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Inhibitory effect of glucocorticoids on human-cloned 5-hydroxytryptamine3A receptor expressed in xenopus oocytes.

BACKGROUND: Methylprednisolone, dexamethasone, and other glucocorticoids have been found effective against nausea and vomiting induced by chemotherapy and surgery. Although the specific 5-hydroxytriptamine3 (5-HT3) receptor antagonists such as ondansetron and ramosetron are used as antiemetics, reports show that the use of 5-HT3 receptor antagonists with some glucocorticoids brings additional effects. Glucocorticoids are reported to be antiemetic. The effect of glucocorticoids on 5-HT3 receptor, however, has not been well characterized. This study was designed to examine whether dexamethasone and methylprednisolone had direct effects on human-cloned 5-HT3A receptor expressed in Xenopus oocytes. METHODS: Homomeric human-cloned 5-HT3A receptor was expressed in Xenopus oocytes. The authors used the two-electrode voltage-clamping technique to study the effect of methylprednisolone and dexamethasone on 5-HT-induced current. RESULTS: Both dexamethasone and methylprednisolone concentration-dependently attenuated 5-HT-induced current. Dexamethasone inhibited 2 microm 5-HT-induced current, which was equivalent to EC30 concentration for 5-HT3A receptor, with an inhibitory concentration 50% of 5.29 +/- 1.02 microm. Methylprednisolone inhibited 2 microm 5-HT-induced current with an inhibitory concentration 50% of 1.07 +/- 0.15 mm. The mode of inhibition with either dexamethasone or methylprednisolone was noncompetitive and voltage-independent. When administered together with the 5-HT3 receptor antagonists, ramosetron or metoclopramide, both glucocorticoids showed an additive effect on 5-HT3 receptor. CONCLUSION: The glucocorticoids had a direct inhibitory effect on 5-HT3 receptors. The combined effect of glucocorticoids and the 5-HT3 receptor antagonists seems additive.

Animals↗

The effect of intrathecal fentanyl added to hyperbaric bupivacaine on maternal respiratory function during Cesarean section.

BACKGROUND: Subarachnoid blockade with local anesthetics induces respiratory depression. Although the addition of fentanyl to bupivacaine has become popular in subarachnoid blockade for Cesarean section, there is no information on the effect of intrathecal fentanyl on maternal spirometric respiratory function in parturients undergoing Cesarean section. METHODS: We tested the effect of the addition of intrathecal fentanyl to hyperbaric bupivacaine on maternal spirometric performance in 40 consenting parturients undergoing Cesarean section. The parturients were randomized into two groups: those receiving 2.0 ml of hyperbaric bupivacaine 0.5% and 0.4 ml of saline intrathecally and those receiving 2.0 ml of hyperbaric bupivacaine and 0.4 ml of fentanyl (20 microg) intrathecally. We performed spirometry on arriving at the operation room and 15 min after subarachnoid blockade. RESULTS: Subarachnoid blockade with bupivacaine significantly decreased the peak expiratory flow rate, but did not induce significant changes in vital capacity and forced vital capacity. The addition of intrathecal fentanyl to bupivacaine improved the quality of subarachnoid blockade, but did not lead to a deterioration in respiratory function compared with intrathecal bupivacaine alone. CONCLUSIONS: The addition of intrathecal fentanyl to hyperbaric bupivacaine did not lead to a deterioration in maternal spirometric respiratory function in parturients undergoing Cesarean section.

Adult↗

Clinical study on 53 cases of cadaveric kidney transplantation at Osaka City University Hospital.

BACKGROUND: In this study, we examined the effects of nonimmunological factors on cadaver kidney transplant. METHODS: Fifty-three cadaver kidney transplant recipients were studied. They were divided into two groups, Group I ( donor age<60, n=38 ) and Group II ( donor age > or = 60, n=15). These patients were studied to determine whether donor age and recipient Body Mass Index (BMI) affected transplant outcome. RESULTS: The 3 and 5-year overall graft / patient survival was 80.6 / 100% and 72.7 97.3%, respectively. The best S-Cr after transplantation was significantly (p<0.05) lower in Group I compared to Group II. The 1, 5 and 8-year graft survival was significantly (p<0.05) better in Group I. In the low BMI patients of Group II, 5-year graft survival was significantly (p<0.01) better than high BMI patients. DISCUSSION: An aged cadaver donor was a risk factor for decreased posttransplant renal functions and lower graft survival. However, if a recipient with a low BMI can be selected, the outcome of cadaver kidney transplants from aged donors may be improved.

