Outcomes of Operatively Treated Acute Knee Dislocations

Knee dislocation is a complex and rare injury often presenting in the context of high velocity trauma. The aim of this study is to establish the subjective outcomes of surgically treated knee dislocations. A total of 20 knees dislocations treated by open repair were reviewed. Their progress and outcomes were assessed by using a modified Lysholm score questionnaire. Data was obtained on patient demographics, details of injury, investigation, treatment, rehabilitation, 24 months objective outcome and subjective outcomes. Six patients had a vascular deficit and six had neurological deficits. The median range of motion was 0°-100°. Patients with an initially lower pre-injury level of function were able to return an activity level comparable to their pre-injury status. 22% of competitive athletes retuned to competitive sports. 38% of patients undertaking heavy activity returned to comparable pre-injury level of activity and 67% of patients undertaking moderate level of activity before injury returned to a comparable level after repair. 68% regularly had problems running, 70% problem squatting, 40% swelling and 42% problem with stairs. Most patients however did not have locking of the knee or problems with knees giving way. Patients pain scores decreased over time to an acceptable level. Despite the severity of the injury, majority of patients achieved a satisfactory outcome, although none of the patients reached the same level of function as before the injury. 80% of the patients were satisfied with their outcome. All dissatisfied patients suffered postoperative complications

An Introduction to Sphingolipid Metabolism and Analysis by New Technologies

Sphingolipids (SP) are a complex class of molecules found in essentially all eukaryotes and some prokaryotes and viruses where they influence membrane structure, intracellular signaling, and interactions with the extracellular environment. Because of the combinatorial nature of their biosynthesis, there are thousands of SP subspecies varying in the lipid backbones and complex phospho- and glycoheadgroups. Therefore, comprehensive or “sphingolipidomic” analyses (structure-specific, quantitative analyses of all SP, or at least all members of a critical subset) are needed to know which and how much of these subspecies are present in a system as a step toward understanding their functions. Mass spectrometry and related novel techniques are able to quantify a small fraction, but nonetheless a substantial number, of SP and are beginning to provide information about their localization. This review summarizes the basic metabolism of SP and state-of-art mass spectrometric techniques that are producing insights into SP structure, metabolism, functions, and some of the dysfunctions of relevance to neuromedicine

Inter- and intrachromosomal asynchrony of cell division cycle events in root meristem cells of Allium cepa: possible connection with gradient of cyclin B-like proteins

Alternate treatments of Allium cepa root meristems with hydroxyurea (HU) and caffeine give rise to extremely large and highly elongated cells with atypical images of mitotic divisions, including internuclear asynchrony and an unknown type of interchromosomal asynchrony observed during metaphase-to-anaphase transition. Another type of asynchrony that cannot depend solely on the increased length of cells was observed following long-term incubation of roots with HU. This kind of treatment revealed both cell nuclei entering premature mitosis and, for the first time, an uncommon form of mitotic abnormality manifested in a gradual condensation of chromatin (spanning from interphase to prometaphase). Immunocytochemical study of polykaryotic cells using anti-β tubulin antibodies revealed severe perturbations in the microtubular organization of preprophase bands. Quantitative immunofluorescence measurements of the control cells indicate that the level of cyclin B-like proteins reaches the maximum at the G2 to metaphase transition and then becomes reduced during later stages of mitosis. After long-term incubation with low doses of HU, the amount of cyclin B-like proteins considerably increases, and a significant number of elongated cells show gradients of these proteins spread along successive regions of the perinuclear cytoplasm. It is suggested that there may be a direct link between the effects of HU-mediated deceleration of S- and G2-phases and an enhanced concentration of cyclin B-like proteins. In consequence, the activation of cyclin B-CDK complexes gives rise to an abnormal pattern of premature mitotic chromosome condensation with biphasic nuclear structures having one part of chromatin decondensed, and the other part condensed

Production of HIV Particles Is Regulated by Altering Sub-Cellular Localization and Dynamics of Rev Induced by Double-Strand RNA Binding Protein

Human immunodeficiency virus (HIV)-1 encoded Rev is essential for export from the nucleus to the cytoplasm, of unspliced and singly spliced transcripts coding for structural and nonstructural viral proteins. This process is spatially and temporally coordinated resulting from the interactions between cellular and viral proteins. Here we examined the effects of the sub-cellular localization and dynamics of Rev on the efficiency of nucleocytoplasmic transport of HIV-1 Gag transcripts and virus particle production. Using confocal microscopy and fluorescence recovery after bleaching (FRAP), we report that NF90ctv, a cellular protein involved in Rev function, alters both the sub-cellular localization and dynamics of Rev in vivo, which drastically affects the accumulation of the viral protein p24. The CRM1–dependent nuclear export of Gag mRNA linked to the Rev Response Element (RRE) is dependent on specific domains of the NF90ctv protein. Taken together, our results demonstrate that the appropriate intracellular localization and dynamics of Rev could regulate Gag assembly and HIV-1 replication

Malnutrition in patients treated for oral or oropharyngeal cancer—prevalence and relationship with oral symptoms: an explorative study

This study aimed to assess prevalence of malnutrition after treatment for oral/oropharyngeal cancer and to explore how oral symptoms relate to malnutrition after treatment. In this cross-sectional study, malnutrition (weight loss a parts per thousand yenaEuro parts per thousand 10% in 6 months or a parts per thousand yen5% in 1 month), oral symptoms (EORTC QLQ-H&N35 questionnaire and additional questions to assess chewing problems), dental status, trismus and dietary intake were assessed in 116 adult patients treated for oral/oropharyngeal cancer. Prevalence of malnutrition was 16% (95%CI: 10% to 23%). Prevalence of malnutrition in the period 0-3 months after treatment was significantly higher (25%) than in the periods > 3-12 months (13%) and > 12-36 months after treatment (3%, p = 0.008). Logistic multivariate regression analysis revealed that swallowing problems (p = 0.021) and insufficient protein intake were significantly related to malnutrition (p = 0.016). In conclusion, malnutrition is a considerable problem in patients treated for oral/oropharyngeal cancer, shortly after treatment. Of all oral symptoms, only swallowing problems were significantly related to malnutrition in the period after treatment for oral/oropharyngeal cancer

