Anthralin derivatives--inhibition of 5-lipoxygenase--antipsoriatic efficacy.

Inhibition of 5-lipoxygenase by anthralin (1) and 41 derivatives is determined: the acids 38 and 39, the lactones 40-42 and 9-anthrone (8) are the most potent inhibitors, the lactone 41 reaching the efficacy of nordihydroguaiaretic acid (NDGA). The results were correlated with the hydrophilic/lipophilic balance of the test compounds and their clinical efficacy as far as known. There is no correlation between the "minimum structure" of Krebs and Schaltegger concerning antipsoriatic activity and the inhibitory effects against 5-lipoxygenase.     

Determination of the spread of epidural anesthesia. A comparison between pin-prick and a new method using a metallic roller]

A new method (metal roller) for testing the spread of analgesia in regional anesthesia is introduced. The possible advantages of testing with a metal roller (cold sensation) in comparison to the pinprick method are investigated and discussed to determine whether loss of cold-sensation is comparable to loss of pinprick-sensation and thus reliable in clinical practice. METHOD AND MATERIAL. Spread of analgesia was tested with both the metallic roller and the conventional pinprick method in 40 patients (20 epidural and 20 spinal blocks), and pain perception or cold perception were compared. RESULTS. In epidural as well as in spinal anesthesia, similar levels of loss of pain perception and cold perception were found. DISCUSSION. Testing the spread of analgesia after nerve bock by the pinprick method is sometimes unpleasant for the patient. The metal roller is not unpleasant, and the possible danger of contamination or pinprick pain is virtually impossible because physical integrity is preserved and the feeling of "cold" is not harmful.     

Indications and results of skin flaps in painful digital neuroma

Of the many procedures for treating painful neuromas, resection and proximal translocation are the most usual techniques, but these can decrease distal sensibility increasing deafferentation pain. In cases of intricate pain (nociception plus deafferentation), certain types of flaps allow the treatment of both components of the pain. We have used 30 such flaps in 28 patients: local flaps (exchange, advancement or lasso island flaps) and distant flaps (free "custom-made" toe flaps). The results of the different techniques provides 86.6% excellent or good results.     

Kinetics of interaction between beta-receptors, GTP protein, and the catalytic unit of turkey erythrocyte adenylate cyclase.

The kinetics of turkey erythrocyte membrane adenylate cyclase activation by beta-agonists and guanyl-5'-yl imidodiphosphate is explored as a function of the concentration of the GTP regulatory protein and of the catalytic unit. It was found that the overall kinetics of activation is first order and is independent of the concentration of the GTP regulatory unit N, the catalytic unit C, and of hormone over a very wide concentration range. It was established that the rate-limiting step does not involve GDP dissociation from the inactive N unit or the association between activated N' and C. Also, it was found that guanyl-5'-yl imidodiphosphate binding occurs in a random fashion and is not hormone dependent. These results enable us to exclude models of the sequential type in which N in its inactive form is bound to receptor R, is released in an active form N' upon hormone activation, and then binds to C, activating the latter. An acceptable model that accounts for all of the data conforms to the original formulation of "collision coupling" in which N is tightly associated to C at all times.     

Dense cystic craniopharyngiomas

Characteristic computed tomographic (CT) findings of craniopharyngioma include calcification, contrast enhancement, and cyst formation. Sharp margins associated with a hypodense centrum usually characterize the CT appearance of a cystic tumor. The appearance of "dense" cysts in craniopharyngiomas has not been emphasized. Four cases of craniopharyngiomas with isodense to hyperdense cysts are reported. Comparative biochemical and in vitro CT analysis of cyst aspirates taken from these lesions demonstrate that high intracystic protein concentration accounts for the greater part of the hyperdensity. Various mechanisms for intracystic protein accumulation are discussed. Lesion characteristics, and not necessarily attenuation coefficients, are stressed in differentiating "dense" cystic from solid craniopharyngiomas.     

Die Technik der Fibrinspongiosaplastik

Zusammenfassung Es wird über die klinische Anwendung eines Fibrinklebesystems in Verbindung mit Knochentransplantaten zur Auffüllung von Knochendefekten berichtet. Neben der genauen Beschreibung der Klebetechnik, wird über 11 klinische Fälle mit einem Nachbeobachtungszeitraum von 9–21 Monaten berichtet. Durch die Anwendung des biologischen Klebesystems kam es zu einem beschleunigten, homogenen Einbau des transplantierten Knochens, wobei das Ausbleiben einer Sklerosierung der Plomben bemerkenswert erschien. Als weitere Vorteile werden die hämostyptische, die adhäsive und die Eigenschaft der plastischen Formbarkeit hervorgehoben.

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The technic of fibrin glue in cancellous bone transplants

Summary The paper deals with the clinical experience in the use of a biological adhesive system in conjunction with bone transplants to close large bone defects. The gluing technique has been exactly described, 11 patients with a follow-up between 9 and 21 months are being presented. The application of this system which consists of highly concentrated native fibronogen, thrombin, and clotting factor XIII results in an acceleration of homogenous incorporation of the implants. No deterioration of wound healing occurred. The advantages of this method are: exact local hemostasis, adhesive strength, and plasticity.

