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A force of magical activity: the introduction of insulin treatment in Britain 1922-1926.

The discovery of insulin by Banting and Best in 1992 is the subject of many papers and one authoritative book (Bliss M. The Discovery of Insulin. Chicago: University of Chicago Press, 1982. See also Bliss M. Rewriting medical history: Charles Best and the Banting and Best myth. J Med Hist 1993; 48: 253-274.). This paper charts the introduction of insulin in England and examines its effects on medical practice. Before 1922 there were few effective drugs and only one (thyroid extract) which had to be taken continuously. Insulin was radically different; it restored weight and vigour and allowed survival in diabetic coma and after surgery but was potentially dangerous because of the possibility of hypoglycaemia, had to be given by injection, and the dose varied with the amount of food and exercise. The immediate questions to be answered after the supply of insulin was assured were how could such a powerful drug be kept out of the hands of ignorant people (a phrase used by The Times), who would administer it, and who would supervise the treatment? Within a year further problems were identified. Should the aims of treatment be the same as those in the starvation era? Could the diet be liberalized? How much biochemical monitoring was necessary? I set the scene by describing how, from Minkowski's announcement (1889) that pancreatectomy caused severe diabetes, most clinicians and physiologists believed that the pancreas (and specifically the islets of Langerhans) produced an internal secretion which controlled carbohydrate metabolism. After Murray's (1891) demonstration that myxoedema could be cured by thyroid extract, it was assumed that diabetes would soon yield in the same way. Yet by the beginning of the First World War most experts were pessimistic about isolating the hypothetical internal secretion and had pinned their hopes on starvation treatment. In the decade before the introduction of insulin the management of diabetes was grim; patients were kept in hospital for weeks or months, while their calorie intake and glucose excretion was meticulously recorded. They were in the wards of physicians with a strong interest in biochemistry whose forte was analysing urine not looking after patients. When the Medical Research Council set up a multicentre trial of insulin in late 1922 they enrolled the physician biochemists who produced the early publications and became the experts. The narrow views and innate conservatism of these doctors with the inflexibility of the system in (London) teaching hospitals meant that insulin treatment became a straightjacket for many patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Canada↗

Development of the MAGIC congenital heart disease catheterization database for interventional outcome studies.

As the field of catheter-based therapies for congenital heart disease continues to expand, we lack the evidence-based data to make appropriate therapeutic decisions in the catheterization laboratory. A stumbling block to the determination of evidence-based therapies is our inability to simply and reliably share outcome data across multiple centers. We investigated whether a commonly used congenital heart disease catheterization database program (PedCath) could be used as an automatic catheterization data submission tool to a central database for outcome analysis. To test the feasibility of such a tool for collaborative outcomes research we formed a national group of seven congenital heart disease centers, the Mid-Atlantic Group of Interventional Cardiology, to warehouse and analyze catheterization data. We successfully modified PedCath to transfer the results of catheter-based therapies on 256 therapeutic procedures for atrial septal defect (ASD) closure, coarctation of the aorta angioplasty and stenting, and pulmonary and aortic balloon valvuloplasties over a 13-month pilot period. Short-term follow-up within the 13-month period was received on 31 patients. This study demonstrated the successful development of a simple process, requiring minimal data entry for investigators from around the world to share cardiac catheterization data for long-term outcome determination of catheter-based therapies for congenital heart disease.

Adolescent↗

Mushrooms by magic: making connections between signal transduction and fruiting body development in the basidiomycete fungus Schizophyllum commune.

The basidiomycete fungus Schizophyllum commune has been utilised as a model system for examining the genetic regulation of sexual reproduction, a process that culminates in the production of mushrooms in this and many other related species. Recent studies have suggested that conserved elements of the cyclic AMP (cAMP) signalling pathway play a role in the control of mushroom development in S. commune. The small G-protein Ras also appears to impinge on the process, either by inputting into the cAMP pathway, or by acting in parallel. The molecular connections between nutrient sensing and mushroom development are now beginning to be examined.

Adaptation, Physiological↗

High resolution magic angle spinning NMR spectroscopy used to investigate the ability of drugs to bind to synthetic melanin.

