Attenuation of the pressor response to laryngoscopy and tracheal intubation with intravenous verapamil

This study was undertaken in surgical patients in order to evaluate the effects of intravenous verapamil on the circulatory responses to laryngoscopy and tracheal intubation. Laryngoscopy for tracheal intubation was initiated 1 min after thiamylal 5 mg.kg-1 and succinylcholine 1.5 mg.kg-1 in the control group (n = 21). The verapamil group (n = 23) received intravenous verapamil 0.1 mg.kg-1 immediately after thiamylal-succinylcholine administration. The resulting changes in mean arterial pressure (MAP) and heart rate (HR) were continuously measured. Compared with the control group, MAP increased less in response to laryngoscopy and tracheal intubation (56 +/- 13% versus 25 +/- 15% above baselines, P less than 0.01) and returned toward baseline sooner in patients receiving verapamil. For hypertensive patients, MAP increases from baseline after intubation were 18 +/- 9% in the verapamil group, and 53 +/- 14% in the control group, respectively (P less than 0.001). Increases in HR response to laryngoscopy for intubation were comparable in both groups. We conclude that intravenous verapamil is effective in reducing pressor responses during endotracheal intubation, especially in hypertensive patients.     

Carcinoembryonic Antigen (CEA) Levels in Pleural Effusions and Sera of Lung Cancer Patients

For determining the value of carcinoembryonic antigen (CEA)levels in diagnosis of malignant tumors of the lung, the CEAlevels in 187 specimens of pleural fluid and sera obtained simultaneouslyfrom patients with pleural fluid were measured. In all 70 patientswith benign diseases, the CEA levels in the effusions were lessthan the cut-off value of 5 ng/ml (mean±SD: 1.44±1.01ng/ml). In contrast, in 88 of 117 patients (75.2%) with malignantdiseases, the CEA levels in the effusions were over 5 ng/ml(25.3±24.5 ng/ml) and in 58 of the 117 patients (50.4%),the CEA levels in the serum were values of 5 ng/ml or more (11.9±18.4ng/ml). There was a significant correlation between the CEAlevels in the effusions and in the sera. The CEA levels in effusionsin patients with malignant lung tumors were usually much higherthan those in their sera. The incidence of CEA levels of 5 ng/mlor more in both the serum and effusion was highest in the patientswith adenocarcinoma. These data indicate that determination of the CEA level in effusions,when done in combination with cytological examinations, mayhave additional value in diagnosis of lung cancer.     

Antitumor effect of reduction of 150-kDa oxygen-regulated protein expression on human prostate cancer cells

BACKGROUND: The 150-kDa oxygen-regulated protein ORP150, a new member of the heat shock protein family that functions as a molecular chaperone in the endoplasmic reticulum, was found to increase in infiltrating cancer cells. Since enhancement of ORP150 expression and the presence of vascular endothelial growth factor (VEGF) in human prostate cancer glands were immunohistochemically demonstrated, we examined whether transduced antisense ORP150 cDNA can reduce angiogenicity and tumorigenicity through suppression of VEGF secretion. METHODS: Human prostate cancer specimens were immunohistochemically stained with fluorescein isothiocyanate (FITC) for ORP150 or vascular endothelial growth factor (VEGF). An adenovirus vector (Ad) carrying antisense ORP150 cDNA (AdCA-Antisense ORP150) was constructed and infected to prostate cancer DU145 cells. Expression of ORP150 in the cells was analyzed with western blotting and secretion of VEGF into the supernatant with an enzyme-linked immunoabsorbent assay (ELISA). Angiogenicity was evaluated by chorioallantoic membrane (CAM) assay. A nude mouse xenograft model was used to examine tumorigenicity. RESULTS: Immunohistochemical study proved that the expression of ORP150 and VEGF was enhanced in the cytoplasm of prostate cancer cells. The Ad showed 100% transduction efficiency and minimum cytotoxicity when the cells were infected at a multiplicity of infection (MOI) of 20 for 24 h. Expression of ORP150 was substantially reduced by the antisense treatment. Secretion of VEGF into the culture supernatant was reduced to 30%. Consequently, the CAM assay showed relatively low angiogenicity, while marked suppression of tumor formation was observed in the xenograft model. CONCLUSION: Adenoviral-mediated antisense ORP150 cDNA transfer is well worth considering as an option for prostate cancer gene therapy.     

