Antiemetic prophylaxis after laparoscopic cholecystectomy: comparative study of dehydrobenzperidol, metoclopramide, ondansetron and placebo

OBJECTIVES: To compare the efficacy of ondansetron to that of metoclopramide, dehydrobenzperidol and placebo for the prevention of postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy in a double-blind random study. PATIENTS AND METHOD: A total of 100 ASA I, II and III patients undergoing scheduled laparoscopic cholecystectomy were divided into 4 groups according to whether they received one of the following intravenously just prior to anesthetic induction: 1.25 mg dehydrobenzperidol (group D), 10 mg metoclopramide (group M), 4 mg ondansetron (group O) or 2 ml of saline (group P). All received general anesthesia with induction by thiopental, analgesia with fentanyl, muscle relaxation with atracurium and maintenance with oxygen-air and isoflurane. Episodes of nausea and/or vomiting during the first 24 h after surgery were recorded. Treatment was considered effective if no episodes occurred during this period. RESULTS: Nine of the 100 patients were excluded from the study. There were no significant differences in demographic variables among the 4 groups. The incidence of PONV was significantly greater in group P than in any of the other groups. There were no significant differences in PONV among groups D, M and O. CONCLUSIONS: Ondansetron provides safe, effective prophylaxis for PONV after laparoscopic cholecystectomy, but it is not superior to the antiemetic drugs usually used. Its use may be justified in patients in whom dehydrobenzperidol or metoclopramide are contraindicated.     

A randomized, double-blind, placebo controlled comparison of droperidol, ondansetron, and metoclopramide for the prevention of vomiting following outpatient strabismus surgery in children

STUDY OBJECTIVE: To compare the efficacy of ondansetron, droperidol, or metoclopramide with placebo in preventing postoperative vomiting following strabismus surgery. STUDY DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: University outpatient surgery center. PATIENTS: 160 ASA physical status I and II children ages 1 to 12 years who were scheduled for strabismus surgery. INTERVENTIONS: Administration of either ondansetron 100 mcg/kg, metoclopramide 250 mcg/kg, droperidol 75 mcg/kg, or placebo intravenously after induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Both ondansetron and droperidol were superior to metoclopramide and placebo in preventing predischarge vomiting, with incidences of 5%, 5%, 32%, and 25%, respectively. However, there was no difference in the incidence of postdischarge vomiting among the groups (ondansetron 25%, droperidol 25%, metoclopramide 20%, and placebo 25%). CONCLUSIONS: While both ondansetron and droperidol are more effective than metoclopramide when compared with placebo in decreasing the incidence of predischarge vomiting, none of these drugs was more effective than placebo in decreasing the incidence of postdischarge vomiting. Recovery from anesthesia was not significantly different among the groups as assessed by time to awakening, initial Steward score, and time to discharge.     

Post-laparoscopic vomiting in females versus males: comparison of prophylactic antiemetic action of ondansetron versus metoclopramide

PURPOSE: To evaluate the clinical usefulness of the continuous intra-arterial blood gas (CIABG) monitoring system, Paratrend 7, during differential lung ventilation (DLV) in 12 patients undergoing oesophagectomy. METHODS: Anaesthesia was induced with propofol and was maintained with isoflurane, oxygen and air, supplemented by an epidural infusion of mepivacaine. Arterial samples for estimation of blood gases (ABG) were taken just before and 5, 10, 20, 30, 60, and 90 min after the pleura was opened. The pH, PO2, and PCO2 values displayed by the CIABG monitor, which were recorded prior to the arterial blood sampling, were compared with the results of ABG analysis. RESULTS: Eighty-four blood samples were obtained and the ranges for the measured variables were PCO2 24.8-57.4 mmHg, PO2 47-449 mmHg, and pH 7.30-7.49. The correlation between CIABG and ABG measurements was strong and significant (r values: PCO2 0.80, PO2 0.93, pH 0.94). The overall bias +/- precision between the two methods was PCO2 0.9 +/- 3.1 mmHg, PO2 -1 +/- 40 mmHg, %PO2 0.8 +/- 21.6%, pH 0.00 +/- 0.02. For PO2 values < 150 mmHg, the biases +/- precision were PO2 -5 +/- 17 mmHg, %PO2 -2.1 +/- 20.7%. CONCLUSION: The agreement between CIABG and ABG measurements was better for PCO2 and pH than for PO2. Although the CIABG system is clinically useful for monitoring trends in blood gas changes, the accuracy of the PO2 value may be unacceptable during DLV because the error is theoretically < 34 mmHg with 95% reliability in the clinically important range of PO2, < 150 mmHg.     

