Chromosome 6 abnormalities correlated with thymoma progression.
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Chromosome Aberrations↗
Biomedical subjects
Yoshitaka Fujii
Publications and source records attributed to Yoshitaka Fujii.
Saber-sheath malacic trachea remodeled and fixed into a normal shape by long-term placement and then removal of gianturco wire stent.
We report the case of a 59-year-old man who presented with major dyspnea due to saber-sheath malacic trachea associated with chronic pulmonary obstructive disease. The placement of a temporary tracheal stent alleviated his dyspnea very well; hence the stent was replaced with a Gianturco wire stent (Cook Cardiology, Bloomington, IN). However, this required removal due to wire-stent-related complications 2 years after the replacement. Surprisingly the trachea had been remodeled to a normal shape resulting in comfortable, functional respiratory status. A review of the literature reveals our case to be the first report of curing saber-sheath malacic trachea without leaving any prostheses or other foreign materials.
Bronchoscopy↗
The immunologic role of thymectomy in the treatment of myasthenia gravis: implication of thymus-associated B-lymphocyte subset in reduction of the anti-acetylcholine receptor antibody titer.
BACKGROUND AND PURPOSE: Thymectomy is generally accepted as the major option of treatment for myasthenia gravis. To elucidate the biological role of thymectomy in the treatment of myasthenia gravis, the immunologic characteristics of the thymus was studied in association with the postoperative kinetics of the anti-acetylcholine receptor antibody titer. MATERIALS AND METHODS: Thirty-four patients with nonthymomatous myasthenia gravis who had positive anti-acetylcholine receptor antibody titer and undergoing extended thymectomy were subjected to the study. Reduction of anti-acetylcholine receptor antibody titer was evaluated in terms of the proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy to that before the operation. The numbers of B lymphocytes (CD19(+) cells) and the germinal center B lymphocytes (CD19(+)CD38(high) cells) present in 1 g of the thymic tissue were calculated by flow cytometry. RESULTS: The proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy ranged from 27.5% to 150%. The numbers of B lymphocytes and the germinal center B lymphocytes in 1 g of the thymic tissue ranged from 0.19 x 10(6)/g to 162.8 x 10(6)/g and from 0.09 x 10(6)/g to 33.4 x 10(6)/g, respectively. The proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy had a significant inverted correlation with the number of B lymphocytes (P =.002) as well as that of the germinal center B lymphocytes (P =.007). CONCLUSION: Effectiveness of thymectomy was dependent on predominance of B lymphocytes and the germinal center B lymphocytes in the thymus, suggesting that one of the biological roles of thymectomy in the treatment of myasthenia gravis is removing the thymus-associated germinal centers.
ADP-ribosyl Cyclase↗
A comparison of granisetron, droperidol, and metoclopramide in the treatment of established nausea and vomiting after breast surgery: a double-blind, randomized, controlled trial.
BACKGROUND: Women undergoing breast surgery are at particular risk for post-operative nausea and vomiting (PONV), with an incidence of emesis as high as 50% when no prophylactic antiemetic is used. OBJECTIVE: This study compared the efficacy of the selective 5-hydroxytryptamine(3) receptor antagonist granisetron with that of the traditional antiemetics droperidol and metoclopramide in the treatment of established PONV after breast surgery. METHODS: In this prospective, randomized, double-blind trial, patients who had undergone breast surgery and were experiencing PONV during the first 3 hours after anesthesia received either granisetron 40 microg/kg IV, droperidol 20 microg/kg IV, or metoclopramide 0.2 mg/kg IV. Patients were observed for 24 hours after administration of study drug. Emetic episodes were recorded by nursing staff who were blinded to treatment assignment. RESULTS: Seventy-five patients were enrolled in the study, 25 in each treatment group. Their age ranged from 41 to 65 years. There were no significant between-group differences in patients' demographic or surgical characteristics at study entry. The number of patients who were emesis free (no nausea, retching, or vomiting) was significantly higher in patients who received granisetron (88% [2225]) than in those who received droperidol (64% [1625]; P = 0.047) or metoclopramide (56% [1425]; P = 0.013). In patients who experienced nausea (3, 8, and 9 patients in the granisetron, droperidol, and metoclopramide groups, respectively), the severity of nausea was significantly lower with granisetron compared with droperidol (P = 0.028) and metoclopramide (P = 0.025). No clinically serious adverse events were observed in any group. CONCLUSION: Granisetron was significantly more effective than the traditional antiemetics droperidol and metoclopramide for the treatment of PONV in this population of patients undergoing breast surgery.
