Clinical assessment of hand oedema: A systematic review

Introduction: Assessment of oedema after trauma or surgery is important to determine whether treatment is effective and to detect change over time. Volumetry is referred to as the ‘gold standard’ method of measuring volume. However, this has practical limitations and other methods are available. The aim of this systematic review was to evaluate the psychometric properties of alternative methods used to assess hand oedema. Methods: A search of electronic bibliographic databases was undertaken for any studies published in English reporting the psychometric evaluation of a method for measuring hand oedema, in an adult population with hand swelling from surgery, trauma or stroke. The Consensus‐based Standards for the Selection of health Measurement Instruments (COSMIN) checklist was used to evaluate the methodological quality. Results: Six studies met the inclusion criteria. Three methods were identified assessing hand oedema: perometry, visual inspection and the figure-of-eight tape measure, all were compared to volumetry. Four different psychometric properties were assessed. Studies scored fair or poor on COSMIN criteria. There is low-quality evidence supporting the use of the figure-of-eight tape measure to assess hand volume. The perometer systematically overestimated volume and visual estimation had poor sensitivity and specificity. Discussion: The figure-of-eight tape measure is the best alternative to volumetry for hand oedema. Benefits include reduced cost and time while having comparable reliability to the ‘gold standard’. Further research is needed to compare methods in patients with greater variability of conditions and with isolated digit oedema. Visual estimation of hand oedema is not recommended

Complications arising from a misdiagnosed giant lipoma of the hand and palm: a case report

<p>Abstract</p> <p>Introduction</p> <p>Lipomas are benign tumors which may appear in almost any human organ. Their diagnosis rate in the hand region is not known.</p> <p>Case Presentation</p> <p>We present the case of a 63-year-old Greek Caucasian woman with a giant lipoma of the hand and palm which was not initially diagnosed. After repeated surgical decompression of the carpal tunnel the patient was referred with persisting symptoms of median and ulnar nerve compression and a prominent mass of her left palm and thenar eminence. Clinical examination, magnetic resonance imaging, nerve conduction study and biopsy, revealed a giant lipoma in the deep palmar space (8.0 × 4.0 × 3.75 cm), which was also infiltrating the carpal tunnel. She had already undergone two operations for carpal tunnel syndrome with no relief of her symptoms and she also ended up with a severed flexor pollicis longus tendon. Definitive treatment was performed by marginal resection of the lipoma and restoration of the flexor pollicis longus with an intercalated graft harvested from the palmaris longus. Thirty months after surgery the patient had a fully functional hand without any neurological deficit.</p> <p>Conclusion</p> <p>Not all lipomas of the wrist and hand are diagnosed. Our report tries to emphasize the hidden danger of lipomas in cases with carpal tunnel symptoms. The need for a high index of suspicion in conjunction with good clinical evaluation and the use of appropriate investigative studies is mandatory in order to avoid unnecessary operations and complications. Marginal excision of these tumors is restorative.</p

Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins.

Cyclic AMP is a ubiquitous second messenger used to transduce intracellular signals from a variety of Gs-coupled receptors. Compartmentalisation of protein intermediates within the cAMP signaling pathway underpins receptor-specific responses. The cAMP effector proteins protein-kinase A and EPAC are found in complexes that also contain phosphodiesterases whose presence ensures a coordinated cellular response to receptor activation events. Popeye domain containing (POPDC) proteins are the most recent class of cAMP effectors to be identified and have crucial roles in cardiac pacemaking and conduction. We report the first observation that POPDC proteins exist in complexes with members of the PDE4 family in cardiac myocytes. We show that POPDC1 preferentially binds the PDE4A sub-family via a specificity motif in the PDE4 UCR1 region and that PDE4s bind to the Popeye domain of POPDC1 in a region known to be susceptible to a mutation that causes human disease. Using a cell-permeable disruptor peptide that displaces the POPDC1-PDE4 complex we show that PDE4 activity localized to POPDC1 modulates cycle length of spontaneous Ca2+ transients firing in intact mouse sinoatrial nodes

Cell-type-specific profiling of protein-DNA interactions without cell isolation using targeted DamID with next-generation sequencing.

