Lipid peroxidation in all-in-one admixtures for preterm neonates: impact of amount of lipid, type of lipid emulsion and delivery condition.

AIM: To evaluate the effect of lipid emulsion composition and delivery condition on lipid peroxidation in typical all-in-one parenteral admixtures for preterm neonates. METHODS: Malonedialdehyde (MDA) concentrations were assessed in different all-in-one admixtures. We evaluated the effects of fat blend (three lipid emulsions) and the amount of lipids, as well as the effects of protecting bags and/or tubing from ambient light and storage for 72 h. MDA was measured by liquid chromatography/mass spectrometry. RESULTS: Three hundred and sixty samples were collected from 114 admixtures. Neither the type of lipid (p = 0.43) nor the interaction between light and type of lipid (p = 0.49) had any influence on final MDA concentrations, but the increase in MDA concentration at 24 h (T(24)) was related to light exposure (p < 0.001). The increase in MDA concentration was related to the increase in lipid amount in the admixture at T(0) (r = 0.77) and T(24) (r = 0.86). MDA concentrations in solutions stored for 72 h showed no significant increase, with no difference between the three lipid emulsions (p = 0.69). CONCLUSION: All-in-one admixtures may be interesting for the parenteral nutrition of preterm neonates. Protection from light and restricting the amount of lipid to what is required for appropriate energy provision are essential to limit lipid peroxidation.

Full-length cytokeratin-19 is released by human tumor cells: a potential role in metastatic progression of breast cancer.

INTRODUCTION: We evaluated whether CK19, one of the main cytoskeleton proteins of epithelial cells, is released as full-length protein from viable tumor cells and whether this property is relevant for metastatic progression in breast cancer patients. METHODS: EPISPOT (EPithelial ImmunoSPOT) assays were performed to analyze the release of full-length CK19 by carcinoma cells of various origins, and the sequence of CK19 was analyzed with mass spectrometry. Additional functional experiments with cycloheximide, Brefeldin A, or vincristine were done to analyze the biology of the CK19-release. CK19-EPISPOT was used to detect disseminated tumor cells in bone marrow (BM) of 45 breast cancer patients who were then followed up over a median of 6 years. RESULTS: CK19 was expressed and released by colorectal (HT-29, HCT116, Caco-2) and breast (MCF-7, SKBR3, and MDA-MB-231) cancer cell lines. The CK19-EPISPOT was more sensitive than the CK19-ELISA. Dual fluorescent EPISPOT with antibodies against different CK19 epitopes showed the release of the full-length CK19, which was confirmed by mass spectrometry. Functional experiments indicated that CK19 release was an active process and not simply the consequence of cell death. CK19-releasing cells (RCs) were detectable in BM of 44% to 70% of breast cancer patients. This incidence and the number of CK19-RCs were correlated to the presence of overt metastases, and patients with CK19-RCs had a reduced survival as compared with patients without these cells (P = 0.025, log-rank test; P = 0.0019, hazard ratio, 4.7; multivariate analysis). CONCLUSIONS: Full-length CK19 is released by viable epithelial tumor cells, and CK19-RCs might constitute a biologically active subset of breast cancer cells with high metastatic properties.

[Assessment of inappropriate prescriptions in psychiatric in-patients]. / Evaluation des prescriptions médicales non conformes dans un service de psychiatrie adulte.

OBJECTIVE: To evaluate occurrence of the inappropriate prescriptions in a psychiatric department. METHODOLOGY: In this prospective survey over a two-month period, the medical orders were analysed. Inappropriate prescription was defined as any discrepancy with summary of product characteristics (SPC) or our hospital treatment guidelines. RESULTS: One hundred inpatients (72 women, mean age 37.5+/-15 years) were included. We reviewed 495 medication orders, which represent 1875 prescribed drugs. We found 2636 discrepancies with SPC or our hospital treatment guidelines. The proportion of discrepancies related to legal informations was 21.28% and them related to pharmacotherapy was 55.04%. The proportion of discrepancy per patient was estimated to 4.93%. CONCLUSION: Our study shows a high proportion of inappropriate prescriptions, none of them having induced adverse-drug effects.

