[Reconstruction of the examination of the laryngeal carcinoma of Emperor Frederick III by Rudolf Virchow]. / Rekonstruktion der Befundung des Larynxkarzinoms Kaiser Friedrichs III. durch Rudolf Virchow.

Rudolf Virchow is one of the founders of modern pathology, and many of his ideas on inflammatory and neoplastic diseases are still valid today. Even for Virchow, determination of malignancy was not always easy. As an example, the laryngeal disease of Crown Prince Frederick William, the later Emperor Frederick III, is presented.The clinical findings at the beginning of the disease were suggestive of a carcinoma, though an inflammatory lesion was also discussed. Several attempts were made to remove the lesion bioptically, but local recurrences occurred and the first tissue samples were not examined histopathologically. Since laryngeal tumour operations had a high mortality at that time, histopathologic examinations were made in order to decide for or against an operation. The samples taken after pre-treatment did not meet Virchow's criteria for determining a carcinoma. Contrary to the present concept of a carcinoma in situ-carcinoma sequence, Virchow's concept was based on the assumption that carcinomas are not derived from the epithelium, but arise from a mesenchymal-epithelial transformation from the connective tissue. The clinical suspicion of a laryngeal carcinoma was confirmed only shortly before the patient's death and later by a post-mortem examination.The question repeatedly asked is whether Virchow should have diagnosed a carcinoma at the beginning of the disease. The answer has been the same for more than a hundred years: the clinician is dissatisfied with the histopathological diagnosis, so the pathologist is to blame.

The intubation scoop (i-scoop) - a new type of laryngoscope for difficult and normal airways.

The i-scoop is an intubation device with a curved guiding bar with laterally located lenses at its tip, rather than a blade. Twenty-five anaesthesiologists intubated a manikin that simulated first a normal and then a difficult airway. All participants were able to intubate the difficult airway with a good view of the glottis using the i-scoop. None was able to intubate using seven other laryngoscopes (Macintosh laryngoscope, GlideScope(®) GVL and AVL, McGrath(®) (Series 5/MAC), C-MAC(®) , A.P. Advance(™) ). Intubation was successful only with the Airtraq(®) (n = 10), the Airway Scope (n = 5), the C-MAC D-Blade (n = 2), the A.P. Advance DAB (n = 1) and the GlideScope DL Trainer (n = 1) (p < 0.001, success rate of i-scoop vs all 12 laryngoscopes combined). In contrast to all other videolaryngoscopes, intubation of the normal airway with the i-scoop was achieved even faster than with the Macintosh laryngoscope (p < 0.02). The i-scoop outperformed all other laryngoscopes in both difficult and normal airways, and therefore has potential as an easier and safer alternative to present devices.

X inactivation: Tsix and Xist as yin and yang.

A new study shows that expression of Tsix, an antisense Xist gene, can be controlled by imprinting, and that high Tsix activity during X inactivation can protect the future active X chromosome from silencing by Xist. Tsix and Xist seem to have a yin and yang relationship, with opposite effects on X inactivation.

Activation of RNA polymerase III transcription of human Alu repetitive elements by adenovirus type 5: requirement for the E1b 58-kilodalton protein and the products of E4 open reading frames 3 and 6.

We found that transcription of endogenous human Alu elements by RNA polymerase III was strongly stimulated following infection of HeLa cells with adenovirus type 5, leading to the accumulation of high levels of Alu transcripts initiated from Alu polymerase III promoters. In contrast to previously reported cases of adenovirus-induced activation of polymerase III transcription, induction required the E1b 58-kDa protein and the products of E4 open reading frames 3 and 6 in addition to the 289-residue E1a protein. In addition, E1a function was not required at high multiplicities of infection, suggesting that E1a plays an indirect role in Alu activation. These results suggest previously unsuspected regulatory properties of the adenovirus E1b and E4 gene products and provide a novel approach to the study of the biology of the most abundant class of dispersed repetitive DNA in the human genome.

Messenger RNAs encoding mouse histone macroH2A1 isoforms are expressed at similar levels in male and female cells and result from alternative splicing.

