The importance of genetic susceptibility in Dupuytren's disease.

Dupuytren's disease (DD) is a progressive fibromatosis that causes the formation of nodules and cords in the palmar aponeurosis leading to flexion contracture of affected fingers. The etiopathogenesis is multifactorial with a strong genetic predisposition. It is the most frequent genetic disorder of connective tissues. We have collected clinical data from 736 unrelated individuals with DD who underwent surgical treatment from Germany and Switzerland. We evaluated a standardised questionnaire, assessed the importance of different risk factors and compared subgroups with and without positive family history. We found that family history clearly had the strongest influence on the age at first surgery compared to environmental factors, followed by male sex. Participants with a positive family history were on average 55.9 years of age at the first surgical intervention, 5.2 years younger than probands without known family history (p = 6.7 × 10(-8) ). The percentage of familial cases decreased with age of onset from 55% in the 40-49 years old to 17% at age 80 years or older. Further risk factors analysed were cigarettes, alcohol, diabetes, hypertension, and epilepsy. Our data pinpoint the importance of genetic susceptibility for DD, which has long been underestimated.

c-kit/CD 117 positive cells in the myometrium of pregnant women and those with uterine endometriosis.

PURPOSE: Abnormal myometrial motility may play a role in the pathogenesis of endometriosis. Uterine contractility is a major contribution to labour. Myometrial motility might be controlled by CD 117-positive uterine smooth muscle cells. METHODS: Myometrial tissues from 8 cases with uterine endometriosis, 9 pregnant uteri (31.1 ± 8.7 weeks of gestation), 10 cases from non-pregnant pre-menopausal and 9 cases from post-menopausal women were immunohistochemically evaluated using a polyclonal antibody against c-kit/CD 117. The number of CD 117 positive cells was counted within 10 microscopic high power fields (× 400) and compared with the clinical diagnoses. RESULTS: Overall, a mean number of 15.7 (range 0-43) CD 117-positive cells within the myometrium was seen. Significant highest count occurred in the myometrium of non-pregnant pre-menopausal women without uterine endometriosis (30.78 ± 9.52), followed by post-menopausal women (15.5 ± 8.37) and those with uterine endometriosis (9.98 ± 4.9; p ≤ 0.01). The lowest count of CD 117-positive cells was seen in pregnant uteri (4.09 ± 2.33; p < 0.001). CONCLUSIONS: The lowest count of CD 117-positive cells was seen in the myometrium of pregnant women suggesting a role of preventing premature uterine contractility. There is no increase of CD 117-positive cells in the myometrium of women affected by uterine endometriosis.

[Long-term static overnight extension splinting following percutaneous needle fasciotomy]. / Die langfristige statische Extensions-Nachtschiene nach perkutaner Nadelfasziotomie.

The author reports on his experience with static night splinting after percutaneous needle fasciotomy (PNF). A conventional glove splint and custom made silicone bed splints were used. According to the experience of the author 3 typical case studies demonstrate that static night splinting of the Dupuytren fingers can achieve 2 things: reduction of the risk of recurrent curvature and remodeling of the Dupuytren tissue.

Decreased cytosolic glucocorticoid receptor levels in critically ill patients.

The immune system and the hypothalamic-pituitary-adrenal axis are linked by several mechanisms. Intracellular glucocorticoid receptors represent one important connection. The aim of this study was to examine the coherence between the number of glucocorticoid receptors, activation of the hypothalamic-pituitary-adrenal axis, inflammatory cytokine levels and the severity of illness in critically ill patients. In a prospective study, blood was collected from 20 healthy members of the hospital staff (control group) and 50 ventilated patients (sample group) within the first 24 hours after intubation and within three days of extubation. 3H-dexamethasone-binding assay was used to assess cytoplasmatic free glucocorticoid receptors levels. ACTH, cortisol, IL-6 and TNFa levels were measured by ELISA. In the sample group, specific binding of 3H-dexamethasone was significantly decreased compared to the control group. Glucocorticoid receptor levels tended to be lower in more severely ill patients. Plasma cortisol and ACTH levels were significantly different from the control group after extubation but not at intubation. Severe illness is associated with rapid down-regulation of 3H-dexamethasone binding. This decrease occurs before elevation of plasma cortisol. Therefore, down-regulation of cortisol binding may be directly associated with the stress response and not due to feedback regulation following increase in plasma cortisol levels.

