The Functional Status of the ACL in Varus OA of the Knee: The Association With Varus Deformity and Coronal Tibiofemoral Subluxation

BackgroundThe present article analyzes the association of the functional anterior cruciate ligament (ACL) status and the overall varus deformity and coronal tibiofemoral subluxation (CTFS) in varus OA of the knee.MethodsOne hundred consecutive knees with varus OA in 84 patients were prospectively included. Knees were divided into two groups, in accordance with the ACL status (functionally sufficient or insufficient). All included patients were potential candidates for unicompartmental knee arthroplasty with predominantly medial compartment OA. Knees with Kellgren/Lawrence ≥ grade 3 in the lateral compartment were excluded leaving 79 knees to be included in this study. Mechanical varus deformity and CTFS were evaluated on AP radiographs and valgus stress radiographs, and compared between the two groups.ResultsKnees with a functionally insufficient ACL had significantly more varus deformity on hip-to-ankle AP standing radiographs (P = .001) and on valgus stress radiographs (P = .017). CTFS on AP standing radiographs was significantly higher (P = .045) in knees with a functionally insufficient ACL. Seventy-three percent (8/11) of the ACL-insufficient knees had a varus deformity of ≥10° and 64% (7/11) of ACL-insufficient knees had CTFS ≥ 6mm. By contrast, only one patient (2%, 1/41) with an insufficient ACL had< 10° varus deformity and a CTFS of < 6mm.ConclusionFunctional ACL insufficiency in osteoarthritic varus knees is associated with greater varus deformity and more advanced CTFS. Seventy-three percent of ACL-insufficient knees had a varus deformity of ≥10° and 64% of ACL-insufficient knees a CTFS of ≥ 6mm. In the work-up for medial unicompartmental knee arthroplasty, functional ACL insufficiency is likely in knees with varus deformity of ≥10° and CTFS of ≥ 6mm.     

Autogenous Arteriovenous Bundle Implantation Maintains Viability Without Increased Immune Response in Large Porcine Bone Allotransplants

BackgroundTransplantation of living allogeneic bone segments may permit reconstruction of large defects, particularly if viability is maintained without immunosuppression. Development of a new autogenous osseous blood supply accomplishes this goal in rodent experimental models. This study evaluates potential systemic and local inflammatory responses to this angiogenesis in a large-animal model.MethodsVascularized allogeneic tibia segments were transplanted orthotopically into matched tibial defects in Yucatan minipigs. Microvascular anastomoses of bone nutrient artery and vein were supplemented by intramedullary placement of an autogenous arteriovenous (AV) bundle in group 1. Group 2 served as a no-angiogenesis control. A 3-drug immunosuppression regimen was withdrawn after 2 weeks. During the 20-week survival period, periodic leukocyte counts and inflammatory cytokine levels were measured. Thereafter, osteocyte survival was quantified and transplant rejection graded by histologic examination and quantitative real-time polymerase chain reaction of immunologic markers.ResultsBoth groups developed an initial systemic response, which resolved after 4 to 6 weeks. No differences were seen in blood cytokine levels. Interleukin 2 expression was diminished in group 1 tibiae. As expected, nutrient pedicles had thrombosed without sustained immunosuppression, occluded by intimal hyperplasia. In group 1, angiogenesis from the autogenous AV bundle resulted in significantly less osteonecrosis (P = .04) and fibrosis (P = .02) than group 2 allotransplants.ConclusionsSystemic immune responses to large-bone allotransplants were not increased by generation of an autogenous osseous blood supply within porcine tibial bone allotransplants. Implanted AV bundles diminished inflammation and fibrosis and improved bone viability when compared to no-angiogenesis controls.     

Challenges and Opportunities for Real-World Evidence in Metastatic Luminal Breast Cancer

BackgroundThe therapeutic armamentarium for patients with metastatic breast cancer is becoming more and more specific. Recommendations from clinical trials are not available for all treatment situations and patient subgroups, and it is therefore important to collect real-world data.SummaryTo develop recommendations for up-to-date treatments and participation in clinical trials for patients with metastatic breast cancer, the Prospective Academic Translational Research PRAEGNANT Network was established to optimize the quality of oncological care in the advanced therapeutic setting. The main aim of PRAEGNANT is to systematically record medical care for patients with metastatic breast cancer in the real-life setting, including the outcome and side effects of different treatment strategies, to monitor quality-of-life changes during therapy, to identify patients eligible for participation in clinical studies, and to allow targeted therapies based on the molecular structures of breast carcinomas.Key MessagesThis article describes the PRAEGNANT network and sheds light on the question of whether the various end points from clinical trials can be transferred to the real-world treatment situation.     

Die Lipoide der weißen Hirnsubstanz während der Autolyse und bei der anämischen Erweichung

Zusammenfassung Während der sterilenAutolyse der weißen Hirnsubstanz bis zu 24 Tagen verändern sich die Lipoide nur geringfügig. Die erst vom 9. Tage an verstärkte Abnahme des Lipoid-P beruht auf der Spaltung von Lecithin und Plasmalogen und wird von einer entsprechenden Zunahme freier Fettsäuren (FFS), geringerer der Aldehyde begleitet. FFS sind in der frischen weißen Substanz nur in Spuren nachweisbar. Lysophosphatide treten—im Gegensatz zu anderen Organen—in papierchromatographisch nachweisbarer Menge nicht auf. Cholesterin und seine Ester bleiben unverändert. Kephaline, Inositphosphatide, Sphingomyelin, Cerebroside und Sulfatide verhalten sich chromatographisch weitgehend konstant. Die postmortale Autolyse hat bis mehrere Tage nach dem Tode keinen nennenswerten Einfluß auf die Lipoidzusammensetzung.Bei der Untersuchung von 20 verschiedenenErweichungsherden des Gehirns fand sich eine vom Alter der Herde nicht unbedingt abhängige Zunahme der FFS, Aldehyde, Triglyceride und Cholesterinester. Freie wie auch glycerid- und cholesteringebundene Fettsäuren und freie höhere Aldehyde stammen offensichtlich aus den strukturbildenden Lipoiden des Myelin. In verschiedenen Herden treten spurenweise Lysophosphatide auf.

