Vergleich veränderter Bewußtseinszustände unter den Halluzinogenen (−)-Δ9-trans-Tetrahydrocannabinol (Δ9-THC) und N,N-Dimethyltryptamin (DMT)

Zusammenfassung Die Untersuchung vergleicht unter Verwendung zweier Placebo-Kontrollgruppen veränderte Bewußtseinszustände, die unter den Halluzinogenen (–)⁹-trans-Tetrahydrocannabinol (⁹-THC) und N,N-Dimethyltryptamin (DMT) auftreten. 24 Probanden erhielten 250g ⁹-THC p.o. pro kg Körpergewicht, und 26 Probänden wurde 250g DMT pro Körpergewicht i.m. appliziert. Die Placebogruppe bestand aus insgesamt 24 Probanden. Die Effekte wurden retrospektiv mit einem Fragebogen erfaßt, dessen Items nach inhaltlichen und testtheoretischen Gesichtspunkten zu den folgenden 8 Skalen zusammengefaßt wurden: Optische Sinnestäuschungen, akustische Sinnestäuschungen, Konzentrations- und Gedächtnisstörungen, Derealisationserscheinungen, Depersonalisationserscheinungen, Leiberlebensveränderungen, euphorisches Zustandsbild und dysphorisches Zustandsbild.In allen acht Syndromen unterschieden sich die beiden Halluzinogene signifikant von Placebo. Zwischen den Halluzinogenen konnte jedoch keine signifikante Differenz nachgewiesen werden. In der Skala optische Sinnestäuschungen zeigte sich als Tendenz, daß DMT hier eine stärkere Wirkung als ⁹-THC entfaltet.Methodische Probleme des Vergleichs verschiedener Halluzinogene werden diskutiert.     

Improved survival of embryonic porcine dopaminergic neurons in coculture with a conditionally immortalized GDNF-producing hippocampal cell line

Transplantation of embryonic nigral tissue is used as an experimental therapy for patients with Parkinson's disease but is hampered by a limited survival rate of dopaminergic neurons. Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for nigrostriatal dopaminergic neurons, and the present in vitro study aimed at improving the survival of dopaminergic neurons in porcine mesencephalic brain slice cultures by adding transfected, immortalized, temperature-sensitive GDNF-releasing HiB5 cells (HiB5-GDNF). Embryonic (E27/28) porcine ventral mesencephalic brain slices were placed on membrane inserts in six-well plates with serum-containing medium, and HiB5-GDNF, nontransfected HiB5 cells (HiB5-control), or green fluorescent protein-producing HiB5 cells (HiB5-GFP) were seeded onto each tissue slice. The concentration of GDNF in the coculture medium was 0.49 +/- 0.13 ng/ml at day 9 and 0. 22 +/- 0.05 ng/ml at day 19 (mean +/- SEM) as measured by GDNF ELISA. The decrease in release of GDNF over time was paralleled by a gradual reduction in the number of HiB5-GFP cells expressing the reporter gene (EGFP). At day 12, HPLC analysis revealed that medium from HiB5-GDNF cocultures contained 2.0 times more dopamine than medium from HiB5-control cocultures. At day 21 there was 1.6 times more dopamine. Similar results were obtained for the dopamine metabolite 3,4-dihydroxyphenylacetic acid. At day 21, cell counts showed that HiB5-GDNF cocultures contained 1.5 times more tyrosine hydroxylase immunoreactive neurons than HiB5-control cocultures, which must be compared with a 1.8 fold increase after chronic treatment with rhGDNF (10 ng/ml). In conclusion, the better survival of HiB5-GDNF cocultures is promising for the generation of effective cell lines for local delivery of neurotrophic factors to intracerebral nigral grafts.     

Crohn's disease of the appendix

A giant appendix is an extremely rare and improbable finding during surgery in suspected cases of acute appendicitis. Although this condition is primarily suggestive of neoplasia, it is usually due to an inflammatory or infectious disease. We report a case of Crohn's disease limited to the appendix, which was diagnosed after a short right ileocolectomy. Only 156 similar diagnoses have been reported in the literature to date. This disease appears to have a benign course and therefore differs from classical Crohn's ileocolitis. For this reason, these patients do not require any specific investigation or follow-up.     

