Behavioural activity of rats measured by a new method based on the piezo-electric principle

Spontaneous and drug-induced (haloperidol, apomorphine, and amphetamine) motor activity of rats was measured simultaneously via two distinct and independent methods: the classical optical scanning technique and a new procedure based on the piezo-electric principle. The latter procedure measured animal-induced mechanical vibrations of a flexible cage floor which were transduced into electric signals via piezo-electricity. The piezo method appeared to be relatively more sensitive in recording the small, stereotyped motor movements induced by apomorpine (0.63–10 mg/kg) and high doses of amphetamine (2.5–20 mg/kg). The optical scanning technique, on the other hand, was more sensitive in recording horizontal displacements across the cage such as induced by low doses of amphetamine (0.31–2.5 mg/kg). Both methods showed comparable sensitivity in recording the depression of behaviour induced by haloperidol (0.04–1.25 mg/kg) or low doses of apomorphine (0.04–0.16 mg/kg). The piezo method may complement the optical scanning procedure, and thereby enhance the information on the extent that test compounds modify animal behaviour.     

Citation indexes do not reflect methodological quality in lung cancer randomised trials.

BACKGROUND: Citation factors are applied to assess scientific work despite the fact that they were developed commercially in order to compare competing journals. The aim of the present study was to determine whether there is a relationship between citation factors and a trial's methodological quality using published randomised trials in lung cancer clinical research. Material and methods All of the randomised trials included in nine systematic reviews performed by the European Lung Cancer Working Party (ELCWP) were assessed using two quality scales (Chalmers and ELCWP). RESULTS: One hundred and eighty-one articles were eligible. The median overall ELCWP and Chalmers quality scores were 61.8% and 49.0%, respectively, with a correlation coefficient (r(s)) of 0.74 (P <0.001). A weak association was observed between citation factors and quality scores with the respective correlation coefficients ranging from 0.18 to 0.40 (ELCWP scale) and from 0.21 to 0.38 (Chalmers scale). American authors published trials significantly more often in journals with high citation factors than European or non-American authors (P <0.0001), despite no better methodological quality. Positive trials, which were significantly more likely to be published in journals with higher citation factors, were of no better quality than negative ones. CONCLUSION: Journals with higher citation factors do not appear to publish clinical trials with higher levels of methodological quality, at least for trials in the field of lung cancer research.     

Clinical characteristics of respiratory syncytial virus infections in healthy versus previously compromised host

In an effort to delineate the clinical characteristics of respiratory syncytial virus (RSV) infection in the compromised host, we compared children with bronchopulmonary dysplasia (BPD), congenital heart disease (CHD), premature birth, failure to thrive, and gastroesophageal reflux to previously healthy children. During a four-year period, 262 patients were admitted to the hospital with RSV infection diagnosed by a rapid RSV antigen detection test. Children with BPD or CHD had more hospital days and supplemental oxygen days than the previously healthy group (P less than 0.05). Patients with BPD also had more ICU days, ventilator days, and NPO days, as well as a higher physiologic stability index and therapeutic intervention score than the previously healthy group (P less than 0.05). Premature infants were more likely to present with apnea from RSV (P less than 0.001). Patients with underlying illness tended to be older, although significant difference was demonstrated only for the BPD group (7.0 +/- 5.3 vs. 3.5 +/- 3.3, P less than 0.05). Patients with BPD and CHD had more nosocomial infections than the previously healthy group (P less than 0.0001) and death occurred only in patients with underlying illness. We conclude that previously compromised patients are at risk for more severe and prolonged RSV disease. Earlier diagnosis and therapeutic intervention may be necessary in such patients to improve outcome.     

Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: Long-term follow up of a phase III study

We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m²), mitoxantrone (MXR, 12 mg/m²), or idarubicin (IDA, 10 mg/m²) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered. At an 11-year median follow-up, the 5-year, 10-year and 15-year overall survival (OS) rates were 33.2%, 30.1% and 28.0%, respectively. No significant difference between the three randomized groups regarding OS was observed (P = .38). In young patients, 15-45 years old, no treatment difference (P = .89) regarding OS was observed, while in patients 46-60 years old, MXR and IDA groups had a trend for a longer OS as compared to the DNR group (P = .029). Among younger patients without a favorable MRC cytogenetic risk subgroup who achieved a CR/CRi after induction chemotherapy, those with a HLA-identical sibling donor had higher 10-year and 15-year OS rates than those without. In older patients who reached CR/CRi, the long-term outcomes of those with or without a donor was similar. In conclusion, long-term outcomes of the study confirmed similar OS in the three randomized groups in the whole cohort of patients.     

A phase III randomised trial comparing sequential chemotherapy using cisplatin-based regimen and paclitaxel to cisplatin-based chemotherapy alone in advanced non-small-cell lung cancer.

