Endovascular Treatment of Cerebral Aneurysm with Coils and Onyx. in-vivo experiment.

SUMMARY: We investigated endovascular treatment of cerebral aneurysm by coil and Onyx in vivo experiment in order to promote the advantages of coil embolization,. The aim of this study was to clarify the advantages and problems of coil and Onyx embolization and to evaluate its potentials for application in clinical medicine. We set experimental aneurysms made of external jugular vein to bilateral carotid arteries of 10 Beagle dogs and embolized aneurysm with coils and Onyx.Two months later, the dogs were sacrificed and took out the experimental aneurysms and examined them histologically. We have experienced Onyx migration into the vessel at the beginning of our experiment. Technical problems were as follows; Onyx was not easily visible on DSA monitor particularly in tight coil packing. Catheter tip was often stuck to the Onyx in the aneurysm. Protect balloon could not completely protect the Onyx leakage into the vessel. Microscopic examinations were as follows; The aneurysm was filled with Onyx, coils, and inflammatory reactants. The orifice of the aneurysm was packed with augmented fibrous tissue. 1. This method increased contact between the aneurysm wall and coils. 2. Onyx filled the intra-aneurismal space more tightly. 3. Coils prevented Onyx from flowing out into the vessel. 4. In Onyx, intimal layer was more rapidly formed at the neck of the aneurysm than coils only. 5. The most important problems during Onyx embolization is how to prevent Onyx migration into the vessel. We should like to propose the guideline for Onyx embolization.

Theoretical studies of the ATP hydrolysis mechanism of myosin.

The ATP hydrolysis mechanism of myosin was studied using quantum chemical (QM) and molecular dynamics calculations. The initial model compound for QM calculations was constructed on the basis of the energy-minimized structure of the myosin(S1dc)-ATP complex, which was determined by molecular mechanics calculations. The result of QM calculations suggested that the ATP hydrolysis mechanism of myosin consists of a single elementary reaction in which a water molecule nucleophilically attacked gamma-phosphorus of ATP. In addition, we performed molecular dynamics simulations of the initial and final states of the ATP hydrolysis reaction, that is, the myosin-ATP and myosin-ADP.Pi complexes. These calculations revealed roles of several amino acid residues (Lys185, Thr186, Ser237, Arg238, and Glu459) in the ATPase pocket. Lys185 maintains the conformation of beta- and gamma-phosphate groups of ATP by forming the hydrogen bonds. Thr186 and Ser237 are coordinated to a Mg(2+) ion, which interacts with the phosphates of ATP and therefore contributes to the stabilization of the ATP structure. Arg238 and Glu459, which consisted of the gate of the ATPase pocket, retain the water molecule acting on the hydrolysis at the appropriate position for initiating the hydrolysis.

[Anterior cerebral artery dissecting aneurysm associated with fibromuscular dysplasia (FMD): a case report].

We have recently encountered a rare case of anterior cerebral artery dissecting aneurysm, presenting cerebral infarction and subarachnoid hemorrhage, associated with fibromuscular dysplasia (FMD). A 50-year-old woman was admitted to our hospital with complaints of headache and hemiparesis. A right carotid angiogram obtained 9 hours after the onset revealed stenosis and slight dilatation in the A1 portion of the anterior cerebral artery. At 12 hours after the onset, the patient fell into a coma. CT scan showed diffuse subarachnoid hemorrhage. An angiogram had revealed aneurysmal dilatation and double lumen in the A1 portion, but, 34 days after the onset, angiogram showed growth of the aneurysm in the A1 portion and stenosis in the A2 and A3 portions. At 38 days after the onset, the trapping of the dilated aneurysm to prevent rerupture was performed. Pathological diagnosis was concluded to be FMD. We concluded that FMD caused stenosis as well as the formation and rupture of the dissecting aneurysm in the anterior cerebral artery.

Thrombin promotes fibroblast proliferation during the early stages of experimental radiation pneumonitis.