Adult↗
Granisetron versus granisetron/dexamethasone combination for the treatment of nausea, retching, and vomiting after major gynecologic surgery: a randomized, double-blind study.
BACKGROUND: Granisetron, a selective 5-hydroxytryptamine3 antagonist, is effective for the treatment of patients with postoperative nausea and vomiting. Dexamethasone decreases chemotherapy-induced emesis when added to an antiemetic regimen. OBJECTIVE: This study compared the efficacy of granisetron alone with granisetron/dexamethasone combination for the treatment of nausea and vomiting after major gynecologic surgery. METHODS: In this randomized, double-blind study, patients who were experiencing emetic symptoms during 0 to 3 hours after the end of anesthesia administration received granisetron 40 microg/kg i.v. either alone or in combination with dexamethasone 8 mg. Patients then were observed for 24 hours after study drug administration, with emetic episodes recorded and tolerability assessments performed by nursing staff blinded to treatment. RESULTS: A total of 120 women were enrolled (n = 60 in each treatment group; mean [SD] age in the granisetron group, 44 [9] years [range, 23-63 years]; combination group, 45 [8] years [range, 21-65 years]). No significant differences in patient demographic characteristics were found between the 2 treatment groups. However, the percentage of patients free of emetic symptoms (nausea, retching, vomiting) was higher in the granisetron/dexamethasone combination group than in the granisetron group (95.0% and 80.0%, respectively; P = 0.012). No clinically serious adverse events attributed to the study drugs were observed in either group. CONCLUSION: In this study, the granisetron/dexamethasone combination was more effective than was granisetron alone for the management of nausea and vomiting during 0 to 3 hours after anesthesia in women undergoing major gynecologic surgery.
Adult↗
Randomized, double-blind, placebo-controlled, dosed-finding study of the antiemetic effects and tolerability of ramosetron in adults undergoing middle ear surgery.
BACKGROUND: Ramosetron is a selective serotonin receptor antagonist (SSRA) that is approved for the treatment of emetic symptoms induced by cytotoxic drugs in Japan. We have reported that ramosetron 0.3 mg had comparable efficacy to granisetron 3 mg, another SSRA, in preventing emetic symptoms in adults in the first 48 hours after the start of anesthesia for middle ear surgery. Although it has been shown that a high dose of ramosetron can cause adverse effects (AEs), such as severe headache, the minimal effective dose of ramosetron is unknown. OBJECTIVE: The aim of this study was to determine the minimum effective and tolerable dose of ramosetron needed to prevent postoperative emetic symptoms in adult patients undergoing middle ear surgery. METHODS: This randomized, double-blind, placebo-controlled, dose-finding study was conducted at the Department of Anesthesiology, Toride Kyodo General Hospital (Toride, Japan). Patients aged > or =20 years scheduled for middle ear surgery were randomized to receive either placebo or ramosetron at 1 of 3 doses (0.15, 0.3, or 0.6 mg), regardless of body weight, i.v. immediately before anesthesia induction. Emetic symptoms (nausea, retching, or vomiting) occurring from 0 to <24 and 24 to 48 hours after the start of anesthesia were recorded. Other AEs also were assessed. RESULTS: A total of 100 patients (55 women, 45 men; mean [SD] age, 44 [12] years; mean [SD] body weight, 56 [8] kg; mean [SD] height, 159 [8] cm) were enrolled. Each treatment group comprised 25 patients. The treatment groups were comparable with regard to demographic characteristics and type of surgery After the second 24 hour postanesthesia period, significantly more patients in the ramosetron 0.3-mg and 0.6-mg groups were emesis free than in the placebo group (both P<0.001). The number of emesis-free patients in the ramosetron 0.15-mg group and the placebo group were similar after both study periods. No significant difference in antiemetic efficacy was found between the ramosetron 0.3-mg and 0.6-mg groups. No relationship between body weight and the efficacy of ramosetron was observed. The incidence of AEs was similar in all 4 groups. CONCLUSIONS: Ramosetron 0.3 mg, regardless of body weight, was more effective than either ramosetron 0.15 mg or placebo and as effective as ramosetron 0.6 mg for the prevention of emetic symptoms in the first 48 hours after the start of anesthesia in this selected population of adult patients who underwent middle ear surgery.
Adult↗
Results of a prospective, randomized, double-blind, placebo-controlled, dose-ranging trial to determine the effective dose of ramosetron for the prevention of vomiting after tonsillectomy in children.
