Superior prolonged antiemetic prophylaxis with a four-drug multimodal regimen - comparison with propofol or placebo.

BACKGROUND: The purpose of this study was to compare the effects of a low-dose propofol infusion with a four-drug multimodal regimen for prophylaxis of postoperative nausea and vomiting (PONV). METHODS: : PONV was studied in two patient groups with a known high incidence. Through a stratified randomization, 60 patients undergoing breast surgery and 120 patients undergoing abdominal surgery were randomized to three groups of equal size: the propofol group (P), the multidrug group (M) and the control group (C). All patients received general anesthesia, induction with propofol and maintenance with sevoflurane. After induction, patients in the P group received a continuous infusion of propofol 1 mg/kg/h during the operation and the first 4 postoperative h. Patients in the M group received dexamethasone 4 mg and three antiemetics, ondansetron 4 mg, droperidol 1.25 mg and metoclopramide 10 mg i.v. In the control group no prophylaxis was given. Nausea and pain were evaluated by incidence and a visual analog scale (0-10 cm). All emetic episodes were noted by the staff during the first 4 h and by the patients during the next 20 h. RESULTS: The overall incidence of PONV during the first 24 h postoperatively was significantly lower in the M group (24%) than in the P group (49%) (P<0.01) or the C group (70%) (P<0.001). The incidence of PONV increased significantly both in patients undergoing breast surgery and abdominal surgery after termination of propofol. The number of patients who vomited was significantly lower in the M group, both in breast surgery patients (5%) and abdominal surgery patients (3%) compared to patients in the propofol groups (breast 16% NS; abdominal 29%, P<0.05) and in the control groups (breast 37%, P<0.01; abdominal 29%, P<0.01). CONCLUSION: The incidence of PONV is very high in patients undergoing breast and abdominal surgery. In the present study antiemetic prophylaxis with a combination of droperidol, ondansetron, metoclopramide and dexamethasone was more effective in preventing PONV, especially vomiting, than a postoperative low-dose infusion of propofol, which had a short lasting effect.

Propofol and gastric effects of morphine.

OBJECTIVE: The purpose of this study was to evaluate whether propofol abolishes morphine-induced effects on gastric emptying and gastric tone. METHOD: The study was carried out before anesthesia in 40 patients (ASA I-II). Gastric tone was measured in 20 patients by an electronic barostat. Volume changes were thereby registered continuously in an intragastric flaccid bag with a constant preset pressure. All patients received i.v. morphine 0.1 mg x kg(-1) before the measurements and, in a randomized order, 10 of the patients also received a bolus dose of propofol 1 mg. kg-1 before morphine. Gastric emptying was studied with the paracetamol method in 20 patients. All patients received morphine 0.1 mg x kg(-1) i.v. 10 min before oral ingestion of 1.5 g paracetamol in 200 ml water and, in a randomized order, 10 of the patients also received propofol, a bolus dose of 0.3 mg x kg(-1) before morphine, followed by an infusion of 1 mg x kg(-1) x h(-1) during the whole study (2 h). RESULTS: The volume in the intragastric bag increased in all patients receiving morphine without propofol. In the group that received propofol before morphine, the volume in the intragastric bag decreased in all patients. The volume differences between the groups were statistically significant (P<0.01). There were no statistically significant differences of the AUC60, Cmax and Tmax of serum paracetamol concentrations between the morphine and propofol-morphine groups. CONCLUSION: Propofol did not abolish morphine-induced delay of gastric emptying even if propofol abolished the decrease of gastric tone induced by morphine.

Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees.

Two human monoclonal antibodies (mAbs) against hepatitis B surface antigen (HBsAg) generated in the Trimera mouse system are described. Both mAbs 17.1.41 and 19.79.5 are of the IgG1 isotype and have high affinity constants for HBsAg binding in the range of 10(-10) mol/L. Monoclonal antibody 17.1.41 recognizes a conformational epitope on the a determinant of HBsAg whereas mAb 19.79.5 recognizes a linear one. The 2 mAbs bind to a panel of hepatitis B virus (HBV) subtypes with distinct patterns. The neutralizing activity of these antibodies was tested in 2 different animal model systems. Administration of each mAb to HBV-Trimera mice, a system that provides a mouse model for human hepatitis B infection, reduced the viral load and the percentage of HBV-DNA-positive mice in a dose-dependent manner. These 2 mAbs were more effective than a polyclonal antibody preparation (Hepatect; Biotest Pharma, Dreieich, Germany) in both inhibition of HBV liver infection and reduction of viral load. A single administration of a mixture of these mAbs into HBV chronic carrier chimpanzees resulted in immediate reduction in HBsAg levels followed by recurrence to initial levels within few days. Thus, these mAbs may be potential candidates for preventive therapy or in combination with other antiviral agents against HBV. Further studies in humans are needed to assess these mAbs in various clinical indications.