A comparison of prophylactic ondansetron and metoclopramide administration in patients undergoing major neurosurgical procedures

In a prospective, randomised, double-blind trial, we assessed the relative efficacy of prophylactic ondansetron and metoclopramide administration in the reduction of postoperative nausea and vomiting in 60 patients undergoing routine major neurosurgical procedures. The patients were randomly allocated into one of two groups. Both groups received a standardised anaesthetic. When the dura mater was closed, patients in group A received an intravenous injection of metoclopramide 10 mg whilst group B received ondansetron 8 mg intravenously. Patients who received metoclopramide experienced less postoperative nausea and vomiting than those who received ondansetron in the 48 h following surgery (17 (56%) versus 9 (30%) p = 0.038). In the light of these findings, we believe that ondansetron is an inappropriate agent for the prevention of postoperative nausea and vomiting in the neurosurgical population.     

Prevention of postoperative nausea and vomiting with ondansetron: a prospective, randomized, double-blind study in 90 patients

Cortical variation in mammals and other terrestrial vertebrates, re-examined by current comparative methodology (out-group analysis), indicates that separate lateral (olfactory), dorsal and medial (hippocampal) pallial or cortical formations arose with the origin of vertebrates. Although the exact origin of mammalian isocortex (so-called neocortex) is still disputed, it appears that the earliest mammals already had a six-layered isocortex with ten to 20 functional subdivisions. Among placental mammals, at least, isocortex has expanded numerous times, producing additional cortical subdivisions. Because these expansions were independent transformations of a simpler cortex, they produced subdivisions that are not homologous.     

Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind, randomized comparative trial of ondansetron versus placebo

PURPOSE: To investigate the efficacy and safety of oral ondansetron in the control of cisplatin-induced delayed emesis in patients who do not require rescue antiemetic therapy for acute emesis. PATIENTS AND METHODS: Five hundred thirty-eight chemotherapy-naive patients who received cisplatin chemotherapy (> or = 70 mg/m2), and who were not rescued for acute emesis, were eligible to be randomized to receive one of the three oral regimens to control delayed emesis. Group I received placebo on days 2 to 6; group II received ondansetron 8 mg twice daily on days 2 and 3 and placebo on days 4 to 6; group III received ondansetron 8 mg twice daily on days 2 to 6. All patients received intravenous ondansetron (0.15 mg/kg every 4 hours for three doses) for the control of acute emesis on day 1. The number of emetic episodes on days 2 and 3 combined (days 2/3, when incidence and severity of delayed emesis were expected to be greatest) was considered the primary measure of efficacy. RESULTS: Patients who received odansetron had significantly fewer emetic episodes on days 2/3, 4, and 5 than those who received placebo (P < or = .002 on each day). Additionally, significantly more patients who received ondansetron had a complete plus major response (C+MR; < or = two two emetic episodes) than those who received placebo on days 2/3 (56% v 37%, P = .001), 4 (94% v 85%, P = .005), and 5 (98% v 88%, P = .006). Patients who received ondansetron had significantly less nausea on day 2/3 when day-1 nausea was used as the baseline score (P = .025). Patients who received ondansetron also had significantly less nausea on day 4 (P = .042) and the results approached significance on day 5 (P = .066). CONCLUSION: Oral ondansetron had a significant effect in the control of cisplatin-induced delayed emesis and nausea in patients who had not required rescue antiemetics during the acute emesis period. The control of delayed nausea and vomiting was most notable in the immediate 2 days following cisplatin administration, with the clinical difference narrowing between the two treatment arms on subsequent days.     

