Evaluation of LBM415 (NVP PDF-713), a novel peptide deformylase inhibitor, for treatment of experimental Mycoplasma pneumoniae pneumonia

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. We evaluated the efficacy of LBM415, a novel peptide deformylase inhibitor antimicrobial agent, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were intranasally inoculated once with 10(7) CFU of M. pneumoniae. Groups of mice were treated with LBM415 (50 mg/kg of body weight) or placebo subcutaneously daily for 13 days, starting 24 h after inoculation. Groups of mice were evaluated at the baseline; at days of treatment 1, 3, 6, and 13; and at 7 days after treatment. The MIC of LBM415 against M. pneumoniae was <0.005 microg/ml. LBM415-treated mice had significantly lower bronchoalveolar lavage fluid M. pneumoniae concentrations than placebo-treated mice on days 6 and 13 of treatment. Compared with placebo treatment, therapy with LBM415 significantly decreased lung histopathology scores at days 3, 6, and 13 of treatment and at 7 days after treatment. Airway obstruction was significantly lower in LBM415-treated mice than in placebo-treated mice on days 1, 3, and 6 of treatment and after 7 days of therapy, while airway hyperresponsiveness was significantly lower only on day 3 of therapy. The bronchoalveolar lavage fluid concentrations of tumor necrosis factor alpha, gamma interferon (IFN-gamma), interleukin-6 (IL-6), IL-12, KC (functional IL-8), monocyte chemotactic protein 1, macrophage inflammatory protein 1alpha, monokine induced by IFN-gamma, and IFN-inducible protein 10 were significantly reduced in LBM415-treated mice compared with the levels in placebo-treated mice. There were no differences in the bronchoalveolar lavage fluid concentrations of granulocyte-macrophage colony-stimulating factor, IL-1beta, IL-2, IL-4, IL-5, and IL-10 between the two groups of mice. LBM415 therapy had beneficial microbiologic, histologic, respiratory, and immunologic effects on acute murine M. pneumoniae pneumonia.     

Anti-respiratory syncytial virus (RSV) neutralizing antibody decreases lung inflammation, airway obstruction, and airway hyperresponsiveness in a murine RSV model

Numerous studies have described a strong association between respiratory syncytial virus (RSV) infection in infancy and the development of recurrent wheezing and airway hyperresponsiveness. We evaluated the effect of an anti-RSV neutralizing monoclonal antibody (palivizumab) on different aspects of RSV disease by using a murine model. BALB/c mice were intranasally inoculated with RSV A2. Palivizumab or an isotype-matched control antibody was administered once at 24 h before inoculation, 1 h after inoculation, or 48 h after inoculation. Regardless of the timing of administration, all mice treated with the neutralizing antibody showed significantly decreased RSV loads in bronchoalveolar lavage (BAL) and lung specimens compared with those of infected controls. Pulmonary histopathologic scores, airway obstruction measured by plethysmography, and airway hyperresponsiveness after methacholine challenge were significantly reduced in mice treated with the anti-RSV antibody 24 h before inoculation compared with those for untreated controls. Concentrations of interferon-gamma, interleukin-10, macrophage inflammatory protein 1alpha, regulated on activation normal T-cell expressed and secreted (RANTES), and eotaxin in BAL fluids were also significantly reduced in mice treated with palivizumab 24 h before inoculation. This study demonstrates that reduced RSV replication was associated with significant modulation of inflammatory and clinical markers of acute disease severity and significant improvement of the long-term pulmonary abnormalities. Studies to determine whether strategies aimed at preventing or reducing RSV replication could decrease the long-term morbidity associated with RSV infection in children should be considered.     

Reliability of human and machine measurements in patient monitoring

Summary In a study on 29 patients for 152 hours a continuous monitoring system has been shown to have a reliability of 90.53 % for pulse rate and 82.20% for arterial blood pressure, but for approximately half of the period of unreliable monitoring a not obviously artifactual reading was being displayed. The relevance of this to possible incorrect diagnosis and management is discussed. The monitor and a nurse using traditional chart keeping methods gave equivalent charts with respect to average levels and trends, but the monitor assisted chart showed a much greater variability. The latter tended to obscure underlying trends and render clinical diagnosis from the chart more difficult     

Safety assessment of the use of ultrasonic energy in the proximity of the recurrent laryngeal nerve in a porcine model

Background

Advanced bipolar and ultrasonic energy have demonstrated reduction of operating time and blood loss in thyroidectomy. However, these devices generate heat and thermal dispersion that may damage adjacent structures such as the recurrent laryngeal nerve (RLN). This study was designed to evaluate the safety profile of the Harmonic Focus+^® (HF+) device through the evaluation of thermal injury to the RLN using different algorithms of distance and time with state of the art technology.

Selective decontamination of the digestive tract improves survival in patients receiving differential lung ventilation

In a review of the literature on differential lung ventilation (DLV) the average mortality was found to be 47%. The major cause of death (66%) was infection. The effect of a novel infection prevention regimen on the colonisation and infection rate of the respiratory tract and on outcome was studied in polytrauma patients. Nineteen patients who presented with asymmetric pulmonary contusion were treated with DLV (103±72 h) and conventional mechanical ventilation (CMV) (16±10 days). They were treated with selective decontamination of the digestive tract with topical non-absorbable antibiotics in combination with systemic antibiotic prophylaxis starting immediately after admission. In one patient colonisation of the respiratory tract was found with Staphylococcus aureus. This disappeared after continued systemic antibiotic prophylaxis. Colonisation with hospital-acquired Gram-negative bacteria or yeasts was not observed. No patient developed pneumonia throughout the period on conventional mechanical ventilation or on DLV. One patient died from cerebral injury. It is concluded that prolonged endobronchial intubation for DLV can be used without increased risk for pneumonia with this antibiotic regimen and that the very low mortality in this study may be attributed to the prevention of infectious complications.     