Adult↗

The McCoy levering laryngoscope in patients with limited neck extension.

PURPOSE: The McCoy levering laryngoscope is a modified Macintosh laryngoscope, which has a hinged tip controlled by a lever on the handle. The purpose of this study was to investigate whether the tip elevation of this laryngoscope results in better laryngeal visualization than using the Macintosh laryngoscope when the patient's neck is fixed in the neutral position. METHODS: Fifty female patients (ASA physical status I-II) undergoing elective surgery during general anaesthesia were investigated. The patient's neck was manually fixed in the neutral position by an assistant, and laryngeal visualization was attempted first with a size #3 Macintosh laryngoscope (Macintosh trial), and then with a size #3 McCoy levering laryngoscope with blade tip elevation (McCoy trial), and tracheal intubation was attempted. Trials of laryngeal visualization were evaluated with the Cormack score. RESULTS: In the Macintosh trial, 36 of 50 (72%) patients were evaluated grade 3, and two grade 4. In most of the patients graded 2 and 3 in the Macintosh trial (70% of the grade 2 and 83% of the grade 3 cases), the laryngeal view was improved by using the McCoy levering laryngoscope. The Cormack grade in the McCoy trial was less than that in the Macintosh trial (P < 0.01). No complications were observed during the study. CONCLUSION: The McCoy levering laryngoscope improved laryngeal visualization in patients whose neck cannot be extended.

Female↗

Usefulness of a multidetector-row computed tomography scanner for detecting pannus formation.

BACKGROUND: Prosthetic valve dysfunction (PVD) as a result of pannus or thrombus formation is an infrequent but serious complication. Currently available diagnostic tools, however, are insufficient to detect a minute pannus and thrombi. The use of a more advanced diagnostic image, multidetector-row computed tomography scanner, may enable us to determine the anatomic and functional causes of PVD. METHODS: Patients who underwent aortic valve replacement with a St. Jude Medical valve were examined by transthoracic echocardiography and cineradiography to diagnose PVD. Sixteen patients with PVD (PVD group) and 12 patients with normal prosthetic valve function (control group) were studied using the multidetector-row computed tomography scanner. The multidetector-row computed tomography findings in 2 patients with PVD were validated by the observations during reoperation. RESULTS: In 13 of 16 patients (81%) in the PVD group and 3 of 12 patients (25%) in the control group, multidetector-row computed tomography demonstrated that an abnormal small tissue, regarded as pannus, was found to extend from the left ventricular septum into the pivot guard. These findings were confirmed by the observations during reoperation in 2 patients in the PVD group. CONCLUSIONS: Multidetector-row computed tomography can be a useful diagnostic technique for anatomic and functional evaluation of PVD as a result of pannus formation.

Adult↗

Motility-related protein (MRP-1/CD9) and KAI1/CD82 expression inversely correlate with lymph node metastasis in oesophageal squamous cell carcinoma.

