Feasibility of stereotactic MRI-based image guidance for the treatment of vascular malformations: a phantom study.

PURPOSE Treatment of vascular malformations requires the placement of a needle within vessels which may be as small as 1 mm, with the current state of the art relying exclusively on two-dimensional fluoroscopy images for guidance. We hypothesize that the combination of stereotactic image guidance with existing targeting methods will result in faster and more reproducible needle placements, as well as reduced radiationexposure, when compared to standard methods based on fluoroscopy alone. METHODS The proposed navigation approach was evaluated in a phantom experiment designed to allow direct comparison with the conventional method. An anatomical phantom of the left forearm was constructed, including an independent control mechanism to indicate the attainment of the target position. Three interventionalists (one inexperienced, two of them frequently practice the conventional fluoroscopic technique) performed 45 targeting attempts utilizing the combined and 45 targeting attempts utilizing the standard approaches. RESULTS In all 45 attempts, the users were able to reach the target when utilizing the combined approach. In two cases, targeting was stopped after 15 min without reaching the target when utilizing only the C-arm. The inexperienced user was faster when utilizing the combined approach and applied significantly less radiation than when utilizing the conventional approach. Conversely, both experienced users were faster when using the conventional approach, in one case significantly so, with no significant difference in radiation dose when compared to the combined approach. CONCLUSIONS This work presents an initial evaluation of a combined navigation fluoroscopy targeting technique in a phantom study. The results suggest that, especially for inexperienced interventionalists, navigation may help to reduce the time and the radiation dose. Future work will focus on the improvement and clinical evaluation of the proposed method.

A New Multidisciplinary Home Care Telemedicine System to Monitor Stable Chronic Human Immunodeficiency Virus-Infected Patients: A Randomized Study

BACKGROUND: Antiretroviral therapy has changed the natural history of human immunodeficiency virus (HIV) infection in developed countries, where it has become a chronic disease. This clinical scenario requires a new approach to simplify follow-up appointments and facilitate access to healthcare professionals. METHODOLOGY: We developed a new internet-based home care model covering the entire management of chronic HIV-infected patients. This was called Virtual Hospital. We report the results of a prospective randomised study performed over two years, comparing standard care received by HIV-infected patients with Virtual Hospital care. HIV-infected patients with access to a computer and broadband were randomised to be monitored either through Virtual Hospital (Arm I) or through standard care at the day hospital (Arm II). After one year of follow up, patients switched their care to the other arm. Virtual Hospital offered four main services: Virtual Consultations, Telepharmacy, Virtual Library and Virtual Community. A technical and clinical evaluation of Virtual Hospital was carried out. FINDINGS: Of the 83 randomised patients, 42 were monitored during the first year through Virtual Hospital (Arm I) and 41 through standard care (Arm II). Baseline characteristics of patients were similar in the two arms. The level of technical satisfaction with the virtual system was high: 85% of patients considered that Virtual Hospital improved their access to clinical data and they felt comfortable with the videoconference system. Neither clinical parameters [level of CD4+ T lymphocytes, proportion of patients with an undetectable level of viral load (p = 0.21) and compliance levels >90% (p = 0.58)] nor the evaluation of quality of life or psychological questionnaires changed significantly between the two types of care. CONCLUSIONS: Virtual Hospital is a feasible and safe tool for the multidisciplinary home care of chronic HIV patients. Telemedicine should be considered as an appropriate support service for the management of chronic HIV infection. TRIAL REGISTRATION: Clinical-Trials.gov: NCT01117675.

