What we've learnt about autoimmune neurological diseases from neuropathology.

Antibody-associated autoimmune neurological diseases are a group of disorders with various immune effector mechanisms that result in significant differences in disease course and prognosis. Paraneoplastic or idiopathic autoimmune encephalitis associated with antibodies against intracellular antigens are mostly characterized by a T-cell-dominated inflammation with neuronal loss, astrogliosis, and microglial nodules. In anti-Yo paraneoplastic cerebellar degeneration CD8+/granzymeB+ T cells were demonstrated in close apposition to neurons along with a nuclear upregulation of the activator of transcription 1, suggesting an important role of interferon-gamma in disease pathogenesis. Early and late disease stages may show different lesion types. For example, tissue samples from patients with temporal lobe epilepsy associated with antiglutamic acid decarboxylase 65 antibodies in early disease stages show numerous infiltrating T cells targeting hippocampal neurons and high numbers of B cells and plasma cells, while in chronic stages inflammation gets less and is followed by hippocampal sclerosis. Similarly, antiglial fibrillary acidic protein meningoencephalomyelitis may show loss of astrocytes only in the very early lesions, whereas in subacute and chronic stages astrocytes can get replenished most likely due to their high regeneration potential. In contrast, neuropathology of autoimmune neurological diseases mediated by surface antibodies is mostly characterized by a dysfunction of neurons in the absence of immune-mediated neuronal damage. The interaction of surface antibodies with their target antigen and the resulting downstream mechanisms are variable and can range from an internalization of the receptor in well-preserved neurons in anti-N-methyl-D-aspartate receptor encephalitis to an irreversible internalization and blocking of the receptor that may be associated with an accumulation of phosphorylated tau in specific brain regions in anti-IgLON5 disease. Interestingly, anti-IgLON5 patients with short disease duration were shown to present prominent deposition of IgG4 in the neuropil and on neuronal membranes in the absence of neuronal tau deposits, suggesting that the immune mechanisms precede neurodegeneration. Knowledge about pathomechanisms and patterns of tissue damage in different disease stages of antibody-associated autoimmune diseases will help to identify novel biomarkers and can give important clues for possible therapeutic interventions.

Decline of lactate in tumor tissue after ketogenic diet: in vivo microdialysis study in patients with head and neck cancer.

In head and neck squamous cell carcinoma (HNSCC) aerobic glycolysis is the key feature for energy supply of the tumor. Quantitative microdialysis (µD) offers an online method to measure parameters of the carbohydrate metabolism in vivo. The aim was to standardize a quantitative µD-study in patients with HNSCC and to prove if a ketogenic diet would differently influence the carbohydrate metabolism of the tumor tissue. Commercially available 100 kDa-CMA71-µD- catheters were implanted in tumor-free and in tumor tissue in patients with HNSCC for simultaneous measurements up to 5 days. The metabolic pattern and circadian rhythm of urea, glucose, lactate, and pyruvate was monitored during 24 h of western diet and subsequent up to 4 days of ketogenic diet. After 3 days of ketogenic diet the mean lactate concentration declines to a greater extent in the tumor tissue than in the tumor-free mucosa, whereas the mean glucose and pyruvate concentrations rise. The in vivo glucose metabolism of the tumor tissue is clearly influenced by nutrition. The decline of mean lactate concentration in the tumor tissue after ketogenic diet supports the hypothesis that HNSCC tumor cells might use lactate as fuel for oxidative glucose metabolism.

Evaluation of the efficacy of a probiotic containing Lactobacillus, Bifidobacterium, Enterococcus, and Pediococcus strains in promoting broiler performance and modulating cecal microflora composition and metabolic activities.

