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Abstract Background Observational studies, if conducted appropriately, play an important role in the decision-making process providing invaluable information on effectiveness, patient-reported outcomes and costs in a real-world environment. We conducted a systematic review of large-scale, prospective, cohort studies with the aim of (a) summarising design characteristics, the interventions or aspects of the disease studied and the outcomes measured and (b) investigating methodological quality. Methods We included prospective, cohort studies which included at least 100 adults with psoriasis or psoriatic arthritis. Studies were identified through searches in electronic databases (Pubmed, Medline, Cochrane library, Centre for Reviews and Dissemination). Information on study characteristics were extracted and tabulated and quality assessment, using a checklist of 18 questions, was conducted. Results Thirty five papers covering 16 cohorts met the inclusion criteria. There were ten treatment-related studies, only two of which provided a comparison between treatments, and six non-treatment studies which examined a number of characteristics of the disease including mortality, morbidity, cost of illness and health-related quality of life. All studies included a clinical outcome measure and 11 included patient-reported outcomes, however only two studies reported information on patient utilities and two on costs. The quality of the assessed studies varied widely. Studies did well on a number of quality assessment questions including having clear objectives, documenting selection criteria, providing a representative sample, defining interventions/characteristics under study, defining and using appropriate outcomes, describing results clearly and using appropriate statistical tests. The quality assessment criteria least adhered to involved questions regarding sample size calculations, describing potential selection bias, defining and adjusting for confounders and losses to follow-up, and defining and describing a comparison group. Conclusion The review highlights the need for well designed prospective observational studies on the effectiveness, patient-reported outcomes and economic impact of treatment regimes for patients with psoriasis and psoriatic arthritis in a real-world environment.

Abstract Background Dishevelled (Dsh) is a key component of multiple signaling pathways that are initiated by Wnt secreted ligands and Frizzled receptors during embryonic development. Although Dsh has been detected in a number of cellular compartments, the importance of its subcellular distribution for signaling remains to be determined. Results We report that Dsh protein accumulates in cell nuclei when Xenopus embryonic explants or mammalian cells are incubated with inhibitors of nuclear export or when a specific nuclear-export signal (NES) in Dsh is disrupted by mutagenesis. Dsh protein with a mutated NES, while predominantly nuclear, remains fully active in its ability to stimulate canonical Wnt signaling. Conversely, point mutations in conserved amino-acid residues that are essential for the nuclear localization of Dsh impair the ability of Dsh to activate downstream targets of Wnt signaling. When these conserved residues of Dsh are replaced with an unrelated SV40 nuclear localization signal, full Dsh activity is restored. Consistent with a signaling function for Dsh in the nucleus, treatment of cultured mammalian cells with medium containing Wnt3a results in nuclear accumulation of endogenous Dsh protein. Conclusions These findings suggest that nuclear localization of Dsh is required for its function in the canonical Wnt/β-catenin signaling pathway. We discuss the relevance of these findings to existing models of Wnt signal transduction to the nucleus.

Treatment for lymphoma often involves regimens containing doxorubicin and/or cyclophosphamide. Both are cardiotoxic and we have previously shown that the ascending and descending aorta can also be affected. In view of this we have measured the ambulatory blood pressures of patients newly diagnosed with lymphoma undergoing chemotherapy with and without cardiotoxic agents. Three separate 24 h recordings were taken: at the beginning, half-way through and on completion of treatment. There was no significant change in the blood pressure whether or not treatment included doxorubicin and/or cyclophosphamide containing regimens. Our findings suggest that the peripheral vasculature is not affected by standard first-line cardiotoxic chemotherapy in patients without known cardiovascular disease.

Avascular necrosis of bone (AVNB) is a well-known but rare complication of chemotherapy for lymphoma with a reported incidence ranging from 1 to 10 per cent. Early diagnosis is essential for optimal therapeutic management. Using MRI, the most sensitive means of detecting the earlier stages of AVNB, 100 patients treated with standard chemotherapy for lymphoma were assessed. Fifteen were found to have changes of AVNB, 10 with early changes but five with advanced segmental collapse of the femoral head. None with AVNB had more than the standard course of corticosteroids. Almost a quarter of the study group complained of joint pain during and/or after their treatment, a third of whom were found to have AVNB; a strong indicator to screen all those with pain. However, 40 per cent of those with AVNB were asymptomatic. The clinical significance of the 'silent hip' is yet to be elucidated.

