Placebo controlled comparison of acute effects of ebastine and clemastine on performance and EEG

Summary The effects of single oral doses of 10 and 20 mg ebastine were compared with placebo and 2 mg clemastine in a double-blind cross-over study in 16 healthy male volunteers.Clemastine produced the known pattern of changes, namely impairment of psychomotor performance, drowsiness, and a selective effect on cognitive processes. Earlier encoding in a perceptual stage was slowed whereas abstract classification processes were not affected. Electrophysiological measures of vigilance showed a general decrease in vigilance especially 2.5 and 4.5 h after dosing.In contrast at no time was any effect of ebastine different from that of the placebo.Ebastine 10 and 20 mg differed positively from clemastine in its effect on pursuit tracking, subjective rating of drowsiness and general discomfort. Ebastine 10 mg also differed positively from clemastine in the EEG features of vigilance.It is concluded that 10 and 20 mg ebastine were free from sedative adverse effects.     

Adding a selective obturator nerve block to the parasacral sciatic nerve block: an evaluation

Our aim was to objectively evaluate the efficacy of obturator nerve anesthesia after a parasacral block. Patients scheduled for knee surgery had a baseline adductor strength evaluation. After a parasacral block with 30 mL 0.75% ropivacaine, sensory deficit in the sciatic distribution (temperature discrimination) and adductor strength were assessed at 5-min intervals. Patients with an incomplete sensory block (defined as a temperature discrimination score of less than 2 in the 3 cutaneous distributions of the sciatic nerve tested) 30 min after the parasacral block were excluded from the study. Subsequently, a selective obturator block was performed with 7 mL 0.75% ropivacaine and adductor strength was reassessed at 5 min intervals for 15 min. Finally, a femoral block was performed using 10 mL 0.75% ropivacaine. Patient discomfort level during each block was assessed using a visual analog scale (VAS). Thirty-one patients completed the study. Five patients were excluded as a result of inadequate sensory block in the sciatic distribution 30 min after the parasacral block (success rate of 89%). Thirty min after the parasacral block, adductor strength decreased by 11.3% +/- 7% compared with baseline (85 +/- 24 versus 97 +/- 28 mm Hg, P = 0.002). Fifteen min after the obturator nerve block, adductor muscle strength decreased by an additional 69% +/- 7% (16.6 +/- 15 versus 85 +/- 24 mm Hg, P < 0.0001). VAS scores were similar for all blocks (26 +/- 19, 28 +/- 24, and 27 +/- 19 mm for parasacral, obturator, and femoral respectively). Four parasacral blocks were simulated in 2 fresh cadavers using 30 mL of colored latex solution. The spread of the die in relation to the obturator nerve was assessed. Injection of 30 mL colored latex into cadavers resulted in spread of the injectate restricted to the sacral plexus. These findings demonstrate the unreliability of parasacral block to achieve anesthesia of the obturator nerve. A selective obturator block should be considered in the clinical setting when this is desirable.     

Postoperative analgesia after total knee replacement: the effect of an obturator nerve block added to the femoral 3-in-1 nerve block

Femoral nerve block (FNB) does not consistently produce anesthesia of the obturator nerve. In this single-blind, randomized, controlled study we added a selective obturator nerve block (ONB) to FNB to analyze its influence on postoperative analgesia after total knee replacement (TKR). Before general anesthesia, 90 patients undergoing TKR received FNB (Group 1), FNB and selective ONB (Group 2), or placebo FNB (Group 3). Postoperative analgesia was further provided by morphine IV via patient-controlled analgesia. Analgesic efficacy and side effects were recorded in the first 6 h after surgery. Adductor strength decreased by 18% +/- 9% in Group 1 and by 78% +/- 22% in Group 2 (P < 0.0001). Total morphine consumption was reduced in Group 2 compared with Groups 1 and 3 (P < or = 0.0001). Patients in Group 2 reported lower pain scores than those in Groups 1 and 3 (P = 0.0003). The incidence of nausea was more frequent in Groups 1 and 3 (P = 0.01). We conclude that FNB does not produce complete anesthesia of the obturator nerve. Single-shot FNB does not provide additional benefits on pain at rest over opioids alone in the early postoperative period. The addition of an ONB to FNB improves postoperative analgesia after TKR.     

