Evoked electromyographic technique for quantitative assessment of the innervation status of laryngeal muscles

OBJECTIVES: The purpose of this study was to develop a minimally invasive, noninjurious evoked electromyographic technique that could accurately quantitate the level of innervation of laryngeal muscles with recurrent laryngeal nerve stimulation. METHODS: A four-phase study was conducted in 24 canines, including 1) identification of the best stimulation-recording configuration, 2) statistical analysis of sensitivity and accuracy, 3) evaluation of safety, and 4) identification of the laryngeal muscle(s) that contribute to the evoked response. RESULTS: The results demonstrated that an entirely noninvasive technique is not feasible. The stimulating cathode must be invasive to ensure discrete activation of the recurrent laryngeal nerve, whereas both recording electrodes should remain on the surface with one overlying the thyroid ala. This configuration proved to be highly accurate, with an error rate of only 6% to 7%, and with sensitivity sufficient to detect a signal in a nerve with fewer than 1% of the axons intact. There was no evidence of nerve injury in any animal over the course of 350 stimulus needle penetrations. By use of neuromuscular blockade to identify those muscles generating the surface response, the thyroarytenoid muscle was found to be the primary contributor, whereas the posterior cricoarytenoid muscle was uninvolved. CONCLUSIONS: This evoked electromyographic technique could provide quantitative information regarding the extent of muscle innervation during denervation and regeneration in case of laryngeal paralysis.     

Altered hetero- and homeometric autoregulation in the terminally failing human heart

OBJECTIVE AND METHODS: To further investigate length-dependent force generation in human heart, nonfailing (donor hearts, NF) and terminally failing (heart transplants, dilated cardiomyopathy, DCM) left ventricular myocardium was studied under various preload (4-40 mN/mm2) or length conditions. In addition, morphological studies (van Giesson Trichrome staining, electron microscopy) were performed. RESULTS: In NF, a biphasic increase in force of contraction (FOC) was observed after elevating the preload (4-40 mN/mm2): there was an immediate fast increase (FOCf,), followed by a slow increase over several minutes (FOCs), which was paralleled by an increase in the systolic fura-2 transient. In DCM, FOCf, FOCs and the systolic fura-2 transient were blunted and diastolic tension was increased at increasing muscle length. Only in NF, a stretched induced increase in diastolic fura-2 ratio was observed. In DCM, no obvious interstitial fibrosis and no difference in basement membrane structure and attachment were observed. CONCLUSIONS: Since FOCf has been attributed to the Frank-Starling mechanism, whereas FOCs represents a length-dependent increase in the intracellular Ca2+-transient, the impaired length-dependent force generation in failing myocardium results from a dysregulation of both myofibrillar Ca2+-sensitivity as well as the intracellular Ca2+-homeostasis. Interstitial fibrosis may have only minor impact on force generation in human end-stage heart failure.     

Community-acquired methicillin-resistant Staphylococcus aureus outbreak in a local high school football team unsuccessful interventions

A retrospective review of an outbreak of community-acquired methicillin-resistant Staphylococcus aureus soft tissue infections in a high school football team was conducted. Thirteen players had 20 infections. Available community-acquired methicillin-resistant S. aureus isolates showed identical antibiotic susceptibility and field inversion gel electrophoresis analysis band patterns. Nasal cultures and mupirocin were ineffective at predicting and controlling infection, respectively. Infections treated with beta-lactam antibiotics were at risk for recurrence.     

The Use of an Hydrogen Peroxide Multipurpose Isolator for Inhouse Preparation of Human Embryo Culture Media: A Unique Successful Swiss Randomized Prospective Study

Purpose: To develop inhouse made (IHM) embryo culture medium with a Multipurpose Isolator and compare the embryo development in a prospective randomized study with commercial media.Methods: Fertilization by intracytoplasmic single sperm injection (ICSI) of Metaphase II oocytes obtained after 96 controlled ovarian hyperstimulation cycles in patients not older than 37 years. Transfer of zygotes to IHM or commercial Cook Sydney IVF Cleavage medium (SIC) immediately after pronucleus observation. Evaluation of embryo cleavage and score, pregnancy, and implantation rate.Results: From 100 zygotes cultured in SIC, 61% were at the 4 cell stage 45 h after ICSI compared to 77% (78/101) in the IHM, P<0.05. The mean embryo score with IHM was 3.9±0.9 compared to 3.5±1.2 with SIC, P<0.05. The clinical pregnancy rate per transfer was 38.9% (37/95), the implantation rate was 23% (46/200), and no differences were observed between the groups.     

A novel connexin 26 mutation associated with autosomal recessive sensorineural deafness

Mutations in the connexin 26 (Cx26) gene (GJB2) are a common cause of hereditary hearing impairment which affects approximately 1 in 2000 newborn children. We report the identification of a novel Cx26 point mutation (439 G-->A) linked to familial, autosomal recessive, sensorineural hearing loss. This missense mutation (E147K) is located in the highly conserved, putative K(+) channel lining sequence of the third transmembrane domain (TM3) of Cx26. Hearing impairment associated with this mutation was congenital, moderate to profound and showed no signs of progressive deterioration.     

