Roles of prostanoids in the pathogenesis of cardiovascular diseases.

The roles of prostanoids in the pathogenesis of cardiovascular diseases and in the development of pathological conditions have been examined using mice lacking the individual, specific prostanoid receptor. Prostaglandin (PG) I2 protected the heart from ischemia-reperfusion injury in a model of acute myocardial infarction. In addition, PGI2 suppressed the development of pressure overload-induced cardiac hypertrophy. Aside from its potent vasodilatory action, PGI2 contributed critically to the development of renovascular hypertension via the activation of the renin-angiotensin-aldosterone system. Thromboxane (TX) A2 and PGF2alpha were found to be the mediators of inflammatory tachycardia under a systemic inflammatory condition induced by lipopolysaccharide. Under a septic condition leading to a vascular hypo-responsive state, TXA2 worked to maintain vascular tone by inhibiting the induction of inducible nitric oxide synthase in vascular smooth muscle cells. Mice lacking the PGE2 receptor subtype EP3 had a bleeding tendency and were resistant to thromboembolism, due to a defective activation of platelets. From these studies, the important and novel roles of prostanoids in the pathogenesis of cardiovascular diseases have been clarified.

Endothelin-1 production is enhanced by rotenone, a mitochondrial complex I inhibitor, in cultured rat cardiomyocytes.

In chronic heart failure and acute myocardial infarction, the tissue level of endothelin (ET)-1 in the heart, as well as its plasma level, has been reported to increase markedly. There is, however, little information about what in these pathologic conditions leads to increased production of ET-1, and which type of cell in the heart produces ET-1. We examined the mRNA and peptide expression of ET-1 using cultured rat neonatal cardiomyocytes, in which mitochondrial dysfunction was induced by rotenone, a mitochondrial respiratory chain complex I inhibitor, because one of the common features in failing or ischemic hearts is an alteration in energy metabolism due to mitochondrial dysfunction. Rotenone increased glucose use by the culture cells within 12 h of addition without affecting cell viability, and depressed the mitochondrial membrane potential after 72 h, indicating the induction of mitochondrial dysfunction in cardiomyocytes. Rotenone induced significant increase in the expression level of mRNA for ET-1 within 1 h of addition. In accordance with this finding, immunoreactive ET-1 in culture medium increased 3 times after 24 h of incubation, suggesting active secretion of ET-1 from cultured cells treated with rotenone. Immunocytochemical analysis verified significant increase of ET-1 peptide in cardiomyocytes, confirming the production of ET-1 by cardiomyocytes. These results suggest that derangement of mitochondrial function in cardiomyocytes itself could lead to the increased production of ET-1 in cardiomyocytes, and that this mechanism may contribute to the increased production of ET-1 in failing and ischemic hearts.

Roles of prostaglandin I(2) and thromboxane A(2) in cardiac ischemia-reperfusion injury: a study using mice lacking their respective receptors.

BACKGROUND: Prostaglandin (PG) I(2) and thromboxane (TX) A(2), the most common prostanoids in the cardiovascular system, are produced abundantly during cardiac ischemia/reperfusion (I/R); their roles in I/R injury, however, remain undetermined. We intended to clarify these roles of PGI(2) and TXA(2) using mice lacking the PGI(2) receptor, IP(-/-) mice, or the TXA(2) receptor, TP(-/-) mice. METHODS AND RESULTS: The left anterior descending coronary artery was occluded for 1 hour and then reperfused for 24 hours. The size of myocardial infarct in IP(-/-) mice was significantly larger than that in wild-type mice, although the size of the area at risk was similar between the 2 groups of mice. In contrast, there was no such difference between TP(-/-) and wild-type mice. To further determine whether PGI(2) and TXA(2) act directly on the cardiac tissue or indirectly through their action on blood constituents, we perfused excised heart according to the Langendorff technique. The isolated heart was then subjected to global ischemia followed by reperfusion. In IP(-/-) mice, developed tension and coronary flow rate during reperfusion were significantly lower and release of creatine kinase was significantly higher than those in wild-type mice. There were no such differences, however, between TP(-/-) and wild-type mice. CONCLUSIONS: PGI(2), which was produced endogenously during cardiac I/R, exerts a protective effect on cardiomyocytes independent of its effects on platelets and neutrophils. In contrast, TXA(2) has little role in the cardiac I/R injury.

[The relationship between delayed traumatic intracerebral hematoma and coagulopathy in patients diagnosed with a traumatic subarachnoid hemorrhage].

