Low-dose Docetaxel Enhanced the Anticancer Effect of Temsirolimus by Overcoming Autophagy in Prostate Cancer Cells.

BACKGROUND/AIM: Chemotherapy with docetaxel (DTX) is used for castration-resistant prostate cancer (CRPC), but it is inadequate. MATERIALS AND METHODS: We evaluated the effect of the combination treatment DTX and the mTOR inhibitor temsirolimus (TEM) in the PC3 prostate cancer cell line, by focusing on the induction of autophagy and apoptosis. RESULTS: TEM induced autophagy but not apoptosis even at a high dose, whereas DTX induced apoptosis. The combination of low-dose DTX and TEM caused a 34% suppression in cell proliferation compared to monotherapy with a higher dose of DTX. The induction of apoptosis was increased by their combination. The combination with DTX overcame the induction of autophagy by TEM. The combination treatment suppressed tumor growth 72% less than the control group after 14 days of treatment in vivo. CONCLUSION: The combination of TEM and DTX induced apoptosis by overcoming autophagy and enhanced the anticancer effect compared to monotherapy.

Studies on a microchemical method for the determination of the degree of polymerization of neutral oligo- and polysaccharides. I. Quantitative separation of trace amounts of alditols from mixtures with a large excess of monosaccharides.

A method has been devised for the quantitative separation of trace amounts of alditols from mixtures with large amounts of monosaccharides, using a strongly basic ion-exchange resin. Ten kinds of common reducing monosaccharides used were strongly retained by a very basic anion-exchange resin in the hydroxyl form, whereas the corresponding alditols showed no significant affinity for the basic resin. Model studies showed excellent recoveries of alditol from known mixtures of alditol and the corresponding aldose at ratios in the range from 1 : 1X10(3) TO 1 : 1X10(4) (by weight). Application of this procedure to dextrans after reduction and hydrolysis resulted in quantitative separation of the terminal alditol.

One-minute wave in body fluid volume change enhanced by postural sway during upright standing.

To analyze how the 1-min oscillation in postural sway and 1-min wave in body fluid volume change contribute to human circulatory homeostasis, several levels of body circumference, foot pressure center, electromyograms, and volumes of the leg, abdomen, and thorax were measured during upright standing for 40 min in 20 healthy young men. Spectral analyses of these parameters revealed that a 1-min rhythm is found in all parameters and that the 1-min wave in body fluid volume changes in the lower leg, which occur in fluid pooling caused by gravity, propagate upward. Muscle pumping in the lower leg triggered by the postural sway was found to increase the power of this 1-min wave. A quantitative analysis of body circumferences disclosed that the 1-min wave in body fluid volume change compensates for gravitational downward fluid shift, with the volume of 6.3 +/- 5.0 ml/cycle at the heart level. We concluded that a coupling mechanism between the 1-min oscillation in postural sway and the upward propagation of 1-min wave in body fluid volume change contributes to maintain systemic blood pressure during upright standing in humans.

Intracerebroventricular administration of nocistatin reduces inflammatory hyperalgesia in rats.

Nocistatin is a biologically active peptide derived from prepronociceptin, and its intrathecal administration has been reported to reduce nociceptin- or prostaglandin E2-induced hyperalgesia and allodynia in mice. In this study, we investigated the effects of intracerebroventricular (i.c.v.) administration of nocistatin on the inflammatory hyperalgesia induced by hindlimb intraplantar injection of carrageenan/kaolin in the rat paw-pressure test. Intracerebroventricular administration of nocistatin (0.5-50 pmol/rat) dose-dependently reduced carrageenan/kaolin-induced hyperalgesia, which peaked at 15-30 m. However, i.c.v. administration of nocistatin (50 pmol/rat) had no effect on the nociceptive threshold of non-inflamed rats. These results indicate that nocistatin has anti-hyperalgesic effects on the inflammatory hyperalgesia induced by carrageenan/kaolin at the supraspinal level.

A case of accessory mitral valve leaflet associated with solitary mitral cleft.

