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Background: Inflammatory back pain (IBP) is an early feature of ankylosing spondylitis (AS) and its detection offers the prospect of early diagnosis of AS. However, since back pain is very common but only a very small minority of back pain sufferers have ASpA or AS, screening of back pain sufferers for AS is problematic. In early disease radiographs are often normal so that fulfilment of diagnostic criteria for AS is impossible though a diagnosis of axial SpA can be made if MRI evidence of sacroiliitis is present. This pilot study was designed to indicate whether a cost-effective pick up rate for ASpA/early AS could be achieved by identifying adults with IBP stratified on the basis of age. Methods: Patients aged between 18 and 45 years who were referred to a hospital physiotherapy service with back pain of more than 3 months duration were assessed for IBP. All were asked to complete a questionnaire based on the Berlin IBP criteria. Those who fulfilled IBP criteria were also asked to complete a second short questionnaire enquiring about SpA comorbidities, to have a blood test for HLA-B27 and CRP level and to undergo an MRI scan of the sacroiliac joints. This was a limited scan, using STIR, diffusion-weighted, T1 and T2 sequences of the sacroiliac joints to minimize time in the scanner and cost. The study was funded by a research grant from Abbott Laboratories Ltd. Results: 50 sequential patients agreed to participate in the study and completed the IBP questionnaire. Of these 27 (54%) fulfilled criteria for IBP. Of these, 2 patients reported a history of an SpA comorbidity - 1 psoriasis; 1 ulcerative colitis - and 3 reported a family history of an SpA comorbidity - 2 psoriasis; 1 Crohn's disease. 4 were HLA-B27 positive, though results were not available for 7. Two patients had marginally raised CRP levels (6, 10 -NR ≤ 5). 19 agreed to undergo MRI scanning of the sacroiliac joints and lumbar spine; 4 scans were abnormal, showing evidence of bilateral sacroiliitis on STIR sequences. In all cases the changes met ASAS criteria but were limited. Of these 4 patients 3 were HLA-B27 positive but none gave a personal or family history of an SpA-associated comorbidity and all had normal CRP levels. Conclusions: This was a pilot study yielding only limited conclusions. However, it is clear that: Screening of patients referred for physiotherapy for IBP is straightforward, inexpensive and quick. It appears that IBP is more prevalent in young adults than overall population data suggest so that targeting this population may be efficient. IBP questionnaires could be administered routinely during a physiotherapy assessment. HLA-B27 testing in this group of patients with IBP is a suitable screening tool. The sacroiliac joint changes identified were mild and their prognostic significance is not yet clear so that the value of early screening needs further evaluation. Disclosure statement: C.H. received research funding for this study from Abbott. A.K. received research funding for this study, and speaker and consultancy fees, from Abbott. All other authors have declared no conflicts of interest

The treatment of advanced mycosis fungoides is a therapeutic challenge. A variety of treatment approaches have been used. In our experience, chemotherapy has been most useful. The purpose of this study was to evaluate the effectiveness of the synergy previously demonstrated between methotrexate and fluorouracil in the treatment of advanced mycosis fungoides. Ten patients with mycosis fungoides and Sézary syndrome stages IIa (n = 1), II-b (n = 4), III (n = 1), IVa (n = 2), and IVb (n = 2) were treated with sequential methotrexate followed by fluorouracil and leucovorin rescue. Each patient received several courses of chemotherapy at varying intervals, as required for control of their disease.The duration of treatment ranged from 3 to 78 months, with an average duration of 33 months. The number of cycles of chemotherapy administered to each patient ranged from five to 45, with an average of 18 infusions per patient. The average survival in patients with tumors was 5.25 years, with a median survival of 6 years. Eight of 10 patients achieved at least 80% clearing and the remaining two achieved at least 60% clearing. Adverse reactions were minimal and included nausea and vomiting, mucositis, and leukopenia in only one patient.Sequential methotrexate and fluorouracil chemotherapy is an effective and safe treatment for advanced mycosis fungoides and Sézary syndrome. This regimen is extremely well tolerated, with minimal toxic side effects.

Recent advances in tests for the genotype for hemochromatosis and suggestions that the tests be used in mass screening programs for the disease raise the possibility of a large increase in the incidence of discrimination against people who are found to be homozygous for hemochromatosis. This paper presents cases of genetic discrimination drawn from a study of discrimination against people with a variety of genetic conditions. The cases discussed here involve employment and several types of insurance discrimination against people diagnosed with hemochromatosis who either are currently asymptomatic or whose condition is controlled by means of phlebotomies. There is no justification for these types of discrimination since people with controlled hemochromatosis suffer no excess mortality or morbidity. Our study suggests that genetic discrimination is already a serious problem and that any proposed screening program for hemochromatosis or other genetic condition must consider and attempt to mitigate its effects.

Recent advances in molecular genetics methods have provided new means of determining the genetic bases of human behavioral traits. The impetus for the use of these approaches for specific behaviors depends, in large part, on previous familial studies on inheritance of such traits. In the past, a finding of a genetic basis for a trait was often accompanied with the idea that that trait is unchangeable. We discuss the definition of "genetic trait" and heritability and examine the relationship between these concepts and the malleability of traits for both molecular and nonmolecular approaches to behavioral genetics. We argue that the malleability of traits is as much a social and political question as it is a biological one and that whether or not a trait is genetic has little relevance to questions concerning determinism, free will, and individual responsibility for actions. We conclude by noting that "scientific objectivity" should not be used to conceal the social perspectives that underlie proposals regarding social change.

We describe a patient with Sezary syndrome and seronegative symmetric polyarthritis. Detailed analysis of the synovial membrane, including T lymphocyte subset delineation, demonstrated that malignant synovial infiltration was the direct cause of arthritis in this patient.

As genetic screening becomes more widespread, it becomes increasingly important to analyze the manifold implications of genetic screening programs. This paper characterizes the various types of programs and discusses some of the scientific, ethical, social, and economic issues that arise in evaluating any genetic screening program. Two examples of successful programs, newborn screening for phenylketonuria and carrier detection for Tay-Sachs disease, are presented. We then discuss three other screening programs that have not yet been fully implemented but which have already engendered a great deal of controversy: mass screening for heterozygosity for cystic fibrosis, DNA fingerprinting in the criminal justice system, and genetic screening in the workplace.

In spite of all that has been discussed, there are no hard data documenting what influences a couple's decision to have more children after the birth of a child with a genetic disorder. It is likely that recurrence risk does not play a major role. The difference between a 25 per cent and a 50 per cent recurrence risk with each pregnancy probably does not have a great deal of personal significance. However, the burden of a disease is something to which every couple can relate. They know how the disease has affected the living situation of their family, and that is very meaningful. Because genetic counseling services are not standardized and the prediction of the outcome of these services is so difficult to quantify, third parties have not been very agreeable to pay for genetic counseling. I think it is important, however, to realize that the standardization of procedures may be less important than the emotional support given to a couple during the difficult time after they have been informed that their child has a genetic disease.

A patient with a congenital claw-like lesion of the finger was studied to determine the nature of the tissue. A variety of biochemical techniques and histological examinations indicated that the lesion was an example of rudimentary polydactyly covered with stratum corneum rather than an accessory nail.

Two patients had an unusual ichthyosiform dermatosis, neurosensory deafness, and vascularizing keratitis. There was no family history of the disorder and no consanguinity. A squamous cell carcinoma of the tongue developed in one child. The association of such an eruption and deafness in previously reported cases is reviewed.

Metabolic pathways and toxic effects of long-term selenium exposure in animal models and humans have both similarities and significant differences. In animal models the target organ is the liver, in which chronic cirrhosis develops. In man the target organ appears to be the lung, which manifests acute "rose cold," or, as in our patient, a chronic granulomatous hypersensitivity. Our data indicate not only a different target organ than would have been predicted from animal models, but also a difference in the distribution of selenium in human tissues. Long-term use of selenium favors production of dimethylselenide, which is excreted by the lungs and should be considered a pulmonary toxin. The ramifications of these findings may require a change in the monitoring techniques of long-term industrial exposure and mandate a close follow-up of selenium as a health fad.

This article presents a detailed discussion of six genetic disorders with major cutaneous manifestations that might commonly be seen by the dermatologist or pediatrician. These include neurofibromatosis, tuberous sclerosis, xeroderma pigmentosum, incontinentia pigmenti, incontinentia pigmenti achromians, and Down's syndrome. The appearance of each disease at birth is described, and all manifestations of each entity are discussed in detail. Disorders with different inheritance patterns were chosen so that important genetic principles could be elucidated. The article concludes with a general discussion of genetic counseling, which draws upon the six genetic diseases for specific examples of important concepts.