Endothelial markers in chronic heart failure: training normalizes exercise-induced vWF release

BACKGROUND: Chronic heart failure (CHF) is characterized by endothelial dysfunction. Vascular endothelium is important for control of haemostasis and vasoregulation. The aim of the present study was to investigate plasma levels of several endothelial markers and the exercise-induced changes on these plasma levels in CHF patients. Subsequently, the effect of a 6-month training programme on these markers is described. MATERIALS AND METHODS: Twenty-nine male CHF patients (NYHA II/III, age 60 +/- 8 year, body mass index 26.7 +/- 2.3 kg m(-2), left ventricular ejection fraction 26.3-7.2%; mean +/- SD) participated. Patients were randomly assigned to a training or control group. Training (26 weeks; combined strength and endurance exercises) was four sessions/week: two sessions supervised and two sessions at home. Before and after intervention, anthropometry, endothelial markers (haemostasis and vasoregulation), maximal workload and peak oxygen uptake were assessed. RESULTS: Physical training positively affected maximal workload. Plasma levels of endothelial markers were not affected by physical training and not related to exercise tolerance. After training, stimulated (maximal exercise) plasma von Willebrand Factor (vWF) release was present, whereas at baseline this release was absent. CONCLUSION: Physical training led to normalization of the stimulated plasma vWF release. Plasma levels of other endothelial markers were not affected by physical training either at rest or under stimulated (maximal exercise) conditions.     

Guideline 'Chronic heart failure'

A new Dutch clinical practice guideline has been developed for the diagnosis, treatment and supportive care of patients with chronic heart failure. This has been formulated by a multidisciplinary working group, set up by the Netherlands Heart Foundation and the Netherlands Society of Cardiology, in cooperation with the Dutch Institute for Healthcare Improvement. Heart failure is defined as: 'a complex of complaints and symptoms resulting from an inadequate pumping function of the heart'. Indications for heart failure are dyspnoea on exertion, reduced exertion tolerance and oedema. By using data from the medical history, case history, physical examination and simple additional tests (laboratory tests, ECG, chest X-ray photos) it is possible to demonstrate or exclude heart failure in clear-cut cases. Doppler ultrasonography should be performed in all patients where heart failure is suspected but cannot be clearly demonstrated. The initial treatment for patients with heart failure with reduced systolic LV function generally consists of the administration of a thiazide or loop diuretic together with an angiotensin-converting enzyme inhibitor and a beta-blocker, to which digoxin and/or spironolactone may be added. For very old patients extra attention should be given to the comorbidity and the medication and dosing scheme should be as simple as possible. The worse the cardiac function, the more the salt and fluid intake should be limited and the more strictly the weight should be monitored.     

Differential effects of rapamycin, cyclosporine A, and FK506 on human coronary artery smooth muscle cell proliferation and signalling

BACKGROUND: Immunosuppressive agents are at the forefront of preventing organ rejection after transplantation. However, their effects on vascular smooth muscle cell-mediated intimal hyperplasia that occurs in post-transplant coronary artery disease are less well known. METHODS AND RESULTS: We investigated the in vitro effects of three immunosuppressive agents cyclosporine A (CsA), FK506 (tacrolimus), and rapamycin (sirolimus, Rapa) on cultured human coronary artery smooth muscle cells (cSMC). CsA inhibited both platelet-derived growth factor (PDGF)-stimulated DNA synthesis and serum-induced proliferation at high concentrations (> or =1000 ng/ml). The growth-inhibitory effect of CsA was not altered by anti-TGF-beta neutralising antibodies nor was autocrine TGF-beta release detected in CsA-treated culture medium. At inhibitory doses, CsA inhibited ERK kinase activation by PDGF, although cytotoxicity was also apparent. Most notably, CsA visibly prevented PDGF-induced altered cell morphology. Rapa was a highly potent and effective inhibitor of cSMC proliferation (reduction in DNA synthesis by >50% from 0.01 ng/ml), acting through inhibition of 70-kDa S6 kinase (p70S6k). FK506 (1-1000 ng/ml) did not affect cSMC proliferation alone, although a > or =250-fold excess of FK506 over Rapa completely reversed the inhibitory effect of Rapa, confirming that these two agents share a common intracellular receptor, the FK506-binding protein (FKBP). CONCLUSION: Rapa is a powerful inhibitor of cSMC proliferation, while CsA slighly inhibits cSMC proliferation, although only at higher concentrations that may be toxic. These results indicate that therapeutic immunosuppression with Rapa may be additionally useful in prevention or delay of posttransplant coronary artery disease.     

CD95/Fas expression on peripheral blood T lymphocytes in patients with multiple sclerosis: effect of high-dose methylprednisolone therapy

Recent data indicate that the apoptotic process, mediated by the CD95/Fas cell surface receptor, is impaired in activated lymphocytes of patients with relapsing-remitting multiple sclerosis. Using flow cytometric-immunophenotyping, we analyzed the expression of CD95/Fas on peripheral blood CD4+ and CD8+ T lymphocytes (PBL) in 10 MS patients in relapse, and the effect of pulse corticosteroid therapy on the apoptosis of autoreactive lymphocytes. The proportions of CD8+ and CD8+CD95+ T lymphocytes were significantly higher in MS patients in relapse before than after pulse corticosteroid therapy. Conversely, the proportions of CD4+ and CD4+CD95+ T cells were significantly lower before than after therapy, but not significantly different from healthy persons. The different expression of CD95/Fas on peripheral blood CD8+ T lymphocytes in relapsing RRMS and in healthy controls suggests a possible involvement of apoptosis in the pathogenesis of MS. Our results also show that pulse corticosteroid therapy influences the CD95/Fas expression on CD8+ and CD4+ T lymphocytes in patients with RRMS.