Evoked potentials in severe herpes simplex encephalitis

Diagnostic and prognostic value of evoked potentials (EP) were studied in 5 patients with severe herpes simplex encephalitis (HSE). Latency of the third negative cortical N70 peak, elicited by median nerve stimulation, was prolonged in 3 survivors with Glasgow coma score of 6 (115 vs 71 ms in controls,p<0.05), but normal after improvement of the acute disease, N70 right to left interhemisphere difference was increased initially in the 4 survivors (26 vs 3 ms in controls,p<0.05) indicating focal brain involvement, a crucial finding in HSE. The first cortical N 20 peak was preserved in all survivors even during deep coma where evaluation of brain function is difficult. Auditory brainstem EP were normal in all patients and useful to exclude brainstem death. In severe HSE, somatosensory long-latency EP are an effective monitor of the level of impaired consciousness and can detect brain focal signs. Short-latency N20 components may be predictive of the outcome.The study was supported by the Fonds zur Förderung der wissenschaftlichen Forschung P7382M     

贯叶连翘提取物和盐酸赖氨酸复方的镇痛作用研究

目的:研究贯叶连翘提取物和盐酸赖氨酸复方(贯叶连翘提取物与盐酸赖氨酸以质量比2∶1配比,简称赖金丝)的镇痛抗炎作用。方法:采用小鼠醋酸扭体实验、甲醛实验和热板实验。结果:赖金丝125,250和500mg/kg灌胃能:①显著减少小鼠扭体次数,抑制率分别为29%,32%和54%。②显著抑制甲醛引起的第2时相疼痛反应,分别使小鼠舔脚时间缩短至(23±20),(18±22)和(12±19)s。③显著减轻甲醛所致小鼠足跖水肿,小鼠左右足重量差值较阴性对照组(34±15)减轻至(16±15),(18±12)和(15±6)mg。但不能抑制甲醛引起的第1时相疼痛反应和小鼠热板反应。结论:赖金丝在125～500mg/kg剂量范围内对炎症性疼痛效果显著,能抑制皮下注射甲醛引起的水肿,可能在外周抑制炎症过程的某个环节。     

Induction and detection of disturbed homeostasis in cardiopulmonary bypass

During cardiopulmonary bypass (CPB) haemodynamic alterations, haemostasis and the inflammatory response are the main causes of homeostatic disruption. Even with CPB procedures of short duration, the homeostasis of a patient is disrupted and, in many cases, requires intensive postoperative treatment to re-establish the physiological state of the patient. Although mortality is low, disruption of homeostasis may contribute to increased morbidity, particularly in high-risk patients. Over the past decades, considerable technical improvements in CPB equipment have been made to prevent the development of the systemic inflammatory response syndrome (SIRS). Despite all these improvements, only the inflammatory response, to some extent, has been reduced. The microcirculation is still impaired, as measured by tissue degradation products of various organs, indicating that CPB may still be considered as an unphysiological procedure. The question is, therefore, whether we can detect the pathophysiological consequences of CPB in each individual patient with valid bedside markers, and whether we can relate this to determinant factors in the CPB procedure in order to assist the perfusionist in improving the adequacy of CPB. The use of these markers could play a pivotal role in decision making by providing an immediate feedback on the determinant quality of perfusion. Therefore, we suggest validating the proposed markers in a nomogram to optimize not only the CPB procedure, but also the patient's safety.     

Left ventricular function during weaning of patients with chronic obstructive pulmonary disease

Objective Determine the evolution of left ventricular ejection fraction during weaning.Design Prospective study.Setting Intensive care unit of a university teaching hospital.Patients and participants 12 consecutive mechanically ventilated patients, without documented coronary artery disease, suffering from acute exacerbation of chronic obstructive pulmonary disease and able to be weaned.Measurements and results Left ventricular ejection fraction was determined during mechanical ventilation, inspiratory pressure support (10 cmH₂O) and spontaneous ventilation with constant inspiratory oxygen fraction using technetium^99m radionuclide angiography. Spontaneous ventilation induced a significant decrease in left ventricular ejection fraction from 54.5±12.4 to 47.0±13% (p<0.01). Inspiratory pressure support induced a slight but non-significant decrease in left ventricular ejection fraction from 55.0±12.1 to 50.3±12.4%. Left ventricular ejection fraction was homogeneously reduced by spontaneous ventilation without patent regional wall motion abnormalities of the left ventricle. Myocardial²⁰¹thallium imaging performed 15 min after weaning showed a normal perfusion in the left ventricle anterior and posterior free wall.Conclusion Weaning of patients suffering from chronic obstructive pulmonary disease without coronary artery disease induced a significant reduction in left ventricular ejection fraction. The non significant decrease in left ventricular ejection fraction observed with inspiratory pressure support suggested that our results might be explained by a weaning induced increase in afterload.