Physikalische grundlagen der blasenbildung

Zusammenfassung Die physikalischen Kräfte, die bei der Bildung einer Blase die Flüssigkeitsansammlung bewirken, waren bisher nicht gemessen worden. Es wurde der kolloidosmotische Druck in der Blasenflüssigkeit von mit einem modifizierten Dermovac erzeugten Saugblasen und in der Blasenflüssigkeit von Patienten mit Dermatitis herpetiformis, bullösem allergischem Kontaktekzem und Pemphigus vulgaris sowie im Serum von Normalpersonen mit Hilfe eines Membranosmometers bestimmt. Der kolloidosmotische Druck in den Saugblasen, die so schonend wie möglich produziert wurden, betrug etwa 7 cm H₂O, in den durch eine Hautkrankheit entstandenen Blasen lag er etwa bei 20cm H₂O, im Serum von Normalpersonen etwa bei 38 cm H₂O. Der kritische kolloidosmotische Druck in einer Blase, der überwunden werden muß, damit eine Wanderung der Interstitialflüssigkeit in den Blasenraum erfolgt, errechnet sich aus dem Gewebsflüssigkeitsdruck und dem kolloidosmotischen Druck der Interstitialflüssigkeit, er beträgt etwa 15 cm H₂O.

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Physical forces in blister formationI. Direct Measurement of Blister Fluid Colloid Osmotic Pressure in Suction Blisters and in Bullous Diseases

Summary The physical forces operative in the fluid migration from the interstitial spaces into the blister cleft have not been directly measured until now. The colloid osmotic pressure was determined in suction blister fluid after mild suction blister production by a modified Dermovac and in blister fluid of patients with dermatitis herpetiformis, bullous allergic contact dermatitis and pemphigus vulgaris and in the sera of healthy persons. The colloid osmotic pressure was measured by means of a recently developed osmometer with a semipermeable membrane between two chambers, one of them filled with Ringer solution, the other with the blister fluid sample. The negative pressure in the first chamber was determined. The colloid osmotic pressure of suction blister fluid averages approximately 7 cm H₂O, the values reach about 20 cm H₂O in bullous diseases and about 38 cm H₂O in the normal sera. The blister fluid colloid osmotic pressure has to rise to about 15 cm H₂O or more to cause the fluid transport from the interstitial spaces of the surrounding tissue into the blister because of the negative interstitial fluid pressure and the colloid osmotic pressure of the interstitial fluid. Otherwise the blister fluid is reabsorbed back into the interstitial spaces.

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Fräulein R. Brandmüller danke ich für die gewissenhafte Assistenz     

Amperozide and clozapine but not haloperidol or raclopride increase the secretion of oxytocin in rats

The aim of the present study was to investigate whether amperozide, an antipsychotic drug which possesses anti-aggressive and anxiolytic-like properties, stimulates the secretion of oxytocin and if so, by which receptor mechanism. For this purpose, female or male Sprague Dawley rats were given amperozide (0.5, 2.5 and 5.0 mg/kg IP), ritanserin (5.0 mg/kg), raclopride (2.0 mg/kg) and prazosin (1.0 mg/kg) and were subsequently decapitated for collection of blood (30 and 120 min) after injection. Oxytocin levels were measured with radioimmunoassay. Amperozide 2.5 and 5 mg/kg increased plasma levels of oxytocin significantly (P<0.05 and <0.001). The effect appeared maximal about 30 min after injection of the drug and oxytocin levels were almost back to basal within 120 min. Similar effects were obtained in female and male rats as well as in animals that were freely fed or food deprived for 24 h. CSF levels of oxytocin were also increased. Ritanserin, a 5-HT₂-receptor antagonist but not the D₂ receptor antagonist raclopride or the ₁-adrenoceptor antagonist prazosin stimulated oxytocin release. In addition, clozapine, a neuroleptic with potent HT₂-antagonistic properties, was a potent releaser of oxytocin, whereas haloperidol was without effect. A possible role for oxytocin in the behavioural effects of amperozide and clozapine remains to be explored.     