Young women with a chemotherapy-induced early menopause are theoretically at considerable risk of developing post-menopausal osteoporosis with problems developing earlier and more severely. In this study bone mineral density (BMD) measurements were made, using a dual-energy X-ray absorptiometer (DXA), at the spine and hip of 50 young women who had been treated for lymphoma, 24 of whom were post-menopausal and 78, healthy age-matched controls. On analysis of the results, there was no significant difference between the control group and the 26 post-treatment, pre-menopausal patients, but the BMD levels were significantly lower than the controls in the post-menopausal group particularly in 16 patients who had been menopausal greater than 18 months. The results confirm that these young women with treatment-induced premature menopause are at considerable risk of developing osteoporotic problems. Early recognition of this is important so that preventative measures with hormone replacement therapy can be initiated where this is safely possible. The results also indicate that chemotherapy for lymphoma (cytotoxics and high dose intermittent steroids), are unlikely to contribute directly to the lowering of the BMD of these patients.

CD4+ T cells of patients with B cell non-Hodgkin's lymphoma (NHL) were analysed for expression of CD45RA and CD29. It was found that CD45RA expression was significantly lower, and CD29 expression significantly higher, in lymphoma patients compared to normal controls. Moreover absolute numbers of CD4+ T cells were significantly lower in NHL patients, due to selective depletion of CD4+ CD45RA+ cells.

CD4+ T cells of 57 patients with B cell chronic lymphocytic leukaemia (CLL) were analysed for expression of CD45RA and CD29. The majority of CLL patients (33 cases) showed a novel coexpression of these markers on a significant proportion of CD4+ T cells; however, analysis of a single blood sample revealed no apparent prognostic value associated with the markers. Expression of CD45RA and CD29 correlated with parameters of immune function consistent with the known attributes of these markers.

Cytotoxic chemotherapeutic agents, particularly the anthracyclines, are known to be cardiotoxic, but toxic effects on the aorta have not previously been documented. In this study, diameters of ascending and descending thoracic aortae were measured by computerized tomography in 69 patients with lymphoma, before and after first-line treatment with one of 7 different regimes. Minor increases in aortic diameter over the study period due to the aging process were expected. These increases were greater than anticipated in both the ascending and the descending aortae after chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and CVP (cyclophosphamide, vincristine, and prednisolone) regimes. Smaller changes, or changes which were not statistically significant, were noted after MVPP (mustine, vinblastine, procarbazine, and prednisolone), ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisolone), ChlVP (chlorambucil, vincristine and prednisolone), mediastinal radiotherapy, and radiotherapy plus MVPP (MVPP/XRT). Cardiovascular damage associated with certain forms of cytotoxic therapy is not confined to the heart, but also affects the aorta.

All young patients in the Grampian area attending the lymphoma review clinic who had received first line treatment for Hodgkin's disease and had attained complete remission without subsequent relapse were studied between 1980 and 1983. Chemotherapy with MVPP (mustine, vinblastine, procarbazine, and prednisolone) had more severe effects on the fertility of men than that of women; younger women and those taking oral contraceptives were more likely to retain fertility than those over 30 or not taking the pill at the time of chemotherapy, but these two effects could not be differentiated. Premature menopause was common after treatment with MVPP. Mantle radiotherapy had no discernible effect on gonadal function.

The activity of the lysosomal hydrolase N-acetyl-beta-D-glucosaminidase (NAG) was measured in the urine of patients with leukaemia or myeloma. Elevated pre-treatment enzymuria was noted in all patient groups with acute myeloblastic leukaemias (AML) FAB type M4 or 5 displaying higher activities than AML patients FAB types M1-3, which in turn were higher than those found in patients with myelomatosis and chronic lymphocytic leukaemia. The ratio of the major isoenzymes of NAG, A/B was reduced significantly only in patients with AML. Following treatment, AML patients who entered remission demonstrated NAG levels which approached normal values. In those AML patients who were either in relapse, in the terminal phase of their illness or treated with aminoglycoside antibiotics, NAG enzymuria was similar to pre-treatment values. A reduction in urinary NAG levels and both serum and urine beta 2 microglobulin concentrations was also observed following treatment in myeloma patients. The use of enzymuria both as a guide to progress towards remission in AML patients and for assessing prognosis and progress in myeloma patients is discussed.