Phenotype-dependent apoptosis signalling in mesothelioma cells after selenite exposure

<p>Abstract</p> <p>Background</p> <p>Selenite is a promising anticancer agent which has been shown to induce apoptosis in malignant mesothelioma cells in a phenotype-dependent manner, where cells of the chemoresistant sarcomatoid phenotype are more sensitive.</p> <p>Methods</p> <p>In this paper, we investigate the apoptosis signalling mechanisms in sarcomatoid and epithelioid mesothelioma cells after selenite treatment. Apoptosis was measured with the Annexin-PI assay. The mitochondrial membrane potential, the expression of Bax, Bcl-XL, and the activation of caspase-3 were assayed with flow cytometry and a cytokeratin 18 cleavage assay. Signalling through JNK, p38, p53, and cathepsins B, D, and E was investigated with chemical inhibitors. Furthermore, the expression, nuclear translocation and DNA-binding activity of p53 was investigated using ICC, EMSA and the monitoring of p21 expression as a downstream event. Levels of thioredoxin (Trx) were measured by ELISA.</p> <p>Results</p> <p>In both cell lines, 10 μM selenite caused apoptosis and a marked loss of mitochondrial membrane potential. Bax was up-regulated only in the sarcomatoid cell line, while the epithelioid cell line down-regulated Bcl-XL and showed greater caspase-3 activation. Nuclear translocation of p53 was seen in both cell lines, but very little p21 expression was induced. Chemical inhibition of p53 did not protect the cells from apoptosis. p53 lost its DNA binding ability after selenite treatment and was enriched in an inactive form. Levels of thioredoxin decreased after selenite treatment. Chemical inhibition of MAP kinases and cathepsins showed that p38 and cathepsin B had some mediatory effect while JNK had an anti-apoptotic role.</p> <p>Conclusion</p> <p>We delineate pathways of apoptosis signalling in response to selenite, showing differences between epithelioid and sarcomatoid mesothelioma cells. These differences may partly explain why sarcomatoid cells are more sensitive to selenite.</p

Role of Sphingomyelin Synthase in Controlling the Antimicrobial Activity of Neutrophils against Cryptococcus neoformans

The key host cellular pathway(s) necessary to control the infection caused by inhalation of the environmental fungal pathogen Cryptococcus neoformans are still largely unknown. Here we have identified that the sphingolipid pathway in neutrophils is required for them to exert their killing activity on the fungus. In particular, using both pharmacological and genetic approaches, we show that inhibition of sphingomyelin synthase (SMS) activity profoundly impairs the killing ability of neutrophils by preventing the extracellular release of an antifungal factor(s). We next found that inhibition of protein kinase D (PKD), which controls vesicular sorting and secretion and is regulated by diacylglycerol (DAG) produced by SMS, totally blocks the extracellular killing activity of neutrophils against C. neoformans. The expression of SMS genes, SMS activity and the levels of the lipids regulated by SMS (namely sphingomyelin (SM) and DAG) are up-regulated during neutrophil differentiation. Finally, tissue imaging of lungs infected with C. neoformans using matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS), revealed that specific SM species are associated with neutrophil infiltration at the site of the infection. This study establishes a key role for SMS in the regulation of the killing activity of neutrophils against C. neoformans through a DAG-PKD dependent mechanism, and provides, for the first time, new insights into the protective role of host sphingolipids against a fungal infection

Prevalence of hallux valgus in the general population: a systematic review and meta-analysis

BACKGROUND: Hallux valgus (HV) is a foot deformity commonly seen in medical practice, often accompanied by significant functional disability and foot pain. Despite frequent mention in a diverse body of literature, a precise estimate of the prevalence of HV is difficult to ascertain. The purpose of this systematic review was to investigate prevalence of HV in the overall population and evaluate the influence of age and gender. METHODS: Electronic databases (Medline, Embase, and CINAHL) and reference lists of included papers were searched to June 2009 for papers on HV prevalence without language restriction. MeSH terms and keywords were used relating to HV or bunions, prevalence and various synonyms. Included studies were surveys reporting original data for prevalence of HV or bunions in healthy populations of any age group. Surveys reporting prevalence data grouped with other foot deformities and in specific disease groups (e.g. rheumatoid arthritis, diabetes) were excluded. Two independent investigators quality rated all included papers on the Epidemiological Appraisal Instrument. Data on raw prevalence, population studied and methodology were extracted. Prevalence proportions and the standard error were calculated, and meta-analysis was performed using a random effects model. RESULTS: A total of 78 papers reporting results of 76 surveys (total 496,957 participants) were included and grouped by study population for meta-analysis. Pooled prevalence estimates for HV were 23% in adults aged 18-65 years (CI: 16.3 to 29.6) and 35.7% in elderly people aged over 65 years (CI: 29.5 to 42.0). Prevalence increased with age and was higher in females [30% (CI: 22 to 38)] compared to males [13% (CI: 9 to 17)]. Potential sources of bias were sampling method, study quality and method of HV diagnosis. CONCLUSIONS: Notwithstanding the wide variation in estimates, it is evident that HV is prevalent; more so in females and with increasing age. Methodological quality issues need to be addressed in interpreting reports in the literature and in future research