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The self-assembly of small colloidal clusters, so-called colloidal molecules, into crystalline materials has proven extremely challenging, the outcome often being glassy, amorphous states where positions and orientations are locked. In this paper, a new type of colloidal molecule is therefore prepared, assembled from poly(N-isopropylacrylamide) (PNIPAM)-based microgels that due to their well documented softness and temperature-response allow for greater defect tolerance compared to hard spheres and for convenient in situ tuning of size, volume fraction and inter-particle interactions with temperature. The microgels (B) are assembled by electrostatic adsorption onto oppositely charged, smaller-sized microgels (A), where the relative size of the two determines the valency (n) of the resulting core-satellite ABn-type colloidal molecules. Following assembly, a microfluidic deterministic lateral displacement (DLD) device is used to effectively isolate AB4-type colloidal molecules of tetrahedral geometry that possess a repulsive-to-attractive transition on crossing the microgels' volume phase transition temperature (VPTT). These soft, temperature-responsive colloidal molecules constitute highly promising building blocks for the preparation of new materials with emergent properties, and their optical wavelength-size makes them especially interesting for optical applications.

Minor emergency departments (ED) struggle to access sufficient expertise to supervise learners of lung and cardiac point-of-care ultrasound (POCUS). Using tele-ultrasound (tele-US) for remote supervision may remedy this situation. We aimed to evaluate the feasibility of real-time supervision via tele-US when applied to an everyday ED clinic. We conducted a mixed methods study that assessed practical feasibility, determined performance, and explored users' acceptability of supervision via tele-US. Technical performance was assessed quantitatively by the ratio in mean gray value between images on site and as received by the supervisor, and by after-compression frame rate. Qualitatively, 12 exploratory semi-structured interviews were conducted with exposed junior doctors and supervisors. Remote supervision via tele-US was performed with 10 junior doctors scanning 45 included patients. During performance assessment, neither alternating internet connection nor software significantly changed the mean gray value ratio. The lowest median frame rate of 4.6 (interquartile range [IQR]: 3.1-5.0) was found by using a 4G internet connection; the highest of 28.5 (IQR: 28.5-29.0) was found with alternative computer and local area network internet connection. In interviews, supervisors stressed the importance of preserving frame rate, and junior doctors emphasized a need for shared ultrasound terminology. In the qualitative analysis, setup mobility, accessibility, and time consumption were emphasized as being of key importance for future clinical implementations. Remote supervision via a commercially available and low-cost tele-US setup is operational for both junior doctors and supervisors when applied to lung and cardiac POCUS scans of hospitalized patients.

Background: Maintenance of kidney function in kidney allografts remains a challenge, as the allograft often progressively develops fibrosis after kidney transplantation. Fibrosis is caused by the accumulation of extracellular matrix proteins like type I and III collagen (COL I and III) that replace the functional tissue. We assessed the concentrations of a neo-epitope fragment of COL III generated by matrix metalloproteinase-9 cleavage (C3M) in two rat models resembling the ischaemic injury taking place following kidney transplantation., Methods: We measured C3M in urine (U-C3M) and plasma (P-C3M) samples of rats subjected to unilateral nephrectomy followed by sham operation (NTx) or ischaemia reperfusion injury (NTxIRI) as well as in rats subjected to bilateral ischaemia reperfusion injury (BiIRI). Levels of U-C3M were normalized to urinary creatinine and were correlated to plasma creatinine, blood urea nitrogen, messenger ribonucleic acid (mRNA) of markers of kidney injury, and mRNA and protein levels of markers of tissue repair and fibrosis., Results: Levels of U-C3M were significantly elevated 7 days after ischaemia reperfusion in the NTxIRI. BiIRI animals showed higher levels of U-C3M after 7 and 14 days of reperfusion but not at 21 days. P-C3M did not change in any of the models. There was a significant correlation between U-C3M and mRNA levels of fibronectin, COL I alpha 1 chain (COL Ia1) and neutrophil gelatinase-associated lipocalin (NGAL), and protein levels of alpha smooth muscle actin (αSMA), fibronectin and COL III in NTxIRI but not in NTx animals. Levels of U-C3M increased significantly in the BiIRI animals subsequent to reperfusion, and mirrored the histological alterations. Furthermore, U-C3M was associated with the extent of fibrosis, and remained elevated even after plasma creatinine levels decreased., Conclusions: These results demonstrate that degradation of COL III increases after ischaemia reperfusion injury, and that U-C3M may be a non-invasive marker of tissue repair and fibrosis in the ischaemic kidney., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Skeletal stem cells (SSCs) are present in bone marrow (BM) and offer great potential for bone regenerative therapies. However, in the absence of a unique marker, current sorting approaches remain challenging in the quest for simple strategies to deliver SSCs with consistent regeneration and differentiation capacities. Microfluidics offers the possibility to sort cells marker-free, based on intrinsic biophysical properties. Recent studies indicate that SSCs are stiffer than leukocytes and are contained within the larger cell fraction in BM. This paper describes the use of deterministic lateral displacement (DLD) to sort SSCs based on cell size and stiffness. DLD is a technology that uses arrays of micropillars to sort cells based on their diameter. Cell deformation within the device can change the cell size and affect sorting - here evidenced using human cell lines and by fractionation of expanded SSCs. Following sorting, SSCs remained viable and retained their capacity to form clonogenic cultures (CFU-F), indicative of stem cell potential. Additionally, larger BM cells showed enhanced capacity to form CFU-F. These findings support the theory that SSCs are more abundant within the larger BM cell fraction and that DLD, or other size-based approaches, could be used to provide enriched SSC populations with significant implications for stem cell research and translation to the clinic.

Cardiovascular Disease (CVD) is the most common cause of death in industrialized countries, and myocardial infarction (MI) is a major CVD with significant morbidity and mortality. Following MI, the left ventricle (LV) undergoes a wound healing response to ischemia that results in extracellular matrix (ECM) scar formation to replace necrotic myocytes. While ECM accumulation following MI is termed cardiac fibrosis, this is a generic term that does not differentiate between ECM accumulation that occurs in the infarct region to form a scar that is structurally necessary to preserve left ventricle (LV) wall integrity and ECM accumulation that increases LV wall stiffness to exacerbate dilation and stimulate the progression to heart failure. This review focuses on post-MI LV ECM remodeling, targeting the discussion on ECM biomarkers that could be useful for predicting MI outcomes., (Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.)

