Viral infections of the autonomic nervous system and its target organs: Pathogenetic mechanicsms

The possibility that viruses can infect the peripheral autonomic nervous system (ANS) and cause a variety of acute, chronic or recurrent diseases, including such disorders as peptic ulcer, is proposed. By altering the functional activity of autonomic neurons or by seeding the target organs of these neurons with virus, infection of the ANS may produce a broad spectrum of clinical manifestations. Whether these manifestations are anatomically circumscribed or widespread will depend upon the route by which autonomic infection is acquired as well as the character of interaction between the virus and the infected autonomic neuron. In addition, it is proposed that autonomic ganglia may serve as reservoirs of latent viruses, insuring their preservation and intermittent transmission in the human community.     

Production of Chemotactic Factor and Lymphotoxin by Human Leukocytes Stimulated with Herpes Simplex Virus

Peripheral blood leukocytes (PBL) of 41 subjects were tested for their ability to be stimulated by herpes simplex virus antigens as measured by [(3)H]thymidine incorporation and lymphokine production (i.e., lymphocyte-derived chemotactic factor and lymphotoxin). The PBL of seronegative subjects failed to respond to viral antigens as measured by stimulation or lymphokine production. In contrast, PBL from seropositive subjects without clinical lesions of herpes labialis were stimulated by herpes simplex virus antigens and produced lymphokines. PBL from seropositive patients with clinical lesions of herpes labialis also produced lymphokines, but [(3)H]thymidine incorporation was slightly depressed. These findings suggest that lymphocytes from patients with a recent herpes simplex virus infection may respond less vigorously to in vitro stimulation by herpes antigens, but our study fails to show any basic defect in the responsiveness of the lymphocytes to account for recurrent herpetic episodes.     

Integration of conservative surgery, radiotherapy, and chemotherapy for the treatment of early-stage, node-positive breast cancer: sequencing, timing, and outcome

The optimal means of combining breast-conserving surgery, radiation therapy, and chemotherapy for the treatment of patients with early-stage, node-positive breast cancer is not known. We reviewed the results in 295 patients treated at the Joint Center for Radiation Therapy and affiliated institutions from 1976 to 1985. All patients had positive axillary nodes on dissection, had no gross residual disease in the breast or axilla after surgery, and received breast irradiation (with or without nodal irradiation) and three or more cycles of a cyclophosphamide, methotrexate, and fluorouracil (CMF)-based or doxorubicin-containing regimen. Median follow-up in patients without any failure was 78 months. Breast failure rates were assessed in relation to the sequencing of radiotherapy and chemotherapy. The different sequences were not randomly assigned, and the characteristics of the sequence groups differed. The actuarial 5-year breast failure rate was 4% in 99 patients receiving radiotherapy before chemotherapy; 8% in 54 patients sequentially receiving some chemotherapy, then radiotherapy without concurrent chemotherapy, then further chemotherapy; and 6% in 116 patients receiving concurrent chemotherapy and radiotherapy. However, the failure rate was 41% in 26 patients who received all chemotherapy before radiotherapy. The crude incidences of local failure within 4 years of treatment in these groups were 3%, 2%, 4%, and 15%, respectively (P = .065 for all four groups not being the same). The actuarial 5-year local failure rate was 5% for 252 patients irradiated within 16 weeks after surgery compared with 35% for 34 patients irradiated more than 16 weeks after surgery. The 4-year crude incidences were 4% and 12% for the two groups, respectively (P = .06). These results suggest that delaying the initiation of radiotherapy may result in an increased likelihood of local failure. Formal randomized controlled trials will be needed to confirm these results and to improve the integration of these treatment modalities.     

Melanoma differentiation-associated gene 7/interleukin (IL)-24 is a novel ligand that regulates angiogenesis via the IL-22 receptor

The melanoma differentiation-associated gene 7 (mda-7), also called interleukin (IL)-24, suppresses the growth of some cancers in vitro and in vivo as a result of the ectopic expression of its protein. However, the function of the secreted form of the protein in cancer has not been previously studied. The purpose of this study was to determine the antiangiogenic function of a secreted form of the MDA-7/IL-24 protein (sMDA-7/IL-24). In vitro, sMDA-7/IL-24 inhibited both endothelial cell differentiation and migration of endothelial cells induced by vascular endothelial growth factor and basic fibroblast growth factor. The sMDA-7/IL-24-mediated inhibitory effect was 10-50 times more potent than endostatin, IFN-gamma, and IFN-inducible protein 10 in vitro. Furthermore, the inhibitory effect was not mediated by IFN or IFN-inducible protein 10. IL-22 receptor mediated the antiangiogenic activity of sMDA-7/IL-24. Administration of a blocking antibody to IL-22 receptor in conjunction with sMDA-7/IL-24 led to abrogation of inhibition of endothelial differentiation. sMDA-7/IL-24 inhibited vascular endothelial growth factor-induced angiogenesis as evidenced by reduced vascularization and hemoglobin content in in vivo Matrigel plug assays. In vivo, the growth of human lung tumor cells was significantly inhibited, and vascularization was reduced when the cells were mixed with 293 cells stably expressing sMDA-7/IL-24. Systemic administration of sMDA-7/IL-24 inhibited lung tumor growth in a mouse xenograft model. Associated with tumor growth inhibition was decreased tumor microvessel density and hemoglobin content, indicating the presence of antiangiogenic activity. These data demonstrate that sMDA-7/IL-24 is a novel and potent antiangiogenic effector and support the development of MDA-7/IL-24-based therapeutics.     

Association of antiepileptic drugs, vitamin D, and calcium supplementation with bone fracture occurrence in epilepsy patients

The aim of this study is to determine whether calcium and vitamin D supplementation reduces the risk of bone fractures in adult epilepsy patients. Records were obtained on 7716 patients with epilepsy prescribed antiepileptic drugs (AED) from the Veteran Affairs Hospital in Lexington, Kentucky. We performed a single center, retrospective cohort study to examine the proportion of fractures in 3303 patients on AED who took supplements compared to patients on AED not taking supplements. Patients prescribed long-term AEDs taking calcium and vitamin D were as likely to have fractures as those who did not take these supplements (11.7% vs. 9.9%, χ² = 0.59, p = 0.44). Phenytoin use was associated with a statistically significant increased risk of fractures OR = 1.55 (1.10-2.24). Thus, in this group of patients with epilepsy on AED, bone fractures were not prevented in individuals taking calcium and vitamin D supplementation.     

Medication-related dizziness in the older adult

With increased medication use among the older adult population, adverse drug events and polypharmacy can be significant causes of dizziness in the elderly. The evidence evaluated in this review is helpful in clinical practice but requires an additional detailed investigation into the agents discussed to understand the risk/benefit ratio associated with medications. Examples of medications highly associated with dizziness in older adults and discussed in this review include cardiovascular and central nervous system agents. Several other medication classes associated with dizziness are among the medications most commonly used by older patients.     

实验性变态反应性脑脊髓炎T淋巴细胞增殖和肿瘤坏死因子—α变化的意义

目的：探讨实验性变态反应性脑脊髓炎（EAE）T淋巴细胞增殖和肿瘤坏死因子（TNF）－α变化的意义。方法：观察Lewis大鼠主动免疫性EAE临床症状,T淋巴细胞增殖以及血清TNF－α水平,结果：EAE临床发病过程中,T淋巴细胞增殖活跃,血清TNF－α水平异常升高,并与临床症状呈正相关。结论：研究表明：EAE时,TI林巴细胞增殖旺盛和TNF－α生成增多。进而导致血脑屏障的破坏,炎细胞浸润,从而诱发EAE。