Accessory mitral valve leaflet is a rare congenital anomaly. More than half of the cases show other congenital cardiac defects and almost all of the cases show subaortic obstruction. We report a case of an accessory mitral valve tissue without outflow obstruction associated with mitral cleft of the posterior mitral leaflet. To our knowledge, this is the first reported case of the combination of these two congenital anomalies.

[Differential diagnosis between aneurysm and infundibular dilatation in the IC-PC region with 3D-CTA].

In cases of asymptomatic internal carotid-posterior communicating artery (IC-PC) protrusions, it is sometimes difficult to differentiate infundibular dilatation (ID) from aneurysm by digital subtraction angiography. We applied three-dimensional CT angiography (3D-CTA) in 32 cases of these IC-PC protrusions. SOMATOM PLUS 4 was used under such conditions as to provide images with high spatial resolution. The shaded surface display (SSD) method was adopted to reconstruct the 3D images because of its advantage in separating overlapped vasculature. We also made reference to source images and maximum intensity projection (MIP) to make sure of our diagnoses. In all cases including 4 aneurysms and 28 IDs, we were able to distinguish between ID and aneurysm. The accuracy of 3D-CTA was confirmed by 9 surgical cases. Our technique was as follows: 1) To inject a high dose of diluted contrast medium rapidly to smaller arteries for opacification of contrast medium. 2) To exclude neighboring useless structures except for the very close structures such as posterior clinoid process from the target image focusing on the IC-PC region. 3) To observe the reconstructed image of MIP and SSD from various angles. The contralateral and craniocaudal view were valuable. 4) To change the threshold level gradually and observe the configurational changes of the apex of protrusion. Poorly developed PcomA was mostly delineated at the optimum threshold level. Otherwise, the apex of protrusion remained spherical in an aneurysm and became pyramidal in shape in an ID when the threshold level was gradually decreased. In conclusion, 3D-CTA was a useful modality for IC-PC protrusions to distinguish between ID and aneurysm.

[Diffusion-weighted MRI in patients with occlusive cerebrovascular disease: the initial DWI findings within 6 hours after onset].

We performed this study to evaluate the accuracy of diffusion-weighted imaging (DWI) in detecting focal ischemia, and to predict the role of DWI in the management of patients with ischemia in the superacute phase. 99 patients with clinically diagnosed acute occlusive cerebrovascular disease were studied with DWI within 6 hours after onset of symptoms. In 88 of 99 patients, early ischemic lesions were identified on initial DWI as hyperintensity areas. The initial DWI findings were classified into 4 types according to the location and extent of the hyperintensity area. The patients with type 1 (no hyperintensity area) were clinically diagnosed as TIA or complete stroke within 2 hours after the onset. 28 patients out of the patients with type 2 (hyperintensity area in the perforator's territory) were diagnosed with lacunar infarction, and the remaining 13 patients were diagnosed as victims of stroke caused by main trunk occlusion. Except for 2 patients with TIA, the patients with type 3 (scattered hyperintensity areas in the cortex) had main trunk occlusion and showed a more extended ischemic area on SPECT than hyperintensity area on DWI. All the patients with type 4 (extended hyperintensity area) had main trunk occlusion and showed severe hypoperfusion in the affected area on SPECT, and the area of hypoperfusion was well matched with the hyperintensity area on DWI. Comparing DWI findings with rCBF on SPECT, a significant difference was noted in rCBF between hyperintensity and non-hyperintensity area. We considered that emergence of hyperintensity on DWI was related to both the time of duration and the degree of hypoperfusion, and the reduced perfusion area where DWI showed no hyperintensity was thought to be the "ischemic penumbra". Our study indicated DWI had high diagnostic accuracy in superacute occlusive cerebrovascular disease and could furnish useful information to reveal the pathologic condition. In addition, DWI is expected to be available for selection as a therapeutic strategy.

[Surgical indication and problems of patients aged over 70 years with unruptured aneurysms].