Postdural puncture headache after spinal anaesthesia in young orthopaedic outpatients using 27-g needles

PURPOSE: Two large studies reported a very low rate (0.5-1.8%) of postdural puncture headache (PDPH) with the use of 27-G spinal needles. We suspected that it might be higher in young ambulatory patients. The purpose of this study was to establish the rate prospectively in such a patient population using two types of needles. METHODS: Two hundred male and female, outpatients, 18-45 yr, undergoing knee arthroscopy under spinal anaesthesia were randomly assigned to receive spinal anaesthesia with hyperbaric lidocaine 5% using either a Quincke or a Whitacre 27-G needle. Twenty patients choosing general anaesthesia formed a comparative group. Using a previously validated questionnaire, the incidence and nature of PDPH were evaluated by telephone three to five days after surgery by an anaesthetist unaware of the anaesthetic technique used. Once all data were collected, an anaesthetist not involved in the study determined in a blinded fashion which headaches were likely to be PDPH. Grading and classification of headaches were based on several criteria: postural nature, duration, intensity and confinement to bed. RESULTS: The overall incidence of PDPH in both spinal groups was 9.3%. The incidence in women, 20.4%, was higher than in men, 5.5%, (P < 0.05). Only one patient required a blood patch. Both types of needle were comparable with respect to the incidence, severity and duration of PDPH, number of dural punctures and failed spinal blocks. CONCLUSION: The rate of PDPH was higher than in large published studies with 27-G Quincke and Whitacre needles and greater in women than in men.     

Klinisch-pharmakologische,cytochemische und Feulgen-photometrische Untersuchungen bei unreifzelligen Erwachsenenleukosen unter kombinierter Chemotherapie mit Vincristin,Daunorubicin und Prednison

Zusammenfassung Es wird über die klinischpharmakologische Prüfung (Phase I) der Cytostatikakombination Daunorubicin — Vincristin — Prednison (ViDaP) an allen akuten Leukämien berichtet, die in der Zeit vom 1. 3. 67–31. 12. 68 in die Medizinische Univ.-Klinik Freiburg i. Br. zur Behandlung eingewiesen wurden. Die Beobachtungszeit endete am 30. 4. 70. Die Behandlung gliederte sich in cine erste Phase zur Einleitung der Remission, an die sich bei den Fällen, in denen das Knochenmark sich normalisiert bzw. gebessert hatte, die zweite Phase, die sog. Erhaltungstherapie anschloß. Letztere bestand aus einer Dauertherapie mit 6-Mercaptopurin sowie zusätzlich Reinduktionsstößen mit ViDaP, die in sechswöchigen Intervallen verabreicht wurden.Die Klassifizierung der akuten Leukämien erfolgte auf Grund des cytomorphologischen Bildes der Pappenheim-Färbung und nach cytochemischen Kriterien. Die Leukosen vom Peroxydase-, Peroxydase-Esterase-Misch-und Esterasetyp wurden als akute myeloische Leukosen (AML) zusammengefaßt und den akuten lymphatischen Leukämien (ALL, cytochemisch PAS-Typ) sowie den akuten undifferenzierten Leukämien (AUL) gegenübergestellt. Zusätzlich wurden quantitative cytophotometrische DNS-Bestimmungen durchgeführt.Das Ziel der Untersuchung war, die therapeutische Wirkung von ViDaP vor allem an der Remissionsrate und der Dauer der Remission sowie seine Toxicität zu beurteilen. Außerdem sollte geprüft werden, ob zwischen den einzelnen cytochemisch differenzierten Leukosetypen und dem DNS-Gehalt der Leukosezelle einerseits sowie dem Therapieeffekt andererseits Beziehungen bestehen.Insgesamt wurden 22 Patienten mit akuten Leukämien mit ViDaP behandelt. Die Remissionsrate belief sich auf 32% (komplette+Teilremissionen). Die höchste Rate (3/7) ergab sich bei der PAS-positiven ALL. Bei der AML konnten unter 12 Patienten 2 komplette und 1 Teilremission erzielt werden. Von den 3 Patienten mit AUL erreichte einer eine Vollremission.Die Dauer der Remission betrug bis zum Stichtag (30. 4. 70) bei der ALL 227, 446+ und 667+Tage, bei AML 210, 213, 646+ und bei der AUL 666+Tage.Die Untersuchung der Abhängigkeit des Therapieeffektes vom Ploidiegrad der Leukosezellen ließ eine schlcchtere therapeutische Ansprechbarkeit bei denjenigen Fällen erkennen, deren DNS-Zellstammlinien ausschließlich im diploiden Bereich lagen.Die Therapie mit ViDaP wurde vergleichsweise gut vertragen. Im Vordergrund standen neurotoxische Erscheinungen, die durch das Vincristin bedingt waren. Auf die Kardiotoxicität von Daunorubicin wird ausführlich eingegangen. Fatale Aplasien des Knochenmarks wurden nicht beobachtet.

