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1.
Azasetron, a selective 5-HT3 receptor antagonist, has been previously shown to be highly effective in the prophylaxis of nausea and vomiting induced by anticancer drugs and is widely used in the clinical setting in Japan. In order to improve the antiemetic effect of azasetron, we designed a continuous intravenous infusion method of this drug and compared the antiemetic effect of this method with that of standard bolus intravenous injection on nausea and vomiting associated with anticancer drugs including 75 mg/m2 cisplatin (CDDP). A continuous group is intravenous bolus injection of 2.5 mg azasetron followed by 7.5 mg continuous intravenous infusion for 24 hrs, and a bolus group is intravenous bolus injection of 10 mg azasetron. The inhibitory effect on nausea of the continuous group was significantly superior to those of the bolus group on day 3 and 4 (p < 0.05) and inhibitory effect on vomiting of the continuous group was significantly superior to those of bolus group on day 2 (p < 0.05). No adverse effects were observed in either group of this study. From these data, continuous intravenous infusion of azasetron was considered to be highly effective in prophylaxis of nausea and vomiting induced by anticancer drugs.  相似文献   

2.
In this prospective, randomized, double-blinded study, we evaluated the efficacy of the oral antiemetics, granisetron and domperidone, for the prevention of postoperative nausea and vomiting (PONV) in 100 women undergoing major gynecologic surgery. Patients received either granisetron 2 mg or domperidone 20 mg (n = 50 in each group) orally 1 h before surgery. Standardized anesthetic techniques and postoperative analgesia regimens were used. Complete response (defined as no PONV and no administration of rescue antiemetic medication) for 0-3 h after anesthesia was 88% with granisetron and 52% with domperidone; the corresponding incidence for 3-24 h after anesthesia was 86% and 48% (P < 0.05). No clinically important adverse events due to the drugs were observed in any of the groups. In conclusion, the efficacy of preoperative oral granisetron is superior to that of domperidone for the prevention of PONV after major gynecologic surgery. IMPLICATIONS: We compared the efficacy of granisetron and domperidone administered orally for the prevention of postoperative nausea and vomiting in women undergoing gynecologic surgery. Preoperative oral granisetron was more effective than domperidone.  相似文献   

3.
4.
OBJECTIVES: The main aim was to calculate the prevalence of mental pathology in women between 18 and 70 in a Health District of Pamplona; second, to describe comorbidity and to analyse how mental pathology was recorded in the clinical histories. DESIGN: An observational crossover study with randomised selection. SETTING: A community study in the Txantrea quarter of Pamplona, covering 21,590 inhabitants, with 7605 women between 18 and 70. PATIENTS: Randomised sample, stratified by age, of 237 women between 18 and 70 taken from the 1991 Census. MEASUREMENTS AND RESULTS: In a face-to-face interview at the Health Centre, the DIS Questionnaire, which diagnoses mental illness, was administered to all participants. A check was made to see if mental pathology was recorded in their clinical history. The prevalence of mental illnesses, mainly Phobias and Depression, in the "last year of life" was 33.3% (27.5-39.5), which fell to 24.9% (19.7-30.7) when tobacco abuse was excluded. The most common pathologies were: Depression (17.3%), Tobacco dependency (17.3%), simple Phobia (14.8%), Agoraphobia (13.5%), social Phobia (8.9%) and post-traumatic stress (8.0%). CONCLUSIONS: Understanding the high psychological morbidity in these urban women can contribute to the development of Mental Health Promotion and Prevention Programmes and foment fuller mental health training for Primary Care professionals.  相似文献   