Base of tongue schwannoma: a case report

Both malignant and benign lesions may be found on the base of the tongue, including metastasis from other sites. Various surgical approaches to the base of tongue have been described. Here, we report a case of a 26-year-old woman with a schwannoma in the base of tongue removed through a suprahyoid pharyngotomy approach. The biology and pathology of schwannoma in the oral cavity are discussed. The advantage of the suprahyoid pharyngotomy approach for complete excision of a mass in the base of tongue is demonstrated.     

Cerebrospinal fluid indices in cryptococcal and tuberculous meningitis: the spider web coagulum and its diagnostic significance

The differentiation between a chronic cryptococcal meningitis and a chronic tuberculous meningitis may cause problems for the clinician only if standard microbiological methods are not applied to the diagnosis of both infections. In a male non-AIDS patient (50 y), 11 years after a suggested diagnosis of "tuberculous meningitis", meningoencephalitis with hydrocephalus was diagnosed and treated accordingly without success. Mycobacterium tuberculosis was never found. Because fibrin fibres of a spider web coagulum in the CSF resembled Aspergillus mycelium, the patient was then treated with amphotericin B + flucytosine. Finally, a mycological examination led to the true diagnosis: (1) In the CSF, resembling Aspergillus hyphae were found to be spider web coagulum fibres. (2) Cryptococcal meningoencephalitis based on the detection of Cryptococcus neoformans in CSF and its antigen in serum and CSF. - At post-mortem, cryptococcal meningoencephalitis was established as cause of death. Residual signs of tuberculosis could not be detected in the brain and the meninges. Common clinical similarities of cryptococcal and tuberculous meningitis and the possibility of a double infection are discussed. A comparison of the presence of Cr. neoformans in the meninges of non-AIDS and AIDS patients is made. The formation of spider web coagulum in the CSF is discussed. Proposals for the diagnosis, therapy and prophylaxis of cryptococcal meningitis are made.     

Altered NKG2D function in NK cells induced by chronic exposure to NKG2D ligand-expressing tumor cells

NKG2D is an activation receptor that allows natural killer (NK) cells to detect diseased host cells. The engagement of NKG2D with corresponding ligand results in surface modulation of the receptor and reduced function upon subsequent receptor engagement. However, it is not clear whether in addition to modulation the NKG2D receptor complex and/or its signaling capacity is preserved. We show here that the prolonged encounter with tumor cell-bound, but not soluble, ligand can completely uncouple the NKG2D receptor from the intracellular mobilization of calcium and the exertion of cell-mediated cytolysis. However, cytolytic effector function is intact since NKG2D ligand-exposed NK cells can be activated via the Ly49D receptor. While NKG2D-dependent cytotoxicity is impaired, prolonged ligand exposure results in constitutive interferon gamma (IFNgamma) production, suggesting sustained signaling. The functional changes are associated with a reduced presence of the relevant signal transducing adaptors DNAX-activating protein of 10 kDa (DAP-10) and killer cell activating receptor-associated protein/DNAX-activating protein of 12 kDa (KARAP/DAP-12). That is likely the consequence of constitutive NKG2D engagement and signaling, since NKG2D function and adaptor expression is restored to normal when the stimulating tumor cells are removed. Thus, the chronic exposure to tumor cells expressing NKG2D ligand alters NKG2D signaling and may facilitate the evasion of tumor cells from NK cell reactions.     

Diagnosis of Heerfordt's syndrome by state-of-the-art ultrasound in combination with parotid biopsy: a case report

The parotid gland is rarely affected by sarcoidosis (6% of all cases). If there is initial parotitis, and other major symptoms include fever, uveitis, or facial paralysis, the condition is referred to as Heerfordt's syndrome. The case presented here describes the diagnostic work-up and differentiation of swelling of the parotid gland by employing state-of-the-art ultrasound techniques in a 33-year-old patient with Heerfordt's syndrome. Color-coded duplex ultrasound demonstrated hypervascularization. Tissue harmonic and photopic imaging ultrasound additionally depicted hypoechoic, septated structural lesions of the glandular parenchyma with an optimized contrast. Since such structural changes are not a specific sonographic criterion for sarcoidosis, ultrasound-guided biopsy was performed for further clarification of the etiology of parotitis and for excluding lymphoma. In conclusion, state-of-the-art ultrasound with the option of obtaining a biopsy at low risk is a useful procedure for diagnosing unclear pathology of the parotid gland with rapid histological confirmation.     