Iodobenzamides are known to possess an affinity for melanoma tissue dependent on tumor pigmentation. In order to investigate the molecular interactions of drugs with melanin in vitro, a synthetic pigment swelled in deuterium buffer at physiological pH was used. The spectra of various mixtures of each Iodobenzamide (BZ) with melanin were studied at 25 degrees C by NMR under MAS conditions. The drug which interacts with the pigment exhibits linewidths greater than those observed for the free drug in solution. Line-broadening of the resonance occurred for the N-methyl group of acetylcholine or N-ethyl and aromatic groups of BZ. However, linewidths associated with methanol or hippuric acid were less altered by the presence of melanin. These observations indicate the specificity of the interaction between some drug moieties and the sites of melanin. From the concentration dependence of line-broadening, the apparent equilibrium dissociation constant (K(d)) of drug interaction with melanin was approached. It seems that the residual concentration-dependent line-broadening is caused by perturbations of ligand exchange between free and bound states and by differences in magnetic susceptibility present in the sample at the pigment-interacting drug moiety interface. Taken together, these results demonstrate the utility of this technique for investigating binding drugs.

Electron Spin Resonance Spectroscopy↗

Regenerating the periodontium: is there a magic formula?

OBJECTIVE: Left untreated, periodontal disease results in destruction of periodontal tissues including cementum, bone and the periodontal ligament, and subsequently, tooth loss. Increased research efforts focused on understanding periodontal disease at the cellular, molecular and clinical level have resulted in improved modalities for arresting disease progression; however, outcomes of existing procedures are not predictable and often disappointing. Critical to improving the predictability of regenerative therapies is targeting studies toward enhancing our understanding of the cellular and molecular events required to restore periodontal tissues. DESIGN: Toward this goal our laboratory has focused on defining cells, mechanisms and factors regulating development of periodontal tissues, using in vitro and in vivo rodent models. RESULTS AND CONCLUSION: Results from these studies have enabled us to identify attractive candidate factors/cells including: 1) products secreted by epithelial cells that act on mesenchymal cells (amelogenins): we observed that both follicle cells and cementoblasts are responsive to amelogenin-like molecules resulting in changes in the expression of genes associated with cell maturation; 2) morphogens (bone morphogenetic proteins, BMP): we report that follicle cells respond differently to BMPs vs. cementoblasts, depending on dose of and specific BMP used; 3) phosphates: existing data suggest that phosphates act as signaling molecules regulating the expression of genes associated with cementoblast maturation. Knowledge gained from these studies has provided insight as to the cells/factors required for designing improved regenerative therapies.

Amelogenin↗

The epigenetic magic of histone lysine methylation.

Epigenetic mechanisms control eukaryotic development beyond DNA-stored information. There are several pathways, including histone tail modifications, histone variant incorporation, nucleosome remodelling, DNA methylation and noncoding RNAs that together all contribute to the dynamic 'make-up' of chromatin under distinct developmental options. The histone tail modifications are most variable and over 50 marks have by now been mapped. While the majority of these modifications are transient, histone lysine methylation and, in particular, a histone lysine tri-methyl state has been regarded as a more robust signal, consistent with proposed roles to impart long-term epigenetic memory. Based on the paradigm of SET-domain histone lysine methyltransferases (HMTases) and chromo-domain adaptor proteins, and in conjunction with the Sir Hans Krebs Medal 2005, I describe here my personal view on the discovery of the first HMTase in 2000, and the subsequent advances on the biology of histone lysine methylation. This discovery has changed my scientific career and significantly contributed to a better understanding of epigenetic control, with important implications for heterochromatin formation, X inactivation, Polycomb group silencing and novel insights into stem cell research, nuclear reprogramming and cancer.

Animals↗

The magic of nursing.

Explore the source record for details and available documents.

Career Choice↗

Fat loading: the next magic bullet?

The depletion or reduction of bodily carbohydrate reserves is associated with fatigue during endurance exercise. Various carbohydrate supplementation and exercise regimens have been used experimentally to increase carbohydrate reserves before exercise or to maintain the availability of carbohydrate for oxidation during exercise. On the other hand, the improved endurance capability observed after aerobic training has been attributed to an increased oxidation of fat relative to carbohydrate; this carbohydrate sparing presumably delays the point at which reduced carbohydrate reserves cause fatigue. This effect has led to the suggestion that a greater availability of fat during exercise can improve performance via the carbohydrate-sparing effect of "fat loading." Although this is a plausible hypothesis, it is not supported by a sufficient number of valid, credible, and replicated studies. Thus, it appears prudent to advise endurance athletes to consume a diet that is largely carbohydrate to optimize training and competitive performance and, more importantly, to promote optimal health.

Carbohydrate Metabolism↗