Voluntary femoro-tibial subluxations: a benign differential diagnosis in the snapping knee of a child.

PURPOSE: Voluntary femoro-tibial subluxation is a rare entity predominantly found in pretoddlers. It presents as a dynamic phenomenon with uni- or bilateral audible snapping of the knee, often in a context of fatigue or irritation at the end of the day. The aim of the study was to observe the evolution and recovery in these patients. METHODS: Ten children were included. Other causes of dislocating joints and pathologies with snapping of the lateral meniscus were excluded from this study. Six-week immobilisation with a splint at 70° of knee flexion was primarily recommended to all patients. RESULTS: The mean age at onset of symptoms was 10 months. Forty percent of the patients presented with bilateral symptoms. Clinically, four patients were hyperlax. In all patients, subluxations could be reproduced passively by rotating the foot externally and advancing the internal tibial plateau anteriorly. Three of the patients were treated with a dorsal splint and experienced significantly less or cessation of symptoms. Two patients underwent surgery, one for a concomitant anterior cruciate ligament (ACL) rupture and meniscus tear that worsened the symptoms, another for concomitant patella dislocation and a meniscus tear. One patient's parents refused treatment and four patients experienced less symptoms at the time of consultation and were not immobilized. Except for the two patients undergoing surgeries, no sequelae were observed. In general, the symptoms got less frequent when the patient began to walk. CONCLUSION: Voluntary femoro-tibial subluxation in children is a rare and benign condition that often resolves spontaneously without sequelae. The risk of meniscus tear should, however, be considered if subluxations do not cease. LEVEL OF EVIDENCE: IV.

[Ramp lesions : Tips and tricks in diagnostics and therapy]. / Rampenläsionen : Tipps und Tricks in Diagnostik und Therapie.

There is an increasing biomechanical and anatomical understanding of the different types of meniscal lesions. Lesions of the posterior part of the medial meniscus in the meniscosynovial area have recently received increased attention. They generally occur in association with anterior cruciate ligament (ACL) injuries. They are often missed ("hidden lesions") due to the fact that they cannot be seen by routine anterior arthroscopic inspection. Furthermore, meniscosynovial lesions play a role in anteroposterior knee laxity and, as such, they may be a cause of failure of ACL reconstruction or of postoperative persistent laxity. Little information is available regarding their cause with respect to injury mechanism, natural history, biomechanical implications, healing potential and treatment options. This article presents an overview of the currently available knowledge of these ramp lesions, their possible pathomechanism, classification, biomechanical relevance as well as repair techniques.

Combined anterior and rotational knee laxity measurements improve the diagnosis of anterior cruciate ligament injuries.

PURPOSE: This study analysed whether associating the side-to-side difference in displacement and the slope of the load-displacement curve of anterior and rotational knee laxity measurements would improve the instrumental diagnosis of anterior cruciate ligament (ACL) ruptures and help to detect different types of ACL tears. METHODS: Anterior and rotational knee laxity was measured in 128 patients with an arthroscopically confirmed ACL injury and 104 healthy controls. Side-to-side differences were determined for three variables in anterior laxity: anterior displacement at 200 N (ATD200), primary compliance from 30 to 50 N (PCA) and secondary compliance from 100 to 200 N (SCA). Furthermore, four variables in rotational laxity were considered: internal and external rotation at 5 N m (IR5/ER5) and compliance from 2 to 5 N m (C IR/C ER). Receiver operating characteristic curves allowed to determine thresholds, specificities and sensitivities to detect ACL lesions, based on single variables considered and combinations thereof. RESULTS: Sensitivity and specificity reached, respectively, 75 and 95 % for ATD200 (threshold: 1.2 mm) and 38 and 95 % for IR5 (threshold: 3.2°). If either two out of the three variables were positive for anterior laxity or both IR5 and C IR were positive, 81 % of patients were identified without a false positive. All patients for whom ATD200 was >3.7 mm, PCA > 48 µm/N or SCA > 17.5 µm/N had ACL remnants that were either totally resorbed or healed on the posterior cruciate ligament. CONCLUSION: Combined instrumented anterior and rotational knee laxity measurements have excellent diagnostic value for ACL injury, provided that several measurements be considered concomitantly. LEVEL OF EVIDENCE: Diagnostic study, Level III.

Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia.