Huang, L., Ogushi, F., Tani, K., Ogawa, H., Kawano, T., Endo, T., Izumi, K., Ueno, J., Nishitani, H. and Sone, S. Thrombin Promotes Fibroblast Proliferation during the Early Stages of Experimental Radiation Pneumonitis. Radiat. Res. 156, 45-52 (2001). To clarify the role of thrombin in the pathogenesis of radiation-induced pneumonitis, we measured the thrombin activity and fibroblast growth-inducing activity in bronchoalveolar lavage fluid obtained from the irradiated lungs of rats at 1, 2, 4, 8 and 18 weeks after irradiation. Thrombin activity was not detected in the bronchoalveolar lavage fluid from unirradiated rats, but the bronchoalveolar lavage fluid from irradiated rats showed significantly increased thrombin activity which reached a maximum at 4 weeks after treatment. Higher fibroblast growth-inducing activity was detected in the bronchoalveolar lavage fluid from irradiated rats at 4 and 18 weeks than in fluid from unirradiated rats. Bronchoalveolar lavage fluid from irradiated rats that were pretreated with the thrombin inhibitors antithrombin III and argatroban showed significantly inhibited fibroblast growth-inducing activity and thrombin activity at 4 weeks. However, these thrombin inhibitors did not inhibit fibroblast growth-inducing activity in bronchoalveolar lavage fluid from irradiated rats at 18 weeks. Purified rat thrombin similarly induced proliferation of fibroblasts derived from irradiated and unirradiated rats. These findings suggest that thrombin may play an important role as a fibroblast growth-inducing factor during the early stages of radiation pneumonitis.

Intracranial electroencephalographic changes in deep anesthesia.

OBJECTIVE: It is well known that electroencephalograms (EEGs) show electrical silence in deep anesthesia as well as brain death. This is the first report on intracranial EEG changes in deep anesthesia. METHODS: We developed a new direct brain monitoring system capable of recording intracranial EEGs. This study included 13 patients with head trauma or cerebrovascular accident under deep anesthesia. RESULTS: The intracranial EEGs showed different patterns of wave activity in depth compared with the cortical surface. In 3 of the cases, the scalp EEG showed a flat tracing at 2.0-2.5% of isoflurane. In two of the cases, the intracranial EEGs showed electrical silence when the scalp EEG was flat. Decreasing the concentration of isoflurane to 1.5%, the intracranial EEG showed single paroxysmal appearance of 'revival' theta waves on the electrocorticogram (ECoG) or electroventriculogram (EVG). The intracranial 'revival' wave was followed by high-voltage burst-waves. In another case, at 2.0-2.5% of isoflurane, the amplitude of the waves was greatest on the EVG. CONCLUSION: There is wave activity difference in the brain depth, which the scalp EEG is unable to show. Intracranial EEGs are able to show the first signs of revival after a nearly flat tracing in deep anesthesia.

Transvaginal videopelviscopy, a new technique for assessing pelvic cysts.

We evaluated a new technique, transvaginal videopelviscopy, of inspecting the internal architecture of pelvic cysts and verifying the possibility of performing intracystic biopsy through the posterior fornix. The procedure was performed in 33 women with pelvic cysts just before operative videolaparoscopy. A 1.2-mm scope was introduced through the pouch of Douglas under transvaginal ultrasound guidance. The inner surface of adnexal cysts was visualized and attempts were made to secure biopsy tissue. Good images of the inner wall of the lesion were obtained in 26 patients (77.8%). Specimens for histopathology were obtained in 27 women (81. 8%) and were sufficient for classifying the tumor as neoplastic or nonneoplastic. On histopathologic analysis, intracystic biopsy tissue and specimens obtained by laparoscopy were concordant in 25 (92.6%) of 27 patients. No complications occurred. Transvaginal videopelviscopy is an effective procedure for assessing pelvic cysts.

Endovascular treatment for ruptured cerebral aneurysms in acute stage.