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Summary Lipides change slightly during sterile autolysis of human white matter up to the 24 th day. From the 9 th day on, there is a decrease of lipid-phosphorus caused by a breakdown of lecithin and plasmalogen accompanied by a comparable increase of free fatty acids (FFA) and aldehydes. In fresh white matter there are only traces of FFA. In the autolysing brain, contrary to several other autolysing organs, there are no lysophosphatides detectable by means of paper chromatography. Free and esterified cholesterol, cephalins, phosphoinositides, sphingomyelin, cerebrosides and sulfatides remain chromatographically constant during sterile autolysis. According to the above findings it can be concluded that postmortem autolysis up to several days duration has only neglectable effects on the lipid-composition of the white matter.After analysis of 20 different foci of anaemic softening of human brain we found an increase of FFA, aldehydes, triglycerides and of esterified cholesterol which is independent on the age of the lesion. FFA as well as those fatty acids which are bound to glycerol and cholesterol and free higher aldehydes derive from the myelin lipides. Also in contrast to autolysis there were traces of lysophosphatides found in several foci.

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Herrn Prof. Dr.E. Letterer zum Geburtstag am 30. Juni 1966 gewidmet.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Endoscopic cordectomy. a proposal for a classification by the Working Committee, European Laryngological Society

The European Laryngological Society is proposing a classification of different laryngeal endoscopic cordectomies in order to ensure better definitions of postoperative results. We chose to keep the word “cordectomy” even for partial resections because it is the term most often used in the surgical literature. The classification comprises eight types of cordectomies: a subepithelial cordectomy (type I), which is resection of the epithelium; a subligamental cordectomy (type II), which is a resection of the epithelium, Reinke’s space and vocal ligament; transmuscular cordectomy (type III), which proceeds through the vocalis muscle; total cordectomy (type IV); extended cordectomy, which encompasses the contralateral vocal fold and the anterior commissure (type Va); extended cordectomy, which includes the arytenoid (type Vb); extended cordectomy, which encompasses the subglottis (type Vc); and extended cordectomy, which includes the ventricle (type Vd). Indications for performing those cordectomies may vary from surgeon to surgeon. The operations are classified according to the surgical approach used and the degree of resection in order to facilitate use of the classification in daily practice. Each surgical procedure ensures that a specimen is available for histopathological examination. Received: 29 December 1998 / Accepted: 2 July 1999     

Characterization of the trp5-27 allele used to monitor drug-induced mitotic gene conversion in the Saccharomyces cerevisiae tester strain D7

Mitotic gene conversions, among other recombinagenic events,can play an important role in the multistep process of carcinogenesis.The ability of chemicals to induce such gene conversions caneasily be monitored in the Saccharomyces cerevisiae tester strainYHE2, a derivative of strain D7. For the detection of drug-inducedgene conversions, two mutations in the TRP5 locus are used,trp5–12 and trp5–27. Here we report on the characterizationof the stable allele trp5–27. Our analysis revealed tworelevant mutations in trp5–27: (a) a transition C to Tat position 121 after ATG that results in an amber stop codonand abolishes gene expression and (b) a transversion A to Tat position 1555 that creates an ochre stop codon. Simultaneousamber and ochre suppression with the suppressors SUP3 and SUP11,respectively, was capable of relieving the tryptophan-requiringphenotype of strains carrying the trp5–27 allele. Thesefindings have implications on the length of gene conversiontracts in conversion events between trp5–12 and trp5–27:conversion tracts can cover several kilobases, if the site ofthe mutation in trp5–12 lies outside of the positionsmutated in trp5–27. Conversely, the maximal length islimited to 1435 bp, if the mutation in trp5–12 is locatedbetween the positions mutated in trp5–27. ¹To whom correspondence should be addressed     

Response of multicellular tumor spheroids to liposomes containing TNF-α

Summary This publication describes a new model to investigate the influence of tumor necrosis factor- (TNF-) on a three-dimensional glial cell aggregate under defined, standardized, reproducible conditions using the glioma cell line A 172.The cells are initially grown as normal monolayer culture until they reach a cell density of up to 1×10⁶. Subsequently they are grown as spheroids by the liquid overlay technique. Spheroids grown in this way were divided into ten groups of more than 50 cell aggregates. Three groups were coincubated with free TNF- in increasing dosages (100 ng/ml, 200 ng/ml and 1000 ng/ml); three groups were incubated with empty liposomes (0.2 mg/ml, 0.4 mg/ml and 2 mg/ml); three groups received liposomes which had been loaded with TNF-, and one group, which received no treatment, served as control.The diameter of the spheroids ranged from 80 m to 350 m. There was no significant difference in growth between the 3 groups treated with free TNF-. Comparing spheroids treated with TNF- with those which had been coincubated with empty liposomes, there was a significant difference (p<0.001) in growth, which correlated with the amount of liposomes. Similarly, free TNF- had a significantly (P<0.001) stronger growth-inhibiting effect as compared to liposomes loaded with TNF-. Comparing the groups treated with liposomes only to those treated with liposomes loaded with TNF-, the latter exhibited a more marked (although not significantly) growth-inhibiting effect.The preliminary conclusion is that the major growth-inhibiting effect seems to be mediated by the liposomes. This phenomenon is in agreement with results obtained in monolayer cultures.