Prophylactic antiemetic therapy with patient-controlled analgesia: a double-blind, placebo-controlled comparison of droperidol, metoclopramide, and tropisetron

This placebo-controlled, randomized, double-blind trial was designed to evaluate the efficacy of three prophylactic antiemetic regimens on postoperative nausea and vomiting (PONV) during patient-controlled analgesia (PCA) with morphine. We studied 286 elective surgical patients for 36 h postoperatively. Group 1 was saline control. In Groups 2 and 3, metoclopramide or droperidol was administered as an intravenous (i.v.) bolus and then added to morphine in the PCA device. In Group 4, tropisetron, a long-acting investigational 5-hydroxytryptamine subtype 3 (5-HT3) antagonist was given as a single i.v. dose. We assessed the frequency and severity of PONV, as well as the need for rescue, frequency of side effects, and overall patient satisfaction. Severity of PONV was measured with a symptom-severity score (STS) which was based on both intensity and duration. The average total doses of antiemetics were metoclopramide 53.8 +/- 2.2 mg, droperidol 5.99 +/- 0.3 mg, and tropisetron 6.1 +/- 0.2 mg. Control patients had a 54% incidence of PONV. Droperidol reduced both the incidence (P < 0.001) and severity (P < 0.01) of PONV for the entire 36 h. Tropisetron reduced incidence and severity (P < 0.05), but the effect of the single bolus dose lasted only 18 h. Metoclopramide had a marginally significant effect under these conditions. Only droperidol decreased the need for rescue medication (P < 0.01), although rescue with tropisetron was highly effective. Side effects and patient satisfaction were comparable among the groups, but patients receiving droperidol were sleepier (P < 0.05) than control patients and recalled somewhat more anxiety (P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of prophylactic ondansetron hydrochloride and droperidol for strabismus repair in adults

BACKGROUND: Prophylactic administration of an antiemetic is a common procedure for patients undergoing strabismus surgery. Droperidol and ondansetron hydrochloride are commonly used antiemetics. This study compared the rates of postoperative nausea and vomiting (PONV) in adult patients undergoing strabismus surgery with prophylactically administered Droperidol or ondansetron hydrochloride. METHODS: A double-masked, randomized, prospective study was conducted comparing droperidol with ondansetron hydrochloride when administered prophylactically to adults undergoing strabismus surgery. RESULTS: Forty-five patients entered the study with a mean age of 30 years. Twenty percent of patients had nausea immediately postoperatively and 37% had nausea before discharge with no significant differences between groups. Overall rate of emesis, time in the recovery room, and time to discharge was not significantly different between the droperidol and ondansetron hydrochloride group. CONCLUSION: No real differences in the ability to prevent PONV between the two medications were found in this study.     

Treatment of pruritus in chronic liver disease with the 5-hydroxytryptamine receptor type 3 antagonist ondansetron: a randomized, placebo-controlled, double-blind cross-over trial

BACKGROUND: Recently, the serotonin antagonist ondansetron has been reported to have a positive effect on cholestasis-associated pruritus. OBJECTIVES: To study the effect of orally administered ondansetron on pruritus in chronic liver disease in a randomized, placebo-controlled, double-blind, cross-over study. METHODS: Subjective severity of pruritus was assessed using a visual analogue scale (VAS) recorded four times daily by the patients. After a one week pretreatment baseline period the patients were randomized to receive ondansetron tablets 8 mg tds or placebo tablets tds for one week. Following a one week wash-out period patients were switched to the other treatment for one week. The study was ended by an additional follow-up week without medication. For each day peak VAS values were determined and the mean value of the last five days of each week was calculated and referred to as the composite peak VAS score. RESULTS: We observed a significant but moderate reduction of the composite peak VAS score of 1.34 points (CI(95%): 0.12-2.56; P=0.033) during treatment with ondansetron as compared to placebo (treatment effect). In addition, a period effect was observed: a reduction of composite peak VAS score by 1.26 points (C1(95%): 0.04-2.48; P=0.044) was seen in the second treatment period as compared to the first period, irrespective of the kind of treatment. Although under treatment with ondansetron a significant improvement of itching as assessed by the VAS score was demonstrated, this treatment was not preferred over placebo by the patients. CONCLUSIONS: The 5-hydroxytryptamine receptor type 3 antagonist ondansetron has a small, but significant positive effect on pruritus in chronic liver disease as compared to placebo.     

