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At least 1,351 records · Page 75Linked to original sources
PubMed2005

Mortality of british radiologists: a lecture note.

The precautions introduced after the first 23 years experience of the use of x-rays for medical diagnosis proved adequate to eliminate the acute hazards of exposure, but it was much longer before it was realized that small doses that did not produce any acute effect could increase the risk of cancer. British radiologists who took up the specialty at different periods have, therefore, been studied to see if the risk has now been adequately controlled. Four groups have been studied starting respectively before 1921, in 1921-34, 1935-54, and 1955-77, corresponding approximately to periods when different limits of exposure were applied. Altogether 2698 male radiologists have been identified and all but 27 followed successfully to emigration, death, or survival to January 1st 1997. Of the 1198 who had died, 228 are known to have died of cancer. Two problems arise in evaluating the carcinogenic hazard to which they were exposed: the assessment of the doses received and the selection of an appropriate control group with which to compare their mortality. The most appropriate comparison group would seem to be medical practitioners in general. In comparison with them, radiologists entering in the first 3 periods had increased risks of death from cancer though appreciably less than would have been predicted from the expected effect of the radiation they had received. Those who joined in the latest period had a relatively reduced risk, irrespective of any effect of the small dose of radiation they are likely to have received. Independent evidence suggests, however, that since 1951 radiologists have smoked less than other doctors and the lower than predicted risk in the groups exposed since 1920 is limited to smoking related cancers, the mortality from other cancers being higher than in doctors generally. In assessing the risk of occupational exposure to radiation, life-style has to be taken into consideration, as well as dose of radiation.

Clinical Trials as Topic↗
PubMed2001

Belle Maudsley Lecture 2001. Risk management in orthodontics--making clinical practice safer.

Facing a civil claim for negligence or prosecution for breach of Health and Safety law is something that any sensible clinician wishes to avoid. This review discusses the main areas of risk in clinical practice and how such risks can be minimized when acting as a clinician and as an employer. Although orthodontic examples are used to highlight particular points, this paper is also relevant to general dental practice.

Confidentiality↗
PubMed2003

Arris & Gale lecture. Regulation and responses of gallbladder muscle activity in health and disease.

A complex relationship links biliary symptoms with the mechanisms of gallbladder emptying and the presence of gallstones. This relationship has been investigated by clinical studies of symptoms associated with gallstones, by investigation of gallbladder emptying and cholecystokinin (CCK) release in patients with gallstones, and after cholecystectomy, or truncal vagotomy, and in the irritable bowel syndrome (IBS). Laboratory studies examined receptor density on bovine gallbladder, and contractility of human gallbladder in response to a variety of stimuli was studied in vitro. A set of six symptoms associated with the presence of gallstones was identified; IBS appeared to be present in two-fifths of patients before cholecystectomy but only one-third of these patients had persistent IBS symptoms one year after operation. Gallbladder emptying studies confirmed the poor contraction of stone-bearing gallbladders; abnormal patterns of emptying were also found in patients with IBS. Gallbladder emptying and filling appear to be largely neurally regulated. CCK receptor density was very low in gallbladder tissue, suggesting that receptors on nerve cells might mediate the action of CCK. Relaxation of gallbladder muscle was mediated by adrenergic and nitrergic nerves. The inflammatory mediator bradykinin, however, had a strong direct action on muscle cells to cause gallbladder contraction. The work reported here gives an overview of the symptoms and mechanisms of disease associated with the presence of stones in the gallbladder.

Cholelithiasis↗
PubMed2004

Hunterian Lecture: Insulin resistance in human sepsis: implications for the nutritional and metabolic care of the critically ill surgical patient.