Phospholipase D in heart: basal activity and stimulation by phorbol esters and aluminum fluoride

Summary Evidence for a general role of phospholipase D in signal transduction is accumulating. In the present study, the activity of the enzyme was investigated in heart tissue under basal conditions and after addition of phorbol esters or aluminum fluoride (AlF _inf4 ^sup– ; 10 mM NaF plus 10 M AlCl₃). Atria of rats and chickens were incubated with [³H]-myristic acid in order to label preferentially phosphatidylcholine. Under basal conditions, the tissues generated choline and phosphatidic acid (PtdOH), the primary catalytic products of phospholipase D. When 0.5 or 2.0% ethanol was present, [³H]-phosphatidyl-ethanol (PETH) was rapidly formed at the expense of [³H]-PtdOH. This transphosphatidylation reaction is specific for phospholipase D activity. The basal formation of PETH was not inhibited by a Ca²⁺-free, EGTA-containing medium. - The phorbol ester 4-phorbol-12,13-dibutyrate (PDB), which is known to activate protein kinase C, enhanced the net formation of choline, whereas the inactive 4-phorbol-13-acetate (PAc) was ineffective. PDB (0.2 M), in contrast to PAc, also increased the formation of [³H]-PtdOH and, in the presence of ethanol, of [³H]-PETH. The PDB-evoked formation of PETH occurred again at the expense of PtdOH. Treshold and maximum effective concentrations of PDB were 10 nM and 0.2–0.6 M, respectively. The effects of PDB on either choline efflux and generation of PETH showed the same Ca^t+-dependency, i.e., both effects were blocked by a Ca²⁺-free, EGTA-containing medium, but not by a Ca²⁺-free medium without EGTA. In protein kinase C-deficient tissue which was prepared by pretreatment with 0.61 M PDB for 27 h, PDB failed to enhance the formation of PtdOH and PETH. - A1F4–, a known activator of G-proteins, increased not only the tissue content of inositol phosphates, but also markedly enhanced choline efflux and formation of [³H]-PtdOH and PETH. In conclusion, in mammalian and avian atria a high phospholipase D activity was found even under basal conditions. The enzyme was stimulated by protein kinase C and presumably by a G protein.Abbreviations IP inositol phosphate - DAG diacylglycerol - PL phospholipase - PtdOH phosphatidic acid - PETH phosphatidylethanol - PDB 4-phorbol-12,13-dibutyrate - PAc 4-phorbol-13-acetate - AlF _inf4 ^sup– aluminum fluoride - DMSO dimethylsulfoxide Correspondence to K. Löffelholz at the above address     

Immediate postembolization excision of glomus jugulare tumors: advantages of new combined techniques.

Preoperative percutaneous transfemoral catheter embolization of feeding vessels in glomus jugulare tumors, followed by immediate application of standard surgical techniques, presents the treatment of choice, allowing meticulous microsurgery with virtually complete hemostasis. Therefore, the surgeon can operate in a bloodless environment throughout the compressed and intricate anatomic field, amidst such important yet vulnerable structures as cranial nerves, inner ear, carotid artery, jugular bulb, venous sinuses, and dura, while reducing surgical error and functional deficit for the patient. Review of the last 11 cases of glomus jugulare tumors at UCLA shows that even extensive Alford grade 2 tumors of the middle ear, jugular bulb, and mastoid had only minor blood losses with this combined technique of embolization-immediate surgery, as compared with earlier surgical methods. Pertinent literature on glomus jugulare and its treatment is reviewed. Combined embolization and immediate surgery offer the best approach for treatment of resectable glomus jugulare tumors.     

Tumor recurrence and survival in patients treated for thymomas and thymic squamous cell carcinomas: a retrospective analysis.