Comparison of lens and Fresnel null correctors.

Fresnel null correctors are compared with classical Offner and Hindle null correctors for both optical performance and system sensitivities to errors of construction and placement in the test setup. Fresnel null correctors are closely related to circular diffractive null correctors, the main difference being that a Fresnel uses tilted grooves functioning like a blazed diffraction grating. The Fresnel has an advantage in that specific power terms can produce an aspheric wave front directly and not as the byproduct of bending lenses as in the traditional lens null correctors. The parametric relationships are summarized for a range of configurations of lens null correctors and for Fresnel null correctors. The sensitivities to construction and deployment errors are presented for each of these examples. The performance of two Fresnel correctors for an autocollimation test of a full three-mirror Cassegrain configuration is presented.

Spherical primary telescope with aspheric correction at a small internal pupil.

The aspheric plate at the center of curvature of a spherical primary is replaced by a small aspheric corrector at a minified pupil located inside a reimaging camera. The correctors are identical for each reimaging camera because the spherical aberration of the primary sphere is identical and symmetrical for all field positions. The magnitude of the field aberrations is evaluated over a range of primary focal ratios and minified pupil diameters. The major term is the increased field angle through the minified aspheric corrector. The field and chromatic aberrations in such a camera are compared with the equivalent full-aperture Schmidt corrector. Field-of-view partitioning enables each subfield to be designed for specific observational requirements, such as multiple-fiber spectrography or CCD imaging. Field partitioning is shown to be a powerful means for the replacement of the large aspheric corrector of a Schmidt telescope by a multiplicity of small reimaging subsystems. The cost to fill the typical wide field of a Schmidt telescope with reimaging modules is approximately 1% the cost of a Schmidt aspheric plate.

[Dupuytren contracture: new aspects on form pathogenesis and surgical principle]. / Morbus Dupuytren: Neue Aspekte zu Formalgenese und Operationsprinzip.

More than 20 years ago, the author formulated the proposition "extension inhibition instead of contraction" to explain the pathogenesis of Dupuytren's disease. This concept and the limited surgery derived from it are presented with preliminary long-term results. The tissue dynamics at the palmodigital zone were investigated. Subcutaneous microdissection and the first slices of adult hands (plastination) served to investigate the intact skin-covered subcutaneous tissue layer. On the flexor side, the hand has a complex skin anchoring system which effects mobile attachment of the digital subcutaneous tissue and stationary attachment of the palmar subcutaneous tissue. The disease fixes the flexion position of the tissue layer and impedes extension of the subcutaneous tissue and fingers. It is not the open but the closed hand from which fibromatosis starts. The principle "retention of flexion position" does not imply a contraction mechanism. The pathological substrate undergoes tendinous straightening by traction. There is secondary hypertrophy of the longitudinal fascicles of aponeurosis. The derived principle of limited surgery leaves the aponeurosis in situ. The preliminary results of follow-up examinations after five years and more show that there is no increased danger of recurrence when the aponeurosis is not removed. Out of 72 hands, 34 (47%) proved to be free of disease. Recurrences were found in 17 (24%) hands.

Glucocorticoid receptors are down-regulated in inflamed colonic mucosa but not in peripheral blood mononuclear cells from patients with inflammatory bowel disease.