Background: The prevalence of lower extremity artery disease (LEAD) is high (20%-25%) in the population older than 65 years, but patients are seldom identified until the disease is advanced. Circulating markers of disease activity might provide patients with a key opportunity for timely treatment. We tested the hypothesis that measuring blood-specific fragments generated during degradation of the extracellular matrix (ECM) could provide further insight into the pathophysiologic mechanism of arterial remodeling., Methods: The protein profile of diseased arteries from patients undergoing infrainguinal limb revascularization was assessed by a liquid chromatography and tandem mass spectrometry, nontargeted proteomic approach. The information retrieved was the basis for measurement of neoepitope fragments of ECM proteins in the blood of 195 consecutive patients with LEAD by specific enzyme-linked immunosorbent assays., Results: Histologic and proteomic analyses confirmed the structural disorganization of affected arteries. Fourteen of 81 proteins were identified as differentially expressed in diseased arteries with respect to healthy tissues. Most of them were related to ECM components, and the difference in expression was used in multivariate analyses to establish that severe arterial lesions in LEAD patients have a specific proteome. Analysis of neoepitope fragments in blood revealed that fragments of versican and collagen type IV, alone or in combination, segregated patients with mild to moderate symptoms (intermittent claudication, Fontaine I-II) from those with severe LEAD (critical limb ischemia, Fontaine III-IV)., Conclusions: We propose noninvasive candidate biomarkers with the ability to be clinically useful across the LEAD spectrum., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Acute myocardial infarction (AMI) is often underdiagnosed in women. It is therefore of interest to identify biomarkers that indicate increased risk of AMI and thereby help clinicians to have additional focus on the difficult AMI diagnosis. Type I Collagen, a component of the cardiac extracellular matrix, is cleaved by matrix metalloproteinases (MMPs) generating the neo-epitope C1M. We investigated the association between serum-C1M and AMI and evaluated whether C1M is a prognostic marker for outcome following AMI. This study is based on The Prospective Epidemiological Risk Factor (PERF) Study including postmenopausal women. 316 out of 5,450 women developed AMI within the follow-up period (14 years, median). A multivariate Cox analysis assessed association between serum-C1M and AMI, and re-infaction or death subsequent to AMI. The risk of AMI increased by 18% (p = 0.03) when serum-C1M was doubled and women in the highest quartile had a 33% increased risk compared to those in the low quartiles (p = 0.025). Serum-C1M was, however not related to reinfarction or death subsequent to AMI. In this study C1M was be an independent risk factor for AMI. Measuring MMP degraded type I collagen could be useful for prediction of increased risk of AMI if replicated in other cohorts.

Introduction: Fine-needle aspiration (FNA) is a cornerstone in diagnosing thyroid nodules. For decades, Danish FNA has been categorised into the groups: "FNA not performed", "Inadequate", "Cystic", "Inconclusive", "Benign", "Suspicious", "Malignant" and "Information missing". Internationally, The Bethesda Classification System (TBCS) is increasingly accepted, especially owing to a detailed specification of FNA suspicious for malignancy. The Danish "Suspicious" group is very broad and includes atypia, follicular neoplasia and FNA suspicious of other malignancies. The purpose of this study was to apply TBCS to the Danish "Suspicious" FNA group and to estimate the frequency of malignancy in the individual Bethesda groups (BG)., Methods: This descriptive study is based on a prospective cohort from the THYKIR database. It includes 479 patients with a "Suspicious" FNA and surgical treatment in The Region of Southern Denmark from 2001 to 2013. Based on pathology records, FNA was classified according to the TBCS. Malignancy was determined by the histological diagnosis from the THYKIR database., Results: The Danish "Suspicious" group was allocated to the BG I, II, III, IV, V and VI with a malignancy risk of 36.4%, 13.3%, 17.2%, 16.1%, 55.3% and 88.2%, respectively., Conclusions: The Danish "Suspicious" group contains a broad spectrum of BG with varying malignancy risk. The results indicate a need for standardisation of the Danish FNA classification. A national introduction of the TBCS might secure an international and comparable standard., Funding: none., Trial Registration: not relevant., (Articles published in the Danish Medical Journal are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

African trypanosomes are responsible for significant levels of disease in both humans and animals. The protozoan parasites are free-living flagellates, usually transmitted by arthropod vectors, including the tsetse fly. In the mammalian host they live in the bloodstream and, in the case of human-infectious species, later invade the central nervous system. Diagnosis of the disease requires the positive identification of parasites in the bloodstream. This can be particularly challenging where parasite numbers are low, as is often the case in peripheral blood. Enriching parasites from body fluids is an important part of the diagnostic pathway. As more is learned about the physicochemical properties of trypanosomes, this information can be exploited through use of different microfluidic-based approaches to isolate the parasites from blood or other fluids. Here, we discuss recent advances in the use of microfluidics to separate trypanosomes from blood and to isolate single trypanosomes for analyses including drug screening.

Background: The identification of biomarkers that predict susceptibility to major depressive disorder and treatment response to antidepressants is a major challenge. Vortioxetine is a novel multimodal antidepressant that possesses pro-cognitive properties and differentiates from other conventional antidepressants on various cognitive and plasticity measures. The aim of the present study was to identify biological systems rather than single biomarkers that may underlie vortioxetine's treatment effects., Results: We show that the biological systems regulated by vortioxetine are overlapping between mouse and rat in response to distinct treatment regimens and in different brain regions. Furthermore, analysis of complexes of physically-interacting proteins reveal that biomarkers involved in transcriptional regulation, neurodevelopment, neuroplasticity, and endocytosis are modulated by vortioxetine. A subsequent qPCR study examining the expression of targets in the protein-protein interactome space in response to chronic vortioxetine treatment over a range of doses provides further biological validation that vortioxetine engages neuroplasticity networks. Thus, the same biology is regulated in different species and sexes, different brain regions, and in response to distinct routes of administration and regimens., Conclusions: A recurring theme, based on the present study as well as previous findings, is that networks related to synaptic plasticity, synaptic transmission, signal transduction, and neurodevelopment are modulated in response to vortioxetine treatment. Regulation of these signaling pathways by vortioxetine may underlie vortioxetine's cognitive-enhancing properties.

Kidney allograft failure due to chronic injury/rejection remains the main cause of graft loss in renal transplant recipients (RTR). Here, we investigated whether specific biomarkers of extracellular matrix (ECM) turnover are associated with allograft function and chronic kidney disease (CKD) stage in RTR. Seventy-eight patients who attended the University Medical Center Groningen for a routine check-up after kidney transplantation were enrolled in the study. Plasma and/or 24h-urine samples were collected and specific matrix-metalloproteinase-generated neo-epitope fragments of collagens were measured by enzyme-linked immunosorbent assay. Our results demonstrated that urinary levels of C3M, a marker for collagen type III degradation, correlated with estimated glomerular filtration rate (eGFR; r = 0.58, p<0.0001), with lower levels detected in the urine of patients with advanced CKD. In addition, plasma levels of Pro-C6, a marker for collagen type VI formation, significantly increased with disease progression and correlated with eGFR (r = -0.72, p<0.0001). Conversely, plasma C3M and urinary Pro-C6 levels showed no correlation with renal function. We identified two neo-epitope biomarkers of tissue turnover associated with ECM remodeling and fibrosis that can stratify patients by CKD stage. This is as promising first step towards non-invasive monitoring of ECM turnover in the kidneys.

Introduction: Fine-needle aspiration biopsy (FNAB) is the cornerstone of thyroid nodule evaluation. In most cases, FNAB can discriminate between benign and malignant disease. In other cases, it is only indicative of malignancy and the results are considered "suspicious". In Denmark, thyroid FNAB results are categorised into six groups: "inadequate", "cystic", "inconclusive", "benign", "suspicious" and "malignant". The risk of malignancy in the Danish "suspicious" group is of interest for patients as well as doctors participating in the diagnosis and treatment. The Danish Thyroid Surgery Database (THYKIR) registers preoperative thyroid FNAB and final histology. The aim of this study was to assess the malignancy risk among patients with a suspicious thyroid FNAB according to the Danish criteria and to identify possible predictors of malignant histology., Methods: A prospective cohort counting 483 patients with a "suspicious" thyroid FNAB who had been treated surgically in The Region of Southern Denmark in the 2001-2013 period was retrieved from the THYKIR database., Results: The risk of malignancy in the Danish thyroid FNAB "suspicious" group is 22%. Serum thyroid-stimulating hormone outside the normal range and vocal cord palsy may be patient-related predictors of malignancy., Conclusion: Awaiting the introduction of reliable tools for preoperative evaluation, the current practice with histo-logical clarification of the "suspicious" thyroid FNAB seems justified., Funding: none., Trial Registration: not relevant.

