Proton spin tomography in children and adolescents with so-called idiopathic scoliosis]

Somato-sensory evoked potentials (SSEP) were found to be pathological mostly in the lower extremities in 26 out of 45 children suffering from so called idiopathic scoliosis. We examined the vertebral spine and the spinal cord of 8 of them (with controlled SSEP-findings) by use of conventional MR-imaging and (where necessary) 3-dimensional-data-set following the Fournier-procedure. 6 of the 8 children showed alterations as follows: 1. A lipoma spreading partly extra-, partly intraspinally. 2. Subligamentous protrusions of the intervertebral disc (2 patients). 3. Dysraphic processes (2 patients). 4. An abnormally cranial ending myelon surrounded by a widened spinal channel. The findings are demonstrated and discussed concerning the questions whether the pathological SSEP and, furthermore, the deformity of the vertebral spine could be explained thereby. We are at least able to prove that some of the children with so called idiopathic scoliosis show pathological evoked potentials and MRI-findings.     

Long-term adjuvant tamoxifen in early breast cancer: effect on bone mineral density in postmenopausal women

The decrease in sex steroid hormone levels after the onset of menopause is associated with bone loss and subsequent osteoporosis. Tamoxifen has antiestrogenic properties and may thus theoretically decrease bone mineral density, particularly after long-term treatment. Bone mineral density (BMD) was assessed in 75 recurrence-free postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen (40 mg daily) for 2 or 5 years versus no adjuvant endocrine therapy. The measurements were done about 7 years after the initial randomization. BMD was measured with single-photon absorptiometry (SPA) at two levels of the distal forearm representing cortical and trabecular bone. The BMD was found to be similar among tamoxifen patients compared with the controls. For cortical bone, the BMD was 1.03 g/cm2 (95% confidence interval [Cl], 0.97 to 1.09) among tamoxifen patients and 1.03 g/cm2 (95% Cl, 0.96 to 1.11) in controls. For trabecular bone, the values were 0.74 g/cm2 (95% Cl, 0.70 to 0.79) and 0.73 g/cm2 (95% Cl, 0.68 to 0.79), respectively. The results thus did not indicate an accelerated postmenopausal bone loss with long-term adjuvant tamoxifen.     

Assessing impact of differential symptom functioning on post‐traumatic stress disorder (PTSD) diagnosis

This article explores the generalizability of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV) diagnostic criteria for post‐traumatic stress disorder (PTSD) to various subpopulations. Besides identifying the differential symptom functioning (also referred to as differential item functioning [DIF]) related to various background variables such as gender, marital status and educational level, this study emphasizes the importance of evaluating the impact of DIF on population inferences as made in health surveys and clinical trials, and on the diagnosis of individual patients. Using a sample from the National Comorbidity Study‐Replication (NCS‐R), four symptoms for gender, one symptom for marital status, and three symptoms for educational level were significantly flagged as DIF, but their impact on diagnosis was fairly small. We conclude that the DSM‐IV diagnostic criteria for PTSD do not produce substantially biased results in the investigated subpopulations, and there should be few reservations regarding their use. Further, although the impact of DIF (i.e. the influence of differential symptom functioning on diagnostic results) was found to be quite small in the current study, we recommend that diagnosticians always perform a DIF analysis of various subpopulations using the methodology presented here to ensure the diagnostic criteria is valid in their own studies. Copyright © 2014 John Wiley & Sons, Ltd.     

Serum antibodies in first-degree relatives of patients with IBD: a marker of disease susceptibility? A follow-up pilot-study after 7 years

INTRODUCTION: Various disease-specific serum antibodies were described in patients with inflammatory bowel disease and their yet healthy first-degree relatives. In the latter, serum antibodies are commonly regarded as potential markers of disease susceptibility. The present long-term follow-up study evaluated the fate of antibody-positive first-degree relatives. PATIENTS AND METHODS: 25 patients with Crohn's disease, 19 patients with ulcerative colitis and 102 first-degree relatives in whom presence of ASCA, pANCA, pancreatic- and goblet-cell antibodies had been assessed were enrolled. The number of incident cases with inflammatory bowel disease was compared between antibody-positive and antibody-negative first-degree relatives 7 years after storage of serum samples. RESULTS: 34 of 102 (33%) first-degree relatives were positive for at least one of the studied serum antibodies. In the group of first-degree relatives, one case of Crohn's disease and one case of ulcerative colitis were diagnosed during the follow-up period. However, both relatives did not display any of the investigated serum antibodies (p=1). DISCUSSION: The findings of our pilot study argue against a role of serum antibodies as a marker of disease susceptibility in first-degree relatives of patients with inflammatory bowel disease. However, these data have to await confirmation in larger ideally prospective multicenter studies before definite conclusions can be drawn.     