BACKGROUND: Postoperative vomiting (POV) is an important adverse effect of anesthesia and surgery, and children undergoing tonsillectomy may be particularly at risk. OBJECTIVE: The aim of this study was to determine the effective dose of ramosetron, a 5-hydroxytryptamine type 3 receptor antagonist, for prophylaxis of severe POV (> or =2 episodes) in children undergoing general anesthesia for tonsillectomy. METHODS: Standard general anesthetic technique and postoperative analgesia were used in this prospective, randomized, double-blind, placebo-controlled, dose-ranging trial of pediatric patients. Patients who had experienced POV, had taken an antiemetic medication within 24 hours before surgery of had a history of motion sickness were excluded. Only patients aged 4 to 10 years were included, because of their ability to answer questions. Patients received a single administration of either i.v. placebo or i.v. ramosetron at 3, 6, or 12 microg/kg immediately after the end of surgery. During the first 48 hours after anesthesia, episodes of retching, vomiting, and adverse events were recorded by nursing staff blinded to treatment assignment. RESULTS: Eighty children (20 in each group)--42 girls and 38 boys--were enrolled. There were no differences in patient demographic characteristics among the treatment groups. The rates of complete response (no vomiting, retching, or need for another antiemetic medication) from 0 to 24 hours after anesthesia were 35% (7/20) with ramosetron 3 microg/kg, 90% (18/20) with ramosetron 6 micro/kg, and 90% (18/20) with ramosetron 12 microg/kg compared with placebo (30% [620], P=NS, P=0.001, and P=0.001 vs placebo, respectively); the corresponding rates from 24 to 48 hours after anesthesia were 35% (7/20), 90% (18/20), and 95% (19/20) compared with placebo (35% [7/20]; P=NS, P=0.001, and P=0.001 vs placebo, respectively). No difference in antiemetic efficacy was observed between ramosetron 6 and 12 microg/kg. No clinically serious adverse events attributable to the study drug were observed in any group. CONCLUSIONS: In the pediatric population studied, ramosetron 6 microg/kg was effective for the prevention of vomiting after tonsillectomy from 0 to 48 hours after anesthesia. Increasing the dose to 12 microg/kg did not appear to provide further benefit.
Antiemetics↗
Gelatinolytic activity of matrix metalloproteinase in lung cancer studied using film in situ zymography stamp method.
In this study, we investigated activity of matrix metalloproteinase (MMP) of lung cancer by newly developed film in situ zymography (FIZ) stamp method, which allows visual localization of gelatinolytic activity within the cut surface of a tumor. We performed FIZ stamp method and conventional gelatin zymography in 39 resected specimen of lung cancer. The degree of gelatinolytic activity was scored (FIZ score) and correlated with the clinicopathological factors of the tumor. FIZ score of normal lung was very low. Lung cancer tissue had consistently higher FIZ score than the matched normal lung tissue. There were statistically significant differences in the FIZ score according to the pathological stage (P = 0.0015), nodal status (P = 0.0007) and lymphatic invasion (P = 0.0004). Direct correlation was observed between the FIZ score and MMP-2 activity (rho = 0.568, P = 0.0030) as quantitated using conventional gelatin zymography. MMP-2 may play an important role in the lymphatic invasion of lung cancer. FIZ stamp method may be a simple and useful diagnostic aid for the presence of cancer cells in the resected specimen.
Adenocarcinoma↗
Cten mRNA expression was correlated with tumor progression in lung cancers.
Cten is a recently isolated gene, which has homology with tensin suggesting that it is a focal adhesion molecule. Tensin family proteins play an important role in cell motility. We attempted to determine the influence of cten expression on clinicopathological features in patients with lung cancer who had undergone surgery. Expression of cten messenger RNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in 89 lung carcinomas and adjacent histological normal lung samples using LightCycler. Cten/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression was not significantly different between lung cancer tissue (1.479+/-2.060) and normal lung tissue (1.528+/-1.592, P=0.8267). There was no relationship between cten/GAPDH expression and age, gender or N-status. However, tumor/normal ratio (T/N ratio) of cten/GAPDH expression was significantly higher in stage II-IV lung cancer (3.113+/-6.493) when compared with stage I lung cancer (1.237+/-1.820, P=0.0316). T/N ratio of cten/GAPDH expression was significantly higher in T4 lung cancer (4.612+/-9.726) when compared with T1 lung cancer (0.896+/-0.860, P=0.0252), and T2 lung cancer (1.636+/-2.066, P=0.0470), respectively. Thus cten/GAPDH mRNA expression has been correlated with evidence of tumor progression in terms of T and overall stage of lung cancer. Alternatively, cell motility or migration might play a role in progression of lung cancer.