Therapeutic hypothermia (TH) enhances pulmonary surfactant performance in vivo by molecular mechanisms still unknown. Here, the interfacial structure and the composition of lung surfactant films have been analysed in vitro under TH as well as the molecular basis of its improved performance both under physiological and inhibitory conditions. The biophysical activity of a purified porcine surfactant was tested under slow and breathing-like dynamics by constrained drop surfactometry (CDS) and in the captive bubble surfactometer (CBS) at both 33 and 37 °C. Additionally, the temperature-dependent surfactant activity was also analysed upon inhibition by plasma and subsequent restoration by further surfactant supplementation. Interfacial performance was correlated with lateral structure and lipid composition of films made of native surfactant. Lipid/protein mixtures designed as models to mimic different surfactant contexts were also studied. The capability of surfactant to drastically reduce surface tension was enhanced at 33 °C. Larger DPPC-enriched domains and lower percentages of less active lipids were detected in surfactant films exposed to TH-like conditions. Surfactant resistance to plasma inhibition was boosted and restoration therapies were more effective at 33 °C. This may explain the improved respiratory outcomes observed in cooled patients with acute respiratory distress syndrome and opens new opportunities in the treatment of acute lung injury.

Fracture risk increases after diagnosis of breast or other cancers in postmenopausal women: results from the Women's Health Initiative.

SUMMARY: Risk for falls and fractures increases after breast cancer or other cancer diagnosis in postmenopausal women. Factors other than falls may be the major causes for the increased fracture risk. INTRODUCTION: Cancer treatment and prognosis may have detrimental effects on bone health. However, there is a lack of prospective investigations on fracture risk among incident cancer cases. METHODS: In this study, postmenopausal women (N = 146,959) from the Women's Health Initiative prospective cohort, who had no cancer history at baseline, were followed for up to 9 years and classified into no cancer, incident breast cancer (BC) and incident other cancer (OC) groups. The main outcomes measured were incident fractures and falls before and after cancer diagnosis. Hazards ratios (HR) and 95% confidence intervals (CI) were computed from Cox proportional hazards model. RESULTS: While hip fracture risk before a cancer diagnosis was similar between the no cancer and cancer groups, hip fracture risk was significantly higher after BC diagnosis (HR = 1.55, CI = 1.13-2.11) and the elevated risk was even more notable after OC diagnosis (HR = 2.09, CI = 1.65-2.65). Risk of falls also increased after BC (HR = 1.15, CI = 1.06-1.25) or OC diagnosis (HR = 1.27, CI = 1.18-1.36), but could not fully explain the elevated hip fracture risk. Incident clinical vertebral and total fractures were also significantly increased after OC diagnosis (p < 0.05). CONCLUSIONS: Postmenopausal women have significantly elevated risks for falls and fractures after a cancer diagnosis. The causes for this increased risk remained to be investigated.

[Acquired and repeated factor VII deficiency during two infectious episodes: a case report]. / Déficit acquis et répété en facteur VII au cours d'épisodes infectieux : à propos d'un cas.

We described the management of a patient with acquired and severe FVII deficiency appeared during two infections outbreaks. This case report focused on both biological diagnosis and treatment of the F VII deficiency.

Current trends in tendinopathy: consensus of the ESSKA basic science committee. Part II: treatment options.

The treatment of painful chronic tendinopathy is challenging. Multiple non-invasive and tendon-invasive methods are used. When traditional non-invasive treatments fail, the injections of platelet-rich plasma autologous blood or cortisone have become increasingly favored. However, there is little scientific evidence from human studies supporting injection treatment. As the last resort, intra- or peritendinous open or endoscopic surgery are employed even though these also show varying results. This ESSKA basic science committee current concepts review follows the first part on the biology, biomechanics and anatomy of tendinopathies, to provide a comprehensive overview of the latest treatment options for tendinopathy as reported in the literature.

Role of lipoxygenase products in murine pulmonary granuloma formation.

