Left vagus nerve stimulation suppresses experimentally induced pain

OBJECTIVE: To test whether electric stimulation of the vagus nerve has an antinociceptive effect in humans. BACKGROUND: In a variety of animal studies, vagus nerve stimulation was shown to inhibit nociceptive behavior as well as electric responses of spinal nociceptive neurons. In humans, chronic left vagus nerve stimulation is used to treat pharmacologically refractory epilepsy. METHODS: The authors investigated experimental pain in 10 patients with seizures before and twice after implantation of a vagus nerve stimulator by using different controlled stimuli, including noxious heat, tonic pressure, and short impact. Pain was quantified on a visual analogue scale. Twelve nonepileptic age- and gender-matched individuals served as control subjects. RESULTS: Vagus nerve stimulation reduced increasing pain associated with trains of five consecutive stimuli at 1.5-second intervals ("wind-up"; p < 0.001). In a similar manner, pain on tonic pressure was reduced by vagus nerve stimulation (p < 0.03). Pain associated with single-impact stimuli as well as heat pain thresholds were unaltered under vagus nerve stimulation. Thus, vagus nerve stimulation led to pain relief predominantly in experimental procedures in which pain magnitude was amplified by central processing. The antinociceptive effect was independent of the acute on-off cycles of vagus nerve stimulation. CONCLUSIONS: Vagus nerve stimulation is effective in reducing pain in humans. In humans, the antinociceptive effect might rely on central inhibition rather than alterations of peripheral nociceptive mechanisms. These results indicate a promising, potential future role of vagus nerve stimulation in pain treatment.     

Pathophysiology of human epilepsy: imaging and physiologic studies

Recent advances in research into the pathophysiology of human epilepsies and in neuroimaging, especially magnetic resonance imaging, magnetic resonance spectroscopy, positron emission tomography and magnetoelectroencephalography, have resulted in improvements in the localization of both the epileptogenic tissue and functionally important areas. The ability to correlate functional disturbances and lesions has been clarified, which has led to a better understanding of plasticity and epilepsy.     

In vitro evaluation of teratogenic effects by time-varying MR gradient fields on fetal human fibroblasts

The purpose of this study was to evaluate the influence on fetal cell growth in vitro of rapidly changing magnetic gradient fields such as those produced by the gradient coils of a typical magnetic resonance (MR) imager. The static magnetic field and the radiofrequency pulses were disabled during all measurements. Human fetal fibroblasts were placed within a specially designed MR-compatible incubation system inside the magnet. Trapezoid-shaped waveforms of 500 and 75 Hz base frequency and an amplitude of 2 mT were applied for 2-24 hours. Proliferation of the cells was monitored for 3 weeks after exposure. Cell cycle analysis was performed until 24 hours after exposure to detect alterations in cell division. Tests were performed under two different conditions of growth to detect increased as well as decreased proliferation effects. None of these tests showed differences in proliferation and cell cycle distribution between exposed and nonexposed cells.     

Phase II study of oxaliplatin for treatment of patients with mucosa-associated lymphoid tissue lymphoma.

PURPOSE: Various chemotherapeutic regimens have been applied for treatment of mucosa-associated lymphoid tissue (MALT) lymphoma, but no standard regimen has been identified to date. In view of the activity of oxaliplatin (L-OHP) in various types of lymphoma, we performed a phase II study to evaluate the activity of L-OHP for treatment of MALT lymphoma. The primary objective of this study was to determine the objective response rate according to WHO standard criteria. PATIENTS AND METHODS: A total of 16 patients with MALT lymphoma of various sites of origin (four of the ocular adnexa, five of the salivary glands, three of the stomach, two of the lung, and one of the colon and the breast) were administered L-OHP at a dose of 130 mg/m2 infused during 2 hours every 3 weeks. Restaging was performed every two cycles; treatment was continued until complete remission (CR) or for a maximum of six cycles in responders. RESULTS: Sixty-five cycles were administered (median, four; range, two to six); toxicity consisted of transient sensory neuropathy in eight patients and nausea/emesis WHO grade 2 in two patients, whereas hematologic adverse effects (thrombocytopenia and leukocytopenia grade 2) occurred in only one patient each. Fifteen patients responded to chemotherapy, with nine achieving CR (56%), six (37.5%) achieving partial response, and one achieving stable disease; the median time to response was 4 months (range; 2 to 4 months). CONCLUSION: These data suggest L-OHP is a highly active agent for treatment of MALT lymphoma. However, a longer follow-up is needed to judge whether these remissions are durable.     

The role of choroidal hypoperfusion associated with photodynamic therapy in neovascular age-related macular degeneration and the consequences for combination strategies

The clinical benefits of verteporfin therapy have been documented in a wide variety of patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), and there is encouraging evidence of improved outcomes when this angioocclusive modality is combined with antiangiogenic agents. Although the clinical benefits of verteporfin mono- and combination therapy are well established, there has been concern that treatment with verteporfin results in hypoperfusion in the treated area and that concomitant use of antiangiogenic agents could prolong this effect. However, despite well-documented occurrences of hypoperfusion on fluorescein and indocyanine green angiography, there is little evidence of associations with functional impairment or other adverse effects. It has also been suggested that hypoperfusion might actually help to reduce recanalization of CNV and permit neuronal recovery by decreasing exposure to oxygen and oxidative radicals. The reduced need for frequent retreatments clearly has a major appeal due to the lower costs associated with fewer interventions and reduced burden of clinical monitoring and diagnostic reevaluations. Ongoing evaluation in randomized clinical trials will provide further clarification on the effect of verteporfin plus ranibizumab compared with ranibizumab monotherapy in terms of visual acuity, anatomical outcomes, treatment frequency, and health economics. The results of these large-scale clinical trials will provide a strong basis for determining the benefits and risks of combination therapy.