The aim of this work was to investigate the efficacy of a new multibacterial species probiotic in broiler nutrition. The probiotic contained 2 Lactobacillus strains, 1 Bifidobacterium strain, 1 Enterococcus strain, and 1 Pediococcus strain. Four hundred 1-d-old male Cobb broilers were allocated in 4 experimental treatments for 6 wk. The experimental treatments received a corn-soybean basal diet and were as follows: "control," with no other additions; "probiotic in feed and water," (PFW) with probiotic administered at 1 g/kg of feed for the whole period and in water on scheduled intervals during the first 4 wk; "probiotic in feed," (PF) with probiotic in feed as in PFW; and "antibiotic," (AB) with addition of avilamycin at 2.5 mg/kg of feed. Salinomycin Na was used as a coccidiostat. Each treatment had 5 replicates of 20 broilers. Treatment effects on parameters of broiler performance and cecal microbial ecology were determined. Broiler BW, feed intake, and feed conversion ratio were determined on a weekly and overall basis. Cecal microflora composition, concentration of volatile fatty acids, and activities of 5 bacterial glycolytic enzymes (alpha-galactosidase, beta-galactosidase, alpha-glucosidase, beta-glucosidase, and beta-glucuronidase) were determined at the end of the experiment. Overall, treatment PFW displayed a growth-promoting effect that did not differ from AB. Overall, feed conversion ratio in treatment AB was significantly better (P < or = 0.01) than the control treatment, whereas treatments PFW and PF were intermediate and not different from AB. Concentrations of bacteria belonging to Bifidobacterium spp., Lactobacillus spp., and gram-positive cocci were significantly (P < or = 0.05) higher in treatments PFW and PF compared with the control and AB treatments. Treatments PFW and PF had significantly higher specific activities of alpha-galactosidase and beta-galactosidase compared with the control and AB treatments. In conclusion, probiotic treatment PFW displayed a growth-promoting effect that was comparable to avilamycin treatment. In addition, treatments PFW and PF modulated the composition and, to an extent, the activities of the cecal microflora, resulting in a significant probiotic effect.

[Integration of the active middle ear implant Vibrant Soundbridge in total auricular reconstruction]. / Integration des aktiven Mittelohrimplantates in die plastische Ohrmuschelrekonstruktion.

BACKGROUND: Patients with high-grade microtia and atresia require a sophisticated and specific treatment. Apart from the plastic reconstruction of the auricle, in some cases hearing rehabilitation is medically indicated or is desired by the patients. The long-term results of simultaneous middle ear reconstruction with tympanoplasty are often inadequate owing to a persisting air-bone gap, and new techniques in hearing rehabilitation are needed for these patients. METHODS: We present three cases of unilateral atresia to illustrate a combined approach integrating hearing rehabilitation using the active middle ear implant Vibrant Soundbridge (VSB) into plastic auricular reconstruction. The VSB was attached to the stapes suprastructure via the titanium clip in two of these cases and in the third case a subfacial approach was used to attach it directly to the membrane of the round window. RESULTS: The air-bone gap was reduced to 17 dB, 14 dB and 0.25 dB HL. In free-field speech recognition tests at 65 dB SPL the patients achieved 100%, 90% and 100% recognition with the activated implant. No postoperative complications such as facial nerve paresis, vertigo or inner ear damage were found. CONCLUSIONS: The integration of active middle ear implants in auricular reconstruction opens up a new approach in complete hearing rehabilitation. The additional implantation of the VSB does not have any negative effect on the healing process or the cosmetic outcome of the auricular reconstruction.

[Epidemiology of auricular trauma]. / Zur Epidemiologie von Ohrmuschelverletzungen.

BACKGROUND: Auricular trauma is rare but can seriously reduce self-acceptance and function. Epidemiologic data on the causes of trauma causes and patient characteristics are limited. PATIENTS AND METHODS: The case notes of 141 from 197 patients with ear injuries have been reviewed retrospectively according to trauma cause and to the distribution of age and gender. RESULTS: Two thirds of the documented cases occurred between the age of 11 and 40 years. Men outnumbered women at a ratio of 2 to 1. The most frequent causes for ear trauma were traffic accidents (43 %), accidents at home (33 %), and fights (14 %). CONCLUSIONS: Mainly younger and active groups of the population are affected by ear trauma. Therefore, it is of particular concern in the acute setting to select those therapeutic options that have turned out good aesthetic and functional results in the long-term perspective.

Relation between perceived driving disability and scores of vision screening tests.

AIM: To determine the relation between perceived driving disability and vision screening tests. METHODS: 93 subjects, aged 50 years and over, with binocular visual acuity of at least 20/80. Perceived driving disability (PDD) was assessed by a questionnaire. Subtracting daytime from night-time driving question scores revealed PDD at night (PDDN), subtracting scores of questions for driving in familiar places from those in unfamiliar places revealed PDD at unfamiliar places (PDDU). RESULTS: PDD was strongly related to visual acuity, contrast sensitivity and useful field of view (UFOV). Specific relations existed between PDDN and Nyktotests and Mesotests and between PDDU and UFOV. These associations were enhanced in a subset of subjects with better visual acuities. CONCLUSIONS: Vision screening tests correlate well with perceived driving disabilities, especially when a subtraction method is used in the questionnaire to reveal condition dependent disabilities. Additional tests for visual acuity are useful, especially in subjects with better visual acuity.

In vivo perfusion analysis of normal and dysplastic ears and its implication on total auricular reconstruction.

