Can local Erythropoietin administration enhance bone regeneration in osteonecrosis of femoral head?

Osteonecrosis of femoral head (ONFH) is a challenging disease. Regardless of underlying causes, the ultimate result in all cases is disruption of femoral head blood supply. Once the disease starts, it is progressive in 80% of cases. Since the majority of the affected individuals are young, every effort should be focused on preserving the patients own femoral head. These years, the role of angiogenic growth factors has been investigated with promising results in animal models of ONFH. Erythropoietin (EPO) is a well known hormone that has been used in treatment of chronic anemia for many years with few side effects. Considering the angiogenic properties of EPO, we hypothesize that local delivery of recombinant human EPO during core decompression will enhance bone regeneration in ONFH. In this way we also can avoid systemic side effects of EPO.     

Supercritical CO2 fluid-foaming of polymers to increase porosity: A method to improve the mechanical and biocompatibility characteristics for use as a potential alternative to allografts in impaction bone grafting?

Disease transmission, availability and cost of allografts have resulted in significant efforts to find an alternative for use in impaction bone grafting (IBG). Recent studies identified two polymers with both structural strength and biocompatibility characteristics as potential replacements. The aim of this study was to assess whether increasing the polymer porosity further enhanced the mechanical and cellular compatibility characteristics for use as an osteogenic biomaterial alternative to allografts in IBG. Solid and porous poly(DL-lactide) (P(DL)LA) and poly(DL-lactide-co-glycolide) (P(DL)LGA) scaffolds were produced via melt processing and supercritical CO(2) foaming, and the differences characterized using scanning electron microscopy (SEM). Mechanical testing included milling and impaction, with comparisons made using a shear testing rig as well as a novel agitation test for cohesion. Cellular compatibility tests for cell number, viability, and osteogenic differentiation using WST-1 assays, fluorostaining, and ALP assays were determined following 14 day culture with skeletal stem cells. SEM showed excellent porosity throughout both of the supercritical-foam-produced polymer scaffolds, with pores between 50 and 200 μm. Shear testing showed that the porous polymers exceeded the shear strength of allograft controls (P<0.001). Agitation testing showed greater cohesion between the particles of the porous polymers (P<0.05). Cellular studies showed increased cell number, viability, and osteogenic differentiation on the porous polymers compared to solid block polymers (P<0.05). The use of supercritical CO(2) to generate porous polymeric biodegradable scaffolds significantly improves the cellular compatibility and cohesion observed compared to non-porous counterparts, without substantial loss of mechanical shear strength. These improved characteristics are critical for clinical translation as a potential osteogenic composite for use in IBG.     

Does complement play a role in bone development and regeneration?

The skeletal and the immune system are not two independent systems, rather, there are multifaceted and complex interactions between the different cell types of both systems and there are several shared cytokines. As a part of the innate immunity, the complement system was found to be an important link between bone and immunity. Complement proteins appear to be involved in bone development and homeostasis, and specifically influence osteoblast and osteoclast activity. This review describes the complex mutual regulation of the two systems, and indicates some of the negative side effects as a result of inappropriate or excessive complement activation.     

Future developments in the medical treatment of abnormal uterine bleeding: what can we expect?

New therapies for abnormal uterine bleeding have been slow to reach the marketplace for a variety of reasons. These reasons include the availability of cost-effective therapies already available and the extraordinarily difficult and expensive regulatory barriers emphasizing long-term safety. Common comorbidities like bleeding diatheses, adenomyosis, and leiomyomata further complicate clinical development, necessitating large study samples and making it more expensive. Even the accurate measurement of menstrual blood loss adds an additional hindrance to novel drug development. These obstacles and the currently available therapies will be reviewed in the context of developing new methods for approaching this complicated and prevalent clinical problem.     

How can we improve compliance in pediatric pneumology and allergology?

Not too long ago, physicians took 'compliance' or 'adherence' to mean the strict obedience of patients and parents - doing what the physician said, suggesting that the success or failure of the treatment lay entirely in the hands of the patient. But it is preferable to improve compliance rather than enforce it. As there is no single solution that will ensure compliance, several steps should be taken: (i) 'exploration' includes open questions, and allows admission of non-compliance, e.g. in terms of failure to take drugs, or smoking; (ii) 'education' means explaining pathomechanisms, and reducing corticophobia; (iii) 'tailoring' is reached by focussing therapeutic options on individual requirements, and simplifying treatment regimens; (iv) 'contracting' involves negotiating a realistic therapeutic regimen on an individual basis; (v) 'reminders' are practical tips, which may help to overcome reluctance, e.g. by placing drugs in the toothbrush glass, and on the breakfast table, or in the sports bag; (vi) 'follow-up' ensures long-term compliance, with regular visits to the physician, and self-management programmes. In conclusion, non-compliance of patients and parents is a challenging problem in daily practice. Including the aspects of the abovementioned factors can help build up a relation of trust and partnership, which is the prerequisite of any therapeutic success. However, this is an ongoing process, which has to be continuously reviewed.     