The efficacy of lamotrigine in children and adolescents with refractory generalized epilepsy: a randomized, double-blind, crossover study

In the 9L rat brain tumour model the damage to tumour and normal brain by photodynamic therapy after intratumoural photosensitizer administration (intratumoural PDT) was studied. Twenty four rats received an intratumoural injection of 4 or 40 mm3 haematoporphyrin derivative (HpD, 5 mg ml-1), followed by interstitial irradiation with 20 Joule (J) (630 nm) 5 h later. For comparison, seven rats were treated with 20 Joule 24 h after an intravenous injection of 10 mg kg-1 HpD (intravenous PDT). With the chosen PDT parameters there was no important difference between the damaged areas produced by intratumoural PDT or intravenous PDT. No selective tumour kill was observed. Even though normal brain tissue was heavily damaged, vital tumour parts were still present. Intravenous PDT caused extensive diffuse damage to small blood vessels in tumour and surrounding normal brain. Intratumoural PDT was characterised by an infiltration of polymorphonuclear cells into damaged tissue, dilatation of larger blood vessels and gross haemorrhage. These results suggest an immediate vascular shutdown in the intravenous approach, while in the intratumoural approach the vasculature remained patent initially. Because of the severe side effects observed, the use of HpD seems not advisable for intratumoural PDT of brain tumours.     

Clonidine for major vascular surgery in hypertensive patients: a double-blind, controlled, randomized study

The utility of clonidine for hypertensive patients presenting for major vascular procedures remains debatable. Twenty-one hypertensive patients presenting for aortic surgery were given clonidine (n = 11) or placebo (n = 10) in a double-blind, randomized manner. Clonidine was administered 6 micrograms/kg per os 120 min before induction of anesthesia and 3 micrograms/kg intravenously (i.v.) over 60 min from aortic declamping to skin closure. Anesthesia was induced with alfentanil 20 micrograms/kg, midazolam, and atracurium and maintained with nitrous oxide 70%, an alfentanil infusion (0.25 microgram.kg-1. min-1), and isoflurane. Anesthetic requirements, circulatory variables, interventions, and isoproterenol dose-response curves (pre- and postoperatively) were determined. Plasma concentrations of clonidine, alfentanil, and vasoactive hormones were measured. When the clonidine group was compared with the placebo group, (a) isoflurane, alfentanil, and midazolam requirements were reduced by 38%, 42%, and 41%, respectively (P = 0.04, 0.03, 0.0002, respectively); (b) supplemental circulatory and anesthetic adjustments were reduced by 51% (P = 0.0006); (c) interventions with vasopressors were not significantly increased (placebo: two; clonidine: five); (d) systolic and mean arterial pressures and heart rate were reduced; (e) increases in norepinephrine, epinephrine, and plasma renin activity were suppressed, whereas vasopressin surge was attenuated; and (f) chronotropic response to isoproterenol was unaffected. Clonidine was effective in reducing anesthetic requirements and in improving circulatory stability in hypertensive patients presenting for major vascular procedures.     

A randomized, double-blind comparison of methoxamine and epinephrine in human cardiopulmonary arrest

The beneficial effect of epinephrine has been attributed to its alpha-adrenergic properties. The present study was designed to compare the effects of epinephrine and methoxamine in witnessed cardiac arrests. Consecutive, witnessed cardiac-arrest victims presenting to the emergency room or from the inpatient population of our institution were enrolled in this study. Patients were randomized to receive either epinephrine (2 mg bolus followed by 2 mg every 4 min) or methoxamine (40 mg bolus followed after 4 min by 40 mg) in a blind design. Patients were followed prospectively for survival and neurologic outcome. A total of 199 patients were randomized into the study, but 54 had to be retrospectively dropped from analysis for failure to comply with the study protocol. Of the 145 patients remaining, 77 received methoxamine (M) and 68 epinephrine (E). There was no difference in rate of successful resuscitation (42% versus 53%, M versus E, respectively), or in neurologic outcome as measured by the Glasgow-Pittsburgh Coma Score (GPCS). This study failed to demonstrate any difference in the rate of initial resuscitation, survival to discharge from the hospital, or neurologic status with methoxamine as opposed to epinephrine in the setting of cardiac arrest.     

Prevention of nausea and vomiting in female patients undergoing breast surgery: a comparison with granisetron, droperidol, metoclopramide and placebo

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.     

