Arthroscopic Shoulder Stabilization: Is There Ever a Need to Open?

Recent studies show comparable results of arthroscopic shoulder stabilization techniques compared with the gold standard open Bankart reconstruction. Great technical advances and ever-increasing surgeon experience have rendered pathology once deemed an indication for open surgery as treatable by arthroscopic means. With this movement toward a more universal application of all-arthroscopic techniques, we might consider the following question: Is there ever a need to open? To answer this question, we must first consider normal anatomy and then appreciate the contribution of deranged pathoanatomy to recurrent instability in each individual case. The surgeon must then determine whether this is best addressed via an arthroscopic or open technique. Arthroscopy, as compared with open stabilization procedures, holds the potential benefits of decreased morbidity rates, early functional rehabilitation, and improved range of motion. Despite potential advantages, arthroscopic stabilization is clearly contraindicated when a significant pathologic lesion contributing to recurrent instability cannot be adequately addressed as a result of the limitations of current techniques or instrumentation. On the basis of this principle, we believe that sizable glenohumeral bone defects remain the only absolute contraindication to an all-arthroscopic approach. Many complicating issues, such as attenuated capsule, humeral avulsion of the glenohumeral ligament lesions, cases of revision surgery, and collision or contact athletes, exist and warrant close attention. We prefer to think of these situations as “challenges” for which both arthroscopic and open surgery should be considered, rather than as true contraindications to arthroscopic shoulder stabilization. We are, by no means, advocating arthroscopic treatment in all cases of shoulder instability, because this would represent a gross oversimplification of the issues at hand. However, we do acknowledge that the steadfast contraindications to arthroscopic shoulder stabilization are decreasing every day.     

The human CD40 gene lies within chromosome 20q deletions associated with myeloid malignancies

Deletions of chromosome 20q are associated with myeloid malignancies and have been previously shown to arise in a multipotent progenitor of both myeloid and B cells. However, B-cell differentiation from the abnormal progenitor was impaired. The CD40 antigen is a surface glycoprotein which is expressed in B cells and haemopoietic stem cells and is important for B-cell growth and development. Following the recent mapping of CD40 to chromosome 20q we sought to determine its position relative to 20q deletions. Analysis of lymphoblastoid cell lines carrying 20q deletions placed CD40 within a 19–21 cM interval which is almost coincidental with the common deleted region defined by previous analysis of patient samples. Our results raise the possibility that genetic alteration of this locus may contribute to the pathogenesis of myeloid disorders associated with 20q deletions.     

Clonal haemopoiesis in normal elderly women: implications for the myeloproliferative disorders and myelodysplastic syndromes

Studies of X chromosome inactivation patterns are central to many aspects of our understanding of the pathogenesis of haematological malignancies. In patients with myeloproliferative disorders and myelodysplastic syndromes the demonstration of skewed X inactivation patterns in multiple haemopoietic lineages has been taken to indicate a stem cell origin for these groups of diseases. However, stem cell depletion or selection pressures can also produce skewed X inactivation patterns and might increase with age. We have therefore used the HUMARA assay to study X inactivation patterns of elderly patients with myeloproliferative disorders together with an age-matched control group of normal elderly women.   A clonal pattern (clonal granulocytes and polyclonal T cells) was observed in 23.1% of normal women and 63.4% of patients with myeloproliferative disorders. This is the first report of X inactivation patterns in purified subpopulations of blood cells in normal elderly women. These results have three significant implications. Firstly, the finding of clonal granulocytes and polyclonal T cells in normal elderly women is likely to reflect age-related stem cell depletion or selection pressures. Secondly, the demonstration of clonal granulocytes and polyclonal T cells is not a useful diagnostic marker for myeloproliferative disorders or myelodysplastic syndromes in elderly women. Thirdly, our data raise the possibility that clonal blood cell patterns may precede rather than follow mutations which subsequently give rise to myelodysplastic or myeloproliferative phenotypes.     

Lipophilicity and biomimetic properties to support drug discovery

Introduction: Lipophilicity, expressed as the octanol-water partition coefficient, constitutes the most important property in drug action, influencing both pharmacokinetic and pharmacodynamics processes as well as drug toxicity. On the other hand, biomimetic properties defined as the retention outcome on HPLC columns containing a biological relevant agent, provide a considerable advance for rapid experimental – based estimation of ADME properties in early drug discovery stages.

Areas covered: This review highlights the paramount importance of lipophilicity in almost all aspects of drug action and safety. It outlines problems brought about by high lipophilicity and provides an overview of the drug-like metrics which incorporate lower limits or ranges of logP. The fundamental factors governing lipophilicity are compared to those involved in phospholipophilicity, assessed by Immobilized Artificial Membrane Chromatography (IAM). Finally, the contribution of biomimetic properties to assess plasma protein binding is evaluated.

Expert opinion: Lipophilicity and biomimetic properties have important distinct and overlapping roles in supporting the drug discovery process. Lipophilicity is unique in early drug design for library screening and for the identification of the most promising compounds to start with, while biomimetic properties are useful for the experimentally-based evaluation of ADME properties for the synthesized novel compounds, supporting the prioritization of drug candidates and guiding further synthesis.     

Sleep disorders in pediatric chronic kidney disease patients

The prevalence of sleep disorders during childhood has been estimated to range from 25 to 43 %. The aim of this review is to determine the prevalence of sleep disorders and possible associations with chronic kidney disease (CKD)-related factors and health-related quality of life (HRQOL) in children with CKD. An electronic systematic literature search for sleep disorders in children with CKD in Pubmed, Embase and the Cochrane Library Databases identified seven relevant articles for review, all of which reported an increased prevalence of sleep disorders in children with CKD. Five studies included children with CKD undergoing dialysis, and two studies included only non-dialysis patients. In all studies the presence of sleep disturbances was assessed by questionnaires; only one study compared the results of a validated questionnaire with laboratory-based polysomnography. The prevalence of any sleep disorder ranged from 77 to 85 % in dialysis patients, to 32–50 % in transplanted patients and 40–50 % in non-dialysis patients. The most commonly studied disorder was restless legs syndrome, which presented at a prevalence of 10–35 %. Three studies showed significant associations between presence of sleep disorders and HRQOL. We found consistent evidence of an increased prevalence of sleep disturbances in children with CKD, and these seemed to play a critical role in HRQOL.