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.     

Granulomatous balanoposthitis after intravesical Bacillus-Calmette-Guerin instillation therapy

We report a rare case of granulomatous balanoposthitis after intravesical Bacillus-Calmette-Guerin (BCG) instillation therapy in a 58-year-old man, which followed transurethral resection (TUR) for recurrent bladder cancer, when his anterior urethra was slightly narrow and his foreskin was with phimosis. Intravesical BCG instillation therapy was started for prophylaxis of recurrent bladder cancer after TUR. Multiple painless firm papules on glans penis, edema in the foreskin and low-grade fever appeared after the seventh instillation, for which the single antituberculous agent isoniazid (300 mg/day) was administered. Biopsy of the papules on glans penis and foreskin revealed granulomatous balanoposthitis. Low-grade fever normalized and the papules disappeared within 1 week. The patient continued chemotherapy with isoniazid for the next 12 months. There was no recurrence of bladder cancer or balanoposthitis for 15 months and to date.     

Phase II Study of Mitoxantrone in Patients With Non-Small Cell Lung Cancer

A phase II study of mitoxantrone was performed in 24 patientswith non-small cell lung cancer (NSCLC). Mitoxantrone was administeredby intravenous drip infusion of 12 mg/m² every three weeks.There were no responders among the 21 evaluable patients includingfive patients without prior therapy. The major hematologicaltoxic effect was leukocytopenia. Thrombocytopenia and decreasein hemoglobin were slight. A change in the electrocardiogramwas observed in one patient and one patient experienced cardiogenicshock. Mitoxantrone is not acceptable for the treatment of NSCLC becauseof its low antitumor activity, and careful observation is neededfor administration of this agent to patients with pre-existingrisk factors, such as prior anthracycline exposure, mediastinalradiation or underlying cardiovascular disease.     

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.     

Expulsion of Hymenolepis nana from mice with congenital deficiencies of IgE production or of mast cell development

The roles of IgE and mast cells on expulsion of adult Hymenolepis nana from the intestine were examined in mice. IgE-dependency was determined by comparing congenitally IgE-deficient SJA/9 and IgE-producing SJL/J mice infected with 50 H. nana eggs. Anti-H. nana IgE antibody was detected at three weeks post infection (p.i.) in SJL but not in SJA mice. The number of adult worms in the intestines of SJA and of SJL mice were similar at two weeks, but significantly more were found in SJA mice at three weeks p.i. Treatment of mice with anti-ɛ antibody also resulted in an increased worm burden at three weeks, suggesting participation of IgE in expulsion of H. nana. Intestinal mastocytosis was induced by infection regardless of the IgE status of the mice. Mast cell-dependency was tested in mast cell-deficient W/W^u and in normal littermate +/+ mice infected with 100 H. nana eggs. Anti-H. nana antibody was detected in both groups of mice at three weeks p.i. Worm expulsion seemed to be mast cell dependent because expulsion was less complete in W/W^u mice at three weeks p.i. Peripheral blood eosinophilia was comparable at three weeks p.i. in both IgE and mast cell sufficient and deficient mice. These results suggest that IgE and mast cells participate in the expulsion of H. nana adults from intestine in mice.     

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.     

Effects of Acute Lead Acetate Exposure on Adult Guinea Pigs: Electrophysiological Study of the Inner Ear

The effects on humans of lead acetate exposure may involve thecranial nerves, since vertigo and sensory neuronal deafnesshave been reported in lead workers; however, there exist onlya few reports concerning the dose effects of lead acetate bothon the cochlea and the eighth cranial nerve. The effects oflead acetate on the cochlea and the eighth nerve were investigatedsystematically using cochlear microphonics (CM), wholenerveaction potential (AP), and endocochlear potential (EP) in guineapigs (male albino Hartley). Guinea pigs were injected with 2ml of a 1% solution of lead acetate (20 mg) once a week for1–5 weeks. The threshold of whole-nerve AP (N₁) was elevatedby injection of lead acetate, even 40 mg, and whole-nerve AP(N₁) output voltage decreased after injection of 100mg of leadacetate. On the other hand, no change was observed in CM afterlead acetate injection (100 mg) or in EP after lead acetateexposure (40 mg). The blood concentrations of lead acetate wereas follows (mean): control, 4.5 µg/dl; Expt 1, 80 µg/dl;Expt 2, 126 µg/dl; Expt 3, 142 µg/dl;. We concludethat dysfunction of the eighth nerve is induced by high-doselead exposure, but that lead exposure does not induce electrophysiologicaldysfunction of the organ of Corti and the stria vascularis.     

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.