Diabetic mastopathy: a distinctive clinicopathologic entity.

Insulin-dependent diabetics may manifest evidence of autoimmune diseases involving endocrine or other organs. Rare cases of a peculiar fibrous and inflammatory lesion of the breast in diabetic patients have been previously described; however, the pathologic and clinical features that uniquely characterize these cases have not been defined or distinguished from other chronic inflammatory and fibrosing conditions in the breast. We studied eight patients with breast masses and longstanding insulin-dependent diabetes and compared them with 36 nondiabetic or short-duration diabetic patients with fibrosis and chronic mastitis. The longstanding diabetic patients presented with clinical breast masses ranging in size from 2 to 6 cm. Six of the eight patients had documented diabetic nephropathy, retinopathy, or neuropathy. Pathologically, these lesions showed lymphocytic lobulitis and ductitis, lymphocytic vasculitis (predominantly B cell), and dense keloid-like fibrosis that in many cases (six of eight) contained peculiar epithelioid cells embedded in dense fibrous stroma. We have provisionally labeled these cells "epithelioid fibroblasts" (EFBs). Although the features of lymphocytic lobulitis, ductitis, and/or vasculitis may occasionally be encountered in nondiabetic breast biopsies, EFBs appear to be unique to the diabetic condition. Control cases of chronic mastitis in nondiabetic or short-duration diabetes patients failed to show the complete constellation of lymphocytic lobulitis and ductitis, vasculitis, keloidal fibrosis, and EFBs. Diabetic mastopathy may represent an immune reaction to abnormal matrix accumulation. A hypothesis is presented.     

Behavioral evidence for supersensitivity after chronic bromocriptine administration

Behavioral evidence for tolerance and supersensitivity during and after chronic (30 day) administration of bromocriptine (BRC) or bromocriptine + L-dopa in mice was assessed by measuring wheel running (WR) behavior during and after chronic drug administration, and apomorphine- and methylphenidate-(MP-) induced stereotyped gnawing after termination of chronic injections. In both BRC and BRC +L-dopa groups, tolerance developed fairly quickly to the depressing effect of BRC on WR seen on day 1 of drug administration. Mice receiving BRC showed significant increases in WR by week 2 of chronic drug administration, which persisted for at least two days after the termination of chronic injections. During the first week after termination of chronic injections, low doses of both apomorphine and MP induced significantly more stereotyped gnawing in BRC and BRC + L-dopa mice than in the control mice or the mice treated with L-dopa alone. This behavioral evidence for dopaminergic supersensitivity after chronic BRC administration may have relevance for the clinical use of BRC in combination with L-dopa or other dopamine agonists.     

High blood pressure and the kidney: the forgotten contribution of William Senhouse Kirkes

The realization of the key role for raised intra-arterial pressure as a pathogenetic agent in hypertension is usually credited to Ludwig Traube, but Traube in his writings gives credit for the idea to a little-known English doctor, William Senhouse Kirkes (1822-1864). Kirkes' main interest was in cardiology and vascular disease, and he gave the first account of embolism from vegetations in infective endocarditis in 1852. Three years later, he published a study of apoplexy in Bright's disease, in which he pointed clearly to the role of raised intra-arterial tension in the causation of arterial disease, a point that had eluded Bright, Johnson, and other contemporaries. Kirkes died at the age of only 42 while working on a book summarizing his work on cardiology and renal disease, and the neglect of his contribution probably resulted from his early death. We have traced his life history from the few available records; as a boy, Kirkes was apprenticed to become a surgeon and only later trained as a physician. We place his contributions within the setting of the development during the 19th century of understanding of the relationship between the kidney, vascular disease, and high blood pressure.     

The new GMS contract: impact and implications for managing the changes.

BACKGROUND: In February 2003, a new General Practitioner (GP) contract was agreed between the profession's leaders and the government, which was later accepted following a national ballot of GPs. However, the ballot simply required respondents to vote for or against the proposal; it did not provide any opportunity to identify which aspects of the new contract were more or less acceptable. Since the proposed changes were far reaching, the implications of implementing and managing these were considerable. Consequently, some information about how GPs viewed various components of the new contract would enable a more targeted and effective management strategy to be developed that would facilitate the introduction of all aspects of the contract. OBJECTIVES: To survey GPs working within the West Midlands region regarding their opinions on each of the key features of the new contract. METHOD: A postal survey of 360 GPs was undertaken, using a specially devised questionnaire. RESULTS: Four factors emerged as the most acceptable aspects of the contract: option to opt out of out-of-hours work, flexibility in the services provided, prediction of future income levels and linking practice to performance targets. Least acceptable were: performance monitoring systems, the new financial formula for calculating income, greater patient involvement in service development and 24/48 hour access. With regard to potential outcomes of the contract, the most positive were considered to be increased proportion of salaried GPs, increased salaries, appropriate quality standards for care, earlier retirement; the factors least likely to be of potential benefit were: reduction in occupational stress, simplification of the regulatory framework, improved equity of workload and improved staff retention. Further analysis of the results using inferential statistics revealed a range of subgroup differences in reaction to the contract. CONCLUSION: Overall, those aspects of the new contract that are perceived to reduce workload and enhance salary were supported, while those that increase targets and bureaucracy were not. Generally, there was only moderate support for the changes, which could be explained by a general scepticism about any top-down modifications, the practicality and power of the changes to impact upon practice and/or a genuine belief that the modifications are unacceptable. Taken together, these results provide an indicative focus for managing the implementation of the new contract, especially with regard to its least acceptable components and the emerging differences between subgroups of GPs.