Paroxetine in the treatment of Chinese patients with depressive episode: a double-blind randomized comparison with imipramine

The application of the concept of ray vector fields to optical systems is reexamined. Paraxial or linear optics defines a four-dimensional ray vector field for any optical system: the vector field maps the incident ray vector into the emergent ray vector. In the case of thin systems, including thin astigmatic lenses, one can define a vector field of reduced dimensionality: the vector field is two-dimensional and maps the ray's incident position into the change in reduced direction. When the index of refraction is the same before and after a thin system, the change in reduced direction is the reduced deflection through the system or the reduced prismatic effect. Contrary to what has recently been claimed, this type of two-dimensional vector field does not apply in general to thick systems. However, a number of different types of two-dimensional vector fields can be defined for various particular classes of optical systems. Thick systems differ qualitatively from thin systems. They do not have equivalent thin lenses and cannot generally be replaced by thin lenses. Equations are derived for the change in reduced direction and deflection for a ray through optical systems in general and through separated two- and three-lens systems in particular.     

Prevention of nausea and vomiting with granisetron, droperidol and metoclopramide during and after spinal anaesthesia for caesarean section: a randomized, double-blind, placebo-controlled trial

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.     

The Nordic multicenter double-blind randomized controlled trial of prophylactic ursodeoxycholic acid in liver transplant patients

BACKGROUND: Prophylactic treatment with ursodeoxycholic acid (UDCA) has been reported to reduce the incidence of acute rejection after liver transplantation compared with historical controls. We investigated this in a prospective, randomized, placebo-controlled multicenter study. METHODS: Fifty-four liver transplant patients were allocated to the UDCA treatment group (15 mg/kg/day), and 48 patients were allocated to the placebo group. Trial medicine was started on the first postoperative day and was given for 3 months. Follow-up was for 12 months. Treatment was stratified for adults with chronic liver disease (n=77), adults with acute liver failure (n=10), and children (n=15). RESULTS: The frequency of patients with acute rejection was 65% in the UDCA treatment group and 68% in the placebo group. The frequency of steroid-resistant rejection was similar in both groups. The probability of acute rejection, analyzed according to the intention-to-treat policy with Kaplan-Meier analysis, was similar in both treatment groups. No significant differences were found in patient survival and graft survival probabilities. For the biochemical markers of cholestasis, only gamma-glutamyltransferase was significantly improved after 2 months of UDCA treatment. CONCLUSIONS: The initial optimistic report of a beneficial effect of prophylactic treatment with UDCA on acute rejection after liver transplantation was not confirmed in this controlled study.     

Dexamethasone decreases the incidence of shivering after cardiac surgery: a randomized, double-blind, placebo-controlled study

Shivering after cardiac surgery is common, and may be a result of intraoperative hypothermia. Another possible etiology is fever and chills secondary to activation of the inflammatory response and release of cytokines by cardiopulmonary bypass. Dexamethasone decreases the gradient between core and skin temperature and modifies the inflammatory response. The goal of this study was to determine whether dexamethasone can reduce the incidence of shivering. Two hundred thirty-six patients scheduled for elective coronary and/or valvular surgery were randomly assigned to receive either dexamethasone 0.6 mg/kg or placebo after the induction of anesthesia. All patients received standard monitoring and anesthetic management. After arrival in the intensive care unit (ICU), nurses unaware of the treatment groups recorded visible shivering, as well as skin and pulmonary artery temperatures. Analysis of shivering rates was performed by using chi2 tests and logistic regression analysis. Compared with placebo, dexamethasone decreased the incidence of shivering (33.0% vs 13.1%; P = 0.001). It was an independent predictor of reduced incidence of shivering and was also associated with a higher skin temperature on ICU admission and a lower central temperature in the early postoperative period. IMPLICATIONS: Dexamethasone is effective in decreasing the incidence of shivering. The effectiveness of dexamethasone is independent of temperature and duration of cardiopulmonary bypass. Shivering after cardiac surgery may be part of the febrile response that occurs after release of cytokines during cardiopulmonary bypass.     