Surgical indication and problems of patients aged over 70 years with unruptured aneurysms were investigated. Clinical features of eighteen cases of unruptured cerebral aneurysms were analyzed. The location of the cerebral aneurysms were in the internal carotid artery in five cases, in the middle cerebral artery in ten cases, in the anterior cerebral artery in 2 cases and in the basilar artery in 1 case. The size of the aneurysms was less than 10 mm in diameter in 17 cases and giant in one case. Treatment of these aneurysms was classified into two groups as follows; the conservative treatment group (four cases) and the surgical treatment group (14 cases). The therapeutic results of the conservative group were good recovery in 2 cases, and death in 2 cases. On the other hand, the results of surgical group were good recovery in 12 cases and fair in 2 cases. Operative complications were recognized in two cases. Consciousness disturbance and left hemiparesis was recognized in one case. Right hemiparesis was recognized in the another case. Postoperative MR imagings or CT scan presented small cerebral infarctions in the corona radiata in both cases. The cause of infarction was thought to be the occlusion of lenticulostriate arteries. From these data, in patients aged over 70 years with unruptured cerebral aneurysms, surgery should be considered not only from the aspect of aneurysmal size and its site, but also from the aspect of cerebral blood flow of the patient.

[A case of diploic epidermoid invading intradurally, which was diagnosed by MR diffusion-weighted image].

A case of diploic epidermoid in the right parietal bone was presented. A 66-year-old male was admitted to our hospital because of aphasia. Plain skull radiogram showed an osteolytic lesion in the right parietal bone. Computed tomography revealed a mass with destruction of the parietal bone extending from an inner to an outer table. The mass was shown by MR imaging as hypointensity on the T1-weighted image and as hyperintensity on the T2-weighted image. The hyperintensity became more remarkable by using a diffusion technique. Based on these findings, a preoperative diagnosis of right parietal epidermoid was made. The mass was totally removed and diagnosed pathologically as epidermoid. It was concluded that diploic epidermoid invading intradurally could be differentiated from other osteolytic tumors by using MR diffusion-weighted image.

[Glioblastoma fed by meningeal branches of the external carotid artery: a case report].

A rare case of glioblastoma fed by meningeal branches of the external carotid artery was reported. A 63-year-old female was transferred to our hospital suffering from gait disturbance and dysarthria. CT and MRI revealed brain tumor and paratumoral hemorrhage with a large cyst that was heterogeneously enhanced and existed in the right fronto-temporal region. Right external carotid arteriography demonstrated the tumor stain markedly fed by the right middle meningeal artery and the accessory meningeal artery. Subtotal removal operation was carried out uneventfully using the right fronto-temporal craniotomy. The histological diagnosis was glioblastoma. After the operation the patient was in good condition, and was transferred to another hospital for the purpose of the synchronized chemoradiotherapy. It is well known that any glioma invades the meninges. However, we rarely encountered an intra-axial glioma fed by a meningeal blood supply. A meningeal-invaded glioma may make difficult its differentiation from meningioma. We concluded that there is necessity for close examination of the intra-axial brain tumors invaded and fed by meningeal blood supply.

[Improvement of MRA and 3D-CTA does away with the need for cerebral angiography in many cerebral aneurysm operations].

The purpose of this investigation was to study the indication of cerebral angiography in recent operations for cerebral aneurysms. Cerebral angiography has been used for diagnoses and operations for cerebral aneurysms, but, as the diagnostic procedures such as magnetic resonance angiography (MRA) and three dimensional computed tomographic angiography (3D-CTA) have made remarkable progress, cerebral angiography is not always an indispensable diagnostic tool for cerebral aneurysm operations. One hundred nineteen patients (including 40 patients with ruptured aneurysms) out of 165 patients (including 61 patients with ruptured aneurysms) were diagnosed and operated on following MRA and 3D-CTA. All of these cases of cerebral aneurysms were operated uneventfully without the need for cerebral angiography. We concluded that cerebral angiography is not needed for diagnoses and operations of small common cerebral aneurysms such as middle cerebral artery aneurysms, internal carotid artery-posterior communicating artery aneurysms and anterior communicating artery aneurysms. Cerebral angiography is necessary only in relatively large aneurysms to confirm the dynamic circulation of the cerebral blood flow before operation.

