Mirror therapy for phantom limb pain: brain changes and the role of body representation.

BACKGROUND: Phantom limb pain (PLP) is a common consequence of amputation and is difficult to treat. Mirror therapy (MT), a procedure utilizing the visual recreation of movement of a lost limb by moving the intact limb in front of a mirror, has been shown to be effective in reducing PLP. However, the neural correlates of this effect are not known. METHODS: We investigated the effects of daily mirror training over 4 weeks in 13 chronic PLP patients after unilateral arm amputation. Eleven participants performed hand and lip movements during a functional magnetic resonance imaging (fMRI) measurement before and after MT. The location of neural activity in primary somatosensory cortex during these tasks was used to assess brain changes related to treatment. RESULTS: The treatment caused a significant reduction of PLP (average decrease of 27%). Treatment effects were predicted by a telescopic distortion of the phantom, with those patients who experienced a telescope profiting less from treatment. fMRI data analyses revealed a relationship between change in pain after MT and a reversal of dysfunctional cortical reorganization in primary somatosensory cortex. Pain reduction after mirror training was also related to a decrease of activity in the inferior parietal cortex (IPC). CONCLUSIONS: Experienced body appearance seems to be an important predictor of mirror treatment effectiveness. Maladaptive changes in cortical organization are reversed during mirror treatment, which also alters activity in the IPC, a region involved in painful perceptions and in the perceived relatedness to an observed limb.

CD137 ligand prevents the development of T-helper type 2 cell-mediated allergic asthma by interferon-gamma-producing CD8+ T cells.

BACKGROUND: Allergic asthma is a T-helper type 2 (Th2) cell-mediated chronic disease that is characterized by airway hyperreactivity (AHR) and chronic eosinophilic airway inflammation. Several studies suggest co-stimulatory molecules like CD137 as potential targets for therapeutic interventions in allergic airway disease. Recently, we could show in a murine asthma model that administration of an agonistic antibody against the receptor of the co-stimulatory molecule CD137 prevented and even reversed an already-established asthma phenotype. OBJECTIVE: The purpose of this study was to analyse the effect of stimulation of the CD137 ligand by a monoclonal antibody (CD137L mAb). METHODS: To induce an asthma-like phenotype, BALB/c mice were sensitized to ovalbumin (OVA), followed by an intrapulmonary allergen challenge. Anti-CD137L or control mAb were applied 1 day before OVA immunization or after the asthma phenotype was already established. RESULTS: Stimulation of the CD137L instead of the receptor by CD137L mAb prevents the development of an asthma-like phenotype but does not reverse established disease. While the receptor-mediated effect is partly mediated by anergy of CD4(+) T cells and partly by induction of IFN-gamma-producing CD8(+) T cells, the effect of the CD137L mAb is completely dependent on IFN-gamma-producing CD8(+) T cells: blockade of IFN-gamma and depletion of CD8(+) T cells fully abrogated the observed protective effect. In vitro experiments showed that the anti-CD137L mAb ligates directly to CD8(+) T cells and induces the generation of IFN-gamma by this cell population. CONCLUSION: Our results demonstrate that anti-CD137L mAb prevents disease development via IFN-gamma-producing CD8(+) T cells but is inferior to stimulation of the receptor that reverses established disease by a mechanism including CD4(+) T cell anergy.

A novel HLA-B*35 (B*3570) allele of a Caucasian family differing with one amino acid mismatch from HLA-B*3503 allele in exon 4.

A novel human leucocyte antigen (HLA)-B35 (HLA-B*3570) allele has been identified in a Caucasian family from Middle Europe using single allele-specific sequencing strategy. This allele is identical to the HLA-B*3503 allele except for one point mutation in exon 4 at codon 188 (CAC-->CGC), resulting in an amino acid change from histidine to arginine.

Successful treatment with voriconazole of Aspergillus brain abscess in a boy with medulloblastoma.

