RESUMEN
Gulf War Illness (GWI) is a multi-symptom illness that continues to affect over 250,000 American Gulf War veterans. The causes of GWI remain equivocal; however, prophylactic use of the acetylcholinesterase inhibitor pyridostigmine bromide (PB), and the stress of combat have been identified as two potential causative factors. Both PB and stress alter acetylcholine (ACh), which mediates both cognition and anti-inflammatory responses. As inflammation has been proposed to contribute to the cognitive deficits and immune dysregulation in GWI, the goal of this study was to determine the long-term effects of PB and stress on the cholinergic anti-inflammatory pathway in the central nervous system and periphery. We used our previously established rat model of GWI and in vivo microdialysis to assess cholinergic neurochemistry in the prefrontal cortex (PFC) and hippocampus following a mild immune challenge (lipopolysaccharide; LPS). We then examined LPS-induced changes in inflammatory markers in PFC and hippocampal homogenates. We found that PB treatment produces a long-lasting potentiation of the cholinergic response to LPS in both the PFC and hippocampus. Interestingly, this prolonged effect of PB treatment enhancing cholinergic responses to LPS was accompanied by paradoxical increases in the release of pro-inflammatory cytokines in these brain regions. Collectively, these findings provide evidence that neuroinflammation resulting from dysregulation of the cholinergic anti-inflammatory pathway is a mechanistic mediator in the progression of the neurochemical and neurocognitive deficits in GWI and more broadly suggest that dysregulation of this pathway may contribute to neuroinflammatory processes in stress-related neurological disorders.
RESUMEN
Radiation therapy led to local resolution of a case of lichen myxedematosus, which, to our knowledge, is the first reported successful treatment of the disease by radiation therapy. Radiation therapy is only the second therapeutic modality that is effective in the treatment of lichen myxedematosus. We propose specific criteria for the diagnosis of lichen myxedematosus to facilitate future studies into the nature of this disease.
Asunto(s)
Mixedema/radioterapia , Enfermedades de la Piel/radioterapia , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Mixedema/complicaciones , Mixedema/diagnóstico , Enfermedades de la Piel/complicaciones , Enfermedades de la Piel/diagnóstico , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/radioterapiaRESUMEN
Between 1976 and 1983, 267 patients with non-oat cell carcinoma of the lung were treated with radiation therapy alone. One hundred thirty-four patients had squamous cell carcinoma; 69, large cell carcinoma; and 64, adenocarcinoma. Stage III carcinoma was diagnosed in 87% of the patients. Total radiation dose was less than 45 Gy in 69 patients (low dose group), 45-55 Gy in 161 (middle dose group), and 55-65 Gy in 37 (high dose group); dosage was 180-200 cGy daily, 5 days per week. Minimum follow-up was 3 years (median, 6 years). Tumor control within the radiation fields was achieved in 12%, 43%, and 78% of the low, middle, and high dose groups, respectively. A complete response rate of 13%, 23%, and 35% and an overall response of 43%, 71%, and 86% were seen in the low, middle, and high dose groups, respectively. The 5-year recurrence-free survival rate for all patients was 7% and was dependent on radiation dose and tumor response. This study indicates that tumor control and complete response rates are improved with a radiation dose of 55-65 Gy and that complete responders have improved survival.