5.
Recently, Granisetron (KYT) was proved to have a strong effect for cisplatin (CDDP)-induced emesis. We compared the effect of KYT for CDDP-induced emesis between two different administration schedules. Forty micrograms/kg of KYT was administered either by 30-minute drip infusion with 100 ml of saline (Group A) or 30-second injection with 10 ml of saline (Group B). We investigated the therapeutic effect of KYT in both group A and Group B by the crossing-over method. After the patients who had a malignant tumor and were going to receive CDDP (over 50 mg/m2) in two courses were selected, KYT was administered by the method of Group A or Group B in a double-blind comparison. The clinical efficacy was at least "effective" in 70% (7/10) of Group A and Group B. The study treatment was considered "useful" in 80% (8/10) of Group A, 90% (9/10) of Group B, and "safe" in 100% of Group A and B. There was no difference between two groups in this respect. The results showed that the slow intravenous injection of KYT also has an excellent antiemetic effect on CDDP-induced emesis and a high degree of safety.  相似文献   

6.
Thirty patients receiving cisplation or non-cisplatin (containing cyclophosphamide and adriamycin) chemotherapy were enrolled in a randomized, crossover study comparing the efficacy of single dose of Navoban (tropisetron, 5 mg) and Kytril (granisetron, 3 mg). The effective control of acute vomiting induced by cisplatin was achieved in 95.2% (20/21) of patients receiving Navoban and 90.5% (19/21) in those receiving Kytril. Complele control rate was 71.4% (15/21) in Navoban arm, and 81.0% (17/21) in Kytril arm. Total control of delayed vomiting (day 2-5) was 71.4%-90.4% in Navoban arm, while it was 66.7%-4% in Kytril arm. The effective control of vomiting induced by non-cisplatin drugs was achieved in 9/9 in both arms. It is concluded that both agents are effective in the control of vomiting induced by chemotherapy. They have identical adverse effects and are well tolerated by the patients.  相似文献   

7.
PURPOSE: The antiemetic effectiveness and safety of single-dose oral granisetron were compared with intravenous (I.V.) ondansetron in chemotherapy-naive patients who received moderately emetogenic chemotherapy. PATIENTS AND METHODS: In this double-blind, parallel-group study, patients naive to emetogenic chemotherapy (N = 1,085) who were scheduled to receive cyclophosphamide- (500 to 1,200 mg/m2) or carboplatin (> or = 300 mg/m2) based chemotherapy, were randomized to receive either oral granisetron (n = 542) or I.V. ondansetron (n = 543). Efficacy assessments included the proportion of patients in each treatment group with total control over the 24 and 48 hours following chemotherapy initiation, as well as incidence and severity of nausea and emesis and use of antiemetic rescue medication. Prophylactic corticosteroids were allowed. Safety assessment was based on patients' reports of adverse experiences. RESULTS: Approximately 80% of patients received prophylactic corticosteroids. Single-dose oral granisetron (2 mg) and I.V. ondansetron (32 mg) resulted in equivalent levels of total emetic control during the first 48 hours after chemotherapy. The proportion of nausea- and emesis-free patients at 24 and 48 hours were also approximately equivalent. The most commonly reported adverse experiences were headache, asthenia, and constipation. More patients who received ondonsetron than granisetron reported dizziness (9.6% v 5.4%, respectively; P = .011) and abnormal vision (4.2% v 0.6%, respectively; P < .001). CONCLUSION: A single oral dose of granisetron (2 mg) resulted in equivalent levels of antiemetic protection as I.V. ondansetron (32 mg). Both agents were well tolerated, although more dizziness and abnormal vision were reported with ondansetron. Because the two antiemetic regimens exhibited equivalent efficacies, additional factors such as convenience and cost of therapy should be considered.  相似文献   

8.
9.
We investigated the efficacy and safety of two methods of granisetron injection to treat nausea and vomiting induced by chemotherapy for tumors in hematopoietic organs. The methods of administration were intravenous drip infusion over 30 minutes, which is the conventional method, and intravenous bolus injection. In this study, 89.5% of patients in both groups (17/19 for each) were free from vomiting. No serious adverse events were observed in either administration group. Abnormal laboratory test values suspected to be related to granisetron were observed in 3 cases in the bolus injection group and in 2 cases in the drip infusion group. but did not pose any clinical problem. These results demonstrated the safety of both methods of administration. In conclusion, it is considered that granisetron intravenous bolus injection can be considered as the method of choice for the prevention of nausea and vomiting induced by chemotherapy for tumors in hematopoietic organs.  相似文献   

