Surgical hip dislocation for osteochondral transplantation as a salvage procedure for a femoral head impaction fracture

Obturator anterior hip dislocation is very rare. Poor results are described in patients with additional large transchondral fractures and treatment of these injuries remains challenging. Appropriate treatment recommendations are missing in the literature. This case report introduces surgical hip dislocation for osteochondral autograft transplantation with graft harvest from the nonweightbearing area of the head-neck junction as a salvage procedure in a large femoral head defect. We report the treatment and outcome of a 48-year-old man who sustained an anterior dislocation of the left hip after a motorcycle accident. After initial closed reduction in the emergency room, imaging analysis revealed a large osteochondral defect of the femoral head within the weightbearing area (10 × 20 mm, depth: 5 mm). The hip was exposed with a surgical hip dislocation using a trochanteric osteotomy. An osteochondral autograft was harvested from a nonweightbearing area of the femoral head and transferred into the defect. The patient was prospectively examined clinically and radiologically. Two years postoperatively, the patient was free of pain and complaints. The function of the injured hip was comparable to that of the contralateral, healthy hip and showed satisfying radiologic results. Surgical hip dislocation with a trochanteric flip osteotomy is a simple, one-step technique that allows full inspection of the hip to treat osteochondral femoral defects by osteochondral transplantation. The presented technique, used as a salvage procedure in a large femoral head defect, yielded good clinical and satisfying radiologic outcomes at the midterm.

A differential concentration-dependent effect of IVIg on neutrophil functions: relevance for anti-microbial and anti-inflammatory mechanisms

Background Polymorphonuclear neutrophils (PMN) play a key role in host defences against invading microorganisms but can also potentiate detrimental inflammatory reactions in case of excessive or misdirected responses. Intravenous immunoglobulins (IVIg) are used to treat patients with immune deficiencies and, at higher doses, in autoimmune, allergic and systemic inflammatory disorders. Methodology/Principal Findings We used flow cytometry to examine the effects of IVIg on PMN functions and survival, using whole-blood conditions in order to avoid artifacts due to isolation procedures. IVIg at low concentrations induced PMN activation, as reflected by decreased L-selectin and increased CD11b expression at the PMN surface, oxidative burst enhancement, and prolonged cell survival. In contrast, IVIg at higher concentrations inhibited LPS-induced CD11b degranulation and oxidative burst priming, and counteracted LPS-induced PMN lifespan prolongation. Conclusions/Significance IVIg appears to have differential, concentration-dependent effects on PMN, possibly supporting the use of IVIg as either an anti-microbial or an anti-inflammatory agent.

[Allergies to animals and fungi]

Allergies to animals are behind the house-dust mite allergy the most frequent cause for indoor allergic respiratory symptoms. In case of persistent allergen exposure symptoms like rhinitis, itch of the skin or asthma are usually not perceived intensively and, thus, can not assigned to an animal or an animal source. In many cases animal allergies are based on a perennial allergen exposure. Although most likely all animals may be the cause of a respiratory allergy, cats, dogs, and horses are the most frequent elicitors. The diagnosis of an allergy to an animal needs to be set with due care, since it often causes emotional reactions, diverse conflicts, but also lack of understanding. Rarer are allergies to fungi even though fungi as allergen sources since decades belong to the differential diagnosis in respiratory allergies particularly in case of late summer asthma. Fungi are ubiquitous and present indoors as well as outdoors. Unfortunately the field of fungal allergy is not well explored and diagnostic possibilities are limited. The most promising therapy in both allergy to animals and fungi would be complete avoiding of contact with the respective allergen source. Indeed many preventive recommendations are given; however, realization is often not successful. In selected cases specific immunotherapy for both animal and fungal allergies is a potential therapeutic option.