Since the introduction of endovascular embolization with Guglielmi Detachable Coils (GDC) (1-3) in April 1997, we have performed 56 endovascular treatments for ruptured cerebral aneurysms in the acute stage based on our definition of candidates for this modality. Overall outcomes are as follows. 1) Rebleeding within one year was limited to one case (2.5%). 2) Vasospasm occurrences: four cases (7.1 %) infarction and three cases (5.4%) as transient ischemia. 3) H&K Grade IV: 60% of cases resulted in improved outcomes. 4) H&K Grade II: One case of rupture during an operation. 5) Three out offive older subjects (over 80 years old) resulted in GR or MD. In this study, we reviewed endovascular embolization in acute stage in terms of candidates and technical problems.

Antitumor spectra of anthracyclines against gastric cancer tissues obtained from surgical specimens with reference to P-glycoprotein expression.

BACKGROUND AND OBJECTIVES: Although the mechanism of P-glycoprotein (Pgp)-related resistance of doxorubicin is known, it has not been clarified for other anthracycline derivatives. We have examined the chemosensitivity of gastric cancer tissues to three anthracyclines in relation to Pgp expression. METHODS: Sixty-six surgical specimens obtained from patients with gastric cancer were subjected to histoculture drug response assay using doxorubicin (DXR), epirubicin (EPI), and 4'-O-tetrahydropyranyldoxorubicin (pirarubicin; THP). The cutoff concentrations used were 15 microg/ml for DXR and EPI and 17 microg/ml for THP. RESULTS: A 50% or more inhibition index (I.I.) was regarded as sensitive, at which the correlation rates were 95.8% (23/24) and 74.2% (49/66) for DXR-EPI and DXR-THP, respectively. Twenty-six specimens were immunohistochemically stained with monoclonal antibody to Pgp, with a positive rate of 53.8% (14/26). In Pgp-positive specimens, all cases were resistant to DXR and 28.6% (4/14) of cases were sensitive to THP, while the antitumor activity of EPI was essentially identical to that of DXR. CONCLUSIONS: The expression of Pgp might affect resistance to DXR and EPI, although THP may partially impair this resistance, suggesting the clinical usefulness of THP in treatment of DXR-refractory gastric carcinoma.

[Cone beam CT utilizing a rotational digital radiographic system: early clinical experience on pulmonary and skeletal lesions].

Utilizing a rotational digital radiographic system (SF-VA 100, Hitachi) 289 digital images were obtained during a 360-degree rotation in 4.8 seconds. The images were transferred to a high-speed workstation and post-processed to create volume data in 9 minutes. The multi-planar reconstruction method reconstructed high-quality tomographic images with equal resolution in any direction. We applied this system as a cone beam CT in order to demonstrate pulmonary and spinal lesions. Early clinical experience suggested the usefulness of the method in the evaluation of diseases in organs with high radiographic contrast.

Pirarubicin might partly circumvent the P-glycoprotein-mediated drug resistance of human breast cancer tissues.

BACKGROUND: Anthracyclines are the first line antitumor agents against breast cancer, and P-glycoprotein (Pgp) is thought to be the main resistance mechanism against these agents. We have evaluated the chemosensitivity of fresh surgical specimens of breast cancer and compared them with their Pgp-expression. MATERIALS AND METHODS: The in vitro chemosensitivity of 65 surgical specimens obtained from 63 patients with advanced breast cancer was assessed by the histoculture drug response assay (HDRA) using doxorubicin (DXR), pirarubicin [(2"R)-4'-tetrahydropyranyladriamycin: THP], and epirubicin (EPIR). Breast cancer tissues were plated onto collagen gel matrix and incubated with 15 micrograms of DXR or EPIR, or 17 micrograms of THP per ml for 7 days with MTT assessed at the endpoint. The efficacy of the agents was evaluated by the inhibition index (I.I.) of the optical density detected by ELISA reader. RESULTS: When 60% or more I.I. was regarded as in vitro sensitive at each cut-off concentration of the drugs, the overall efficacy rates were 60.7%, 48.6%, and 78.6% for DXR, EPIR, and THP, respectively. Fifty-one surgical specimens were evaluated for the immunohistochemical analysis of Pgp and the correlation between the sensitivity to anthracyclines and the expression of Pgp was compared. Pgp was expressed in 23.5% (12/51) specimens and the efficacy of anthracyclines was reduced in Pgp-positive breast cancer tissues, although this reduction was low in THP with a statistically significant difference when comparing with DXR and EPIR. CONCLUSION: The present results suggest that THP might partly circumvent the mdr1/PgP-mediated drug resistance mechanism in human breast cancer tissue and would have some different antitumor spectra on breast cancer comparing with DXR and EPIR.