Recent advances in cell sorting aim at the development of novel methods that are sensitive to various mechanical properties of cells. Microfluidic technologies have a great potential for cell sorting; however, the design of many micro-devices is based on theories developed for rigid spherical particles with size as a separation parameter. Clearly, most bioparticles are non-spherical and deformable and therefore exhibit a much more intricate behavior in fluid flow than rigid spheres. Here, we demonstrate the use of cells' mechanical and dynamical properties as biomarkers for separation by employing a combination of mesoscale hydrodynamic simulations and microfluidic experiments. The dynamic behavior of red blood cells (RBCs) within deterministic lateral displacement (DLD) devices is investigated for different device geometries and viscosity contrasts between the intra-cellular fluid and suspending medium. We find that the viscosity contrast and associated cell dynamics clearly determine the RBC trajectory through a DLD device. Simulation results compare well to experiments and provide new insights into the physical mechanisms which govern the sorting of non-spherical and deformable cells in DLD devices. Finally, we discuss the implications of cell dynamics for sorting schemes based on properties other than cell size, such as mechanics and morphology.

Ethnopharmacological Relevance: The present study was carried out to investigate the traditional use, pharmacology and active compounds of four plants commonly used as excipients in herbal medicine in Ghana., Materials and Methods: A comprehensive literature search was conducted to gain knowledge about the traditional use, pharmacology and active compounds of the four plant excipients. The broth dilution antibacterial assay and the DPPH radical scavenging antioxidant assay were used to evaluate the antibacterial and antioxidant activity of the plants, respectively. Ethanol, warm water and cold water extracts were prepared from the dried seeds/fruits of Aframomum melegueta, Piper guineense, Xylopia aethiopica and Monodora myristica, and tested in the assays., Results: A. melegueta and P. guineense seemed to act as pharmacoenhancers, since they have been shown to inhibit specific CYP-enzymes. A. melegueta could act as an antioxidant to preserve herbal preparations. None of the plant excipients had antibacterial activity against the bacteria tested in this study. Compounds with an aromatic or pungent smell had been identified in all the plant excipients. An explanation for the use of the plants as excipients could rely on their taste properties., Conclusion: The present study suggests that there may be more than one simple explanation for the use of these four plants as excipients. Plausible explanations have been proven to be: (1) a way to increase the effect of the medicine, (2) a way to make the medicine more palatable or (3) a way to preserve the activity of the medicinal preparation over time., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of this study was to examine the general psychological functioning of patients suffering from bulimia nervosa (BN) using the Karolinska Psychodynamic Profile (KAPP). Furthermore, KAPP data and data from the Reflective Functioning scale (RF), measuring the ability to mentalize, were combined in order to examine differences in alexithymia, impulse control and affect regulation in patients with high or low RF., Method: Seventy patients with BN were interviewed with both the KAPP and the Adult Attachment Interview (AAI) from which RF is coded. Differences in KAPP scores of patients with high or low RF were analyzed., Results: Most of the patients with BN were found to have a personality structure within the normal or neurotic range (n=50 of 70). BN patients with a high RF had significantly lower scores on KAPP's alexithymia scale than patients with a low RF score, demonstrating that poor mentalizing is related to alexithymia. Concurrently, patients with high RF showed problems with impulse control and coping with aggressive affects according to KAPP scores., Conclusion: Although BN patients with high RF showed good capacities for describing their mental states, they still had difficulties regulating the emotions and impulses related to these states., Significant Outcome: Among patients suffering from BN, patients with high RF were significantly less alexithymic than low RF patients., Limitations: The findings of this study are limited by the relatively small numbers of participants especially in the RF subgroups, posing a danger of not finding as significant existing differences in character pathology between high and low RF groups., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The theory of mentalization has recently been applied in the area of eating disorders (Skårderud 2012). This article reports a qualitative study based on interviews with five women suffering from bulimia nervosa. All five scored high on the Reflective Functioning Scale, indicating a highly developed ability to mentalize. The present qualitative study, which focuses on the women's capacity to relate to and regulate affects, supports the finding that they are relatively skilled at reflecting on their own and others' thoughts and emotions. However, this highly developed capacity for mentalization is apparently not helping them regulate their emotions. This suggests that the capacity to mentalize may not be as closely related to the capacity to regulate affects as Fonagy et al. (2002) have proposed. Indeed, the concept of mentalization may be overinclusive and in need of stricter definition. Thus, it might be envisaged that while the ability to mentalize is closely related to the ability to put feelings into words (the opposite of alexithymia), an ability to mentalize may not necessarily entail a capacity to regulate affects. Finally, the study illustrates that far from all eating-disordered patients have problems mentalizing., (© 2015 by the American Psychoanalytic Association.)

Objective: Few studies have reported procedure complications or adverse events for transcatheter interventions in unselected congenital heart disease cohorts. We report our 23-year experience with transcatheter interventions in congenital heart disease and examine predictors for adverse events., Design and Setting: This study was a population-based cohort study of children and adults with congenital heart disease, covering a population of 3 million inhabitants in western Denmark. Adverse events were subdivided into 5 levels according to their severity. Procedure-type risk category, age, weight, and year of procedure were included in multivariate logistic models to identify risk factors for adverse events., Results: Between 1990 and 2012, 1595 patients had 1878 catheter-based interventions performed. We identified 241 adverse events, corresponding to 13% of the procedures; 58 (3%) were considered to be of high severity. During the study period, there was an increase in number of procedures per year (P < .001) and a decrease in frequency of adverse events (P = .01). Procedure-type categories 3 and 4 had increased risk of adverse events when compared with category 2, with odds ratios of 1.7 (95% confidence interval [CI]: 1.2-2.3) for category 3 and 2.3 for category 4 (95% CI: 1.4-3.6). Age and weight at catheterization were not independently associated with adverse events., Conclusions: We found an increase in number of procedures over time and a decrease in frequency of adverse events. Higher procedure-type risk categories were associated with increased risk of adverse events., (© 2014 Wiley Periodicals, Inc.)

Objective: Platypnoea-orthodeoxia is a rare cause of dyspnoea and hypoxaemia induced by a change from supine to upright position resulting in veno-arterial shunting, usually through a patent foramen ovale. We aimed to describe our experience with closure of a patent foramen ovale in patients with platypnoea-orthodeoxia, and to increase awareness of this diagnosis., Design: Eight patients (mean age 63 ± 12 years) were identified from hospital records between 2000 and 2013., Results: The underlying diseases were aortic aneurism (n = 3), cardiac transplantation (n = 2), left ventricular dilatation (n = 1), pulmonary fibrosis (n = 1), and recurrent pleural/pericardial effusion (n = 1). At presentation, mean oxygen saturation was 81 ± 8% in the upright position. All patients underwent transthoracic and transoesophageal echocardiography. Pulmonary pressures were normal at rest in all patients. A right-to-left shunt through a patent foramen was demonstrated after changing posture from supine to sitting. Closure of the patient foramen ovale was performed uncomplicated in all patients. Mean oxygen saturation post-procedure was 96 ± 2%. All but one patient experienced marked symptom relief., Conclusion: The majority of patients with platypnoea-orthodeoxia can benefit from treatment of the underlying condition. In the present cohort, patients underwent uncomplicated catheter-based closure of the patient foramen ovale with subsequent improvement of oxygen saturation and symptom improvement.