Is hydroxyapatite cement an alternative for allograft bone chips in bone grafting procedures? A mechanical and histological study in a rabbit cancellous bone defect model

To evaluate in vivo performance of hydroxyapatite cement (HAC) as a porous bone graft substitute, HAC was mixed (1:1 ratio) with either porous calcium-phosphate granules (80% tricalcium phosphate, 20% hydroxyapatite) or defatted morsellized cancellous bone (MCB) allograft and implanted bilaterally in cylindrical drill holes in distal femurs of rabbits. Groups with empty defects and impacted MCB were used for reference. After 8 weeks, one femur from each pair was examined histologically. All contralateral specimens and Time-0 specimens were used for mechanical indentation tests. Histology showed that some empty defects were filled with newly formed osteopenic bone after 8 weeks. The impacted MCB showed remodeling into new vital bone. Incorporation of the HAC/MCB composite was incomplete, whereas minimal new bone ingrowth was found in the HAC/granule composites. Though not different from each other, both composites were significantly stronger than empty defects, incorporated impacted MCB, and intact cancellous bone. At Time 0, the mechanical behavior of impacted MCB was similar to both HAC composites. In conclusion, composites of HAC and porous biomaterials can maintain relatively high strength over 8 weeks in vivo, but their incorporation into a new bony structure is slower than impacted MCB. The HAC/MCB composite showed favorable incorporation behavior.     

Anodal block: can this occur during routine nerve conduction studies?

The median nerves of five normal subjects were electrically excited at the wrist with fine-tipped stimulating electrodes in a bipolar fashion. Compound sensory nerve action potentials (CSNAPs) were recorded from the index finger and compound muscle action potentials (CMAPs) from the thenar muscles. Both the cathode and the anode were positioned over the length of the nerve. Recordings were performed with different cathode-to-anode distances of 5, 10, 20, and in some cases, 30 mm. Just supramaximal CSNAPs and CMAPs were obtained initially with the cathode situated distal to the anode and then with the stimulus polarity reversed. There were no significant differences in the amplitude, duration, and morphology of the CSNAPs or CMAPs that were recorded by using different stimulus polarities. There was a consistent increase in the onset latency of the responses when the stimulus polarity was reversed (cathode located proximal to anode). This increase in latency was proportionate to the increase in distance from the cathode to the recording electrode. The effect of anodal block could not be observed from the above experiment.     

Options for bronchodilation in children: can we rely on adult data?

Bronchodilators, especially β₂-agonists, are effective in relieving asthma symptoms. Therefore, short-acting β₂-agonists are recommended in all guidelines on a p. r. n. basis, usually in combination with anti-inflammatory treatment, at least in moderate to severe asthma. Although for adult asthma some concerns have been raised about regular use of short-acting β₂-agonists, studies in children do not suggest that continuous use results in deterioration of asthma. This question is more relevant to the chronic use of the long-acting β₂-agonists, salmeterol and formoterol. These drugs may be used instead of antiinflammatory drugs, especially inhaled corticosteroids. Recent studies in adult asthmatics have supported the use of a longacting β₂-agonist in combination with a lower dose of inhaled corticosteroid in preference to a higher dose of inhaled corticosteroid. So far, data in children are less convincing for this therapeutic strategy. It may be that differences in the disease process between adults and children are likely to account for these different responses in treatment regimens. Furthermore, it has to be determined whether treatment should primarily aim at symptom reduction or whether other disease parameters should also be taken into account.     

Memory-guided saccades in Parkinson’s disease: long delays can improve performance

A recent study in control subjects suggested the existence of separate pathways for oculomotor spatial working memory tasks depending on whether the delay before movement execution is either short or long (>20 s). The long delay pathway might bypass brain areas commonly affected by Parkinsons disease (PD). This study aimed to assess spatial working memory in Parkinsons disease using short (3 s) and long (30 s) delays in a memory-guided saccade task. Fifteen mild-moderately affected PD subjects off-medication, and 15 age and sex-matched controls were tested (PD mean age 65.3; control 65.9). Subjects were tested in a darkened room using a horizontal LED bar to generate eye movements which were recorded using an infrared limbus tracker. Percentage error in amplitude of the primary saccade was analysed by repeated measures ANOVA. There was a significant interaction between the groups and their response to the short and long delay periods (P<0.02). PD subjects were more strongly impaired in the short delay than the long delay trials when compared with controls. Analysis of the percentage error in amplitude of the final eye position showed the same pattern but only in female subjects. This study provides the first evidence that the proposed parallel spatial memory pathway utilised in longer delay periods is relatively unimpaired in PD. In a broader sense, our results suggest there might be other alternative pathways to overcome deficits in functions impaired by PD.     

