Proton beam radiotherapy for choroidal and ciliary body melanoma in the UK-national audit of referral patterns of 1084 cases.

INTRODUCTION: Proton beam therapy has been utilised for the treatment of uveal melanoma in the UK for over 30 years, undertaken under a single centre. In the UK, all ocular tumours are treated at one of four centres. We aimed to understand the variation in referral patterns to the UK proton service, capturing all uveal melanoma patients treated with this modality. METHODS: Retrospective analysis of data regarding all patients treated at the Clatterbridge Proton service between January 2004 and December 2014. RESULTS: A total of 1084 patients with uveal melanoma were treated. The mean age was 57 years (range 9-90 years), basal diameter of 11.5 mm (range 2.0-23.4 mm) and tumour thickness of 3.9 mm (range 0.1-15.4 mm). The majority were TNM stage I (39%) or II (36%). The distance to the optic nerve varied from 0 to 24.5 mm with 148 (14%) of patients having ciliary body involvement. There were variations in the phenotypic characteristic of the tumours treated with protons from different centres, with London referring predominantly small tumours at the posterior pole, Glasgow referring large tumours often at the ciliary body and Liverpool sending a mix of these groups. DISCUSSION: In the UK, common indications for the use of proton treatment in uveal melanoma include small tumours in the posterior pole poorly accessible for plaque treatment (adjacent to the disc), tumours at the posterior pole affecting the fovea and large anterior tumours traditionally too large for brachytherapy. This is the first UK-wide audit enabling the capture of all patients treated at the single proton centre.

The use of cell and tissue culture techniques in the study of regulatory peptides.

Cell and tissue culture preparations have a number of general advantages for the study of biological processes: cells are more accessible for study, diffusion delays and barriers to applied substances are minimised, the humoral and cellular components of the culture environment can be controlled and progressive changes in intracellular and intercellular events can be directly monitored. These significant advantages mean that culture preparations can provide unique opportunities for investigation of the properties and functions of regulatory peptides. Culture preparations also have disadvantages and not all cultures are suitable for use in all types of experiments; therefore, the choice of preparation must be made accordingly. Here we describe different types of culture preparation and give examples where cultures have been used to examine peptide synthesis, storage, secretion and receptor localisation, as well as the short-term and trophic actions of regulatory peptides.

Physiological enteric stimulation elicits cardiovascular reflexes in the rat.

By use of anesthetized rats, parameters for the activation of cardiovascular reflexes by stimulation of gastric or hepatic receptors have been established. For reflex activation, the mean minimum intragastric volume was 4 ml, and the mean minimum rate of hepatic portal vein infusion was 0.3 ml/min. Subdiaphragmatic vagotomy affected the response to gastric distension but did not appear to affect the response to hepatic portal vein infusion, indicating that vagal afferents are involved in mediating gastric-cardiovascular but not hepatic-cardiovascular reflexes. Experiments designed to emphasize the vagal component of the response to gastric distension confirmed this finding. Antagonist effects indicated that the tachycardia was mediated by beta-adrenoreceptor stimulation and that the pressor response was mainly mediated by alpha-adrenoreceptors. The data show that stimuli used in experiments to assess central processing of sensory information from the gastrointestinal tract can activate cardiovascular reflexes. Caution in the design of such experiments and in the interpretation of the data generated is indicated.

Urinary bladder intramural neurones: an electrophysiological study utilizing a tissue culture preparation.

An enzymic dispersion technique was used to free the intramural ganglia from their usual close association with the other components of the urinary bladder wall. The isolated ganglia obtained were viable and could be kept in culture for several weeks. The development of the cultures was monitored by phase-contrast microscopy and their electrophysiological properties were investigated using intracellular recording techniques. Neurones could be visually identified after 2-3 days in culture; cell groups contained from 2-50 neurones. Three types of spontaneous activity were seen: small changes in membrane potential and action potentials, and slow oscillatory conductance changes. These events were not blocked by hexamethonium but were abolished by hyperpolarizing current. Most neurones spiked without adaptation to direct stimulation; in a few cells the train of spikes was damped out. No neurones generated long afterhyperpolarizations. Indirect stimulation produced responses in the ganglia which are consistent with synaptic activity. Summation of inputs was demonstrated. These results provide evidence for local intraganglionic circuits since the ganglia or neurone groups are unequivocally extrinsically denervated. It was concluded that the intramural ganglia have the capacity to integrate preganglionic input and the question of whether or not they might mediate reflex activity is raised.

Convergence of sensory information from abdominal viscera in the rat brain stem.

This study was carried out to establish whether there was convergence of sensory information in the rat brain stem stimulated by physiological activation of gastric mechanoreceptors and hepatic glucoreceptors. Extracellular recordings were made from single neurons in the region of the dorsal vagal nucleus and nucleus of the solitary tract in the medulla. The responses of these neurons to gastric distension, hepatic portal vein perfusion of isotonic D-glucose, and hepatic portal vein infusion of isotonic saline were studied. Fifty-six neurons were studied; it was found that there was no significant difference in the proportion of neurons responding to gastric distension compared with the number responding to either form of hepatic stimulation. In 20 neurons (all 3 types of stimulation were tested on the same neuron), both excitation and inhibition were observed with both forms of visceral stimulation. Of the seven of these neurons that responded to hepatic portal vein infusion, four of them also had an input from gastric mechanoreceptors. Only three of the neurons that responded to hepatic stimulation showed a specific response to hepatic glucose perfusion; in the remainder a component of the response was due to the infusion of the volume itself. The results from these experiments have demonstrated an apparently weak functional synaptic projection carried by hepatic vagal afferents, particularly those responding to changes in portal glucose concentration, which may indicate a rather diffuse and nonspecific sensory system in the liver. These results have also demonstrated the convergence onto neurons in the brain stem of information from gastric and hepatic enteroceptors.(ABSTRACT TRUNCATED AT 250 WORDS)