Gergely and colleagues' state that their "Social Biofeedback Theory of Parental Affect Mirroring" can be seen as a kind of operationalization of the classical psychoanalytic concepts of holding, containing and mirroring. This article examines to what extent the social biofeedback theory of parental affect mirroring may be understood as a specification of these concepts. It is argued that despite similarities at a descriptive level the concepts are embedded in theories with different ideas of subjectivity. Hence an understanding of the concept of affect regulation as a concretization and specification of the classical concepts dilutes the complexity of both the concept of affect regulation and of the classical concepts., (Copyright © 2014 Institute of Psychoanalysis.)

Objectives: We investigated whether open-heart surgery with the use of extracorporeal circulation has an impact on menstrual bleeding., Methods: The menstrual bleeding pattern was registered in fertile women undergoing open-heart surgery in 2010-12. Haematocrit and 24-h postoperative bleeding were compared with those of men undergoing cardiac surgery., Results: Women (n = 22), with mean age of 36 (range 17-60) years, were operated on and hospitalized for 4-5 postoperative days. The mean preoperative haematocrit was 40% (range 32-60%), and mean haematocrit at discharge was 32% (range 26-37%). Mean postoperative bleeding in the first 24 h was 312 (range 50-1442) ml. They underwent surgery for atrial septal defect (n = 5), composite graft/David procedure (n = 4), pulmonary or aortic valve replacement (n = 6), myxoma (n = 2), mitral valvuloplasty (n = 2), ascending aortic aneurysm (n = 1), aortic coarctation (n = 1) and total cavopulmonary connection (n = 1). Unplanned menstrual bleeding (lasting 2-5 days) was detected in 13 (60%) patients. Of them, 4 were 1-7 days early, 4 were 8-14 days early, 3 were 1-7 days late and 2 had menstruation despite having had menstrual bleeding within the last 2 weeks. None had unusually large or long-lasting menstrual bleeding. Ten women took oral contraceptives, 8 of whom had unexpected menstrual bleeding during admission. Men (n = 22), with a mean age of 35 (range 17-54) years, had mean bleeding of 331 (range 160-796) ml postoperatively, which was not statistically significantly different from the women's. The mean preoperative haematocrit was 40% (range 29-49%) among men, while haematocrit at discharge was 32% (28-41), not significantly different from that seen in the female subgroup., Conclusions: Menstrual bleeding patterns are disturbed by open-heart surgery in the majority of fertile women. Nevertheless, the unexpected menstrual bleeding is neither particularly long-lasting nor of large quantity, and the postoperative surgical bleeding is unaffected. We recommend that information about menstrual cycle disturbances related to cardiac surgery be provided, but no special precautions be taken, when operating on women of fertile age.

Objective: To test whether a complex intervention facilitating early cancer rehabilitation by involvement of the general practitioner (GP) soon after diagnosis improves patients' satisfaction with their GPs., Design: A cluster randomised controlled trial. All general practices in Denmark were randomised to an intervention or a control group before the start of the study. Patients included those with cancer who were subsequently allocated to either group based on the randomisation status of their GP., Participants: Adult patients with cancer treated for incident cancer at the public regional hospital (Vejle Hospital, Denmark) were included between May 2008 and February 2009. A total of 955 patients registered with 323 practices were included, of which 486 patients were allocated to the intervention group and 469 to the control group., Intervention: The intervention included a patient interview assessing the need for rehabilitation, improved information from the hospital to GPs including information on the patients' current needs along with information about needs of patients with cancer in general. Further, GPs were encouraged to proactively contact the patients and facilitate the patients' rehabilitation course., Outcome Measures: 6 months after inclusion of the patient, patient satisfaction with their GP during the last 12 months in five different dimensions of GP care was assessed using the Danish version of the EuroPEP (European Patients Evaluate General Practice Care) questionnaire (DanPEP). 14 months after inclusion, patient satisfaction with the GP regarding the cancer course and GP's satisfaction with own contribution to the patients' rehabilitation course were assessed using ad hoc questions specifically designed for this study., Results: No overall effect of the intervention was observed. Subgroup analysis of the patients with breast cancer showed statistically significant improvement of satisfaction with the GP in two of the five DanPEP dimensions., Conclusions: This complex intervention aiming at improving GPs' services in cancer rehabilitation had no impact on patient satisfaction., Trial Registration: ClinicalTrials.gov, registration ID number NCT01021371.

Progressive cyanosis often develops following Kawashima operation in patients with left atrial isomerism, interrupted inferior vena cava and hepatic veins draining to the atria. Knowledge on the timing and extend of resolution following hepatic venous redirection is sparse. A girl developed progressing cyanosis following Kawashima operation at the age of ten months. Arterial oxygen saturations at rest dropped to 60-65%. Surgical redirection of hepatic veins into the cavopulmonary circulation at the age of three years had no immediate effect. However, arterial oxygen saturations increased gradually over nine months to 90-93% and 95-100% after three years.

Background: Two conceptually different morbidity outcomes unmet needs and health-related quality of life are used to identify cancer patients in need of clinical attention and to evaluate rehabilitation programmes. The knowledge on the interrelation between unmet needs and health-related quality of life is scarce. This paper studies the hypothesis that patient-perceived unmet needs of rehabilitation during the cancer trajectory are associated with decreased quality of life., Material and Methods: Based on registers, a Danish population-based cohort of adult, incident, mixed-site cancer patients diagnosed between 1 October 2007 and 30 September 2008 was established. At 14 months following diagnosis participants completed a questionnaire including health-related quality of life (EORTC QLQ C-30), psychological distress (POMS-SF), and unmet needs with regard to physical, emotional, family-oriented, sexual, work-related, and financial problems. Unmet needs were assessed through six ad hoc questions., Results: Questionnaires were received from 3439 of 4947 patients, resulting in a response rate of 70%. The three most frequent cancer types were breast (28.4%), prostate (14.6%) and colorectal cancer (15.2%). Overall, 60.1% expressed an unmet need of rehabilitation in at least one area, physical and emotional problems being the most frequent (40.0% and 37.5%). For all scales of the EORTC QLQ C-30 and POMS, significant adjusted mean differences were observed between patients with unmet needs in at least one area and patients with no unmet needs (p-values < 0.001). These differences were well above levels usually considered clinically relevant. Further, impairment increased with increasing number of areas in which unmet needs were reported., Discussion: We confirmed the hypothesis that patient-perceived unmet needs of rehabilitation during the cancer trajectory are associated with decreased quality of life. This study supports the use of unmet needs questions to identify patients in need of clinical attention. Interventions reducing cancer patients' perceived needs of rehabilitation may enhance quality of life.

