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.     

Functional mechanism underlying cyclooxygenase-2 expression in rat small intestine following administration of indomethacin: Relation to intestinal hypermotility

Background and Aim:  We recently reported that cyclooxygenase (COX)-2 is upregulated in the rat small intestine after administration of indomethacin, and this may be the key to non-steroidal anti-inflammatory drug (NSAID)-induced intestinal damage. The present study investigated the mechanism for COX-2 expression induced in the rat small intestine by indomethacin, in relation with ulcerogenic processes.
Methods:  Animals were given indomethacin or SC-560 p.o., and the intestinal mucosa was examined 24 h later.
Results:  Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility, bacterial invasion and inducible nitric oxide synthase (iNOS) activity, as well as the expression of COX-2 mRNA in the mucosa. Although SC-560 did not cause any damage, this agent caused intestinal hypermotility, the bacterial invasion and the upregulation of COX-2 expression. The mucosal PGE₂ content was decreased by SC-560 at 3 h but recovered 12 h later, and this recovery of PGE₂ was attenuated by both atropine and ampicillin, in addition to rofecoxib. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE₂ and atropine, but not ampicillin. Yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 and iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in the prevention of intestinal lesions.
Conclusion:  These results suggest that COX-2 expression in the intestinal mucosa following the administration of indomethacin is associated with intestinal hypermotility and bacterial invasion. The intestinal hypermotility caused by COX-1 inhibition may be a key to COX-2 expression after administration of NSAIDs and their intestinal ulcerogenic properties.     

Recording of electroencephalograms and electrocardiograms during daytime sleep in trained canines: Preparation of the sleeping dogs

Abstract  Although respiration in trained canines is well investigated, the process of preparing dogs has not been described in any great detail. Moreover, their daytime patterns of sleep and wakefulness during 1 or 2 h of electroencephalogram (EEG) and electrocardiogram (ECG) recordings are not clear. Therefore, we describe the process of selecting and training dogs, in which we recorded EEG and ECG in the laboratory. First, 14 of 1242 dogs dealt with over a 1 year period were chosen. They were trained for 2 h to lie quietly and to sleep in the laboratory; this training procedure was repeated 152 times. Three dogs were then selected and a permanent tracheostomy was performed in one. Finally, EEG and ECG were recorded with the bipolar fine needle electrodes; respiration was recorded simultaneously through a tube inserted to a tracheostomy in one dog. Wakefulness, slow wave sleep (SWS) and rapid eye movement (REM) sleep (REMS) were identified according to the EEG pattern and on the basis of the behavioral criteria. Recordings were performed 12 or 13 times in each dog. Complete sleep cycles, including wakefulness, SWS and REMS in this sequence, were observed 3.9–4.1 times. The mean duration of SWS was 2.2–4.4 min and that of REMS was 3.5–4.6 min. The REMS latency was 33.9–41.8 min. Fluctuation of heart rate with respiration, termed respiratory sinus arrhythmia, was noted in the ECG. Heart beat increased with inspiration and decreased with expiration. The present study demonstrates how to select and train sleeping dogs and shows their undisturbed daytime sleep and wakefulness patterns.     

Quality of ulcer healing influences the relapse of gastric ulcers in humans

The usefulness of dye-contrast endoscopy for the evaluation of the quality of gastric ulcer healing and the prediction of relapse was investigated. Sixty consenting patients whose ulcers healed during 3 months of treatment underwent endoscopy for the identification of the pattern of mucosal regeneration. Patients were monitored for relapses for up to 18 months after antiulcer therapy had ended. The pattern of regeneration was flat in 24 patients, nodular in 25 and intermediate in 11. Internal hypoechoic areas seen by endoscopic ultrasonography were less common and histological maturity was better in the patient group with the flat pattern compared with the patient group with the nodular pattern of mucosal regeneration. Prostaglandin E, synthesis was highest in the group with the flat pattern of mucosal regeneration and the relapse rate was lowest in this group. We conclude that the evaluation of the quality of ulcer healing is possible and that findings in individuals may aid the prediction of relapse for particular patients.     

Leiomyosarcoma of the renal vein: Arterial encasement on contrast-enhanced dynamic computed tomography

We report a case of leiomyosarcoma of the renal vein, which is a rare tumor with no more than 30 cases found in the published English language literature. This case demonstrates encasement of the renal artery by the tumor mass, a previously unreported manifestation. The present study could be useful in considering this rare tumor in the differential diagnosis of renal hilar tumors.     

Complete response, as determined by prostate-specific antigen level, to chlormadinone acetate withdrawal persisting longer than 2 years in patients with advanced prostate cancer: Two case reports

Antiandrogen withdrawal syndrome (AWS) is a well-established phenomenon in prostate cancer. However, responses to AWS are usually of limited duration, and a complete response (CR) is extremely rare. We present two patients who exhibited a chemical CR for more than 2 years after the discontinuation of steroidal antiandrogen chlormadinone acetate use. Whether patients who respond to antiandrogen withdrawal include a group of patients with a better prognosis remains uncertain. However, considering that the usual survival period of patients with hormone-resistant prostate cancer is approximately 12 months, both of the patients reported here, who are present in excellent physical condition, exhibiting an improved quality of life, and attending their hospital as outpatients, obviously acquired a prolonged survival because of AWS.     