Although the mechanisms of action of the transmembrane superfamilies, motility-related protein-1 (MRP-1/CD9) and KAI1/CD82, are not well known, they are reported to suppress the metastasis of several kinds of cancers. The suppression of cell motility by MRP-1/CD9 may cause suppression of the metastasis. As we could not find any reports concerning the expression of MRP-1/CD9 and KAI1/CD82 in oesophageal cancers we investigated their expression in oesophageal specimens. We conducted immunohistochemical staining for MRP1/CD9 against 108 cases of oesophageal squamous cell carcinoma using anti-MRP-1/CD9 monoclonal antibody M31-15, and for KAI1/CD82 against 104 cases using anti-KAI1/CD82 monoclonal antibody C33. To investigate the gradual expression of MRP-1/CD9 and KAI1/CD82, 24 oesophageal dysplasias were immunohistochemically stained using the same method and then investigated. The expression of both MRP-1/CD9 and KAI1/CD82 were positive on the cell membranes of normal oesophageal epithelial cells, but reduced or negative in the cancer cells. Reduced MRP-1/CD9 expressions significantly correlated to tumour depth (P = 0.0009). We found a significantly greater number of reduced or negative expression of MRP-1/CD9 and KAI1/CD82 in lymph node metastatic cases (P = 0.0003 and P= 0.0129, respectively), but not in distant metastatic cases. The 5-year survival rate of MRP-1/CD9-negative and reduced patients was significantly worse than those of positive patients (n = 108, curative cases, RO). Few cases remained KAI1/CD82-positive (9.6%; 10/104) in oesophageal cancer. Twenty (83.3%) and twenty-two (91.7%) cases out of 24 dysplasias were defined as KAI1/CD82-positive and MRP1/CD9-positive, respectively. The decrease in MRP-1/CD9 and KAI1/CD82 expression may facilitate lymph node metastasis in oesophageal squamous cell carcinomas. Knowing the status of the expression of MRP-1/CD9 appears helpful in predicting the prognosis for each patient.

Adult↗

Antiemetic efficacy of granisetron: a randomized crossover study in patients receiving cisplatin-containing intraarterial chemotherapy.

BACKGROUND: Cisplatin (CDDP) is one of the most active chemotherapeutic agents but is among the most emetogenic drugs. The emetic side-effects of CDDP-containing intraarterial chemotherapy have not been evaluated in a prospective randomized trial and the efficacy of serotonin antagonists in preventing the emesis associated with this method of CDDP administration has not been assessed. METHODS: CDDP 50 mg/m2 and methotrexate 30 mg/m2 were administered every 3 weeks through intraarterial catheters placed in the bilateral internal iliac arteries. Patients were classified into two groups: granisetron treatment group (group G) and no treatment group (group NG) with the first course of chemotherapy, crossing over with the second course. The patients in group G received granisetron 40 micrograms/kg by intravenous infusion. RESULTS: Although intraarterial CDDP administration produced less emesis than intravenous CDDP administration, at the same concentration, gastrointestinal toxicity is still the most unpleasant side-effect for patients. Granisetron administration significantly reduced nausea and vomiting during the acute emetic phase (an evaluation of treatment as very effective and effective was made in 89% in group G and 33% in group NG (P < 0.001). Complete control of emesis was achieved in 68 and 18% of patients in groups G and NG, respectively (P < 0.0001). CONCLUSION: A single prophylactic infusion of granisetron was effective in preventing the nausea and vomiting associated with intraarterial CDDP-containing therapy.

Adolescent↗

Colonic absorption of menaquinone-4 and menaquinone-9 in rats.

The colonic absorption of menaquinones was examined in rats by the in situ loop method. The overall disappearance of [14C]menaquinone-4 from the colonal loop was approximately 6% at 3 h and much slower than that of menadione. After administration of [14C]menaquinone-4 into the jejunal loop with bile, approximately 17% of unchanged menaquinone-4 was recovered in the lymph after 6 h, but none was found when the administration had been into the colonal loop. Portal absorption of menaquinone-4 from the colon was detected and the unchanged form (approximately 23% of the absorbed radioactivity) was identified in the mesenteric venous blood. When menaquinone-9 was administered into the colon, almost all was recovered from the colonal loop. No transfer of menaquinone-9 from the colon into the lymph or blood was observed at 6 h after dosing. The present observations indicate that only a part of bacterially produced menaquinones is absorbed from the colon via the portal pathway, but the absorption rates of menaquinones decrease markedly with an increase in the number of isoprenoid units.

Animals↗

[A comparative analysis of zoonosis and vector surveillance systems].

PURPOSE: To investigate zoonosis and vector surveillance systems in major countries, conducted by quarantine, health and environment authorities, and compare the results with the current Japanese systems. METHODS: We elaborated a questionnaire for zoonosis and vector surveillance systems regarding target diseases, vectors, period and area of operation, type of surveillance (active and/or positive), and feedback mechanisms which was then mailed to ten countries having strong trade and tourism links with Japan. We visited some authorities for further discussions. RESULTS: Eight countries which responded answered that all were conducting zoonosis and vector surveillance. Target diseases included those designated by the International Health Regulations and others with a higher priority for control and prevention in the individual countries. The type of surveillance was classified as: regular monitoring of the vector population, active detection of pathogens in vectors during a specific time period of a year, and intensive pathogen characterization when problems occurred. CONCLUSIONS: The significance of zoonosis and vector surveillance was recognized through this investigation, where we found differences in target diseases, and type of operation. The results should be utilized for generation of more useful and efficient surveillance systems in Japan.