This protocol is an extension to: Nat. Protoc. 2, 1467-1478 (2007); doi:10.1038/nprot.2007.148; published online 7 June 2007The ability to profile transcription and chromatin binding in a cell-type-specific manner is a powerful aid to understanding cell-fate specification and cellular function in multicellular organisms. We recently developed targeted DamID (TaDa) to enable genome-wide, cell-type-specific profiling of DNA- and chromatin-binding proteins in vivo without cell isolation. As a protocol extension, this article describes substantial modifications to an existing protocol, and it offers additional applications. TaDa builds upon DamID, a technique for detecting genome-wide DNA-binding profiles of proteins, by coupling it with the GAL4 system in Drosophila to enable both temporal and spatial resolution. TaDa ensures that Dam-fusion proteins are expressed at very low levels, thus avoiding toxicity and potential artifacts from overexpression. The modifications to the core DamID technique presented here also increase the speed of sample processing and throughput, and adapt the method to next-generation sequencing technology. TaDa is robust, reproducible and highly sensitive. Compared with other methods for cell-type-specific profiling, the technique requires no cell-sorting, cross-linking or antisera, and binding profiles can be generated from as few as 10,000 total induced cells. By profiling the genome-wide binding of RNA polymerase II (Pol II), TaDa can also identify transcribed genes in a cell-type-specific manner. Here we describe a detailed protocol for carrying out TaDa experiments and preparing the material for next-generation sequencing. Although we developed TaDa in Drosophila, it should be easily adapted to other organisms with an inducible expression system. Once transgenic animals are obtained, the entire experimental procedure-from collecting tissue samples to generating sequencing libraries-can be accomplished within 5 d.This work was funded by a Wellcome Trust Senior Investigator Award (103792), Wellcome Trust Programme Grant (092545) and BBSRC Project Grant (BB/L00786X/1) to A.H.B. A.H.B acknowledges core funding to the Gurdon Institute from the Wellcome Trust (092096) and CRUK (C6946/A14492).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nprot.2016.08

Measurement of the Absolute Magnitude and Time Courses of Mitochondrial Membrane Potential in Primary and Clonal Pancreatic Beta-Cells

The aim of this study was to simplify, improve and validate quantitative measurement of the mitochondrial membrane potential (ΔψM) in pancreatic β-cells. This built on our previously introduced calculation of the absolute magnitude of ΔψM in intact cells, using time-lapse imaging of the non-quench mode fluorescence of tetramethylrhodamine methyl ester and a bis-oxonol plasma membrane potential (ΔψP) indicator. ΔψM is a central mediator of glucose-stimulated insulin secretion in pancreatic β-cells. ΔψM is at the crossroads of cellular energy production and demand, therefore precise assay of its magnitude is a valuable tool to study how these processes interplay in insulin secretion. Dispersed islet cell cultures allowed cell type-specific, single-cell observations of cell-to-cell heterogeneity of ΔψM and ΔψP. Glucose addition caused hyperpolarization of ΔψM and depolarization of ΔψP. The hyperpolarization was a monophasic step increase, even in cells where the ΔψP depolarization was biphasic. The biphasic response of ΔψP was associated with a larger hyperpolarization of ΔψM than the monophasic response. Analysis of the relationships between ΔψP and ΔψM revealed that primary dispersed β-cells responded to glucose heterogeneously, driven by variable activation of energy metabolism. Sensitivity analysis of the calibration was consistent with β-cells having substantial cell-to-cell variations in amounts of mitochondria, and this was predicted not to impair the accuracy of determinations of relative changes in ΔψM and ΔψP. Finally, we demonstrate a significant problem with using an alternative ΔψM probe, rhodamine 123. In glucose-stimulated and oligomycin-inhibited β-cells the principles of the rhodamine 123 assay were breached, resulting in misleading conclusion

Evolving health information technology and the timely availability of visit diagnoses from ambulatory visits: A natural experiment in an integrated delivery system

<p>Abstract</p> <p>Background</p> <p>Health information technology (HIT) may improve health care quality and outcomes, in part by making information available in a timelier manner. However, there are few studies documenting the changes in timely availability of data with the use of a sophisticated electronic medical record (EMR), nor a description of how the timely availability of data might differ with different types of EMRs. We hypothesized that timely availability of data would improve with use of increasingly sophisticated forms of HIT.</p> <p>Methods</p> <p>We used an historical observation design (2004–2006) using electronic data from office visits in an integrated delivery system with three types of HIT: Basic, Intermediate, and Advanced. We calculated the monthly percentage of visits using the various types of HIT for entry of visit diagnoses into the delivery system's electronic database, and the time between the visit and the availability of the visit diagnoses in the database.</p> <p>Results</p> <p>In January 2004, when only Basic HIT was available, 10% of office visits had diagnoses entered on the same day as the visit and 90% within a week; 85% of office visits used paper forms for recording visit diagnoses, 16% used Basic at that time. By December 2006, 95% of all office visits had diagnoses available on the same day as the visit, when 98% of office visits used some form of HIT for entry of visit diagnoses (Advanced HIT for 67% of visits).</p> <p>Conclusion</p> <p>Use of HIT systems is associated with dramatic increases in the timely availability of diagnostic information, though the effects may vary by sophistication of HIT system. Timely clinical data are critical for real-time population surveillance, and valuable for routine clinical care.</p