Two protein isoforms of histone macroH2A1 (mH2A1) are found in mammalian cells. One isoform, mH2A1.2 is highly concentrated on the heterochromatinized inactive X chromosome (Xi) of female cells. mH2A1.2 protein is also present in male cells, but fails to form dense concentrations. Another protein isoform, mH2A1.1, differs from mH2A1.2 by a single short segment of amino acids. In this study, we cloned and characterized the genomic locus of the mouse mH2A1 gene and mapped it to chromosome 13. Two alternatively spliced transcripts derived from the mH2A1 locus are responsible for the generation of the two mH2A1 protein isoforms with mH2A1.2 mRNA being the most abundant spliced form in all tissues examined. The absolute amount of mH2A1 mRNA is similar in male and female cells for most tissues with the exception of testes where it is par-ticularly abundant. Both spliced forms are present in all adult tissues analyzed as well as in female embryonic stem cells. In contrast, male embryonic stem cells expressed mH2A1.1 at low levels if at all. The relatively abundant expression of mH2A1 in both sexes suggests that mH2A1 has functions in addition to a possible involvement in X chromosome inactivation.

Activation of expression of multiple subfamilies of human Alu elements by adenovirus type 5 and herpes simplex virus type 1.

The nearly one million Alu repetitive elements in the human genome can be grouped into a number of subfamilies. Comparisons between subfamily consensus sequences suggest that Alu evolution is characterized by the sequential amplification and dispersal of a limited number of Alu founder sequences. The S, Sb and Sb1 subfamilies provide an example of such a related series of Alu subfamilies. We have previously demonstrated that adenovirus type 5 and herpes simplex virus type 1 activate RNA polymerase III transcription of endogenous Alu elements in HeLa cells. Here, we report that expression of Alu sequences belonging to the S, Sb and Sb1 subfamilies was activated following infection with these viruses. The data indicate that transpositionally inactive Alu elements can give rise to high levels of pol III transcripts in the presence of appropriate trans-acting factors and demonstrate that the class III promoters of a significant number and variety of Alu sequences are functional in vivo. Multiple subfamilies of Alu sequences were induced in transformed and non-transformed cell types, suggesting that induction of Alu expression may be part of the normal cellular response to viral infection.

Mammalian X chromosome inactivation.

X chromosome inactivation in mammals requires expression of the gene Xist, which maps to the X chromosome inactivation centre (Xic) and encodes an untranslated RNA. Truncation of Xist RNA by gene targeting is lethal for female embryos and prevents the inactivation of the X chromosome carrying the deletion. This indicates that Xist RNA is necessary for initiation and propagation of the inactivation process. Xist is transcribed from the inactive X and its expression is silenced by DNA methylation, suggesting that methylation is crucial for shielding the active X chromosome against the inactivation process. Gene transfer experiments using transgenes the size of yeast artificial chromosomes have determined that a 450 kb fragment of DNA carrying Xist acts as an inactivation centre and is sufficient for initiation, propagation and maintenance of the inactive state. The elements for counting and choosing X chromosomes are part of the transgene. We have shown that X inactivation is mediated by a post-translational mechanism, i.e. the stabilization of Xist RNA, rather than by the regulation of the Xist promoter.

Determination of circulating blood volume by measurement of indocyanine green dye in hemolysate: a preliminary study.

In 8 emergency care patients blood volume was determined using Cr5I labelled erythrocytes and indocyanine green (ICG). Prior to measurement of ICG in blood with a spectrophotometer, the blood was hemolyzed with Triton-X. A close correlation of r = 0.97 between the Cr51 and the ICGTR-X estimates was found; the ICGTR-X volume was about 3% lower than the Cr51 volume. In five additional in vitro experiments the ICGTR-X method was found to reflect real volumes with an insignificant error of less than 1%. Blood volume determination with ICGTR-X cannot be applied in cases of circulatory failure. ICG should be administered in a dose of 0.5 mg/kg of body weight. For calibration purposes, a two point calibration curve (point 1: point of intersection of x and y axis; point 2: 5 mg ICG/1 of blood) is sufficient. From these preliminary experiments it is concluded that the ICGTR-X method is a rapid and simple technique of blood volume determination with multiple reproducibility which can be carried out in any clinical laboratory.

Neuroendocrine phenotype differentiation in a hamster lung epithelial cell line under low oxygen pressure or after transformation by diethylnitrosamine.

Oxygen pressure as low as 5% in the gas phase or 87 mmHg in the liquid phase induced various neuroendocrine cell (NEC) phenotypes in more than 80% of cells of a cloned fetal Syrian hamster lung epithelial cell line (M3E3/C3). Further, cells from a number of colonies transformed in an anchorage-independent manner by diethylnitrosamine (DEN) demonstrated a NEC phenotype. Since the cell line used is of a pluripotent stem cell type, both hypoxia and DEN appear to possess a potency for NEC phenotype induction.

Acute apnea caused by an epiglottic cyst.

