Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (I)

Occupational diseases Nos. 2108 and 2110 correspond to intervertebral disc-related diseases of the lumbar spine from many years of carrying or lifting heavy loads, occupations in extreme postures of full flexion or oscillation of the whole body when seated, and which compel the cessation of all activities which are or could be the cause for the origin, exacerbation or recurrence of the disease. These occupational diseases came into force at the start of 1993, but there have been considerable problems in their implementation. The present Part I of the contribution is the result of the work of an interdisciplinary study group and contains medical criteria for the assessment of possibly strain-related clinical characteristics and the evaluation of other possible causes. Part II is to be published in Volume 4/2005 and will deal with questions related to forced cessation and to the assessment of the loss of earning ability. Agreement was reached in many areas related to the assessment of occupational claims. This should allow for evidence-based decision making in the future for the occupational diseases Nos. 2108 and 2110.     

Modelling Germline Mosaicism and Different New Mutation Rates Simultaneously for Appropriate Risk Calculations in Families with Duchenne Muscular Dystrophy

For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic tests for females can only screen for deletions. Negative deletion test results can now be included in the risk calculations.     

Detergent fractionation with subsequent subtractive suppression hybridization as a tool for identifying genes coding for plasma membrane proteins

Abstract:  The identification of tumor-specific proteins located at the plasma membrane is hampered by numerous methodological pitfalls many of which are associated with the post-translational modification of such proteins. Here, we present a new combination of detergent fractionation of cells and of subtractive suppression hybridization (SSH) to gain overexpressed genes coding for membrane-associated or secreted proteins. Fractionation of subcellular components by digitonin allowed sequestering mRNA of the rough Endoplasmatic reticulum and thereby increasing the percentage of sequences coding for membrane-bound proteins. Fractionated mRNAs from the cutaneous T-cell lymphoma (CTCL) cell line HuT78 and from normal peripheral blood monocytes were used for SSH leading to the enrichment of sequences overexpressed in the tumor cells. We identified some 21 overexpressed genes, among them are GPR137B, FAM62A, NOMO1, HSP90, SLIT1, IBP2, CLIF, IRAK and ARC. mRNA expression was tested for selected genes in CTCL cell lines, skin specimens and peripheral blood samples from CTCL patients and healthy donors. Several of the detected sequences are clearly related to cancer, but have not yet been associated with CTCL. qPCR confirmed an enrichment of these mRNAs in the rough endoplasmic reticulum fraction. RT-PCR confirmed the expression of these genes in skin specimens and peripheral blood of CTCL patients. Western blotting verified protein expression of HSP90 and IBP2 in HuT78. GPR137B could be detected by immunohistology in HuT78 and in keratinocytes of dysplastic epidermis, but also in sweat glands of healthy skin. In summary, we developed a new technique, which allows identifying overexpressed genes coding preferentially for membrane-associated proteins.     

A novel GalR2-specific peptide agonist

The galanin peptide family and its three receptors have with compelling evidence been implicated in several high-order physiological disorders. The co-localization with other neuromodulators and the distinct up-regulation during and after pathological disturbances has drawn attention to this neuropeptide family. In the current study we present data on receptor binding and functional response for a novel galanin receptor type 2 (GalR2) selective chimeric peptide, M1145 [(RG)₂-N-galanin(2-13)-VL-(P)₃-(AL)₂-A-amide]. The M1145 peptide shows more than 90-fold higher affinity for GalR2 over GalR1 and a 76-fold higher affinity over GalR3. Furthermore, the peptide yields an agonistic effect in vitro, seen as an increase in inositol phosphate (IP) accumulation, both in the absence or the presence of galanin. The peptide design with a N-terminal extension of galanin(2-13), prevails new insights in the assembly of novel subtype specific ligands for the galanin receptor family and opens new possibilities to apply the galanin system as a putative drug target.     

Discrimination of idiopathic pain syndromes from neurogenic pain syndromes and healthy volunteers by means of clinical rating,personality traits,monoamine metabolites in CSF,serum cortisol,platelet MAO and urinary melatonin

Summary The aim of the present study was to investigate the discriminative power of a series of variables (including determination of depressive symptomatology by means of a visual analogue scale, determination of personality traits by means of the Karolinska Scales of Personality, determination of monoamine metabolites in CSF, platelet MAO activities, serum cortisol before and after dexamethasone suppression and urinary melatonin) in differentiating (a) chronic pain patients from healthy subjects, and (b) patients with idiopathic pain syndromes from patients with neurogenic pain syndromes. Separately each of the measures gave a significant but often low contribution to the discrimination, while a combination of several measures gave a complete discrimination both between healthy subjects and patients with chronic pain syndromes and between patients with idiopathic and neurogenic pain syndromes, respectively.Supported in part by grants from the Swedish Medical Research Council (grants no. 3371, 4145 and 5740) and by a grant from Stiftelsen Söderström-Königska Sjukhemmet     

Effect of impact exercise on bone mineral density in elderly women with low BMD: a population-based randomized controlled 30-month intervention

Evidence of the effect of exercise on bone loss comes mainly from studies in voluntary postmenopausal women, and no population-based, long-term interventions have been performed. The purpose of this population-based, randomized, controlled trial was to determine the effect of long-term impact exercise on bone mass at various skeletal sites in elderly women with low bone mineral density (BMD) at the radius and hip. Participants ( n =160) were randomly assigned to 30 months either of supervised and home-based impact exercise training or of no intervention. The primary outcome measures were femoral neck, trochanter and total hip BMD, and the secondary outcomes were bone density measures at the radius and calcaneum. Outcomes were assessed at baseline, 12 months and 30 months using blinded operators. The analyses were performed on an intention-to-treat analysis. Mean femoral neck and trochanter BMD decreased in the control group [–1.1%, 95% confidence interval (CI) –0.1% to –2.1% and –1.6%, 95% CI –0.4% to –2.7%], while no change occurred in the exercise group. Mean trochanter BMC decreased more in the control group (–7.7%, 95% CI –9.7% to –5.6% vs. –2.9%, 95% CI –5.3 to –0.9). There were six falls that resulted in fractures in the exercise group and 16 in the control group during the 30-month intervention ( P =0.019). A significant bone loss occurred in both groups at the radius and calcaneum. In multivariate analysis, weight gain was associated with increased BMD and BMC at all femur sites both in the exercise group and in the pooled groups. In conclusion, impact exercise had no effect on BMD, while there was a positive effect on BMC at the trochanter. Exercise may prevent fall-related fractures in elderly women with low bone mass.There was no conflict of interest.