Invasive aspergillosis is an increasing problem in immuno-incompetent patients after prolonged steroid therapy, cancer radio-chemotherapy, and bone marrow or solid organ transplantation. Cerebral aspergillosis is a well-described complication of the invasive aspergillosis but only in rare cases, the brain is the sole site of infection. Despite increasing availability of antifungal drugs, the prognosis of cerebral aspergillosis is poor. We report on an 11-year-old boy with medulloblastoma in the area of the fourth ventricle. Following tumor surgery and radio-chemotherapy, several abscess-like structures occurred in the operating field. After incomplete abscess, resection histology and culture confirmed a localized Aspergillus fumigatus infection. The initial treatment of the Aspergillus fumigatus infection with conventional amphotericin B failed, and treatment with the triazole voriconazole was started. Intravenous treatment with voriconazole resulted in a reduction of the Aspergillus fumigatus abscess. After switching to oral ambulatory therapy, the Aspergillus fumigatus abscess increased in size. To improve treatment, voriconazole dosage was adapted to reach drug concentrations in cerebrospinal fluid (CSF) above the minimal fungicidal concentration and plasma specimens. During the concentration-controlled voriconazole therapy for a period of 18 months, a complete response was achieved.

Lethal double infection with Acremonium strictum and Aspergillus fumigatus during induction chemotherapy in a child with ALL.

Fungal infections are a major cause of morbidity and mortality in patients during chemotherapeutic treatments and malignant hematologic disease. We present a case of a double fungal infection with disseminated Acremonium strictum (A. strictum) and pulmonary Aspergillus fumigatus (A. fumigatus) and its rapid clinical course. A 17-year-old boy with prolonged neutropenia developed a disseminated fungal infection during induction chemotherapy of his acute lymphoblastic leukemia. The infection was rapidly lethal despite neutrophil recovery and early antifungal combination therapy with amphotericin B and caspofungin. Since there are only a few reports about invasive Acremonium infections, we present this case with regard to differences in the clinic pathologic features of Aspergillosis and other opportunistic fungal infections due to Fusarium or Acremonium species.

Reduction in density of transverse tubules and L-type Ca(2+) channels in canine tachycardia-induced heart failure.

OBJECTIVE: Persistent supraventricular tachycardia leads to the development of a dilated cardiomyopathy with impairment of excitation-contraction (EC) coupling. Since the initial trigger for EC coupling in ventricular muscle is the influx of Ca(2+) through L-type Ca(2+) channels (I(Ca)) in the transverse tubules (T-tubules), we determined if the density of the T-tubule system and L-type Ca(2+) channels change in canine tachycardia pacing-induced cardiomyopathy. METHODS: Confocal imaging of isolated ventricular myocytes stained with the membrane dye Di-8-ANEPPS was used to image the T-tubule system, and standard whole-cell patch clamp techniques were used to measure I(Ca) and intramembrane charge movement. RESULTS: A complex staining pattern of interconnected tubules including prominent transverse components spaced every approximately 1.6 microm was present in control ventricular myocytes, but failing cells demonstrated a far less regular T-tubule system with a relative loss of T-tubules. In confocal optical slices, the average % of the total cell area staining for T-tubules decreased from 11.5+/-0.4 in control to 8.7+/-0.4% in failing cells (P<0.001). Whole-cell patch clamp studies revealed that I(Ca) density was unchanged. Since whole-cell I(Ca) is due to both the number of channels as well as the functional properties of those channels, we measured intramembrane charge movement as an assay for changes in channel number. The saturating amount of charge that moves due to gating of L-type Ca(2+) channels, Q(on,max), was decreased from 6.5+/-0.6 in control to 2.8+/-0.3 fC/pF in failing myocytes (P<0.001). CONCLUSIONS: Cellular remodeling in heart failure results in decreased density of T-tubules and L-type Ca(2+) channels, which contribute to abnormal EC coupling.