A model of sequential heart and composite tissue allotransplant in rats.

BACKGROUND: Some of the 600,000 patients with solid organ allotransplants need reconstruction with a composite tissue allotransplant, such as the hand, abdominal wall, or face. The aim of this study was to develop a rat model for assessing the effects of a secondary composite tissue allotransplant on a primary heart allotransplant. METHODS: Hearts of Wistar Kyoto rats were harvested and transplanted heterotopically to the neck of recipient Fisher 344 rats. The anastomoses were performed between the donor brachiocephalic artery and the recipient left common carotid artery, and between the donor pulmonary artery and the recipient external jugular vein. Recipients received cyclosporine A for 10 days only. Heart rate was assessed noninvasively. The sequential composite tissue allotransplant consisted of a 3 x 3-cm abdominal musculocutaneous flap harvested from Lewis rats and transplanted to the abdomen of the heart allotransplant recipients. The abdominal flap vessels were connected to the femoral vessels. No further immunosuppression was administered following the composite tissue allotransplant. Ten days after composite tissue allotransplantation, rejection of the heart and abdominal flap was assessed histologically. RESULTS: The rat survival rate of the two-stage transplant surgery was 80 percent. The transplanted heart rate decreased from 150 +/- 22 beats per minute immediately after transplant to 83 +/- 12 beats per minute on day 20 (10 days after stopping immunosuppression). CONCLUSIONS: This sequential allotransplant model is technically demanding. It will facilitate investigation of the effects of a secondary composite tissue allotransplant following primary solid organ transplantation and could be useful in developing future immunotherapeutic strategies.

Botulinum toxin type A injections for the management of muscle tightness following total hip arthroplasty: a case series.

BACKGROUND: Development of hip adductor, tensor fascia lata, and rectus femoris muscle contractures following total hip arthroplasties are quite common, with some patients failing to improve despite treatment with a variety of non-operative modalities. The purpose of the present study was to describe the use of and patient outcomes of botulinum toxin injections as an adjunctive treatment for muscle tightness following total hip arthroplasty. METHODS: Ten patients (14 hips) who had hip adductor, abductor, and/or flexor muscle contractures following total arthroplasty and had been refractory to physical therapeutic efforts were treated with injection of botulinum toxin A. Eight limbs received injections into the adductor muscle, 8 limbs received injections into the tensor fascia lata muscle, and 2 limbs received injection into the rectus femoris muscle, followed by intensive physical therapy for 6 weeks. RESULTS: At a mean final follow-up of 20 months, all 14 hips had increased range in the affected arc of motion, with a mean improvement of 23 degrees (range, 10 to 45 degrees). Additionally all hips had an improvement in hip scores, with a significant increase in mean score from 74 points (range, 57 to 91 points) prior to injection to a mean of 96 points (range, 93 to 98) at final follow-up. There were no serious treatment-related adverse events. CONCLUSION: Botulinum toxin A injections combined with intensive physical therapy may be considered as a potential treatment modality, especially in difficult cases of muscle tightness that are refractory to standard therapy.

Smartphone ECG for evaluation of STEMI: Results of the ST LEUIS Pilot Study

© 2015 Elsevier Inc. All rights reserved.Background 12-lead ECG is a critical component of initial evaluation of cardiac ischemia, but has traditionally been limited to large, dedicated equipment in medical care environments. Smartphones provide a potential alternative platform for the extension of ECG to new care settings and to improve timeliness of care. Objective To gain experience with smartphone electrocardiography prior to designing a larger multicenter study evaluating standard 12-lead ECG compared to smartphone ECG. Methods 6 patients for whom the hospital STEMI protocol was activated were evaluated with traditional 12-lead ECG followed immediately by a smartphone ECG using right (VnR) and left (VnL) limb leads for precordial grounding. The AliveCor™ Heart Monitor was utilized for this study. All tracings were taken prior to catheterization or immediately after revascularization while still in the catheterization laboratory. Results The smartphone ECG had excellent correlation with the gold standard 12-lead ECG in all patients. Four out of six tracings were judged to meet STEMI criteria on both modalities as determined by three experienced cardiologists, and in the remaining two, consensus indicated a non-STEMI ECG diagnosis. No significant difference was noted between VnR and VnL. Conclusions Smartphone based electrocardiography is a promising, developing technology intended to increase availability and speed of electrocardiographic evaluation. This study confirmed the potential of a smartphone ECG for evaluation of acute ischemia and the feasibility of studying this technology further to define the diagnostic accuracy, limitations and appropriate use of this new technology.

Adjunctive β2-agonist treatment reduces glycogen independently of receptor-mediated acid α-glucosidase uptake in the limb muscles of mice with Pompe disease.

