Deposition of calcium pyrophosphate in tissue after revision arthroplasty of the hip

We reviewed histologically the incidence and pathogenesis of the deposition of calcium pyrophosphate dihydrate (CPPD) crystals in the pseudocapsule, femoral and acetabular membranes and periprosthetic tissue at revision of 789 cases of failed total hip replacement. In 13, periprosthetic tissues were found to have deposits of CPPD crystals in areas of cartilaginous metaplasia; four also showed evidence of localised deposition of amyloid. None of the patients had a history of chondrocalcinosis in the hip or other joints. Cartilaginous metaplasia and other changes in periprosthetic tissues may predispose to the deposition of CPPD and associated localised amyloid.     

Do women 'over-report' morbidity? Men's and women's responses to structured prompting on a standard question on long standing illness

It is frequently observed in contemporary industrialised societies that although women live longer than men, they are sicker than men in that they report higher rates of morbidity, disability and health care use. One common element of the explanation for women's higher rates of morbidity is that there are gender differences in the way that symptoms are perceived, evaluated and acted upon. It is widely assumed that women will be more ready to report illness and to seek help and that they have greater flexibility in their lives to accommodate illness. The few studies that have examined men and women with the same conditions or symptoms are contradictory, but lend little support to this hypothesised greater propensity, yet it is still widely believed. Here we compare men's and women's answers to a global, commonly used question about chronic illness and to a series of more specific prompts and classify the conditions reported by an externally defined categorisation of severity and International Classification of Disease chapter. Contrary to the common expectation that women report higher rates of morbidity and are more ready to report mental health problems, we found: no gender differences in the initial reporting of conditions; men reported a higher proportion of their conditions in response to the initial global question; and no evidence that women were more likely to report 'trivial' or mental health conditions in response to the initial question.     

Shaping the future: a primary care research and development strategy for Scotland

Primary care is at the centre of the National Health Service (NHS) in Scotland; however, its R & D capacity is insufficiently developed. R&D is a potentially powerful way of improving the health and well-being of the population, and of securing high quality care for those who need it. In order to achieve this, any Scottish strategy for primary care R&D should aim to develop both a knowledge-based service and a research culture in primary care. In this way, decisions will be made based upon best available evidence, whatever the context. Building on existing practice and resources within primary care research, this strategy for achieving a thriving research culture in Scottish primary care has three key components: A Scottish School of Primary Care which will stimulate and co-ordinate a cohesive programme of research and training. A comprehensive system of funding for training and career development which will ensure access to a range of research training which will ensure that Scotland secures effective leadership for its primary care R&D. Designated research and development practices (DRDPs) which will build on the work of existing research practices, in the context of Local Health Care Co-operatives (LHCCs) and Primary Care Trusts (PCTs), to create a co-operative environment in which a range of primary care professionals can work together to improve their personal and teams' research skills, and to support research development in their areas. A modest investment will create substantial increases in both the quality and quantity of research being undertaken in primary care. This investment should be targeted at both existing primary care professionals working in service settings in primary care, LHCCs and PCTs, and at centres of excellence (including University departments). A dual approach will foster collaboration and will allow existing centres of excellence both to undertake more primary care research and to support the development of service based primary care professionals in their research. Resources should be distributed equitably, taking into account demography, geography and the health needs of patients in Scotland. The strategy and its components must be seen as a whole. The Scottish School of Primary Care will stimulate and co-ordinate both research and training programmes. DRDPs will become research active and will participate in School-led training and research, and will contribute to research programmes. Comprehensive funding for training and career development will ensure that staff have the skills to participate in both DRDPs and in the School's activities. Thus, inadequate commitment to any one component of the strategy will mean that other components will be less successful. Commitment to all three components will maximise the chances of success.     

Enhanced retinal longwave sensitivity using a chlorophyll-derived photosensitiser in Malacosteus niger, a deep-sea dragon fish with far red bioluminescence.

