Clinicopathologic features of small cell glioblastomas.

Small cell glioblastoma (SCGBM) is a variant of glioblastomas characterized by a predominant population of small and monomorphic glial cells. The aim of the present study was to investigate clinical, neuroimaging, pathologic, and genetic features of SCGBM. The clinicopathologic and genetic features were evaluated in 14 patients with SCGBM. All cases were divided into multifocal and solitary type by MRI, and extent of microvascular proliferation, intratumoral necrosis, and perivascular lymphocytic accumulation were investigated. IDH1 mutations by immunohistochemistry (IDH1 R132H) and 1p 19q codeletion by fluorescence in situ hybridization were detected. Patients ranged from 23 to 92 years of age (median: 71 years), with three females and eleven males. The overall survival time of the patients ranged from 7 to 23 months (mean: 11 months). Nine patients (64%) were the multifocal type. Pathologic study revealed that the microvascular proliferation, necrosis, and lymphocytic infiltration were limited in SCGBM. Immunohistochemically, tumor cells were negative for IDH1 R132H in all patients. FISH analysis demonstrated that no SCGBM had 1p/19q codeletion in informative patients. Our investigation suggested that an elderly onset and multifocal lesions were characteristics of SCGBM associated with degradation of the immune response, infiltrative feature of tumor cells, and an unfavorable prognosis.

Pancreaticoduodenal artery aneurysm involving papilla of vater successfully treated with endovascular approach despite intraoperative rupture.

An 81-year-old woman presented with dizziness and nasal bleeding. Gastrointestinal fiberscopy (GIF) showed a pulsatile aneurysm in the duodenum, and that the orifice of the papilla of Vater was involved. Three-dimensional computed tomography imaging showed an unruptured aneurysm in the pancreatic duodenal arcade. The patient underwent an emergent endovascular embolization of the donor arteries using coils and gelatin sponge particles. She was discharged without any complications. This case was extremely rare because of the anatomic location of the unruptured pancreaticoduodenal artery aneurysm and the fact that it involved the papilla of Vater, was detected with GIF, and was successfully treated endovascularly.

[The importance of p53 and ras mutation as predictive markers for adjuvant chemotherapy in non-small-cell lung cancer].

OBJECTIVE: A previous large, randomized, control trial(JBR.10)revealed that adjuvant chemotherapy with cisplatin(CDDP) and vinorelbine(VNR)was effective for non-small-cell lung cancer(NSCLC). It was also reported that adjuvant chemotherapy was not effective for p53-negative or K-ras mutation-positive patients. To clarify whether p53 and ras statuses are true predictive markers for chemotherapy with cisplatin, chemosensitivity was examined using an in vitro drug sensitivity assay. MATERIALS AND METHODS: Surgically resected fresh tumor specimens obtained from 27 patients at our institute with NSCLC were used for this study. Histoculture Drug Response Assay(HDRA)was applied to evaluate the chemosensitivity of CDDP and VNR in these specimens. p53 expression was evaluated by immunohistochemistry, and K-ras mutation by direct sequencing. RESULT: Four of the 27 patients were positive for K-ras mutation. The inhibition rate of CDDP was 54±5% for K-ras mutation positive-patients, and 50±13% for negative-patients. There was no significant difference between these two groups. p53 overexpression was observed in 14 patients, but not in 13 patients. The inhibition rate of CDDP was 50±12% for p53- overexpressed patients, and 50±12% for patients not overexpressed. The inhibition rate of VNR was 36±17% for p53- overexpressed patients, and 33±14%for patients not overexpressed. As for 8 adenocarcinoma patients, the inhibition rate of CDDP of p53-overexpressed patients(59±8%)was significantly(p=0. 018)higher than that of patients not overexpressed (45±9%). p53 overexpression may be a predictive marker for chemotherapy using CDDP in lung adenocarcinoma. CONCLUSION: p53 overexpression may be a possible predictive marker for adjuvant chemotherapy using CDDP in NSCLC.

Pathophysiologic evaluation of MELAS strokes by serially quantified MRS and CASL perfusion images.