Nasal continuous positive airway pressure decreases respiratory muscles overload in young infants with severe acute viral bronchiolitis.

OBJECTIVE: To determine the efficacy of nasal continuous positive airway pressure (nCPAP) on respiratory distress symptoms and respiratory effort in young infants with acute respiratory syncytial virus bronchiolitis. DESIGN: Prospective study. SETTING: The paediatric intensive care unit of a university hospital. PATIENTS: Twelve infants less than 3 months of age, with severe respiratory distress. INTERVENTIONS: Respiratory distress was quantified with a specific scoring system. Oesophageal pressure (Pes) was measured during spontaneous ventilation before and after nCPAP, delivered through an infant-adapted ventilator. Simultaneous recording of gastric pressure (Pgas) was performed in the five oldest patients. MEASUREMENTS AND RESULTS: The respiratory distress score decreased after nCPAP, particularly accessory muscles' use and expiratory wheezing. The breathing pattern was modified, with shorter inspiratory and longer expiratory time. Pes swings and PTPes(insp), two indices of inspiratory effort, were reduced by 54 (+/-4)% and 59 (+/-5)%. PTPgas(exp), an indicator of expiratory muscles activity, was completely abolished. A significant correlation was observed between the respiratory distress score and Pes swings at baseline and after nCPAP. CONCLUSIONS: In young infants with severe acute respiratory syncytial virus bronchiolitis, nCPAP rapidly unloads respiratory muscles and improves respiratory distress symptoms.

Diagnosis of diffuse and localized arrhythmogenic right ventricular dysplasia by gated blood-pool SPECT.

UNLABELLED: This study aimed to assess the ability of global and local systolic parameters measured with gated blood-pool SPECT (GBPS) to diagnose and characterize the severity of diffuse or localized arrhythmogenic right ventricular dysplasia (ARVD). METHODS: Fifty-nine subjects with symptomatic ventricular arrhythmias were prospectively included in the study. With the International Society and Federation of Cardiology criteria for ARVD as a gold standard, these subjects were classified as subjects without ARVD (21 control subjects) and patients with localized ARVD (16 patients) or diffuse ARVD (22 patients). Right ventricular volumes, right ventricular ejection fractions (EF), the SD of local EF (sigma-EF), and the SD of the local times of end systole (sigma-TES) were computed from GBPS data and compared among the groups in the study population. RESULTS: sigma-EF did not differ between control subjects and patients with diffuse or localized ARVD. Right ventricular EF and volumes differed between patients with diffuse ARVD and control subjects, with similar areas under the receiver-operating-characteristic curves, but right ventricular EF and volumes failed to differentiate patients with localized ARVD. In contrast, sigma-TES differed between patients with diffuse or localized ARVD and control subjects. Regression analysis showed that the systolic parameter most strongly associated with the diagnosis of ARVD was sigma-TES. The probabilities of a randomly chosen patient in the diffuse ARVD group and of a randomly chosen patient in the localized ARVD group having sigma-TES values greater than that of a randomly chosen control subject were 98.5% and 96.7%, respectively. For the diagnosis of localized ARVD, a threshold of 80 ms for sigma-TES corresponded to sensitivity, specificity, and positive and negative predictive values of 100%, 81%, 80%, and 100%, respectively. CONCLUSION: With GBPS, both diffuse ARVD and localized ARVD can be accurately diagnosed by computing sigma-TES for all of the pixels on the surface of the right ventricle.

The diagnostic accuracy of reverse transcription-PCR quantification of cytokeratin mRNA in the detection of sentinel lymph node invasion in oral and oropharyngeal squamous cell carcinoma: a comparison with immunohistochemistry.

