During its existence in the 1980s and 1990s, it was the most popular medical school in the country, with an application to place ratio of 27:1 in 1996.St Mary's continued comparatively unmoved by the other nomadic medical schools in the area, until its merger with Imperial College in 1988, and the foundation of Imperial College School of Medicine in 1997 by the merger with Charing Cross and Westminster Medical School..
After qualifying from St Mary’s Hospital Medical School in London, Philippa Fleur Keyes-Evans took up her first appointment at the Central …
The proof of the equivalence of the four valencies of the carbon atom which was originally furnished by Henry (Bull. Acad. Roy. Belg. 1886, Classe des Sciences, 12, (111), 644, 1888,15, 333 and 1906, 722) can no longer be regarded as rigid in view of the possibilities of intramolecular rearrangement on the lines of the so-called Walden inversion. Fischer and Brieger (Berichte, 1915, 48, 1517) have accordingly taken up this question once more, making use of a series of reactions in which no substitutions are called into play and which all take place at low temperatures, thereby reducing the chances of a Walden inversion to a minimum. Starting with the optically active half amide of ethyl isopropyl malonic acid [FORMULA NOT REPRODUCIBLE IN ASCII] they have obtained by the action of nitrous acid the optically inactive ethyl isopropyl malonic acid, thus demonstrating the equivalence of the two carboxyl groups. Similarly, dextrorotatory allyl propyl cyanacetic acid [FORMULA NOT REPRODUCIBLE IN ASCII] on reduction has yielded the inactive dipropyl cyanacetic acid which proves the equivalence of the two alkyl groups. It is proposed next to prepare the optically active form of vinyl ethyl cyanacetic acid [FORMULA NOT REPRODUCIBLE IN ASCII] and to reduce a portion of it to the inactive diethyl cyanacetic acid and also if possible to oxidise some of it to ethyl cyanomalonic acid [FORMULA NOT REPRODUCIBLE IN ASCII] If these latter reactions are successfully accomplished the equivalence of all the four valencies will have been established. The intricate question of the assimilation of carbon dioxide by the plant forms the subject of an interesting paper by Willstatter and Stoll (Berichte, 1915, 48, 1540). The authors' method of experimenting was to pass a regular stream of air containing a known amount of carbon dioxide through a small illuminated glass vessel immersed in a constant temperature water bath and containing from 5 to 20 grams of leaves. By estimating the amount of carbon dioxide in the issuing gas and the amount of chlorophyll in the leaves they determined the ratio between the number of grams of carbon dioxide assimilated in one hour and the weight of chlorophyll concerned, to which ratio they gave the name of assimilation number. Experiments with normal, autumnal, and etiolated leaves showed that the assimilative effect is not always proportional to the chlorophyll content, which is explained by assuming that the process of assimilation is to some extent effected by an enzyme, probably acting at the surface of contact between the chloroplast and the plasma. The fact that in leaves rich in chlorophyll an increase in illumination produces no effect on assimilation, whereas a rise in temperature brings about increased assimilation is explained by the accelerating effect of a rise of temperature upon the enzyme action. In the case of leaves deficient in chlorophyll a rise of temperature has but little influence, whereas increased illumination has a very marked effect. The explanation offered in this case is that there is more than sufficient enzyme present for the chlorophyll present, but that the greatest assimilative effect can only be attained when all the chlorophyll is exerting its maximum activity. All attempts to bring about assimilation by means of chlorophyll isolated from the leaf failed, in all probability owing to absence of enzyme. …
This chapter focuses on the prospects for using a fundamental molecular approach to identification of novel lead compounds for new drug development. A section reviews existing and potential drug targets in Mycobacterium tuberculosis. The chapter then discusses distinctive features of mycobacteria relevant to drug design, and considers experimental approaches applicable to rational drug discovery programs. Most antibacterial agents inhibit biosynthetic pathways involved in the production of macromolecules. Streptomycin, the first antibiotic available for widespread use in treatment of tuberculosis, is a member of the aminoglycoside family that disrupts bacterial protein synthesis. An important strategy for enhancing the activity of sulfonamides against some bacteria has been their use in combination with trimethoprim, a drug that inhibits a subsequent step in the tetrahydrofolate pathway catalyzed by the enzyme dihydrofolate reductase. Rifampin is a key drug in mycobacterial therapy that has a broad antibacterial spectrum and a well-defined target. Ethambutol has a polyamine-like structure and was originally thought to interfere with RNA synthesis. M. tuberculosis isolates with defects in the katG gene encoding a catalase-peroxidase enzyme develop resistance to isoniazid (INH), indicating a possible role for the enzyme in intracellular activation of the drug. The recent development of molecular genetic systems for mycobacteria opens a range of novel opportunities for drug discovery.
The effect of utilising granulocyte colony-stimulating factor (G-CSF) to maintain chemotherapy dose intensity in non-Hodgkin's lymphoma (NHL) on long-term mortality patterns has not been formally evaluated. We analysed prolonged follow-up data from the first randomised controlled trial investigating this approach. Data on 10-year overall survival (OS), progression-free survival (PFS), freedom from progression (FFP) and incidence of second malignancies were collected for 80 patients with aggressive subtypes of NHL, who had been randomised to receive either VAPEC-B chemotherapy or VAPEC-B+G-CSF. Median follow-up was 15.7 years for surviving patients. No significant differences were found in PFS or OS. However, 10-year FFP was better in the G-CSF arm (68 vs 47%, P = 0.037). Eleven deaths from causes unrelated to NHL or its treatment occurred in the G-CSF arm compared to five in controls. More deaths occurred from second malignancies (4 vs 2) and cardiovascular causes (5 vs 0) in the G-CSF arm. Although this pharmacovigilance study has insufficient statistical power to draw conclusions and is limited by the lack of data on smoking history and other cardiovascular risk factors, these unique long-term outcome data generate hypotheses that warrant further investigation.
