CT colonography training for radiographers--a formal evaluation.

AIMS: To evaluate the efficacy of a new intensive "hands-on" course designed to train small teams of radiographers in computed tomography colonography (CTC) technique and initial interpretation for patient triage. MATERIALS AND METHODS: The course comprised small-group lectures, active participation in the daily CTC service with practical technique and image interpretation training by experienced radiologists and radiographers. Evaluation was by assessment of knowledge using randomized sets of multiple choice questions (MCQ; pre/post-course), practical technique using checklists and expert global scores, and interpretation performance outcomes using randomized pre/post-course test datasets (five validated CTC examinations each). Paired t-tests were used to investigate change in performance for MCQ score and interpretation accuracy. RESULTS: Thirteen courses with 49 participants were evaluated over 2 years. Practical skills were high, with mean (SD) checklist scores of 14/15 (0.85) and global scores of 26/30 (2.3). MCQ scores increased significantly from a mean of 59% pre-course to 69% post-course, p<0.001. Correct classification of CTC examination improved significantly from a mean of 55% pre-course to 71% post-course, p<0.001. Cancer and large polyp (>10mm) detection rates also improved significantly from 49% to 60%, p=0.002. CONCLUSION: Structured training in CTC can significantly improve knowledge and interpretation skills of radiographers, while assessing safe procedural performance. Implementation of similar programmes nationally may help reduce performance gaps between centres.

CT colonography: accuracy of initial interpretation by radiographers in routine clinical practice.

AIM: To investigate performance of computed-assisted detection (CAD)-assisted radiographers interpreting computed tomography colonography (CTC) in routine practice. MATERIALS AND METHODS: Three hundred and three consecutive symptomatic patients underwent CTC. Examinations were double-read by trained radiographers using primary two-dimensional/three-dimensional (2D/3D) analysis supplemented by "second reader" CAD. Radiographers recorded colonic neoplasia, interpretation times, and patient management strategy code (S0, inadequate; S1, normal; S2, 6-9 mm polyp; S3, > or = 10 mm polyp; S4, cancer; S5, diverticular stricture) for each examination. Strategies were compared to the reference standard using kappa statistic, interpretation times using paired t-test, learning curves using logistic regression and Pearson's correlation coefficient. RESULTS: Of 303 examinations, 69 (23%) were abnormal. CAD-assisted radiographers detected 17/17 (100%) cancers, 21/28 (72%) polyps > or = 10 mm and 42/60 (70%) 6-9 mm polyps. The overall agreement between radiographers and the reference management strategy was good (kappa 0.72; CI: 0.65, 0.78) with agreement for S1 strategy in 189/211 (90%) exams; S2 in 19/27 (70%); S3 in 12/19 (63%); S4 in 17/17 (100%); S5 in 5/6 (83%). The mean interpretation time was 17 min (SD = 11) compared with 8 min (SD = 3.5) for radiologists. There was no learning curve for recording correct strategies (OR 0.88; p = 0.12) but a significant reduction in interpretation times, mean 14 and 31 min (last/first 50 exams; -0.46; p < 0.001). CONCLUSION: Routine CTC interpretation by radiographers is effective for initial triage of patients with cancer, but independent reporting is currently not recommended.

Acute ventricular and aortic thrombosis post chemotherapy.

We present a rare case of spontaneous arterial thrombosis in a 42-year-old male with an acute history of bilateral lower limb pain and weakness. The previous day he had received the first cycle of cisplatin-based chemotherapy for oesophageal adenocarcinoma (T2/3N0/M0). Computed tomography (CT) and angiography showed extensive abdominal aortic thrombus in a native non-aneurysmal or grossly atheromatous aorta with separate thrombus in the left ventricle. We suggest that poor left ventricular function, a hypercoaguable state secondary to malignancy and cisplatin based chemotherapy may have induced severe arterial and intra-cardiac thrombosis.

Multiresidue screening of pesticides in foods using retention time locking, GC-AED, database search, and GC/MS identification.