PURPOSE: To clarify the roles of serial MR spectroscopy (MRS) and continuous arterial spin labeling (CASL) perfusion images for evaluating cerebral lesions in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). MATERIALS AND METHODS: Two cases of MELAS followed up serially using MRS and CASL images in addition to routine MR imaging were enrolled. RESULTS: Newly appeared lesions assessed by MRS revealed increased lactate doublets which correlated well with CSF lactate level, and these showed a decreasing trend after treatment, although conventional T2 weighted images revealed hyper-intensity in both phases. Spectra from normally appearing white matter depicted slight lactate peaks during clinical exacerbation periods with marked elevation of CSF lactate and showed a decreasing NAA concentration during the prolonged course. In CASL images, acute lesions of the disease were clearly visible as hyper-perfusion foci, and chronic lesions were demonstrated as hypo- or iso-perfusion regions. CONCLUSION: The detection of lactate peaks in the MR spectrum from normally appearing white matter may be considered as systemic lactic acidosis or an exacerbation of MELAS, and active lesions can be distinguished from chronic inactive lesions by the increase of lactate peaks in MRS or the state of hyper-perfusion in CASL images.

[Histoculture drug response assay guided adjuvant chemotherapy in patients with ERCC1-positive non-small cell lung cancer].

PURPOSE: A previous large randomized control study(IALT)revealed that cisplatin(CDDP)-based adjuvant chemotherapy was not effective for patients with ERCC1-positive non-small cell lung cancer(NSCLC). We evaluated the chemosensitivity of surgically resected specimens of NSCLC using in vitro chemosensitivity test and searched for promising adjuvant chemotherapy protocols in the ERCC1-positive subgroup of NSCLC. PATIENTS AND METHODS: Chemosensitivities of 10 anticancer agents including cisplatin were evaluated by histoculture drug response assay(HDRA) using 28 surgically resected NSCLC specimens. ERCC 1 status was evaluated by immunohistochemistry. RESULTS: ERCC1 was positive in 22 and negative in 6 specimens. All ERCC1-negative specimens were sensitive for CDDP in HDRA, and all CDDP-resistant specimens in HDRA showed positive ERCC1 staining. ERCC1 status was significantly correlated with CDDP sensitivity(p=0.01). HDRA showed average 3(0-6)sensitive anticancer agents except for CDDP even in ERCC1-positive specimens. CONCLUSION: HDRA may provide effective non-platinum adjuvant chemotherapy protocols for patients with ERCC1-positive, i.e. CDDP resistant, NSCLC.

Histoculture drug response assay for gefitinib in non-small-cell lung cancer.

OBJECTIVE: There are many predictive factors for gefitinib sensitivity, including epidermal growth factor receptor (EGFR) gene mutation, EGFR copy number, and k-ras mutation. To investigate all of them is too expensive. We evaluated the chemosensitivity for gefitinib in non-small-cell lung cancer (NSCLC) using a histoculture drug response assay (HDRA). METHODS: Surgically resected fresh tumor specimens from 22 patients with NSCLC were used. There were 13 male and 9 female patients, ranging in age from 49 to 84 (average 70) years old. Sixteen patients (73%) were smokers. Sixteen adenocarcinomas, four squamous cell carcinomas, and two other histological types were included. Small pieces of viable cancer tissue were placed on the collagen gel and then cultured for 7 days in the presence of gefitinib. RESULTS: The HDRA was successful in all specimens. A dose-response relation was observed between inhibition rates and gefitinib concentration (p = 0.016). The inhibition rate at 20 microg/ml (IR(20)) in adenocarcinoma without smoking (39.2% +/- 35.1%, n = 6) was higher than that with smoking (2.2% +/- 5.0%, n = 10, P = 0.001) and that of nonadenocarcinoma (16.9% +/- 23.6%, n = 6, P = 0.09). Gene mutation analysis was performed in two of three adenocarcinomas without smoking, which showed especially high IR(20) values, and sensitizing mutations were observed in these specimens. A cutoff inhibition rate of approximately 40%-50% appeared to be suitable for a concentration of 20 microg/ml. CONCLUSION: HDRA appears to be applicable for evaluating sensitivity to gefitinib in NSCLC. It provides a convenient method for predicting the response to gefitinib in patients with NSCLC whose fresh tumor specimens are available.