Effects of propofol on ipecacuanha-induced nausea and vomiting.

BACKGROUND: The purpose of this study was to evaluate if propofol has 5-HT3 antagonistic effects. Ipecacuanha is known to release serotonin (5-HT) in the gastrointestinal tract and therefore ipecacuanha syrup was used to induce nausea and vomiting. The 5-HT3 antagonist ondansetron was used as a control substance. METHOD: Ten healthy male volunteers (20-37 years) were studied on three occasions and were randomly allocated to receive a concomitant infusion of propofol (initial bolus 0.1 mg kg(-1) then 1 mg kg(-1)h(-1)), ondansetron (initial bolus 0.11 mg kg(-1) then 14 microg kg(-1)h(-1)) and placebo on either occasion. The infusions started 30 min before oral ingestion of 30 ml of ipecacuanha and continued until 150 min after the intake. The number of retchings was recorded and the intensity of nausea was estimated by the subjects on a visual analog scale. RESULTS: During the first 150 min after ingestion of ipecacuanha there were no retchings during the ondansetron infusion (P=0.01 vs placebo, P=0.02 vs propofol) and significantly fewer retchings during propofol infusion compared to placebo (P<0.02). There was no nausea during the ondansetron infusion (P<0.01 vs placebo and propofol) but the volunteers experienced nausea both during the placebo and propofol infusion (NS). CONCLUSION: This study in volunteers has shown that propofol reduces the intensity of retching after oral intake of ipecacuanha syrup. As ipecacuanha releases 5-hydroxytryptamine, it can be concluded that propofol may have a weak 5-HT3 antagonistic effect.

Propofol sedation and gastric emptying in volunteers.

BACKGROUND: The purpose of this study was to evaluate the effects of light propofol sedation on gastric emptying and orocecal transit time (OCT). METHODS: Ten healthy male volunteers were studied on 2 occasions separated by at least 1 week and were randomly allocated to receive either propofol sedation or i.v. saline as a control. During propofol sedation the volunteers were sedated to grade 2-3 on a 5-grade scale. This was achieved by a propofol infusion of 5 mg kg(-1) h(-1) initially, which was then titrated down to a dose of 2.4+/-0.7 mg kg(-1) h(-1). Paracetamol absorption was used as an indirect measure of the rate of gastric emptying and OCT was determined by use of the hydrogen breath test after ingestion of raffinose. Student's t-test for paired samples was used and the results are presented as means+/-SD. RESULTS: During propofol sedation the maximum concentration of paracetamol (Cmax) was 115+/-26.8 micromol/L, time to peak concentration (Tmax) 50+/-38.8 min, and the area under the curve during the first 60 min (AUC60) 4793+/-1538 micromol x min/L, versus Cmax 99+/-20.8, Tmax 69+/-41.9 and AUC60 3897+/-1310 during saline infusion. These differences were not statistically significant. OCT was significantly shorter during the control study, 180+/-32.4 min, than during propofol sedation, 217+/-64.9 min (P<0.05). CONCLUSION: This study in volunteers has shown that gastric emptying of liquids seems uninfluenced by light propofol sedation. OCT was slightly prolonged during light propofol sedation.

The influence of propofol on vomiting induced by apomorphine.

It has been proposed that propofol has antiemetic effects even in nonsedative doses. The aim of this study was to investigate whether propofol influences vomiting induced by the dopamine agonist apomorphine. Ten healthy male volunteers received apomorphine infusion (1 mg/min) until vomiting was induced on four different occasions in a randomized order: a) during propofol infusion (2.4 +/- 0.7 mg.kg-1.h-1, mean +/- SD) at a sedation score of Grade 2-3 on a 5-grade scale; b) during midazolam infusion (0.13 +/- 0.04 mg.kg-1.h-1) at a sedation score of Grade 2-3 on a 5-grade scale; c) after a single nonsedating bolus dose propofol 0.4 mg/kg; and d) during infusion of normal saline. The amount of apomorphine needed to induce vomiting was increased after sedation with propofol (P = 0.005) as well as midazolam (P = 0.001). There was no difference in the sensitivity to apomorphine between these sedative regimens. The nonsedating single bolus propofol did not change the sensitivity to apomorphine compared to the saline infusion. We conclude that propofol given in a nonsedative dose has no effect on apomorphine-induced vomiting. However, the total amount of apomorphine given to induce vomiting was significantly larger during propofol sedation than during saline infusion. This was probably an effect of sedation inasmuch as a similar result was achieved during midazolam sedation.

Genetic relatedness of hepatitis B viral strains of diverse geographical origin and natural variations in the primary structure of the surface antigen.

