A detrimental effect of platelets on mouse embryo development

We reported previously that serum prepared by delayed centrifugation of whole blood (DC serum), which is used widely in human in vitro fertilization and embryo transfer programs, has a detrimental effect on embryonic development. In an attempt to understand the mode of production of embryo-toxic factors in DC serum, we developed a model in which blood coagulation is initially blocked and later induced. The serum prepared in this fashion from whole blood (WB serum) is detrimental to mouse embryo development, as is DC serum. The toxicity of WB serum appears to derive mainly from the platelet release reaction during blood coagulation. Adenosine diphosphate and/or its degradation products may act directly to impair embryonic development and appear to be the main embryo-toxic substance(s) resulting from the platelet release reaction.     

Treatment of peritoneal dissemination from gastric cancer by peritonectomy and chemohyperthermic peritoneal perfusion

BACKGROUND: There is no standard treatment for peritoneal dissemination from gastric cancer. A novel treatment consisting of peritonectomy and intraoperative chemohyperthermic peritoneal perfusion (CHPP) was compared with conventional surgery and CHPP. METHODS: Records of all patients who underwent CHPP after cytoreductive surgery between 1992 and 2002 were reviewed. RESULTS: Data for 107 patients with peritoneal dissemination were available. Complete cytoreduction was achieved in 47 (43.9 per cent) of the 107 patients: 18 of 65 who underwent conventional surgery and 29 of 42 who had peritonectomy. Twenty-three patients (21.5 per cent) suffered from complications. The overall operative mortality rate was 2.8 per cent. Seventeen patients (15.9 per cent) were disease free and 87 subsequent deaths were related to disease progression. The median survival for all patients was 11.5 months, with a 5-year survival rate of 6.7 per cent. Median survival after complete cytoreduction was 15.5 months and that after incomplete cytoreduction was 7.9 months, with 5-year survival rates of 13 and 2 per cent respectively. Completeness of cytoreduction and peritonectomy were independent prognostic factors. The 5-year survival rate after complete cytoreduction by peritonectomy with CHPP was 27 per cent. CONCLUSION: Complete cytoreduction after peritonectomy and CHPP may improve the survival of patients with peritoneal dissemination from gastric cancer.     

Bromocriptine treatment of prolactinoma restores growth hormone secretion and causes catch-up growth in a prepubertal child

A 13-year-old Japanese boy with pituitary prolactinoma whose growth had been retarded for more than 2 years was treated with bromocriptine alone for 140 weeks. After treatment, the serum level of prolactin, which was 1200 ng/ml before treatment, returned to normal and the pituitary tumour seen on the initial brain MRI had rapidly decreased in size after 16 weeks of treatment. Thereafter, his height improved (from -2.1 to -1.7 SDS). Conclusion:the favourable response obtained in this patient implies that bromocriptine monotherapy can be an effective first-line treatment for children with prolactinoma.Abbreviation GH growth hormone     

A primary choriocarcinoma of the stomach with a review of 45 cases in Japan

A case of a primary choriocarcinoma of the stomach is reported together with review of 44 cases in the Japanese literature. The patient, a 79-year-old male complaining of severe anemia, was admitted to hospital. As a result of a gastric endoscopy, a carcinoma was diagnosed and a laparotomy was performed. Because of an extensive metastasis, however, the surgery was limited to a palliative proximal gastrectomy. Pathologically, the tumor was a choriocarcinoma, and the HCG in the blood was slightly elevated. Immunohistologically, however, no HCG was detected. Although most cases reported in Japan support the theory of differentiations in gastric carcinomas, this choriocarcinoma suggests a separate type of differentiation in both the function and the morphology or a morphological mimicking.     

Beneficial effects of a new 20-hydroxyeicosatetraenoic acid synthesis inhibitor, TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide], on hemorrhagic and ischemic stroke