10.
In this in vitro study the retentive strength of enamel, either conventionally etched with a phosphoric acid gel or conditioned with an oxalic acid containing etching agent, was investigated. Five experimental restorative resins with filler contents between 0 and 78% by weight were polymerized on the etched enamel surfaces. In spite of the pronounced micromorphological differences of the patterns generated with the two etching agents, the bond strengths mediated were very similar. Application of an intermediate low-viscous or adhesive resin had no influence on bond strength. Exponential relationships were found between the filler content of the resins on the one hand and their flexural moduli and flexural strengths on the other. Significant exponential relations were also demonstrated between filler content and bond strength to the etched enamel surface. The linear relationship between mechanical properties of the resins and their bond strengths to etched enamel indicates that debonding occurred by cohesive failure in resin.  相似文献   

11.
Apoptosis mediated by anticancer drugs may involve activation of death-inducing ligand/receptor systems such as CD95 (APO-1/Fas), cleavage of caspases, and perturbance of mitochondrial functions. We investigated the sequence of these events in SHEP neuroblastoma cells transfected with Bcl-2 or Bcl-X(L) using two different drugs, namely, doxorubicin (Doxo), which activates the CD95/CD95 ligand (CD95-L) system, and betulinic acid (Bet A), which does not enhance the expression of CD95 or CD95-L and which, as shown here, directly targets mitochondria. Apoptosis induced by both drugs was inhibited by Bcl-2 or Bcl-X(L) overexpression or by bongkrekic acid, an agent that stabilizes mitochondrial membrane barrier function, suggesting a critical role for mitochondria. After Doxo treatment, enhanced CD95/CD95-L expression and caspase-8 activation were not blocked by Bcl-2 or Bcl-X(L) and were found in cells with a mitochondrial transmembrane potential (delta psi(m)) that was still normal (delta psi(m)high cells). In marked contrast, after Bet A treatment, caspase-8 activation occurred in a Bcl-2- or Bcl-X(L)-inhibitable fashion and was confined to cells that had lost their delta psi(m) (delta psi(m)low cells). Mitochondria from cells treated with either Doxo or Bet A induced cleavage of both caspase-8 and caspase-3 in cytosolic extracts. Thus, caspase-8 activation may occur upstream or downstream of mitochondria, depending on the apoptosis-initiating stimulus. In contrast to caspase-8, cleavage of caspase-3 or poly(ADP-ribose)polymerase was always restricted to delta psi(m)low cells, downstream of the Bcl-2- or Bcl-X(L)-controlled checkpoint of apoptosis. Cytochrome c, released from mitochondria undergoing permeability transition, activated caspase-3 but not caspase-8 in a cell-free system. However, both caspases were activated by apoptosis-inducing factor, indicating that the mechanism of caspase-8 activation differed from that of caspase-3 activation. Taken together, our findings demonstrate that perturbance of mitochondrial function constitutes a central coordinating event in drug-induced cell death.  相似文献   

12.
Centromerically located alphoid satellite DNAs are present in all primates. They typically consist of arrays of a 340-bp monomeric unit that is composed of related, but diverged, 170-bp subunits. A unique monomeric unit has recently been described: the alphoid satellite monomers of the neotropical primate Chiropotes satanas (bearded saki) are typically 539 bp in length. In addition, a number of smaller satellite sequences are present in this species. Analysis of two primates closely related to Chiropotes, Pithecia irrorata (saki) and Cacajao melanocephalus (uakari), show that they also contain unique alphoid satellites that are different from those of Chiropotes and different from one another. Southern blot and sequence analyses suggest that an alphoid satellite rearrangement(s) occurred early in the history of the tribe Pitheciini (Chiropotes, Pithecia, Cacajao) and that rearrangements are continuing to occur in this group of primates.  相似文献   