BACKGROUND: The purpose of this study is to determine whether in advanced non-small-cell lung cancer (NSCLC), the sequential administration of cisplatin-based chemotherapy and paclitaxel (Taxol) is superior to a cisplatin-based chemotherapy, followed by paclitaxel as salvage treatment. PATIENTS AND METHODS: A total of 485 chemotherapy naive patients with advanced NSCLC were treated with three courses of GIP (gemcitibine + ifosfamide + cisplatin), consisting of cisplatin 50 mg/m(2) on day 1, ifosfamide 3 g/m(2) on day 1 and gemcitabine 1 g/m(2) on days 1 and 8. Patients with nonprogressive disease were then randomised to further similar courses of GIP or courses of paclitaxel (225 mg/m(2) over 3 h every 3 weeks). RESULTS: Objective response or nonprogression after induction GIP occurred in 174 and 115 patients, respectively. After randomisation, there were 140 patients in the GIP arm and 141 in the paclitaxel arm. In terms of postrandomisation survival, there was no statistically significant difference (P = 0.17) between the two arms. Median times were 9.7 [95% confidence interval (CI) 7.8-11.6] and 11.9 (95% CI 9.4-14.3) months for paclitaxel and GIP, respectively. Multivariate analysis demonstrated that sex and haemoglobin were independent prognostic factors. After adjustment for these factors, the observed hazard ratio was 0.81 (95% CI 0.63-1.04) in favour of GIP (P = 0.10). Toxicity was tolerable; there was a significantly higher rate of grades III/IV thrombocytopenia with GIP and more alopecia with paclitaxel. CONCLUSION: Sequential chemotherapy using cisplatin-based regimen followed by paclitaxel does not result in better outcome than cisplatin-based chemotherapy using taxane as salvage treatment.     

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

In order to determine whether angiogenesis is a prognostic marker in lung cancer, we performed a systematic review of the literature to assess the prognostic value on survival of microvessel count in patients with lung cancer. Published studies were identified by an electronic search in order to aggregate survival results, after a methodological assessment using a quality scale designed by the European Lung Cancer Working Party. To be eligible, a study had to deal with microvessel count assessment in lung cancer patients on the primary site and to provide survival analysis according to microvessel count expression. Microvessel count has been assessed on surgical samples by immunohistochemistry using factor VIII in 14 studies, CD34 in 10 and CD31 in eight. Respectively 1866, 1440 and 1093 non-small cell lung cancer patients were considered. The overall median quality scores were respectively 52, 59 and 59% for studies assessing microvessel count via factor VIII, CD34 and CD31, without significant difference between studies evaluable or not for meta-analysis nor between studies with significant or non significant results. Seven 'factor VIII' studies, nine 'CD34' and seven 'CD31' provided sufficient data allowing a meta-analysis on survival and were evaluable for results aggregation. This showed that a high microvessel count in the primitive lung tumour was a statistically significant poor prognostic factor for survival in non small cell lung cancer whatever it was assessed by factor VIII (HR: 1.81; 95% CI: 1.16-2.84), CD34 (HR: 1.99; 95% CI: 1.53-2.58) or CD31 (HR: 1.80; 95% CI: 1.10-2.96). Variations in survival among the individual studies can be explained in addition to patients selection criteria by the heterogeneous methodologies used to stain and count microvessels: different antibody clones, identification of 'hotspots', Weidner or Chalkey counting method, cut-off selection. Microvessel count, reflecting the angiogenesis, appears to be a poor prognostic factor for survival in surgically treated non small cell lung cancer but standardisation of angiogenesis assessment by the microvessel count is necessary.     

Interactions of NMDA antagonists and an alpha 2 agonist with mu,delta and kappa opioids in an acute nociception assay

Animal and clinical studies have reported potentiation of opioid antinociception by co-administration of alpha-2 adrenoceptor agonists such as clonidine and NMDA receptor antagonists such as ketamine and dextromethorphan. The aim of this study was to compare these clinically available compounds in combination with classical morphine, fentanyl-like opioids, the delta opioid agonist SNC80 and the kappa opioid agonist U50,488H. Using a mouse hot-plate test, dose-response relationships were first determined for all compounds individually and then for opioids co-administered with fixed doses of clonidine, ketamine or dextromethorphan. Clonidine was also evaluated in combination with ketamine and dextromethorphan. ED50 values were calculated from the proportion of animals reaching a fixed cut-off criterion of 30 s. To varying degrees, all compounds produced increases in response latencies over time. Dextromethorphan produced lower ED50 values for morphine, fentanyl and sufentanil but exerted no effect on SNC80 or U50,488H. Similarly, ketamine potentiated the antinociceptive efficacy of morphine and sufentanil but not SNC80 or U50,488H. By contrast, clonidine potentiated all opioids tested. In addition, the potency of clonidine was found to increase with co-administration of ketamine but not dextromethorphan. The strongest opioid sparing interactions occurred between clonidine and the lipophilic mu opioids fentanyl and sufentanil and the delta opioid SNC80. In summary, these results suggest an important role for lipophilic opioids in combination therapies particularly with clonidine as well as possible advantages of specific delta or kappa opioid combinations with alpha-2 agonists.