It has long been recognized that a traumatic insult to brain tissue may result in substantive coagulation abnormalities. The present study was carried out in an attempt to find out the association of coagulopathy and the development of delayed traumatic intracerebral hematoma (DTICH) in patients diagnosed with a traumatic subarachnoid hemorrhage (TSAH). Sixty-three patients were diagnosed as having TSAH from the initial CT scans obtained within 2 hours after trauma. On admission, peripheral blood samples for coagulation studies were taken within 6 hours after injury. All patients had subsequent CT scans performed within 24 hours of admission. Thirty (47.6%) of 63 patients exhibited radiological evidence of DTICH on their subsequent CT scans. There was a significant correlation between the increased value of serum fibrinogen degradation product (FDP > 40 micrograms/ml) and the development of DTICH. We observed that the origin of the hematoma might be caused by those radiographically unidentifiable parenchymal lesions often found with TSAH on the initial CT scan. We conclude that a clotting study at the time of admission is of value in predicting the occurrence of DTICH associated with TSAH.

[A ruptured aneurysm of the anterior and posterior inferior cerebellar artery: a case report].

We report a case of an anterior and posterior-inferior cerebellar artery (AICA-PICA) aneurysm. The patient was a 62-year-old woman who suffered from sudden onset of severe headache and nuchalgia. Computed tomography (CT) scan revealed subarachnoid hemorrhage in the ambient cistern and blood clots in the 3rd and 4th ventricles. Vertebral angiography demonstrated an aneurysm located at the distal segment of the left AICA-PICA. Three demensional CT scan was very useful for the decision concerning surgical strategy. The patient underwent bilateral occipital craniectomy and the aneurysm was clipped successfully via the midline suboccipital approach. Her postoperative course was uneventful. Postoperative angiography showed successful clipping of the aneurysm. Distal AICA-PICA aneurysm is a very rare disease and only one case has been reported in the literature. The clinical features, CT findings, and surgical approach of distal AICA-PICA aneurysms are briefly discussed while reviewing the literature.

[Crushing head injuries: report of six cases].

We report 6 cases of crushing head injuries produced by static loading forces, which are defined as those that occur over a longer period of time (> 200 ms) and are applied over a large area. Patients ranged in age from 4 to 53 years. There were five male and one female. The causes of injuries in 5 cases were industrial accidents. In one case, the patient's head was run over by a motor vehicle in a parking lot. Glasgow Coma Scale scores ranged from 3 to 12. Three patients had cerebrospinal fluid otorrhea and rhinorrhea. Computed tomograms showed multiple calvarial and basilar cranial fractures, as well as intracranial hematomas, pneumocephalus and diffuse cerebral swelling. In 4 cases, fatal compressive brain damage occurred. Compression of the skull beyond a certain degree causes damages to the brain itself and the great vessels through cerebral compression. We consider that this damage may contribute to mortality in such injuries.

Infected subdural hematoma.

A case is presented in which Escherichia coli seeded a pre-existing chronic subdural hematoma. A 77-year-old woman was admitted to our hospital because of lethargy, left hemiparesis and fever. Drainage through a burr hole was performed with the diagnosis of bilateral chronic subdural hematoma. Operative findings revealed the infected subdural hematoma on the right side and non-infected subdural hematoma on the left side. Cultures of the subdural hematoma grew Escherichia coli. In view of the pyuria, the etiology of the infected subdural hematoma was postulated to be a urinary tract infection. In the majority of 14 reported cases, the causative organisms were Escherichia coli, Salmonella, and the systemic sources of infection included the urinary tract, gastrointestinal disease, or were unknown. The possibility of infected subdural hematoma should be considered when computed tomography findings suggestive of chronic subdural hematoma exist in a patient with signs of infection.

[Intracranial invasion of neuroendocrine carcinoma: a case report].

A rare case of neuroendocrine carcinoma arising from the nasal cavity is reported. A 57-year-old female, who had been complaining of anosmia for 8 years, was admitted to the otolaryngological department because an intranasal tumor was found. Then, removal of the tumor and radiotherapy was carried out. After these procedures, the patient suffered from a high fever and CSF rhinorrhea. At this stage, our neurosurgical department was consulted. CT scan revealed a partially calcified low density mass with a slight enhancement effect at the left frontal base. Under the diagnosis of intracranial invasion by intranasal neuroendocrine carcinoma, the patient was operated on. Through bifrontal craniotomy and a combination of extra- and intradural approach, the tumor was excised. After that, the dura and the skull base were reconstructed. On histological examination, the tumor was found to consist of NSE positive cells forming some glandular structures. Electron microscopic study disclosed neurosecretory granules in the cytoplasmic process. These findings are typical of neuroendocrine carcinoma and compatible to those of the intranasal tumor previously removed. Neuroendocrine carcinoma is rare in itself and there have been reported only two cases of its invasion of the skull base. The clinical features, diagnostic procedures, pathological findings, and treatment of this tumor are discussed in this report.

