Archive of Medical Research

A national conference to determine research priorities in pediatric solid organ transplantation.

The need for evidence-based practice guidelines requires high quality, carefully controlled clinical research trials. This multidisciplinary conference attempted to: identify urgent clinical and research issues, identify obstacles to performing clinical trials, develop concepts for organ-specific and all-organ research and generate a report that would serve as a blueprint for future research initiatives. A few themes became evident. First, young children present a unique immunologic environment which may lead to tolerance, therefore, including young children in immunosuppression withdrawal and tolerance trials may increase the potential benefits of these studies. Second, adolescence poses significant barriers to successful transplantation. Non-adherence may be insufficient to explain poorer outcomes. More studies focused on identification and prevention of non-adherence, and the potential effects of puberty are required. Third, the relatively naive immune system of the child presents a unique opportunity to study primary infections and alloimmune responses. Finally, relatively small numbers of transplants performed in pediatric centers mandate multicenter collaboration. Investment in registries, tissue and DNA repositories will enhance productivity. The past decade has proven that outcomes after pediatric transplantation can be comparable to adults. The pediatric community now has the opportunity to design and complete studies that enhance outcomes for all transplant recipients.

Bartosh SM, Ryckman FC, Shaddy R, Michaels MG, Platt JL, Sweet SC.

Department of Pediatrics, 600 Highland Ave., University of Wisconsin, Madison, WI 53792, USA. smbartosh@wisc.edu

Enhanced in vitro activation of immunocompetent cells in healthy individuals being subcutaneously \’vaccinated\’ with placebo (physiological saline).

The effect of subcutaneous injection of physiological saline (given as \’placebo\’ in a randomized double-blinded placebo-controlled study) on immunocompetent cells from healthy individuals was analyzed. In two studies in 1998/1999 and 2002, 16 and 13 healthy individuals, respectively, were injected subcutaneously with 1 ml physiological saline twice a week for up to 12 weeks. Lymphocytes were isolated before and during exposure and incubated with recall antigens (purified protein derivative [PPD], tetanus toxoid [TT], bacillus Calmette-Guerin [BCG]). The production of T-helper type 1-, type 2-, and macrophage/monocyte-related cytokines was analyzed by ELISA. There was a significant increase of the recall-antigen-induced production of IFNgamma, IL-5, IL-13, TNFalpha, and GM-CSF in both groups during the observation period. Subcutaneous injection of placebo, therefore, enhances immunoreactivity. Psychological aspects, activation of the autonomous nerve system or local activation of mast cells or dendritic cells may be responsible for this phenomenon.

Klein R, Buck S, Classen K, Rostock M, Huber R.

Department of Internal Medicine II, University of Tuebingen, Otfried-Müller-Strasse 10, 72076 Tuebingen, Germany. reinhild.klein@med.uni-tuebingen.de

Pharmaceuticals and medical devices: medical devices.

Tiffany S.

Seymour Benzer (1921-2007).

Greenspan RJ.

The Neurosciences Institute, 10640 John Jay, Hopkins Drive, San Diego, California 92121, USA. greenspan@nsi.edu

All tanked up.

Williams N.

A phase I/II study to evaluate the toxicity and efficacy of accelerated fractionation radiotherapy for the palliation of dysphagia from carcinoma of the oesophagus.

AIMS: We hypothesised that accelerated fractionated radiotherapy may provide a good palliative approach for dysphagia relief in patients with incurable oesophageal cancer, significantly reducing the overall duration of treatment, while providing symptom response with an acceptable toxicity profile. A phase I/II accelerated fractionation study was conducted to evaluate the efficacy and toxicity of this approach. MATERIALS AND METHODS: Patients with incurable oesophageal cancer, symptomatic with dysphagia, Eastern Cooperative Oncology Group performance status<or=3, without fistula or oesophageal stent in situ, were eligible. Treatment consisted of 40 Gy in 20 fractions, twice a day (2 Gy per fraction, >or=6 h apart), 5 days a week, over 2 weeks. RESULTS: Of the 39 evaluable patients, the dysphagia response rate was 69% (27/39) with a median response duration of 5.5 months. The median time to response was 4 weeks. Twenty-eight per cent (11/39) of patients had transient worsening in their dysphagia scores. Acute toxicity (weeks 1-8) occurred in 41% (16/39) of patients. An improvement in global quality of life by week 8 was seen in 42% of patients. There were no late neurological sequelae. The median overall survival was 8 (range 1.7-58+) months. CONCLUSION: The ideal palliative regimen should be relatively short, with minimal toxicity, while offering a favourable response profile. Accelerated fractionation fulfils these criteria and is a suitable treatment alternative for the palliation of dysphagia, especially if the goal is to deliver a higher total biological dose within a shorter (2 week) period of time.

Kassam Z, Wong RK, Ringash J, Ung Y, Kamra J, DeBoer G, O\’Brien M, Kim J, Loblaw DA, Wong S, Cummings B, Davey P.

Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Canada.

Cloned beef hash.

Harris RF.

Elucidating the role of chest wall irradiation in \’intermediate-risk\’ breast cancer: the MRC/EORTC SUPREMO trial.

Kunkler IH, Canney P, van Tienhoven G, Russell NS; MRC/EORTC (BIG 2-04) SUPREMO Trial Management Group.

Pseudoventricular tachycardia.

Tomcsányi J, Bózsik B.

Mimicking acute coronary syndrome.

Tomcsány J, Bózsik B.