Treatment of cisplatin-related nausea and vomiting with a combination of ondansetron and metoclopramide: a pilot study

Forty chemotherapy-naive patients receiving high-dose cisplatin were included in a pilot study of a combination of ondansetron plus metoclopramide as antiemetic therapy. Patients received ondansetron 16 mg plus metoclopramide 0.5 mg/kg in 250 cm3 of normal saline i.v. 15 min before cisplatin administration on day 1; then ondansetron 8 mg was given orally b.i.d. and metoclopramide 0.5 mg/kg was given intramuscularly t.i.d. for 4 days. This combination was given to all patients receiving the first cycle of chemotherapy. At the second cycle of chemotherapy all patients received the same antiemetic treatment as above plus methylprednisolone 125 mg i.v. on day 1 and the intramuscularly once a day for 4 days. There were 20 females and 20 males with a mean performance status of 1 (range 0-2) and a mean age of 58 years (range 36-68). Ten patients had ovarian carcinoma, eight patients had uterine adenocarcinoma and 22 and non-small cell lung carcinoma. The mean cisplatin dose was 96 mg/m2. All patients denied significant alcohol consumption. At cycle 1, complete protection against acute emesis was achieved in 22 patients (55%), major protection in 12 cases (30%), minor protection in four patients (10%) and failure in two cases (5%). On the other hand, the efficacy of this combination on delayed vomiting was not striking. For delayed vomiting, complete protection was observed in nine patients (23%), major protection in 13 cases (33%), minor protection in 10 patients (25%) and failure in eight cases (20%). At cycle 2, patients also received methylprednisolone showing complete protection from vomiting in 19 cases (47%) and major protection on 12 cases (30%). Results achieved with ondansetron plus metoclopramide are in the range reported for ondansetron alone in the medical literature. Although this study was not prospectively carried out in a randomized fashion, the results are not suggestive of a possible positive effect of metoclopramide addition to ondansetron. On the other hand, these results stress the role that corticosteroids may play in the control of delayed emesis. Toxicity was predictable and the frequency of side-effects was in the range reported in other studies with ondansetron.     

The combination of oral lysine-acetylsalicylate and metoclopramide compared with oral sumatriptan in the treatment of migraine attacks. A randomized, double-blind, placebo-controlled clinical trial

A combination of lysine acetylsalicylate (equivalent to 900 mg aspirin) and 10 mg metoclopramide (LAS + MTC) was compared with oral sumatriptan (100 mg) and placebo in 421 patients with migraine in a randomized, double-blind, clinical trial. LAS + MTC was as effective as sumatriptan with a decrease in headache from severe or moderate to mild or none in 57% and 53%, respectively, for the first migraine attack treated, the primary efficacy parameter. Both treatments were better than placebo (success rate 24%, p < 0.001). LAS + MTC was better tolerated than sumatriptan (adverse events in 18% and 28%, respectively, p < 0.05).     

A multicenter, randomized, blind comparison of amrinone with milrinone after elective cardiac surgery

The ability of transglutaminase-synthesized 1,3-diaminopropane, spermidine (Spd), spermine (Spm), and monodansylcadaverine gamma-(glutamyl5)derivatives of substance P (SP) to produce bronchoconstriction was investigated. In urethane-anaesthetized guinea pigs, intravenous injections of SP derivatives contracted differently bronchial smooth muscle and caused hypotension. The most effective bronchoconstrictor among SP analogs was the gamma-(glutamyl5)Spd derivative of SP (Spd-SP; EC50 = 5.3 nmol/kg), which was more potent than the native peptide (EC50 = 26.5 nmol/kg). In contrast, the gamma-(glutamyl5)Spm derivative of SP (Spm-SP) was found completely unable to cause bronchoconstriction and was significantly less effective than SP in determining hypotension. The contractile effect of Spd-SP and Spm-SP was investigated in vitro on rat isolated colon, a well-characterized preparation rich in NK2 receptors. In addition, Spd-SP was tested on the endothelium-denuded rabbit pulmonary artery (RPA) and the hamster isolated trachea (HT), both tissue preparations containing only a single functional receptor subtype (NK2A and NK2B, respectively). The results obtained showed that Spd-SP recognizes NK2 receptors occurring on rat isolated colon more effectively (EC50 = 11 nM) than the native peptide (EC50 = 45 nM). Conversely, Spm-SP evokes a contractile response less effective than that elicited by SP (EC50 = 312 nM). Furthermore, Spd-SP (0.1-10 microg kg(-1)) produced a concentration-dependent contraction of both HT and RPA, exhibiting a potency respectively 12 and 30 times higher than SP in contracting HT and RPA. Our results indicate that the introduction of a Spd moiety at the level of glutamine-5 of SP gives rise to an analog that possesses a different capability to recognize NK2 receptors than the parent peptide. Moreover, since Spd-SP seems to contract more effectively RPA than HT, we conclude that it preferentially recognizes the NK2A receptor subtype.