The present study characterized the effects of TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide], a new selective inhibitor of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), on the metabolism of arachidonic acid by human and rat renal microsomes and the inhibitory effects of this compound on hepatic cytochrome P450 enzymes involved in drug metabolism. The effects of TS-011 on the fall in cerebral blood flow following subarachnoid hemorrhage (SAH) and in reducing infarct size in ischemic stroke models were also examined since 20-HETE may contribute to the development of cerebral vasospasm. TS-011 inhibited the synthesis of 20-HETE by human renal microsomes and recombinant CYP4A11 and 4F2, 4F3A, and 4F3B enzymes with IC50 values around 10 to 50 nM. It had no effect on the activities of CYP1A, 2C9, 2C19, 2D6, or 3A4 enzymes. TS-011 inhibited the synthesis of 20-HETE by rat renal microsomes with an IC50 of 9.19 nM, and it had no effect on epoxygenase activity at a concentration of 100 microM. TS-011 (0.01-1 mg/kg i.v.) reversed the fall in cerebral blood flow and the increase in 20-HETE levels in the cerebrospinal fluid of rats after SAH. TS-011 also reduced the infarct volume by 35% following transient ischemic stroke and in intracerebral hemorrhage in rats. Injection of 20-HETE (8 or 12 mg/kg) into the carotid artery produced an infarct similar to that seen in the ischemic stroke model. These studies indicate that blockade of the synthesis of 20-HETE with TS-011 opposes cerebral vasospasm following SAH and reduces infarct size in ischemic models of stroke.     

A new technique in endoscopic ultrasonography of the upper gastrointestinal tract

Endoscopic ultrasonography (EUS) of the upper GI tract was unsuccessful in 42 out of 274 patients (15%) due to inaccurate guidance of the probe to small, shallow lesions, or to difficulty in clearly demonstrating the surrounding layer structure and boundary of the lesion. We applied the saline injection technique in these 42 patients. Saline was injected into the submucosal layer of the esophagogastric wall. The ultrasonographic image of adjacent saline accurately guided the probe to the lesion. Injected saline enabled the mucosal layer to be distinguished from the muscularis propria surrounding the lesion and provided clear ultrasonographic imaging of the boundary between the lesion and the surrounding layer structure. This new method was found to be effective in 38 out of 42 patients in whom EUS was unsuccessful. A study comparing the depth of tumor invasion diagnosed by the saline injection technique with histological findings obtained in 12 cases showed good correlation. These results indicate that the saline injection technique would seem to be very useful as an adjuvant to conventional EUS.     

Proliferative activity of micrometastases in the lymph nodes of patients with gastric cancer

BACKGROUND: Immunohistochemically detectable isolated tumour clusters (ITCs) with a diameter of less than 0.2 mm have been regarded as non-metastatic lesions, because of a lack of proliferative activity. This study investigated the proliferative activities of ITCs. METHODS: Three hundred and eight patients with primary gastric cancer diagnosed as pN0 by routine histological examination were studied. All patients underwent curative resection. Sections of lymph nodes were stained by double-immunostaining methods using anti-cytokeratin and anti-Ki-67 antibody (MIB-1). RESULTS: ITCs were detected in 77 nodes from 37 patients, designated as having pN0(i+) lesions. Seventy of 77 lymph nodes with ITCs were detected in the N1 station, and seven were found in the N2 station. Of 25 single isolated cancer cells, 12 showed positive labelling with MIB-1, and 49 of 52 ITCs with clusters of cancer cells had positive MIB-1 labelling (mean(s.d.) 46.6(30.1) per cent). Five of the 37 patients with ITCs (pN0(i+)) versus one of the 271 patients with no evidence of ITCs (pN0(i-)) died from recurrence. Patients with ITCs had a significantly worse prognosis than those without (P = 0.014). CONCLUSION: ITCs have a high proliferative activity and may have the potential to evolve into established lymph node metastasis.     

A resected case of advanced gastric cancer with complete remission of liver metastasis by chronic daily administration of oral etoposide and UFT]

An advanced gastric cancer with liver metastasis was treated with the combination MMC, Etoposide and UFT. Etoposide was administered orally at 25-50 mg/day to the gastric cancer patient with liver metastasis. In operative findings, there was no liver and lymphoid node metastasis. The gastric tumor diminished in size and changed its characteristics due to the chemotherapy. In 19 months, no liver nor LN metastasis was observed by CT scan. Presently, the patient feels well and receives outpatient treatment.     

Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on chronic heart failure. Examination by 123I-MIBG imaging

To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62 +/- 11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n = 7), hypertension (n = 2), and atrial fibrillation (n = 1). Radioiodinated metaiodobenzyl guanidine (123I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, (1) left ventricular ejection fraction (LVEF) increased significantly from 38.3 +/- 6.9% to 47.5 +/- 14.7%; (2) sub-maximal exercise time increased significantly from 205 +/- 112 to 272 +/- 120 seconds; (3) the heart to mediastinum (H/M) ratio of 123I-MIBG increased significantly (early image: 1.99 +/- 0.38 versus 2.20 +/- 0.50; delayed image: 1.86 +/- 0.44 versus 2.09 +/- 0.51); and (4) the washout rate of 123I-MIBG decreased slightly from 29.1 +/- 9.1% to 25.4 +/- 7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and 123I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure.