von Hippel-Lindau syndrome (HLS), an autosomal-dominant inherited disease, was studied in 92 affected subjects from 29 kindreds. In an initial survey to identify HLS gene carriers, all patients treated at the University of Freiburg for angiomatosis retinae (22), haemangioblastoma of the central nervous system (CNS) (63), and phaeochromocytoma (54) were examined as potential HLS gene carriers. HLS was diagnosed in 86% of the patients with angiomatosis retinae, 19% of the patients with haemangioblastoma of the CNS, and 19% of the patients with phaeochromocytoma. Based on these and on an additional 49 newly diagnosed cases (24 by clinical examination and 25 by pedigree analysis), the calculated prevalence of the disease in the district of Freiburg, Germany, with a population of 1.909 million is 1/38 951. There was a striking tendency for familial clustering of HLS features in affected kindreds. Both angiomatosis retinae and haemangioblastoma of the CNS occurred in most families, whereas renal lesions and/or pancreatic cysts and phaeochromatocytoma were mutually exclusive. This finding suggests that HLS is caused by different mutations within a complex genetic locus, or additional genetic lesions, which cooperate with the HLS gene on chromosome 3p. The data point to a linear sequence of features as follows: phaeochromocytoma, angiomatosis retinae, haemangioblastoma of the CNS, renal lesions, pancreatic cysts, and epididymal cystadenoma.

Radon and its daughter decay products are thought to be the cause of 5% of lung cancer in the UK. This assessment has been made by the National Radiological Protection Board (NRPB) after a national survey of radon levels in homes, when more houses than anticipated were found to have high levels, and after a reappraisal upwards of the effectiveness of radon and its daughter products in causing lung cancer. A review of the scientific evidence reveals no direct evidence to incriminate radon or its decay products at the levels found in our homes in lung cell carcinogenesis. The issue involves different scientific disciplines and is highly complex. Debate between scientists is required and more epidemiological studies of lung cancer and low radon exposure are necessary. Meanwhile the indirect evidence linking low levels of radon exposure to lung cancer is insufficient to warrant the remedial action proposed by the NRPB and accepted by the UK government.

Many surgeons, particularly in the UK, give inadequate primary treatment to patients with operable breast cancer. For spurious reasons they regard axillary clearance as unnecessarily extensive surgery and rely instead upon total mastectomy or tumour excision and node sampling, with or without postoperative radiotherapy. But it is now clear that relapse-free and overall survival can be improved by appropriate adjuvant therapy. Thus inadequate exploration of the axilla is doubly unjustified. Not only is there the obvious risk of failure to remove nodes that contain metastases--so that some patients are deprived of cure by primary treatment--but the extent of tumour spread will be inadequately assessed in many more patients, with the risk that they may not receive appropriate adjuvant treatment.

The limitations of the kappa statistic method to measure inter-observer variation of categorical assessments are shown by means of a hypothetical example. Another method for assessing the inter-observer variation of categorical variables, the proportion of agreement, is used for the same example, and reasons why it is preferable to the kappa statistic are given. Since this method allows measurement of the inherent difficulty of carrying out a particular assessment, it has wide applicability in the introduction of new technology. If a proportion of agreement study shows poor inter-observer agreement for a new method, the technology must either be improved or abandoned.

Environmental stimuli responsible for inducing cutaneous inflammation include contact allergens and ultraviolet light. We postulate that these diverse stimuli trigger a cutaneous inflammatory response by directly inducing epidermal keratinocytes to elaborate specific pro-inflammatory cytokines and adhesion molecules. The consequences are activation of dermal microvascular endothelial cells and selective accumulation of specific mononuclear cells in the dermis and epidermis. Thus, keratinocytes may act as "signal transducers", capable of converting exogenous stimuli into the production of cytokines, adhesion molecules, and chemotactic factors (acting in an autocrine and paracrine fashion) responsible for initiation of "antigen-independent" cutaneous inflammation. The initiation phase may facilitate or promote an amplification phase with additional production of tumour-necrosis factor alpha and interferon gamma via an "antigen-dependent" pathway, and keratinocyte/T cell/antigen-presenting dendritic cellular associations. The direct activation of keratinocytes, with their ability to produce the complete repertoire of pro-inflammatory cytokines, can profoundly influence endogenous and recruited immunocompetent cells, thereby providing the critical trigger responsible for the swift and clinically dramatic alterations that occur following contact between the epidermis and a host of "noxious" agents.

The novel macrolide immunosuppressant FK 506 is a powerful and selective anti-T-cell agent which has a similar mode of action to that of cyclosporin. Clinical studies of FK 506 in liver allograft recipients indicate a lower risk/benefit ratio than with cyclosporin, and wider evaluation of FK 506 in transplant recipients is now under way in multicentre, prospective, controlled trials in both Europe and North America.