PURPOSE: The main goal of sentinel lymph node (SLN) detection in head and neck squamous cell carcinomas is to limit neck dissections to pN+ cases only. However, intraoperative + diagnosis cannot be routinely done using the current gold standard, serial step sectioning with immunohistochemistry. Real-time quantitative reverse transcription-PCR (RT-PCR) is potentially compatible with intraoperative use, proving highly sensitive in detecting molecular markers. This study postoperatively assessed the accuracy of quantitative RT-PCR in staging patients from their SLN. EXPERIMENTAL DESIGN: A combined analysis on the same SLN by serial step sectioning with immunohistochemistry and quantitative RT-PCR targeting cytokeratins 5, 14, and 17 was done in 18 consecutive patients with oral or oropharyngeal squamous cell carcinoma and 10 control subjects. RESULTS: From 71 lymph nodes examined, mRNA levels (KRT) were linked to metastasis size for the three cytokeratins studied (Pearson correlation coefficient, r = 0.89, 0.73, and 0.77 for KRT 5, 14, and 17 respectively; P < 0.05). Histopathology-positive SLNs (macro- and micrometastases) showed higher mRNA values than negative SLNs for KRT 17 (P < 10(-4)) and KRT 14 (P < 10(-2)). KRT 5 showed nonsignificant results. KRT 17 seemed to be the most accurate marker for the diagnosis of micrometastases of a size >450 mum. Smaller micrometastases and isolated tumor cells did not provide results above the background level. Receiver operating characteristic curve analysis for KRT 17 identified a cutoff value where patient staging reached 100% specificity and sensitivity for macro- and micrometastases. CONCLUSION: Quantitative RT-PCR for SLN staging in cN(0) patients with oral and oropharyngeal squamous cell carcinoma seems to be a promising approach.

Initial endoscopic description of esophageal squamous cell carcinomas.

INTRODUCTION: The aim of this study was to evaluate initial endoscopic practices at diagnosis of esophageal squamous cell carcinoma in comparison with current recommendations. We wanted to develop a standard model for the endoscopy report which could be used in routine practice. PATIENTS AND METHODS: From January 2000 to December 2002, 122 patients were hospitalized for esophageal squamous cell carcinoma. The initial endoscopic reports were reviewed retrospectively and compared with a model report established on the basis of current recommendations. RESULTS: One hundred and nineteen reports were re-examined. The principal reason for performing the endoscopic examination was dysphagia in 73.9% of patients. Tumor measurements (height, upper and lower extremities) were recorded in 51.2%, 79% and 41% of reports, respectively. 14.4% of the analyzed reports concerned endoscopic procedures which were performed after a first endoscopic examination because the initial report provided an imprecise tumor description. Tissue samples taken during the initial endoscopy allowed a pathological diagnosis in 94.2% of patients. Lugol staining was performed in 2.5% of procedures. CONCLUSION: Insufficiently rigorous reporting compromises the reliability of initial upper digestive endoscopic procedures. Application of a standardized model for routine practice would favor more complete reports, starting with the first procedure.

Acoustic and aerodynamic measurement of speech production after supracricoid partial laryngectomy.

BACKGROUND: Supracricoid partial laryngectomy (SCPL) results in laryngeal preservation in more than 95% of patients with T2 glottic carcinoma. After surgery, glottis function is characterized by an absence of vocal cords and poor glottis closure. Voice is an important postSCPL quality of life factor. OBJECTIVE: Enhance postSCPL vocal function. Obtain postsurgical acoustic and aerodynamic measurements and correlate multiple objective parameters with perceptual results. METHOD: Continuous speech voice samples from 61 patients who had undergone SCPL more than 1 year before were scored according to the global, roughness, breathiness, asthenia, and strain (GRBAS) scale by a jury of listeners. Acoustic and aerodynamic parameters were recorded: fundamental frequency (F0), intensity, jitter, shimmer, signal-to-noise ratio (SNR), signal-to-noise ratio greater than 1 kHz (SNR>1), oral airflow (OAF), maximum phonation time (MPT), and estimated subglottic pressure (ESGP). Nonparametric tests and logistic regression analysis were used to compare objective measurements and perceptual evaluations. RESULTS: All patients had various degrees of dysphonia: grade 1, 4.9%; grade 2, 55.7%; and grade 3, 39.4%. Correlations between perceptual grades and objective parameters were obtained for jitter, shimmer, SNR, SNR>1, ESGP, and OAF. No correlations were obtained between the different parameters and age, number of arytenoids, and time elapsed since surgery (TESS). Logistic regression analysis of jitter, SNR, ESGP, and OAF parameters revealed 92.6% agreement with the perceptual evaluation results.