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.     

HtrA2 is up-regulated in the rat testis after experimental cryptorchidism

AIM: The aim of the present study was to elucidate the role of high temperature requirement A2 (HtrA2) in germ cell loss in the heat-stressed testis. METHODS: We examined the expression of HtrA2, caspase-9 activity and proteolytic activity of HtrA2 in the rat testis, and their in vivo responses to experimental cryptorchid treatment. RESULTS: Northern analysis revealed the expression of HtrA2 mRNA peaked at days 1 and 7 after cryptorchid treatment. While expression of HtrA2 mRNA was seen in the spermatogonium, spermatocytes and some spermatids in normal adult rat testis, experimental cryptorchidism treatment resulted in a marked increase in its signal intensity in spermatocytes and some spermatids, and the layers of spermatogonium and early primary spermatocytes became negative at days 1 and 7 after the treatment. However, the spermatogonium, Sertoli cells and interstitial cells appeared to have strong intensities at days 14, 28 and 56 after the treatment. Western analysis revealed the expression of HtrA2 protein peaked at day 2 coinciding with the increase of positive spermatogonium, the appearance of protein-positive interstitial cells, and day 28 coinciding with the reappearance of protein-positive interstitial cells. Caspase-9 activity peaked at day 2 and HtrA2 proteolytic activity peaked at day 28. Consequently, the first peak of HtrA2 mRNA expression was followed by the peak of caspase-9 activity and the second peak was followed by the peak of proteolytic activity; however, the second peak of mRNA expression had considerable chronological difference from that of the protein. CONCLUSION: These findings suggest the probabilities that the heat stress results in germ cell death by a caspase-independent manner with the elevation of HtrA2 proteolytic activity, as well as a caspase-dependent manner with the elevation of caspase-9 activity.     

Relationship between cellular ATP content and cellular functions of primary cultured rat hepatocytes in hypoxia

The importance of oxygen in maintaining the functional integrity of hepatocytes has been well established in a variety of experimental models, such as in vivo , perfused liver and isolated hepatocytes. However, one of the shortcomings of these systems is their short life span. Therefore, we have examined the effects of long-term hypoxia on cellular adenine nucleotide content and cellular functions, such as albumin production, urea production and DNA synthesis, in adult rat hepatocytes in primary culture. Hepatocytes were cultured at a density of 11 × 10⁴ and 5 × 10⁴ cells/0.18 mL per cm² for the study of albumin and urea production and DNA synthesis, respectively, at various oxygen tensions (20, 12, 8 and 5%) for 24 h. Cellular ATP content in cultured hepatocytes in hypoxia gradually declined, corresponding to the decrease in oxygen tension, and the cellular ATP level at 5% oxygen was approximately 20% of that at 20% oxygen. Albumin production also decreased in parallel with the decrease in cellular ATP content in cultured hepatocytes in hypoxia. However, even when cellular ATP content gradually declined corresponding with the decrease in oxygen tension in cultured hepatocytes in hypoxia, such as at 8 or 5% oxygen, urea production remained at a high level; in contrast, DNA synthesis was completely suppressed. These results suggest that the cellular ATP content decreases in cultured hepatocytes during long-term hypoxia in relation to oxygen tension and that the relationship between decreased ATP levels and liver function in cultured hepatocytes during hypoxia differs for albumin production, urea production and DNA synthesis.     

Functional thrombomodulin expression on epithelial skin tumours as a differentiation marker for suprabasal keratinocytes

Summary In normal human skin, immtmoreactive thrombomodulin (TM) is expressed in a strict differentiation related pattern. solely in suprabasal spinous layer keratinocytes. To evaluate the polential application of TM as a differentiation marker for keratinocyte-derived skin tumours, we have studied immunohistopathological, biochemical and functional TM activities in various skin tumours. Immunoreactive, full sized and enzymatically active TM was expressed in keratinocyte-derived skin tumours (squamous cell carcinoma, seborrhoeic keratosis and partly Bowen's disease), as well as normal epidermal keratinoeytes and endothelial cells. However, no TM was detected in basal cell carcinotnas, senile keratosis or non-squanious epithelial tumours such as malignant melanoma, naevus pigmentosus and Paget's disease. Interestingly, decreased expression was observed in verruca vulgaris. These findings suggested that differentiation-dependent TM expression was restricted to epithelial skin tumours and undetectable on neural crest derived tumours. TM is a differentiation marker for spinous layer keratinocytes and is a useful tool in histopathological study of epithelial tumours.