INTRODUCTION: During the first stage of total auricular reconstruction with autologous rib cartilage, according to Nagata, the cartilage framework is placed in a subcutaneous pocket. Its posterior skin flap is relatively large and can be prepared with or without a subcutaneous pedicle. This represents the crucial part of the procedure, as impaired healing and infection can occur due to low perfusion. Nothing was known about the blood supply of ear remnants or flap perfusion during reconstruction. It was not clear whether the preservation of the additional subcutaneous pedicle secures high blood supply. METHODS: We used laser fluorescence angiography with indocyanine green dye for anatomical and functional perfusion studies in eight normal ears. Subsequently the anatomical and functional vessel architecture of 18 dysplastic ears was investigated. Finally, five patients each were operated on with or without subcutaneous pedicle during auricular reconstruction and intraoperatively monitored with laser fluorescence angiography. RESULTS: We showed that the vessel structure of normal ears detected by fluorescence angiography is equivalent to anatomical preparations. The surrounding skin in high grade microtia remnants is biphasically perfused by deep perforators and by the cutaneous vessel network. The preservation of the subcutaneous pedicle during auricular reconstruction leads to significantly better perfusion of the posterior skin flap. No signs of critical perfusion or complications were observed in these patients. DISCUSSION: We present the feasibility of laser fluorescence angiography to simultaneously gain anatomical and functional data about skin blood supply. The first anatomical and functional description of blood supply of ear remnants in third grade microtia is given. Functional data of skin flap perfusion during and after complete ear reconstruction were evaluated. The present study shows that the subcutaneous pedicle of Nagata's procedure is of great importance for success of the first stage operation as it prevents impaired wound healing. In contrast, patients without a subcutaneous pedicle had a broad spectrum of reduced perfusion and therefore some had complications.

[Auricular reconstruction for severe microtia. Schedule of treatment, operative strategy, and modifications]. / Ohrmuschelrekonstruktion bei hochgradiger Mikrotie. Behandlungsplan, plastische Operation und deren Sonderformen.

The incidence of microtia in Germany is 100-150 per year. These cases require a specific and challenging therapy. All patients need audiologic consultation. If desired plastic reconstruction is performed, which is aiming at achieving a lifelike as possible appearance corresponding to the shape of the opposite ear including an excellent skin color. The present paper describes background information, the interdisciplinary schedule of treatment, and the results of our operative strategy in two to three steps using autologous rib cartilage. Furthermore we expand on anomalous cases of microtia which require a modified procedure. In dystopic microtia, repositioning of the rudiment is necessary before reconstruction. In cases of excessive scar tissue due to injuries or previous operations, a one-step reconstruction using an axial fascia flap can be useful.

Use of Trichosporon mycotoxinivorans to suppress the effects of ochratoxicosis on the immune system of broiler chicks.

(1) The objective of this study was to determine whether the dietary inclusion of Trichosporon mycotoxinivorans (TRM) could suppress the detrimental effects of ochratoxin A (OTA) on the immune system of broiler chicks. (2) Six experimental treatments were tested in 300 1-d-old broiler chicks. Treatments included addition to a standard broiler ration of neither OTA nor TRM (Diet 1), OTA alone (500 microg/kg), OTA plus TRM at three inclusion rates (10(4) CFU/g of feed, 10(5) CFU/g, 10(6) CFU/g) and TRM alone at 10(5) CFU/g of feed. The ration was fed to chicks for 42 d. (3) Blood samples were collected at d 10, 20, 30 and 40 and macrophages and heterophils were isolated. The following variables were determined in macrophages and heterophils activated by phorbol myristate acetate (65 microM): cell viability, total cell-associated urokinase-plasminogen activator (u-PA), membrane-bound u-PA, free u-PA binding sites and superoxide production. (4) There was a decrease in the viability of macrophages and heterophils from chicks receiving OTA-contaminated feed compared to the viability of cells from control birds at d 40. Dietary TRM completely blocked the effect of OTA on cell viability; all three inclusion rates were equally effective. There was a decrease in total cell-associated and membrane-bound u-PA in macrophages and heterophils of chicks receiving OTA-contaminated feed compared to the corresponding values in control birds for heterophils at d 30 and 40 and for the macrophages at d 40. (5) Similarly, dietary TRM abolished the effect of OTA on total cell-associated and membrane-bound u-PA activity. All three inclusion rates of yeast were equally effective. Heterophils, but not macrophages, isolated from chicks receiving OTA-contaminated diet produced less superoxide anion compared to all other diet groups at d 30 and 40. (6) The immune system is a primary target of OTA toxicity in broilers: several functional properties of macrophages and heterophils were depressed in chicks fed OTA-contaminated feed. There was a delay of 30d before the immunosuppressive effect became apparent. The dietary inclusion of TRM completely blocked the detrimental effects of OTA on several immune properties in broilers.