Loss of the anabolic effect of insulin (insulin resistance) is a key component of the adverse metabolic consequences of sepsis and may contribute to the apparent lack of efficacy of feeding regimens in critically ill patients. The mechanisms which underlie the development of insulin resistance in stress remain unclear. In this series of studies, the locus of insulin resistance in the septic patient was shown to lie within the metabolic pathways of glucose storage (glycogen synthesis) within skeletal muscle, was noted to be unrelated to the actions of hormone mediators such as leptin and was shown not to be associated with altered nutrient-induced thermogenesis during total parenteral nutrition (TPN). Clinically applicable maximal rates of glucose-based TPN for septic patients were calculated. A technique was also developed in which insulin resistance could be induced and studied in healthy volunteers. These studies demonstrated that insulin resistance develops within 7 h of an inflammatory stimulus and, as in clinical sepsis, is characterised by selective impairment of glucose storage. Finally, a series of related studies indicated that the magnitude and nature of the inflammatory response in vivo could be enhanced by exogenous insulin infusion, indicating links between the hormone systems involved in intermediary metabolism and the inflammatory response. These findings have significant implications for the optimal design of feeding regimens for critically ill patients.

Critical Care↗
PubMed2005

Hunterian Lecture. Regulation of hypoxia-inducible factor 1 (HIF-1) by nitric oxide in oral squamous cell carcinoma.

INTRODUCTION: Hypoxia is a common feature of many cancers, contributing to tumour progression as well as potentially compromising radiotherapy and chemotherapy. Hypoxia-inducible factor 1 (HIF-1) is an essential component in changing the transcriptional response of tumours under hypoxia and it targets the transcription of many genes involved in cancer biology. Over-expression of HIF-1 has been associated with increased patient mortality in several cancer types. Regulation of HIF-1 by the signalling molecule nitric oxide (NO) is becoming increasingly recognised. METHOD: Three oral cancer cell lines were used to investigate the effects of NO synthase enzymes (NOS) on HIF-1alpha expression under both normal oxygen and hypoxic conditions. The effect of NOS inhibition was evaluated with the drug L-NMMA. Protein expression was determined with Western blotting. RESULTS & CONCLUSIONS: HIF-1alpha expression occurred following exposure of cells to 3% oxygen for 8 h in all three cell lines, and its expression was found to be dependent on NOS activity, being reduced or inhibited by L-NMMA. Although the mechanism remains to be established, NO appears to play a role in the expression of HIF-1alpha in oral cancer. The possible clinical implications of targeting HIF-1 in cancer are discussed.

Carcinoma, Squamous Cell↗
PubMed1999

Rho Chi lecture. Pharmaceutical sciences in the next millennium.

Even a cursory survey of this article suggests that the pharmaceutical sciences are being rapidly transformed under the influence of both the new technologies and sciences and the economic imperatives. Of particular importance are scientific and technological advances that may greatly accelerate the critical process of discovery. The possibility of a drug discovery process built around the principles of directed diversity, self-reproduction, evolution, and self-targeting suggests a new paradigm of lead discovery, one based quite directly on the paradigms of molecular biology. Coupled with the principles of nanotechnology, we may contemplate miniature molecular machines containing directed drug factories, circulating the body and capable of self-targeting against defective cells and pathways -- the ultimate "drug delivery machine." However, science and technology are not the only factors that will transform the pharmaceutical sciences in the next century. The necessary reductions in the costs of drug discovery brought about by the rapidly increasing costs of the current drug discovery paradigms means that efforts to decrease the discovery phase and to make drug development part of drug discovery will become increasingly important. This is likely to involve increasing numbers of "alliances," as well as the creation of pharmaceutical research cells -- highly mobile and entrepreneurial groups within or outside of a pharmaceutical company that are formed to carry out specific discovery processes. Some of these will be in the biotechnology industry, but an increasing number will be in universities. The linear process from basic science to applied technology that has been the Western model since Vannevar Bush's Science: The Endless Frontier has probably never been particularly linear and, in any event, is likely to be rapidly supplanted by models where science, scientific development, and technology are more intimately linked. The pharmaceutical sciences have always been an example of use-directed basic research, but the relationships between the pharmaceutical industry, small and large, and the universities seems likely to become increasingly developed in the next century. This may serve as a significant catalyst for the continued transformation of universities into the "knowledge factories" of the 21st century. Regardless, we may expect to see major changes in the research organizational structure in the pharmaceutical sciences even as pharmaceutical companies enjoy record prosperity. And this is in anticipation of tough times to come.

Chemistry, Pharmaceutical↗