Fruit and vegetable extracts were screened for over 400 pesticides by gas chromatography with atomic emission detection (GC-AED) and an experimental database. A technique called retention time locking was used to match GC-AED and GC with mass spectrometry (MS) retention times to those of the database. Samples were analyzed for sulfur, nitrogen, phosphorus, and chlorine by GC-AED. Possible pesticides were suggested by database search and identified by GC/MS. Forty-four pesticide standards were analyzed to determine the precision of retention time matching and the accuracy of the database search. Analytical retention times matched database retention times within 0.32 min. Using elemental criteria, the database search identified the correct compound for 41 of 44 pesticide standards. For blind spikes of fruit and vegetable extracts, the database suggested 22 of 26 spiked pesticides as matches. Nineteen were identified by GC/MS. The combination of retention time locking, GC-AED, database search, and GC/MS can be a powerful tool for identifying pesticides in a complex matrix.

Regulation of extracellular-signal regulated kinase and c-Jun N-terminal kinase by G-protein-linked muscarinic acetylcholine receptors.

Extracellular signal-regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs, or stress-activated protein kinases) are activated by diverse extracellular signals and mediate a variety of cellular responses, including mitogenesis, differentiation, hypertrophy, inflammatory reactions and apoptosis. We have examined the involvement of Ca2+ and protein kinase C (PKC) in ERK and JNK activation by the human G-protein-coupled m2 and m3 muscarinic acetylcholine receptors (mAChR) expressed in Chinese hamster ovary (CHO) cells. We show that the Ca2+-mobilizing m3 AChR is efficiently coupled to JNK and ERK activation, whereas the m2 AChR activates ERK but not JNK. Activation of JNK in CHO-m3 cells by the agonist methacholine (MCh) was delayed in onset and more sustained relative to that of ERK in either CHO-m2 or CHO-m3 cells. The EC50 values for MCh-induced ERK activation in both cell types were essentially identical and similar to that for JNK activation in CHO-m3 cells, suggesting little amplification of the response. Agonist-stimulated Ins(1,4,5)P3 accumulation in CHO-m3 cells was insensitive to pertussis toxin (PTX), consistent with a Gq/phosphoinositide-specific phospholipase C-beta mediated pathway, whereas a significant component of ERK and JNK activation in CHO-m3 cells was PTX-sensitive, indicating Gi/o involvement. Using manipulations that prevent receptor-mediated extracellular Ca2+ influx and intracellular Ca2+-store release, we also show that ERK activation by m2 and m3 receptors is Ca2+-independent. In contrast, a significant component (>50%) of JNK activation mediated by the m3 AChR was dependent on Ca2+, mainly derived from extracellular influx. PKC inhibition and down-regulation studies suggested that JNK activation was negatively regulated by PKC. Conversely, ERK activation by both m2 and m3 AChRs required PKC, suggesting a novel mechanism for PKC activation by PTX-sensitive m2 AChRs. In summary, mAChRs activate JNK and ERK via divergent mechanisms involving either Ca2+ or PKC respectively.

Epidemiology and clinical management of meningococcal disease in west Gloucestershire: retrospective, population based study.

OBJECTIVE: To study changes in the epidemiology and management of meningococcal disease in one health district during a period of high local incidence of disease. DESIGN: Prospective case ascertainment and data collection over 14 years, with retrospective analysis of cases. SETTING: West Gloucestershire (population 320,000). SUBJECTS: Residents developing meningococcal disease between 1 January 1982 and 31 December 1995. RESULTS: 252 cases of invasive meningococcal disease were identified, of which 102 (40%) were officially notified and 191 (76%) were confirmed by culture from a deep site. The observed disease incidence of 5.6/100,000/year was about 2.7 times the national incidence (as measured by either statutory notifications or reference laboratory reports). The period 1983-90 was characterised by a prolonged localised outbreak due to serogroup B serotype 15 sulphonamide resistant (B15R) strains. General practitioners gave benzylpenicillin before hospital admission to 18% of patients who presented with meningococcal disease in the first half of the study period and to 40% who presented in the second half. The overall case fatality rate was 6.7% (17/252). Four deaths were directly or indirectly related to lumbar puncture. Of 120 patients whose lumbar puncture yielded meningococci, nine (8%) showed no abnormality on initial examination. CONCLUSIONS: Neither laboratory records nor formal notifications alone can give an accurate estimate of the incidence of meningococcal disease. Because of the dangers of lumbar puncture, the frequency of misleading negative initial findings, and the advent of new diagnostic techniques, the need for samples of cerebrospinal fluid should be critically questioned in each case of suspected meningococcal disease.

Improved gas chromatographic analysis of organophosphorus pesticides with pulsed splitless injection.