PREDIRCAM eHealth platform for individualized telemedical assistance for lifestyle modification in the treatment of obesity, diabetes, and cardiometabolic risk prevention: a pilot study (PREDIRCAM 1)

Background: Healthy diet and regular physical activity are powerful tools in reducing diabetes and cardiometabolic risk. Various international scientific and health organizations have advocated the use of new technologies to solve these problems. The PREDIRCAM project explores the contribution that a technological system could offer for the continuous monitoring of lifestyle habits and individualized treatment of obesity as well as cardiometabolic risk prevention. Methods: PREDIRCAM is a technological platform for patients and professionals designed to improve the effectiveness of lifestyle behavior modifications through the intensive use of the latest information and communication technologies. The platform consists of a web-based application providing communication interface with monitoring devices of physiological variables, application for monitoring dietary intake, ad hoc electronic medical records, different communication channels, and an intelligent notification system. A 2-week feasibility study was conducted in 15 volunteers to assess the viability of the platform. Results: The website received 244 visits (average time/session: 17 min 45 s). A total of 435 dietary intakes were recorded (average time for each intake registration, 4 min 42 s ± 2 min 30 s), 59 exercises were recorded in 20 heart rate monitor downloads, 43 topics were discussed through a forum, and 11 of the 15 volunteers expressed a favorable opinion toward the platform. Food intake recording was reported as the most laborious task. Ten of the volunteers considered long-term use of the platform to be feasible. Conclusions: The PREDIRCAM platform is technically ready for clinical evaluation. Training is required to use the platform and, in particular, for registration of dietary food intake.

In vivo inhibition of rat stellate cell activation by soluble transforming growth factor β type II receptor: A potential new therapy for hepatic fibrosis

Transforming growth factor β (TGF-β) is a well characterized cytokine that appears to play a major role in directing the cellular response to injury, driving fibrogenesis, and, thus, potentially underlying the progression of chronic injury to fibrosis. In this study, we report the use of a novel TGF-β receptor antagonist to block fibrogenesis induced by ligation of the common bile duct in rats. The antagonist consisted of a chimeric IgG containing the extracellular portion of the TGF-β type II receptor. This “soluble receptor” was infused at the time of injury; in some experiments it was given at 4 days after injury, as a test of its ability to reverse fibrogenesis. The latter was assessed by expression of collagen, both as the mRNA in stellate cells isolated from control or injured liver and also by quantitative histochemistry of tissue sections. When the soluble receptor was administered at the time of injury, collagen I mRNA in stellate cells from the injured liver was 26% of that from animals receiving control IgG (P < 0.0002); when soluble receptor was given after injury induction, collagen I expression was 35% of that in control stellate cells (P < 0.0001). By quantitative histochemistry, hepatic fibrosis in treated animals was 55% of that in controls. We conclude that soluble TGF-β receptor is an effective inhibitor of experimental fibrogenesis in vivo and merits clinical evaluation as a novel agent for controlling hepatic fibrosis in chronic liver injury.

Eradication of established intracranial rat gliomas by transforming growth factor beta antisense gene therapy.

Like human gliomas, the rat 9L gliosarcoma secretes the immunosuppressive transforming growth factor beta (TGF-beta). Using the 9L model, we tested our hypothesis that genetic modification of glioma cells to block TGF-beta expression may enhance their immunogenicity and make them more suitable for active tumor immunotherapy. Subcutaneous immunizations of tumor-bearing animals with 9L cells genetically modified to inhibit TGF-beta expression with an antisense plasmid vector resulted in a significantly higher number of animals surviving for 12 weeks (11/11, 100%) compared to immunizations with control vector-modified 9L cells (2/15, 13%) or 9L cells transduced with an interleukin 2 retroviral vector (3/10, 30%) (P < 0.001 for both comparisons). Histologic evaluation of implantation sites 12 weeks after treatment revealed no evidence of residual tumor. In vitro tumor cytotoxicity assays with lymph node effector cells revealed a 3- to 4-fold increase in lytic activity for the animals immunized with TGF-beta antisense-modified tumor cells compared to immunizations with control vector or interleukin 2 gene-modified tumor cells. These results indicate that inhibition of TGF-beta expression significantly enhances tumor-cell immunogenicity and supports future clinical evaluation of TGF-beta antisense gene therapy for TGF-beta-expressing tumors.