Alterations of the CARD15/NOD2 gene and the impact on management and treatment of Crohn's disease patients

The recent identification of the CARD15/NOD2 gene as a susceptibility locus for Crohn's disease represents an important step towards the delineation of the immunopathogenesis of inflammatory bowel disease. CARD15 functions as an intracellular receptor for bacterial components and thus represents an important link between inflammatory bowel disease and innate immunity. Three major CARD15/NOD2 gene mutations have been associated with Crohn's disease in Caucasians in several independent studies. Together, they explain about 20% of the genetic susceptibility for Crohn's disease. Genotype-phenotype analyses demonstrated an association of these mutations with ileum-specific disease, an increased incidence of the fibrostenotic phenotype and an earlier age of disease onset. Beside these associations, no other relationship between the CARD15/NOD2 genotype and disease behavior or response to treatment has been detailed so far. Thus, the clinical impact of knowing the patient's genotype is limited at this time. Screening for CARD15 mutations in order to identify high-risk individuals or to introduce an individualized disease management is therefore currently not recommended.     

Randomized trial of adjuvant tamoxifen combined with postoperative radiation therapy or adjuvant chemotherapy in postmenopausal breast cancer

From 1976 to 1984, 427 postmenopausal women with high-risk breast cancer (pN + or pT greater than 30 mm) were randomized between postoperative radiation therapy (RT), radiation therapy plus tamoxifen (RT-TAM), adjuvant chemotherapy (CT), or chemotherapy plus tamoxifen (CT-TAM). Surgery was a modified radical mastectomy in all cases. The radiation therapy was given with high-voltage techniques and included the chest wall and regional nodes. The dose was 4600 cGy/4 1/2 weeks. Tamoxifen was given at a dose of 40 mg daily for 2 years. The adjuvant chemotherapy consisted of 12 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (or chlorambucil, methotrexate, and 5-fluorouracil [LMF] for patients entered before 1978). At a median follow-up time of 6 1/2 years the recurrence-free survival was significantly better for patients allocated to radiation therapy compared to chemotherapy and for patients allocated to tamoxifen compared to no adjuvant endocrine treatment (P less than 0.01). At 10 years the recurrence-free survival for patients in the RT-TAM, RT, CT-TAM, and CT groups was 63%, 57%, 47%, and 31%, respectively. A significant reduction of treatment failures with tamoxifen was only observed among patients with estrogen receptor-positive tumors. The overall survival difference in favor of patients allocated to radiation therapy or tamoxifen was not significant: the respective survival percentage at 10 years in the RT-TAM, RT, CT-TAM, and CT group was 65%, 62%, 52%, and 50%. The results indicate that postoperative radiation therapy continues to play an important role in the primary management of postmenopausal women with high-risk breast cancer and that the addition of tamoxifen may further improve the results among ER-positive patients.     

Morphometric evaluation of dark and clear epidermal basal cells during early 2-stage chemical skin carcinogenesis in the hairless mouse using two different fixation methods

Ultrastructural morphometric characteristics of basal keratinocytes in hairless mouse epidermis were analyzed statistically. The following variables were assessed: (i) low versus physiological osmolality during fixation, (ii) alterations induced by a 2-stage carcinogenesis regimen using DMBA and TPA, (iii) criteria for a cell being dark versus being clear, (iv) inter-observer variation. The results show that with low fixation osmolality most basal cells swell and become electron lucent. The few cells which apparently do not swell stand out as shrunken electron dense dark cells. Morphometrically they are more differentiated than clear cells, but do share many features with the basal cell type which appears after fixation in a buffer of physiological osmolality. Iso-osmolality during fixation seems to induce a homogeneous basal cell population of relatively electron dense cells without typical dark and clear elements. Treatment with DMBA/TPA induces not only intercellular edema and reduced desmosomal contacts, but causes injury to the plasma membrane leading to hydropic changes in the cells. This general intra- and intercellular DMBA/TPA induced hydration might induce secondary compression of some of the cells, leading to an increased number of compressed dark cells. It is, however, only after fixation in low buffer osmolality that these effects of DMBA/TPA are statistically significant and clearly observable. The inter-person variation was, apart from a few instances, either not statistically significant or did not interfere with the other effects. We did not find clear arguments in favor of the view that dark cells are primitive epidermal stem cells. They seem only to reflect non-specific toxic effects of tumor promoters, which appear only under certain fixation conditions, that have been used by most authors. The results suggest that dark and clear cells are mainly a consequence of the degree of cellular hydration.