Enzyme or gene replacement therapy with acid α-glucosidase (GAA) has achieved only partial efficacy in Pompe disease. We evaluated the effect of adjunctive clenbuterol treatment on cation-independent mannose-6-phosphate receptor (CI-MPR)-mediated uptake and intracellular trafficking of GAA during muscle-specific GAA expression with an adeno-associated virus (AAV) vector in GAA-knockout (KO) mice. Clenbuterol, which increases expression of CI-MPR in muscle, was administered with the AAV vector. This combination therapy increased latency during rotarod and wirehang testing at 12 wk, in comparison with vector alone. The mean urinary glucose tetrasaccharide (Glc4), a urinary biomarker, was lower in GAA-KO mice following combination therapy, compared with vector alone. Similarly, glycogen content was lower in cardiac and skeletal muscle following 12 wk of combination therapy in heart, quadriceps, diaphragm, and soleus, compared with vector alone. These data suggested that clenbuterol treatment enhanced trafficking of GAA to lysosomes, given that GAA was expressed within myofibers. The integral role of CI-MPR was demonstrated by the lack of effectiveness from clenbuterol in GAA-KO mice that lacked CI-MPR in muscle, where it failed to reverse the high glycogen content of the heart and diaphragm or impaired wirehang performance. However, the glycogen content of skeletal muscle was reduced by the addition of clenbuterol in the absence of CI-MPR, as was lysosomal vacuolation, which correlated with increased AKT signaling. In summary, β2-agonist treatment enhanced CI-MPR-mediated uptake and trafficking of GAA in mice with Pompe disease, and a similarly enhanced benefit might be expected in other lysosomal storage disorders.

The Impact of Worsening Heart Failure in the United States.

In-hospital worsening heart failure represents a clinical scenario wherein a patient hospitalized for acute heart failure experiences a worsening of their condition, requiring escalation of therapy. Worsening heart failure is associated with worse in-hospital and postdischarge outcomes. Worsening heart failure is increasingly being used as an endpoint or combined endpoint in clinical trials, as it is unique to episodes of acute heart failure and captures an important event during the inpatient course. While prediction models have been developed to identify worsening heart failure, there are no known FDA-approved medications associated with decreased worsening heart failure. Continued study is warranted.

Thinking Outside the Box: Treating Acute Heart Failure Outside the Hospital to Improve Care and Reduce Admissions.

The management of acute heart failure is shifting toward treatment approaches outside of a traditional hospital setting. Many heart failure providers are now treating patients in less familiar health care settings, such as acute care clinics, emergency departments, and skilled nursing facilities. In this review we describe the current pressures driving change in the delivery of acute heart failure and summarize the evidence regarding treatments for acute heart failure outside of the inpatient setting. We also provide considerations for the design of future treatment strategies to be implemented in alternative care settings.

Ventricular conduction and long-term heart failure outcomes and mortality in African Americans: insights from the Jackson Heart Study.

BACKGROUND: QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. METHODS AND RESULTS: We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0-14.4) versus 7.1% (95% CI, 6.3-8.0) and 8.2% (95% CI, 6.9-9.7) versus 4.4% (95% CI, 3.7-5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03-1.56; P=0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01-1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation. CONCLUSIONS: QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities.

Identifying Barriers and Practical Solutions to Conducting Site-Based Research in North America: Exploring Acute Heart Failure Trials As a Case Study.

Although the prognosis of ambulatory heart failure (HF) has improved dramatically there have been few advances in the management of acute HF (AHF). Despite regional differences in patient characteristics, background therapy, and event rates, AHF clinical trial enrollment has transitioned from North America and Western Europe to Eastern Europe, South America, and Asia-Pacific where regulatory burden and cost of conducting research may be less prohibitive. It is unclear if the results of clinical trials conducted outside of North America are generalizable to US patient populations. This article uses AHF as a paradigm and identifies barriers and practical solutions to successfully conducting site-based research in North America.

Two Cases of Late Shone Syndrome With Pulmonary Hypertension: Heart-Lung Transplant or Valve Surgery?

Two cases of Shone syndrome with severe mitral and aortic valve problems and pulmonary hypertension were referred for heart-lung transplantation. Severely elevated pulmonary vascular resistance (PVR) was confirmed as was severe periprosthetic mitral and aortic regurgitation. Based on the severity of the valve lesions in both patients, surgery was decided upon and undertaken. Both experienced early pulmonary hypertensive crises, one more than the other, that gradually subsided, followed by excellent recovery and reversal of pulmonary hypertension and PVR. These cases illustrate Braunwald's concept that pulmonary hypertension secondary to left-sided valve disease is reversible.

Muscle Logic: New Knowledge Resource for Anatomy Enables Comprehensive Searches of the Literature on the Feeding Muscles of Mammals.

