The source of 'paradoxical lateralization' of cortical evoked potentials to posterior tibial nerve stimulation

We report the potentials elicited by posterior tibial nerve stimulation and recorded simultaneously from the scalp and from electrodes within the interhemispheric fissure. The primary cortical potential was recorded from cortex contralateral but from scalp ipsilateral to the stimulated nerve. The scalp recordings thus demonstrated "paradoxical lateralization" as reported previously, and the similar morphology of the scalp and contralateral cortical recordings confirm that this "paradoxical lateralization" is most likely the result of a horizontal dipole located within the interhemispheric fissure.     

Endobronchiale Applikation von Adrenalin in der kardiopulmonalen Reanimation Pharmakokinetische und -dynamische Untersuchungen beim Hund

Zusammenfassung Das Ziel der vorliegenden Untersuchungen bestand darin, das pharmakokinetische Profil von Adrenalin bei endobronchialer (e.b.) und intravenöser (i.v.) Applikation zu erarbeiten und die gemessenen Adrenalin-Plasmaspiegel mit hämodynamischen Messungen zu korrelieren. Die e.b. Applikation von 100 g/kg Adrenalin erwies sich als ebenso effektiv, wie die i.v.-Gabe von 10 g/kg. Dabei war der Wirkungseintritt der e.b.-Gabe von Adrenalin nur geringfügig um einige Sekunden verzögert. Die Bioverfügbarkeit für e.b. verabreichtes Adrenalin lag zwischen 80 und 85%. Der therapeutische Effekt blieb nach e.b.-Applikation von 100 g/kg Adrenalin wesentlich länger erhalten (ca. 30 min) als nach i.v.-Gabe von 10 g/kg (ca. 3–5 min). Aus den Ergebnissen wird geschlossen, daß die tiefe endobronchiale Instillation von 2–3 mg Adrenalin (verdünnt in 5–10 ml Kochsalzlösung) als alternative Dosierungstechnik bei klinischen Reanimationen betrachtet werden kann.

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Pharmacokinetics and -dynamics of epinephrine administered endobronchially

Summary The present animal study was designed to investigate the pharmacokinetic behavior of epinephrine after endobronchial (e.b.) and intravenous (i.v.) administration and its correlation to pharmacodynamic measurements. We found the effectiveness of e.b.-epinephrine (100 g/kg BW) to be in the same magnitude as i.v.-epinephrine (100 g/kg BW) with only a slight delay in the pharmacodynamic onset of a few seconds. The bioavailability of e.b.-administration of epinephrine was in the range of 80–85%. The therapeutic effect of e.b.-epinephrine (100 pg/kg BW) lasted much longer (30 min) when compared to i.v.-epinephrine (10 g/kg BW) where the pharmacodynamic effect was terminated after 3 to 5 min. For the clinical situation of cardiopulmonary resuscitation a dose of 2–3 mg epinephrine in 5–10 ml of physiological saline instilled deeply into the bronchial system should be considered as alternative administration technique with fast onset and good effectiveness.

Herrn Prof. Dr. Dr. h.c. F. Stelzner zum 65. Geburtstag gewidmet     

Reversibility of the acute toxic effect of Cyclosporin A on pancreatic B cells of Wistar rats

Summary. This study investigated if and to what extent the acute toxic effect of Cyclosporin A on pancreatic Wistar rat B cells is reversible. After 2 weeks of treatment rats developed marked glucose intolerance accompanied by reduced pancreatic insulin content due to a loss of B cells, diminished islet DNA synthesis and decreased B-cell insulin content. Cyclosporin A had accumulated in the pancreas. Three weeks after withdrawal of Cyclosporin A, pancreatic tissue concentrations of Cyclosporin A were still 100 times larger than in serum. Glucose tolerance, however, had already improved, associated with an increase of B-cell insulin content and apparent islet replication, and the insulin response of isolated islets was reduced. Five weeks after the withdrawal of Cyclosporin A, glucose tolerance was normal, but pancreatic insulin content and relative B-cell volume were still diminished in comparison to vehicle-treated controls. Eight weeks after withdrawal, the morphometric parameters had also been normalized. The results suggest that the loss of pancreatic B cells is caused by a toxic destruction, possibly combined with an apparent decrease of replicatory activity. The acute toxic effects of Cyclosporin A in pancreatic B cells are stepwise reversible.     