[Psychological rehabilitation as social learning process--on the application of the communication therapy in rehabilitation (author's transl)]. / Psychologische Rehabilitation als sozialer Lernprozess--Zur Anwendung der Kommunikationstherapie in der Rehabilitation

As, from the socio-psychological point of view, disability constitutes a communication problem, it was studied in how far the principles of communication therapy - originally developed for the treatment of marriage and family problems - can be applied to the psychological rehabilitation of the disabled. The author and her colleagues are of the opinion that the communication therapeutic approach can essentially improve the rehabilitation process, especially through the direct involvement of everyday social partners.

[Automobile drivers with retinal diseases - a prospective analysis]. / Kraftfahrzeuglenker mit Netzhautleiden - eine prospektive Studie.

BACKGROUND: The study was designed to prospectively evaluate the driving habits of patients with retinal diseases, who were referred to the specialised retinal ambulatory care center of the Landesaugenklinik Salzburg. The main purpose of this study was to compare the legal requirements for visual acuity, as currently valid in Austria and Germany for driving motor vehicles, with the results found in this patients cohort and to analyse driving patterns of the patients with valid licenses. With these data, it seems possible to suggest a suitable time for a legally mandatory eye examination as to identify subjects with a potentially rising higher accident risk when driving. MATERIALS AND METHODS: In this study, 100 patients - all holders of a valid driving licence - with diabetic retinopathy or age related macular degeneration were enrolled. From each patient, the visual acuity (corrected or uncorrected depending on the driving habit) was recorded and a detailed questionnaire regarding the actual driving habits was requested. The resulting data were analysed in view of the legal requirements of both countries, Austria and Germany. RESULTS: Of 100 patients holding a valid driving licence a total of 31 were driving their motor vehicles with a legally insufficient visual acuity, 26 of 50 still driving. Of 50 patients suffering from diabetic retinopathy, 26 drove their cars illegally. Only 4 out of the above mentioned 31 patients had received sufficient information from their referring ophthalmologists. The average age of "illegal" drivers was 66.2 years. CONCLUSIONS: Within the European Community common legal requirements for driving a motor vehicle (regarding mainly the visual acuity) be clearly defined and a mandatory eye exam performed by qualified ophthalmologists for older subjects should be postulated. An individual and age related time limit to be placed on the driving licences of persons suffering from systemic diseases associated with relevant visual loss should to be discussed. Furthermore, ophthalmologists should be obliged to give detailed information to the patient with adequate documentation.

Investigation of different yeast strains for the detoxification of ochratoxin A.

High concentrations of ochratoxin A (OTA) in feed lead to growth depression in animals. It has been reported that binders can be used for deactivating aflatoxins but not for other mycotoxins without negatively influencing the animals health. In this study a strain from the genus ofTrichosporon with the ability to cleave ochratoxin A very selectively into phenylalanine and the non-toxic ochratoxin α (OTα) could be isolated. This strain was selected from a pool of OTA detoxifying microorganism by carrying out several investigations.Trichosporon sp. nov. can be fermented and stabilized. In a feeding trial with broilers lyophilizedTrichosporon-cells could compensate performance losses caused by OTA.

Isolation of viable Hodgkin and Reed-Sternberg cells from Hodgkin disease tissues.

Hodgkin disease (HD) is characterized by a small number of malignant Hodgkin and Reed-Sternberg (H/RS) cells among a major population of nonmalignant cells. The analysis of H/RS cells has been hampered by their low frequency and fragility. Here, we describe the isolation of viable H/RS cells from HD affected tissues by high gradient magnetic cell sorting (MACS) according to expression of CD30. The cells were enriched to a purity of up to 50%. H/RS cells were distinguished from other CD30(+) cells by the expression of CD15, their size and granularity. No CD30/CD15 double-positive cells could be enriched from a lymph node affected by the lymphocyte predominant subtype of HD, activated lymph nodes or peripheral blood of healthy donors. For two cases of HD individual MACS-purified H/RS cells and H/RS cells micromanipulated from tissue sections of the same lymphoma specimens were analyzed for Ig gene rearrangements. In both cases, identical V gene rearrangements were amplified from both sources of H/RS cells, showing that H/RS cells were successfully enriched. Moreover, the finding that in both cases no additional Ig gene rearrangements other than the ones identified in the H/RS cells micromanipulated from tissue sections were amplified from the MACS-purified H/RS cells further supports the monoclonality of these cells throughout the affected lymph nodes. The isolation of viable H/RS cells ex vivo is prerequisite for a direct study of gene expression by those cells and of their interaction with cells in their vicinity.