BACKGROUND: In recent years large bibliographic databases have made much of the published literature of biology available for searches. However, the capabilities of the search engines integrated into these databases for text-based bibliographic searches are limited. To enable searches that deliver the results expected by comparative anatomists, an underlying logical structure known as an ontology is required. DEVELOPMENT AND TESTING OF THE ONTOLOGY: Here we present the Mammalian Feeding Muscle Ontology (MFMO), a multi-species ontology focused on anatomical structures that participate in feeding and other oral/pharyngeal behaviors. A unique feature of the MFMO is that a simple, computable, definition of each muscle, which includes its attachments and innervation, is true across mammals. This construction mirrors the logical foundation of comparative anatomy and permits searches using language familiar to biologists. Further, it provides a template for muscles that will be useful in extending any anatomy ontology. The MFMO is developed to support the Feeding Experiments End-User Database Project (FEED, https://feedexp.org/), a publicly-available, online repository for physiological data collected from in vivo studies of feeding (e.g., mastication, biting, swallowing) in mammals. Currently the MFMO is integrated into FEED and also into two literature-specific implementations of Textpresso, a text-mining system that facilitates powerful searches of a corpus of scientific publications. We evaluate the MFMO by asking questions that test the ability of the ontology to return appropriate answers (competency questions). We compare the results of queries of the MFMO to results from similar searches in PubMed and Google Scholar. RESULTS AND SIGNIFICANCE: Our tests demonstrate that the MFMO is competent to answer queries formed in the common language of comparative anatomy, but PubMed and Google Scholar are not. Overall, our results show that by incorporating anatomical ontologies into searches, an expanded and anatomically comprehensive set of results can be obtained. The broader scientific and publishing communities should consider taking up the challenge of semantically enabled search capabilities.

Muscle activation patterns in shoulder impingement patients

Introduction: Shoulder impingement is one of the most common presentations of shoulder joint problems 1. It appears to be caused by a reduction in the sub-acromial space as the humerus abducts between 60o -120o – the 'painful arc'. Structures between the humeral head and the acromion are thus pinched causing pain and further pathology 2. Shoulder muscle activity can influence this joint space but it is unclear whether this is a cause or effect in impingement patients. This study aimed to observe muscle activation patterns in normal and impingement shoulder patients and determine if there were any significant differences. Method: 19 adult subjects were asked to perform shoulder abduction in their symptomatic arm and non-symptomatic. 10 of these subjects (age 47.9 ± 11.2) were screened for shoulder impingement, and 9 subjects (age 38.9 ± 14.3) had no history of shoulder pathology. Surface EMG was used to collect data for 6 shoulder muscles (Upper, middle and lower trapezius, serratus anterior, infraspinatus, middle deltoids) which was then filtered and fully rectified. Subjects performed 3 smooth unilateral abduction movements at a cadence of 16 beats of a metronome set at 60bpm, and the mean of their results was recorded. T-tests were used to indicate any statistical significance in the data sets. Significance was set at P<0.05. Results: There was a significant difference in muscle activation with serratus anterior in particular showing a very low level of activation throughout the range when compared to normal shoulder activation patterns (<30%). Middle deltoid recruitment was significantly reduced between 60-90o in the impingement group (30:58%).Trends were noted in other muscles with upper trapezius and infraspinatus activating more rapidly and erratically (63:25%; 60:27% respectively), and lower trapezius with less recruitment (13:30%) in the patient group, although these did not quite reach significance. Conclusion: There appears to be some interesting alterations in muscle recruitment patterns in impingement shoulder patients when compared against their own unaffected shoulders and the control group. In particular changes in scapula control (serratus anterior and trapezius) and lateral rotation (infraspinatus), which have direct influence on the sub-acromial space, should be noted. It is still not clear whether these alterations are causative or reactionary, but this finding gives a clear indication to the importance of addressing muscle reeducation as part of a rehabilitation programme in shoulder impingement patients.

Reducing the incidence of coronary heart disease

The incidence of coronary heart disease (CHD) has been significantly reduced by the introduction of the National Service Framework in 2000 but has not yet reached set targets. This article analyses the adverse effects of specific CHD risk factors to the cardiovascular system and proposes local and national strategies for further reduction in the incidence, morbidity and mortality of CHD. It provides an example of how nurses can use a health promotion programme to support patients in giving up smoking, a major contributing factor in CHD. The programme uses cognitive behaviour therapy to improve patients' uptake and adherence.

Art always at heart

The Art Workers Guild, brother body to the SPAB and once presided over by William Morris and his followers, is 125 years old this year. Alan Powers looks back over its history, and sheds light on the characters and common bonds between the two bodies – while present Brothers of the Guild are pictured at work by photographer Lara Platman for new book to mark the event.