BACKGROUND: Growing evidence indicates that the immune system and the hypothalamic-pituitary-adrenal system are linked by several mechanisms, for example intracellular glucocorticoid receptors (hGR). Glucocorticoids are the standard treatment of acute attacks of inflammatory bowel disease (IBD). Binding of glucocorticoids to hGR down-regulates the transcription of inflammatory genes that can propagate IBD. PATIENTS AND METHODS: IBD patients were either treated with 5-60 mg of prednisolone for more than 1 week or were without glucocorticoid treatment for more than 4 weeks. hGR levels were determined from isolated cytosol of peripheral blood mononuclear cells (PBMCs) or mucosal biopsies using a radioassay with [3H]-dexamethasone. Interleukin (IL) 6 levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The systemic (PBMC) hGR levels of corticosteroid-treated IBD patients were significantly lower than those of control subjects (59.6 +/- 57.1 dpm mg-1 cytosol protein vs. 227.0 +/- 90.8 dpm mg-1 cytosol protein, P = 0.007) and IBD patients not receiving glucocorticoid treatment (179.7 +/- 171.3 dpm mg-1 cytosol protein, P = 0.002). Systemic hGR levels in untreated IBD patients did not differ significantly from those in control subjects. In patients with connective tissue diseases, systemic hGR levels were also found to be decreased in the absence of glucocorticoid treatment. Systemic hGR levels in patients with Crohn's disease (CD) treated with steroids (66.6 +/- 61.0 dpm mg-1 cytosol protein) were not different from those in patients with ulcerative colitis (UC) (56.1 +/- 51.6 dpm mg-1 cytosol protein). In contrast to these findings, mucosal hGR levels were significantly decreased in both steroid-treated (18.0 +/- 15.5) and not steroid-treated (37.8 +/- 30.5) patients compared with control subjects (125.6 +/- 97.1; P = 0.00009 and P = 0.0008 respectively). IL-6 levels in all IBD groups with and without steroids were significantly different from those in control subjects. CONCLUSION: In IBD there is no difference in systemic hGR levels between not steroid-treated patients and control subjects, in spite of inflammatory activity (IL-6). Mucosal hGR levels were decreased independently of treatment, probably leading to a decreased protection against NF-kappaB action in the intestinal mucosa.

[Dupuytren disease--formal pathogenesis without contraction and a new surgery concept]. / Morbus Dupuytren--Formalpathogenese ohne Kontraktion und ein neues operationstaktisches Konzept.

The palmar fibromatosis holds the finger in the flexed position--extension inhibition rather than contraction. According to this extrinsic concept, only a passive, secondarily reactive effect can be attributed to the palmar aponeurosis. Out of 72 hands examined 5 or more years after an operation in which the aponeurosis had been left intact, 47% proved to be clear of disease.

Determination of the Hubble Space Telescope effective conic-constant error from direct image measurements.

Direct measurement of discernible features in the Hubble Space Telescope (HST) imagery has enabled a self-consistent determination to be made of the effective conic constant of HST images taken with planetary camera 6 (PC-6) of the wide field and planetary camera. Before being corrected for the contribution from PC-6, the conic constant is - 1.01429 +/- 0.0002. The correction for PC-6 is less accurately determined but probably lies between -0.0002 and 0.0004. As a result the HST optics are characterized best by a conic constant of - 1.0140 +/- 0.0003 as obtained from direct image measurements.

[Changes in the hand in Ehlers-Danlos syndrome type IV]. / Veränderungen an der Hand beim Ehlers-Danlos-Syndrom Typ IV.

The authors report a lethal course of Ehlers-Danlos syndrome type IV. In this patient hypermobility of the finger joints had been seen. The patho-biochemical structure of fibrous tissue is discussed.

Ehlers-Danlos syndrome type IV (EDS IV) as model of a defective biopolymer composite material.

The connective tissue of a lethal EDS IV case was investigated for the reasons of the manifested disturbances of the arterial wall. This functional disorder was attributed to the mechanical decoupling of elastin and collagen, with the premise of a composite material consisting of cellular, fibrillar, lamellar and other matrix components. A conceivable relation between the manifested deficiency of type III collagen and a disturbed anchoring of elastin is shown. These findings are supported by biochemical, morphological, x-ray and mechanical data.