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Biomedical subjects

M Fried

Publications and source records attributed to M Fried.

At least 55 records · Page 3Linked to original sources
PubMed2002

[Choice of surgical procedure in operations for chronic pancreatitis--personal experience].

The First Surgical Clinic of the First Medical Faculty of Charles University and General Faculty Hospital in Prague made operations of the pancreas ever since 1971. In the work sooner or later all approaches to surgical treatment pancreatitis were reflected. The authors present a brief review of results and their own experience since 1994 when duodenum-sparing operations were introduced. Indications for surgical treatment were based on the diagnosis by US, CT and ERCP, in exceptional case MR, after evaluation by a pancreatologist, roentgenologist and surgeon. The group of patients with chronic pancreatitis was extended by 21 patients from a group operated because of preoperative suspicion of a malignant pancreatic tumour not confirmed during and after surgery. In those Whipple's operation was preformed. The same operation was performed in three patients with chronic pancreatitis with serious changes in the area of the head of the pancreas. In 123 patients a drainage and duodenum sparing operation was preformed, of these in 57 according to Beger, 19 according to Frey, 37 Partington-Rochelle's procedure. The authors record two sepsis postoperative complications after the classical Beger operation and the hospital stay was on average by five days shorter as compared with the classical method of Whipple. When evaluating postoperative complaints and problems (pain, malnutrition, physical constitution and social position) the authors recorded equally favourable results as after non-complicated duodenopancreatectomy. They varied, depending on the patients co-operation round 84-87% while authors consider Beger's operation logical because of the removal of the main tissue mass of the head of the pancreas, responsible for pain, complications caused by fibrosis in the area round the bile duct and duodenum, responsible for the deteriation of the compartment syndrome in the left half of the gland. Its result is destruction of the remainder of exocrine and endocrine tissue. Of 187 operated patients one patient with decompensated diabetes died postoperatively. Based on their own experience the authors do not consider repeated re-operations an absolute contraindication of Beger's operation when conditions permit. A problem is, in their opinion, fibrosis in the vicinity of the pancreas and portal overpressure.

Chronic Disease↗
PubMed2002

[Are complications of gastric banding decreased with cuff fixation?].

The gastric bandage is reliable method for long time control of weight loss in failed conservative cure of morbid obese patients. Since 1983 we have been concerned with bariatric surgery at the First Surgical Department of General Faculty Hospital of Charles University. 691 morbid obese patients (BMI 49.7 kg/m2, mean age of 38.1) underwent gastric banding (GB)--by laparotomy 58 obese patients and since 1993 by laparoscopy 633 obese patients. After 12 months the mean weight loss was 21.1 kg (14-32 kg) and after 24 month the mean weight loss was 38.7 kg (27-73 kg). In period of 1993-1998 the most frequent late complication in the group of 517 obese patients after laparoscopic nonadjustable gastric banding (LNGB) was in 5.1% dilatation of upper gastric pouch or slippage of anterior stomach wall above the band with vomiting and failure of gastric evacuation. In majority we removed GB laparoscopically. To prevent this complication we modified GB with fixing band with a cuff made from the anterior gastric wall. To test the effectiveness of this method we implemented in 1998-1999 a prospective randomized study. In the group of 80 morbid obese patients we created in 40 patients (n1-GB+C) LNGB with the cuff fixation and in 40 patients (n2-GB-C) without fixation. We followed-up of this patients after LNGB was in 6 weeks, 6 months and 12 months with measurement of pouch volume by endoscopy with calibrate endocannula. One year after GB in the group n1-GB+C the mean increase of the pouch volume was 14.6 ml, i.e. 124% of the original size, while in group n2-GB-C the mean increase of the pouch volume was 33.6 ml, i.e. 154.1% of the original size. The slippage or dilatation of the pouch was in group nl in one case while in group n2 in three cases (p < 0.001).

Female↗
PubMed2002

[Cardiovascular stress in laparoscopic surgery].

AIM: To evaluate response of cardiovascular system in laparoscopic surgery. The main aim was: 1--comparison of healthy subjects and morbid obese population, 2--comparison of healthy subjects and cohort of patients with organic cardiopathy. Secondly we compared the influence of the operation position. PATIENTS AND METHODS: Patients (n = 17) were divided into 3 subgroups:--Control group of "normal" subjects: mean age 36.8 +/- 11.2 years; BMI 25.33 +/- 3.62; BSA 1.84 +/- 0.21 m2; two men and four women; op. diagnosis: 3x cholecystectomy, 1x appendectomy, 1x inguinal herniotomy, 1x hiatal hernia operation. --Group of patients with morbid obesity: mean age 38 +/- 8.1 years; BMI 45.82 +/- 7.54!; BSA 2.66 +/- 0.32 m2; one man and five women; all of them were operated for obesity (laparoscopic gastric banding).--Group of patients with severe cardiopathy: mean age 64.0 +/- 11.55; BMI 26.4 +/- 4.09; BSA 1.89 +/- 0.23; three men and two women; card. diagnosis: 2x aortic stenosis, 1x combined aortic valvulopathy, 1x aortic stenosis with secondary mitral regurgitation, 1x secondary mitral regurgitation (both caused by coronary artery disease); op. diagnosis: 4x cholecystectomy; 1x extraction of catheter for peritoneal dialysis. The method of our examination was transesophageal echocardiography with use of omni planar sond with continual monitoring of each patient. Our data are based on repeated measurements (3x minimal for each state and each patient) before and after peritoneal cavity insufflation and third after positioning of patient (in Trendelenburg or Fowler position). Examinations were recorded and data analysed off-line. Following parameters were analysed: mean age, BMI, BSA, heart rate, mean arterial pressure (MAP), ejection fraction of left ventricle (EF), E/A ratio of transmitral flow, cardiac output (CO), cardiac index (CI), systemic (peripheral) vascular resistance (SVR) and pressure-rate-product (PRP). For statistical analysis were used: ANOVA tests, t-tests with Benforroni correction and Friedman's tests. RESULTS AND DISCUSSION: In comparison of normal and obese patients statistically significant differences were found (after exclusion of BMI and BSA) in cardiac output values, after recalculation on body surface (cardiac index) remained only non-significant trend to fall. Differences between control group and group of cardiacs were also non significant with exclusion of E/A ratio of transmitral flow. This result we explain by pseudonormalization. All 17 operations were successfully done without any complication. CONCLUSIONS: Our data were obtained on relatively small cohort of patients but the number of patients was respected by statistics and results might be borderline but significant. Laparoscopic gastric band (operation is done in semi-sitting position) in morbid obese patients is well tolerated without any differences in comparison to healthy population. The population of patients with severe organic cardiopathy needs careful approach. Our data are favourable but significant change in the left ventricle filling together with non-significant hemodynamic disadvantageous trends in EF, CI and MAP requires care. Further investigations are needed and with intraoperative monitoring (transesophageal echocardiography is preferred) can be considered as safe.

