Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma

Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months’duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage II or III disease received postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non-radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71 % and 79%, respectively.     

An analgesic role for cannabinoids

Cannabinoids have significant analgesic properties in animal models, particularly for chronic pain states, but there are few human studies. An endogenous cannabinoid system, with specific receptors and transmitters, has recently been discovered. This discovery has led pharmacologists to explore the potential of synthetic cannabinoids to selectively target chronic pain disorders without producing the side effects associated with cannabis. Well-controlled clinical trials on cannabinoids, and cannabinoid delivery systems, are now required.     

Practical applications of snake venom toxins in haemostasis

Snake venom toxins affecting haemostasis have facilitated extensively the routine assays of haemostatic parameters in the coagulation laboratory. Snake venom thrombin-like enzymes (SVTLE) are used for fibrinogen/fibrinogen breakdown product assay and for the detection of fibrinogen dysfunction. SVTLE are not inhibited by heparin and can thus can be used for assaying antithrombin III and other haemostatic variables in heparin-containing samples. Snake venoms are a rich source of prothrombin activators and these are utilised in prothrombin assays, for studying dysprothrombinaemias and for preparing meizothrombin and non-enzymic forms of prothrombin. Russell's viper (Daboia russelli) venom (RVV) contains toxins which have been used to assay blood clotting factors V, VII, X, platelet factor 3 and, importantly, lupus anticoagulants (LA). Other prothrombin activators (from the taipan, Australian brown snake and saw-scaled viper) have now been used to assay LA. Protein C and activated protein C resistance can be measured by means of RVV and Protac^®, a fast acting inhibitor from Southern copperhead snake venom and von Willebrand factor can be studied with botrocetin^® from Bothrops jararaca venom. The disintegrins, a large family of Arg-Gly-Asp (RGD)-containing snake venom proteins, show potential for studying platelet glycoprotein receptors, notably, GPIIb/IIIa and Ib. Snake venom toxins affecting haemostasis are also used in the therapeutic setting: Ancrod (from the Malayan pit viper, Calloselasma rhodostoma), in particular, has been used as an anticoagulant to achieve ‘therapeutic defibrination’. Other snake venom proteins show promise in the treatment of a range of haemostatic disorders.     

Recording and quantifying sympathetic outflow to muscle and skin in humans: methods,caveats and challenges

The development of microneurography, in which the electrical activity of axons can be recorded via an intrafascicular microelectrode inserted through the skin into a peripheral nerve in awake human participants, has contributed a great deal to our understanding of sensorimotor control and the control of sympathetic outflow to muscle and skin. This review summarises the different approaches to recording muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA), together with discussion on the issues that determine the quality of a recording. Various analytical approaches are also described, with a primary emphasis on those developed by the author, aimed at maximizing the information content from recordings of postganglionic sympathetic nerve activity in awake humans.

     

A pilot study to examine the effect of the Tulip® oropharyngeal airway on ventilation immediately after mask ventilation following the induction of anaesthesia

The Tulip^® airway is an adult, disposable, single‐sized oropharyngeal airway, that is connectable to an anaesthetic circuit. After a standardised induction of anaesthesia in 75 patients, the ease of insertion, intracuff pressure and intracuff volume were measured, as were the end‐tidal carbon dioxide levels, airway pressures and tidal volumes over three breaths. Successful first‐time insertion was achieved in 72 patients (96%, CI 88.8–99.2%) and after two attempts in 74 patients (99%, CI 92.8–100%). There was outright failure only in one patient. In 60 patients (80%, CI 72.2–90.4%), the Tulip airway provided a patent airway without additional manoeuvres, but in 14 patients, jaw thrust or head extension was necessary for airway patency. The main need for these adjuncts appeared to be an initial under‐inflation of the cuff. These promising results are consistent with recent manikin studies using this device.