Various arachidonic acid (AA) metabolites are known to regulate immune cell function(s) and dictate the progression of both acute and chronic inflammatory reactions. Using a model of Schistosoma mansoni egg-induced hypersensitivity granulomas, we have delineated the in vivo effects of inhibitors of cyclooxygenase (CO) and lipoxygenase (LO) pathways on granuloma development and granuloma macrophage I-region-associated (Ia) antigen expression. In addition, by high performance liquid chromatography (HPLC) we have profiled the metabolism of AA by macrophages that are isolated from granulomatous foci, and have biochemically characterized the in vitro specificity and activity of selected CO and LO inhibitors. The development of hypersensitivity-type pulmonary granulomas in mice was dramatically suppressed by inhibitors with anti-LO activity (nordihydroguairetic acid (NDGA), nafazatrom, and BW755c) in a dose-dependent manner, while indomethacin, which is primarily CO-selective, had no significant effect. Furthermore, NDGA and nafazatrom profoundly arrested the normal progression of preformed granulomatous lesions. The inhibitors of the LO pathway also suppressed the in vivo kinetics of Ia antigen expression by granuloma macrophages. In contrast, indomethacin augmented Ia-antigen expression. The major AA metabolites that were synthesized by the granuloma macrophages were shown to be leukotriene C4 and mono-hydroxyeicosatetraenoic acids. HPLC analysis of AA metabolites from granuloma macrophages that were treated with the various inhibitors confirmed that indomethacin was most CO-selective and NDGA most LO-selective. Nafazatrom and BW755c inhibited AA metabolism by both pathways. Notably, high concentrations of the compounds (5 X 10(-5) M) tended to suppress all products. Our results suggest that LO products may be important in the generation and maintenance of immune granulomatous inflammatory responses.

Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility.

The coordinated interplay of substrate adhesion and deadhesion is necessary for cell motility. Using MCF-7 cells, we found that insulin-like growth factor I (IGF-I) induces the adhesion of MCF-7 to vitronectin and collagen in a dose- and time-dependent manner, suggesting that IGF-I triggers the activation of different integrins. On the other hand, IGF-I promotes the association of insulin receptor substrate 1 with the focal adhesion kinase (FAK), paxillin, and the tyrosine phosphatase SHP-2, resulting in FAK and paxillin dephosphorylation. Abrogation of SHP-2 catalytic activity with a dominant-negative mutant (SHP2-C>S) abolishes IGF-I-induced FAK dephosphorylation, and cells expressing SHP2-C>S show reduced IGF-I-stimulated chemotaxis compared with either mock- or SHP-2 wild-type-transfected cells. This impairment of cell migration is recovered by reintroduction of a catalytically active SHP-2. Interestingly, SHP-2-C>S cells show a larger number of focal adhesion contacts than wild-type cells, suggesting that SHP-2 activity participates in the integrin deactivation process. Although SHP-2 regulates mitogen-activated protein kinase activity, the mitogen-activated protein kinase kinase inhibitor PD-98059 has only a marginal effect on MCF-7 cell migration. The role of SHP-2 as a general regulator of cell chemotaxis induced by other chemotactic agents and integrins is discussed.

Current trends in tendinopathy: consensus of the ESSKA basic science committee. Part I: biology, biomechanics, anatomy and an exercise-based approach.

Chronic tendinopathies represent a major problem in the clinical practice of sports orthopaedic surgeons, sports doctors and other health professionals involved in the treatment of athletes and patients that perform repetitive actions. The lack of consensus relative to the diagnostic tools and treatment modalities represents a management dilemma for these professionals. With this review, the purpose of the ESSKA Basic Science Committee is to establish guidelines for understanding, diagnosing and treating this complex pathology.

There is no such thing like a single ACL injury: Profiles of ACL-injured patients.

BACKGROUND: Current ACL registries rarely include non-operatively treated patients thus delivering an incomplete picture of the ACL-injured population. The aim of this study was to get an image of the population and treatment decision of an intrahospital registry. Our hypotheses were that patient-specific subtypes can be identified and that the percentage of operated patients differs between them. MATERIAL AND METHODS: Three hundred and forty-six operated and non-operated patients were included from March 2011 to December 2013. Standardized questionnaires allowed for data collection on gender, age, sports practice and previous ACL injuries. Chi-square tests allowed to compare these parameters between genders and age groups. A cluster analysis was computed to determine profiles of patients with similar characteristics. RESULTS: Three age groups were considered (I: ≤20; II: 21-35; III: ≥36 years). For males, the highest frequency of injuries was noted in group II with a greater proportion of injuries compared to females. In group III, more females were injured than males. Before injury, 54% patients were involved in competitive sports. Males were more likely to be injured in pivoting/contact sports before 35 and females during recreational skiing after 35. Twenty-one percent of the patients had had a previous ACL injury. The percentage of surgical treatment was superior to 80% in patients under 35 years involved in competitive sports, of 60-80% for those not involved in competitive sports and inferior to 60% for patients above 35 years. DISCUSSION: Systematic data collection allowed to identify specific subtypes of ACL-injured patient according to gender, age, previous ACL injury and preinjury level of practice. The decision-making process for or against ACL reconstructions at time of presentation depended on these characteristics. Consideration of these parameters will serve as a basis for an individualized treatment approach and a better understanding of patients at risk for ACL injuries. LEVEL OF EVIDENCE: III.