Euthanasia in the Third Reich--only a problem of psychiatry? On the development of the euthanasia debate 1933-1941 in Germany

The devastating consequences of the Fascist dictatorship in Germany for the ethical thinking of the physicians are particularly clearly recognizable by the mass killings of severely damaged children and patients with chronic psychic diseases which were performed at that time. Recent investigations of the developments which began in 1938 show that by way of intensive efforts for a juridicial legalization of the "active euthanasia" an enlargement of this killing practice has been striven after. References to a motive of compassion and the free decision of the affected persons should cover the real intention for reducing welfare services. A bill presented in 1940 for a law "on euthanasia for incurable ill persons" found the unanimous consent of the renowned physicians consulted for this purpose. Though this law finally did not become legal beginning with 1941 the medical practice showed further forms of the repressive and antihumane association with ill persons who were regarded as incurable, which must be valuated as practical consequences of an unadmissible relativation of the life-preserving task of medicine.     

Mathematical model of volume kinetics and renal function after burn injury and resuscitation

This paper presents a mathematical model of blood volume kinetics and renal function in response to burn injury and resuscitation, which is applicable to the development and non-clinical testing of burn resuscitation protocols and algorithms. Prior mathematical models of burn injury and resuscitation are not ideally suited to such applications due to their limited credibility in predicting blood volume and urinary output observed in wide-ranging burn patients as well as in incorporating contemporary knowledge of burn pathophysiology. Our mathematical model consists of an established multi-compartmental model of blood volume kinetics, a hybrid mechanistic-phenomenological model of renal function, and novel lumped-parameter models of burn-induced perturbations in volume kinetics and renal function equipped with contemporary knowledge on burn-related physiology and pathophysiology. Using the dataset collected from 16 sheep, we showed that our mathematical model can be characterized with physiologically plausible parameter values to accurately predict blood volume kinetic and renal function responses to burn injury and resuscitation on an individual basis against a wide range of pathophysiological variability. Pending validation in humans, our mathematical model may serve as an effective basis for in-depth understanding of complex burn-induced volume kinetic and renal function responses as well as development and non-clinical testing of burn resuscitation protocols and algorithms.     

Kann man balancierte Infusionslösungen verbessern?

Die Anaesthesiologie -     

Site of metastatic recurrence impacts prognosis in patients with high-grade upper tract urothelial carcinoma

PurposeMetastatic recurrence occurs in over 25% of upper tract urothelial carcinoma patients treated with radical nephroureterectomy. While metastatic recurrence suggests poor prognosis, the impact of the specific site of recurrence on prognosis is not well documented.Materials and methodsWe retrospectively analyzed 188 patients who underwent radical nephroureterectomy for high-grade, node-negative upper tract urothelial carcinoma at our institution from 2003 to 2018 without receiving neoadjuvant or adjuvant chemotherapy. Competing-risks survival analysis was performed to evaluate the cumulative incidence and predictors of metastatic recurrence. The Kaplan-Meier method and log-rank test were used to estimate and compare recurrence site-specific survival probabilities following metastatic recurrence. Cox regression analyses were performed to assess site-specific prognoses.ResultsOf the 188 patients, 47 (25%) developed metastatic recurrence over a median follow-up of 30 months (interquartile range: 10.5–58.5 months). The 1- and 2-year cumulative incidences of metastatic recurrence were 13.6% and 23.6%, respectively. On multivariable analysis, lymphovascular invasion was significantly predictive of metastatic recurrence (subhazard ratio: 2.6, P = 0.01). Of the 47 patients who developed recurrence, 38 (80.9%) died over a median follow-up of 10 months (interquartile range: 5–20 months). Metastatic recurrence was most common in the lungs (n= 13, 28%) and at multiple sites (n= 14, 30%). Median time to recurrence was shorter for recurrences at multiple sites (6.5 months) and those in the liver (13 months) and bone (18 months) compared to other sites. Patients who recurred in the liver (hazard ratio: 6.3, P = 0.007), bone (hazard ratio: 4.9, P = 0.02), and multiple sites (hazard ratio: 4.6, P = 0.01) had significantly worse prognosis compared to those who recurred in lymph nodes. Statistical significance persisted after adjusting for treatment with salvage therapy.ConclusionsA significant proportion of high-grade upper tract urothelial carcinoma patients recur systemically after radical nephroureterectomy. Lymphovascular invasion is a predictor of metastatic recurrence and may inform decisions regarding perioperative chemotherapy. Hepatic and osseous recurrences have relatively quicker onset and less favorable prognosis compared to other sites. These findings may benefit future efforts to develop recurrence site-specific treatment plans and highlight the necessity of subsequent endeavors to explore the genetic associations of recurrence in upper tract urothelial carcinoma.     

