A selective thromboxane A2 (TXA2) synthase inhibitor, ozagrel, attenuates lung injury and decreases monocyte chemoattractant protein-1 and interleukin-8 mRNA expression in oleic acid-induced lung injury in guinea pigs.

This study examined the effect of ozagrel, a thromboxane A(2) synthase inhibitor, on the accumulation of leucocytes and chemokine mRNA expression in lungs experimentally injured using oleic acid (OA). OA injection into guinea pigs rapidly increased thromboxane A(2) generation and subsequently increased total protein concentration and the numbers of macrophages and neutrophils in bronchoalveolar lavage fluid and increased monocyte chemoattractant protein-1 and interleukin-8 mRNA expression in the whole lung. Administration of ozagrel prevented these changes associated with OA injection. Ozagrel is a promising drug candidate for preventing acute lung injury.

[Pathological and biochemical studies of 30 Niigata autopsy cases related to Minamata disease].

OBJECTIVES: To reevaluate pathologically and biochemically 30 autopsy cases related to Minamata disease (MD) in Niigata Prefecture (NP) and compare the findings with those of autopsy cases related to MD in Kumamoto Prefecture (KP). METHODS: Recently, a set of pathological materials of these 30 autopsy cases has been sent from the Brain Research Institute at the University of Niigata to the National Institute for Minamata Disease (NIMD). The materials from each autopsy case were reexamined at the NIMD. RESULTS: There were no postnatal and fetal cases of MD in the NP autopsy materials. The contents of total mercury (T-Hg), methylmercury (Me-Hg), inorganic mercury (I-Hg) and selenium were measured in the organs of cerebrum, cerebellum, liver and kidney. The contents of T-Hg, Me-Hg and I-Hg were much higher in two cases than in controls. The pathological findings leading to the diagnosis of MD in the NP cases were essentially the same as those in KP, including the peripheral nerve lesions. In the most severely affected case of MD in NP, formation of multiple vacuoles of various sizes was observed in the cerebellar cortex, which was never encountered in the KP cases. The KP lesions were similar to that observed in an acute case of Me-Hg-treated common marmoset studied in the NIMD. CONCLUSION: The pathological features were essentially the same between the adult cases of MD in NP and KP.

[Clinical significance of fine-needle aspiration biopsy in major salivary gland tumors].

We compared preoperative evaluations of 93 fine-needle aspiration biopsies (FNAB) of major salivary gland tumors done over a 5 year period with pathologic diagnoses of surgically resected specimens. The overall accuracy was 88.5%. Eight of 15 aspirates from malignant tumors were correctly diagnosed by FNAB, for a sensitivity of 53.3%, while 69 of 72 aspirates from benign tumors were correctly diagnosed by FNAB, for a specificity of 95.8%. Five malignant tumors diagnosed as benign by FNAB were squamous cell carcinoma, carcinoma in pleiomorphic adenoma, malignant lymphoma, low-grade mucoepidermoid carcinoma, and acinic cell carcinoma. The false negatives in the first 2 cases appeared to be due to inaccurate placement of the aspiration site. The other 3 cases showed lack of atypia, leading to a benign diagnosis. Malignant lymphoma is difficult to diagnose as malignant, even in properly aspirated specimens, so we recommend open biopsy when malignant lymphoma is suspected from physical and radiological examinations. A case confirmed pathologically as benign myoepithelioma was diagnosed as adenoid cystic carcinoma preoperatively, based on the finding of a cribriform pattern containing mucin. It should be borne in mind that myoepithelioma and adenoid cystic carcinoma are difficult to distinguish by FNAB. Although FNAB is useful in diagnosing major salivary gland tumors, its low sensitivity (high percentage of false negatives) is undesirable. It may thus be helpful in intraoperative decision-making when combined with frozen sectioning.

Extensive intraoperative peritoneal lavage and chemotherapy for gastric cancer patients with peritoneal free cancer cells.