[Size and location of ruptured cerebral aneurysms diagnosed by three dimensional computed tomographic angiography].

The purpose of this study is to confirm the correct size and the location of ruptured cerebral aneurysms diagnosed and measured using three dimensional computed tomographic angiography. The size and the location were investigated in 136 ruptured cerebral aneurysms encountered in our hospital during 3 years and 10 months. As regards the location of 136 ruptured cerebral aneurysms, 40 were anterior communicating artery aneurysms, 35 were middle cerebral artery aneurysms, 33 were internal carotid artery aneurysms, 12 were distal anterior cerebral artery aneurysms and 16 were posterior circulatory aneurysms. Twenty-seven aneurysms (19.9%) were smaller than 3.0 mm, and 74 aneurysms (54.4%) were less than 5.0 mm in maximum diameter. The maximum diameter of aneurysms located on the anterior communicating artery was 4.8 mm. On the middle cerebral artery it was 6.7 mm, and on the internal carotid artery it was 7.4 mm. We concluded that the rate of small aneurysmal rupture was comparatively more frequent than is reported. The results led to the speculation that the aneurysmal rupture occurred more often in smaller size, and the rate of occurrence may be also related to the aneurysmal location.

Surgical treatment of infective endocarditis.

From February, 1975 through October, 1990, 26 patients underwent surgical treatment for infective endocarditis at Tokai University Hospital. The overall operative mortality rate was 11.5% (3/26). The three patients who died were suffering from aortic prosthetic valve endocarditis (PVE) in the active stage. Among 16 patients in the active stage, the mortality rate was 18.7% (3/16) Among 10 patients with native valve endocarditis (NVE) in the healed stage, all survived. Among the total of 21 patients with NVE, the mortality rate was zero and among those with PVE, the rate was 60% (3/5). Various species of streptococci were the most common organisms encountered, followed by Staphylococcus epidermides. The two PVE patients with S. epidermides died. Nine of the 11 NVE cases in the active stage were of the localized type. Only one case of the localized type of PVE suffered from an infected mitral bioprosthetic valve. The 6 extensive-type cases had aortic valve endocarditis (2NVE, 4PVE). Three patients with the extensive type of PVE died. We conclude that patients with infective endocarditis who develop progressive congestive heart failure, recurrent embolization, or progressive sepsis despite antimicrobial treatments, should undergo prompt valve replacement within 7 days after institution of therapy.

Surgical treatment of non-penetrating injury to the aorta.

During a 17-year period, eight cases of blunt traumatic injury to the aorta were surgically treated at our hospital. The locations of the lesions were the descending thoracic aorta in four cases, abdominal aorta in two cases, and traumatic DeBakey type IIIb dissection in two cases. Surgical repairs were carried out during the acute or subacute period in four cases and others were electively treated during the chronic period. One patient suffering from acute traumatic dissection of the aorta died of acute renal failure following acute ischemia in the lower extremities 10 days after surgery. Accordingly, the overall mortality rate was 12.5% in this series. We believe that elective operations should be carefully considered if they are possible.

Diagnosis and treatment of acute cardiac tamponade by the subxiphoid approach.

Emergency cardiac surgery has been performed on 18 cases of acute cardiac tamponade whose etiologies were as follows: 11 cases of metastatic carcinoma, four cases of idiopathic pericarditis and three with other causes. In most cases, the chief complaint was dyspnea. In many cases, the cardiac silhouette of frontal chest X-ray films showed the shape of a water-filled ice-bag placed on a table. The electrocardiogram showed a low voltage and a flat T-wave in approximately half of the patients. In cases of an echo-free space 1 cm or larger on the M-mode echocardiogram, the average amount of pericardial fluid drained was 850 ml and in those in which the space was less than 1 cm, the average drained was 557 ml. The CT values were 9-40 for patients with malignant pericardial effusion and 20-22 for cases of idiopathic pericarditis. In general, pericardiocentesis was performed in almost all the patients with acute tamponade, but if the drainage was inadequate, the subxiphoid pericardial window procedure was performed under local anesthesia. Surgical invasion in this technique was minimal and the operative results proved effective. For the operation, we resected a 2 X 2 cm pericardial segment. Since two of the patients with malignant pericardial effusion developed postoperative reaccumulation, resection of a 4 X 4 cm segment in the future has been contemplated.