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Summary It is reported about the clinico-pharmacologic evaluation (Phase I) of the combination of cytostatic drugs Daunorubicine — Vincristine — Prednisone (ViDaP) in all acute leukemias treated at the Medizinische Universitätsklinik Freiburg between 3-1-1967 and 12-31-1968. The observations were continued till to 30-4-70. In the treatment two phases were distinguished: in the first phase the goal was to obtain a remission (=induction phase). If the bone marrow examination had shown a remission (M1 or M2), the maintenance treatment was instituted (reinduction-pulses). This consisted of 6-Mercaptopurine with ViDaP at 6 weeks intervals.Classification of acute leukemias was made according to morphologic features of the Pappenheim stain, and cytochemical criteria in 3 types: AML=acute myelocytic leukemia; ALL=acute lymphoblastic leukemia; AUL=acute undifferentiated leukemia. Leukemias of the peroxydase, mixed peroxydase-esterase and esterase types were called acute myelogenous leukemias in contrast to acute lymphatic leukemias. In addition quantitative cytophotometric DNS measurements were carried out.The therapeutic effects of ViDaP-therapy were evaluated by the rate and duration of remissions in relation to the different types of leukemias.22 Adults were treated with ViDaP. The remission rate (complete and partial) was 32%. The highest rate (3/7) was seen in ALL. Among the 12 patients with AML 2 complete and 1 partial remission were achieved. Only one of 3 patients with AUL went into complete remission.By April 30-1970 the remissions had lasted 227, 446+, and 667+ days for ALL, 210, 213, 646+ days for AML and 666+ for AUL respectively.There was a correlation between effect of therapy and degree of ploidie of leukemic cells. Cells with diploid stem lines responded less favorable to therapy than polyploid ones.Side effects of ViDaP-therapy were moderate. The therapy was well tolerated. The side-effects were mainly neurological caused by Vincristine. The toxic effects of Daunorubicine on the heart are discussed. The hematologic toxicity was tolerable. Fatal bone marrow aplasias were not observed.

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Wir sind der Deutschen Farmitalia für die großzügige Überlassung des Medikamentes zu großem Dank verpflichtet. Mit freundlicher Genehmigung der EORTC, Groupe Cooperateur Leucemies et Hematosarcomes.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Neutrophil kinetics in man studies using autotransfusion of3H-DFP labeled blood cells and autoradiography

Summary Neutrophil kinetic studies were performed by autotransfusion of³H-DFP labeled blood cells and subsequent autoradiographic analysis of the circulating neutrophils. This method allowed neutrophil specific data to be determined under normal as well severe neutropenic and neutrophilic conditions. This was demonstrated by examination of hematologically normal subjects, patients with neutropenia, infection or polycythemia vera whose blood neutrophil counts ranged between 50 and 21,500 per l. Moreover studies at different stages of chronic myelocytic leukemia were performed.

