Measurement of fractional anisotropy using diffusion tensor MRI in supratentorial astrocytic tumors

In vivo, water diffusion displays directionality due to presence of complex microstructural barriers in tissue. The extent of directionality of water diffusion can be expressed as a fractional anisotropy (FA) value, using diffusion tensor MR imaging (DTI). The aim of this study was to determine whether FA values indicate microstructures in astrocytic tumors. We performed DTI in 31 patients with astrocytic tumor, and measured the FA values of tumor and normal brain regions prior to CT-guided stereotactic biopsy. After biopsy, FA values were compared to assess the cellularity and vascularity of tumor tissue. Although mean FA values trended to differ among histological types, all mean tumor FA values were lower than those of normal brain regions. Positive correlation was observed between FA values and both cellularity (r = 0.65, p < 0.05) and vascularity (r = 0.45, p < 0.05). We had hypothesized that the FA value of an astrocytic tumor would be determined by a balance between factors increasing the directionality of water diffusion, such as high cellularity and/or vascularity, and factors decreasing the directionality of water diffusion, such as fiber destruction. However, our results suggest that the FA values of glioblastoma, anaplastic astrocytoma, diffuse astrocytoma and pilocytic astrocytoma are largely affected by cellularity and/or vascularity, whereas that of gliomatosis cerebri are largely affected by the preservation of nerve fibers. Measurement of FA value using DTI will allow prediction of histological characteristics such as cellularity, vascularity and/or fiber structure in astrocytic tumors.     

A phase II study of radiotherapy after hyperbaric oxygenation combined with interferon-beta and nimustine hydrochloride to treat supratentorial malignant gliomas

Hypoxic cells play a key role in the radioresistance of malignant glioma. Interferon-beta, ACNU as nimustine hydrochloride and radiotherapy (IAR) is a common therapy for malignant glioma in Japan. Since hyperbaric oxygenation (HBO) increases oxygen pressure in glioma tissue, we applied a modified IAR therapy, radiotherapy after HBO combined with interferon-beta and ACNU (HBO/IAR therapy), for supratentorial malignant gliomas. Daily radiation therapy was completed within 15min after HBO. We assessed HBO/IAR with respect to toxicity, response rates and the time of tumor progression (TTP). We also examined the incidence of responses by some prognostic factors before HBO/IAR, namely, age, Karnofsky performance scale (KPS), histological type, tumor size, tumor site and operation type. Of 39 patients who participated in this study, 35 underwent a complete schedule of HBO/IAR therapy in which toxicity was permissible. Thirty patients (76.9%) either maintained or increased KPS during HBO/IAR with a mean duration of 68±14 days. The response rates (CR+PR%) for glioblastoma, anaplastic astrocytoma and overall were 50%, 30% and 43%, respectively. The incidence of therapeutic responses among all prognostic factors before HBO/IAR did not significantly differ. Median TTP for patients with glioblastoma, patients with anaplastic astrocytoma, and overall were 38, 56 and 43 weeks, respectively. The present study suggested that HBO/IAR therapy could be applied to especially patients with poor prognostic factors, because of its short treatment period, its permissible toxicity and identical response to patients with good prognostic factors.     

17 Beta-estradiol increases nitric oxide and prostaglandin I2 production by cultured human uterine arteries only in histologically normal specimens

These experiments were designed to investigate whether 17beta-estradiol (E2) modulates the endothelial function of perimenopausal human uterine arteries. After the artery specimen was cultured in the presence or absence of E2 at a physiologic concentration of 200 pg/ml, changes in isometric tension and cyclic nucleotide production were determined. Degree of intimal hyperplasia was assessed histologically and expressed as intima-to-media ratio. Acetylcholine produced an endothelium-dependent relaxation in six specimens (group I) of 12, which was inhibited by NG-nitro-L-arginine or indomethacin. However, the agonist failed to produce a definite relaxation in the remaining 6 (group II). The endothelium-dependent relaxation was significantly augmented after incubating with E2 only in group I specimens. Cyclic nucleotide production was significantly increased after E2 incubation only in group I specimens, whereas it was inhibited by NG-nitro-L-arginine or indomethacin. Histologic study revealed that the six specimens of group I had normal intima (intima-to-media ratio = 19.1+/-1.8%) and the remaining six of group II had intimal hyperplasia (intima-to-media ratio = 53.6+/-5.3%). Increased production of cyclic nucleotides occurred in uterine arteries with normal intima but not in arteries with intimal hyperplasia derived from perimenopausal women.     

Treatment strategy for cervical node metastasis from squamous cell carcinoma of the oropharynx

The purpose of this study is to ascertain the role of neck surgery and radiation therapy for cervical lymph node metastasis in oropharyngeal cancer patients. We reviewed 217 previously untreated patients with squamous cell carcinoma of the oropharynx who were treated at the Cancer Institute Hospital in Tokyo between 1971 and 1995. The N stage distribution was; N0: 83(38.2%), N1: 42(19.4%), N2a: 23(10.6%), N2b: 27(12.4%), N2c: 33(15.2%), and N3: 9(4.2%). A predominance of cervical node metastases in level II and III was revealed and there were no skip metastases outside of level II and III. The control rate of cervical metastasis for each N stage was; N0: 96.9%, N1: 90.0%, N2a: 76.5%, N2b: 62.5%, N2c: 50.0%, and N3: 0%. Definitive irradiation provided sufficient treatment for small nodes, when the primary tumor growth was well controlled by radiation therapy. Neck dissection was necessary for more advanced neck metastases. Selective limited neck dissection (level II and III) is recommended for N0 and N1 patients, and modified or classical RND is considered to be better for most cases with N2 and N3.     