First rib resection in the treatment of the thoracic outlet syndrome.

The thoracic outlet syndrome is now generally accepted as an entity that involves all neurovascular compression symptoms of the upper extremities at the tight thoracic outlet. We have treated 19 patients who developed significant symptoms of neurological, arterial or venous compression. Twelve patients presented predominantly and their angiograms demonstrated tight thoracic outlets as the underlying cause of vascular compression. Twenty three first rib resections were performed through the transaxillary approach with apparently complete relief of the syndrome. The similar etiology of the thoracic outlet syndrome and subclavian vein thrombosis was discussed on the basis of angiographic findings. We emphasize to thoracic and cardiovascular surgeons that first rib removal through the transaxillary route is an easy and safe method as a modified thoracoplasty.

[Successful excision of a left ventricular fibroma in an adult patient].

A 48-year-old woman with negative T waves in leads I, a VL and V4-6 in the ECG was examined. The cross-sectional echography and the MRI revealed that she had a tumor in the free wall of the left ventricle. Under the cardiopulmonary bypass, the intramural fibroma (6 by 6 by 4 cm) of the left ventricle was resected and the defect was repaired by sutures of the outer myocardial layers to keep the left ventricular volume. Forty eight days after the initial operation, a reoperation was performed by interrupted sutures of the whole myocardial layers. She is doing well without any troubles 14 months after the reoperation.

[Improvement of heart failure after intracardiac operation for tetralogy of Fallot by transcatheter embolization of major aortopulmonary collateral arteries].

A two-year-and-ten-month-old female with tetralogy of Fallot with major aortopulmonary collateral arteries (MAPCAs) developed a persistent heart failure after an intracardiac repair. Angiograms revealed four MAPCAs originating from the upper portion of the descending thoracic aorta and draining into the left pulmonary artery, one MAPCA from the inferior phrenic artery into bilateral pulmonary arteries, and remaining one from the left subclavian artery into left pulmonary artery. Three of these MAPCAs were occluded by transcatheter embolization by the use of the steal coil. The heart failure was improved dramatically by this treatment.

[Fontan-type operation in a 14-month-old patient with tricuspid atresia who had [I, D, D], pulmonary atresia and right pulmonary artery stenosis].

A 14-month-old male with tricuspid atresia who had [I, D, D], pulmonary atresia, right pulmonary stenosis and a Blalock-Taussig shunt successfully underwent a Fontan-type operation accomplished by making a direct right atrial-pulmonary arterial connection with a Gore-Tex roof patch. The patient had an uneventful postoperative course without development of the heart failure.

[Combined medical and surgical treatment of 74 cases of acute type III aortic dissection].

In the early period up to 1986, our treatment of acute type III dissection was anti-hypertension drug therapy as a rule, and Collins operations were performed in two cases of progressive hemothorax. Among 21 patients receiving medical therapy, five died of rupture, and three operated cases died of multiple organ ischemia, and then the hospital mortality was 40%. Since 1987, we have selected hypotensive treatment of strictly maintaining blood pressure less than 120mmHg for the completely thrombosed type of the dissected lumen, and the emergency operation of ringed intraluminal graft insertion (RIG operation) for the blood-flow type and aneurysm formation type of the dissected lumen, diagnosed by the emergency cine-angiography. As the result, among 51 cases having hypotensive therapy, one died of respiratory failure. In the 23 operated cases, in which RIG operation and/or arterial reconstruction was performed, four died of multiple organ ischemia. The hospital mortality was 8%, which was significantly improved compared with that of the early period.