Gas chromatographic (GC) analysis of 6 organophosphorus pesticides (methamidophos, acephate, omethoate, diazinon, dimethoate, and chlorpyrifos) was performed with cool on-column, splitless, and pulsed splitless injections and with nitrogen-phosphorus or mass-selective detection. The pulsed splitless technique uses a high column flow rate during injection to sweep the sample out of the inlet rapidly, reducing analyte loss due to adsorption or thermal decomposition. After injection, the column flow rate is automatically reduced to normal values for chromatographic analysis. Pesticide recoveries for splitless and pulsed splitless injections were determined by comparison of GC peak areas with those obtained with cool on-column injection. With conventional splitless injection at a column flow rate of 5 mL/min, recoveries of acephate, omethoate, and methamidophos were only 57, 63, and 71%, respectively. Pulsed splitless methods with very fast injection flow rates dramatically improved recoveries, with all 6 pesticides falling in the 97-102% range. Because column flow rates are much less for GC with mass spectral detection (GC/MS), recoveries with splitless injection were lower and improvements with pulsed splitless injection were less dramatic for GC/MS. When splitless injection was used, recoveries of the 6 pesticides spiked into a green bean matrix were better than those of pesticides dissolved in pure solvent, presumably because matrix compounds compete with pesticides for active sites in the inlet. By using pulsed splitless injection of solvent standards with very fast initial column flow rates, systematic analyte losses in the inlet were eliminated, making recoveries of pesticides from solvent and green bean matrix very similar.

Pesticide analysis by gas chromatography with a novel atomic emission detector.

An atomic emission detector, consisting of a microwave-induced helium plasma and atomic emission spectrometer, has been used for the gas chromatographic analysis of pesticides. In principle, it is possible to detect any element in the periodic table (except helium) which can elute from a gas chromatograph. Detection limits for C, H, D, N, O, Br, Cl, F, S, Si, P, Sn and Hg were found to range from 0.1 to 75 pg/s with selectivities over carbon of 5000 or more. The gas chromatography-atomic emission detection system has been used for the detection and elemental characterization of 27 different pesticides by obtaining element-specific chromatograms for C, H, N, O, Br, Cl, F, P and S. By performing quantitative analysis for each element, it was possible to calculate the approximate empirical formulas for 20 different herbicides in two different mixtures. An extract from an apple doped with three pesticides was analyzed by gas chromatography-atomic emission detection.

Clinical aspects of postirradiation sarcomas.

The number of cancer patients who live longer and are cured of their disease is increasing. Many of them have received radiotherapy as part of their treatment. Postirradiation sarcoma (PIS), while still uncommon, is a complication which is appearing more frequently as the number of long-term survivors increases. Studies of the clinical characteristics of PIS, such as stage of disease, grade, survival, and prognosis, are therefore of increasing importance, and may lead to different strategies for early detection and prevention. In a literature review of PIS, we identified 344 cases with sufficient data for analysis of these clinical characteristics. In these selected cases, we found that: (a) PIS was most often diagnosed at an advanced stage and high grade; (b) most of the tumors were located in areas where radical surgery could not be performed; (c) the response rate to chemotherapy was almost always poor; and (d) most patients with PIS died from locally advanced and/or metastatic disease within a few months after diagnosis. PIS is a serious, usually fatal, late complication of radiotherapy and it should be weighed in the decision to use this modality of therapy. In the follow-up of cancer patients, a low threshold of suspicion for PIS is recommended in order to detect it early for possible resection. Because of the poor prognosis, more aggressive and investigative chemotherapeutic regimens are warranted.

Improved 125I radioimmunoassay for cotinine by selective removal of bridge antibodies.

We describe an 125I-based RIA for cotinine, the major metabolite of nicotine. The slope of the dose-response curve was quite shallow (6-8% change in binding per doubling dose), resulting in between-assay CVs of 15 to 20%. This effect occurred because the radioligand formed by linking a cotinine derivative to tyramine manifested greater affinity for the anti-cotinine antibodies than did cotinine itself. We absorbed the serum with a derivative of nicotine coupled to the carrier protein via a chemical bridge similar to that used to form the cotinine/carrier protein immunogen. An RIA in which we used such absorbed serum showed a significantly increased slope of the dose-response curve (11-13% change in binding per doubling dose), and between-assay CVS were only 6 to 8%. We suggest that this improvement results because absorption removes anti-bridge antibodies directed against the chemical-bond common to the cotinine/carrier-protein immunogen and to the cotinine/tyramine radioligand.