Intensity dependence of auditory evoked potentials (AEPs) as biological marker for cerebral serotonin levels: effects of tryptophan depletion in healthy subjects

Rationale: The intensity dependence of the auditory evoked potentials (AEP) has been suggested to be a specific biological marker of central serotonergic activity. Objective: While previous studies used circumstantial evidence to support this hypothesis, we manipulated (decreased) cerebral levels of serotonin directly by using tryptophan depletion. Methods: Twelve healthy young subjects were investigated using placebo and two different amino acid mixtures in a double blind cross over design on three different occasions. AEPs recorded during tryptophan depletion were analyzed by dipole analysis and regional sources using methods published in the literature. Results: For none of the mixtures a significant effect of tryptophan depletion was found. There was a trend towards reduced intensity dependency after tryptophan depletion, especially in the right hemisphere. This reduction correlated with the amount of reduced tryptophan in plasma. Conclusions: The results indicate, in contrast to earlier indirect studies, that the intensity dependence of AEPs is not a specific marker of central serotonergic activity. Received: 8 March 1999 / Final version: 25 May 1999     

Incudostapedial joint in health and disease.

The incudostapedial joint was studied in tomograms of 370 normal and 80 diseased middle ears. The Guillen view was found to be superior to the anteroposterior view in demonstrating this joint in normal middle ears (85% and 62% visualization, respectively). In the presence of disease, visualization was markedly reduced to 19%; this lack of visualization is a nonspecific finding since early cholesteatomas, chronic otitis media, and retraction pockets could not be differentiated radiologically. Nonvisualization of the incudostapedial joint in the Guillen view is a more objective indicator of middle ear disease than such terms as "indistinct of hazy" middle ear cavities.     

Metastasiertes osteosarkom mit undifferenzierten karzinomähnlichen anteilen

Zusammenfassung Es wird über ein Osteosarkom bei einem 64jährigen Mann berichtet, bei dem aufgrund des Biopsiebefundes mit undifferenzierten Tumoranteilen sowie auch wegen des Alters and des Röntgenbefundes an Karzinommetastasen im Knochen gedacht wurde. Ein Primartumor konnte jedoch nicht gefunden werden. Die Autopsie ergab ein z.T undifferenziertes karzinomähnliches, daneben jedoch deutlich tumor-, knochen- and knorpelbildendes Osteosarkom im Bereich des linken Hüftgelenks mit multiples Skelettund Lungenmetastasen, ohne daß dabei trotz hohem Alter and ausgedehnter Ausbreitung des Sarkoms ein M. Paget als Vorerkrankung oder Risikofaktor nachgewiesen werden konnte.

---

Summary This was the case of a 64-year-old man with osteosarcoma. The biopsy yielded undifferentiated tumor without bone or cartilage formation. Because of high age of the patient and radiological changes present, a metastatic carcinoma was suspected. However, no primary could be found. Autopsy revealed an osteosarcoma in the region of the hip joint with alternating formation of tumor cartilage and tumor bone. There were also undifferentiated portions of endocrine osteosarcoma, simulating carcinoma. In spite of extensive skeletal involvement and pulmonary metastases-and high age-no evidence of morbus Paget of bone as possible preneoplastic disease was found.

     

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.

---

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.

---

---

Fräulein R. Brandmüller danke ich für die gewissenhafte Assistenz     

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.     

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.