[Perioperative anticoagulation management for prosthetic heart valves]. / Gestion en période périopératoire de l'anticoagulation des valves prothétiques cardiaques.

OBJECTIVES: The practices and the guidelines over the perioperative management of the anticoagulation of patients with cardiac valves prothesis are the object of no consensual attitude. The thrombotic risk over the time is well known. It depends of the type or the location on the valve, of their associations and the age of the patient. In the perioperative period, the antithrombotic treatment must be interrupted according to the surgical haemorrhagic risk. STUDY DESIGN: Short review. RESULTS: Only patients, without associated risk factor, carriers of bioprosthesis from more than 3 months, can be maintained only under antiplatelets agents. In others situations, the caution imposes a bridge of anticoagulants from 48 to 72 hours with unfractionated heparin (subcutaneous at home, intravenous at the hospital). Low molecular weight heparin has no commercial authorization in this indication. The resumption of the anticoagulation by unfractionated heparin in postoperative period must be the most premature possible after the decrease of the surgical bleeding. The relay by vitamin K antagonists has to be made over 48 to 72 hours. Within the framework of the urgency, the surgical haemorrhagic risk is weak for an INR <1.5. According to the urgency of the surgery, a treatment by vitamin K (if the delay is over 12 hours) or by prothrombinic complex allows to correct this INR. The identification of thrombotic complications requires a particular attention. In the postoperative period, as soon as there is suspicion of thrombosis, clinical manifestations must be consolidated by the practice of a transoesophageal echography, which only confirm the diagnosis.

Food contains the bioactive peptide, cyclo(His-Pro).

Cyclo(His-Pro) (CHP) is a cyclic dipeptide with numerous biological activities. As small di- and tripeptides may be absorbed intact when ingested orally, we were interested in examining several common foods for the presence of cyclo(His-Pro)-like immunoreactivity (CHP-LI). In all foods tested, CHP-LI was found at levels 5-1500 times those previously found in human plasma. This CHP-LI was identical to authentic CHP by immunoidentity and chromatographic behavior. We conclude that 1) CHP-LI is readily detectable in several common food sources; 2) this CHP-LI is indistinguishable from authentic CHP; and 3) it is likely the CHP-LI in foods is absorbed in quantities sufficient to cause elevations of CHP-LI in plasma to biologically significant levels.

Physical mapping of human insulin-like growth factor-I using specific monoclonal antibodies.

The primary structure of recombinant human (h) insulin-like growth factor-I (IGF-I) epitopes recognized by a panel of 28 monoclonal antibodies (mAbs) is characterized. Pairwise mAb epitope mapping defines eight 'epitopic clusters' (I-VIII) which cover nearly the entire solvent-exposed IGF-I surface. Monoclonal antibody reactivity with 32 overlapping synthetic peptides and with IGF-I mutants is used to associate these epitopic clusters with the probable primary IGF-I sequences recognized. Epitopic cluster I involves residues in the C-domain and the first alpha-helix of the A-domain; clusters II, V and VII involve principally the B-domain; clusters III and IV map to amino acid sequences (55-70) and (1-13) respectively; cluster VI includes the A- and B-domains; and cluster VIII involves mainly the C-terminal part of the B-domain. Data indicate that this mAb panel defines 14 distinct IGF-I epitopes. The specific inhibition of HEL 92.1.7 IGF-I-promoted proliferation by these mAbs was explored. Direct correlation between mAb affinity and inhibitory activity was observed except in the case of clusters III- and VIII-specific mAbs. Finally, the combination of epitopic cluster I and II mAbs detect 0.5-10 ng/ml hIGF-I in a sandwich immunoassay, with no IGF-II crossreactivity. These anti-IGF-I mAbs are, therefore, useful for both the inhibition of IGF-I mitogenic activity and for the quantification of this growth factor. The potential use of this mAb panel in tumor cell growth control is discussed.

Phenotypic characterization of human and animal biotypes within the species Porphyromonas gingivalis.

