Combined treatment of squamous cell carcinoma of the anal canal: Radical radiation therapy with 5-fluorouracil and mitomycin-C,a preliminary report

Radical radiation therapy combined with 5-fluorouracil and mitomycin-C was studied in six patients with previously untreated operable squamous cell carcinoma of the anal canal. All six patients achieved local tumor control and have retained anal continence. There has been no evidence of late recurrence to date. This preliminary report demonstrates that this method of treatment warrants further study.     

Cumulative effects of repeated surfactant treatments in the rabbit

The responses of the adult rabbit lung to multiple doses of surfactant after intratracheal injections of either natural calf surfactant or Surfactant-TA were evaluated. For each surfactant, four groups of 1.4-kg rabbits were studied: group 1 received 100 mg of surfactant containing isotopically-labeled dipalmitoylphosphatidylcholine; group 2 received the same labeled surfactant and then three tracheal injections of vehicle; group 3 received labeled surfactant and then three doses (100 mg) of unlabeled surfactant; group 4 was treated in the same way as group 3 except that the final dose was of the labeled surfactant. All rabbits were killed, and alveolar washes were recovered 24 h after the labeled surfactant dose had been given. The amount of labeled palmitate-saturated phosphatidylcholine (Sat PC) in alveolar washes did not change after multiple doses of calf surfactant, indicating that subsequent doses did not alter the clearance of previous doses. The four doses of calf surfactant increased the alveolar Sat PC pool size by a factor of 2.5 only when measured 6 h after the last dose, but the total lung Sat PC pool size doubled, indicating a loss of most of the surfactant Sat PC to the lung tissue. In contrast, Surfactant-TA increased the alveolar pool size by a factor of 4 after the single dose and by a factor of 11 after the multiple doses, and the percentage clearance of labeled Sat PC from the lungs decreased with multiple doses, indicating an effect of subsequent doses on the initial dose. The quantity of Sat PC cleared from the lungs increased by about a factor of 2 after the multiple doses of Surfactant-TA. Although repetitive surfactant doses changed alveolar and lung Sat PC pool sizes the quantity of Sat PC cleared from the lungs increased, and the lungs accommodated the large amount of surfactant without short-term adverse effects.     

Phase III Trials of New Oral Anticoagulants in the Acute Treatment and Secondary Prevention of VTE: Comparison and Critique of Study Methodology and Results

The traditional treatment of venous thromboembolism (VTE) has been use of heparin and vitamin K antagonists (VKA), and although shown to be effective, they have numerous limitations. New oral anticoagulants (NOACs) including direct thrombin (factor IIa) inhibitors (dabigatran) and selective factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) have emerged as promising alternatives with the potential to overcome the limitations of traditional treatments. Clinical trials have been performed with a view to making significant changes to the acute, long-term and extended treatment of VTE. Data are now available on the efficacy and safety, including bleeding rates, of the NOACs in comparison with VKA in the acute treatment and secondary prevention of VTE as well as in comparison with placebo extended VTE treatment. This review compares and contrasts the design and results of the Phase III trials of NOACs in VTE and discusses the implications of the NOACs in terms of treatment strategies in VTE patients.     

Exercise rapidly increases eukaryotic elongation factor 2 phosphorylation in skeletal muscle of men

Protein synthesis in skeletal muscle is known to decrease during contractions but the underlying regulatory mechanisms are unknown. Here, the effect of exercise on skeletal muscle eukaryotic elongation factor 2 (eEF2) phosphorylation, a key component in protein translation machinery, was examined. Eight healthy men exercised on a cycle ergometer at a workload eliciting ∼67% peak pulmonary oxygen consumption     with skeletal muscle biopsies taken from the vastus lateralis muscle at rest as well as after 1, 10, 30, 60 and 90 min of exercise. In response to exercise, there was a rapid (i.e. < 1 min) 5- to 7-fold increase in eEF2 phosphorylation at Thr56 that was sustained for 90 min of continuous exercise. The in vitro activity of skeletal muscle eEF2 kinase was not altered by exercise indicating that the increased activity of eEF2 kinase to eEF2 is not mediated by covalent mechanisms. In support of this, the increase in AMPK activity was temporally unrelated to eEF2 phosphorylation. However, skeletal muscle eEF2 kinase was potently activated by Ca²⁺–calmodulin in vitro , suggesting that the higher eEF2 phosphorylation in working skeletal muscle is mediated by allosteric activation of eEF2 kinase by Ca²⁺ signalling via calmodulin. Given that eEF2 phosphorylation inhibits eEF2 activity and mRNA translation, these findings suggest that the inhibition of protein synthesis in contracting skeletal muscle is due to the Ca²⁺-induced stimulation of eEF2 kinase.     

Fibrosing alveolitis: CT-pathologic correlation

Computed tomography (CT) was performed within 10 days of open lung biopsy in nine patients with fibrosing alveolitis. One-centimeter collimation contiguous scans through the chest were obtained in all patients. Additional 1.5-mm collimation scans were obtained in the area in which lung biopsy was later performed in six patients. In seven patients, CT demonstrated patchy involvement of the lung parenchyma, areas with a reticular pattern being intermingled with areas of normal lung. The reticular pattern was associated with cystic spaces 2-4 mm in diameter and was more severe in the lung periphery. Histologically, the reticular pattern corresponded to areas of irregular fibrosis. One patient had diffuse honeycombing (2-20-mm cysts), and one had honeycombing only in the lung periphery. In all patients, CT clearly defined the architectural changes seen on open lung biopsy. These changes were much better seen on the 1.5-mm than on the 10-mm collimation scans. CT may be helpful in determining the pattern and distribution of lung involvement in patients with fibrosing alveolitis and in guiding the surgeon to the most appropriate area(s) for biopsy.     

The changing academic role of the nurse teacher in the United Kingdom

This paper presents findings from a national study conducted over a 3-year period (1991–94) which examined the changing role of the nurse teacher The study used multiple methods to collect data from a wide variety of respondents (nurse teachers, midwife teachers, clinical nurses, health service managers and higher education lecturers) This paper presents the findings relating to the development of the nurse teacher's academic role following the introduction of Project 2000 The issues presented and discussed include specialization within the nurse teacher's role, the nature of this specialization and the development of academic credibility and scholarship The implications of these changes in terms of the development of nursing as an academic subject area and the opportunity to contribute to the establishment of research based practice are explored