Validation of a neonatal pain scale adapted to the new practices in caring for preterm newborns.

UNLABELLED: BACKGROUND Neonatal pain assessment generally requires access to facial expression. Improved neonatology practices, such as greater protection against bright lights and non-invasive mask ventilation, have made facial observation more difficult. OBJECTIVE: To validate a 'faceless' acute neonatal pain scale (FANS), which does not depend on facial expression. METHODS: In a prospective, multicentre study, 24-40-week-old neonates were videotaped during a painful procedure (heel prick). Three investigators then scored the pain using FANS and a previously validated scale: DAN (Douleur aiguë du Nouveau-né). FANS is based on assessment of limb movement, cry and autonomic reaction. Reliability was assessed by inter-rater agreement and internal consistency (Cronbach's alpha). Validity was evaluated by agreement between scales (intraclass correlation coefficient (ICC)). The Wilcoxon test evaluated the FANS score differences between conditions. Results are expressed as medians (25th and 75th percentiles). Ranges are presented for outcome parameters. RESULTS: From April 2006 to September 2007, 53 preterms of 32 (30-35) gestational weeks and 1500 (1000-2200) g were observed. Cronbach's alpha was 0.72. The ICC was 0.92 (0.9-0.98) for inter-rater agreement and 0.88 (0.76-0.93) for agreement between scales. CONCLUSION: FANS, which is reliable and valid, is the first scale to score pain in preterm newborns when facial expression is not accessible.

Flow cytometric assessment of vasodilator-stimulated phosphoprotein: prognostic value of recurrent cardiovascular events after acute coronary syndromes.

BACKGROUND: Clopidogrel fails to elicit an adequate antiplatelet response in 4-30% of patients. Assessing the phosphorylation of intraplatelet vasodilator-stimulated phosphoprotein (VASP) is an easy and reliable method of evaluating biological response to clopidogrel. AIM: To assess the prognostic value of clopidogrel in patients with an acute coronary syndrome (ACS) without persistent ST-segment elevation. METHODS: We studied clopidogrel response prospectively in 49 patients treated with a loading dose of 300 mg clopidogrel followed by a maintenance dose of 75 mg/day. VASP index was calculated from the median fluorescence intensity (MFI) of samples incubated with prostaglandin E1 (PGE1) and adenosine diphosphate according to the formula [(MFI(PGE1)-MFI(PGE1-ADP))/MFI(PGE1)]x100, and was determined at baseline and at days 1 and 4 after starting clopidogrel. We correlated VASP index with occurrence of recurrent cardiovascular events over six-month follow-up. RESULTS: There was a significant stepwise decrease in VASP index from baseline (86+/-6%) to day 1 (71+/-13%) and day 4 (61+/-16%; p<0.001) with marked interindividual variability. Patients who experienced recurrent cardiovascular events displayed a higher VASP index compared with those free of events (76+/-3% versus 59+/-16%, p=0.006). Five of six recurrent events occurred in patients in the upper quartile of VASP index measured at day 4. The best cut-off of platelet reactivity index of VASP to predict high-risk ACS patients was at 70%. CONCLUSION: Assessment of VASP index in ACS patients identifies low responders to clopidogrel who are at increased risk of recurrent cardiovascular events.

Accuracy and precision of perfusion lung scintigraphy versus 133Xe-radiospirometry for preoperative pulmonary functional assessment of patients with lung cancer.

