Vaccine genotype and route of administration affect pseudorabies field virus latency load after challenge

The influence of vaccine genotype and route of administration on the efficacy of pseudorabies virus (PRV) vaccines against virulent PRV challenge was evaluated in a controlled experiment using five genotypically distinct modified live vaccines (MLVs) for PRV. Several of these MLVs share deletions in specific genes, however, each has its deletion in a different locus within that gene. Pigs were vaccinated with each vaccine, either via the intramuscular or intranasal route, and subsequently challenged with a highly virulent PRV field strain. During a 2-week period following challenge with virulent PRV, each of the vaccine strains used in this study was evaluated for its effectiveness in the reduction of clinical signs, prevention of growth retardation and virulent virus shedding. One month after challenge, tissues were collected and analyzed for virulent PRV latency load by a recently developed method for the electrochemiluminescent quantitation of latent herpesvirus DNA in animal tissues after PCR amplification. It was determined that all vaccination protocols provided protection against clinical signs resulting from field virus challenge and reduced both field virus shedding and latency load after field virus challenge. Our results indicated that vaccine efficacy was significantly influenced by the modified live vaccine strain and route of administration. Compared to unvaccinated pigs, vaccination reduced field virus latency load in trigeminal ganglia, but significant differences were found between vaccines and routes of administration. We conclude that vaccine genotype plays a role in the effectiveness of PRV MLVs.     

The Australian Incident Monitoring Study. Oesophageal intubation: an analysis of 2000 incident reports

There were 35 oesophageal intubations in the first 2000 incidents reported to the Australian Incident Monitoring Study (AIMS). These reports confirm existing impressions that misplacement of the endotracheal tube can occur in trained as well as untrained hands, and that auscultation is an unreliable test. On the other hand, the value of capnography is emphasised, with no false positives in the 16 cases in which the instrument was used. There was one false negative. Over the 4 years of the AIMS study, reports have declined in frequency. It is possible that the early detection of oesophageal intubation by capnography has altered its status to the extent that anaesthetists no longer regard it as a "critical" incident. It is highly recommended that the presence of the expected concentration of carbon dioxide in expired air be confirmed by capnography immediately after any endotracheal intubation.     

Boxplot‐based phase I control charts for time between events

To monitor the quality/reliability of a (production) process, it is sometimes advisable to monitor the time between certain events (say occurrence of defects) instead of the number of events, particularly when the events occur rarely. In this case it is common to assume that the times between the events follow an exponential distribution. In this paper, we propose a one‐ and a two‐sided control chart for phase I data from an exponential distribution. The control charts are derived from a modified boxplot procedure. The charting constants are obtained by controlling the overall Type I error rate and are tabulated for some configurations. A numerical example is provided for illustration. The in‐control robustness and the out‐of‐control performance of the proposed charts are examined and compared with those of some existing charts in a simulation study. It is seen that the proposed charts are considerably more in‐control robust and have out‐control properties comparable to the competing charts. Copyright © 2011 John Wiley & Sons, Ltd.     

p53 and K-ras status in duodenal adenomas in familial adenomatous polyposis

BACKGROUND: The genetic alterations in patients with familial adenomatous polyposis (FAP) and duodenal adenomas are poorly characterized when compared with data relating to colorectal tumorigenesis in the same patients. METHODS: Point mutation of the K-ras oncogene and point mutation and overexpression of the TP53 tumour suppressor gene were investigated in 32 duodenal polyps (seven without mucosal pathology, 23 with mildly dysplastic adenomas and two with moderately dysplastic adenomas) from 21 patients with FAP. RESULTS: K-ras mutation, TP53 mutation or positive p53 staining were not found in duodenal polyps without histological abnormality. Of 25 duodenal adenomas, K-ras mutation was found in three (two mildly dysplastic, one moderately dysplastic), 20 showed positive p53 immunostaining, and mutation of the TP53 gene was found in one moderately dysplastic adenoma. p53 protein overexpression in duodenal adenomas was significantly more frequent than mutation of either K-ras or TP53 (P < 0.01). CONCLUSION: p53 dysfunction is a hallmark of duodenal adenomas in patients with FAP. Overexpression may indicate DNA damage and thus an early step in tumorigenesis.     

Cytochrome P450 and dependent activities in unexposed and PAH-exposed terrestrial annelids

The cytochrome P450 system of the oligochaetes Eisenia f. fetida (tiger worm) and Enchytraeus crypticus (pot worm) was analysed using ethoxy-, pentoxy- and benzoxyresorufin as substrates for monooxygenase activity. Whole body microsomes of the earthworm E.f. fetida displayed PentROD activity in the range from 0.26 to 1.05 pmol mg protein-1 min-1 and BenzROD activity in the range from 0.14 to 0.30 pmol mg protein-1 min-1. Exposure of the animals for up to four weeks to 100 mg fluoranthene or benzo[a]pyrene kg-1 soil (dry weight) did not induce significant changes in the activity of these monooxygenases. In E. crypticus EROD activity was in the range from 2.10 to 6.18 pmol mg protein-1 min-1 and PentROD activity in the range from 1.75 to 4.78 pmol mg protein-1 min-1. Short-term exposure to BaP by feeding reduced the EROD activity significantly by 45%, but did not effect PentROD activity. After long-term (8 weeks) exposure to BaP in the agar-agar medium EROD activity was not changed but PentROD had decreased to zero. In both species cytochrome P420 and NADPH-cytochrome C reductase activity were present. In E.f. fetida microsomes are associated with the giant haemoglobin. Both can be separated by gel filtration on a Sepharose B2 column or by hydrophobic interaction chromatography after solubilisation with cholate. NADPH-cytochrome C reductase elutes together with haemoglobin. Cytochrome P420 is eluted with Emulgen 911 and can be further purified by ion exchange chromatography using HA-Ultrogel. By SDS-PAGE of the purified microsomal proteins three protein bands are visualised in the range of cytochrome P450 displaying an apparent molecular mass of 54, 56 and 58 kDa. Only the 54-kDa protein interacts weakly with perch (Perca fluviatilis) CYP1A antibodies, while two proteins with an apparent molecular mass of 65 and 71 kDa give a strong antibody signal.     

Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: a retrospective multivariate analysis

PURPOSE: To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined. METHODS AND MATERIALS: Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beam's eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy). RESULTS: The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure. CONCLUSION: This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.     

Integrated physical and transcript map of 5q31.3-qter

The disposition of S-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (CAS 155680-07-2, S-MTPPA, code: M-5011) was studied after oral administration to rats, dogs and monkeys using the 14C-labeled drug. After oral dosing, S-MTPPA was well absorbed from the gastrointestinal tract, to the extent of 97.7% in rats. The concentration of S-MTPPA in rat plasma reached a peak (Cmax: 13.07 micrograms/ml) at 15 min (tmax) after dosing and declined with a half-life (t1/2) of 2.5 h. The values of the parameters tmax, Cmax and t1/2 for dogs were 30 min, 26.2 micrograms/ml and 7.0 h, and those for monkeys were 15 min, 12.8 micrograms/ml and 3.0 h, respectively. The radioactivity was widely distributed in tissues and almost completely excreted in urine and feces within 48 h after oral administration to rats. The excretion of radioactivity in bile, urine and feces within 48 h after oral administration of 14C-S-MTPPA to bile duct-cannulated rats amounted to 75.0, 18.6 and 1.4% of the dose, respectively. The drug was metabolized mainly by oxidation of the thiophenyl moiety and by glucuronidation of the carboxyl group in rats and monkeys. The major urinary and fecal metabolite in dogs was identified as the taurine conjugate of MTPPA.