated by the observation of a substantial sex differencein the rat. Male and female rat liver cytosol showed highersulphotransferase activities towards 1-hydroxymethylpyrene,9-hydroxymethylanthracene, 7-hydroxymethyl-12-methylbenz[a]anthraceneand 4H-cyclopenta[def]chrysen-4-ol than human liver cytosol.The largest difference in activity was seen with 7-hydroxymethyl-12-methylbenz[a]anthracene,reaching a factor of     

Der Wert der Duplexsonographie nach der orthotopen Lebertransplantation Erfahrungen an 44 Patienten

Zusammenfassung In einer prospektiven Untersuchung wurde an 44 Patienten (33 Männer, 11 Frauen) riach einer elektiven orthotopen Lebertransplantation die Duplexsonographie 196ma1 angewendet. Ziel der Untersuchung war es festzustellen, inwieweit and in welchem zeitlichen Zusammenhang sich die Parameter pulsatiler FluBindex (PFI) und Dämpfungsindex (DI) bei Komplikationen wie Abstoung und Cholangitis verändern. Der Duplex-Doppler-Ultraschall wurde im Mittel 5mal pro Patient durchgeführt. Die letzte Sonographie erfolgte am Entlassungstag. Bei den Messungen fiber der Leberarterie, der Pfortader und den Lebervenen wurden jeweils der PFI und der DI bestimmt. Die Ergebnisse der Indexuntersuchungen wurden mit dem klinischen Verlauf (Abstoung, Cholangitis) sowie mit den Resultaten von 88 Biopsiepräparaten der Lebertransplantate in Beziehung gesetzt. Bezüglich einer histologisch gesicherten AbstoBung ergab der PFI (über der Leberarterie gemessen) eine Sensitivität von 69,4 % and eine Spezifitdt von 72,2 %, der DI (über den Lebervenen gemessen) eine Sensitivität von 89,4% und eine Spezifitdt von 89,1 %. Wenn auch die einfach und beliebig oft anwendbare Untersuchungstechnik die bioptische Sicherung einer Rejektion nicht ersetzen kann, so ist sie in hohem Mae in der Lage, Indikationen zur Biopsie frühzeitig stellen zu lassen und ein Ansprechen auf eine Therapie kurzfristig und mit holier Genauigkeit anzuzeigen.

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Duplex sonography after orthotopic liver transplantation: findings in 44 patients

In a prospective study, 44 patients (11 women, 33 men) who had received orthotopic liver transplants underwent a total of 196 consecutive duplex Doppler ultrasound examinations. The aim of the study was to evaluate the correlation between the pulsatile flow index (PFI) and the damping index (DI) as far as complications as rejection or cholangitis were concerned. The patients were examined five times each on average. The PFI and DI were measured in the hepatic artery, the portal vein and the hepatic veins. The findings were compared with the clinical course (cholangitis, rejection) and the histomorphological diagnosis as determined in biopsy specimens. In biopsy-proven rejection episodes, the sensitivity of the PFI in the hepatic artery was 69.4%, the specificity 72.2%. The sensitivity of the DI in the hepatic vein was 89.4%, the specificity 89.1 %. Combining the two, specificity was more than 90%. PFI and DI in the portal vein bore no apparent relation to clinical course or histomorphological diagnosis. We found duplex Doppler ultrasound extremely beneficial in determining the timing and indication for liver biopsy. In addition, this simple examination, which can be performed as often as desired, accurately shows the transplanted liver's response to measures taken to counter rejection.

     

An evaluation of two methods for chronic central venous access device placement

BACKGROUND: Chronic venous access devices (CVADs), placed for phlebotomy and the administration of medications and nutrition, require fluoroscopy to confirm correct catheter position. Long-term central venous catheters placed using an electromagnetic catheter locating system (EMCLS) could result in decreased radiation exposure and decreased cost without compromising accuracy of position. METHODS: Charts of patients who underwent placement of CVADs at University of New Mexico (UNM) Hospital or UNM Cancer Center were reviewed. Inclusion criteria included age >20 years and placement of a central CVAD utilizing fluoroscopy (group 1) or the EMCLS (group 2). Radiation exposure, complications, cost, and accuracy of placement were determined for each technique. RESULTS: Between June 1996 and June 1998, 196 patients underwent placement of CVADs. Complete data sets were available for 46 patients in each group. There were no statistically significant differences in age, gender, complications, or operating room times (P = 0.26). Fluoroscopy and EMCLS were equally accurate for the correct placement of the tip of the line (P = 0.12). Mean patient radiation exposure was EMCLS, 30 mRem, and fluoroscopy, 771 mRem. EMCLS significantly decreased cost (P = 0.025) when compared with fluoroscopic assisted catheter placement. CONCLUSIONS: The use of EMCLS for CVAD placement reduces radiation exposure and cost without compromising the accuracy of placement when compared with standard fluoroscopic-assisted placement.     