Carcinoma, Non-Small-Cell Lung↗
Reduction of emetic symptoms during cesarean delivery with antiemetics: propofol at subhypnotic dose versus traditional antiemetics.
STUDY OBJECTIVE: To evaluate the efficacy and safety of propofol (at a subhypnotic dose), droperidol, and metoclopramide in reducing emetic symptoms during cesarean delivery. DESIGN: Randomized, double-blinded, placebo-controlled study. SETTING: University hospital. PATIENTS: 100 ASA physical status I and II parturients undergoing cesarean delivery with spinal anesthesia. INTERVENTIONS: Patients received placebo (saline) followed by placebo (Intralipid(R)), placebo (saline) followed by propofol at a subhypnotic dose (1.0 mg/kg/hr), droperidol 1.25 mg followed by placebo (Intralipid(R)), or metoclopramide 10 mg followed by placebo (Intralipid(R)) intravenously (IV) immediately after clamping of the umbilical cord. MEASUREMENT AND MAIN RESULTS: The percentage of patients who were emesis-free, which was defined as experiencing no nausea, retching, or vomiting, in the intraoperative, postdelivery period was 80% with propofol, 80% with droperidol, and 78% with metoclopramide (p < 0.05), compared with placebo (40%). Severity of nausea was less inpatients who received propofol than in those who received placebo (p < 0.05), and there were no differences seen among the droperidol, metoclopramide, and placebo groups. No clinically serious adverse events as a result of the study drugs were observed in any of the groups. CONCLUSIONS: Prophylactic antiemetic efficacy of propofol at a subhypnotic dose (1.0 mg/kg/hr), droperidol 1.25 mg, and metoclopramide 10 mg is comparable in parturients undergoing cesarean delivery. Moreover, propofol at a subhypnotic dose is effective in the prevention of severe nausea.
Adult↗
p33(ING1b) stimulates the transcriptional activity of the estrogen receptor alpha via its activation function (AF) 2 domain.
The ING1 gene was originally cloned as a candidate tumor suppressor of human breast cancer, and recent studies suggest that ING1 proteins are involved in chromatin remodeling functions via physical association with both histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we investigated whether p33(ING1b), one of the major ING1 isoforms, modulated the transcriptional activity of estrogen receptor (ER) alpha. In Cos-7 cells transfected with increasing concentrations of a mammalian expression vector encoding for p33(ING1b), estrogen-induced ERalpha transcriptional activity was found to increase in a dose-dependent manner. As p33(ING1b) expression levels increased, transcription of an ER-responsive reporter gene by either estrogen-inducible full-length ERalpha or activation function (AF) 1 deletion mutant was enhanced, while the AF2 deletion mutant was unaffected by the presence of p33(ING1b). These results showed that p33(ING1b) enhanced estrogen-induced ERalpha activity through the AF2 domain. Our data also demonstrated that the antiestrogens inhibited the transcriptional activity of ERalpha as stimulated by p33(ING1b). Furthermore, a weak physical association was observed between in vitro translated p33(ING1b) and ERalpha. Our data presented here demonstrate that p33(ING1b) acts like a coactivator for ERalpha and stimulates estrogen-induced ERalpha transcriptional activity consistent with a function for p33(ING1b) in chromatin remodeling.
Animals↗
Expression of PPAR-gamma is correlated with the clinical course of neuroblastoma.
BACKGROUND/PURPOSE: Neuroblastoma is a common pediatric tumor of the sympathetic nervous system. Unlike the ones found in older children, the tumors found in patients younger than one year of age often show spontaneous differentiation and regression. Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily is expressed in several human cancers. Recently, PPAR-gamma has been reported to be expressed in neuroblastoma, and the agonist of this receptor caused differentiation of neuroblastoma cells. METHODS: In this report we studied the expression of PPAR-gamma mRNA, using LightCycler in neuroblastoma samples diagnosed in 17 patients under the age of one year. RESULTS: Twelve samples showed PPAR-gamma mRNA expression. There was no significant difference in the PPAR-gamma mRNA expression based on age, histology, staging, and DNA ploidy. The PPAR-gamma mRNA expression level was significantly correlated with the change in urinary vanillyl mandelic acid (VMA). The neuroblastoma samples resected from patients who showed a decrease in their urinary VMA before the operation showed significantly higher PPAR-gamma expression than those from patients who showed an increase in their urinary VMA before the operation. CONCLUSIONS: PPAR-gamma may have played a role in the reduction of VMA and possibly in the regression of early-onset neuroblastoma.