The pharmacokinetics of tranylcypromine enantiomers in healthy subjects after oral administration of racemic drug and the single enantiomers

The pharmacokinetics of the two enantiomers of tranylcypromine were evaluated in six healthy subjects after oral dosage of the racemate (20 mg of the sulphate) and the single enantiomers (10 mg of the sulphate) using an enantiospecific assay. Significant differences in AUC, Cmax, lambda(z), and CLR of the two enantiomers were observed both on administration of the racemate and of the individual enantiomers. The plasma concentrations and urinary excretion rates of (-)-tranylcypromine exceeded those of (+)-tranylcypromine. AUCs of the (-)-enantiomer [arithmetical means 197 ng ml(-1) h after the racemate, 130 ng ml(-1) h after the enantiomer] were greater than those of the (+)-enantiomer [26 ng ml(-1) h after the racemate, 28 ng ml(-1) h after the enantiomer] (P = 0.0001). No in vivo racemisation was detected. The power of the study was insufficient to establish any enantiomer-enantiomer interaction except for a possible interaction at the level of renal clearance (P = 0.013 for both enantiomers).     

Erworbene Bauchhöhlenmuskelstörungen

Zusammenfassung Die Bauchhöhle hat ein Faszienskelett, das durch ihren permanenten veränderhchen Ruhetonus verspannt gehalten wird. Zur Bauchhöhle gehören mit der seitlichen Bauchmuskulatur auch das Zwerchfell und der Beckenboden. Willkürliche und reflektorische Tonusänderungen bedingen ihre Verformung und ihren Verschluß oder ihre Eröffnung. Am Versuchstier haben wir diesen Ruhetonus schon in der Schwanzmuskulatur nachgewiesen, von der der Beckenboden des Menschen stammesgeschichtlich abstammt. Der Beckenboden bildet mit den Sphinkteren das anorektale Kontinenzorgan. Es ist, phylogenetisch erklärbar, bei der Frau viel schwächer entwickelt als beim Mann. Diese unterschiedliche Mächtigkeit ist his zu den Kernen des Rückenmarks, die diese Muskulatur steuern, zu verfolgen. Diese Asthenie des weiblichen Kontinenzorgans wird durch das Gebären und die Obstipation noch zusätzlich belastet. Das gleiche gilt für die Bauchdecke der Frau, die, wie hier nachgewiesen wird, nach einer Gravidität die gleichen, bleibenden Denervationserscheinungen ihrer Muskulatur erkennen läß t. Es sind die gleichen Schäden, die der Beckenboden mit den Sphinkteren erleidet. In schwereren Fällen ist neben der Inkontinenz also auch ein Schlotterbauch die Folge dieser Belastungen. Der ruhetonisierte Beckenboden kann das spastische Beckenbodensyndrom, die kontinente Obstipation, zur Folge haben. Sic kann psychotherapeutisch geheilt werden. Davon muß die inkontinente Obstipation unterschieden werden, die manchmal mit einem Mastdarmvorfall einhergeht. Bei ihr liegt das Hindernis im Darm. Sic kann in schweren Fällen durch eine Sigmaresektion gebessert werden. Die Denervationsinkontinenz ist am besten durch das operative Engerstellen des ganzen Levatortrichters zu bessern. Voraussetzung ist: Der gelähmte Beckenboden muß noch eine Restruheaktivität aufweisen.

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Acquired disturbances of muscles of the peritoneal cavity

The peritoneal cavity has a fascial skeleton that is kept under tension by permanent variable resting tone maintained by the abdominal muscles. The lateral abdominal muscles, the diaphragm and the pelvic floor are all components of this fasciomuscular support system. Voluntary and reflective changes in muscle tension allow the entry and exit of matter into and out of the spherical abdominal cavity by opening and closing of specialized wall segments called sphincters. We have previously demonstrated the existence of a resting tone in the tail muscles of mammals from which the human pelvic floor muscles are derived. The pelvic floor and its integrated sphincters form the anorectal organ of continence. This organ is much weaker in females than in males. The spinal centers that govern continence, contain in the female significantly fewer ganglion cells than the corresponding centers in the male. Childbirth and a commonly found tendency to develop constipation are additional stressors for the congenitally weaker female organ of continence. We explain in this paper why the abdominal wall and the pelvic floor may suffer stretch-induced denervation injuries during pregnancy and delivery. Such damage may persist in later life and can give rise to incontinence and flabby abdomen. Based on our work in this field, we found a new differentiation between continent and incontinent constipation. Continent constipation is caused by spasticity of the pelvic floor characterized by abnormally high sphincter activity. This spastic pelvic floor syndrome can be treated successfully by psychotherapeutic techniques. Incontinent constipation, in contrast, is always associated with subnormal activity of the sphincters and may be a cause of rectal prolapse. It can be treated successfully by anterior rectosigmoid resection. Incontinent constipation will also require operative approximation of the levators in many cases. Improvement cannot be expected to result from this procedure, however, unless the pelvic floor shows some residual resting activity.

Korrespondenz an: em. Prof. Dr. Dr. h. c. mult. F. Stelzner