Epidemiology of genotypes of hepatitis C virus in Japanese patients with type C chronic liver diseases: A multi-institution analysis

Sixteen medical institutions in Japan collaborated in this study of the epidemiology of hepatitis C virus (HCV) genotypes. A total of 4176 patients with type C chronic liver disease, from the four main islands of Japan, were evaluated. Of those evaluated, 2794 had chronic hepatitis, 727 had liver cirrhosis and 655 had hepatocellular carcinoma. The HCV genotype of the patients was determined by an enzyme-linked immunosorbent assay based on serological genotype 1- and 2-specific recombinant peptides (SG-1 and SG-2, respectively) of the NS4 region. The prevalence of SG-1 and SG-2 HCV was similar in the four main islands of Japan. SG-1 HCV predominated in each disease category (69–76%). The percentage of patients with SG-1 HCV increased by 7%, while that of patients with SG-2 HCV decreased by 7%, as liver disease progressed in severity from chronic hepatitis to carcinoma (P < 0.001). Patients with either SG-1 or SG-2 had a similar mean age and history of blood transfusion. In conclusion, SG-1 HCV was found to predominate in Japan, and the HCV genotype was found to be related to the stage of hepatitis C disease.     

REDUCTION OF HUMAN AND RAT TESTICULAR FOLLICLE STIMULATING HORMONE RECEPTORS BY HUMAN MENOPAUSAL GONADOTROPHIN IN VIVO AND IN VITRO

Reduction of human and rat testicular FSH receptors by hMG was studied in vivo and in vitro. After a single injection of hMG, the number of high affinity FSH receptors were significantly reduced for 5 and 3 d in human and rat testes, respectively, without affecting their affinity. FSH receptor numbers recovered to pretreatment values by 14 d after the injection. Radioactivity in rat testes found 48 h after a s.c. injection of 125I-labelled human FSH was less than 10% of the maximum found 10 h after the injection, showing that the prolonged reduction of FSH receptors after hMG injection was not due to occupancy of the binding sites. Occupied FSH receptors measured in rat testes accounted for about 15% of all receptors on the day after an injection of hMG and for less than 5% after the third day. In experiments in vitro using organ culture techniques, an exposure to hMG for 24 h induced a dose-related significant loss of the specific FSH binding sites for 7 and 5 d in human and rat testes, respectively. Thereafter, the loss was gradually recovered. These findings suggest that the reduction in FSH receptors in human and rat testes by hMG is mainly due to down-regulation of the binding sites and that the testicular organ culture method used in the present study is useful to study hormonal regulation of testicular function, especially in human testes.     

Cardiovascular function before and after iron therapy by echocardiography in patients with iron deficiency anemia

BACKGROUND: The aim of the study was to estimate the left ventricular contractility using the ratio of left ventricular end-systolic wall stress to left ventricular end-systolic volume index in patients with iron deficiency anemia, for which there are no previous reports. METHODS: Cardiovascular functions were evaluated using echocardiography and pulsed Doppler echocardiography in 30 children aged 3-14 years (hemoglobin 4.9-8.5 g/dL), before, during and after iron therapy. We also studied 38 healthy children as a control group. RESULTS: The left ventricular preload was significantly higher and the left ventricular afterload was lower in the patients with anemia before iron therapy. The ratio of left ventricular end-systolic wall stress to left ventricular volume, an index of systolic function that is independent of preload and afterload, was significantly lower in the patients with anemia before iron therapy (before iron therapy 2.13 +/- 0.44, after therapy 3.52 +/- 0.76, healthy controls 3.42 +/- 0.70). Left ventricular early diastolic filling was significantly higher in the patients with anemia before iron therapy. The cardiac index was also significantly higher before therapy because of the increases in preload, heart rate and early diastolic filling, as well as the decrease of afterload. There were no significant differences in the indices of cardiovascular function between anemic patients after iron therapy compared with control subjects. CONCLUSIONS: The ratio of left ventricular end-systolic wall stress to the left ventricular volume index and the cardiac index suggested that a hemoglobin concentration < or = 6 g/dL was associated with left ventricular dysfunction and circulatory congestion.     