Changes in the extracellular profiles of neuroactive amino acids in the rat striatum at the asymptomatic stage of hepatic failure

Rats were treated with a hepatotoxin thioacetamide (TAA) and examined 21 days later, when they showed moderate fatty metamorphosis of the liver and morphological changes in brain indicative of excitotoxic neuronal damage, but no evident biochemical or neurophysiological symptoms of hepatic encephalopathy (HE). High-performance liquid chromatography (HPLC) analysis of extracellular amino acids in striatal microdialysates of TAA-treated rats revealed a significant increase in the excitatory amino acids glutamate (Glu) and aspartate (Asp) and their amino acid metabolites glutamine (Gln) and alanine (Ala). Microdialysis in the presence of 50 mM K+ triggered in TAA-treated rats an accumulation of Asp and Glu, and diminished the accumulation of Gln. These effects were virtually absent in control rats. None of the treatments affected the accumulation of the nontransmitter amino acid leucine (Leu). The above changes mirror those previously described in symptomatic HE and are likely to contribute to excitotoxic damage. The basal microdialysate content of taurine (Tau), an amino acid with antioxidant and volume regulatory properties, was 60% lower in TAA-treated rats than in control rats despite its increased blood-to-brain transport. The decrease in extracellular Tau may thus reflect Tau redistribution to adjacent central nervous system (CNS) cells manifesting a cell-protective response. Stimulation with 50 mM K+ increased extracellular Tau in control rats by 182% and in TAA-treated rats by 322%. Stimulation with 100 microM N-methyl-D-aspartate (NMDA) increased extracellular Tau in control rats by 27 % and in TAA-treated rats by as much as 250%. The increase of K+- or NMDA-dependent Tau release may reflect improved cell volume regulation and neuroprotection and contribute to attenuation of neurologic symptoms in rats with liver failure.     

Corneal astigmatism as a special complication after lid-loading in patients with lagophthalmos Hornhautastigmatismus als besondere Komplikation*

Lid-loading with precious metals, described by Illig in 1958, has become increasingly important. Because of its good functional and cosmetic results this method is superior to tarsorrhaphy. Furthermore, lid-loading can be combined with additional surgical techniques to achieve more dynamic lid-closure. In a prospective study we examined the results after lid-loading and discuss postoperative changes of the cornea.     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

• 1 Autoradiographic binding studies have shown that the AT₁ receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT₁ receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
• 2 While there are differences between species, AT₂ receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
• 3 Circulating AngII acts on AT₁ receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
• 4 Centrally administered AngII may act on AT₁ receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
• 5 Recent evidence shows that centrally administered AT₁ antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
• 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT₁ receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.

     

Studies of the binding of diolepoxide metabolites of polycyclic aromatic hydrocarbons to DNA using electrofluorescence polarization spectroscopy

In the electrofluorescence method, a solution of DNA with covalentlybound polycyclic hydrocarbons is placed in an electric field,and changes in the intensity of polarized fluorescence are observed.Under the correct conditions, these changes can be used to determinea value for the angle between the long axis of the hydrocarbonmolecule and the axis of the DNA helix. For DNA or poly(dA-dT)treated with each stereoisomer of anti-benzo[c]phenanthrenediolepoxide, ranged from 55° to 61°, consistent witha mixture of quasi-intercalated adenine adducts and externallybound guanine adducts. Similar results were obtained with anotherset of ‘fjord-region’ diolepoxides, derived frombenzo[c]chrysene. Adducts in DNA treated with diolepoxides derivedfrom chrysene, 5-methylchrysene or 6-methylchrysene gave of53°, so the predominant adducts are externally bound, probablyin the minor groove of DNA.