PURPOSE: Thymic epithelial tumors (TET) are rare epithelial neoplasms of the thymus with considerable histologic heterogeneity. This retrospective study focused on the correlation of WHO-defined TET histotypes with survival and tumor recurrence in a large cohort of patients receiving different modes of treatment. PATIENTS AND METHODS: Two hundred twenty-eight patients were followed for up to 21 years (median, 60 months; range, 1 to 252 months) after primary surgery. Forty-two patients received adjuvant radiotherapy (mean dose, 53 Gy), and 33 patients received adjuvant chemotherapy. RESULTS: Seventy-six (88%) of 86 patients with WHO type A, AB, and B1 thymomas were treated by surgery alone, with three tumor relapses after 3 to 10 years (median, 3.4 years). Twelve of 67 patients with WHO type B2 and B3 thymomas in Masaoka stages I and II were treated by adjuvant radiotherapy without evidence of tumor recurrence after 1 to 12 years (median, 4 years). Among 75 patients with B2 and B3 thymomas with incomplete resection or a tumor stage III or higher, the recurrence rate was 34% (n = 23) after 0.5 to 17 years (median, 5 years) in patients receiving adjuvant radiochemotherapy, compared to 78% (seven of nine patients) in patients without adjuvant radiochemotherapy. Incomplete tumor resection was associated with a high recurrence rate (65%) and a poor prognosis (P <.01). CONCLUSION: The long-term outcome of TET patients is related to tumor stage, WHO histotype, completeness of surgical removal, and type of treatment. Prospective trials are warranted to formally address the efficacy of adjuvant therapy in the treatment of localized and advanced malignant TETs.     

Competing causes of death and second primary tumors in patients with locoregionally advanced head and neck cancer treated with chemoradiotherapy.

PURPOSE: The purpose of this retrospective analysis was to evaluate the emergence of second primary malignancies and the contribution of different causes of death to the outcome of patients with locoregionally advanced head and cancer receiving primary chemoradiotherapy. EXPERIMENTAL DESIGN: We studied 324 patients with stage IV squamous cell head and neck cancer who were enrolled on five consecutive multicenter Phase II studies of concurrent chemoradiotherapy. All of the regimens included concurrent 5-fluorouracil and hydroxyurea on an alternate week schedule with radiotherapy, either alone (FHX) or with cisplatin (C-FHX) or paclitaxel (T-FHX). The cumulative incidence of second primary tumors or death from any cause was estimated using methods of competing risk analysis. RESULTS: Median follow-up of surviving patients was 5.2 years (2-10.6 years). The 5-year overall survival and progression-free survival of the cohort were 46% and 65%, respectively. Causes of death and median time of occurrence were as follows: disease (n = 88; 1.5 years), treatment-associated acute or late complications (n = 30; 4 months), second primary tumors (n = 18; 3.5 years), comorbidities (n = 41; 1.9 years), and unknown (n = 20; 5.1 years). Predominant causes of death from comorbidities were cardiac and respiratory illnesses. Twenty-six patients (8%) developed a second primary tumor at a median time of 2.8 years (4 months to 10 years). The cumulative incidence of second primary tumors was 5%, 7%, and 13% at 3, 5, and 10 years, respectively. The most frequent site of second primaries was the lung (n = 13), followed by the esophagus (n = 3) and head and neck (n = 2) CONCLUSIONS: Patients with locoregionally advanced head and neck cancer treated with concurrent chemoradiotherapy are potentially curable but face significant risks of mortality from causes other than disease progression. Ameliorating toxicity, and implementing secondary screening and chemoprevention strategies are major goals in the management of head and neck cancer.     

High incidence and unique features of antigen receptor gene rearrangements in TEL-AML1-positive leukemias.