Animals↗

Surgery for ductal carcinoma in situ.

BACKGROUND: Ductal carcinomas in situ (DCIS) are sometimes treated too aggressively by surgery. We discuss minimal invasive surgery for DCIS on the basis of our experience at the Cancer Institute Hospital in Tokyo. METHODS: We performed surgery for 667 cases of DCIS between 1987 to 1998. This twelve year period we divided into three periods; 1987-1990,1991-1994, and 1995-1998. RESULTS: DCIS comprised 10% of all breast cancers, and tended to increase in incidence over time. The number of minimally invasive procedures such as breast conserving treatment (BCT), surgery without axillary dissection, and day surgery increased in later periods. In BCT for DCIS the surgical margin status is the most important factor, the rate of negative surgical margins was higher in DCIS than invasive cancer, and especially high in cases of mammographically detected nonpalpable cancer, the incidence of which is increasing yearly. The outcome of the 667 cases was very good. No distant metastases were observed, and the incidence of ipsilateral breast cancer(including second primary cancer) in these cases was 5% CONCLUSIONS: Because small cancers, including nonpalpable cases, will be detected more frequently, minimal invasive surgery will become more common for DCIS.

Axilla↗

Combined measurement of hepatocyte growth factor and carcinoembryonic antigen as a prognostic marker for patients with dukes a and B colorectal cancer: results of a five-year study.

PURPOSE: There is no marker capable of differentiating patients with Dukes A and B colorectal cancer with aggressive diseases from those with indolent diseases. We evaluated the results of five years of actuarial survival data to determine whether serial monitoring of serum hepatocyte growth factor could provide prognostic information on these patients. METHODS: Blood samples of 147 colorectal cancer patients were obtained and the serum concentration of hepatocyte growth factor was measured. RESULTS: Elevated serum hepatocyte growth factor levels were associated with stage progression. Although the overall positive rate of hepatocyte growth factor in the patients was the same as that of the carcinoembryonic antigen, the positive rate of hepatocyte growth factor in the Dukes A patients was two times higher than that of the carcinoembryonic antigen, and nearly 40 percent of the carcinoembryonic antigen-negative patients had a positive serum hepatocyte growth factor in the Dukes A and B classification. In this subgroup, patients with positive serum hepatocyte growth factor or carcinoembryonic antigen levels had a poorer prognosis, whereas positive serum hepatocyte growth factor level after surgery could predict disease recurrence. CONCLUSIONS: A combination of serum hepatocyte growth factor and carcinoembryonic antigen tests might be useful for selecting patients with aggressive diseases in Dukes A and B classification.

Adenocarcinoma↗

On the interaction of ribonuclease U-2 and substrate analogues.

1. The interaction of ribonuclease U-2 (RNAase U-2) with its substrate analogues has been investigated by a gel filtration method. At pH 4.5 and 30 degrees C, the apparent binding strength of the substrate analogues was in the following order; adenylate greater than guanylate greater than inosylate greater than cytidylate among 2'-nucleotides and 2'- greater than 3'- greater than 5'- among adenylate isomers. The formation of an equimolar complex of RNAase U-2 and 2'-nucleotide was indicated from the Scatchard plot. 2. The interaction of RNAase U-2 with 2'-adenylate or 2'-guanylate was observed spectrophotometrically. The complex of RNAase U-2 and 2'-adenylate yielded not only an absorption difference spectrum having a broad positive peak at 280 to 285 nm and a negative trough at 256 nm but also a circular dichroic difference spectrum having a positive peak at around 250 nm and a negative trough at around 290 nm. The complex of RNAase U-2 and 2'-guanylate gave a similar difference spectrum to that of the RNAase T-1 - 3'-guanylate complex, in absorption as well as in circular dichroism.

