[Stem-cell-based approaches for treating inner ear diseases]

The capacity of stem cells to regenerate lost tissue cells has gained recognition among physicians. Despite the successful use of blood stem cells for treating blood cancers, other stem cell types have not yet been widely introduced into clinical practice. Therapy options involving stem cells for inner ear diseases consequently have not been implemented. Nonetheless, several reports have recently been published describing the generation of morphologically and immunologically distinctive inner ear cell types-such as hair cells, supporting cells, and spiral ganglion neurons-from stem cells. Although promising, all of these studies still lack functional results regarding hearing restoration or vestibular function.

Residence near power lines and mortality from neurodegenerative diseases: longitudinal study of the Swiss population

The relation between residential magnetic field exposure from power lines and mortality from neurodegenerative conditions was analyzed among 4.7 million persons of the Swiss National Cohort (linking mortality and census data), covering the period 2000-2005. Cox proportional hazard models were used to analyze the relation of living in the proximity of 220-380 kV power lines and the risk of death from neurodegenerative diseases, with adjustment for a range of potential confounders. Overall, the adjusted hazard ratio for Alzheimer's disease in persons living within 50 m of a 220-380 kV power line was 1.24 (95% confidence interval (CI): 0.80, 1.92) compared with persons who lived at a distance of 600 m or more. There was a dose-response relation with respect to years of residence in the immediate vicinity of power lines and Alzheimer's disease: Persons living at least 5 years within 50 m had an adjusted hazard ratio of 1.51 (95% CI: 0.91, 2.51), increasing to 1.78 (95% CI: 1.07, 2.96) with at least 10 years and to 2.00 (95% CI: 1.21, 3.33) with at least 15 years. The pattern was similar for senile dementia. There was little evidence for an increased risk of amyotrophic lateral sclerosis, Parkinson's disease, or multiple sclerosis.

[Diagnostics of autoimmune diseases]

Autoantibodies play a key role in diagnostic laboratories as markers of autoimmune diseases. In addition to their role as markers they mediate diverse effects in vivo. Autoantibodies with protective effect have been described. Natural protective IgM autoantibodies against tumour-antigens of malignant cells or their precursors may contribute to increased survival rates of carcinoma patients. In a mouse model of systemic lupus erythematosus it has been shown that anti-dsDNA IgM autoantibodies protect from glomerular damage. In contrast, a direct pathogenic role of autoantibodies has been well established e.g. in myasthenia gravis or in Goodpasture syndrome. Similarly autoantibodies against SSA Ro52 are detrimental in neonatal lupus erythematosus with congenital heart block. Moreover, putatively protective autoantibodies may become pathogenic during the course of the disease such as the onconeuronal autoantibodies whose pathogenicity depends on their compartmentalisation. In patients with paraneoplastic syndromes tumour cells express proteins that are also naturally present in the brain. Anti-tumour autoantibodies which temporarily suppress tumour growth can provoke an autoimmune attack on neurons once having crossed the blood-brain barrier and cause specific neurological symptoms. Only a restricted number of autoantibodies are useful follow-up markers for the effectiveness of treatment in autoimmune diseases. Certain autoantibodies hold prognostic value and appear years or even decades before the diagnosis of disease such as the antimitochondrial antibodies in primary biliary cirrhosis or anti-citrullinated protein (CCP)-antibodies in rheumatoid arthritis. It is crucial to know whether the autoantibodies in question recognise linear or conformational epitopes in order to choose the appropriate detection methods. Indirect immunofluorescence microscopy remains a very useful tool for confirmation of results of commercially available immunoassays and for detection of special and rare autoantibodies that otherwise often remain undetected. Standardisation of autoimmune diagnostics is still underway and requires joint efforts by laboratories, clinicians and industry.

[Safety of treatment with tacrolimus ointment for anterior segment inflammatory diseases]

BACKGROUND: The off-label use of topical tacrolimus (Protopic) for inflammatory external eye diseases is gaining popularity. However, there are no reports on the safety profile of this new treatment option. PATIENTS AND METHODS: We treated six patients with different inflammatory eye diseases with topical tacrolimus (Protopic 0.03 %) as off-label use in addition to the conventional anti-inflammatory treatment. Patients were interviewed for side effects and serum drug concentrations were measured under steady state conditions one hour after topical application of tacrolimus ointment. RESULTS: Two patients reported a slight burning sensation immediately after application, in one patient we found a slight worsening of the dry eye problems. No patient abandoned the treatment due to side effects. Serum drug concentrations remained below the analytical threshold in all cases (< 1.5 ng/ml). CONCLUSIONS: Tacrolimus for the topical treatment of anterior segment inflammatory eye diseases is well tolerated without detectable systemic drug resorption.

[Lung transplantation in chronic obstructive lung diseases]

Lung transplantation (uni- or bilateral) is an accepted treatment option for patients with end-stage chronic obstructive pulmonary disease. Pulmonary function improves significantly and 5-year-actuarial survival is more than 70% at acceptable early mortality rates. Careful evaluation of risks and benefits in necessary because of the known donor-organ shortage and the risks of life-long immunosuppressive treatment. The bronchiolitis obliterans syndrome is still a nonsolved problem in the long-term course after LTx and it can influence late graft function and patient survival.