[Therapeutic analysis of autopsy findings in oral cancer].

Thirty-four autopsied patients with oral squamous cell carcinoma were analyzed by multiple regression analysis. The following results were obtained. 1) The suggested metastatic spread was from the highest count of oral cancer patients with metastases in lung to lower key organs, reflecting the cascade theory. 2) Multiple regression analysis revealed that local recurrence was significantly related to the treatment method, indicating that multidisciplinary treatment would be needed. 3) Multiple regression analysis indicated that mediastinal lymph node metastasis was significantly related to both the age of the patient and the stage of cancer development. 4) Multiple regression analysis showed that distant metastasis was significantly related to both the stage and the spleen weight. 5) There were many patients with the pulmonary metastases undergoing irradiation which ranged from 40Gy to 60Gy on the primary tumor. 6) Results showed that immunotherapy tended to control pulmonary metastases.

Imaging diagnosis of von Hippel-Lindau disease: a case report.

A patient with typical manifestations of von Hippel-Lindau disease is presented. In this 44 year-old man, cerebellar hemangioblastoma was found initially and he was operated upon at the age of 25. This was followed by retinal angiomas treated by cryocoagulation and, recently, by paresthesia of both legs and frequent shooting pains over the lower abdomen. A computed tomography disclosed multiple small cysts of the pancreas, bilateral multicentric renal carcinomas and a spinal angioma in the lumbar portion, confirmed by magnetic resonance imaging, and consistent with neurogenic manifestations. Multiple enucleations of the renal cell carcinomas were carried out, most of which were histologically well differentiated adenocarcinomas. There was no family cluster. Six months postoperative, the patient is doing well.

[Spontaneous cerebral ventriculostium (author's transl)].

Two cases of spontaneous cerebral ventriculostium are presented. The first case is that of a 3 year-old girl with a thumb-sized soft scalp tumor of the occipital region (dural hypertrophy) and hydroencephalodysplasia (Picaza). PVG revealed noncommunicating hydrocephalus with asymmetrical deformity of the lateral ventricle and agenesis of corpus callosum (Fig. 1). Ventriculoatrial shunt was performed. Three years passed under the useful life when she readmitted to our clinic complaining headache, nausea and vomiting. On the first hospital day she fell into respiratory arrest accompanied with coma after the tonic convulsion, and eventually, she died on the fourth hospital day. Postmortem examination revealed spontaneous cerebral ventriculostium which communicated with the posteromedial trigone of the left lateral ventricle (Fig. 3). Combined other malformations such as dysgenesis of the corpus callosum and only one anterior cerebral artery, etc. were found. The second case is that of a young adult, a 22 year-old male with rapidly progressing intracranial hypertension. PVG revealed marked dilatation of the lateral and the third ventricle, non-filling of the aqueduct and spontaneous cerebral ventriculostium which communicated with the posterior part of the third ventricle (Fig. 4). And insidiously he fell into akinetic mutism. After suboccipital exploratory craniotomy and ventriculo-peritoneal shunt akinetic mutism improved gradually, and he was discharged on foot after 7 months. PEG performed on June 8, 1973, showed no evidence of aqueduct obstruction and injected air passed from the fourth ventricle to the third one smoothly. He lives on now under a useful condition. These 2 cases are the first report on literatures in Japan, but presumably there must be many other cases. Since W. H. Sweet reported his own two cases of spontaneous cerebral ventriculostium on 1940, more than thirty cases have been published on literatures. However, there are found various expressions to describe the same condition (Table 1). We would like to propose that the most suitable expression is "ventriculostium" not only in deference to the originality of W. H. Sweet but also not to confuse this pathogenetic state with other similar conditions. The author's next interest is the chronological fact that from W. H. Sweet (1940) to A. Torkildsen (1948), all but one ostiums reported situated at the posteromedial trigone of the lateral ventricle, whereas after A. Torkildsen, they were found at the posterior part of the third ventricle in many cases. The reason is unknown. It would appear that three main conditions are necessary for the development of ventricluostium just beneath the tentorium. The first, there must be increased pressure within the lateral or the third ventricle. The second essential feature is the lack of any large space occupying lesion in the the infratentorial space. The third, there must be wider space between the tentorial incisura and the brain stem.