[DGP Interstitial Lung Disease Patient Questionnaire]. / Patientenfragebogen zur Erfassung der Ursachen interstitieller und seltener Lungenerkrankungen ­ klinische Sektion der DGP.

BACKGROUND: Interstitial lung diseases (ILD) encompass different heterogeneous, mainly chronic diseases of the pulmonary interstitium and/or alveoli with known and unknown reasons. The diagnostic of ILD is challenging and should be performed interdisciplinary. The medical history is of major importance and therefore, in German-speaking countries the Frankfurter Bogen (published in 1985) was utilised to scrutinise the medical history of the patient. This by now more than 30-years-old questionnaire requires a revision with regard to content and language. METHOD: Under the auspices of the clinical section of the DGP the new Interstitial Lung Disease Patient Questionnaire was developed in collaboration amongst pulmonologist, occupational medicine physicians and psychologists and supported by patient support groups. The questionnaire was finally optimised linguistically with the help of patients. RESULTS: The newly developed patient questionnaire for interstitial and rare lung diseases encompasses different domains: initial and current symptoms, medical history questions including prior drug treatments, previous pulmonary and extrapulmonary diseases, potential exposition at home, work and leisure time as well as family history and travelling. CONCLUSION: The newly developed questionnaire can facilitate the diagnosis in patients with suspicion on interstitial lung disease in clinical routine.

Prefrontal cognitive deficits in patients with schizophrenia treated with atypical or conventional antipsychotics.

Forty-three patients with schizophrenia were investigated with a short neurocognitive screening battery focussing on working memory and executive functions. As compared to healthy controls, patients showed impairments in the modified card sorting test, in verbal fluency and all span tasks with exception of digit span forward. Patients who were treated with atypicals showed better performance in the digit ordering test (manipulation task) when compared to a group of patients who received conventional antipsychotics; this difference was not due to disease severity, age or education. Manipulation tasks might be useful for neurocognitive follow-up and intervention studies.

Cytotoxic effects of alkylphosphocholines or alkylphosphocholine-liposomes and macrophages on tumor cells.

The influence of the alkylphosphocholines (APC) on macrophage activation to tumor cytotoxicity was investigated in vitro with both mouse peritoneal and rat liver macrophages. For this purpose the compounds were used either in micellar or in liposomal form. The cytotoxic effect of micellar or liposomal APC was increased with prolongation of the aliphatic chain and was reduced for the liposomal form. Peritoneal macrophages incubated with APC-liposomes gave a comparable cytotoxic effect on MethA cells to that of the free, highly toxic APC alone. These liposomes can activate rat liver macrophages (Kupffer cells) in vitro to a moderate tumor cytotoxicity on C26 colon carcinoma cells, while the micellar APC were toxic to macrophages. A significant release of NO-radicals from peritoneal macrophages was obtained with Liposomes but not with micellar lipid. The release of tumor necrosis factor (TNF) was stimulated by incubation with micellar or liposomal HPC. Whereas the micellar HPC was comparable to lipopolysaccharide (LPS) in TNF release stimulation, the HPC-liposomes caused a much higher release.

Switch of anti-VEGF agents is an option for nonresponders in the treatment of AMD.

BACKGROUND: Although anti-VEGF therapy of exudative AMD with bevacizumab and ranibizumab proved efficacious in the majority of patients, CNV activity does not respond to continued treatment after repeated injections in a considerable amount of patients. These are referred to as nonresponders. A change of the drug to bevacizumab or ranibizumab could possibly offer an alternative option for the treatment of nonresponding exudative AMD. METHODS AND MATERIALS: A total of 138 nonresponders who switched therapy from bevacizumab to ranibizumab (n=114) or vice versa (n=24) were included in a retrospective study. Visual acuity (VA) and foveal thickness before and after the switch of therapy were compared. By means of linear regression analysis, we analyzed possible prognostic factors associated with a favorable outcome for visual acuity. RESULTS: Linear regression analysis revealed a statistically significant benefit for nonresponders when treatment was changed to a different anti-VEGF drug (bevacizumab or ranibizumab). VA at the time of the switch was positively correlated with a beneficial development of VA after changing the drug. There was no significant correlation with age, macular thickness, number of injections before the switch, or the development of VA under treatment before the switch. Both patients switching to Avastin and Lucentis benefitted without statistically significant differences. CONCLUSIONS: An exchange of bevacizumab with ranibizumab or vice versa should be considered in nonresponders in the treatment of exudative AMD. Further prognostic factors may help to identify patients who might benefit from a switch. These factors should be investigated in further studies.

Antitumor effects of alkylphosphocholines in different murine tumor models: use of liposomal preparations.

Hexadecylphosphocholine (HPC) and its analogs with a longer alkyl chain (C18 and C20) were examined for antineoplastic activity in the murine tumor models P388 leukemia, B 16 melanoma, the mammary carcinoma C3H and Ca 755, and the human MT-1 mammary tumor in nude mice. The maximum tolerated doses were determined and found to be higher in mice than in rats. The toxicity of the alkylphosphocholines increases with chain length. The murine mammary carcinoma C3H and the human MT-1 mammary carcinoma showed response to HPC whereas the classical screening models did not respond to the synthetic lipids. Furthermore, HPC showed activity in a mitoxantrone-resistant P388 leukemia. Treated/control values between 120 and 160% in survival time could be obtained following a daily application of the lipid. Examination of the activity of possible cleavage products of HPC gave no information about the mechanism of action of the used etherlipids. Liposomes with encapsulated mitoxantrone, formed from alkylphosphocholines, cholesterol and dicetylphosphate had the same activity against P388 mouse leukemia as the free drug. The hemolytic activity of the three lipids tested in vivo was assumed to be related to toxic deaths of single animals; hemolytic activity was observed to be sometimes independent of schedule and dose.

Antineoplastic activity in vitro of free and liposomal alkylphosphocholines.

We investigated the liposome forming properties of three homologues of alkylphosphocholines: hexadecylphosphocholine (HPC), octadecylphosphocholine (OPC) and eicosanylphosphocholine (EPC). In the presence of cholesterol and dicetylphosphate, alkylphosphocholines form liposomes with slow permeability for entrapped carboxyfluorescein. We studied the direct cytotoxicity of alkylphosphocholine vesicles and their ability to attack MethA sarcoma cells, human skin and muscle fibroblasts (M22, GUS, Moscow), and human mouth epidermoid carcinoma cells (KB, ATCC, CCL 17). All alkylphosphocholines show cytotoxic activity against the investigated cells, the degree of which depends on the number of carbon atoms in the alkyl chain, concentration and incubation time. Whereas the etherlipid liposomes are less toxic to MethA cells than the free compounds, the liposomal alkylphosphocholines are more toxic toward KB and M22 cells than the corresponding free lipids.

Antineoplastic activity of alkylphosphocholines (APC) in human breast carcinomas in vivo and in vitro; use of liposomes.

This study examines the in vitro and in vivo activity of alkylphosphocholines (APC) in experimental human breast carcinomas. Three analogs, hexadecylphosphocholine (HPC), octadecylphosphocholine (OPC) and eicosanylphosphocholine (EPC) were investigated. Three hormone receptor negative cell lines were sensitive to all three APCs in vitro whereas the receptor positive MCF-7 line was more resistant. Sensitivity was seen in 4/6 hormone receptor negative tumors in vivo, with HPC being the most active analog. There were no antitumor effects in the four receptor positive models. The reasons for these differences in response between hormone receptor negative and -positive lines are not yet understood and require further study. Gastrointestinal toxicity and hemolysis, the major side effects of the APCs, were reduced by the use of liposomal preparations.