13.
BACKGROUND: Eclampsia remains a serious complication of pregnancy and childbirth and factors related to morbidity require continued evaluation. DESIGN: Retrospective case-control study on the incidence and outcome of eclampsia. SETTING: A defined total island population over 20 years. METHODS: All centrally collected birth registration returns in Iceland for the years 1972-1991 were reviewed to identify women with the diagnosis of eclampsia, selecting women delivering immediately before and after the eclamptic case as controls. Information from all places where women had delivered was obtained to ensure that no case was missed. Maternity records were reviewed to verify the diagnosis and obtain maternal and neonatal data. RESULTS: Forty women had eclampsia (0.046% of deliveries). The incidence diminished between the decades 1972-81 and 1982-91 (p < 0.05), as did the incidence of eclamptic convulsions before delivery. Eclamptic women were more often primiparous, younger and delivered earlier than controls. Preterm delivery and a low ponderal index were more common among offspring of the eclamptic mothers and the male/female ratio was lower. CONCLUSION: The incidence of eclampsia in the population is falling. Common features related to the condition were confirmed. Severe maternal illness is rare, but the babies often appear growth-retarded and are delivered preterm.  相似文献   

14.
We examined the efficacy of concurrent use of ondansetron hydrochloride and dexamethasone, and the effective dose of dexamethasone against nausea and vomiting in lung cancer patients receiving chemotherapy including single high dose cisplatin. The study was carried out on total of 44 courses of chemotherapy in either initial onset or recurrence of lung cancer. The patients were given 4 mg of ondansetron injection on the day of cisplatin injection (Day 1), and 4 mg/day of ondansetron tablet for Days 2 to 4. These patients were randomly allocated into 2 groups, i.e., those who, on Day 2, concomitantly received 10 mg of dexamethasone (D10 Group, 22 courses) or 20 mg (D20 Group, 22 courses), for comparing the antiemetic effects in a different concomitant dose of dexamethasone. An efficacy rate of 70% or more was achieved in each group for acute emesis on Day 1. The efficacy rate was 80% or above for emesis on Day 2 when dexamethasone was concurrently administered, and Days 3 and 4 in both groups. No significant difference was observed between the groups. A higher complete suppression rate against nausea was seen in D20 Group even though the difference from D10 Group was not significant. Furthermore, food intake rate on Day 2 was significantly better in D20 Group. However, in the cases that were graded effective or markedly effective for acute emesis on Day 1, the efficacy rate was also high in both groups through Days 2-4. It was notable that the efficacy rate of Days 2-4 was 100% in D2 Group. The high efficacy rate was shown in male patients regardless of which dose of dexamethasone was used. However, control of emesis was unfavorable in female patients on Day 1 and was still unfavorable even though dexamethasone was combined from Day 2. We considered from the above results that 10 mg/day of concurrent dexamethasone is sufficient in suppression of delayed emesis on Day 2. However, in order to improve nausea or food intake, or to suppress emesis in patients who are highly likely to show unfavorable control for Day 2 and onward, 20 mg/day should also be effective.  相似文献   

15.
OBJECTIVE: To compare the safety and efficacy of a combination of amoxicillin and clavulanate potassium given orally every 12 hours (amoxicillin, 875 mg; clavulanate, 125 mg) with that given every 8 hours (amoxicillin, 500 mg; clavulanate, 125 mg) for the treatment of patients with acute bacterial maxillary sinusitis. DESIGN: Multicenter double-blind randomized double-dummy controlled trial. SETTING: Physicians' offices and ambulatory care clinics. PATIENTS: One hundred seventy patients at least 18 years of age with acute bacterial maxillary sinusitis who could be treated with an oral antimicrobial agent were randomized, and data from 134 were suitable for evaluation. Four patients were withdrawn from this study because of adverse effects. INTERVENTIONS: Patients received a combination of amoxicillin and clavulanate orally every 12 hours (amoxicillin, 875 mg; clavulanate, 125 mg) or every 8 hours (amoxicillin, 500 mg; clavulanate, 125 mg) for 14 days. MAIN OUTCOME MEASURE: Clinical success at the end of therapy. RESULTS: Clinical success at the end of therapy was similar for the 2 treatment groups, 93% and 88% of patients in the every 12-hour and every 8-hour groups, respectively (P = .76; 95% confidence interval, -4.0% to 15.6%). Clinical success rates at follow-up 2 to 4 weeks after the end of therapy were also similar in the 2 groups. Adverse events related to treatment were reported with similar frequency in the 2 groups. CONCLUSION: Amoxicillin and clavulanate given every 12 hours is as effective and as safe as administration every 8 hours for the treatment of acute bacterial maxillary sinusitis.  相似文献   