Cell death in allergic diseases

Apoptosis, the most common form of cell death, is a key mechanism in the build up and maintenance of both innate and adaptive immunity. Central to the apoptotic process is a family of intracellular cysteine proteases with aspartate-specificity, called caspases. Caspases are counter-regulated by multiple anti-apoptotic molecules, and the expression of the latter in leukocytes is largely dependent on survival factors. Therefore, the physiologic rates of apoptosis change under pathologic conditions. For instance, in inflammation, the expression of survival factors is usually elevated, resulting in increased cell survival and consequently in the accumulation of the involved immune cells. In many allergic diseases, eosinophil apoptosis is delayed contributing to both blood and tissue eosinophilia. Besides eosinophils, apoptosis of other leukocytes is also frequently prevented or delayed during allergic inflammatory processes. In contrast to inflammatory cells, accelerated cell death is often observed in epithelial cells, a mechanism, which amplifies or at least maintains allergic inflammation. In conclusion, deregulated cell death is a common phenomenon of allergic diseases that likely plays an important role in their pathogenesis. Whether the apoptosis is too little or too much depends on the cell type. In this review, we discuss the regulation of the lifespan of the participating leukocytes in allergic inflammatory responses.

Treatment of relapsing acute lymphoblastic leukemia in childhood. III. Experiences with 54 first bone marrow, nine isolated testicular, and eight isolated central nervous system relapses observed 1985-1989

Of 54 children with acute lymphoblastic leukemia (ALL) and first hematological recurrence observed between 1985 and 1989, 31 relapsed while still on treatment and 23 after cessation of therapy. Of the former, only one survived. Of the latter, 11 children survived after a minimum follow-up of 25 months. During the same period, a first isolated testicular relapse was observed in nine boys, of whom six survived, and an isolated CNS relapse in eight patients, of whom three survived. As a rule, survivors of a bone marrow or testicular relapse were doing well while those surviving a CNS relapse had considerable neuropsychological sequelae. These results, compared with those of two preceding studies, suggest that with intensification of front-line treatments, it becomes more difficult to rescue children who relapse, particularly those with a bone marrow relapse while on therapy.

[Imaging for hepato-pancreatico-biliary diseases - a short review]

The purpose of this chapter is to give a practical and clinically-orientated overview over the best radiological imaging for the most frequent diseases of the hepato-pancreatico-biliary system. For this purpose the liver parenchyma, the biliary tree, the pancreas and the hepatic vasculature are dealt with separately. According to the presumed pathology, the most cost-saving and time-efficient radiological imaging can then be chosen.

Biliary diseases in heart transplanted patients: a comparison between cyclosporine A versus tacrolimus-based immunosuppression

A cyclosporine (CsA)-based immunosuppression is associated with an increased incidence of cholelithiasis after heart transplantation. It is not known if tacrolimus (Tac) has comparable biliary side effects in humans. We evaluated the incidence of gallbladder sludge and cholelithiasis under Tac-based immunosuppression by ultrasound examinations in 31 cardiac transplants (25 male, 6 female, mean age: 59 ' 11 years). Data were compared to 57 patients (47 male, 10 female, mean age: 58 ' 11 years) who received CsA-based immunosuppression. 6 patients receiving Tac and 6 patients receiving CsA had already gallstones prior to transplantation so that finally 25 patients of the Tac group and 51 patients of the CsA group could be evaluated. In the Tac group the incidence of biliary sludge was 4% (1 of 25), of gallstones 28% (7 of 25). In comparison, patients receiving CsA developed biliary sludge in also 4% (2 of 51) and gallstones in 25% (13 of 51). Nine of 42 males in the CsA group (21%) and eight of 20 males in the Tac group (40%) developed either gallstones or sludge (n.s). Six of nine females in the CsA group (67%), but none of five females in the Tac group (0%) developed either gallstones or sludge (p = 0.01). In summary, the incidence of biliary disease in patients with Tac is comparable with CsA-based immunosuppression. We recommend regular sonographical examinations to detect biliary diseases as early as possible. In cases of clinically, laboratory and sonographical signs of cholecystitis cholecystectomy is indicated. It seems that towards lithogenicity female patients benefit more from a Tac-based treatment because the occurrence of gallstones is rare.

Interactive educational DVD on hoof protection, horseshoeing and diseases of the hoof

Good cooperation between farrier, veterinarian and horse owner is an important prerequisite for optimal support of the horse with regards to shoeing and hoof health. The introduction of a joint educational aid aims to improve the level of education of both veterinarians and farriers. The interactive, multimedia approach represents an innovative new dimension in instruction techniques, predominantly provided through images and videos. The contents of the new teaching aid will focus on detailed anatomy of the foot and distal limb, as well as currently accepted shoeing practices and techniques and pathologic conditions of the hoof and foot.

Histological assessment of testicular residues in lambs and calves after Burdizzo castration

To assess the reliability of the Burdizzo procedure for castrating calves and lambs, testicular tissue from 63 bull calves (15 intact and 48 castrated) and 69 male lambs (35 intact and 34 castrated) was collected at slaughter and assessed histologically. The bull calves were castrated at either one, four to five or 12 to 16 weeks of age and the lambs at either one or 10 weeks. There was clear evidence of spermatogenesis in testicular tissue from all the intact animals. In the samples from the calves that had been castrated at 12 to 16 weeks functional testicular tissue was completely lacking. However, there was evidence of spermatogenesis and steroidogenesis in the calves that had been castrated at one week or four to five weeks, respectively. Failure to achieve complete involution of the testicular parenchyma was observed in the majority of lambs, irrespective of the age at which they had been castrated.