Chemotherapy in the treatment of advanced or recurrent olfactory neuroblastoma

Background: Olfactory neuroblastoma is a rare sino‐nasal tumor arising from the olfactory epithelium and is often characterized by local invasion or metastasis. The role of chemotherapy in the treatment of this tumor is unclear. The purpose of this study was to review our institution’s experience of chemotherapy for advanced or recurrent olfactory neuroblastoma. Methods: Twenty‐one patients with histologically proven olfactory neuroblastoma were treated at our institution between 1992 and 2002. Twelve of these patients received chemotherapy in the setting of unresectable or recurrent disease and were retrospectively reviewed for clinical characteristics, treatment outcome or survival. Results: Eight patients of the 12 patients received cisplatin‐based chemotherapy and the remaining four patients received chemotherapy consisting of docetaxel plus irinotecan (three patients) or cyclophosphamide, doxorubicin, and vincristine (1 patient). A partial response was achieved in five patients, with an overall response rate of 42%, although the chemotherapeutic regimens were heterogeneous. Two partial responses were obtained among the three patients who received docetaxel plus irinotecan. The response rate to chemotherapy was 83% in the younger age group (<40 years), as opposed to 0% in the older age group (≥40 years), and the difference between the two groups was statistically significant (P = 0.02). Conclusion: Our study indicated that olfactory neuroblastoma would be sensitive to chemotherapy, especially with young patients. Docetaxel plus irinotecan has the possibility of showing favorable response, and warrants further investigation.     

Slow-wave photic stimulation relieves patient discomfort during esophagogastroduodenoscopy

Background and Aim: Although pretreatment with a sedative drug is effective in relieving pain during esophagogastroduodenoscopy (EGD), such drugs can cause significant side‐effects. The aim of this study was to examine the effect of slow‐wave photic stimulation on discomfort and/or pain felt during EGD. Methods: Forty consecutive patients (25 men and 15 women) who underwent diagnostic EGD in our hospital were included in the study. Twenty patients received photic stimulation for 25 min, and underwent electroencephalographic recording, in addition to the usual premedications. Twenty control patients received the same treatment but without photic stimulation. All patients evaluated the discomfort/pain felt during endoscopy against a five‐grade scale in comparison with what they had experienced in their previous examination. Results: Patients with an improved discomfort/pain score were 18/20 and 3/20 in the treated and control groups, respectively. Overall comparison of pain scores between both groups was significant (P < 0.0001). The proportion of slow‐wave activity recorded in patients’ electroencephalograms significantly increased in the treated group compared to control values (36.6 ± 6.8% vs 29.1 ± 3.4%, P < 0.001). There was a close correlation between the degree of discomfort/pain felt during endoscopy and the proportion of slow‐wave activity (P < 0.001). Conclusion: Slow‐wave photic stimulation shows promise as a treatment for relieving the discomfort and/or pain felt by patients undergoing EGD.     

Event-related potential correlates of functional hearing loss: Reduced P3 amplitude with preserved Nl and N2 components in a unilateral case

Abstract A female patient exhibiting functional hearing loss in her left ear demonstrated reduced amplitude of P3 component in event-related potentials (ERP) to left monaural stimulation, with preserved N1 and N2 components to stimulation of either ear. This result suggested that stimuli in the affected ear were conducted successfully up to the auditory cortex but that further processing in higher brain regions was 'repressed'. Event-related potential examination for such hysterical disorders could be useful in clarifying their brain mechanism and offer a useful diagnostic clue to its nature.     

Time-dependent Effects of Klebsiella pneumoniae Endotoxin on Hepatic Drug-metabolizing Enzyme Activity in Rats

The time-dependent effects of Klebsiella pneumoniae endotoxin on hepatic cytochrome P450-dependent drug-metabolizing capacity (cytochrome P450 and b₅ content, activity of aminopyrine N-demethylase, p-nitroanisole O-demethylase, aniline hydroxylase and benzphetamine N-demethylase) and on the pharmacokinetics of antipyrine have been determined in rats. Measurement of enzyme activity and antipyrine (after intravenous injection of 20 mgkg^?1) were performed 2, 24 and 96 h after a single intraperitoneal injection of endotoxin (1 mgkg^?1) and after repeated doses (once daily for 4 days). The contribution of tumour necrosis factor α (TNFα) to the endotoxin-induced changes was also examined in rats pretreated with granulocyte colony-stimulating factor (G-CSF). The systemic clearance of antipyrine and the activity of hepatic cytochrome P450-dependent drug-metabolizing enzymes were dramatically reduced 24 h after a single injection of endotoxin, but had returned to control levels by 96 h. The magnitudes of these decreases in these measurements after repeated doses of endotoxin were similar to those seen 24 h after the single dose. The systemic clearance of antipyrine correlated significantly with cytochrome P450 content and aminopyrine N-demethylase activity. In histopathological experiments, moderate hypertrophy of Kupffer cells was observed, with no evidence of severe liver-tissue damage. G-CSF pretreatment suppressed the increased plasma concentrations of TNFα produced 2 h after single endotoxin injection, but did not eliminate the endotoxin-induced decrease in the systemic clearance of antipyrine, suggesting that TNFα is not the sole component responsible for the reduction of cytochrome P450-mediated drug-metabolizing enzyme activity. These results provide evidence that a single intraperitoneal injection of 1·0 mgkg^?1 K. pneumoniae endotoxin in rats reduces hepatic P450 and b₅ levels, and reduces the activity of various cytochrome P450-mediated drug-metabolizing enzymes without causing severe liver-tissue damage. This suggests that the effect of endotoxin on hepatic cytochrome P450-mediated drug-metabolizing isozymes is non-selective.     