Objectives: In a healthcare system with equal access we analysed possible associations between cancer survivors' socioeconomic status (SES) and their: 1) need for rehabilitation; 2) participation in rehabilitation activities; and 3) unmet needs for rehabilitation in a 14-month period following date of diagnosis., Methods: A population-based cohort study including incident cancer patients diagnosed from 1 October 2007 to 30 September 2008 in Denmark. Fourteen months after diagnosis participants completed a mailed out questionnaire developed to measure different aspects and dimensions of rehabilitation. Individual information on cohabitation status, education, income and labour market status was retrieved from national registers. Logistic regression analyses were used to explore associations between socioeconomic status and rehabilitation outcomes., Results: A total of 3439 patients responded (70%). Significant interactions between SES and sex were demonstrated and further analyses were therefore stratified for gender. In general, women and to a lesser extent men with short education and low income participated less often in activities and had in some areas more unmet needs. Women living alone more often expressed a rehabilitation need in the physical, emotional and financial area and had to a higher extent unmet needs in a number of areas. Men living alone and men outside the workforce had increased odds of unmet needs in the physical area., Conclusions: Despite equal access to care, SES had a significant impact on cancer survivors' rehabilitation. In general, the associations were most pronounced for female cancer patients. We suggest that special attention should be paid to socioeconomically disadvantaged groups by taking into account differences in SES in a clinical setting and when developing targeted rehabilitation programmes.

Unlabelled: Few studies have evaluated initiatives targeting implementation of cancer rehabilitation. In this study we aim to test the effects of a complex intervention designed to improve general practitioners' (GPs) involvement in cancer rehabilitation. Outcomes were proactive contacts to patients by their GP reported by the patients and GPs, respectively, and patients' participation in rehabilitation activities., Methods: Cluster randomised controlled trial. All general practices in Denmark were randomised to an intervention group or to a control group (usual procedures). Patients were subsequently allocated to the intervention or the control group based on randomisation status of their GP. Between May 2008 and February 2009, adult patients treated for incident cancer at Vejle Hospital, Denmark, were assessed for eligibility. A total of 323 general practices were included, allocating 486 patients to an intervention and 469 to a control group. The intervention included a patient interview about rehabilitation with a rehabilitation coordinator at the hospital, comprehensive information to the GP about individual needs for rehabilitation, and an encouragement to the GP to contact the patient proactively. Questionnaires were administered to patients and GPs at 14 months after inclusion., Results: At baseline average age of patients was 63 years and 72% were female. The most frequent cancer localisations were breast (43%), lung (15%), and malignant melanoma (8%). The intervention had no effect on either patient- or GP-reported extent of GP proactivity. Further, no effect was observed on patient participation in rehabilitation activities during the 14-month follow-up period., Discussion: The intervention had no effect on GP proactivity or on patient participation in rehabilitation activities. However, analyses showed a significant association between proactivity and participation and we, therefore, conclude that increased GP proactivity may facilitate patient participation in rehabilitation activities.

These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had frozen ovarian tissue transplanted, and two women underwent fresh ovarian tissue transplants. The function of ovarian cortical strips has continued for more than 7 years in these three women, with the birth of eight healthy babies following a single graft per patient. In addition to these three cases, transplantation (repeatedly in some cases) of cryopreserved ovarian tissue has restored reproductive function to all other women in the study centres' programmes for some years. The sustained longevity of function of the transplanted tissue suggests that it may also be possible to postpone the normal time of menopause or to alleviate its symptoms., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: This study is the first to evaluate the reflective functioning abilities of patients suffering from bulimia nervosa (BN)., Method: Seventy patients fulfilling Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for BN were interviewed with the Adult Attachment Interview, which was subsequently coded for reflective functioning (RF)., Results: On average, the sample of patients suffering from BN had close to normal mentalizing abilities. However, the distribution of RF scores was significantly different from the distribution of RF in a non-clinical control group, showing a more polarized pattern with more low and high RF scores., Conclusion: The study indicates that the theory of mentalization may contribute to understanding BN. However, bulimic pathology may develop and be maintained despite good mentalizing abilities., (Copyright © 2012 John Wiley & Sons, Ltd and Eating Disorders Association.)

Objective: To test the hypothesis that a multimodal intervention giving the general practitioner (GP) an enhanced role in cancer rehabilitation improves patients' health-related quality of life and psychological distress., Design: Cluster randomised controlled trial. All general practices in Denmark were randomised to an intervention group or to a control group. Patients were subsequently allocated to intervention or control (usual procedures) based on the randomisation status of their GP., Setting: All clinical departments at a public regional hospital treating cancer patients and all general practices in Denmark., Participants: Adult patients treated for incident cancer at Vejle Hospital, Denmark, between 12 May 2008 and 28 February 2009. A total of 955 patients (486 to the intervention group and 469 to the control group) registered with 323 general practices were included., Intervention: The intervention included an interview about rehabilitation needs with a rehabilitation coordinator at the regional hospital, information from the hospital to the GP about individual needs for rehabilitation and an encouragement of the GP to contact the patient to offer his support with rehabilitation., Main Outcome Measures: The primary outcome was health-related quality of life measured 6 months after inclusion using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Secondary outcomes included quality of life at 14 months and additional subscales of the EORTC QLQ-C30 at 6 and 14 months and psychological distress at 14 months using the Profile of Mood States Scale., Results: No effect of the intervention was observed on primary and/or secondary outcomes after 6 and 14 months., Conclusion: A multimodal intervention aiming to give the GP an enhanced role in cancer patients' rehabilitation did not improve quality of life or psychological distress., Trial Registration: ClinicalTrials.gov, registration ID number NCT01021371.

While size has been widely used as a parameter in cellular separations, in this communication we show how shape and deformability, a mainly untapped source of specificity in preparative and analytical microfluidic devices can be measured and used to separate cells.

Background: We investigated the natural history, outcomes of myectomy, and impact on survival of obstructive hypertrophic cardiomyopathy (HCM) in childhood., Methods: All 120 children diagnosed with HCM between 1971 and 2006 were studied. Available echocardiograms (n=685) were incorporated in regression analyses adjusted for repeated measures. Multiphase parametric models and competing risks methodology were used to define outcomes., Results: Left ventricular outflow tract (LVOT) obstruction (peak gradient>30 mm Hg) developed in 61 (50%) of the cohort. Onset of obstructive features occurred during 2 discrete periods of risk; either during infancy (within 3 years of age), or otherwise later during early adolescence and beyond. Among children with obstructive HCM, the following 2 distinct groups were apparent: (1) those with peak LVOT gradients less than 65 mm Hg showed hemodynamic improvement (p<0.001) with medical strategies; and (2) those with peak gradients greater than 65 mm Hg instead had accelerated septal hypertrophy (p<0.001) with progression of peak gradients (p<0.01), and therefore underwent myectomy. Myectomy restored the gradient (mean 57 mm Hg reduction, 95% confidence interval 25 to 88, p<0.01) to nonobstructive levels. Furthermore, peak gradients and septal hypertrophy did not progress thereafter; they instead mirrored the natural history of nonobstructive HCM. Overall, in our experience, obstructive disease (or need for myectomy) did not influence late risk of death compared with children with nonobstructive HCM., Conclusions: Obstructive HCM is phenotypically heterogeneous in childhood. Peak gradients less than 65 mm Hg respond well to nonsurgical management. The patient subset with higher gradients (>65 mm Hg) instead responds poorly and early myectomy should be pursued. Reassuringly, late survival in this cohort was not compromised by development of obstructive symptoms., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A 84 year-old woman was transferred to the ENT ward for treatment of epistaxis. An anterior rhinoscopy revealed a posterior bleeding source which was cauterised. A submucosal bulge was found in the cavity floor and biopsied. Histologic examination showed diffuse large B-cell lymphoma. Oncologic examination disclosed Ann Arbor stage 1A. The patient was treated with chemotherapy followed by involved field radiation therapy. She responded well to the therapy. Intranasal lymphoma is rare in Denmark with an incidence rate of 0,1-0,2 per 100,000 per year.