[Safety and efficacy of weekly paclitaxel followed by FEC100 as primary systemic therapy for breast cancer].

The efficacy and safety of primary systemic therapy with weekly paclitaxel (wPTX; 80 mg/m2) followed by FEC100 (cyclophosphamide 500 mg/m2, epirubicin 100 mg/m2, 5-fluorouracil 500 mg/m2)were investigated in 52 patients with stage I-III A locally advanced breast cancer. Clinical response was complete in 30 patients (58%) and partial in 19 patients (37%). Pathological complete response was found in 23 primary lesions and 17 sentinel and/or sampling lymph nodes. No patients developed progressive disease and major adverse events except for febrile neutropenia in ten patients. These results showed that primary systemic therapy with wPTX followed by FEC100 is a feasible therapeutic option for breast cancer.

Assessment of cervical venous blood flow and the craniocervical venus valve using ultrasound sonography.

Severe congestion with petechiae and/or small hemorrhages over a wide area consisting of the subcutaneous and mucous level of the head and neck is observed in most cases of strangulation and positional asphyxial death. Congestion present above the strangulation mark is accepted as a vital reaction. Although the congestion results from a disturbance of cervical venous flow, only a few reports concerning a relationship between venous flow and posture were found in the literature. We assessed the physiological situation of cervical venous return and movement of the craniocervical venous valve for many types of valve with respect to posture using color-duplex ultrasound sonography (US). We measured the Doppler wave of cervical veins consisting of internal jugular vein (IJV), external jugular vein (EJV) and vertebral vein (VV) and the motion of IJV valves in three positions on a seat which could be manually moved through +90 degrees to -90. The diameter of IJVs and EJVs were thicker in a head-down position, moderate in a supine position and flat in a sitting position. The diameter of VVs was thick in a sitting position, moderate in supine position and unclear in an upside-down position because of difficulty in scanning owing to very slow velocity and deep lying position. The velocities were high in a sitting position, but very slow and intermittent in an upside-down position. The EJV which is markedly congested in some cardiac tamponade cases and drains mainly the facial superficial region is very important in legal medicine but has not often observed in previous reports. We confirmed that cervical venous return (IJV, EJV, VV) changes its route according to the posture. The motion of IJV valves was very complicated and varied in three positions, even after the Doppler wave and the motion of valve became stable. Asphyxia and strangulation should be studied taking the complex venous structure into consideration. We could not find any consistent explanation for venous valve motion and further studies on the valves are necessary to understand the venous reflux in some diseases in legal medicine.

In vitro evaluation of dose-response curve for paclitaxel in breast cancer.

BACKGROUND: The dose-response curve for anticancer agents cannot be evaluated by studying patients directly. To investigate individual differences in the dose-response curve for paclitaxel in breast cancer, we utilized the histoculture drug response assay (HDRA) technique. MATERIALS AND METHODS: Twenty specimens obtained from breast cancer patients who underwent surgical resection were used in this study. The inhibition rates of paclitaxel at several concentrations were measured and fitted to a sigmoid dose-response curve, using non-linear least squares analysis with the fitting equation y=A(1-1/(1+exp(B(x-log(C))))), where A denotes maximal response; B, slope factor; and C, ED50. RESULTS: A dose-response curve was obtained in all tumors. The mean value (+/-SD) of maximum response, slope factor, and ED50 were 90.2+/-5.5%, 9.4+/-4.3, and 36.8+/-17.2 microg/ml, respectively. The slope factor was higher in nuclear grade 3 tumors compared with nuclear grade 1 and 2 tumors. CONCLUSION: An individual dose-response curve for paclitaxel in breast cancer can be obtained using the HDRA technique. Nuclear grade 3 tumors appeared to have more uniform chemosensitivity to paclitaxel compared with nuclear grade 1 and 2 tumors.

Actors and actions: The role of agent behavior in infants' attribution of goals.