Radiation Complications Following Breast Conserving Therapy.

BACKGROUND: Breast conserving therapy is being established as a standard therapeutic procedure for early breast cancer in Japan. However, the indications of radiotherapy and a standardized therapeutic procedure have not been established yet. In this study, complications following radiotherapy were evaluated in patients who had previously undergone breast conserving therapy at Tokushima University Hospital. METHODS From October 1989 to March 1996, 60 women with stage I or II breast cancer underwent radiation therapy after breast conserving surgery, and all patients were followed-up for a median of 27 months. Radiation morbidity scoring of the breast and adjacent organs was performed using the toxity criteria of the Radiation Therapy Oncology Group (RTOG) and European Organization for Research andTreatment of Cancer (EORTC). RESULTS: Only 1 patient developed local recurrence, and no distant metastasisor death was observed. The cause of recurrence in 1 case was considered to be due to extended intraductal component. Although transient dermal reaction was induced by irradiation of the breast, no side effects that may cause cosmetic problems were found. No serious radiation complications were found in the lungs, ribs, heart or other adjacent organs. CONCLUSION: The adverse reactions caused by irradiation does not reduce the merit of combined use of radiation therapy in breast conserving therapy, and therefore, are not the hesitation factor in application of radiotherapy.

Acute hydrocephalus in posterior fossa injury.

This is the first known report of the use of computerized tomography (CT) scanning to examine acute hydrocephalus in posterior fossa injury. Of the 1802 patients with acute head trauma treated at Funabashi Municipal Medical Center, 53 (2.9%) had suffered injury to the posterior fossa. Of these, 12 patients (22.6%) had associated acute hydrocephalus: nine patients with acute epidural hematoma (AEH) and three with intracerebellar hematoma and contusion (IH/C). There was a significant relationship between cases of AEH with hydrocephalus and supratentorial extension, hematoma thickness of 15 mm or more, and abnormal mesencephalic cisterns. In cases of IH/C, bilateral lesions and no visible fourth ventricle were significant causes of hydrocephalus. According to these results, possible mechanisms of acute hydrocephalus in posterior fossa injury may be as follow: in cases of AEH, hematoma that extends to the supratentorial area compresses the aqueduct posteriorly and causes hydrocephalus; in cases of IH/C, hematoma and contusional lesions may directly occlude the fourth ventricle and cause acute hydrocephalus. Seven patients suffering from AEH with acute hydrocephalus underwent evacuation of their hematoma without external ventricular drainage. In these cases, CT scanning showed that the hydrocephalus improved immediately after evacuation of the hematoma. Two patients suffering from IH/C with hydrocephalus underwent a procedure for evacuation of the hematoma and external ventricular drainage. The authors do not believe that ventricular drainage is necessary in treating posterior fossa AEH. However, both evacuation of the hematoma and ventricular drainage are necessary in cases of IH/C with hydrocephalus to provide the patient with every chance for survival. There was no significant difference in mortality rates when cases of AEH with acute hydrocephalus (0%) were compared with cases of AEH without hydrocephalus (7.7%). The observed mortality rates in cases of IH/C with hydrocephalus and those without hydrocephalus were 100% and 15.4%, respectively; this is statistically significant.

Double adenomas with different pathological and hormonal features in the left adrenal gland of a patient with Cushing's syndrome.