Objectives: The Risk Adjusted Classification for Congenital Heart Surgery can predict early mortality. However, the relation to long-term outcome in terms of mortality and morbidity is unknown., Design: We did a population-based follow-up study of 801 children undergoing congenital heart surgery between 1996 and 2002. All patients were followed from surgery until death or January 1, 2008. Operations were classified according to the Risk Adjusted Classification for Congenital Heart Surgery. Each patient was matched by age and sex with 10 population controls. Cox regression analysis, area under the receiver operator curve and competing risk analysis were used for the analyses., Results: Overall follow-up was 99.6%. The distribution of the Risk Adjusted Classification for Congenital Heart Surgery was: Category one 20%, category two 37%, category three 27%, category four 8%, category five 0% and category six 2%. Overall survival after a median follow-up of 8.2 years was 86% (95% confidence interval: 83-88%), with 54 early deaths occurring within 30 days after surgery and 57 late deaths. Long-term survival in those who were alive 30 days after surgery was 92% (90-94%); ranging from 98% (93-100%) in risk category one to 33% (5-68%) in category six. Survival overall and beyond 30 days was lower in each risk category than in controls (P < .001). During follow-up, 124 (15%) patients had new operations and 106 (13%) catheter-based interventions. These events were more frequent in category three, four, and six compared with category one, with no difference between category one and two. The area under the receiver operator curve for long-term mortality was 0.81 (95% confidence interval 0.75-0.87)., Conclusions: Children operated for congenital heart disease have impaired survival and often undergo new operations or catheter-based interventions. The risk of these events is related to the surgical complexity according to the Risk Adjusted Classification for Congenital Heart Surgery., (© 2011 Copyright the Authors. Congenital Heart Disease © 2011 Wiley Periodicals, Inc.)

We present the use of a simple microfluidic technique to separate living parasites from human blood. Parasitic trypanosomatids cause a range of human and animal diseases. African trypanosomes, responsible for human African trypanosomiasis (sleeping sickness), live free in the blood and other tissue fluids. Diagnosis relies on detection and due to their often low numbers against an overwhelming background of predominantly red blood cells it is crucial to separate the parasites from the blood. By modifying the method of deterministic lateral displacement, confining parasites and red blood cells in channels of optimized depth which accentuates morphological differences, we were able to achieve separation thus offering a potential route to diagnostics.

Background: The effect of interventions that support rehabilitation among cancer patients has to be tested before implementation., Objective: A randomised controlled trial was conducted to test the hypothesis that a multimodal intervention may give the general practitioner (GP) an enhanced role and improve rehabilitation for cancer patients. The intervention included an interview about rehabilitation needs with a rehabilitation coordinator (RC), information from the hospital to the general practitioner about individual needs for rehabilitation and an incentive for the GP to contact the patient about rehabilitation. The objective of this first report from the study was to examine the acceptability and feasibility of the intervention., Material and Methods: Adult patients treated for incident cancer at Vejle Hospital, Denmark were included between May 12, 2008 and February 28, 2009. All general practices in Denmark were randomised. Patients were allocated to intervention or control (usual procedures) based on the randomisation status of their GP. The feasibility of the intervention was analysed with regard to recruitment of patients, acceptability by patients and GPs and the degree to which the planned contacts between patients, RCs and GPs were implemented. The primary outcome of the randomised controlled trial (RCT) will be health-related quality of life at six months (EORTC-30)., Results: Following assessment of 1 896 cancer patients, 955 patients (50%) registered with 323 general practices were included. The interview was conducted at the hospital with 50% of the patients in the intervention group, 31% were contacted by phone. Patients valued the fact that the conversation was dedicated to needs beyond the medical treatment. The GPs were generally available for information by phone and positive towards having a central role in the cancer rehabilitation., Discussion: It was feasible to conduct a RCT to evaluate a complex intervention in the healthcare system. All elements of the intervention were acceptable and feasible and may be implemented in future practice if the effect is positive.

Study Design: Comparison of in vivo biomechanical outcomes between experimental and control group animals., Objective: To quantify the in vivo bulging response of the inner and outer annulus in animals with and without disc degeneration., Summary of Background Data: Prior attempts to quantify the load-deformation response of the inner annulus have most often relied on in vitro preparations. Unfortunately, to visualize the inner annulus, these in vitro approaches rely on disc modifications that may result in nonphysiologic behaviors. In response to this problem, in vivo techniques were developed to quantify regional bulging of the inner and outer annulus during applied axial loading., Methods: Two groups of pigs were tested: a normal group and a group having disc degeneration that was induced surgically 3 months earlier. Eight adolescent pigs were evaluated and for each animal, a miniature servohydraulic actuator was attached to the third and fourth lumbar vertebrae to deliver a cyclic axial loading protocol (300 N, 1 Hz, 10 cycles) whereas regional deformations of the annulus were visualized ultrasonically via retroperitoneal access., Results: For the normal animals, image analysis demonstrated a significantly greater bulging of the inner annular region when compared with the outer annular region. In animals with disc degeneration, the inner and outer annular regions were equal in their bulging response, which ranged from 0 bulging to 37% greater than the average response of the normal animals., Conclusions: This work supports prior in vitro studies that observed maximal disc bulging in the inner annulus and minimal bulging in the external annulus. Results for this in vivo study suggest that this normal bulging gradient is lost with degenerative disc disease. Compared with in vitro approaches, this new in vivo technique has the potential to demonstrate disc behavior in a variety of loading conditions and/or with a variety of induced disc pathologies.

Introduction: Previously, the Mustard operation was the preferred surgical technique in patients with transposition of the great arteries. After this procedure the anatomical right ventricle remains the systemic ventricle, which entails long-term complications, especially heart failure. The Mustard-operated patients are now adults, and pregnancy has become an important issue. We assessed pregnancy and delivery data in a complete cohort of female patients who had previously undergone a Mustard procedure at Aarhus Hospital in the 1971-1991 period. The women giving birth were compared with those who did not., Material and Methods: Information on diagnosis, procedure, functional status, pregnancy, delivery and congenital heart disease in the off-spring were found in registers (The National Register of Health, The National Birth Register) and in medical records. Questionnaires were mailed to the 16 surviving women over 15 years of age., Results: Four women gave birth to nine children. Two women temporally had heart symptoms during pregnancy and delivery, but this caused no objective changes. The women who had children were older than those who did not. None of the children had congenital heart disease nor were they small for their gestational age., Conclusion: Pregnancy and delivery are well-tolerated in the vast majority of Mustard-operated women with no deterioration in functional class during or after pregnancy and delivery.