RADIANCE-A planning software for intra-operative radiation therapy

In the last decades accumulated clinical evidence has proven that intra-operative radiation therapy (IORT) is a very valuable technique. In spite of that, planning technology has not evolved since its conception, being outdated in comparison to current state of the art in other radiotherapy techniques and therefore slowing down the adoption of IORT. RADIANCE is an IORT planning system, CE and FDA certified, developed by a consortium of companies, hospitals and universities to overcome such technological backwardness. RADIANCE provides all basic radiotherapy planning tools which are specifically adapted to IORT. These include, but are not limited to image visualization, contouring, dose calculation algorithms-Pencil Beam (PB) and Monte Carlo (MC), DVH calculation and reporting. Other new tools, such as surgical simulation tools have been developed to deal with specific conditions of the technique. Planning with preoperative images (preplanning) has been evaluated and the validity of the system being proven in terms of documentation, treatment preparation, learning as well as improvement of surgeons/radiation oncologists (ROs) communication process. Preliminary studies on Navigation systems envisage benefits on how the specialist to accurately/safely apply the pre-plan into the treatment, updating the plan as needed. Improvements on the usability of this kind of systems and workflow are needed to make them more practical. Preliminary studies on Intraoperative imaging could provide an improved anatomy for the dose computation, comparing it with the previous pre-plan, although not all devices in the market provide good characteristics to do so. DICOM.RT standard, for radiotherapy information exchange, has been updated to cover IORT particularities and enabling the possibility of dose summation with external radiotherapy. The effect of this planning technology on the global risk of the IORT technique has been assessed and documented as part of a failure mode and effect analysis (FMEA). Having these technological innovations and their clinical evaluation (including risk analysis) we consider that RADIANCE is a very valuable tool to the specialist covering the demands from professional societies (AAPM, ICRU, EURATOM) for current radiotherapy procedures.

Tumores indutores de osteomalácia: diagnóstico, caracterização tumoral e avaliação evolutiva em longo prazo de nove pacientes

INTRODUÇÃO: Tumores indutores de osteomalácia (TIOs) são raros, geralmente apresentam origem mesenquimal, têm produção excessiva de fosfatoninas sendo a mais comum o FGF23 (Fibroblast Growth Factor 23) que, em níveis elevados, provoca osteomalácia hipofosfatêmica. A cura dos TIOs envolve a remoção completa do tumor, o que torna essencial sua localização. OBJETIVOS: (1) caracterizar nove pacientes com TIO ao diagnóstico e avaliá-los evolutivamente em longo prazo; (2) avaliar a eficácia da cintilografia com Octreotida (Octreoscan®) e a da cintilografia de corpo inteiro com Mibi (MIBI) na detecção dos TIOs. MÉTODOS: O acompanhamento dos pacientes consistiu na avaliação clínica, na avaliação laboratorial com ênfase no metabolismo ósseo e na realização de exames de imagem para caracterização das deformidades esqueléticas. Para a localização dos TIOs, os pacientes foram submetidos a exames de Octreoscan®, MIBI, ressonância magnética (RM) e tomografia computadorizada (TC). RESULTADOS: O período de observação dos pacientes variou de dois a 25 anos. Ao diagnóstico, todos exibiam fraqueza muscular, dores ósseas e fraturas de fragilidade. Em relação à avaliação laboratorial, apresentavam: hipofosfatemia com taxa de reabsorção tubular de fosfato reduzida, fosfatase alcalina aumentada e níveis elevados de FGF23. O Octreoscan® permitiu a identificação dos TIOs nos nove pacientes e o MIBI possibilitou a localização dos TIOs em seis pacientes, sendo que ambos os exames foram concordantes entre si e com os exames topográficos (RM ou TC). Os achados histopatológicos das lesões dos nove pacientes confirmaram tratar-se de oito tumores mesenquimais fosfatúricos (PMTs) benignos e um PMT maligno. Após a primeira intervenção cirúrgica para a remoção dos TIOs, quatro pacientes encontram-se em remissão da doença e cinco evoluíram com persistência tumoral. Dos cinco, quatro foram reoperados e um aguarda nova cirurgia. Dos que foram reoperados, um paciente se mantém em remissão da doença, um foi a óbito por complicações clínicas, uma teve doença metastática e o último apresentou recidiva tumoral três anos após a segunda cirurgia. Deformidades ósseas graves foram observadas nos pacientes cujo diagnóstico e/ou tratamento clínico foram tardios. O tratamento da osteomalácia foi iniciado com fosfato e perdurou até a ressecção tumoral, tendo sido reintroduzido nos casos de persistência/recidiva tumoral. Quatro pacientes que fizerem uso regular desse medicamento por mais de seis anos evoluíram com hiperparatireoidismo terciário (HPT). CONCLUSÕES: O estudo revelou que tanto o Octreoscan® como o MIBI foram capazes de localizar os TIOs. Por isso, incentivamos a realização do MIBI nos locais onde o Octreoscan® não for disponível. Uma equipe experiente é indispensável para o sucesso cirúrgico visto que os tumores, embora benignos, costumam ser infiltrativos. Recomendamos o seguimento por tempo indeterminado em função do risco de recidiva tumoral. Assim como o FGF23, consideramos o fósforo um excelente marcador de remissão, persistência e recidiva dos TIOs. O diagnóstico e o tratamento precoce são fundamentais para a melhora dos sintomas podendo minimizar as deformidades esqueléticas e as sequelas ósseas. O uso prolongado do fosfato no tratamento da osteomalácia hipofosfatêmica foi associado ao desenvolvimento do HPT