We report a 52-year-old women with Cushing's syndrome who presented with two adenomas in the left adrenal gland. One tumour appeared dark brown and the other appeared yellow on the cut surface. The non-neoplastic adrenal demonstrated marked cortical atrophy. Upon histological examination, the brown tumour was found to be composed of both compact and clear cells. In contrast, the yellow tumour was composed of clear cells associated with pseudoglandular formation and marked degeneration. Immunohistochemical studies demonstrated positive immunostaining of cytochrome P-450 specific for 17 alpha-hydroxylation (P-450c17) in the brown but not the yellow tumour. Other steroidogenic enzymes except for dehydroepiandrosterone sulphotransferase were detected in both tumours. The biochemical activities of 21-hydroxylase, 17-hydroxylase and 11 beta-hydroxylase in the brown tumour (6.10 nmol/mg protein/4 minutes, 1.87 nmol/mg protein/2 minutes and 5.71 mumol 11-OHCS formed/g protein/10 minutes, respectively) were much greater than those in the yellow tumour. Gel-supported three-dimensional native-state primary culture of the tumours demonstrated a much higher concentration of cortisol in the culture medium for the brown tumour (5750 nmol/l on 4th day). Vimentin expression was detected in both tumours but cytokeratin expression was detected only in the yellow tumour. The Ki67 labelling index in the brown tumour was greater than that in the yellow tumour. These results indicated that these two adenomas had different biological characteristics and the brown tumour was primarily involved in over-production of cortisol in this patient. When analysing unilateral multiple adrenocortical lesions, approaches using immunohistochemical studies for steroidogenic enzymes, enzyme activity assays and cell culture can help to define the steroidogenesis of individual adrenocortical lesions.

Angiographically unrecognized microaneurysms: intraoperative observation and operative technique.

Twenty operated cases of angiographically unrecognized microaneurysm (AUM) have been analysed with special reference to intra-operative observations and clipping-technique. Among the patients with intracranial aneurysms that the authors' facility has operated upon, the incidence of asymptomatic incidental AUM that was 2 mm or smaller amounted to 3.7%. Thirteen cases of AUM were found on the middle cerebral artery; four AUMs arose from the M1 portion, four from the bifurcation, and five from the second bifurcation. Sixty percent of AUMs were recognized on the parent arteries of ruptured aneurysms. In 90% of cases the AUMs were broad based in shape and in 70% of cases exhibited a thin-walled neck and a thin-walled fundus. Intra-operative findings revealed four reasons why AUMs were not visible in the pre-operative angiograms: (1) the AUM was sandwiched between two arteries; (2) the AUM was completely hidden by a contiguous large or giant aneurysm; (3) the AUM was diagnosed by pre-operative angiogram as a bleb of the contiguous aneurysm; (4) the AUM was not visible on angiograms because the height of the AUM was extremely low. Twelve cases of AUM were successfully clipped using four different clipping techniques; (1) clipping parallel to the bifurcation in four, (2) clipping parallel to the parent artery in four, (3) pinch-clipping in two of the cases, and (4) cross clipping in two of the cases. The other eight cases were wrapped and coated. AUMs may be present during the direct operation of intracranial aneurysms and in intravascular surgery. Neurosurgeons and neuroradiologists need to explain the possible existence of AUMs to patients and their families.

Toward a virtual-labo-system for metabolic engineering: development of biochemical engineering system analyzing tool-kit (BEST-KIT).

BEST-KIT is an efficient and user-friendly "biochemical engineering system analyzing tool-kit" integrated the following key modules: 1) mathematical modeling and editing of reaction-scheme, 2) automatic derivation of differential equations, 3) numerical calculation, 4) nonlinear optimization, 5) visualization, 6) retrieve the information on reaction mechanism and kinetic parameters from data-base of metabolic pathways. The users of this simulator are assumed to be unfamiliar with computer technology and with computer programming. The integrated interface (UNIX version) is based on Xlib, XToolkit and OSF/Motif Widget.

Leydig cell tumor of the testis: analysis of testosterone production and secretion by three-dimensional histoculture.