Ninety-nine strains of Gram-negative black-pigmented anaerobic rods, grown on Todd-Hewitt blood agar plates, were identified and characterized according to a typing scheme including UV fluorescence, catalase, trypsin-like and haemagglutinating activities, biochemical tests with the ATB 32A kit, and gas-liquid chromatography. To determine the taxonomic position of the Porphyromonas gingivalis biotypes, 68 strains (31 of human origin and 37 of animal origin) were compared to 31 strains of closely related species or of uncertain generic status. Most animal strains were isolated in our laboratory by subculturing samples from the oral cavity of five mammalian species (bear, cat, coyote, dog and wolf). Those strains differed from human P. gingivalis strains in that they were positive for catalase, beta-galactosidase and glutamyl-glutamic acid arylamidase; from Bacteroides macacae by more rapid pigmentation, positive haemagglutination, failure to produce propionic acid, and negative alpha-galactosidase; and from Bacteroides salivosus by more rapid pigmentation, positive haemagglutination and failure to produce propionic acid. These data demonstrate that phenotypic heterogeneity within the taxon P. gingivalis can be resolved into two biotypes, each corresponding to a human source or an animal source.

Randomly amplified polymorphic DNA analysis confirms the biotyping scheme of Porphyromonas gingivalis.

The application of the arbitrarily primed PCR (AP-PCR) procedure to generate randomly amplified polymorphic DNA (RAPD) fingerprints for the study of the taxon Porphyromonas gingivalis was investigated. Nine human strains and seven animal strains of P. gingivalis as well as eighteen strains other than P. gingivalis were analysed. Four nanomer primers of random sequence were evaluated for their ability to distinguish genetic diversity. Three primers generated RAPD fingerprints that allowed the sixteen strains to be differentiated; two of the primers yielded species-specific markers, and two of the primers permitted biotype distinction. Cluster analysis of the RAPD fingerprints revealed two major phenetic groups that matched the human and animal biotypes. Our results indicate that AP-PCR (i) can generate strain-specific fingerprints, (ii) confirms genetic heterogeneity and the biotype grouping of the P. gingivalis taxon, and (iii) enables identification of potential genetic markers at the species, biotype and subtype levels and is thus a promising tool for bacterial systematics. Our results also underline the potential of AP-PCR for epidemiological studies of periodontal pathogens.

Polymerase chain reaction using arbitrary primer for the design and construction of a DNA probe specific for Porphyromonas gingivalis.

In this work, we used a novel approach for the design and construction of DNA probes which requires no knowledge of target DNA sequence. We demonstrated that species-specific genetic markers, identified as such among monomorphic, randomly amplified DNA segments generated by the polymerase chain reaction with arbitrary primer can be labelled to yield so-called "anonymous probes". We report here on the construction of such an anonymous probe, 1146 bp long, specific for the Gram-negative anaerobe Porphyromonas gingivalis, a suspected major etiologic agent of chronic periodontitis in adults.

Genetic relatedness between oral and intestinal isolates of Porphyromonas endodontalis by analysis of random amplified polymorphic DNA.

Genomic fingerprints from the DNA of 27 strains of Porphyromonas endodontalis from diverse clinical and geographic origins were generated as random amplified polymorphic DNA (RAPD) using the technique of PCR amplification with a single primer of arbitrary sequence. Cluster analysis of the combined RAPD data obtained with three selected 9- or 10-mer-long primers identified 25 distinct RAPD types which clustered as three main groups identifying three genogroups. Genogroups I and II included exclusively P. endodontalis isolates of oral origin, while 7/9 human intestinal strains of genogroup III which linked at a similarity level of 52% constituted the most homogeneous group in our study. Genotypic diversity within P. endodontalis, as shown by RAPD analysis, suggests that the taxon is composed of two oral genogroups and one intestinal genogroup. This hypothesis remains to be confirmed.

Bacteroides fragilis isolates compared by AP-PCR.

Bacteroides fragilis is a component of the normal intestinal flora and an important pathogen in nonintestinal endogenous infections. It has been associated with enteric infections and has already been detected in polluted water. In order to evaluate the genetic diversity of B. fragilis, a total of 31 isolates and two reference strains were examined. This collection included strains from nonintestinal infections [12], intestinal infections [5], intestinal microflora [10], aquatic environments [4], and the reference strains ATCC 25285 and ATCC 23745. DNA fingerprints were detected using two separate PCR reactions with different arbitrary primers. The computer-assisted system Taxotron (Institut Pasteur, Dr P. Grimont) was used to analyze the profiles obtained and dendrograms were generated. By using a distance of 0.65 as the threshold, two clusters (hereafter referred to as genotypes I and II) were defined. Strains of differents origins could be distributed into both genotypes. We were unable to detect any obvious correlation between a given genotype and the specific disease or the source of the corresponding strains.