A life threatening complication in the course of routine sedation in a 5 year old child is reported in a case study. A retention cyst of the epiglottis was found to be responsible for obstruction of the larynx leading to acute apnea. The patient history revealed recurrent episodes of stridor previously diagnosed and treated as acute laryngotracheobronchitis as well as border line psychomotoric retardation. Cerebral magnetic resonance imaging was performed for neuroradiological evaluation. After administration of sedation the child presented with stridor and acute apnea. Emergency orotracheal intubation could prevent tracheotomy but was complicated by the unexpected presence of a tumor at the base of the tongue. Further evaluation revealed a large epiglottic cyst. After endoscopic removal of the cyst no further episodes of apnea or stridor were noted.

[Cerebral hemodynamics during implantation of cardioverter-defibrillator systems]. / Zerebrale Hämodynamik während der Implantation von Kardioverter-Defibrillator-Systemen.

OBJECTIVE: During ICD-implantation it is necessary to prove the function and to determine the optimal threshold by means of induced ventricular fibrillation (VF). Provoked cardiac arrests cause a circulator stop of the cerebral perfusion. Our aim was to examine the changes of cerebral blood flow velocity (CBFV(MCA)) after induced VF depending on the duration of fibrillation and prior values of CBFV(MCA). PATIENTS AND METHODS: Sixty induced episodes of VF in 9 patients (mean age +/- SD 53.5 +/- 8 years) were examined during ICD-implantation. Beside the standardized anaesthesiological monitoring, transcranial Doppler sonography was used to record the cerebral blood flow velocity in the middle cerebri artery CBFV(MCA). The duration of the fibrillation-period and the range and duration of the CBFV increase during the post defibrillation-period were correlated. Additionally, we examined whether systematic differences existed between the episodes of each patient (time-trend) by means of 5 following episodes of a patient. RESULTS: During all episodes of VF and hyperperfusion was present, that means a time interval showing increased values of CBFV(MCA), compared to the values present before VF. The duration of hyperperfusion depended significantly on the fibrillation time (r = 0.57; p < 0.001). The equation of regression is: hyperperfusion time = 11.1 + 1.22 x fibrillation time. The amount of hyperperfusion, that means the maximal CBFV after defibrillation, increase significantly with CBFV(MCA) before VF (correlation = 0.88; p < 0.001). The equations of regression is hyperperfusion height = 6.11 + 1.22 x CBFV(MCA) before VF. The duration of hyperperfusion is not influenced by the maximal CBFV(MCA) after defibrillation (r = 0.08; p = 0.52). In the examined patients no significant differences in the hyperperfusion time maximal CBFV(MCA) after defibrillation between the episodes were found. CONCLUSION: After induced VF you always have to expect a reactive cerebral hyperperfusion. The amount of increase of CBFV after defibrillation depends on the prior values of CBFV before fibrillation and shows a nearly proportional relation to these. The duration of hyperperfusion shows a linear dependency on VF-times. This may show that we had VF-times, in which the cerebral autoregulation and other cerebral physiological reactions compensate the drop of the CBFV(MCA) during VF in the postfibrillation time. In further studies will be examined if there are similar changes in the cerebral metabolism as in CBFV(MCA).

Propofol, remifentanil and mivacurium: fast track surgery with poor intubating conditions.

BACKGROUND: Mivacurium is widespread used because it is the non-depolarizing muscle relaxant with the shortest duration time. Therefore, it seems to be ideal for fast track or ambulatory surgery. However, especially in combination with propofol and remifentanil onset time remains unclear and incidence of poor intubating conditions seems to be higher than in other regimes of anesthesia. METHODS: We included 35 ear, nose and throat (ENT) patients in this study. Muscle relaxation was measured by acceleromyograhpy at the adductor pollicis muscle (a.p.m.) and intubating conditions were evaluated. Anesthesia was induced with 2.5 mg kg-1 propofol and 1 µg kg-1 remifentanil and intubation was performed three minutes after the administration of 0.2 mg kg-1 mivacurium. Open vocal cords conjoined with full relaxation of the a.p.m., easy mouth opening and prevention of coughing and bucking represented the primary endpoint in this study. RESULTS: Only 20% of patients (N.=7) had optimal intubating conditions and achieved the primary endpoint. In 21 patients (60%) a complete block of the a.p.m. could not be achieved and in six patients (17%) the vocal cords were closed. In seven patients (20%) we observed difficult mouth opening and in 11 patients (31%) coughing and bucking. In addition, we found a prolonged onset time of 228±95 seconds (mean±SD). CONCLUSION: In combination with propofol and remifentanil the muscle relaxant agent mivacurium led to uncertain muscle relaxation and to poor intubating conditions. Therefore the study was aborted after 35 patients. Probably mivacurium is not a useful muscle relaxant agent if fast and deep muscle relaxation is needed. The advantage of a short duration time is foiled by intubation complications due to insufficient muscle relaxation.