Hepatocyte growth factor and invasion-stimulatory activity are induced in pleural fluid by surgery in lung cancer patients

Hepatocyte growth factor (HGF) is a stromal cell-derived cytokine that can stimulate matrix invasion by carcinoma cells. We analysed the concentrations of HGF and invasion-stimulatory activity in pleural fluid after lung surgery. The concentration of HGF in pleural fluids was measured by enzyme-linked immunosorbent assay in seven patients who underwent pulmonary resection for primary or metastatic lung cancer. The effect of the pleural fluid on cancer cell invasion across reconstituted basement membrane (Matrigel) was assessed with a Boyden chamber assay using a lung adenocarcinoma cell line, A549. HGF levels in the pleural fluid after lung surgery ranged from 6.0 to 23.0 ng ml(-1) (average: 10.2 +/- 4.3 ng ml(-1)). The matrix invasion of lung carcinoma cells in the presence of the pleural fluid was significantly higher than that in the presence of culture medium alone or sera from normal subjects (P < 0.01). The invasion-stimulatory activity of the pleural fluid was strongly inhibited by HGF-neutralizing antibody. Positive correlation was found between the HGF level and invasion-stimulatory activity in the pleural fluids and normal sera (P = 0.0073). This is the first report demonstrating that the lung surgery induces a considerable amount of HGF, which is closely correlated with the invasion-stimulatory activity of the pleural fluid.     

EFFICACY OF AZATHIOPRINE IN MILD OR MODERATE RELAPSE IN CROHN'S DISEASE: CLINICAL AND ENDOSCOPIC EVALUATION

Aim: The present study was aimed at evaluating the efficacy of azathioprine (AZA) in patients with active and relapsing Crohn's disease (CD) and the usefulness of endoscopy in this evaluation. Methods: The 53 patients with active CD treated with AZA at our hospital were subjected to the following retrospective analysis: (i) evaluation of the clinical efficacy of AZA through comparison of the Crohn's disease activity index (CDAI); (ii) analysis of the relationship of the clinical efficacy to the difference in the mean corpuscular volume (MCV); (iii) evaluation of mucosal healing through analysis of the scores of the endoscopic findings in 16 patients; and (iv) analysis of the relapse rate. Results: (i) Among the 53 patients, treatment was rated as having induced complete remission in 22.6%, as being effective in 41.5%, and as being ineffective in 13.3% of patients. The treatment was discontinued in 22.6% of patients. (ii) The post‐treatment MCV was significantly increased after treatment. (iii) When the ulcer score estimated after treatment was compared with that before the start of treatment, a significant improvement of the score was noted. (iv) When the non‐relapse rate after AZA therapy was calculated in the 41 patients followed up for 12 months, it was 84.8%. Conclusion: AZA was shown to cause endoscopic mucosal healing as well as clinical efficacy. In the present study, it was inferred that the efficacy of AZA therapy in CD patients is manifested clinically first and that mucosal healing is an effect that occurs later.     

Purification and biochemical characterization of streptothricin acetyltransferase coded by the cloned streptothricin-resistance gene of Streptomyces lavendulae

Streptothricin acetyltransferase was purified from Streptomyces lividans harboring a plasmid which carried the streptothricin-resistance gene cloned from a streptothricin-producing strain, Streptomyces lavendulae No. 1080. Some properties of the enzyme were determined and the reaction product was identified to be N beta-acetylstreptothricin by NMR spectroscopy.     

Principle of a noninvasive method of measuring Max(dP/dt) of the left ventricle: Theory and experiments

In early systole, before the effects of reflected waves from the periphery become significant, the following equation applies: PA - PO = rho cu (1) where PA and PO are the instantaneous and end-diastolic pressures in the ascending aorta, rho the density of blood, c the velocity of the pulse wave in the aorta, and u the velocity of blood. Differentiation of Eq. (1) with respect to time t yields: dPA/dt = rho c(du/dt) (2) If there is no aortic stenosis, and if the pressure gradient due to the inertia of the blood during acceleration is neglected, the left ventricular pressure P is nearly equal to PA during the ejection period. Since both dP/dt and dPA/dt take their maximum values at times close to the time of aortic valve opening, the following equation applies: Max(dP/dt) not equal to Max(dPA/dt) (3) where Max signifies the maximum value of a derivative. Equation (2) reduces to: Max(dPA/dt) = rho c Max(du/dt) (4) Substitution of Eq. (4) into Eq. (3) yields: Max(dP/dt) not equal to rho c Max(du/dt) (5) Experiments were performed on seven dogs. Max(dP/dt), Max(du/dt), and c were measured during volume loading, pressure loading and unloading, and before and after administration of positive and negative inotropic agents. There was a good linear correlation (Y = 1.01X-2, r = 0.97) between Max(dP/dt) and rho c Max(du/dt). Therefore, Eq. (5) is a universal equation which holds, irrespective of the dogs and interventions employed to change the hemodynamic state.(ABSTRACT TRUNCATED AT 250 WORDS)     

The value of two-dimensional echocardiography in detecting malignant tumors in the heart

Six unusual cases of tumor involvement of the heart and pericardium, diagnosed antemortem by two-dimensional echocardiography (2DE), are described. The tumors consisted one each of sacral chordoma, mediastinal seminoma, leiomyosarcoma of the uterus, osteosarcoma, invasive thymoma, and lung cancer. The current study again recognizes the concept that any type of malignant tumor has a possibility of involving the heart. If cardiac involvement is suspected, 2DE examination should be performed in patients with any kind of malignant tumor. The information obtained not only provides guidance for therapeutic maneuvers, but also is beneficial for follow-up observation of the patients and assessment of the therapy.