Ongoing MRI remodeling 3-7 years after collagen meniscus implantation in stable knees.

PURPOSE: The purpose of the present study was to evaluate the clinical and radiological 3-7 years outcomes of patients who underwent collagen meniscus implantation in stable or stabilized knees. It was the hypothesis that using the collagen meniscus (CMI) good clinical 3-7 years outcomes with low pain levels are achieved. METHODS: Thirty-nine patients (male:female = 30:9, mean age 34 ± 10 years) underwent arthroscopic CMI after subtotal medial (n = 32) or lateral meniscectomy (n = 7). A 7-mm CMI was performed due to prophylactic (n = 25) or therapeutic indication (n = 14). IKDC score, Tegner score preinjury, preoperatively and at follow-up, Lysholm score and visual analogue scale for pain and satisfaction (follow-up rate 90%) were assessed. MRI scans were analyzed according to the Genovese criteria (n = 19). Implant failure was defined as infection or mechanical failure of the device. The minimum follow-up time was 36 months (range 36-84 months). RESULTS: The mean VAS satisfaction preoperatively and at follow-up was 4.0 ± 0 and 1.6 ± 1.0. The mean VAS pain was 4.3 ± 3.2 preoperatively and at last follow-up 2.1 ± 1.7. The median Tegner score preinjury was 7 (range 3-10), it decreased preoperatively to median 3.5 (range 1-8) and nearly reached the preinjury level at last follow-up 6 (range 3-10). The mean Lysholm score before surgery was 66 ± 20 and 91 ± 8 at last follow-up. Seven patients (38.9%) had a normal total IKDC score (A), 10 patients were nearly normal (B) and 1 patient slightly abnormal (C). In MRI the CMI was entirely resorbed in 4 patients (21%) and partially resorbed in 15 (79%). In 4 patients (21%) the CMI was isointense, in 14 (74%) slightly hyperintense and in 1 (5%) highly hyperintense. Ten patients (53%) showed marked signs of bone marrow edema. In 13 patients (68%) an extrusion of the meniscus > 3 mm at last follow-up was found. CONCLUSIONS: Meniscal substitution with the CMI showed good to excellent clinical 3-7 results. The CMI shows an ongoing remodelling with decreased signal intensity and decreased size. However, as meniscus extrusion remained at the same level and bone marrow edema decreased from 1 year to longer term follow-up, it appears that the remodeling comes to an end at about 5 years after CMI. LEVEL OF EVIDENCE: IV.

One-year clinical and MR imaging outcome after partial meniscal replacement in stabilized knees using a collagen meniscus implant.

PURPOSE: The purpose of the study was to evaluate the clinical and radiological outcomes after medial/lateral collagen meniscus substitution (CMI) at 12 months postoperatively. METHODS: Sixty-seven patients (m:f = 47:20, mean age 36 ± 10 years) underwent arthroscopic CMI after previous subtotal medial (n = 55) or lateral meniscectomy (n = 12) due to persistent joint line pain (n = 25) or to prophylactic reasons (n = 42). Clinical follow-up consisted of IKDC score, Tegner score, Lysholm score, and visual analog scale for pain and satisfaction (preinjury, preoperatively, and 12 months postoperatively; follow-up rate 90 %). MRI scans were analyzed according to the Genovese criteria. RESULTS: Nineteen patients (29 %) showed a normal (A), 35 nearly normal (B), 5 abnormal (C), and 1 patient severely abnormal total IKDC score (D). The median Tegner preinjury score was 7 (range 2-10) and at follow-up 6 (range 2-10). The mean Lysholm score before surgery was 68 ± 20 and 93 ± 9 at follow-up. Preoperatively, the mean VAS pain was 4.4 ± 3.1 and 2.0 ± 1.0 at follow-up. Clinical failure of the CMI occurred in 3 patients (n = 1 infection, n = 1 failure of the implant, n = 1 chronic synovitis). On MRI, the CMI was completely resorbed in 3 patients (5 %), partially resorbed in 55 (92 %), and entirely preserved in 3 (5 %) patients. In 5 patients (8 %) the CMI was isointense, in 54 (90 %) slightly and 1 (2 %) highly hyperintense. 43 (72 %) patients showed an extrusion of the CMI implant of more than 3 mm. CONCLUSIONS: Significant pain relief and functional improvement throughout all scores at 1 year was noted. The CMI undergoes significant remodeling, degradation, resorption, and extrusion in most of the patients. No difference in outcomes between the medial and lateral CMI was observed. LEVEL OF EVIDENCE: Prospective therapeutic study, Level IV.