How does dose impact on the severity of food‐induced allergic reactions,and can this improve risk assessment for allergenic foods?

Quantitative risk assessment (QRA) for food allergens has made considerable progress in recent years, yet acceptability of its outcomes remains stymied because of the limited extent to which it has been possible to incorporate severity as a variable. Reaction severity, particularly following accidental exposure, depends on multiple factors, related to the allergen, the host and any treatments, which might be administered. Some of these factors are plausibly still unknown. Quantitative risk assessment shows that limiting exposure through control of dose reduces the rates of reactions in allergic populations, but its impact on the relative frequency of severe reactions at different doses is unclear. Food challenge studies suggest that the relationship between dose of allergenic food and reaction severity is complex even under relatively controlled conditions. Because of these complexities, epidemiological studies provide very limited insight into this aspect of the dose‐response relationship. Emerging data from single‐dose challenges suggest that graded food challenges may overestimate the rate of severe reactions. It may be necessary to generate new data (such as those from single‐dose challenges) to reliably identify the effect of dose on severity for use in QRA. Success will reduce uncertainty in the susceptible population and improve consumer choice.     

Reflecting on homework in psychotherapy: What can we conclude from research and experience?

This article examines the empirical basis of using homework in psychotherapy and then offers a synthesis of the research literature with the preceding clinical articles. We provide a practitioner-friendly review of psychotherapy process and outcome research literature, concluding that there is now sufficient evidence to support the assertion that homework assignments enhance psychotherapy outcomes. It is also clear that homework compliance is a consistently significant predictor of treatment outcome. Limitations of existing studies and future research directions are outlined, and we suggest that more specific questions are required regarding the integration of homework into therapy process. Clinical recommendations and issues in homework administration described in preceding articles are also synthesized. The research evidence and contributors to this issue converge in recommending homework within the broad context of psychotherapy and using creative ways of administering homework that is customized to the client.     

Chitosan–poly(lactide-co-glycolide) microsphere-based scaffolds for bone tissue engineering: In vitro degradation and in vivo bone regeneration studies

Natural polymer chitosan and synthetic polymer poly(lactide-co-glycolide) (PLAGA) have been investigated for a variety of tissue engineering applications. We have previously reported the fabrication and in vitro evaluation of a novel chitosan/PLAGA sintered microsphere scaffold for load-bearing bone tissue engineering applications. In this study, the in vitro degradation characteristics of the chitosan/PLAGA scaffold and the in vivo bone formation capacity of the chitosan/PLAGA-based scaffolds in a rabbit ulnar critical-sized-defect model were investigated. The chitosan/PLAGA scaffold showed slower degradation than the PLAGA scaffold in vitro. Although chitosan/PLAGA scaffold showed a gradual decrease in compressive properties during the 12-week degradation period, the compressive strength and compressive modulus remained in the range of human trabecular bone. Chitosan/PLAGA-based scaffolds were able to guide bone formation in a rabbit ulnar critical-sized-defect model. Microcomputed tomography analysis demonstrated that successful bridging of the critical-sized defect on the sides both adjacent to and away from the radius occurred using chitosan/PLAGA-based scaffolds. Immobilization of heparin and recombinant human bone morphogenetic protein-2 on the chitosan/PLAGA scaffold surface promoted early bone formation as evidenced by complete bridging of the defect along the radius and significantly enhanced mechanical properties when compared to the chitosan/PLAGA scaffold. Furthermore, histological analysis suggested that chitosan/PLAGA-based scaffolds supported normal bone formation via intramembranous formation.     

