Randomised controlled trial assessing the impact of increasing information to health visitors about children's injuries.

AIMS: To assess the effect on health visitor action of providing community health visitors with information on all injury attendances in children under 5 attending an accident and emergency (A&E) department and of providing additional information about each injury. METHODS: Children under 5 years attending the A&E department at Queen's Medical Centre, Nottingham between October 1998 and April 1999 were studied, using a randomised controlled trial with a 2x2 factorial design. All attendances or selected attendances (all children under 1, burns and scalds, poisonings, head injuries, and repeat attendances in preceding six months) were notified. Provision of standard (diagnosis, circumstances surrounding injury, and disposal) or additional information (standard information plus place of injury, number of A&E attendances for injury in previous year, and any information recorded about safety equipment) was noted. RESULTS: Many notifications (56%) do not result in any action. Health visitors were nearly twice as likely to take action of some kind and three times as likely to undertake a home visit on receipt of notifications for selected attendances than on those for all attendances. A greater number of actions per notification were taken on receipt of information about selected attendances. Providing additional information had little effect on the action taken. CONCLUSIONS: A selective policy for notifying community health visitors of child injury attendances at A&E results in a greater proportion of attendances in which the health visitor takes action and in a greater number of actions per attendance being taken. The utility of notifying all injury attendances is questionable, as many do not result in any action.     

Antigenic stimulation in T-cell cultures in cardiomyopathies: differences in cytokine profiles

Immune-mediated mechanisms are involved in the pathogenesis of cardiomyopathies. In this study, we investigate which pattern of immune response (Th₁ or Th₂) lies behind these diseases by analysing the basic cytokines secreted from PHA-cultured T lymphocytes and determining what differences, if any, exist between dilated cardiomyopathy (DMC) and hypertrophic cardiomyopathy (HCM). Two groups of patients were studied: 10 patients with DCM and 10 patients with HCM. Age- and sex-matched healthy individuals were used as controls. PHA-cultured T lymphocytes in the presence or absence of different myocardial antigen (MA) concentrations were measured. Interleukine-2 (IL-2), Interleukine-6 (IL-6) and Interferon-γ (IFN-γ) levels were measured in culture supernatants by an ELISA method. At the same time, delayed-type hypereactivity (DTH) against the same antigenic preparation was measured by the leukocyte migration inhibitory index technique. Patients were subdivided into DTH-positive and DTH-negative and re-examined for IL-2 cytokine expression. IL-6 levels were found to increase both in the presence and in the absence of MA in the patient groups compared to the controls. IL-2 levels were decreased in both groups, in an antigen dose-related manner. Anergic patients showed a further reduction in IL-2 levels for both groups of patients. IFN-γ remained unaffected in the patient groups. Almost half of the patients exhibited anergy to the DTH reaction against MA. We conclude that, upon antigenic stimulation, the initially mounted immune response (increased IL-6) is somehow blocked/switched off in patients, resulting in an immunologic tolerance/unresponsiveness to MA (IL-2 decreased, IFN-γ unchanged). Finally, increased IL-6 could lead to a perpetuation of immunologic injury through the release of oxygen-free radicals with a cytotoxic effect on the myocardium. We hypothesize an antigen-related, defective macrophage-Th₁ cell reaction, which accounts for the differences in the IL-2 profile between the DCM and HCM groups, that might cause local immune responses to lead to immunosuppression (immune tolerance effect), thus contributing to the pathogenesis of cardiomyopathies.     

Tubular Basement Membrane Immune Deposits in Association with BK Polyomavirus Nephropathy

Tubular basement membrane immune deposits (TBMID) are rare in renal allografts and usually have been found in association with immune complex mediated glomerular injury. We report an association between TBMID and BK polyomavirus nephropathy (BKN). We reviewed clinical data and results of allograft biopsies of 30 patients with BKN (16 with and 14 without TBMID). TBMID were detected by immunofluorescence or electron microscopy. Initial and follow-up biopsies were assessed for degree of interstitial inflammation and fibrosis and severity of viral infection, and were correlated with patients' clinical data. Biopsies initially diagnostic for BKN with TBMID, compared to BKN biopsies without deposits, demonstrated more severe interstitial inflammation and fibrosis, and greater numbers of virally infected cells. Similar findings were present in follow-up biopsies. Utilizing three different antibodies directed against viral epitopes, viral antigens could not be detected within TBMID. Thirty percent of patients with TBMID and 70% without deposits had follow-up biopsies, in which virus could not be detected immunohistochemically. Treatment for all included decreasing immunosuppression, cidofovir and/or leflunomide. Clinical data correlated well with histological findings. We conclude that a significant proportion of patients with BKN show TBMID on kidney biopsy. The prognostic significance of this finding remains to be elucidated.     

Neoadjuvant therapy for localized and locally advanced renal cell carcinoma

Neoadjuvant Targeted Molecular Therapy in the setting of localized and locally advanced renal cell carcinoma has emerged as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron-sparing surgery was not thought to be safe or feasible. Presurgical tumor reduction has been demonstrated in a number of studies including a recently published randomized double-blind placebo-controlled study, and an expanding body of literature suggests benefit in select patients. Nonetheless, most reports are small phase II clinical trials or retrospective reports. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for neoadjuvant strategies. This article reviews the current status and future prospects of neoadjuvant therapy in nonmetastatic renal cell carcinoma.