EXPRESSION OF PARATHYROID HORMONE (PTH)-RELATED PEPTIDE (PTHrP) AND PTH/PTHrP RECEPTOR IN GIANT CELL TUMOUR OF TENDON SHEATH

The giant cell tumour of tendon sheath (GCTTS) is mainly composed of mononucleated stromal cells (SC) and multinucleated giant cells (GC), so-called osteoclast-like GC. It is thought that GC are derived from SC, but their precise relationship is not fully understood. Parathyroid hormone (PTH)-related peptide (PTHrP) is now considered to be a cytokine for cell differentiation, which may stimulate osteoclast-like cell formation in haematopoietic cells. Five cases of GCTTS were evaluated immunohistochemically, using a variety of antibodies against PTHrP, PTH/PTHrP receptor, KP-1 as a histiocytic phenotypic antigen, fibronectin as a fibroblastic phenotypic antigen, and proliferating cell nuclear antigen (PCNA). In situ hybridization and immunohistochemistry revealed that in all cases both SC and GC expressed PTHrP. PTH/PTHrP receptor was observed only in histiocytic SC and GC, but not in fibroblastic SC. Almost all GC showed histiocytic features. PCNA immunoreactivity was detected only in the nuclei of SC, and not in GC. Moreover, SC with PTH/PTHrP receptor immunoreactivity were negative for PCNA. These results suggest that GC are derived from histiocytic SC expressing PTH/PTHrP receptor and losing proliferative activity in the process of transition from mononuclear to multinucleated. PTHrP produced by SC and GC may be involved in the formation of osteoclast-like cells in GCTTS by acting in an autocrine/paracrine fashion.     

EFFECTS OF NIFEDIPINE ON BLADDER OVERACTIVITY IN RATS WITH CEREBRAL INFARCTION

PURPOSE: Our objective was to evaluate the effect of the calcium (Ca2+) channel blocking agent nifedipine on bladder overactivity induced by middle cerebral artery (MCA) occlusion and determine its site of action. MATERIALS AND METHODS: Seven days after implantation of a bladder catheter, a cannula for intracerebroventricular and intrathecal administration was implanted and the left MCA was occluded with 4-0 monofilament nylon thread in male SD rats. Twenty-four hours after the induction of cerebral ischemia, saline was infused into the bladder at a constant rate (200 microL/min.) and cystometrogram was measured in conscious state. Nifedipine was administered intracerebroventricularly (5 microL) or intrathecally (20 microL) at graded doses (0.15 ng.-0.15 microg., 0.15 microg. -1.5 microg., respectively). RESULTS: Bladder capacity in conscious rats was significantly reduced after the left MCA occlusion. Intracerebroventricular administration of nifedipine significantly increased bladder capacity in cerebral infarcted rats but not in sham operated rats. Furthermore there was no significant difference in bladder capacity between before and after intrathecal administration of nifedipine in cerebral infarcted rats. CONCLUSION: These results show that Ca2+ channel blocking agents can operate especially on the supraspinal central nervous system rather than on the spinal system in rats with neurogenic bladder overactivity following cerebral infarction.     

In vitro chemosensitivity test for human genito-urinary tumors using collagen gel matrix

BACKGROUND: Although the aim of chemosensitivity tests is to predict the efficacy of anticancer agents for individual patients, no generally accepted assay has been established. METHODS: A chemosensitivity test was conducted for solid tumors with an organ culture system using collagen gel matrix (CGM). Seventy-five samples of transitional cell carcinoma (TCC), 20 of germ cell tumor (GCT) and 13 of renal cell carcinoma (RCC) were used for the chemosensitivity test, and 20 patients were treated with anticancer drugs on the basis of the test results. RESULTS: Positive rates of anticancer drugs for the 75 TCC samples were 64.9% for carboplatin, 63.4% for cisplatin, 32.1% for etoposide, 19.7% for THP-adriamycin, 16.7% for vinblastine, and 12.3% for methotrexate, indicating that positive rates of the latter three agents consisting of an MVAC regimen were unexpectedly low. The GCT had higher positive rates than the other cancers while RCC had the lowest. In 20 eligible patients (seven patients with bladder tumors and 13 with GCT), the true positive and true negative rates were 42% (5/12) and 75% (6/8), respectively, and the sensitivity and specificity were 71% (5/7) and 46% (6/13), resulting in a 55% (11/20) accurate predictive value. CONCLUSION: Although predictive accuracy was moderate when combination chemotherapy was used, information about chemosensitivity may have some beneficial effect on the treatment of patients with invasive bladder cancer or advanced GCT, because insensitive drugs detected by the test could be deleted or replaced with more sensitive ones.