Avaliação da musculatura inspiratória e expiratória na doença pulmonar obstrutiva crônica leve e grave comparada aos indivíduos saudáveis

Introdução: A DPOC é uma doença respiratória prevenível e tratável, caracterizada por limitação persistente ao fluxo aéreo, hiperinsuflação e aprisionamento aéreo. A dispneia e a intolerância aos esforços, decorrentes destas alterações fisiopatológicas sofre influência de vários fatores. Dentre estes, o recrutamento e a sobrecarga imposta aos músculos inspiratórios e expiratórios são de fundamental importância, porém a participação destes ainda não foi completamente elucidada em diferentes gravidades da doença. Objetivos: O objetivo principal deste estudo foi avaliar a mecânica ventilatória, e o grau de recrutamento da musculatura inspiratória e expiratória na DPOC leve e grave, na condição de repouso e durante um teste máximo de exercício, comparado a um grupo de indivíduos saudáveis. Metodologia: Trata-se de um estudo transversal envolvendo 36 indivíduos, sendo 24 pacientes portadores de DPOC e 12 voluntários sadios. As avaliações foram divididas em 2 visitas. No D1, foram realizadas uma avaliação clínica, avaliação de dispneia (mMRC) e de qualidade de vida (SGRQ), além da prova de função pulmonar completa. Na 2ª visita, realizada com intervalo de 1 semana, foram avaliadas: as pressões respiratórias máximas estáticas por meio de métodos volitivos (PImax, PEmax, SNIP, Pes sniff, Pga sniff e Pdi sniff) e não volitivos (Twitch cervical bilateral e T10); avaliação da sincronia toracoabdominal por pletismografia de indutância; avaliação do recrutamento dos músculos inspiratórios e expiratórios ao repouso pela eletromiografia de superfície; e, posteriormente, um teste de exercício cardiopulmonar incremental para estudo de todas essas variáveis no esforço. Resultados: Foram avaliados 24 pacientes (12 leves e 12 graves) e 12 indivíduos saudáveis da mesma faixa etária. A maioria dos pacientes apresentava comprometimento significativo da qualidade de vida e os pacientes do grupo grave eram mais sintomáticos. A função pulmonar encontrava-se alterada na maioria dos pacientes. Destes, 79,2% apresentavam aprisionamento aéreo e 70,8% tinham redução da DLCO. Tais alterações foram semelhantes nos 2 grupos de pacientes. A força muscular estática medida por métodos volitivos e não volitivos estava reduzida nos 2 grupos e mostrou relação com o VEF1. No exercício, a dispneia foi o principal motivo para interrupção do teste em 70% dos pacientes. A HD esteve presente em 87,5% dos pacientes. O comportamento das pressões respiratórias foi significativamente diferente entre os 3 grupos. Os pacientes com DPOC apresentaram maior atividade diafragmática (Pdi) comparado aos controles e a participação da musculatura expiratória também foi maior neste grupo, principalmente nos graves. Apesar disso, os pacientes com DPOC apresentaram uma eficiência mecânica reduzida, ou seja, esse incremento da força muscular foi insuficiente para manter uma ventilação adequada para uma determinada carga. Com o aumento da demanda ventilatória, houve recrutamento precoce e progressivo dos músculos inspiratórios e expiratórios durante o exercício. O trabalho resistivo e o expiratório foram significativamente diferentes entre os controles e os pacientes com DPOC desde o início do exercício. Como consequência destas alterações, a intensidade da dispneia durante o TECP foi maior nos pacientes com DPOC (leve e grave) para a mesma carga e mesma ventilação-minuto (VE), quando comparada aos indivíduos do grupo-controle. Conclusões: O conjunto destes achados demonstra que o comprometimento dos músculos inspiratórios e expiratórios contribuiu significativamente para a dispneia e a intolerância ao exercício tanto no DPOC leve quanto no DPOC grave. E que este comprometimento pode não ser detectado com os testes máximos de força ao repouso