Diagnostik und Therapie des Bandscheibenvorfalls

Degenerative processes in a movement segment of the vertebral column, which can potentially give rise to herniation of elements of the nucleus pulposus, are complex and of variable clinical and radiological dimensions; however the mere assumption that degenerative changes precede disc herniation remains a matter of debate. By definition, spinal disc herniation (SDH) refers to components of the gelatinous nucleus pulposus protruding beyond the dorsal level of the vertebral body margin through tears in the annulus fibrosus. Clinical presentation may include pain, paresis and sensory disturbances. Magnetic resonance imaging (MRI) is considered the gold standard in the diagnosis of SDH. In the majority of patients a conservative approach with physical therapy exercises and adequate analgesic and antiphlogistic medical treatment results in a substantial improvement of symptoms.     

Inspired Oxygen Fraction of 0.8 Does Not Attenuate Postoperative Nausea and Vomiting after Strabismus Surgery

Background: Postoperative nausea and vomiting (PONV) is a distressing problem after strabismus surgery. An inspired oxygen fraction has been reported to decrease PONV in patients after colon resection and to be more effective than ondansetron after gynecologic laparoscopy. Therefore, in a randomized, prospective, placebo-controlled study, the authors tested whether an inspired oxygen fraction of 0.8 decreases PONV in patients undergoing strabismus surgery and whether oxygen is more effective than ondansetron.

Methods: With approval of the authors' institutional review board, 210 patients were randomly assigned to receive one of three treatments: (1) 30% inspired oxygen in air plus intravenous administration of saline, (2) 80% inspired oxygen in air plus intravenous administration of saline, or (3) 30% inspired oxygen in air plus 75 [mu]g/kg ondansetron intravenously during induction. General anesthesia was standardized and included etomidate, alfentanil, and mivacurium for induction and sevoflurane for maintenance. PONV was evaluated 6 and 24 h postoperatively by an investigator unaware of treatment assignment.

Results: Overall postoperative incidence of nausea and vomiting was 41% for inspired oxygen fraction of 0.3 plus placebo, 38% for inspired oxygen fraction of 0.8 plus placebo, and 28% for inspired oxygen fraction of 0.3 plus ondansetron, respectively (P = 0.279). Therefore, there was no statistically significant difference of PONV incidence among groups.     

Radiosynthesis and in vivo evaluation of fluorinated huprine derivates as PET radiotracers of acetylcholinesterase

IntroductionDeveloping positron emission tomography (PET) radiotracers for non-invasive study of the cholinergic system is crucial to the understanding of neurodegenerative diseases. Although several acetylcholinesterase (AChE) PET tracers radiolabeled with carbon-11 exist, no fluorinated radiotracer is currently used in clinical imaging studies. The purpose of the present study is to describe the first fluorinated PET radiotracer for this brain enzyme.MethodsThree structural analogs of huprine, a specific AChE inhibitor presenting high affinity towards AChE in vitro, were synthesized and labeled with fluorine-18 via a mesylate/fluoro-nucleophilic aliphatic substitution: ([¹⁸ F]-FHUa, [¹⁸ F]-FHUb and [¹⁸ F]-FHUc). Initial biological evaluation included in vitro autoradiography in rat with competition with an AChE inhibitor at different concentrations, and microPET-scan on anesthetized rats. In vivo PET studies in anesthetized cat focused on [¹⁸ F]-FHUa.Results and ConclusionsAlthough radiosynthesis of these huprine analogs was straightforward, they showed poor brain penetration potential, partially reversed after pharmacological inhibition of P-glycoprotein. These results indicated that current huprine analogs are not suitable for PET mapping of brain AChE receptors, but require physicochemical modulation in order to increase brain penetration.