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Herrn Professor Dr. Karl Chiari zum 65. Geburtstag gewidmet     

Volumetrie der Harnblase mittels implantierbaren Ultraschallsensoren

Experimental studies revealed that the contractile response of the urinary bladder to sacral anterior root stimulation depends on the actual bladder volume. Furthermore, no clinical relevant technique is available for continuous monitoring of the bladder wall distension respectively bladder volume in paraplegic patients. The presented study investigates the reliability of especially developed implantable ultrasound sensors as a sensoric system for continuous monitoring of the bladder volume. In six anaesthesized pigs two ultrasound sensors, one transmitter and one receiver, were implanted on the bladder wall at different locations (latero-lateral, dorsal-ventral, rostral-caudal). After closing the abdominal wall, the bladder was filled in 50 ml steps up to 250 ml. After each filling step the running time of the ultrasound signal was measured. In all experiments reproducible results and a high correlation of the measured running times with bladder volume were observed. The latero-lateral configuration of the sensors seemed to be most confidential. The presented study indicates that bladder volumetry with implantable ultrasound sensors is possible with minimal technical prerequisites. This promising technique for continuous bladder volumetry could play an important role in the development of an intelligent and autoadaptive neurostimulator of the urinary bladder in paraplegic patients.     

Evidence for oxidative stress in bronchiolitis obliterans syndrome after lung and heart-lung transplantation. The Munich Lung Transplant Group

Bronchiolitis obliterans syndrome (BOS) is the most serious long-term sequel of lung or heart-lung transplantation (H/LTX). Neutrophilia in the lower respiratory tract is a prominent feature of BOS. Because polymorphonuclear leukocytes (PMN) are capable of releasing large quantities of reactive oxygen species, we measured indicators of oxidative stress and glutathione levels representing antioxidant defense in H/LTX patients (HLTX, n=6; double-LTX, n=7; single-LTX, n=9). We analyzed 19 bronchoalveolar lavage (BAL) samples from 13 non-BOS patients (nine female, four male: age 39+/-4 years) and 17 BAL samples from nine BOS patients (five female, four male: age 33+/-2 years). PMN were the predominant BAL cell population in BOS (61.7+/-7.8% vs. 12.3+/-3.4%, P<0.001). Myeloperoxidase activity in the epithelial lining fluid and oxidized methionine residues in BAL-derived proteins were elevated in BOS (8.6+/-1.6 U/ml vs. 2.2+/-0.6 U/ml, P<0.01; and 12.6+/-1.1% vs. 7.7+/-0.8%, P<0.001, respectively). In addition, the concentration of reduced glutathione in epithelial lining fluid was decreased in BOS (162.6+/-20.1 microM vs. 345.8+/-57.1 microM, P<0.01), whereas the proportion of oxidized glutathione was increased (13.9+/-2.0O% vs. 6.7+/-1.2%, P<0.001). PMN, myeloperoxidase, and oxidized methionine residues were inversely correlated, whereas reduced glutathione was positively correlated with forced expiratory volume in 1 sec (P<0.05 to P<0.001). We conclude that excessive oxidative stress and a lack of glutathione are associated with BOS after H/LTX and may play relevant roles in the development of this disorder.     

Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor.

PURPOSE: To investigate the safety and tolerability and to explore the pharmacokinetic and pharmacodynamic profile of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with solid tumors that express epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: This was a phase I dose-escalation trial of EMD72000 in patients with advanced, EGFR-positive, solid malignancies that were not amenable to any established chemotherapy or radiotherapy treatment. EMD72000 was administered weekly without routine premedication until disease progression or unacceptable toxicity. RESULTS: Twenty-two patients were treated with EMD72000 at five different dose levels (400 to 2,000 mg/wk). National Cancer Institute common toxicity criteria grade 3 headache and fever occurring after the first infusion were dose limiting at 2,000 mg/wk; thus, the maximum-tolerated dose was 1,600 mg/wk. No other severe side effects, especially no allergic reactions or diarrhea, were observed. Acneiform skin reaction was the most common toxicity, but it was mild, with grade 1 in 11 patients (50%) and grade 2 in three patients (14%). Pharmacokinetic analyses demonstrated a predictable pharmacokinetic profile for EMD72000. Pharmacodynamic studies on serial skin biopsies revealed that EMD72000 effectively abrogated EGFR-mediated cell signaling (eg, reduced phosphorylation of EGFR and mitogen-activated protein kinase), with no alteration in total EGFR protein. Objective responses (23%; 95% CI, 8% to 45%) and disease stabilization (27%; 95% CI, 11% to 50%) were achieved at all dose levels, and responding patients received treatment for up to 18 months without cumulative toxicity. CONCLUSION: Treatment with EMD72000 was well tolerated and showed evidence of activity in heavily pretreated patients with EGFR-expressing tumors. EMD72000 at the investigated doses significantly inhibited downstream EGFR-dependent processes.