PURPOSE: This study sought to determine whether (133)Xe-radiospirometry (XRS) successfully selects patients able to undergo lung resection without postoperative respiratory complications and whether perfusion lung scintigraphy (PLS) is likely to provide a similar selection of patients for certain tumour stages. METHODS: Two hundred and eighty-four patients with resectable lung cancer underwent preoperative assessment of postoperative forced expiratory volume in 1 s (FEV(1)) by XRS and PLS. Correlations, Bland and Altman analysis and contingency tables were used to analyse the difference between the two predictive techniques. RESULTS: One hundred and sixty patients underwent lung resection on the basis of XRS preoperative testing only. None of them developed respiratory insufficiency. Despite a close correlation, the limits of agreement between predicted FEV(1) by XRS and PLS exceeded +/-0.3 l/s. For tumour stages T1Nx and T2N0, PLS underestimated postoperative FEV(1) whereas it overestimated this parameter for stage III. CONCLUSION: XRS accurately selects patients able to undergo lung resection without postoperative pulmonary insufficiency. The agreement between XRS and PLS is unacceptable. When only PLS is available, higher thresholds for patients with stage III cancers and lower thresholds for those with stage I cancers should be used to decide on operability.

Mycophenolate mofetil in combination with reduction of calcineurin inhibitors for chronic renal dysfunction after liver transplantation.

UNLABELLED: The purpose of the study was to introduce mycophenolate mofetil (MMF) in liver transplant recipients with renal dysfunction to decrease calcineurin inhibitor (CNI) dosages without increasing rejection risk. In this prospective, multicenter, randomized study, chronic CNI-related renal dysfunction was defined by an increase in serum creatinine with values >140 micromol/L and <300 micromol/L. Patients were randomized in 2 groups. STUDY GROUP: combination of MMF (2 to 3 g/day) and reduced dose of CNI >or=50% of initial dose; control group: no MMF, but with the ability to reduce CNI doses, but not below 75% of initial dose. Fifty-six patients were included, 27 in the study group and 29 in the control group. In the study group, there was a significant decrease in serum creatinine values, from 171.7 +/- 24.2 micromol/L at day 0 to 143.4 +/- 19 micromol/L at month 12 and a significant increase in creatinine clearance, from 42.6 +/- 10.9 mL/min to 51.7 +/- 13.8 mL/min. No rejection episode was observed in the study group. In the control group, there was no improvement of renal function, assessed by the changes in serum creatinine values, from 175.4 +/- 23.4 micromol/L at day 0 to 181.6 +/- 63 micromol/L at month 12, and in creatinine clearance, from 42.8 +/- 12.8 mL/min to 44.8 +/- 19.7 mL/min. The differences between the 2 groups were significant: P = 0.001 for serum creatinine, and P = 0.04 for creatinine clearance. In conclusion, the introduction of MMF combined with the reduction of at least 50% of CNI dose allowed the renal function of liver transplant recipients to significantly improve at 1 year, without any rejection episode and without significant secondary effects.

Impact of systematic evaluation of pain and agitation in an intensive care unit.

OBJECTIVE: To measure the impact of implementation of the systematic evaluation of pain and agitation by nurses using the Behavioral Pain Scale (BPS), the Numerical Rating Scale (NRS) for pain, and the Richmond Agitation Sedation Scale (RASS) associated with medical staff education in analgesia and sedation management in intensive care unit (ICU) patients. DESIGN: Two-phase, prospective, controlled study. SETTING: Twelve-bed medical-surgical ICU in a university hospital. PATIENTS: Consecutive patients staying >24 hrs in ICU. INTERVENTIONS: BPS, NRS, and RASS were measured twice daily, at rest, by independent observers during 21 wks (control group) and after 4 wks of training, by nurses during 29 wks (intervention group). In the intervention group, the treating physician was alerted in case of pain defined by BPS>5 or NRS>3 or in case of agitation defined by RASS>1. MEASUREMENTS AND MAIN RESULTS: A total of 230 patients were included (control group, n=100; intervention group, n=130). Baseline characteristics were not significantly different. The incidence of pain and agitation decreased significantly in the intervention group: 63% vs. 42% (p=.002) and 29% vs. 12% (p=.002), respectively. Rate of severe pain and agitation events defined by NRS>6 and RASS>2, respectively, also decreased significantly. There were significantly more therapeutic changes in the intervention group in the way of an escalation but also in the way of a de-escalation for analgesic and psychoactive drugs. Compared with the control group, there was a marked decrease in the duration of mechanical ventilation (120 [interquartile range 48-312] vs. 65 (24-192) hrs, p=.01) and nosocomial infections rate (17% vs. 8%, p<.05) in the intervention group. There was no significant difference in median length of stay (9 [4, 15] vs. 7 [4, 13] days) and mortality in ICU (12 vs. 15%). CONCLUSIONS: Systematic evaluation of pain and agitation, and analgesics and sedatives need was associated with a decrease in incidence of pain and agitation, duration of mechanical ventilation and nosocomial infections.