Cross-linking of the dermo-epidermal junction of skin regenerating from keratinocyte autografts. Anchoring fibrils are a target for tissue transglutaminase.

Since transglutaminases create covalent gamma-glutamyl-epsilon-lysine cross-links between extracellular matrix proteins they are prime candidates for stabilizing tissue during wound healing. Therefore, we studied the temporo-spatial expression of transglutaminase activity in skin regenerating from cultured epithelial autografts in severely burned children by the specific incorporation of monodansylcadaverine into cryostat sections from skin biopsies obtained between 5 d to 17 mo after grafting. The dansyl label was subsequently immunolocalized in the epidermis, dermal connective tissue, and along the basement membrane. Incubation of cryosections of normal and regenerating skin with purified tissue transglutaminase confirmed the dermo-epidermal junction and the papillary dermis as targets for this enzyme and revealed that in regenerating skin transamidation of the basement membrane zone was completed only 4-5 mo after grafting. Immunoelectron microscopy revealed that three distinct regions on the central portion of anchoring fibrils were positive for monodansylcadaverine in normal skin which were negative during the initial phase of de novo formation of anchoring fibrils in regenerating skin. Biochemically, we identified collagen VII as potential substrate for tissue transglutaminase. Thus, tissue transglutaminase appears to play an important role not only in cross-linking of the papillary dermis but also of the dermo-epidermal junction in particular.

Manufacture of a cell-free amnion matrix scaffold that supports amnion cell outgrowth in vitro.

We manufactured a cell-free extracellular matrix scaffolds in order to obtain a support material for amnion cell outgrowth, eventually being used for repair of prematurely ruptured fetal membrane. Human preterm or term amnion tissue was separated into its collagenous extracellular matrix and cell components. The acellular scaffold was explored for its capacity to support regrowth of isolated human amnion epithelial or mesenchymal cells in vitro. The outgrowth of amnion cells on and in the scaffold was investigated by scanning and transmission electron microscopy, and confocal laser scanning microscopy. Cell-free amnion matrix scaffolds demonstrated a porous collagen fiber network similar as in native amnion. Inoculation of acellular amnion scaffolds with human amnion cells revealed that its property to support amnion cell outgrowth was retained. Amnion epithelial and mesenchymal cells were found to grow into dense layers on the surface of the scaffold within 3-4 days and 7-8 days, respectively, and to some extent, invaded the scaffold during the culture period. Manufactured acellular amnion matrix retains structural and functional properties required for cell outgrowth in vitro. It may become useful to repair prematurely ruptured fetal membranes.

Plant orthologs of p300/CBP: conservation of a core domain in metazoan p300/CBP acetyltransferase-related proteins.

p300 and CBP participate as transcriptional coregulators in the execution of a wide spectrum of cellular gene expression programs controlling cell differentiation, growth and homeostasis. Both proteins act together with sequence-specific transcription factors to modify chromatin structure of target genes via their intrinsic acetyltransferase activity directed towards core histones and some transcription factors. So far, p300-related proteins have been described in animals ranging from Drosophila and Caenorhabditis elegans to humans. In this report, we describe p300/CBP-like polypeptides in the plant Arabidopsis thaliana. Interestingly, homology between animal and plant p300/CBP is largely restricted to a C-terminal segment, about 600 amino acids in length, which encompasses acetyltransferase and E1A-binding domains. We have examined whether this conservation in sequence is paralleled by a conservation in function. The same amino acid residues critical for acetyltransferase activity in human p300 are also critical for the function of one of the plant orthologs. Remarkably, plant proteins bind to the adenovirus E1A protein in a manner recapitulating the binding specificity of mammalian p300/CBP. The striking conservation of an extended segment of p300/CBP suggests that it may constitute a functional entity fulfilling functions that may be essential for all metazoan organisms.

Functional analysis of the p300 acetyltransferase domain: the PHD finger of p300 but not of CBP is dispensable for enzymatic activity.