Production of IL-6 by T cells from the femoral head of patients with rapidly destructive coxopathy (RDC)

RDC is a syndrome with unknown etiology that causes rapid destruction of a hip joint. We have investigated the production of osteoclast-activating cytokines (IL-6, IL-1α and tumour necrosis factor-alpha (TNF-α)), interferon-gamma (IFN-γ) and IL-8 by T cells in the affected joint. The level of IL-6 produced by the T cell lines (TCL) established from the femoral head was significantly higher than that from patients' or healthy donors' peripheral blood mononuclear cells (PBMC). IL-6 production by the TCL from synovial membrane or from patients' PBMC was also significantly higher than that from healthy donors' PBMC. IL-1α production by the TCL from the femoral head was significantly higher than any of the other groups when all the TCL were used for the analysis. TNF-α production was highest in the TCL from patients' PBMC. The levels of IFN-γ or IL-8 were not significantly different among these four groups. The plasma levels of all these cytokines except for IFN-γ, that was rather lower, in RDC patients were not significantly different from those in osteoarthrosis or trauma patients, or healthy donors. These results suggest that T cells at the affected femoral head, and also synovial membrane to some extent, are involved in bone resorption through the production of IL-6 and probably IL-1α in patients with RDC.     

IL-6阳性细胞在小鼠胸腺内的定位

目的：检测IL－6阳性细胞在小鼠胸腺的分布。方法：采用免疫酶细胞化学，免疫荧光双染及免疫电镜技术方法原位显示小鼠胸腺不同部位IL－6阳性神经的表达情况。结果：光镜免疫酶组织化学确定了IL－6阳性细胞的分布范围，即IL－6在胸腺皮质和髓质的某些特定的细胞表达；进一步采用免疫荧光双染色及免疫电镜技术对IL－6阳性细胞进行了解析，确定了小鼠胸腺内IL－6阳性细胞主要是胸腺实质中不同形态的巨噬细胞，IL－6不存在于胸腺上皮细胞及胸腺细胞。结论：巨噬细胞是小鼠胸腺IL－6的主要来源，参与胸腺细胞发育微环境的构成。     

Tripterygium glycosides suppress production of interleukin‐4 by splenocytes in oxazolone‐induced murine colitis

OBJECTIVE: To investigate the in vitro effect of Tripterygium glycosides (TG) on cytokine production by splenocytes in oxazolone (OXZ)‐induced colitis in mice. METHODS: Oxazolone (6 mg in 50% ethanol) was administered to male SJL/J mice intrarectally to induce colitis and the mice were killed 3 days later. Isolated splenocytes were cultured for 24 h in the presence of phorbol myristate acetate and ionomycin. A preparation of Tripterygium glycosides at a concentration of either 0.1 mg/mL or 0.01 mg/mL was added to the culture medium of splenocytes. Production of interferon gamma (IFN‐γ) and interleukin‐4 (IL‐4) in the supernatant were measured by ELISA. RESULTS: Production of IFN‐γ in the normal control group was suppressed by TG at both concentrations (0.01 and 0.1 mg/mL; 1.24 ± 0.13 pg/mL (samples without TG) → 0.97 ± 0.26 pg/mL (0.01 mg/mL TG) → 0.87 ± 0.18 pg/mL (0.1 mg/mL TG); P < 0.02) in a dose dependent manner. In the OXZ‐induced colitis group, the basic level of IFN‐γ was significantly lower than that of the normal control group (1.24 ± 0.13 pg/mL vs 0.65 ± 0.08 pg/mL; P < 0.01); but IL‐4 production was significantly increased in the OXZ‐induced colitis without TG group (7.83 ± 0.69 pg/mL vs 5.65 ± 0.48 pg/mL, P < 0.01). In both groups, TG suppressed IL‐4 production in a dose‐dependent manner (normal control group: 5.65 ± 0.48 pg/mL (samples without TG) → 4.97 ± 0.38 pg/mL (0.01 mg/mL TG) → 3.98 ± 0.32 pg/mL (0.1 mg/mL TG), P < 0.01; OXZ group: 7.83 ± 0.69 pg/mL (samples without TG) → 7.07 ± 0.47 pg/mL (0.01 mg/mL TG) → 6.35 ± 0.48 pg/mL (0.1 mg/mL TG), P < 0.01). CONCLUSION: Oxazalone‐induced IL‐4 overproduction by splenocytes was significantly suppressed by TG in a dose dependent manner and the beneficial effects of TG on ulcerative colitis might be related to the suppression of the Th2 type (e.g. IL‐4) mediated immunological response of splenocytes.