16.
1. P2X-receptors are ligand-gated ion channels which activate within milliseconds of agonist binding, causing rapid cellular depolarization and excitation. This makes them ideally suited to mediate the rapid neurotransmitter functions of adenosine 5'-triphosphate (ATP). 2. The initial postjunctional response of the vas deferens and most blood vessels to sympathetic nerve stimulation is a rapid, transient excitatory junction potential (EJP). With sufficient stimulation EJPs summate and the membrane depolarizes sufficiently to open voltage-dependent calcium channels, initiating a calcium action potential and contraction. 3. EJPs are inhibited by desensitization of the P2X-receptor by the stable agonist alpha, beta-methyleneATP (alpha, beta-meATP) and by the P2X-receptor antagonists ANAPP3, suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, indicating that they are consequent upon activation of the P2X-receptor. 4. The P2X-receptor was originally defined by contractile studies in smooth muscle preparations, where a rank order of agonist potency of alpha, beta-meATP > > 2-methylthioATP (2-meSATP) > or = ATP was found. However, recent results show that the potency of ATP and 2-meSATP, but not alpha, beta-meATP, is decreased by 100-to 1000-fold by breakdown and when this is prevented, ATP and 2-meSATP are more potent than alpha, beta-meATP as agonists at the P2X-receptor. 5. This conclusion was supported by the cloning and functional expression of the P2X1-receptor from the rat bladder. A total of seven P2X-subunits have since been cloned and the P2X1-subunit is thought to be the predominant subunit expressed in vascular smooth muscle cells.  相似文献   

17.
In a prospective, randomized, double-blind, placebo-controlled, multicentre study, the efficacy of prophylactic tropisetron (2 mg) or ondansetron (4 mg) for the prevention of post-operative nausea and vomiting after abdominal or non-abdominal surgery with general balanced anaesthesia was studied in 842 ASA I-III patients. In patients undergoing abdominal surgery, ondansetron and tropisetron reduced the frequency of emetic episodes compared with the placebo (29%, 30% vs. 42% respectively). In men, neither tropisetron nor ondansetron had an effect different from the placebo, whereas in women both drugs led to lower rates of emetic episodes and nausea. In comparison with abdominal surgery, fewer patients in the non-abdominal surgery subgroup had emetic episodes (42% vs. 23% in the placebo group). However, neither tropisetron nor ondansetron was significantly different from the placebo in this patient subgroup. In conclusion, for patients at increased risk of post-operative nausea and vomiting, a prophylactic therapy at the lowest effective dose with tropisetron or ondansetron may be useful.  相似文献   

18.
Caspase-3(-like) proteases play important roles in controlling mammalian apoptosis. However, the downstream events from the caspase-3(-like) protease activation to death of cells are still unclear. Previously, we reported that hydrogen peroxide (H2O2) was generated by the activation of caspase-3(-like) proteases in the process of tyrosine kinase inhibitor-induced apoptosis in human small cell lung carcinoma Ms-1 cells. In the present study, we examined whether generation of H2O2 is a critical event for the apoptotic pathway downstream of caspase-3(-like) protease activation by various anticancer drugs. Anticancer drugs such as camptothecin, vinblastine, inostamycin, and adriamycin induced activation of caspase-3(-like) proteases and apoptosis. Generation of H2O2 was commonly detected after treatment with each of the four anticancer drugs, and scavenging of H2O2 caused cells to fail to undergo apoptosis. Moreover, anticancer drug-induced H2O2 production was inhibited not only by an inhibitor of caspase-3(-like) proteases but also by diphenyleneiodonium chloride, an inhibitor of flavonoid-containing enzymes such as NADPH oxidase. However, activation of caspase-3(-like) proteases was not inhibited by diphenyleneiodonium chloride. These findings suggest that activation of caspase-3(-like) proteases by various anticancer drugs causes generation of H2O2 presumably through the activation of NADPH oxidase, thereby inducing apoptosis. Therefore, H2O2 may function as a common mediator for apoptosis induced by various anticancer drugs.  相似文献   