Binding Sites↗

Visualization of the cervical spinal cord with FDG and high-resolution PET.

PURPOSE: Our aim was to evaluate the visibility of the cervical spinal cord with [18F]2-fluoro-2-deoxyglucose (FDG) and a high-resolution PET scanner and to quantify the glucose utilization by the cervical cord. METHOD: Twenty-one normal subjects and three cervical myelopathy patients were studied. The visibility of the cervical spinal cord in sagittal and coronal sections was evaluated. The metabolic rate of glucose (MRGlu) and standardized uptake value (SUV) of FDG in the cord were calculated. RESULTS: The entire cervical spinal cord was clearly visualized in 57% of the subjects: the upper cord in 81%, the middle cord in 73%, and the lower cord in 57%. The MRGlu of the normal cord was 1.93 +/- 0.37 mg/100 g/min. SUV was constant across all the vertebral levels and negatively correlated with subject age. In the myelopathy patients, the SUV of the entire cervical cord was lower than in the age-matched normal subjects. CONCLUSION: These preliminary results indicate that the cervical spinal cord can be visualized as a normal structure in routine head and neck PET imaging and that FDG-PET may provide quantitative information about spinal cord disorders.

Adult↗

Efficacy of CS-758, a novel triazole, against experimental fluconazole-resistant oropharyngeal candidiasis in mice.

The therapeutic efficacy of CS-758, a novel triazole, was evaluated against experimental murine oropharyngeal candidiasis induced by Candida albicans with various susceptibilities to fluconazole. Against infections induced by strains with various susceptibilities to fluconazole, the efficacy of fluconazole was strongly correlated with the MIC of fluconazole, as measured by the NCCLS method, and agreed with the NCCLS interpretive breakpoints, suggesting that the efficacies of new drugs could be predicted by using this model. The results of the fungal burden study corresponded with the results of the histopathological study. CS-758 exhibited potent in vitro activity (MICs, 0.004 to 0.06 micro g/ml) against the strains used in this murine model including fluconazole-susceptible dose-dependent and fluconazole-resistant strains (fluconazole MICs, 16 to 64 micro g/ml). CS-758 exhibited excellent efficacy against the infections induced by all the strains including a fluconazole-resistant strain, and the reductions in viable cell counts were significant at 10 and 50 mg/kg of body weight/dose. Fluconazole was not effective even at 50 mg/kg/dose against infections induced by a fluconazole-resistant strain (fluconazole MIC, 64 micro g/ml). These results suggest that CS-758 is a promising compound for the treatment of oropharyngeal candidiasis including fluconazole-refractory infections.

Animals↗

Pretreatment with topical all-trans-retinoic acid is beneficial for wound healing in genetically diabetic mice.

OBJECTIVE: Topical pretreatment with aIl-trans-retinoic acid (atRA) is known to improve healing of cutaneous wounds. We tested the effect of atRA on wound healing of genetically diabetic db/db mice. It is known that cutaneous wounds of db/db mice show delayed wound healing due to impaired wound contraction, delayed granulation tissue formation and underexpression of keratinocyte growth factor (KGF). METHODS: 0.1% atRA in 100 mg aqueous gel was applied to the back skin of db/db mice as well as to their normal heterozygous littermates, db/+ mice, for five consecutive days, and 2 days after completion of the atRA treatment, two round excisional wounds were created down the panniculus carnosus with a 6-mm punch biopsy on the back skin of each mouse. RESULTS: After 5 days treatment with 0.1% atRA, significant hypertrophy of the epidermis and dermis, neovascularization, and inflammatory cell invasion were seen in the skin of the db/db mice, but these effects were seen only weakly in db/+ mice. Wounds in atRA-treated db/db mice closed more rapidly than those in vehicle-treated db/db mice. KGF mRNA expression, which is usually significantly lower in db/db mice than in normal mice, in wounds of atRA-treated db/db mice on day 1 of treatment was as strong as in db/+ mice. CONCLUSION: Pretreatment with atRA reversed the impaired wound healing in db/db mice.

Administration, Topical↗

Decreased tissue inhibitor of metalloproteinase-2/matrix metalloproteinase ratio in the acute phase of aortic dissection.

