Involving children and young people in clinical research through the forum of a European Young Persons’ Advisory Group: needs and challenges

Children and young people are seen as fundamental to the design and delivery of clinical research as active and reflective participants. In Europe, involvement of children and young people in clinical research is promoted extensively in order to engage young people in research as partners and to give them a voice to raise their own issues or opinions and for their involvement in planning and decision making in addition to learning research skills. Children and young people can be trained in clinical research through participation in young person advisory groups (YPAGs). Members of YPAGs assist other children and young people to learn about clinical research and share their experience and point of view with researchers, thereby possibly influencing all phases of research including the development and prioritization of research questions, design and methods, recruitment plans, and strategies for results dissemination. In the long term, the expansion of YPAGs in Europe will serve as a driving force for refining pediatric clinical research. It will help in a better definition of research projects according to the patients’ needs. Furthermore, direct engagement of children and young people in research will be favorable to both researchers and young people.     

Botryomycome lingual néonatal (à propos d’une observation)

IntroductionThe botryomycoma is a benign tumor that develops as a response to a local trauma. Generally, it occurs in the fingers, the face and the oral cavity. It is often easily recognized. However, the diagnosis between this tumor and other oral tumors, whether benign or malignant, may be difficult in some cases. We report a particular case of a botryomycoma that occurred with no history of a trauma at an earlier age in the tongue, which is an unusual site for this tumor.Case reportA 7-month-old infant presented with a polypoid and sessile swelling on the dorsal side of the tongue. This tumor gradually increased in size since birth. Clinically, the appearance of this mass with the gathered vessels inside was similar to that of a benign vascular tumor. A possibly malignant nature was not excluded. A complete resection under general anesthesia was performed. The histologic examination confirmed the diagnosis of pyogenic granuloma.DiscussionPyogenic granuloma is a rare benign tumor which is most likely to occur between the age of 11 and 40. The most frequent location encountered for oral cavity is the gingiva. The tongue is rarely a site for its occurrence. Cutaneous pyogenic granuloma may have different aspect from mucosal type and thus may make the diagnosis difficult. Treatment consists on surgical excision and removal of etiological factors that may be source of recurrence.     

State‐dependent blocking mechanism of Kv1.3 channels by the antimycobacterial drug clofazimine

Background and Purpose

K_v1.3 potassium channels are promising pharmaceutical targets for treating immune diseases as they modulate Ca²⁺ signalling in T cells by regulating the membrane potential and with it the driving force for Ca²⁺ influx. The antimycobacterial drug clofazimine has been demonstrated to attenuate antigen‐induced Ca²⁺ oscillations, suppress cytokine release and prevent skin graft rejection by inhibiting K_v1.3 channels with high potency and selectivity.

Experimental Approach

We used patch‐clamp methodology to investigate clofazimine''s mechanism of action in K_v1.3 channels expressed in HEK293 cells.

Key Results

Clofazimine blocked K_v1.3 channels by involving two discrete mechanisms, both of which contribute to effective suppression of channels: (i) a use‐dependent open‐channel block during long depolarizations, resulting in accelerated K⁺ current inactivation and (ii) a block of closed deactivated channels after channels were opened by brief depolarizations. Both modes of block were use‐dependent and state‐dependent in that they clearly required prior channel opening. The clofazimine‐sensitive closed‐deactivated state of the channel was distinct from the resting closed state because channels at hyperpolarized voltages were not inhibited by clofazimine. Neither were channels in the C‐type inactivated state significantly affected. K_v1.3 channels carrying the H399T mutation and lacking C‐type inactivation were insensitive to clofazimine block of the closed‐deactivated state, but retained their susceptibility to open‐channel block.

Conclusions and Implications

Given the prominent role of K_v1.3 in shaping Ca²⁺ oscillations, the use‐dependent and state‐dependent block of K_v1.3 channels by clofazimine offers therapeutic potential for selective immunosuppression in the context of autoimmune diseases in which K_v1.3‐expressing T cells play a significant role.

Abbreviations

CLF

clofazimine

FDA

Food and Drug Administration

IPI

interpulse intervals

WT

wild type

     

Pneumocystis carinii pneumonia in patients with hematologic malignancies: a descriptive study

Objectives. A retrospective multicentric study was conducted over a five-year period to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating hematologic malignancies.Results. The study included 60 HIV-negative patients with 18 non-Hodgkin's malignant lymphoma (30%), 13 chronic lymphocytic leukaemia (21.7%), 10 acute leukemia (16.6%), 5 multiple myeloma (8.3%), 4 Waldenstr?m's diseases (6.6%), 4 chronic myeloid leukemia (6.6%), 3 myelodysplasia (5%), 2 Hodgkin's diseases (3.3%) and 1 thrombopenia. Bronchoalveolar lavage was diagnostic in all patients. Forty-nine patients received cytotoxic drugs (81.7%), 25 (41.7%) a long-term corticotherapy and 15 (25%) underwent bone marrow transplantation. Twenty-seven patients (45%) required admission in the intensive care unit, 35 (58.3%) received an adjunctive corticotherapy and 18 mechanical ventilation (30%). Twenty patients (33.3%) died of PCP. A previous long-term corticotherapy (p=0.04), high respiratory (p=0.05) and pulse rates (p=0.02), elevated C reactive protein (p=0.01) and mechanical ventilation (OR=13.37; IC: 1.9-50) were associated with a poor prognosis. Adjunctive corticotherapy did not modify the prognosis.Conclusions. These results suggest that PCP can occur during the course of various hematologic malignancies, not only lymphoproliferative disorders. Prognosis remains poor. The diagnosis should be advocated more frequently and earlier to improve the prognosis.