Caractérisation tridimensionnelle de l’amplitude articulaire de l’épaule

L’épaule est l’articulation la plus mobile et la plus instable du corps humain dû à la faible quantité de contraintes osseuses et au rôle des tissus mous qui lui confèrent au moins une dizaine de degrés de liberté. La mobilité de l’épaule est un facteur de performance dans plusieurs sports. Mais son instabilité engendre des troubles musculo-squelettiques, dont les déchirures de la coiffe des rotateurs sont fréquentes et les plus handicapantes. L’évaluation de l’amplitude articulaire est un indice commun de la fonction de l’épaule, toutefois elle est souvent limitée à quelques mesures planaires pour lesquelles les degrés de liberté varient indépendamment les uns des autres. Ces valeurs utilisées dans les modèles de simulation musculo-squelettiques peuvent amener à des solutions non physiologiques. L’objectif de cette thèse était de développer des outils pour la caractérisation de la mobilité articulaire tri-dimensionnelle de l’épaule, en passant par i) fournir une méthode et son approche expérimentale pour évaluer l’amplitude articulaire tridimensionnelle de l’épaule incluant des interactions entre les degrés de liberté ; ii) proposer une représentation permettant d’interpréter les données tri-dimensionnelles obtenues; iii) présenter des amplitudes articulaires normalisées, iv) implémenter une amplitude articulaire tridimensionnelle au sein d’un modèle de simulation numérique afin de générer des mouvements sportifs optimaux plus réalistes; v) prédire des amplitudes articulaires sécuritaires et vi) des exercices de rééducation sécuritaires pour des patients ayant subi une réparation de la coiffe des rotateurs. i) Seize sujets ont été réalisé séries de mouvements d’amplitudes maximales actifs avec des combinaisons entre les différents degrés de liberté de l’épaule. Un système d’analyse du mouvement couplé à un modèle cinématique du membre supérieur a été utilisé pour estimer les cinématiques articulaires tridimensionnelles. ii) L’ensemble des orientations définies par une séquence de trois angles a été inclus dans un polyèdre non convexe représentant l’espace de mobilité articulaire prenant en compte les interactions entre les degrés de liberté. La combinaison des séries d’élévation et de rotation est recommandée pour évaluer l’amplitude articulaire complète de l’épaule. iii) Un espace de mobilité normalisé a également été défini en englobant les positions atteintes par au moins 50% des sujets et de volume moyen. iv) Cet espace moyen, définissant la mobilité physiologiques, a été utilisé au sein d’un modèle de simulation cinématique utilisé pour optimiser la technique d’un élément acrobatique de lâcher de barres réalisée par des gymnastes. Avec l’utilisation régulière de limites articulaires planaires pour contraindre la mobilité de l’épaule, seulement 17% des solutions optimales sont physiologiques. En plus, d’assurer le réalisme des solutions, notre contrainte articulaire tridimensionnelle n’a pas affecté le coût de calculs de l’optimisation. v) et vi) Les seize participants ont également réalisé des séries d’amplitudes articulaires passives et des exercices de rééducation passifs. La contrainte dans l’ensemble des muscles de la coiffe des rotateurs au cours de ces mouvements a été estimée à l’aide d’un modèle musculo-squelettique reproduisant différents types et tailles de déchirures. Des seuils de contrainte sécuritaires ont été utilisés pour distinguer les amplitudes de mouvements risquées ou non pour l’intégrité de la réparation chirurgicale. Une taille de déchirure plus grande ainsi que les déchirures affectant plusieurs muscles ont contribué à réduire l’espace de mobilité articulaire sécuritaire. Principalement les élévations gléno-humérales inférieures à 38° et supérieures à 65°, ou réalisées avec le bras maintenu en rotation interne engendrent des contraintes excessives pour la plupart des types et des tailles de blessure lors de mouvements d’abduction, de scaption ou de flexion. Cette thèse a développé une représentation innovante de la mobilité de l’épaule, qui tient compte des interactions entre les degrés de liberté. Grâce à cette représentation, l’évaluation clinique pourra être plus exhaustive et donc élargir les possibilités de diagnostiquer les troubles de l’épaule. La simulation de mouvement peut maintenant être plus réaliste. Finalement, nous avons montré l’importance de personnaliser la rééducation des patients en termes d’amplitude articulaire, puisque des exercices passifs de rééducation précoces peuvent contribuer à une re-déchirure à cause d’une contrainte trop importante qu’ils imposent aux tendons.