Objective: We reviewed our experience with mechanical valves inserted between 1988 and 2002 in children aged 15 years or younger., Methods: Hospital files were extracted retrospectively. Follow-up was completed by March 2005., Results: Of 41 patients, we inserted a valve in atrioventricular position in 27 children, having a median age of 3.1 years, ranging from 0.4 to 14.5 years, and in aortic position in the remaining 14, having a median age of 13.5 years, and a range from 7.0 to 14.9 years. For the valves inserted in atrioventricular position, the underlying disease was congenital in 23, rheumatic in two, post-endocarditic in one, and Marfan's syndrome in one. Mean follow-up was 7.7 years, with standard deviation of 5.3, giving a total follow-up of 209 patient years. Mortality at 30 days was 7%, and survival was 73% at up to 16 years follow-up. Events related to anticoagulation were seen in 3 patients, corresponding to 1.4% per patient year. In 6 patients (22%), heart block ensued which required implantation of a pacemaker treatment, and 5 patients (19%) had reoperations. For the implantations in aortic position, the underlying disease was congenital in 13, stenosis in 10 and insufficiency in three, and post-endocarditis in one. Mean follow-up was 6.8 years, with standard deviation of 4.6, giving a total of 95 patient years. We lost one patient within 30 days (7.7% mortality), and survival was 77% at up to 13 years follow-up. There were no incidents of thrombosis, nor events related to anticoagulation, but one patient (7%) needed insertion of a pacemaker due to a perioperative heart block, and one (7%) required new valvar replacement., Conclusions: Although preferably avoided, mechanical valves can be implanted in children with an acceptable mortality and morbidity, and good long-term results.

Risk adjustment for specialties covering many diagnoses is difficult. The Risk Adjusted classification for Congenital Heart Surgery (RACHS-1) was created to compare the in-hospital mortality rate of groups of children undergoing surgery for congenital heart disease. We applied the classification to the operations performed at Skejby Sygehus (1996-2002) and found that RACHS-1 can be used to predict the in-hospital mortality rate and length of stay in the intensive care unit in a Danish center for congenital heart surgery. The mortality rate was similar to that reported by larger centers.

Aims: Low back pain (LBP) is a major public health problem in both Norway and Sweden. The aim of the study was to estimate the prevalence of LBP and sickness absence due to LBP in two neighbouring regions in Norway and Sweden. The two areas have similar socioeconomic status, but differ in health benefit systems., Methods: A representative sample of 1,988 adults in Norway and 2,006 in Sweden completed questionnaires concerning LBP during 1999 and 2000. For this study only individuals in part or full time jobs, (n = 1,158 in Norway and n = 1,129 in Sweden) were included., Results: In Norway the lifetime prevalence was 60.7% and in Sweden 69.6%, the one-year prevalence was 40.5% and 47.2%, and the point prevalence 13.4% and 18.2% respectively. There was a significantly higher risk of reporting LBP in Sweden, even after controlling for gender, age, education, and physical workload. There was no difference in risk of self-certified short-term sickness absence (1-3 days), but it was a 40% lower risk of sickness absence with medical sickness certification in Sweden compared with Norway., Conclusion: The prevalence of LBP was higher in the Swedish area than in the Norwegian. The risk of self-certified sickness absence, however, showed no differences and the risk of medically certified sickness absence was lower in the Swedish area. This contradiction might partly be explained by the economical "disincentives" in the Swedish health compensation system.

Objective: The Risk Adjusted classification for Congenital Heart Surgery (RACHS-1) was created in order to compare in-hospital mortality for groups of children undergoing surgery for congenital heart disease. The method was evaluated with two large multi-institutional data sets-the Paediatric Cardiac Care Consortium (PCCC) and Hospital Discharge (HD) data from three states in the USA. The RACHS-1 classification was later applied to a large German paediatric cardiac surgery population in Bad Oeynhausen (BO), where it was found that the RACHS-1 categories were also associated with length of stay. We applied the RACHS-1 classification to the 957 operations performed during January 1996 to December 2002 at Skejby Sygehus, Denmark and we examined the association between the RACHS-1 categories, in-hospital mortality and length of stay in the Intensive Care Unit., Methods: The operations were classified according to the six RACHS-1 categories by matching the procedure of each patient with a risk category. The ability of the RACHS-1 classification to predict mortality in our population was examined by estimating the area under the receiver operator characteristic (ROC) curve. Likelihood ratio chi(2) tests were used to compare the distribution of RACHS-1 categories and the distribution of mortality with PCCC, HD and BO. Linear regression was used to examine the correlation between the RACHS-1 categories and length of stay in the Intensive Care Unit., Results: The RACHS-1 category frequencies in our population were: category 1: 18.4%, category 2: 37.4%, category 3: 34.6%, category 4: 8.2%, category 5: 0% and category 6: 1.5%. The overall ability of the RACHS-1 classification to predict in-hospital mortality (area under the ROC curve 0.741; 95% confidence interval=0.690; 0.791) was equal to the findings from larger populations. We found no differences in the category specific mortality when comparing with the larger reported series. There was a positive association between RACHS-1 category and length of stay in the Intensive Care Unit., Conclusions: The RACHS-1 classification can also be used to predict in-hospital mortality and length of stay in the Intensive Care Unit in a small volume centre.

Study Design: The diagnostic performance of a newly described variable was assessed in an in vivo model of disc degeneration using a split-pair experimental design., Objective: To determine if vertebral displacement measures generated from ultrasonic indentation could distinguish between experimental and control groups of animals., Summary of Background Data: Few procedures are available that noninvasively assess subcutaneous vertebral mechanics. Information from such a procedure would be of value in determining potential clinical relevance of spinal mechanics with respect to low back pain., Methods: Eight adolescent pigs underwent endplate perforation surgery to initiate lumbar disc degeneration. After 4 months of recovery, these and eight age-matched controls were assessed by ultrasonic indentation, a noninvasive procedure that quantifies vertebral displacements in the plane of loading-indentation. Each animal then received a facetectomy and was reindented at the same location as confirmed by ultrasonic imaging. Discal materials were removed postmortem for analysis., Results: Degenerative discs exhibited morphologic changes consistent with early degenerative disc disease. Prefacetectomy comparison of vertebral displacement measures between control and experimental animals resulted in sensitivity, specificity, and diagnostic accuracy values of 75.0%, 83.3%, and 77%, respectively. After facetectomy these values increased to 87.5%, 83.3%, and 85%, respectively. These measures of diagnostic performance were comparable or superior to those of existing clinical techniques (invasive or otherwise) used to assess degenerative conditions of the spine., Conclusions: The results of this study suggest that noninvasive measures of vertebral displacement are clinically significant and possess the additional advantages of being objective and noninvasive.

Study Design: A porcine model was used to study whether muscular activation in the paraspinal muscles caused by nerve stimulation in the anulus fibrosus of a lumbar intervertebral disc could be altered by saline injection into the zygapophysial (facet) joint., Objectives: To elucidate possible mechanisms regarding the nerve pathways and interactions between the intervertebral disc, zygapophysial joints, and the paraspinal musculature., Summary of Background Data: The physiologic basis for chronic low back pain, including muscular spasm, is uncertain. Although extensive research involving the lumbar motion segments and the surrounding tissues has been performed, the neuromuscular connection has not been sufficiently investigated., Materials and Methods: Twenty-three adolescent pigs were used to measure the electromyographic response in the paraspinal musculature to electrical stimulation of the posterolateral L3-L4 anulus fibrosus, before and after introduction of physiologic saline into the zygapophysial joint. Motor unit action potentials were recorded using three sets of needle electrodes placed into the deepest fascicles of the multifidus, bilateral to the L4 and L5 spinous processes, and into the central longissimus musculature, bilateral to the L4 spinous process., Results: Stimulation of the nerves within the posterolateral anulus of the disc elicited reactions in the paraspinal muscles, namely the lumbar multifidus and longissimus. Introduction of physiologic saline into the zygapophysial joint resulted in a reduction in the motor unit action potential amplitude. This reduction was manifested as an immediate and constant reduction, a graded reduction, or a delayed reaction, during which the reduction occurred an average of 5 minutes after the saline injection., Conclusions: Introduction of physiologic saline into the zygapophysial joint reduced the stimulation pathway from the intervertebral disc to the paraspinal musculature. The zygapophysial joints may therefore have a regulating function, controlling the intricate neuromuscular balance in the lumbar motion segment.

