2,455 publications from this institution
Patella infera is an uncommon but potentially crippling pathology of the knee, resulting in stiffness and anterior knee pain. Several surgical methods have been described for its treatment, but there remains no clear technique of choice. We present the case of a 63-year-old male with patella infera, affecting a native knee, following Complex Regional Pain Syndrome. This patient was treated with a combined technique of Patellar Tendon lengthening and partial Hourglass Extensor Mechanism Allograft reconstruction. The results were excellent at 24 months of follow-up. To our knowledge, this technique has not yet been published, and we present it as a promising treatment option in selected cases.
For red deer stags, fighting both has appreciable costs and yields considerable benefits. Up to 6% of rutting stags are permanently injured each year, while fighting success and reproductive success are closely related, within age groups as well as across them. Fighting behaviour is sensitive to changes in the potential benefits of fighting: stags fight most frequently and most intensely where potential benefits are high and tend to avoid fighting with individuals they are unlikely to beat. The relevance of these findings to theoretical models of fighting behaviour is discussed.
Although global morbidity and mortality have decreased substantially, malaria, a parasite infection of red blood cells, still kills roughly 2000 people per day, most of whom are children in Africa. Two factors largely account for these decreases; increased deployment of insecticide-treated bednets and increased availability of highly effective artemisinin combination treatments. In large trials, parenteral artesunate (an artemisinin derivative) reduced severe malaria mortality by 22·5% in Africa and 34·7% in Asia compared with quinine, whereas adjunctive interventions have been uniformly unsuccessful. Rapid tests have been an important addition to microscopy for malaria diagnosis. Chemopreventive strategies have been increasingly deployed in Africa, notably intermittent sulfadoxine–pyrimethamine treatment in pregnancy, and monthly amodiaquine–sulfadoxine–pyrimethamine during the rainy season months in children aged between 3 months and 5 years across the sub-Sahel. Enthusiasm for malaria elimination has resurfaced. This ambitious but laudable goal faces many challenges, including the worldwide economic downturn, difficulties in elimination of vivax malaria, development of pyrethroid resistance in some anopheline mosquitoes, and the emergence of artemisinin resistance in Plasmodium falciparum in southeast Asia. We review the epidemiology, clinical features, pathology, prevention, and treatment of malaria.
No abstract is provided for this article.
Population viability analysis (PVA) packages do not always allow realistic simulation of particular life cycle features, so they may produce unrealistic predictions of extinction risk. This was suspected for a cycling Soay sheep population, Ovis aries L., that grows, overeats its habitat and then suffers high winter mortality. We compared projections of PVA models for the sheep that incorporated either an unrealistic ceiling carrying capacity using INMAT (the only choice) and VORTEX (the default), or realistic density dependence for survival (VORTEX). At year 50, the ceiling models predicted extinction probabilities of 60.4% (INMAT) and 87.4% (VORTEX), compared to only 4.6% for the density-dependent model. Small populations were equally likely to increase or decrease with the ceiling models, while they had high probabilities of increase with the density-dependent model, as found in reality. PVA cannot be relied upon to produce realistic projections if inappropriate mechanisms of population regulation are used.