Clonidine added to bupivacaine in neonatal spinal anesthesia: a prospective comparison in 124 preterm and term infants.

BACKGROUND: Spinal anesthesia (SA) remains the 'gold standard' in neonatal anesthesia for inguinal herniorrhaphy but its short duration impedes its usefulness. We previously demonstrated that clonidine prolongs neonatal SA without immediate side effects. METHODS: We conducted a prospective observational study of 124 infants undergoing herniorrhaphy under SA with bupivacaine and clonidine. Two cohorts, term (n = 57) and former preterm (n = 67) infants, were evaluated and compared with regard to episodes of apnea, desaturation, and bradycardia within 24 h of SA. RESULTS: In both groups, postoperative desaturation episodes were unchanged after SA, compared with the 12 preoperative hours, despite significantly increased apnea (P < 0.003 and <0.011 respectively). Transient bradycardias occurred in former preterm infants (P < 0.014): they spontaneously resolved in all cases. Mean arterial pressure did not vary during the study. Upper sensory level of SA, sedation on entering the postanesthesia care unit (PACU) and duration of stay in the PACU were similar in both groups. CONCLUSIONS: The clinical significance of short apneas, recovering spontaneously without desaturation, remains debatable. It is concluded that addition of clonidine to neonatal SA results in acceptable side effects. Side effects must be compared with the potential advantages before future recommendations.

Long-term outcomes after cryoablation for ventricular tachycardia during surgical treatment of anterior ventricular aneurysms.

Intraoperative map-guided procedures have been widely advocated as the best surgical strategy for the treatment of ventricular tachycardia (VT), though favorable results have been reported with subendocardial resection without mapping. This study examined the very long-term results of encircling cryoablation without mapping during surgery for anterior left ventricular aneurysm complicated by VT. Between 1985 and 2003, this procedure was performed in 52 patients, 7 of whom (13.7%) were operated within 1 month of anterior myocardial infarction. Their mean age was 64.4 +/- 8.3 years and mean left ventricular ejection fraction was 31.7%+/- 9.5%. The overall hospital mortality was 1.9%. At 14 years, 86% of patients (95% CI: 75.4-96.6) were free from VT or sudden death. An implantable defibrillator was implanted in five patients (9.6%) during follow-up. The 14-year overall survival was 51.4% (95% CI: 33.8-72.4), and two patients (3.8%) underwent cardiac transplantation during follow-up. The main cause of late death was congestive heart failure in eight patients (40.0%). Favorable long-term results can be achieved with encircling cryoablation without mapping in patients undergoing surgery for anterior left ventricular aneurysm complicated by VT.

Confirmation of the diagnosis of natural rubber latex allergy by the Basotest method.

BACKGROUND: The flow cytometry CD63-based basophil activation test (Basotest has already been validated for the diagnosis of immediate-type allergy such as venom, house dust mite or cypress pollen allergies. The aim of this study was to evaluate the performance (specificity and sensitivity) of Basotest in the diagnosis of natural rubber latex allergy. METHODS: We included 46 latex allergic patients (clinical symptoms of latex allergy, positive latex skin prick tests and/or latex specific IgE) and 33 control subjects and performed Basotest on all subjects. RESULTS: The sensitivity and specificity of Basotest were 84.8 and 87.9%, respectively, when we considered the theoretic cut-off at 15% of CD63-positive cells. Using ROC curves, the optimal cut-off was evaluated at 22%, for which sensitivity and specificity were 79.3 and 96.7%, respectively. CONCLUSION: The Basotest is a reliable test in addition to clinical history and tests already validated (such as skin prick tests and specific IgE) to confirm the diagnosis of natural rubber latex allergy.