19.
Dolasetron (dolasetron mesilate) is a pseudopelletierine-derived 5-HT3 antagonist which has recently become available for clinical use. It is rapidly converted in vivo to its active major metabolite, hydrodolasetron, which appears to be largely responsible for its pharmacological activity. In clinical trials, single intravenous or oral doses of dolasetron were effective in preventing acute chemotherapy-induced nausea and vomiting (CINV). Intravenous doses of 1.8 mg/kg achieved complete suppression of vomiting in approximately 50% of patients receiving highly emetogenic cisplatin-containing chemotherapy and in approximately 60 to 80% of patients receiving moderately emetogenic chemotherapy. In the latter setting, oral doses of 200 mg achieved similar response rates. In comparative studies, intravenous dolasetron 1.8 mg/kg was as effective as intravenous granisetron 3 mg or ondansetron 32 mg after highly emetogenic chemotherapy, and oral dolasetron 200 mg was equivalent to multiple oral doses of ondansetron (3 or 4 doses of 8 mg) after moderately emetogenic chemotherapy. Dolasetron 1.8 mg/kg was superior to metoclopramide in preventing emesis induced by high dose cisplatin or by moderately emetogenic chemotherapy in high risk subgroups. Dolasetron has also shown efficacy in preventing radiotherapy-induced nausea and vomiting (RINV) in preliminary studies. Single intravenous or oral dolasetron doses ranging from 12.5 to 100 mg and 25 to 200 mg, respectively, were significantly more effective than placebo in preventing postoperative nausea and vomiting (PONV) in female surgical patients. A 50 mg intravenous dose was as effective in preventing PONV as ondansetron 4 mg in a mixed-gender group. Intravenously administered dolasetron was also effective in treating established PONV, although complete suppression of vomiting was achieved in < 40% of patients. Dolasetron has a tolerability profile characteristic of this class of compounds, with headache, dizziness and diarrhoea being the most commonly occurring adverse events in clinical trials. Diarrhoea is not thought to be related to dolasetron administration, being experienced mostly by patients receiving chemotherapy. Dolasetron and other 5-HT3 receptor antagonists have been associated with minor changes in ECG intervals, but these generally do not appear to be clinically important. Thus, available evidence suggests that dolasetron will provide an alternative to other 5-HT3 receptor antagonists for the management of CINV and PONV. Further studies are required to determine whether it offers any advantages over other agents in these settings and to determine the optimum dosage for preventing RINV.  相似文献   

20.
The effect of granisetron in preventing nausea and emesis induced by intraarterial chemotherapy was comparatively studied with a historical control group (46 cases) in 50 patients with hepatocellular carcinoma receiving intraarterial anti-tumor drugs such as cisplatin and doxorubicin. Emesis was perfectly controlled in 39 out of 50 patients in the treatment group (78%), in comparison to 33 out of 46 patients (71.7%) in the historical control group. This represented no statistical significance between the two groups. In terms of the severity of nausea, however, the granisetron group demonstrated significant superiority to the control group with 27 out of 50 patients (54%) being free of symptoms compared with 16 out of 46 patients (34.8%) in the control group. A stratified analysis of the data also demonstrated significant superiority of the granisetron group over the historical group in the number of emetic episodes and the severity of nausea in female patients, who are more predisposed to emesis. The above results confirm the usefulness of granisetron as an antiemetic agent used for the prevention of acute nausea and emesis induced by intraarterial chemotherapy.  相似文献   

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