Twelve-month-old infants attribute goals to both familiar, human agents and unfamiliar, non-human agents. They also attribute goal-directedness to both familiar actions and unfamiliar ones. Four conditions examined information 12-month-olds use to determine which actions of an unfamiliar agent are goal-directed. Infants who witnessed the agent interact contingently with a human confederate encoded the agent's actions as goal-directed; infants who saw a human confederate model an intentional stance toward the agent without the agent's participation, did not. Infants who witnessed the agent align itself with one of two potential targets before approaching that target encoded the approach as goal-directed; infants who did not observe the self-alignment did not encode the approach as goal-directed. A possible common underpinning of these two seemingly independent sources of information is discussed.

Experimental infection of calves with Pasteurella multocida Serovar A: 3 isolated in Japan.

Pasteurella multocida, serovar A: 3, selected by pathogenicity in mice from among 10 strains isolated from pneumonic lesions of calves, was adjusted to 10(7), 10(8) and 10(10) colony-forming units (CFU), and inoculated intratracheally into four calves. All calves showed pyrexia and had lungs with congestion and hepatization. Inoculation with 10(10) CFU of bacteria produced respiratory symptoms and abscesses in lungs. This information will aid elucidation of the pathogenicity of P. multocida and the development of vaccines.

[Nicorandil reduces incidence and severity of pain on propofol injection].

BACKGROUND: Propofol is commonly used for induction and maintenance of anesthesia, but the pain during injection of propofol remains a clinical problem. We studied whether nicorandil prevents the pain on propofol injection. METHODS: The study was conducted in 120 adult patients scheduled for elective surgery. The patients were assigned to two groups; Group C (n = 60) received bolus injection of propofol alone; Group N (n = 60) received bolus injection of 2 mg of nicrorandil 3 minutes before propofol injection, and followed by continuous nicorandil infusion at a rate of 6 mg.h-1. The pain on injection was assessed as, none, mild, moderate, or severe at 15-second intervals. RESULTS: The incidence of propofol-induced pain was significantly higher in Group C (77%) than in Group N (30%) (P < 0.05). The severity of pain was significantly higher in Group C than in Group N (P < 0.05). CONCLUSIONS: Nicorandil reduces the incidence and severity of pain on propofol injection.

Magnetic resonance axillography for preoperative diagnosis of the axillopectoral muscle (Langer's axillary arch): a case report.

The axillary arch of Langer is the most common muscular variation in the axilla. Recognition of anatomic variations is important for surgeons to perform safe axillary surgery. We describe a case of a woman with breast cancer, in whom sentinel lymph node biopsy was successfully performed and the presence of this anomaly preoperatively diagnosed by magnetic resonance axillography.

Growth hormone-secreting pituitary adenoma associated with primary moyamoya disease--case report.

A 40-year-old female presented with growth hormone (GH)-secreting pituitary adenoma associated with primary moyamoya disease manifesting as amenorrhea, acromegaly, and transient ischemic attack. Magnetic resonance (MR) imaging revealed a tumor mass extending from the sella turcica to the suprasellar cistern, and MR angiography demonstrated stenoses in the bilateral internal carotid arteries with basal moyamoya vessels. Her blood GH and insulin-like growth factor (IGF-1) levels were elevated to 78.94 and 923.0 ng/ml, respectively. The patient underwent removal of the pituitary adenoma because her ischemic symptoms disappeared after oral aspirin medication. Subtotal resection resulted in persistence of the high blood GH and IGF-1 levels. Postoperative MR angiography showed progression of the stenoses in the bilateral internal carotid arteries. Excess systemic GH and IGF-1 may participate in the progression of vascular disease and so could have caused the deterioration of the moyamoya disease.

Anastrozole-induced remission of diaphragmatic paralysis from metastatic breast cancer treated with multiple prior therapies.

We describe a woman with metastatic breast cancer treated with multiple rounds of prior cytotoxic and endocrine therapies, who presented with ipsilateral diaphragmatic paralysis. The use of anastrozole, a highly selective nonsteroidal aromatase inhibitor (1 mg daily), successfully induced remission of metastatic tumors in our patient, who is partially recovering from diaphragmatic paralysis.

Field study of bovine coronavirus vaccine enriched with hemagglutinating antigen for winter dysentery in dairy cows.