PURPOSE: Aortic dissection is characterized by fragility of the tunica media, and matrix metalloproteinases (MMPs) are enzymes that degrade the extracellular matrix of the aorta. This study examines MMPs in patients with acute aortic dissection (AAD) in an attempt to elucidate the mechanisms of their actions. METHODS: Enzyme-linked immunosorbent assays were used to measure the quantification of MMP-2, MMP-9, and the tissue inhibitor of metalloproteinase (TIMP)-2 in 30 patients with AAD, 12 patients with abdominal aortic aneurysm (AAA), and 16 control (CON) patients who underwent coronary artery bypass grafting. RESULTS: MMP-2 and TIMP-2 were significantly lower in the AAD group than in the CON group, at 36 +/- 19 vs 58 +/- 30 (P < 0.01) and at 21 +/- 25 vs 216 +/- 130 (P < 0.001), respectively. The TIMP-2/MMP-2 ratio was 3.7 +/- 1.7 in the CON group and 0.9 +/- 0.8 in the AAD group (P < 0.001 vs CON), and the TIMP-2/MMP-9 ratio was 200 +/- 170 in the CON group and 37 +/- 80 in the AAD group (P < 0.001 vs CON). CONCLUSION: Low TIMP-2/MMP-2 and TIMP-2/MMP-9 ratios might play an important role in the onset of aortic dissection, when the tunica media becomes fragile with chronic breakage and degradation of the extracellular matrix.

Acute Disease↗

Topographic characteristics of the optic nerve head measured with scanning laser tomography in normal Japanese subjects.

PURPOSE: Few studies have been performed regarding the topographic information obtained with the Heidelberg retina tomograph (HRT) in normal Japanese. In this study, we examined the factors influencing optic disc parameters and hemisphere symmetry obtained with the HRT in normal Japanese subjects. METHODS: Mean values and the standard deviation range for the main HRT parameters were evaluated in 223 eyes of 223 normal Japanese subjects. The influence of age, sex, and disc size on HRT topographic data was analyzed. The superior and inferior hemisphere topographic parameters were compared. RESULTS: Disc area showed a significant difference by sex (P = 0.0493). Rim volume (r = -0.208, P = 0.019), height variation contour (r = -0.275, P = 0.001), and mean retinal nerve fiber layer (RNFL) thickness (r = -0.366, P = 0.001) declined with age. All parameters except height variation contour and mean RNFL thickness showed a clinically significant correlation with disc size (-0.159 < r < 0.719, P < 0.01). Cup parameters in the superior hemisphere were significantly greater than those in the inferior hemisphere. In contrast, rim parameters in the superior hemisphere were significantly smaller than those in the inferior hemisphere. CONCLUSIONS: Some factors, namely, sex, age, and disc size, affected the optic disc parameters in the HRT measurements. Possible parameter asymmetry between the two hemispheres should be considered in normal eyes.

Adolescent↗

High intensity focused ultrasound for benign prostatic hyperplasia.

BACKGROUND: Transurethral resection of the prostate (TURP) has been the gold standard of treatment for patients with symptomatic benign prostatic hyperplasia (BPH). The present paper discusses the safety and effectiveness of transrectal high intensity focused ultrasound (HIFU) for treating patients with symptomatic BPH. METHODS: HIFU was conducted on 28 patients with BPH. At one, three and six months after treatment, all patients were examined for parameters including International Prostate Symptom Scores (I-PSS), Quality of Life (QOL) inquiry, uroflowmetry, and transrectal ultrasound for determining prostate volume. RESULTS: I-PSS and QOL showed statistically significant improvement at one, three, and six months postoperatively (P < 0.0001-0.005, Wilcoxon signed-rank test). Ten of 28 (35.7%), 13 of 28 (46.4%), and 6 of 15 (40.0%) cases were categorized as effective cases with HIFU treatment at one, three, and six months follow-up. CONCLUSIONS: Focused ultrasound is an exciting new technology by which tissue can be destroyed at a site distant from the source of energy without damage to surrounding tissue. Clinical experience with alternative power settings, more accurate spacing of treatment lesions, and further development of HIFU machines may improve the results. Longer follow-up of patients with further clinical evaluation of HIFU is necessary to define the efficacy of this technique.

Aged↗