Short communication: duplication in the 5'-flanking region of the beta-lactoglobulin gene is linked to the BLG A allele

beta-Lactoglobulin (beta-LG) is the major whey protein in the milk of cows and other ruminants. It is well established that the predominant genetic variants beta-LG A and B are differentially expressed. Extensive investigation of the genetic variation in the promoter region of the BLG gene revealed the existence of specific haplotypes associated with the A and B variants. However, the genetic basis for the differentially expressed BLG A and B alleles is still elusive. In this study additional genetic variation further upstream in the 5'-flanking region of the BLG gene was identified, including 6 single nucleotide substitutions, a single nucleotide deletion, and a 7-bp duplication. Comparison of DNA sequences showed that the investigated 5'-flanking region is highly conserved between ruminants, and the duplication g.-1885_-1879dupCTCTCGC and the substitution g.-1888A>G are only found in the BLG A and D alleles in cattle. The cytosine at position g.-1957 and the thymines at positions g.-2008 and g.-2049 are only found in BLG B alleles of cattle. It is suggested that the described genetic variability contributes to the differential allelic expression of the BLG gene.

Differential regulation of human 3β-hydroxysteroid dehydrogenase type 2 for steroid hormone biosynthesis by starvation and cyclic AMP stimulation: studies in the human adrenal NCI-H295R cell model

Human steroid biosynthesis depends on a specifically regulated cascade of enzymes including 3β-hydroxysteroid dehydrogenases (HSD3Bs). Type 2 HSD3B catalyzes the conversion of pregnenolone, 17α-hydroxypregnenolone and dehydroepiandrosterone to progesterone, 17α-hydroxyprogesterone and androstenedione in the human adrenal cortex and the gonads but the exact regulation of this enzyme is unknown. Therefore, specific downregulation of HSD3B2 at adrenarche around age 6-8 years and characteristic upregulation of HSD3B2 in the ovaries of women suffering from the polycystic ovary syndrome remain unexplained prompting us to study the regulation of HSD3B2 in adrenal NCI-H295R cells. Our studies confirm that the HSD3B2 promoter is regulated by transcription factors GATA, Nur77 and SF1/LRH1 in concert and that the NBRE/Nur77 site is crucial for hormonal stimulation with cAMP. In fact, these three transcription factors together were able to transactivate the HSD3B2 promoter in placental JEG3 cells which normally do not express HSD3B2. By contrast, epigenetic mechanisms such as methylation and acetylation seem not involved in controlling HSD3B2 expression. Cyclic AMP was found to exert differential effects on HSD3B2 when comparing short (acute) versus long-term (chronic) stimulation. Short cAMP stimulation inhibited HSD3B2 activity directly possibly due to regulation at co-factor or substrate level or posttranslational modification of the protein. Long cAMP stimulation attenuated HSD3B2 inhibition and increased HSD3B2 expression through transcriptional regulation. Although PKA and MAPK pathways are obvious candidates for possibly transmitting the cAMP signal to HSD3B2, our studies using PKA and MEK1/2 inhibitors revealed no such downstream signaling of cAMP. However, both signaling pathways were clearly regulating HSD3B2 expression.

The dementia cognitive fluctuation scale, a new psychometric test for clinicians to identify cognitive fluctuations in people with dementia.

OBJECTIVES Cognitive fluctuation (CF) is a common feature of dementia and a core diagnostic symptom for dementia with Lewy bodies (DLB). CF remains difficult to accurately and reliably detect clinically. This study aimed to develop a psychometric test that could be used by clinicians to facilitate the identification of CF and improve the recognition and diagnosis of DLB and Parkinson disease, and to improve differential diagnosis of other dementias. METHODS We compiled a 17-item psychometric test for identifying CF and applied this measure in a cross-sectional design. Participants were recruited from the North East of England, and assessments were made in individuals' homes. We recruited people with four subtypes of dementia and a healthy comparison group, and all subjects were administered this pilot scale together with other standard ratings. The psychometric properties of the scale were examined with exploratory factor analysis. We also examined the ability of individual items to identify CF to discriminate between dementia subtypes. The sensitivity and specificity of discriminating items were explored along with validity and reliability analyses. RESULTS Participants comprised 32 comparison subjects, 30 people with Alzheimer disease, 30 with vascular dementia, 29 with DLB, and 32 with dementia associated with Parkinson disease. Four items significantly discriminated between dementia groups and showed good levels of sensitivity (range: 78.6%-80.3%) and specificity (range: 73.9%-79.3%). The scale had very good levels of test-retest (Cronbach's alpha: 0.82) and interrater (0.81) reliabilities. The four items loaded onto three different factors. These items were: 1) marked differences in functioning during the daytime; 2) daytime somnolence; 3) daytime drowsiness; and 4) altered levels of consciousness during the day. CONCLUSIONS We identified four items that provide valid, sensitive, and specific questions for reliably identifying CF and distinguishing the Lewy body dementias from other major causes of dementia (Alzheimer disease and vascular dementia).