Acetylation of nucleosomal histones is a major regulatory step during activation of eukaryotic gene expression. Among the known acetyltransferase (AT) families, the structure-function relationship of the GNAT superfamily is the most well understood. In contrast, less information is available regarding mechanistic and regulatory aspects of p300/CBP AT function. In this paper, we investigate in closer detail the structure and sequence requirements for p300/CBP enzymatic activity. Unexpectedly, we find that the PHD finger of p300, but not of CBP, is dispensable for AT activity. In order to identify residues involved in substrate or acetyl-coenzyme A (acetyl-CoA) recognition, we have introduced 19 different amino acid substitutions in segments that are highly conserved between animal and plant p300/CBP proteins. By performing acetylation reactions with histones, a p53 peptide or the AT domain itself, we define several residues required for histone and p53 substrate recruitment but not for acetyl-CoA binding. Finally, we show that identical mutations in the p300 and CBP AT domain impair AT activity differently. This latter result combined with the finding of a differential requirement for the PHD finger provides evidence for structural differences between p300 and CBP that may in part underlie a previously reported functional specialization of the two proteins.

[Metaanalysis of reference values in hematology]. / Referenzbereiche in der Hämatologie.

The reference values of the most commonly used parameters in hematology were evaluated in a metaanalysis using practices of a group of major hospitals in Switzerland and in detail review of the literature. Extensive differences of the reference values have been noted being caused mainly by selection of different patient/control collectives. Whenever possible, reference values were separately evaluated for age, gender and race. The reported reference values approximated a Gauss distribution allowing for statistical evaluation accordingly. Due to recent standardization (ICSH and NCCLS), differences caused by instrumentation and preanalytics were found to be of less importance. Our presented validated reference values in hematology should allow for better discrimination of classical hematological disease entities such as an iron deficiency anemia, thalassemia and hemolysis.

[Classification of neoplastic disorders of the haematopoietic system]. / Klassifikation von Neoplasien des hämatopoietischen Systems.

The present article is written in an attempt to illustrate the ongoing diagnostic progress by presenting some examples of pre-existing and newly defined entities. The World Health Organisation proposed in 2001 a "Classification of Tumours of the Haematopoietic and Lymphoid Tissues". Relying on the broadest consensus possible, it received high acclamation by both clinicians and pathologists. The approach is based on cell lineage assignment including morphology and immunophenotype, but also relies on cytogenetic and clinical features in order to define disease entities to an extent as far as possible. The diagnostic criteria for myeloid, lymphoid and histiocytic neoplasms have been compiled by an international group of 51 experts assembled in ten disease-related committees. In order to cover the interests of daily haematological practice, selected topics are focussed including chronic and acute myeloid neoplasias, precursor lymphoid neoplasias, mature B-, T- and NK-cell lymphomas, Hodgkin lymphoma as well as histiocytic and dendritic cell neoplasias.

[Blast cells in peripheral blood smear]. / Blasten im peripheren Blutausstrich.

Despite modern technologies such as immunophenotyping and molecular probing cytomorphological examination of stained peripheral blood smears by microscopy remains the mainstay of diagnosis in a large variety of diseases. Although technically simple morphological analysis requires considerable skill. Early diagnosis in several hematological diseases is important (for example acute promyelocytic leukaemia associated frequently with disseminated intravascular coagulation), in order to initiate adjusted therapy. Further, referral of the patient to tertiary care centers is only justified after a solid diagnosis is obtained. Many disorders can be diagnosed by pathognomonic blood smears. The present article is a short overview of important hematological disorders, which are associated with blast cells in the peripheral blood. Important morphological cell characteristics are illustrated by microscopic pictures.

[Area of contact between osteosynthesis plate and bone in internal fixation (author's transl)]. / Kontaktfläche zwischen Osteosyntheseplatte und Knochen.

The bone can be protected against excessive stress if the plate is properly adapted to the surface of the contact area between plate and bone, thus ensuring good and longlasting repositioning of the fracture. The article describes an in-vitro method for the quantitative evaluation of the contact area between plate and bone in osteosynthesis. With four different bones and the requisite plates, six expert surgeons were able to obtain an area of contact between plate and bone which varied between 13 and 60%, the average being 32%. The available data allow us to conclude that the peak loads of pressure occurring with small contact areas may be so great that they exceed the maximum compressive strength of the bone.

[Rheumatic symptoms in a malignant disease]. / Rheumatische Symptome bei Maligner Grunderkrankung.

We report a case of a 75 year old women with increasing deterioration of her general condition. We found a massive lymphadenopathy, an impressive exanthem and an elevation in leukocytes. After conducting a lymphnodebiopsy the diagnosis of an angioimmunoblastic T-Cell-Lymphoma was confirmed. Even with chemotherapy containing antracycline the prognosis of this disease is very poor. However this therapy couldn't be initiated because of the weak condition of the patient. She died a few days after hospitalisation.