Effect of ethanol on cardiac single sodium channel gating.

Alcohol in modest and higher doses has the potential to induce cardiac arrhythmias. The most famous alcohol-related arrhythmia is the "holiday heart syndrome". Furthermore, there is a clear association between excessive alcohol consumption and the risk of sudden cardiac death. However, the acute effects of ethanol on arrhythmia induction are not well understood. The effect of ethanol on single cardiac sodium channels has not been studied yet. To elucidate the effect of ethanol on human cardiac sodium channels we performed a patch clamp study in HEK-293 cells overexpressing the human cardiac sodium channel. We used HEK-293 cells overexpressing the human cardiac sodium channel (Na(1.5)). Single channel gating was investigated by the cell-attached patch clamp technique. Sodium channel currents were elicited by depolarizing pulses from -120 to -20mV for a duration of 150ms. Single channel availability, open probability and peak average current were assessed baseline and after addition of ethanol in increasing concentrations (0.50 per thousand (10.9mM), 1.00 per thousand (21.7mM), 2.00 per thousand (43.5mM) and 4.00 per thousand (87.0mM)). We found a concentration-dependent reduction of open probability which was statistically significant at 2.00 per thousand ethanol (66.5+/-14% of control). At higher concentrations (4.00 per thousand) also availability decreased to 66.5+/-11.0% of control. This resulted in a significant decrease of peak average current at 2.00 per thousand and at 4.00 per thousand ethanol (61.8+/-7.4 and 53.0+/-8.2% of control). For the first time the present study demonstrates acute inhibitory effects of ethanol on single cardiac sodium channel gating and provides one potential mechanism for the well known clinical observation that ethanol triggers supraventricular and ventricular arrhythmias.

[Inner ear deafness following lumbar puncture. A complication requiring patient education?]. / Innenohrschwerhörigkeit nach Lumbalpunktion. Eine aufklärungspflichtige Komplikation?

Deafness after lumbar puncture has been reported occasionally. Until now this complication has been regarded as spontaneously reversible, but a more recent publication of three cases of irreversible hearing loss possibly caused by lumbar puncture casts doubt on this. It has been proposed that this complication should be included in the pre-operative information given to patients, but we oppose this proposal.

[Joseph Weiger and the introduction of anesthesia in Vienna]. / Joseph Weiger und die Einführung der Anästhesie in Wien.

The first administration of ether in Vienna was performed by Schuh in 1847. 2 days later also von Wattmann used ether for anaesthesia. Approximately at the same time the nowadays nearly unknown dentist Joseph Weiger began to give ether anaesthesia for dental surgery. He reported in 1850 about his experiences in more than 21,000 operations. A further publication in 1851 gave a survey about the known ether literature.

[The so-called venous air embolism: historical aspects and current diagnosis, prophylaxis and therapy]. / Die sogenannte venöse Luftembolie: Historische Aspekte und heutiger Stand von Diagnose, Prophylaxe und Therapie.

The so-called venous air embolism is known as a complication not only of surgical operations but also of other procedures. Two conditions must be fulfilled: a lesion of a non collapsible vein; and a pressure gradient from outside to inside the vein, as occurs for instance during puncture of a large vein in a hypovolemic patient. Air entry into veins is a frequent occurrence during neurosurgery in sitting patients, and thus most diagnostic, prophylactic, and therapeutic innovations were proposed by neuroanesthetists. Due to advances in technique, truly dangerous cases of so-called venous air embolism during neurosurgery in patients in the sitting position are very rare.

[Critical comments on reports of fatalities in hereditary fructose intolerance in adulthood from the viewpoint of neuroanesthesia]. / Kritische Bemerkungen zu Berichten über Todesfälle durch hereditäre Fructoseintoleranz im Erwachsenenalter aus der Sicht der Neuroanästhesie.

In view of repeated communications in recent years reporting on lethal infusions of fructose or sorbitol in adults with hereditary fructose intolerance, the known statements on the incidence of 1:20,000 are critically analysed. The validity is relativated. The special indication for sorbitol as an osmotherapeutic preparation for lowering intracranial pressure is pointed out. A modified intravenous fructose tolerance test is suggested.