Reliability of the Knee Examination in Osteoarthritis: Effect of Standardization

Objective. To assess the reliability of physical examination of the osteoarthritic (OA) knee by rheumatologists, and to evaluate the benefits of standardization. Methods. Forty-two physical signs and techniques were evaluated using a 6 X 6 Latin square design. Patients with mild to severe knee OA, based on physical and radiographic signs, were examined in random order prior to and following standardization of techniques. For those signs with dichotomous scales, agreement among the rheumatologists was calculated as the prevalence-adjusted bias-adjusted kappa (PABAK), while for the signs with continuous and ordinal scales, a reliability coefficient (R-c) was calculated using analysis of variance. A PABAK of >0.60 and an Re of >0.80 were considered to indicate adequate reliability. Results. Adequate poststandardization reliability was achieved for 30 of 42 physical signs/techniques (71%). The most highly reliable signs identified by physical examination of the OA knee included alignment by goniometer (R-c = 0.99), bony swelling (R-c = 0.97), general passive crepitus (R-c = 0.96), gait by inspection (PABAK = 0.78), effusion bulge sign (R-c = 0.97), quadriceps atrophy (R. = 0.97), medial tibiofemoral tenderness (R-c = 0.94), lateral tibiofemoral tenderness (R-c = 0.85), patellofemoral tenderness by grind test (R-c = 0.94), and flexion contracture (R-c = 0.95). The standardization process resulted in substantial improvements in reliability for evaluation of a number of physical signs, although for some signs, minimal or no effect of standardization was noted. After standardization, warmth (PABAK = 0.14), medial instability at 30degrees flexion (PABAK = 0.02), and lateral instability at 30degrees flexion (PABAK = 0.34) were the only 3 signs that were highly unreliable. Conclusion. With the exception of physical examinations for instability, a comprehensive knee examination can be performed with adequate reliability. Standardization further improves the reliability for some physical signs and techniques. The application of these findings to future OA studies will contribute to improved outcome assessments in OA.