A field study of a vaccine; prepared by solubilizing cells infected with bovine coronavirus, Triton X-100, and mixing with an oil adjuvant, was performed at 9 farms over 4 prefectures. The cattle tested were Holstein dairy cows aged 2 to 10 years. A vaccination group consisted of 157 animals (including 132 pregnant cows) and a non-vaccinated control group consisted of 50 animals. The cows received 2 intramuscular injections of vaccine (2 mL) at 3-week intervals. Vaccinated cows did not develop abnormalities, such as a decrease in milk production volume, and all pregnant animals calved normally. The geometric mean of the hemagglutination inhibition antibody titer was 34.2 before vaccination in test cows. The titer had increased to 105.6, 3 weeks after the 1st injection and peaked at 755.6, 1 month after the 2nd injection. A high antibody titer persisted at 396.0; 241.0; and 201.5, at 3, 6, and 9 months after the 2nd injection, respectively. This confirms the safety and high antibody-response induced by this prototype vaccine. Therefore, this vaccine may be useful for the prevention of winter dysentery caused by bovine coronavirus infection.

Two-hit inactivation of FHIT by loss of heterozygosity and hypermethylation in breast cancer.

PURPOSE: The FHIT gene, which spans the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene in breast carcinomas. In this study, we would like to delineate more precisely its role in breast tumorigenesis. EXPERIMENTAL DESIGN: To confirm the tumorigenic role of FHIT, 46 sporadic invasive ductal carcinomas of the breast were tested for the "two hits" required to inactivate this gene. Microsatellite loss of heterozygosity (LOH) was considered as the first hit. To examine the possibility that hypermethylation serves as the second hit for FHIT inactivation, methylation of 5'-CpG islands of FHIT was analyzed by methylation-specific PCR. RESULTS: LOH was detected in 8 of 40 informative tumors, and hypermethylation was observed in 22 of 46 (48%) cases. Aberrant FHIT protein expression was found in 31 of 46 (67%) cases examined. All seven tumors showing both LOH and hypermethylation showed complete loss of Fhit protein expression. In addition, a significant positive association was found between the existence of LOH and 5'-CpG island hypermethylation (P = 0.04), which was consistent with the two-hit model. CONCLUSIONS: To our knowledge, this study provides the first evidence that biallelic inactivation of FHIT by LOH and hypermethylation leads to the complete inactivation of FHIT gene in patients with breast cancer. Silencing of the FHIT gene by promoter hypermethylation occurs in primary breast carcinomas, especially those with LOH. These findings support a role for this tumor suppressor gene in sporadic breast tumorigenesis.

Electrocardiographic score as a predictor of mortality after subarachnoid hemorrhage.

Electrocardiographic (ECG) changes are often associated with subarachnoid hemorrhage (SAH), but it is not well known whether these have prognostic value. The present study retrospectively investigated 122 consecutive patients with SAH caused by ruptured aneurysms. The patients were classified based on the in-hospital outcome into 80 survivors and 42 nonsurvivors. In nonsurvivors, abnormalities often observed on the 12-lead ECG on arrival at hospital were abnormal Q wave, ST depression, and T wave inversion. The ECG score was defined as the total number of leads that had any of these 3 ECG abnormalities. Univariate analysis revealed a strong correlation of in-hospital death with the ECG score, the neurological status estimated by the grading of Hunt and Kosnik, age, and QTc interval. In age- and sex-adjusted multiple logistic regression analysis, the ECG score was the most powerful risk stratifier (ECG score > or = 6 vs ECG score < 6; p=0.0026, odds ratio 14.39, 95% confidence interval 2.54-81.71). The ECG score, a new and simple method of semi-quantification, was a powerful risk predictor in the present patients with SAH.

Experimental infection of cats with Chlamydophila felis.

Cats experimentally infected with a British isolate of Chlamydophila felis (C. felis), B166 strain, by droplet into the eye and nose developed conjunctivitis, mild rhinitis and fever. The chlamydophila were first isolated from conjunctiva, nictitating membrane and then from lung, tonsil, liver, spleen, kidney, nasal and vaginal swabs and blood. These results indicate that C. felis B166 strain first infected and replicated in the conjunctiva and nictitating membrane in cats with symptoms which were mostly limited to conjunctivitis, and then pervaded the whole body by bacteremia.