The effects of extensive intraoperative peritoneal lavage (EIPL) for gastric cancer patients with peritoneal free cancer cells were investigated. This study was based on 22 consecutive patients with peritoneal free cancer cells, among 663 patients who underwent curative surgical treatment for advanced gastric cancer. The 22 patients were followed up for 2 years or until death. These patients were divided into three groups: group 1, patients with no additional intraoperative therapy (from 1989 to 1992; n = 8); group 2, patients with intraoperative intraperitoneal chemotherapy alone (from 1992 to 1995; n = 7); and group 3, patients with EIPL followed by intraoperative intraperitoneal chemotherapy (from 1996 to 1999; n = 7). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that viable cancer cells were not detected after the eighth EIPL in a gastric cancer patient with numerous intraperitoneal free cancer cells. In group 3, 4 of the 7 patients survived for more than 2 years, including 3 with cancer-free status, whereas no patient survived cancer-free in groups 1 and 2. The peritoneal recurrence rates and cancer-specific 2-year survival rates in groups 1, 2, and 3 were 100%, 85.7% and 42.9%; and 0%, 14.3%, and 57.1%, respectively. The 2-year survival rate of group 3 was significantly higher than that of group 1 (P = 0.017) and that of group 2 (P = 0.025). In a subset analysis, patients with peritoneal free gastric cancer cells but no macroscopic dissemination showed a statistically significant improvement in survival those treated with EIPL compared with those not treated with EIPL.

An autopsy case of minamata disease (methylmercury poisoning)--pathological viewpoints of peripheral nerves.

The outbreak of methylmercury poisoning in the geographic areas around Minamata Bay, Kumamoto, Japan in the 1950s has become known as Minamata disease. Based on earlier reports and extensive pathological studies on autopsied cases at the Kumamoto University School of Medicine, destructive lesions in the anterior portion of the calcarine cortex and depletion predominantly of granular cells in the cerebellar cortex came to be recognized as the hallmark and diagnostic yardstick of methylmercury poisoning in humans. As the number of autopsy cases of Minamata disease increased, it became apparent that the cerebral lesion was not restricted to the calcarine cortex but was relatively widespread. Less severe lesions, believed to be responsible for the motor symptoms of Minamata patients, were often found in the precentral, postcentral, and lateral temporal cortices. These patients also frequently presented with signs of sensory neuropathy affecting the distal extremities. Because of few sufficiently comprehensive studies, peripheral nerve degeneration has not been universally accepted as a cause of the sensory disturbances in Minamata patients. The present paper describes both biopsy and autopsy findings of the peripheral nerves in a male fisherman who died at the age of 64 years and showed the characteristic central nervous system lesions of Minamata disease at autopsy. A sural nerve biopsy with electron microscopy performed 1 month prior to his death showed endoneurial fibrosis and regenerated myelin sheaths. At autopsy the dorsal roots and sural nerve showed endoneurial fibrosis, loss of nerve fibers, and presence of Büngner's bands. The spinal cord showed Wallerian degeneration of the fasciculus gracilis (Goll's tract) with relative preservation of neurons in sensory ganglia. These findings support the contention that there is peripheral nerve degeneration in Minamata patients due to toxic injury from methylmercury.

Methylmercury poisoning in common marmosets--MRI findings and peripheral nerve lesions.

Common marmosets were used as model animals for methylmercury (MeHg) poisoning. Six marmosets were given MeHg of 5 ppm Hg in drinking water. The animals were divided into 3 groups of 2 each. The first group was examined for acute symptomatic MeHg poisoning. They were given MeHg for 70 and 90 days, respectively, to manifest severe symptoms. The second group was sacrificed after 38 days of MeHg exposure, when they had acute-subclinical MeHg poisoning. The third group of animals was exposed for 21 days, and then observed for 2.5 years without MeHg exposure. One of them showed typical symptoms of MeHg poisoning after MeHg exposure had ended, but the other one showed only slight symptoms without ataxia. This experiment demonstrated that MeHg causes pathological changes in neural tissues including the peripheral nerves in common marmosets. Furthermore, common marmosets were found to show MeHg-induced pathological changes similar to those in humans in the cerebrum and cerebellum.