Oncocytic ependymoma: a new morphological variant of high-grade ependymal neoplasm composed of mitochondrion-rich epithelioid cells

Oncocytomas are defined as tumors containing in excess of 50% large mitochondrion-rich cells, irrespective of histogenesis and dignity. Along the central neuraxis, oncocytomas are distinctly uncommon but relevant to the differential diagnosis of neoplasia marked by prominent cytoplasmic granularity. We describe an anaplastic ependymoma (WHO grade III) with a prevailing oncocytic component that was surgically resected from the right fronto-insular region of a 43-year-old female. Preoperative imaging showed a fairly circumscribed, partly cystic, contrast-enhancing mass of 2 cm × 2 cm × 1.7 cm. Histology revealed a biphasic neoplasm wherein conventional ependymal features coexisted with plump epithelioid cells replete with brightly eosinophilic granules. Whereas both components displayed an overtly ependymal immunophenotype, including positivity for S100 protein and GFAP, as well as "dot-like" staining for EMA, the oncocytic population also tended to intensely react with the antimitochondrial antibody 113-1. Conversely, failure to bind CD68 indicated absence of significant lysosomal storage. Negative reactions for both pan-cytokeratin (MNF 116) and low molecular weight cytokeratin (CAM 5.2), as well as synaptophysin and thyroglobulin, further assisted in ruling out metastatic carcinoma. In addition to confirming the presence of "zipper-like" intercellular junctions and microvillus-bearing cytoplasmic microlumina, electron microscopy allowed for the pervasive accumulation of mitochondria in tumor cells to be directly visualized. A previously not documented variant, oncocytic ependymoma, is felt to add a reasonably relevant novel item to the differential diagnosis of granule-bearing central nervous system neoplasia, in particular oncocytic meningioma, granular cell astrocytoma, as well as metastatic deposits by oncocytic malignancies from extracranial sites.

[Sarcomas and mixed mesodermal tumors of the uterus]

Malignant mesodermal tumors of the uterus are an inhomogenous group of uterine malignancies with different pathogenesis, clinical presentation and prognosis. These rare tumors represent approximately 1 % of all uterine malignancies. The aggressive carcinosarcomas or mixed muellerian tumors are defined by mixed malignant epithelial and malignant mesodermal histopathology and are of the same precursor cell origin like endometrial cancer. Thus, carcinosarcomas were reclassified by the FIGO as an aggressive type of endometrial cancer and treated like type II endometrial cancer. Adenosarcomas are also mixed tumors with benign epithelial proliferation and malignant mesodermal cell growth, have a good prognosis and represent less than 5 % of all mesodermal uterine malignancies. Besides carcinosarcomas, the pure mesodermal leiomyosarcomas are the most common mesodermal malignancies. Patients with leiomyosarcamos are usually perimenopausal, and although more than half of the patients present with symptoms, diagnosis occurs incidentally in most cases in final histopathologic workup of an excised putative myoma or uterus. Adequate anamnesis, gynecologic examination and careful imaging by transvaginal ultrasound in the preoperative setting might hint to correct differential diagnosis in many cases. Overall the prognosis of uterine leiomyomas is poor. Malignancies of the endometrial stroma are very rare and divided in two subgroups, the mostly estrogen receptor positive endometrial stromal sarcoma, which occur preferably in premenopausal women and show a favorable prognosis, and the very aggressive undifferentiated endometrial sarcomas. The more rare undifferentiated endometrial sarcomas occur in postmenopausal women and most patients die in the first two years after diagnosis. Risk stratification of preoperative differential diagnosis requires improvements and the correct histopathologic workup of mesodermal uterine malignancies is still a challenge for pathologists.