Female↗
Glycosylphosphatidyl inositol-anchored protein (GPI-80) gene expression is correlated with human thymoma stage.
Thymoma is one of the most common solid tumors in the mediastinum. Because there is no typical cell line for human thymoma, the development and use of molecular-based therapy for thymoma will require detailed molecular-genetic analysis of patients' tissues. Recent reports showed that genetic aberrations in thymoma were most frequently seen in chromosome 6q regions. We investigated the use of oligonucleotide arrays to monitor in vivo expression levels of genes in chromosome 6 regions in early- (stage I or II) and late- (stage IVa) stage thymoma tissues from patients. These in vivo gene expression profiles were verified by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) using LightCycler for 48 thymoma patients and sandwich ELISA for 33 thymoma patients. Using both methods, a candidate gene was identified which was overexpressed in stage IV thymoma. This was a known glycosylphosphatidyl inositol (GPI)-anchored protein (GPI-80), which is highly homologous with Vanin-1, a mouse thymus homing protein. Serum level of GPI-80 was confirmed to be elevated in stage IV thymoma compared with in stage I thymoma by using sandwich ELISA. The combined use of oligonucleotide microarray, real-time RT-PCR, and ELISA analyses provides a powerful new approach to elucidate the in vivo molecular events surrounding the development and progression of thymoma.
Amidohydrolases↗
The effect of inhaled colforsin daropate on contractility of fatigued diaphragm in dogs.
UNLABELLED: We studied the effect of inhaled colforsin daropate, a water-soluble forskolin derivative, on the contractility of fatigued diaphragm in dogs. Animals were divided into 3 groups of 8. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation applied for 30 min. Immediately after the end of the fatigue-producing period, Group 1 received inhaled vehicle, Group 2 received inhaled colforsin daropate 0.1 mg/mL, and Group 3 received inhaled colforsin daropate 0.2 mg/mL. We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). After fatigue was produced, in each group, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), and there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups 2 and 3, during colforsin daropate inhalation, Pdi at both stimuli increased from fatigued values (P < 0.05). The increase in Pdi was significantly larger in Group 3 than in Group 2. The integrated electrical activity of the diaphragm did not change in any group. We conclude that inhaled colforsin daropate causes an increase in contractility of fatigued canine diaphragm in a dose-related fashion. IMPLICATIONS: Diaphragmatic fatigue may contribute to the development of respiratory failure. Inhaled colforsin daropate improves, in a dose-dependent manner, the contractility of fatigued diaphragm in dogs.
Administration, Inhalation↗
Olprinone for the treatment, but not prevention, of fatigue-induced changes in guinea-pig diaphragmatic contractility.
UNLABELLED: Olprinone, a phosphodiesterase III inhibitor, improves the contractility in fatigued diaphragm in vivo, but no data are available for the treatment and prevention of fatigue-induced changes in vitro. We therefore examined the efficacy of Olprinone for the treatment and prevention of fatigue-induced changes in guinea-pig diaphragmatic contractility. The guinea-pig diaphragm strips were randomly allocated according to dose of Olprinone (0, 10(-6), 10(-5), and 10(-4) M) (n = 7 each) and were stimulated directly in an organ bath. Diaphragmatic contractility was measured by assessing twitch tension and force at 20-Hz and 100-Hz stimulation. Diaphragmatic fatigue was induced by generating rhythmic, repetitive contractions produced by 20-Hz stimulation for 5 min. In the first experiment, after the fatigue-producing period, Olprinone was administered to the organ bath for 5 min. In the second experiment, Olprinone was pretreated for 5 min, and then diaphragmatic fatigue was produced. In Experiment 1, after a fatigue-producing period, tetanic force to each stimulus decreased from baseline values (P < 0.05). Olprinone 10(-5)-10(-4) M caused an increase in force at both stimuli from fatigued values (P < 0.05). In Experiment 2, no change in tetanic force was observed by pretreatment with Olprinone (0-10(-4) M). After producing fatigue, tetanic force to each stimulus decreased from baseline values (P < 0.05). These results suggest that Olprinone 10(-5)-10(-4) M improves the fatigue-induced changes in guinea-pig diaphragmatic contractility and that pretreatment with Olprinone does not prevent diaphragmatic fatigability. IMPLICATIONS: Olprinone is effective for the treatment, but not prevention, of fatigue-induced changes in guinea-pig diaphragmatic contractility.