The t(12;21) translocation resulting in the TEL-AML1 gene fusion is found in 25% of childhood B-cell precursor (BCP) acute lymphoblastic leukemias (ALL). Since TEL-AML1 has been reported to induce cell cycle retardation and thus may influence somatic recombination, we analyzed 214 TEL-AML1-positive ALL by PCR for rearrangements of the immunoglobulin (Ig) and T-cell receptor (TCR) genes. As a control group, 174 childhood BCP ALL without a TEL-AML1 were used. The majority of TEL-AML1-positive leukemias had a higher number of Ig/TCR rearrangements than control ALL. They also had a more mature immunogenotype characterized by their high frequency of complete IGH, IGK-Kde, and TCRG rearrangements. While IGK-Kde and TCRG were more frequently rearranged on both alleles at higher age, IGH and TCRD rearrangements decreased in their incidence along with a decrease in biallelic IGH rearrangements. This suggests that the recombination process continues in these leukemias leading to ongoing rearrangements and possibly also deletions of antigen receptor genes. We here provide first evidence that somatic recombination of antigen receptor genes is affected by the TEL-AML1 fusion, and that further age-related differences are probably caused by the longer latency period of the prenatally initiated TEL-AML1-positive leukemias in older children.     

Effect of acupuncture compared with placebo-acupuncture at P6 as additional antiemetic prophylaxis in high-dose chemotherapy and autologous peripheral blood stem cell transplantation: a randomized controlled single-blind trial.

PURPOSE: The purpose is to investigate an additional antiemetic effect to ondansetron with needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture in patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation. EXPERIMENTAL DESIGN: Eighty patients who were admitted to hospital for high-dose chemotherapy and autologous peripheral blood stem cell transplantation were included into a randomized placebo-controlled single-blind trial. The patients were randomized to receive acupuncture (n = 41) or noninvasive placebo acupuncture (n = 39) at the acupuncture point P6 30 min before first application of high-dose chemotherapy and the day after. All patients received 8 mg ondansetron/day i.v. as basic antiemetic prophylaxis. The main outcome measure was the rate of patients who either had at least one episode of vomiting or required any additional antiemetic drugs on the first 2 days of chemotherapy. RESULTS: The main outcome measure showed no significant difference (P = 0.82): 61% failure in the acupuncture group and 64% in the placebo acupuncture group (95% confidence interval of 3% difference: -18.1 and 24.3%). Comparing nausea, episodes of vomiting or retching and number of additionally required antiemetic drugs did not provide any discrepancy with the main result. CONCLUSIONS: This study suggests that in combination with ondansetron i.v., invasive needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture has no additional effect for the prevention of acute nausea and vomiting in high-dose chemotherapy.     

Weekly carboplatin and paclitaxel followed by concomitant paclitaxel, fluorouracil, and hydroxyurea chemoradiotherapy: curative and organ-preserving therapy for advanced head and neck cancer.

PURPOSE: The paclitaxel, fluorouracil, and hydroxyurea regimen of paclitaxel, infusional fluorouracil, hydroxyurea, and twice-daily radiation therapy (TFHX) administered every other week has resulted in 3-year survival rates of 60% of stage IV patients. Locoregional and distant failure rates were 13% and 23%, respectively. To reduce distant failure rates, we added a brief course of induction chemotherapy to TFHX. PATIENTS AND METHODS: Sixty-nine patients received six weekly doses of carboplatin (AUC2) and paclitaxel (135 mg/m2) followed by five cycles of TFHX. RESULTS: Ninety-six percent had stage IV disease. Response to induction chemotherapy was partial response 52% and complete response (CR) 35%. Symptomatically, there was a significant reduction in mouth and throat pain. The most common grade 3 or 4 toxicity was neutropenia (36%). Best response following completion of TFHX was CR in 83%. Toxicities of TFHX consisted of grade 3 or 4 mucositis (74% and 2%) and dermatitis (47% and 14%). At a median follow-up of 28 months, locoregional or systemic disease progression were each noted in five patients. The overall 3-year progression-free survival was 80% (95% confidence interval [CI], 71% to 90%), and the 2- and 3-year overall survival rates were 77% (95% CI, 66% to 87%) and 70% (95% CI, 59% to 82%), respectively. At 12 months, five patients were completely feeding-tube dependent. CONCLUSION: Administration of carboplatin and paclitaxel before TFHX chemoradiotherapy results in high response activity and may decrease distant failure rates. Overall survival, progression, and organ preservation/functional outcome data support definitive evaluation of this approach.