Distinct DNA methylation patterns in cirrhotic liver and hepatocellular carcinoma

Abberrant DNA methylation is one of the hallmarks of cancerogenesis. Our study aims to delineate differential DNA methylation in cirrhosis and hepatic cancerogenesis. Patterns of methylation of 27,578 individual CpG loci in 12 hepatocellular carcinomas (HCCs), 15 cirrhotic controls and 12 normal liver samples were investigated using an array-based technology. A supervised principal component analysis (PCA) revealed 167 hypomethylated loci and 100 hypermethylated loci in cirrhosis and HCC as compared to normal controls. Thus, these loci show a "cirrhotic" methylation pattern that is maintained in HCC. In pairwise supervised PCAs between normal liver, cirrhosis and HCC, eight loci were significantly changed in all analyses differentiating the three groups (p < 0.0001). Of these, five loci showed highest methylation levels in HCC and lowest in control tissue (LOC55908, CELSR1, CRMP1, GNRH2, ALOX12 and ANGPTL7), whereas two loci showed the opposite direction of change (SPRR3 and TNFSF15). Genes hypermethylated between normal liver to cirrhosis, which maintain this methylation pattern during the development of HCC, are depleted for CpG islands, high CpG content promoters and polycomb repressive complex 2 (PRC2) targets in embryonic stem cells. In contrast, genes selectively hypermethylated in HCC as compared to nonmalignant samples showed an enrichment of CpG islands, high CpG content promoters and PRC2 target genes (p < 0.0001). Cirrhosis and HCC show distinct patterns of differential methylation with regards to promoter structure, PRC2 targets and CpG islands.

Measurement of charged-particle event shape variables in inclusive √(s)=7 TeV proton-proton interactions with the ATLAS detector

The measurement of charged-particle event shape variables is presented in inclusive inelastic pp collisions at a center-of-mass energy of 7 TeV using the ATLAS detector at the LHC. The observables studied are the transverse thrust, thrust minor, and transverse sphericity, each defined using the final-state charged particles' momentum components perpendicular to the beam direction. Events with at least six charged particles are selected by a minimum-bias trigger. In addition to the differential distributions, the evolution of each event shape variable as a function of the leading charged-particle transverse momentum, charged-particle multiplicity, and summed transverse momentum is presented. Predictions from several Monte Carlo models show significant deviations from data.

Adjuvant chemotherapy followed by goserelin compared with either modality alone: the impact on amenorrhea, hot flashes, and quality of life in premenopausal patients--the International Breast Cancer Study Group Trial VIII

The purpose of this article is to compare quality of life (QOL) and menopausal symptoms among premenopausal patients with lymph node-negative breast cancer receiving chemotherapy, goserelin, or their sequential combination, and to investigate differential effects by age.

Treatment of femoro-acetabular impingement: preliminary results of labral refixation

BACKGROUND: Recent advances in the understanding of the anatomy and function of the acetabular labrum suggest that it is important for normal joint function. We found no available data regarding whether labral refixation after treatment of femoro-acetabular impingement affects the clinical and radiographic results. METHODS: We retrospectively reviewed the clinical and radiographic results of fifty-two patients (sixty hips) with femoro-acetabular impingement who underwent arthrotomy and surgical dislocation of the hip to allow trimming of the acetabular rim and femoral osteochondroplasty. In the first twenty-five hips, the torn labrum was resected (Group 1); in the next thirty-five hips, the intact portion of the labrum was reattached to the acetabular rim (Group 2). At one and two years postoperatively, the Merle d'Aubigné clinical score and the Tönnis arthrosis classification system were used to compare the two groups. RESULTS: At one year postoperatively, both groups showed a significant improvement in their clinical scores (mainly pain reduction) compared with their preoperative values (p = 0.0003 for Group 1 and p < 0.0001 for Group 2). At two years postoperatively, 28% of the hips in Group 1 (labral resection) had an excellent result, 48% had a good result, 20% had a moderate result, and 4% had a poor result. In contrast, in Group 2 (labral reattachment), 80% of the hips had an excellent result, 14% had a good result, and 6% had a moderate result. Comparison of the clinical scores between the two groups revealed significantly better outcomes for Group 2 at one year (p = 0.0001) and at two years (p = 0.01). Radiographic signs of osteoarthritis were significantly more prevalent in Group 1 than in Group 2 at one year (p = 0.02) and at two years (p = 0.009). CONCLUSIONS: Patients treated with labral refixation recovered earlier and had superior clinical and radiographic results when compared with patients who had undergone resection of a torn labrum. Although the results must be considered preliminary, we now recommend refixation of the intact portion of the labrum after trimming of the acetabular rim during surgical treatment of femoro-acetabular impingement.