Quantitative myocardial contrast echocardiography for prediction of thrombolysis in myocardial infarction flow in acute myocardial infarction

Clinical evaluation of arterial potency in acute ST-elevation myocardial infarction (STEMI) is unreliable. We sought to identify infarction and predict infarct-related artery potency measured by the Thrombolysis In Myocardial Infarction (TIMI) score with qualitative and quantitative intravenous myocardial contrast echocardiography (MCE). Thirty-four patients with suspected STEMI underwent MCE before emergency angiography and planned angioplasty. MCE was performed with harmonic imaging and variable triggering intervals during intravenous administration of Optison. Myocardial perfusion was quantified offline, fitting an exponential function to contrast intensity at various pulsing intervals. Plateau myocardial contrast intensity (A), rate of rise (beta), and myocardial flow (Q = A x beta) were assessed in 6 segments. Qualitative assessment of perfusion defects was sensitive for the diagnosis of infarction (sensitivity 93%) and did not differ between anterior and inferior infarctions. However, qualitative assessment had only moderate specificity (50%), and perfusion defects were unrelated to TIMI flow. In patients with STEMI, quantitatively derived myocardial blood flow Q (A x beta) was significantly lower in territories subtended by an artery with impaired (TIMI 0 to 2) flow than those territories supplied by a reperfused artery with TIMI 3 flow (10.2 +/- 9.1 vs 44.3 +/- 50.4, p = 0.03). Quantitative flow was also lower in segments with impaired flow in the subtending artery compared with normal patients with TIMI 3 flow (42.8 +/- 36.6, p = 0.006) and all segments with TIMI 3 flow (35.3 +/- 32.9, p = 0.018). An receiver-operator characteristic curve derived cut-off Q value of

Patients with neck pain demonstrate reduced electromyographic activity of the deep cervical flexor muscles during performance of the craniocervical flexion test

Study Design. Cross-sectional study. Objective. The present study compared activity of deep and superficial cervical flexor muscles and craniocervical flexion range of motion during a test of craniocervical flexion between 10 patients with chronic neck pain and 10 controls. Summary of Background Data. Individuals with chronic neck pain exhibit reduced performance on a test of craniocervical flexion, and training of this maneuver is effective in management of neck complaints. Although this test is hypothesized to reflect dysfunction of the deep cervical flexor muscles, this has not been tested. Methods. Deep cervical flexor electromyographic activity was recorded with custom electrodes inserted via the nose and fixed by suction to the posterior mucosa of the oropharynx. Surface electrodes were placed over the superficial neck muscles ( sternocleidomastoid and anterior scalene). Root mean square electromyographic amplitude and craniocervical flexion range of motion was measured during five incremental levels of craniocervical flexion in supine. Results. There was a strong linear relation between the electromyographic amplitude of the deep cervical flexor muscles and the incremental stages of the craniocervical flexion test for control and individuals with neck pain ( P = 0.002). However, the amplitude of deep cervical flexor electromyographic activity was less for the group with neck pain than controls, and this difference was significant for the higher increments of the task ( P < 0.05). Although not significant, there was a strong trend for greater sternocleidomastoid and anterior scalene electromyographic activity for the group with neck pain. Conclusions. These data confirm that reduced performance of the craniocervical flexion test is associated with dysfunction of the deep cervical flexor muscles and support the validity of this test for patients with neck pain.