A 681 nucleotide fragment of the hepatitis B virus (HBV) genome was sequenced that corresponded to the complete gene for hepatitis B surface antigen (HBsAg) in 80 HBsAg- and hepatitis B e antigen (HBeAg)-positive sera of diverse geographical origins. These and 42 previously published HBV sequences within the S gene were used for the construction of a dendrogram. In this comparison, each of the 122 HBsAg genes was found to be related to one or other of the six previously identified genomic groups of HBV, A to F. The HBV strains within each genomic group showed a characteristic geographical distribution. Group A genomes were represented by 23 strains mainly originating in northern Europe and sub-Saharan Africa. The group B and C genomes, represented by 17 and 28 strains respectively, were confined to populations with origins in eastern Asia and the Far East. The group D genomes, represented by 38 strains, were found worldwide, but were the predominant strains in the Mediterranean area, the Near and Middle East, and in south Asia. Group E genomes, represented by nine strains, were indigenous to western sub-Saharan Africa as far south as Angola. There were indications that the F group, made up of six strains, represented the genomic group of HBV among populations with origins in the New World. Thus, HBV has diverged into genomic groups according to the distribution of mankind in the different continents. As well as giving information on the genetic relationship of HBV strains of different geographical origin, this study also provides information on the primary structure of HBsAg in different regions of the world. Such data might prove valuable in explaining the reported failures to obtain protection with current HBV vaccines.

Comparison of the amino acid sequences of nine different serotypes of hepatitis B surface antigen and genomic classification of the corresponding hepatitis B virus strains.

The surface (S) genes of 12 hepatitis B viruses (HBVs) encoding nine different serotypes of hepatitis B surface antigen (HBsAg) were amplified by the polymerase chain reaction and sequenced. These represented the eight strains of HBV, P1 to P8, defined at an international workshop on HBsAg subtypes in Paris in 1975, and the adrq- subtype. The S genes from additional HBV strains, one ayw4, one adw4 and one ayw1, of sub-Saharan African origin, were also sequenced. The relationship of these 12 new S gene sequences to those of the 20 published previously was investigated by constructing a phylogenetic tree, which confirmed a previous classification into four groups, designated A to D, based on 18 complete HBV genomes. When relating our sequenced S genes to these genomic groups, ayw1 of African origin and P6 (adw2) were both allocated to group A, the reference P1 (ayw1 of Vietnamese origin) was allocated to group B, P5 (ayr), P8 (adr) and adrq- were all related to group C, and P2 (ayw2) and P3 (ayw3) could both be allocated to group D. Interestingly, the S genes of w4 serotype viruses, i.e. P4 (ayw4) and P7 (adw4q-), differed by 4% or more from both previous groups and from each other, suggesting their classification into two new groups, for which the designations E and F are proposed. Genomes specifying ayw were also found in groups A and B; previously sequenced genomes specifying the ayw subtype have all been confined to group D. There were indications that the epitope for subdeterminants of w resided at amino acid positions 125 to 127. Thus, at positions 125 and 127, ayw1, ayw2 and adw2 had T and P residues, respectively, whereas M and T residues were at the corresponding positions of ayw3. Both ayw4 and adw4 had L at residue 127, and all strains expressing r, apart from P5, had an I instead of a T residue at position 126.

Detection of HBV DNA by PCR in serum from an HBsAg negative blood donor implicated in cases of post-transfusion hepatitis B.

An HBsAg negative blood donor, and three of her recipients, who developed HBsAg positive post-transfusion hepatitis B, were all positive for serum HBV DNA by polymerase chain reaction (PCR), and by subtype discriminating PCR were found to harbour HBV specifying ayw. Thus HBV specifying ayw. Thus HBV DNA may be detected and sub-typed by PCR in infectious HBsAg negative individuals.

Typing of hepatitis B virus genomes by a simplified polymerase chain reaction.

The amplification of hepatitis B virus (HBV) DNA sequences in sera for molecular epidemiology of HBV is an important application of the polymerase chain reaction (PCR) with regard to HBV. To simplify the PCR for this purpose, the optimal concentrations of SDS and detergents for carrying out the proteinase K digestion and the amplification of DNA by Taq polymerase were evaluated. It was found that by using 1% deoxycholic acid as detergent for the proteinase K step and diluting the digest 10 times before carrying out the PCR, the phenol extraction of DNA became superfluous. The sensitivity of this procedure equalled that of PCR after phenol extraction on comparable amounts of serum. Four pairs of oligonucleotide primers were compared for amplification of HBV DNA sequences in 48 sera previously subtyped with respect to hepatitis B surface antigen (HBsAg), and in eight sera with different genotypes of HBV, representing the subtypes of HBsAg P1 to P8, defined at an international meeting [Couroucé-Pauty et al.: "HBs Antigen Subtypes." Basel: Karger, 1976]. Two primer pairs, selected from conserved regions in the X and S genes of HBV, gave a positive PCR with sera harbouring all the eight different strains of HBV, resulting in DNA fragments consistent with the sizes deduced from genome sequence data. Two other primer pairs were selected in order to discriminate genotypes with regard to differences between d/y and w/r strains.(ABSTRACT TRUNCATED AT 250 WORDS)