Study Design: Experimental models of intervertebral disc and facet joint degeneration were created in vivo in the porcine lumbar spine for studying spinal kinematics, using a dynamic technique., Objectives: To quantify the changes in spinal kinematics and the stabilizing capacity of the lumbar musculature caused by chronic lesions in the intervertebral disc and facet joints., Summary of Background Data: Segmental kinematics are detrimentally altered by acute injury to passive structures of the motion segment. However, stimulation of the surrounding musculature adds stability to the motion segment. The in vivo kinematics of a degenerated lumbar motion segment and the stabilizing function of the surrounding musculature have not been quantified dynamically., Methods: Forty-four pigs were used in six chronic lesions models: sham, disc anulus, disc nucleus, facet capsule, facet joint slit, and facet joint wedge. Three months after injury, an instrumented linkage was used to measure continuously the sagittal kinematics of the L3-L4 motion segment during flexion-extension, with and without stimulation of the lumbar paraspinal musculature. Flexion-extension end point and maximum ranges of motion, and hysteresis were analyzed., Results: Significant alterations in the kinematics caused by chronic lesions were observed, particularly when using the maximum range of motion and when comparing changes in axial translation. Muscular stimulation reduced the hysteresis in the sham, facet capsule, and disc nucleus groups; however, increased hysteresis was observed in the remaining lesion groups., Conclusions: The kinematic behavior of motion segments with chronic lesions was established. The maximum range of motion, which must be measured using a dynamic technique, was a more sensitive parameter for identifying changes in segmental kinematics caused by chronic lesions than was the end range of motion. The lumbar musculature was less efficient overall in stabilizing the motion segment, possibly because of altered mechanisms in the neuromuscular feedback system.

Study Design: An in vivo animal model of lumbar segmental instability, involving both passive and active stabilizing components of the spine, was developed., Objective: The aim of this investigation was to dynamically study the alterations in segmental kinematics as a result of interventions to the passive stabilizing components and to the lumbar musculature., Summary of Background Data: Segmental instability in the lumbar spine is associated with abnormal intervertebral motion. The majority of biomechanical studies have examined the in vitro effects of transecting individual stabilizing structures (i.e., intervertebral disc, facet joints, and ligaments), and have not simultaneously considered the effects of active musculature on spinal kinematics, which exist in the in vivo environment. Also, few studies have evaluated the kinematic behavior in the neutral region, for example, the transition phase between flexion and extension., Methods: Four experimental groups comprised 33 pigs, each of which followed different surgical injury sequences to the L3-L4 motion segment. An instrumented linkage attached to the L3-L4 motion segment was used to measure the sagittal kinematics during dynamic flexion-extension after each surgical injury and after bilateral stimulation of the lumbar paraspinal musculature., Results: Injuries to the disc resulted in greater overall axial translation. Graded injuries to the facet joint mainly caused changes in sagittal rotation and shear translation. When the facet injuries were compounded by removal of the transverse processes, there was significantly greater coupled motion and increased hysteresis in the neutral region for rotation. Extensive muscular stimulation after each of the injuries caused significantly greater rotation and shear translation, along with a tendency toward reduced axial translation, when compared to the unstimulated case. Although increasing the range of motion, increased muscular activity stabilized the injured motion segment by smoothing the erratic rotation pattern of motion, particularly in the neutral region., Conclusions: Because of the direct attachment to the vertebrae, both passive and active strain from the musculature influence the spinal kinematics in normal or destabilized motion segments. Although increasing the range of motion, stimulation of the musculature surrounding the injured motion segment has a stabilizing effect by reducing abrupt kinematic behavior, particularly in the neutral region where the muscles are under reduced tension. A facetectomy produces a paradoxical kinematic behavior, which enhances the unstable condition of the motion segment. Surgical and rehabilitative treatments for patients with segmental instability need to consider the physiologic influences of the spinal musculature.

In vivo creep-recovery and disc pressure measurements were performed on the lumbar spine of immature and mature swine. The creep-recovery measurements were performed using a custom materials testing apparatus designed to apply static or dynamic loads to the spine of anesthetized animals. A series of three separate experiments were performed to assess the effects of: (I) animal death, (II) graded injury to the disc anulus, and (III) respiratory mechanics on the biomechanical response of the porcine L1-L3 vertebral unit (VU). In Experiments I and II, creep rate, modulus, and viscosity parameters were computed using a three-parameter solid rheological analysis of the displacement-time response recorded during the application of a 300-N load. In Experiment III, the effects of respiratory volume and frequency changes on disc pressure were assessed in the unloaded, statically loaded, and immobilized porcine VU. Our results indicated that the adult VU tended to be stiffer, deform or creep more slowly, and had a significantly higher viscosity than the VU of immature pigs. The results of Experiment I demonstrated that the biomechanical response for the VU was significantly altered by the death of the animal; the VU of the living animal (adolescent or mature) was more compliant and deformed at a faster rate than the VU of the same animal after death. Disc injury produced changes in stiffness, viscosity, and creep rate analogous to that of aging, and on the basis of the graded injuries created in this study, it appears that a small defect in the annulus is just as deleterious as removing a large section of anular material. The results of Experiment III indicated that respiration plays an important role in the normal, in vivo mechanical and nutritional behavior of the porcine VU. Altogether, these results demonstrate that, in the absence of normal physiologic conditions, one may not be able to reliably predict the mechanical response of the lumbar spine, and suggest that standards for the testing, handling, and storage of biologic tissue should be established.

The viscoelastic properties of normal and surgically altered lumbar intervertebral disks from eight immature swine were examined in vivo. Rheological models were used to mathematically characterize the compressive creep-relation behavior of the disks before and after alteration by either chemonucleolysis [chymopapain (Chymodyactin) injection] or denucleation. In the normal disks, a significant modulating effect of respiration was observed that tended to increase the creep deformation response in comparison to that observed during similar in vitro and in situ studies. These results suggest that, in terms of assessing the absolute magnitude of the viscoelastic properties of lumbar disks, the influence of normal physiological function on adjacent vertebrae and surrounding tissues cannot be neglected. Preliminary results obtained from the experimentally altered disks indicated that partial denucleation primarily affected the initial stiffness behavior of the disk (24% decrease in elastic modulus), whereas chemonucleolysis caused changes in both the time-dependent (15% increase in creep rate) and instantaneous (23% decrease in elastic modulus) properties of the disk. Both partial denucleation and acute chemonucleolysis produced biomechanical changes that were comparable to grade II or slightly degenerative, age-related changes found in human lumbar intervertebral disks.