Patient and graft survival after liver transplantation for hereditary hemochromatosis: Implications for pathogenesis

The clinical outcome of patients who have undergone liver transplantation for hereditary hemochromatosis (HH) or who have received iron-loaded donor grafts is unclear. We reviewed 3,600 adult primary orthotopic liver transplants and assessed the outcomes in 22 patients with HH. We also evaluated graft function and iron mobilization in 12 recipients of iron-loaded donor grafts. All 22 subjects who received liver transplants for HH were male; 13 had other risk factors for liver disease. HH patients had comparatively poor outcomes following transplantation: survival at 1, 3, and 5 years posttransplantation were 72%, 62%, and 55%, respectively. Recurrent hepatocellular cancer was the most common cause of death. There was no convincing evidence of reaccumulation of iron in the grafted liver in HH; however, 1 subject demonstrated increased serum ferritin concentration and grade 2 hepatic siderosis. Liver iron stores were slow to mobilize in 7 of the 12 recipients of iron-loaded grafts. These recipients had appropriate early graft function, but 2 patients with heavy iron loading and increased hepatic iron developed hepatic fibrosis. In conclusion. (1) HH is an uncommon indication for liver transplantation, and the majority of patients requiring transplantation had other risk factors for chronic liver disease; (2) reaccumulation of liver iron in HH patients is very unusual, but increased iron stores may be slow to mobilize in normal recipients of iron-loaded grafts, potentially compromising late graft function; (3) post-liver transplant survival is reduced in HH, and affected patients require careful clinical evaluation of perioperative and postoperative risk factors. Our data suggest that iron excess in HH does not wholly depend on intestinal iron absorption but is also influenced by liver factors that moderate iron metabolism.

Screening for heart disease in diabetic subjects

Background The prevalence of left ventricular hypertrophy (LVH), coronary artery disease, and subclinical cardiomyopathy in diabetic patients without known cardiac disease is unclear. We sought the frequency of these findings to determine whether plasma brain natriuretic peptide (BNP) could be used as an alternative screening tool to identify subclinical LV dysfunction. Methods Asymptomatic patients with diabetes mellitus without known cardiac disease (n = 10 1) underwent clinical evaluation, measurement of BNP, exercise stress testing, and detailed echocardiographic assessment. After exclusion of overt dysfunction or ischemia, subclinical myocardial function was sought on the basis of myocardial systolic (Sm) and diastolic velocity (Em). Association was. sought between subclinical dysfunction and clinical, biochemical, exercise, and echocardiographic variables. Results Of 101 patients, 22 had LVH and 16 had ischemia evidenced by exercise-induced wall motion abnormalities. Only 4 patients had abnormal BNP levels; BNP was significantly increased in patients with LVH. After exclusion of LVH and coronary artery disease, subclinical cardiomyopathy was identified in 24 of 66 patients: Subclinical disease could not be predicted by BNP. Conclusions Even after exclusion of asymptomatic ischemia and hypertrophy, subclinical systolic and diastolic dysfunction occurs in a significant number of patients with type 2 diabetes. However, screening approaches, including BNP, do not appear to be sufficiently sensitive to identify subclinical dysfunction, which requires sophisticated echocardiographic analysis.

Applications of transcranial Doppler in the ICU: a review

Objective: Transcranial Doppler (TCD) ultrasonography is a technique that uses a hand-held Doppler transducer (placed on the surface of the cranial skin) to measure the velocity and pulsatility of blood flow within the intracranial and the extracranial arteries. This review critically evaluates the evidence for the use of TCD in the critical care population. Discussion: TCD has been frequently employed for the clinical evaluation of cerebral vasospasm following subarachnoid haemorrhage (SAH). To a lesser degree, TCD has also been used to evaluate cerebral autoregulatory capacity, monitor cerebral circulation during cardiopulmonary bypass and carotid endarterectomies and to diagnose brain death. Technological advances such as M mode, colour Doppler and three-dimensional power Doppler ultrasonography have extended the scope of TCD to include other non-critical care applications including assessment of cerebral emboli, functional TCD and the management of sickle cell disease. Conclusions: Despite publications suggesting concordance between TCD velocity measurements and cerebral blood flow there are few randomized controlled studies demonstrating an improved outcome with the use of TCD monitoring in neurocritical care. Newer developments in this technology include venous Doppler, functional Doppler and use of ultrasound contrast agents.