Non-Canonicaly Recruited TCRαβCD8αα IELs Recognize Microbial Antigens

In the gut, various subsets of intraepithelial T cells (IELs) respond to self or non-self-antigens derived from the body, diet, commensal and pathogenic microbiota. Dominant subset of IELs in the small intestine are TCRαβCD8αα+ cells, which are derived from immature thymocytes that express self-reactive TCRs. Although most of TCRαβCD8αα+ IELs are thymus-derived, their repertoire adapts to microbial flora. Here, using high throughput TCR sequencing we examined how clonal diversity of TCRαβCD8αα+ IELs changes upon exposure to commensal-derived antigens. We found that fraction of CD8αα+ IELs and CD4+ T cells express identical αβTCRs and this overlap raised parallel to a surge in the diversity of microbial flora. We also found that an opportunistic pathogen (Staphylococcus aureus) isolated from mouse small intestine specifically activated CD8αα+ IELs and CD4+ derived T cell hybridomas suggesting that some of TCRαβCD8αα+ clones with microbial specificities have extrathymic origin. We also report that CD8ααCD4+ IELs and Foxp3CD4+ T cells from the small intestine shared many αβTCRs, regardless whether the later subset was isolated from Foxp3CNS1 sufficient or Foxp3CNS1 deficient mice that lacks peripherally-derived Tregs. Overall, our results imply that repertoire of TCRαβCD8αα+ in small intestine expends in situ in response to changes in microbial flora

Induction of interleukin-8 preserves the angiogenic response in HIF-1 alpha-deficient colon cancer cells

authorHypoxia inducible factor-1 (HIF-1) is considered a crucial mediator of the cellular response to hypoxia through its regulation of genes that control angiogenesis^1, ^2, ^3, ^4. It represents an attractive therapeutic target^5, ^6 in colon cancer, one of the few tumor types that shows a clinical response to antiangiogenic therapy^7. But it is unclear whether inhibition of HIF-1 alone is sufficient to block tumor angiogenesis^8, ^9. In HIF-1_α knockdown DLD-1 colon cancer cells (DLD-1^HIF-kd), the hypoxic induction of vascular endothelial growth factor (VEGF) was only partially blocked. Xenografts remained highly vascularized with microvessel densities identical to DLD-1 tumors that had wild-type HIF-1_α (DLD-1^HIF-wt). In addition to the preserved expression of VEGF, the proangiogenic cytokine interleukin (IL)-8 was induced by hypoxia in DLD-1^HIF-kd but not DLD-1^HIF-wt cells. This induction was mediated by the production of hydrogen peroxide and subsequent activation of NF-_KB. Furthermore, the KRAS oncogene, which is commonly mutated in colon cancer, enhanced the hypoxic induction of IL-8. A neutralizing antibody to IL-8 substantially inhibited angiogenesis and tumor growth in DLD-1^HIF-kd but not DLD-1^HIF-wt xenografts, verifying the functional significance of this IL-8 response. Thus, compensatory pathways can be activated to preserve the tumor angiogenic response, and strategies that inhibit HIF-1α may be most effective when IL-8 is simultaneously targeted

Phenotypic variation and fitness in a metapopulation of tubeworms (Ridgeia piscesae Jones) at hydrothermal vents

We examine the nature of variation in a hot vent tubeworm, Ridgeia piscesae, to determine how phenotypes are maintained and how reproductive potential is dictated by habitat. This foundation species at northeast Pacific hydrothermal sites occupies a wide habitat range in a highly heterogeneous environment. Where fluids supply high levels of dissolved sulphide for symbionts, the worm grows rapidly in a ‘‘short-fat’’ phenotype characterized by lush gill plumes; when plumes are healthy, sperm package capture is higher. This form can mature within months and has a high fecundity with continuous gamete output and a lifespan of about three years in unstable conditions. Other phenotypes occupy low fluid flux habitats that are more stable and individuals grow very slowly; however, they have low reproductive readiness that is hampered further by small, predator cropped branchiae, thus reducing fertilization and metabolite uptake. Although only the largest worms were measured, only 17% of low flux worms were reproductively competent compared to 91% of high flux worms. A model of reproductive readiness illustrates that tube diameter is a good predictor of reproductive output and that few low flux worms reached critical reproductive size. We postulate that most of the propagules for the vent fields originate from the larger tubeworms that live in small, unstable habitat patches. The large expanses of worms in more stable low flux habitat sustain a small, but long-term, reproductive output. Phenotypic variation is an adaptation that fosters both morphological and physiological responses to differences in chemical milieu and predator pressure. This foundation species forms a metapopulation with variable growth characteristics in a heterogeneous environment where a strategy of phenotypic variation bestows an advantage over specialization