Animals↗
Midazolam-induced muscle dysfunction and its recovery in fatigued diaphragm in dogs.
Midazolam, widely used for sedation and anesthesia, decreases contractility in nonfatigued diaphragm; however, its effects on contractility in fatigued diaphragm that are implicated as a cause of respiratory failure have not been established. We therefore studied the effects of midazolam on diaphragm muscle function and recovery in fatigued diaphragm. Dogs were divided into three groups of eight each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation for 30 min. When fatigue was established, Group I received no study drug; Group II was infused with a sedative dose (0.1 mg x kg(-1) x h(-1)) of midazolam; and Group III was infused with an anesthetic dose (0.5 mg x kg(-1) x h(-1)) of midazolam. We assessed diaphragm muscle function (contractility and electrical activity) by transdiaphragmatic pressure (Pdi) and integrated electrical activity of the diaphragm (Edi). In the presence of fatigue, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), Pdi at high-frequency (100-Hz) stimulation did not change, and Edi to each stimulus did not change. With an infusion of midazolam, in Groups II and III, Pdi at both stimuli and Edi at 100-Hz stimulation decreased from fatigued values (P < 0.05). The decrease in Pdi and Edi was more in Group III than in Group II (P < 0.05). At 60 min after the cessation of midazolam administration, in Group II, Pdi and Edi recovered from midazolam-induced values (P < 0.05) and returned to fatigued values. In Group III, Pdi and Edi did not change from midazolam-induced values. We conclude that midazolam causes, in a dose-related manner, diaphragm muscle dysfunction in fatigued canine diaphragm and that at a sedative dose, but not at an anesthetic dose, midazolam does not delay its recovery.
Anesthetics, Intravenous↗
[Effects of diltiazem on contractility and electromyographic activity of non-fatigued diaphragm in dogs].
BACKGROUND: No data are available for diltiazem on muscle function (contractility and electomyographic activity) of non-fatigued diaphragm. METHODS: Eighteen pentobarbital-anesthetized dogs were divided into 3 groups of 6 each: Group I received no drug; Group II received small-dose of diltiazem (0.1 mg.kg-1.h-1); Group III received large-dose of diltiazem (0.5 mg.kg-1.h-1). Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi), the difference between esophageal and gastric pressures. Diaphragmatic electromyographic activity (Edi) was measured by means of electrodes placed at the anterior portion of the crural and costal parts of the diaphragm. After measuring baseline values of Pdi and Edi at 20 Hz and 100 Hz stimulation, the study drug was administered for 30 min. RESULTS: With infusion of diltiazem, Pdi and Edi to each stimulus did not change in Groups II and III. In Group I, these variables also showed no change. CONCLUSIONS: Diltiazem, at doses below 0.5 mg.kg-1.h-1, does not affect contractility and electromyographic activity of non-fatigued canine diaphragm.
Animals↗
Decreased expression of DFF45/ICAD is correlated with a poor prognosis in patients with esophageal carcinoma.
BACKGROUND: DNA fragmentation factor 45 (DFF45)/inhibotor of caspase activated DNAse (ICAD) forms a complex with DFF40/CAD and inhibits its DNA cleaving function during apoptosis. DFF45 also functions as a chaperone for native DFF40 and is necessary for its function. It has been indicated that defects in the apoptotic pathway may exist in neoplastic cells. METHODS: The authors investigated mRNA expression of DFF45 in a series of 46 esophageal squamous cell carcinoma (ESCC) specimens using polymerase chain reaction amplification. The results were correlated with the patients' clinicopathologic characteristics. RESULTS: DFF45 mRNA expression was significantly lower in tumors with higher pathologic stage, higher tumor status (T status), lymph node metastasis, or more extensive lymphatic invasion. Patients who had low DFF45 mRNA expression (indicated by the ratio of DFF45 mRNA expression in tumor to DFF45 mRNA expression in normal esophageal mucosa [tumor:normal] < 1) had a significantly shorter survival after undergoing surgery compared with patients who had high DFF45 mRNA expression (tumor:normal > 1, P = 0.0006; log-rank test, P = 0.0003; median follow-up, 14.6 months). CONCLUSIONS: Patients with ESCC with decreased DFF45 mRNA expression levels had a poor prognosis compared with patients who had high DFF45 mRNA expression levels.
Aged↗