If today a physician emerged from a time capsule which he had entered 50 years ago, he would recognize very few of the medicines in current use – with one sad exception – the drugs used for tropical diseases. The market forces that drive the development of new drugs, diagnostics and vaccines are absent in poor countries, the colonial incentives have gone, and military investment has declined. Indeed in the profit-driven commercial sector the force may be in the opposite direction – inhibiting the discovery and development of new medicines which are clearly desperately needed, but cannot be afforded. Trouiller et al. (2002) reviewed all new chemical entities introduced into medicine between 1975 and 1999; there were 1393, of which only 16 were for a ‘tropical disease’ indication or for tuberculosis. It is a sad fact that we still treat African trypanosomiasis with the poison arsenic, which probably kills at least 5% of those who receive it, and we still use toxic antimonials for leishmaniasis. Would we be in this sorry situation if these infections were prevalent in wealthy countries? Of course not. Directing resources to drug discovery can be remarkably successful – for example who would have predicted the extent of antiretroviral drug discovery 20 years ago? Meanwhile we are losing the drugs we have relied upon to control infectious diseases in the developing world. Drug resistance is threatening the control of pneumococcal disease, tuberculosis, malaria, shigellosis, typhoid, and leishmaniasis. But at last things may be changing for the better. The richer world has finally woken up to the vast humanitarian and economic toll that infectious diseases exert on poor countries. The recent avian influenza scare has emphasized how small our world really is. Governments and charities based in wealthy countries are now contributing significantly more to addressing these potentially soluble scourges. Within the past 10 years we have seen numerous initiatives started, most notably the Global Fund to combat HIV, TB and malaria. More specifically several not-for-profit organizations have formed to address the dire lack of effective diagnostics, vaccines, and drugs for tropical diseases. Sponsoring drug development are the Medicines for Malaria Venture, the Institute for One World Health, the Global Alliance for TB Drug Development, and the Drugs for Neglected Diseases Initiative. These organizations receive funding from a variety of donors. They provide support both for basic discovery, mainly in the academic sector, and then they aim to carry viable products through a conventional development programme with the objective of finding a suitable industrial partner or partners, obtaining widespread registration in endemic countries, and deploying the new drugs at the lowest possible prices. These initiatives are already bearing fruit, although most of the new drugs that will appear in the next 5 years are not recent innovations. They are directed against known drug targets (the new antimalarials), or are developments of existing products for new indications (nifurtimox for trypanosomiasis, miltefosine for leishmaniasis), or completion of stalled developments (aminosidine for leishmaniasis). We still need to identify genuine new targets both to improve efficacy and tolerability, and also as a necessary insurance in case existing drugs fall to resistance. This research must be commissioned now as it takes years, and sometimes decades (e.g. artemisinin), of gestation for new chemical entities to progress through development to emerge as a new medicine, and, as is well known, most products are stillborn in utero. New drugs allow new treatment strategies to be developed. For example the treatment of falciparum malaria has changed dramatically in recent years. For this we must thank the Chinese scientists who have contributed most of the recently introduced antimalarial drugs. It was they who developed artemisinin and its derivatives, lumefantrine, pyronaridine, and piperaquine. Artemisinin combinations are now considered the treatment of choice for uncomplicated falciparum malaria, extending the rationale developed for antituberculosis treatment that combining drugs with different targets prevents the emergence of resistance. If we had more drugs we would be thinking seriously about this strategy for other important parasitic infections. Our reliance on a single drug (praziquantel) for schistosomiasis and on ivermectin for onchocerciasis is risky. We relied on antimonials alone for leishmaniasis, and arsenicals for late stage sleeping sickness. Resistance has emerged to both, and the future is uncertain. Disparities sometimes work in the reverse direction. Artemisinin derivatives are still unavailable in North America. Other effective, albeit less rapidly acting, antimalarials are available there, but for the unfortunate traveller admitted to hospital in the US or Europe with severe malaria, only inferior treatments are available (quinidine in USA, quinine in most of Europe). Artesunate has recently been shown to reduce the mortality of severe malaria by 35% (Dondorp et al. 2005) yet parenteral artesunate is not registered in many countries, and there is currently no formulation available that meets internationally recognized good manufacturing practices standards. After all what commercial incentive would there be for a pharmaceutical company to register a drug in Europe or USA which would be prescribed fewer than a hundred times a year? This has created a bizarre reverse of the usual situation: patients in rich countries cannot obtain the best drug for a lethal infection. It is time to address these disparities in drug development, and to drag the treatment of tropical diseases from the 19th firmly into to the 21st century.
Independence for Malaya in 1957 (and the enlargement of the federation to form Malaysia in 1963) did not have an immediately adverse effect upon British economic interests there. Indeed, Britain retained, and even revived, its huge commercial, industrial, and financial presence in Commonwealth Southeast Asia well into the 1960s. From the middle of that decade, however, British economic influence in Malaysia declined quite rapidly. The main focus of this article is to examine three possible causes of this downturn: declining competitiveness on the part of British manufactures; UK government policy towards private investment and public expenditure overseas; and entrepreneurial weaknesses among the British agency houses in Malaysia.