We treated an 11-year-old boy with a testicular Leydig cell tumor. We analyzed the testosterone production of this tumor by immunolocalization of steroidogenic enzymes and in vitro three-dimensional histoculture. Spermatic venous blood from the tumor bearing testis had noticeably high concentrations of testosterone and androstenedione. The tumor had the characteristic ultrastructural features of steroid producing cells and was immunoreactive for P450scc (side chain cleavage), 3 beta HSD (hydroxysteroid dehydrogenase) and P450c17 (17 alpha-hydroxylase). Three-dimensional collagengel-supported histoculture demonstrated that the tumor tissue in the culture maintained its histologic architecture, expression of steroidogenic enzymes, and secretion of testosterone into the medium for up to 7 days in culture. Histoculture preserved in vitro testosterone production in this case of testicular Leydig cell tumor.

Ectopic gastric mucosa in the upper esophagus: prevalence and radiologic findings.

OBJECTIVE: Ectopic gastric mucosa of the upper esophagus is an asymptomatic benign lesion that may simulate a more serious lesion on radiographs. We studied the radiographic findings and prevalence of this abnormality. SUBJECTS AND METHODS: During a 1-year period, 1142 consecutive patients (817 men, 325 women) who had an upper gastrointestinal series as part of an annual health checkup were prospectively studied. Routine examination of the esophagus consisted only of fluoroscopy. Radiographs were obtained if any localized irregularities were found in the upper esophageal wall at fluoroscopy. The findings were subsequently confirmed by endoscopy and biopsy. RESULTS: Ectopic gastric mucosa in the upper esophagus was seen in 27 (25 men, two women) of the 1142 patients. Forty-three localized ectopic gastric mucosal patches varying in size from 5 mm to 32 mm were detected at the level of the thoracic inlet in the 27 patients. The most common radiographic finding was a pair of small indentations on the wall of the esophagus (18 patches). Other findings included a rimlike shadow (three patches), a pair of somewhat large indentations with a shallowly depressed area between them (two patches), one indentation (five patches), a small flat elevation (one patch), a serrated irregular outline (five radiologic lesions consisted of 11 patches), other various irregular outlines (two patches), and a polypoid area (one patch). CONCLUSION: Prevalence of radiographic evidence of ectopic gastric mucosa in the upper esophagus is 2.4%. The lesion was found more commonly in men (3.1%) than in women (0.6%). Radiographic findings include a pair of indentations along the lateral margin of the esophagus and a rimlike shadow on the anterior or posterior wall. Recognition of the characteristic radiographic features of this abnormality makes endoscopy and follow-up unnecessary.

[Three-dimensional longitudinal dissection view of hollow viscus].

To visualize the pathologies of hollow viscus and their extension three-dimensionally, volume data of the larynx, trachea, stomach, rectum, and urinary bladder were obtained using helical CT with moderately thin slices. Longitudinal cut sections were made as in a simulated surgical cut, and the interior morphology was displayed along with the pathology. A cylindrical projection profile was made by making a longitudinal incision on one wall and pulling apart the flaps to reveal the interior, providing better visual perception. The detailed outline from the 3D profile and the cylindrical projection views constituted an added advantage over the existing procedures.

Ectopic gastric mucosa in the upper esophagus: detection and radiographic findings.

PURPOSE: To detect and characterize the appearance of islands of ectopic gastric mucosa in the upper esophagus at routine examination of the upper gastrointestinal (GI) tract. MATERIALS AND METHODS: Well-distended upper esophagus was documented with spot radiographs obtained with routine double-contrast examination performed after administration of high-density barium in nine patients. Detected lesions were confirmed by means of endoscopy and biopsy. RESULTS: Twelve lesions were detected. Radiographic findings were characterized by either a discrete, shallow depression surrounded by a subtle, rimlike elevation on double-contrast images or by a pair of small indentations on the same wall on full-column, single-contrast images at the level of the thoracic inlet. Endoscopic examination revealed well-circumscribed areas of reddish mucosa located 15-26 cm from the incisors. CONCLUSION: Ectopic gastric mucosa in the upper esophagus is easily demonstrated at routine examination of the upper GI tract. Diagnosis can be based on location and characteristic radiographic appearance.