Schulterprothetik und Sport

In the last years life duration of shoulder prostheses could be prolonged through improvement of prosthesis quality, instrumentation and surgical techniques. After shoulder total arthroplasty, the patients show signifi cant reduction of pain and good functional mid and long term results. Indication to shoulder arthroplasty can be made by even younger and sportive active patients. Many sport activities remain possible after implantation of a shoulder prosthesis. A systematic rehabilitation is mandatory to yield optimal functional results. Intensity of sports activities should remain in relation with the preoperative status. Activities with total contact and high impaction strength should be avoided to extend the duration of life of the prosthesis.

Testing the structural and cross-cultural validity of the KIDSCREEN-27 quality of life questionnaire

OBJECTIVES: The aim of this study is to assess the structural and cross-cultural validity of the KIDSCREEN-27 questionnaire. METHODS: The 27-item version of the KIDSCREEN instrument was derived from a longer 52-item version and was administered to young people aged 8-18 years in 13 European countries in a cross-sectional survey. Structural and cross-cultural validity were tested using multitrait multi-item analysis, exploratory and confirmatory factor analysis, and Rasch analyses. Zumbo's logistic regression method was applied to assess differential item functioning (DIF) across countries. Reliability was assessed using Cronbach's alpha. RESULTS: Responses were obtained from n = 22,827 respondents (response rate 68.9%). For the combined sample from all countries, exploratory factor analysis with procrustean rotations revealed a five-factor structure which explained 56.9% of the variance. Confirmatory factor analysis indicated an acceptable model fit (RMSEA = 0.068, CFI = 0.960). The unidimensionality of all dimensions was confirmed (INFIT: 0.81-1.15). Differential item functioning (DIF) results across the 13 countries showed that 5 items presented uniform DIF whereas 10 displayed non-uniform DIF. Reliability was acceptable (Cronbach's alpha = 0.78-0.84 for individual dimensions). CONCLUSIONS: There was substantial evidence for the cross-cultural equivalence of the KIDSCREEN-27 across the countries studied and the factor structure was highly replicable in individual countries. Further research is needed to correct scores based on DIF results. The KIDSCREEN-27 is a new short and promising tool for use in clinical and epidemiological studies.

Treatment of femoro-acetabular impingement: preliminary results of labral refixation. Surgical technique

BACKGROUND: Recent advances in the understanding of the anatomy and function of the acetabular labrum suggest that it is important for normal joint function. We found no available data regarding whether labral refixation after treatment of femoro-acetabular impingement affects the clinical and radiographic results. METHODS: We retrospectively reviewed the clinical and radiographic results of fifty-two patients (sixty hips) with femoro-acetabular impingement who underwent arthrotomy and surgical dislocation of the hip to allow trimming of the acetabular rim and femoral osteochondroplasty. In the first twenty-five hips, the torn labrum was resected (Group 1); in the next thirty-five hips, the intact portion of the labrum was reattached to the acetabular rim (Group 2). At one and two years postoperatively, the Merle d'Aubigné clinical score and the Tönnis arthrosis classification system were used to compare the two groups. RESULTS: At one year postoperatively, both groups showed a significant improvement in their clinical scores (mainly pain reduction) compared with their preoperative values (p = 0.0003 for Group 1 and p < 0.0001 for Group 2). At two years postoperatively, 28% of the hips in Group 1 (labral resection) had an excellent result, 48% had a good result, 20% had a moderate result, and 4% had a poor result. In contrast, in Group 2 (labral reattachment), 80% of the hips had an excellent result, 14% had a good result, and 6% had a moderate result. Comparison of the clinical scores between the two groups revealed significantly better outcomes for Group 2 at one year (p = 0.0001) and at two years (p = 0.01). Radiographic signs of osteoarthritis were significantly more prevalent in Group 1 than in Group 2 at one year (p = 0.02) and at two years (p = 0.009). CONCLUSIONS: Patients treated with labral refixation recovered earlier and had superior clinical and radiographic results when compared with patients who had undergone resection of a torn labrum. Although the results must be considered preliminary, we now recommend refixation of the intact portion of the labrum after trimming of the acetabular rim during surgical treatment of femoro-acetabular impingement.