Do optional implants improve the femoral fit during total knee arthroplasty in Asians? Comparison of the femoral fit between single- and dual-option implants

BackgroundThe purpose of this study was to evaluate the femoral fit in Asian patients during total knee arthroplasty by examining whether (1) the advanced single-option implant improves the fit of the femoral component in both the anterior flange and distal cutting surface and (2) the dual-option implants show better fit than the advanced single-option implant.MethodsA total of 950 knees that underwent primary total knee arthroplasty were included. Two types of single-option implant systems (Optetrak Logic and Truliant) and three types of dual-option implant systems (Anthem, Attune, and Persona) were used. The difference between the resected surface of the femur and femoral component dimensions was analyzed in predefined six zones. Appropriateness of fit (good-fit, over-hang, under-hang) was also evaluated.ResultsThe advanced single-option implant showed higher rates of good-fit and lower rates of over-hang and under-hang in almost all distinct zones than the old version single-option implant. The advanced single-option implant demonstrated similar good-fit, higher over-hang and lower under-hang rates than the dual-option implants. All single-option implants showed significantly higher over-hang rate (P < 0.05) and lower under-hang rate (P < 0.05) than all dual-option implant systems in the anterior flange transverse area. The narrow option was only selected in 12–20% of all cases.ConclusionsThe advanced single-option implant system improved the fit of the femoral component when compared with the old version and showed similar good-fit rates when compared with the dual-option implant systems. The narrow option of the dual-option implant systems was used less frequently than expected in Asian knees.     

Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented?

There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual-allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL-33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome.     

Is there any information on micro-structure in microwave tomography of bone tissue?

In this work, two-dimensional simulations of the microwave dielectric properties of models with ellipses and realistic models of trabecular bone tissue are performed. In these simulations, finite difference time domain methodology has been applied to simulate two-phase structures containing inclusions. The results presented here show that the micro-structure is an important factor in the effective dielectric properties of trabecular bone. We consider the feasibility of using the dielectric behaviour of bone tissue to be an indicator of bone health. The frequency used was 950 MHz. It was found that the dielectric properties can be used as an estimate of the degree of anisotropy of the micro-structure of the trabecular tissue. Conductivity appears to be the most sensitive parameter in this respect. Models with ellipse shaped-inclusions are also tested to study their application to modelling bone tissue. Models with ellipses that had an aspect ratio of a/b = 1.5 showed relatively good agreement when compared with realistic models of bone tissue. According to the results presented here, the anisotropy of trabecular bone must be accounted for when measuring its dielectric properties using microwave imaging.     

Depressive and anxiety disorders in the postpartum period: how prevalent are they and can we improve their detection?

The objectives of this study were: (1) to examine Composite International Diagnostic Interview (CIDI) period prevalence and comorbidity for depression and anxiety disorder in a cohort of women assessed during the first 6–8 months postpartum and (2) to examine the benefits of combining the Edinburgh Postnatal Depression Scale (EPDS) with a simple “interval symptom” question to optimize screening postpartum. Women aged over 18 (N = 1,549) were assessed during late pregnancy and reviewed at approximately 2, 4, and 6–8 months postpartum using the EPDS and an “interval symptom” question. The latter asked about any depressive symptoms in the interval since the last EPDS. Women who scored >12 on the EPDS and/or positive on the “interval symptom” question were then administered the CIDI. A further 65 randomly selected women that screened negative were also administered the CIDI. Loss to postnatal follow-up was very significant, and returns rates were inconsistent across the three postnatal time points. Almost 25% of those who screened positive did not complete a CIDI. For screen-positive status, a total of 314 (24.4%) of those that returned questionnaires (N = 1,289) screened positive at least once across the 6- to 8-month interval. Of these, 79 were lost to follow-up; thus, 235 (74.8%) completed a CIDI. In this group, 34.7% had been positive both on the EPDS and the “interval” question, 15.9% on the EPDS alone, and 49.4% on the “interval” question alone. For the CIDI diagnosis and estimated 6- to 8-month period CIDI prevalence, among those 235 women who screened positive and completed a CIDI, 67.2% met the criteria for a CIDI diagnosis, as did 16.9% of those who screened negative. The breakdown in CIDI diagnoses in the 235 women was 32.8% major depression (± anxiety disorder); 26.4% minor depression alone; and 8.1% with a primary anxiety disorder (approximately half with minor depression). Put another way, 20.4% of these women had an anxiety disorder (approximately two thirds with comorbid depression) and 37.7% of women with a major depressive episode (MDE) had a comorbid anxiety disorder. The estimated 6- to 8-month prevalence rate for a CIDI diagnosis of anxiety or depression (major or minor) was 29.2% (95% CI 26.7%–31.7%). The use of the “interval symptom” question alone was 1.7 times more likely to identify positive CIDI cases than the EPDS alone. Almost 40% of postnatal women with a diagnosis of MDE have a comorbid diagnosis of anxiety disorder. The estimated 6- to 8-month period prevalence for CIDI cases of anxiety and depression was 29.2%. Screening for anxiety and depression using the EPDS alone was associated with a lesser capacity to identify CIDI caseness than a simple “interval symptom” question (for the 2 months prior) which almost doubled the yield. This paper demonstrates that combining the EPDS with the “interval symptom” question improves detection of CIDI caseness.