Through partial bleaching of both visual pigment extracts and cell suspensions we show that the deep-sea stomiid Malacosteus niger, which produces far red bioluminescence, has two visual pigments within its retina which form a rhodopsin/porphyropsin pigment pair with lambda max values around 520 and 540 nm, but lacks the very longwave sensitive visual pigments (lambda max > 550 nm) observed in two other red light producing stomiids. The presence of only a single opsin gene in the M. niger genome was confirmed by molecular and cladistic analysis. To compensate for its apparently reduced longwave sensitivity compared to related species, the outer segments of M. niger contain additional pigments, which we identify as a mixture of defarnesylated and demetallated derivatives of bacteriochlorophylls c and d, that are used as a photosensitiser to enhance its sensitivity to longwave radiation.     

Part I. "Behind every problem lies an opportunity": meeting the challenge of diversity in medical schools

The authors describe the historical evolution and present status of affirmative action in medical school admission policies. The demographic transformation of the medical student body between 1965 and 1998 from a homogeneous white and male group to one that includes a significant number of women and minority students is presented. Challenges to affirmative action are outlined. In addition, the authors note the increasing diversity of the general population and discuss the benefits of diversity to medical practice, research, and education. However, the upper ranks of professors and administrators remain white and male. The rationale for an innovative course on the history of bias in medicine and the benefits that diversity brings to the medical enterprise are presented.     

Discovery and structure-activity relationships of imidazole-containing tetrahydrobenzodiazepine inhibitors of farnesyltransferase

2,3,4,5-Tetrahydro-1-(imidazol-4-ylalkyl)-1,4-benzodiazepines were found to be potent inhibitors of farnesyltransferase (FT). A hydrophobic substituent at the 4-position of the benzodiazepine, linked via a hydrogen bond acceptor, was important to enzyme inhibitory activity. An aryl ring at position 7 or a hydrophobic group linked to the 8-position through an amide, carbamate, or urea linkage was also important for potent inhibition. 2,3,4, 5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2-(t rifluo romethoxy)benzoyl]-1H-1,4-benzodiazepine (36), with an FT IC(50) value of 24 nM, produced 85% phenotypic reversion of Ras transformed NIH 3T3 cells at 1.25 microM and had an EC(50) of 160 nM for inhibition of anchorage-independent growth in soft agar of H-Ras transformed Rat-1 cells. Selected analogues demonstrated ip antitumor activity against an ip Rat-1 tumor in mice.     

Anti-ulcerogenic properties of endothelin receptor antagonists in the rat

BACKGROUND: Endothelins have been implicated in gastric mucosal damage in a variety of animal models. Exogenous ET-1 and ET-3 are causally associated with experimental gastric ulcers. Furthermore, clinical reports also show elevated plasma and gastric mucosal endothelin-1 levels in patients suffering from peptic ulcers. AIM: To study the possibility that endothelin receptor antagonists may have beneficial effects and prevent the development of gastric ulcers. We have tested in rats the orally-active endothelin antagonist bosentan (Ro 47-0203) and Ro 48-5695, which is 10-30 times more potent than bosentan on endothelin receptors. METHODS: Water immersion restrained stress (WIRS) and indomethacin were used to provoke gastric mucosal damage. Endothelin receptor antagonists were administered orally prior to the induction of gastric damage. The gastric lesion index (mm), assessed macroscopically, and myeloperoxidase (MPO) activity were used as markers of the extent of mucosal injury. RESULTS: Bosentan at 100 and 30 mg/kg administered orally caused attenuation of gastric damage in the WIRS model by 58% and 42%, respectively. Bosentan also caused complete reduction of MPO activity. In indomethacin-induced gastric damage, 100 mg/kg bosentan attenuated gastric damage by 45% and 61% as measured by the gastric lesion index and MPO activity respectively. Ro 48-5695 was at least 30 times more potent than bosentan in reducing indomethacin-induced mucosal damage and at 3 mg/kg, caused a decrease of 49% in the gastric lesion index and a reduction in MPO activity of 41%. Bosentan and Ro 48-5695 possess weak antisecretory properties as tested in the mouse gastric gland assay, than cannot, alone, account for their anti-ulcer properties. CONCLUSIONS: Both endothelin receptor antagonists prevented the development of gastric mucosal injury in the rat. Disturbances in the gastric microcirculation are responsible for the development of experimental gastric ulcers. The anti-ulcer properties of these two endothelin antagonists suggest possible new therapeutic approaches to controlling gastric inflammation.