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Zusammenfassung Neutrophilen-kinetische Studien wurden mit Hilfe der Autotransfusion von³H-DFP-markierten Blutzellen und anschließender autoradiographischer Analyse der zirkulierenden Neutrophilen durchgeführt. Diese Methode ermöglichte die Bestimmung Neutrophilen-spezifischer Daten sowohl bei normaler als auch bei erhöhter Blutneutrophilenzahl und bei Neutropenie. Untersucht wurden hämatologisch gesunde Probanden, Patienten mit Neutropenie und Polycythaemia vera, deren Neutrophilenzahl in einem Bereich zwischen 50 und 21500 pro l lagen. Außerdem wurden Patienten mit chronisch myeloischen Leukämien untersucht.

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Research supported by Deutsche Forschungsgemeinschaft.

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Mit demArthur-Pappenheim-Preis 1971 der Deutschen Gesellschaft für Hämatologie ausgezeichnete Arbeit.     

Macrophage turnover in Crohn's disease and ulcerative colitis

Monocytopoietic proliferation activity was determined in 8 patients during severe attacks of Crohn's disease and in 6 patients with ulcerative colitis. Similar results were obtained in both groups of patients. A moderate but significant hyperproliferation of monocytopoiesis was found to be present in about half of the patients, and with some of the remainder of cases, part of the criteria for hyperproliferation were also fulfilled. This indicates that Crohn's disease as well as ulcerative colitis are frequently associated with moderate overproduction of monocytes which may be assumed to be induced by macrophage demand of the affected tissues. In comparison with other diseases involving inflammations, the monocytopoietic hyperproliferation was moderate. Therefore, the inflammation in Crohn's disease and ulcerative colitis seems to be characterized by a relatively low macrophage turnover induced by pathogenetic mechanisms of moderate macrophage toxicity.     

Determination of the bacteriostatic capacity of neutrophils and monocytes in mixed cell populations

Summary Cline [1,2] described a method of determining the phagocytic and bacteriostatic activity of individual types of leukocytes within mixed cell populations. We tried to improve the applicability of this method for the investigation of clinical problems. — Bacteria in the log-phase of growth were incubated in test tubes with leukocytes separated from venous blood. After a short period of phagocytosis³H-thymidine was added to label DNA-synthesizing organisms. Smears were prepared and processed by autoradiography. The labeling indices of extracellular bacteria and of those phagocytized by neutrophils and monocytes were determined microscopically. The intracellular inhibition of DNA-synthesis was taken as indicative of the bacteriostatic activity of the leukocytes. The proposed modification ofCline's assay is suited to investigate clinical problems of phagocyte dysfunction.

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Zusammenfassung Cline [1,2] beschrieb eine Methode zur Bestimmung der Phagozytose und der bakteriostatischen Aktivität individueller Leukozyten in gemischten Zellpopulationen. Wir versuchten die Methode dieses Tests zu verbessern, um klinische Fragestellungen angehen zu können. — Bakterien in log-Phase wurden zusammen mit Leukozyten, die aus venösen Blutproben durch Differentialsedimentation gewonnen wurden, inkubiert. Nach einer kurzen Zeit der Phagozytose wurden DNA-synthetisierende Bakterien durch³H-Thymidin markiert. Danach wurden mit Hilfe autoradiographierter Ausstrichpräparate die Markierungsindizes der extrazellulären Keime und der von Neutrophilen und Monozyten phagozytierten Keime bestimmt. Aufgrund der intrazellulären Hemmung der DNA-Synthese wurde die bakteriostatische Aktivität der Phagozyten berechnet. Mit dieser modifizierten Technik läßt sich die bakteriostatische Kapazität der Phagozyten des Blutes ohne Schwierigkeiten bestimmen, auch wenn die Leukozytenzahl erniedrigt ist.