Adult↗
PubMed2002

[Percutaneous electrogastrography in the perioperative period in laparoscopic and classical cholecystectomy and in laparoscopic nonadjustable gastric banding].

Percutaneous electrogastrography (EGG) is a non-invasive measuring method of gastric myoelectrical activity. We measured myoelectrical activity patients after laparoscopic cholecystectomy (16 patients), after laparotomic cholecystectomy (9 patients) and after gastric bandage (14 patients). We used a Microdigitrapper (Medtronic) and data were analysed with a spectral analysis and Fournier's transformation. We measured 24 hours and 5 hours before operation procedure and 24 and 48 hours after operation. After operative procedure we compared results with healthy voluntaries. Bradygastria was found in most frequent cases in early postoperative period. Physiologic conditions were renewed in laparoscopic operative procedure in first day, after laparotomic operation in second day after operation.

Adult↗
PubMed2001

One INK4 gene and no ARF at the Fugu equivalent of the human INK4A/ARF/INK4B tumour suppressor locus.

The INK4A/ARF/INK4B locus, conserved in mammals, encodes three polypeptides that regulate cell proliferation via the pRb and p53 tumour suppressor pathways. The locus is mutated in many cancers. The related, tandemly-linked INK4A and INK4B genes encode the p16(INK4A) and p15(INK4B) members of the INK4 family of cyclin-dependent kinase inhibitors which block phosphorylation of pRb, whereas the third product, ARF, derived from an alternative reading frame of INK4A, regulates p53 activity. We assessed the status of this unusual locus in the puffer fish, Fugu rubripes, and identified two INK4 genes using degenerate PCR and hybridization analyses. Sequence conservation and conservation of synteny between human and Fugu predict one gene to be an INK4A or INK4B homologue and the other an INK4D homologue. Analysis of the Fugu INK4A/B gene and the surrounding 40-kb of genomic DNA did not reveal the presence of any ARF-encoding potential or another related INK4 gene. We conclude that the gene duplication event that generated adjacent INK4A and INK4B genes and the association of ARF with the ancestral INK4A gene occurred after the divergence of the lineage leading to mammals from fish. Thus, unlike mammals, the fish p53 and pRb tumour suppressor pathways are not regulated by a single locus.

Amino Acid Sequence↗
PubMed2001

Polyoma virus disrupts ARF signaling to p53.

Polyoma virus (Py) differs from other small DNA tumor viruses in not encoding a protein that inactivates p53. The complete Py early region encoding the large T-antigen (PyLT), middle T-antigen (PyMT) and small T-antigen (PyST) will transform primary rodent cells and REF52 cells, but PyMT, the main Py oncogene, by itself will only transform these cells when p53 or ARF is inactivated. We have related Py oncogene cooperation with the effects of the Py T-antigens on the ARF-p53 signaling pathway. PyMT activates an ARF-induced p53-mediated block to cell division explaining the inability of PyMT alone to generate dividing transformed cells. In contrast, in REF52 cells transformed by the whole Py early region (PyREF52), ARF is upregulated but p53 is not activated. Thus PyLT and/or PyST negates the PyMT-induced ARF-mediated block to cell division by disrupting the signaling pathway from ARF to p53. Although there is no detectable interaction or co-localization of endogenous ARF (nucleoli) and MDM2 (nucleoplasm) in PyREF52 cells, expression of transfected ectopic ARF results in an MDM2/ARF interaction and sequestration of MDM2 into the nucleoli. Sequestration of MDM2 by ARF in the nucleoli is not essential for a p53 response in REF52 cells as activation of Raf in REF52Raf-ER cells results in an ARF-induced p53-mediated cell cycle block in the absence of a detectable ARF-MDM2 interaction. Py may provide new insights into the cellular ARF-p53 signaling pathway.

ADP-Ribosylation Factor 1↗
PubMed2001

Thromboagglutination by anticardiolipin antibody complex in the antiphospholipid syndrome: a possible mechanism of immune-mediated thrombosis.

The tendency for patients with antiphospholipid syndrome (APLS) to thromboembolism and the criteria for its detection are well established, whereas the mechanism of this thrombophilic syndrome is still obscure. Using immunofluorescent techniques and a microscopic spontaneous platelet aggregation test (mSPAT), we have previously demonstrated platelet binding by antibody followed by aggregation in patients with lupus anticoagulant. In the present study, we investigated 18 anticardiolipin antibody-positive (ACLA pos.) patients, comprised of 12 primary APLS and 6 secondary APLS lupus patients. We demonstrated direct platelet microaggregate formation in 16/18 cases, whereas this finding was not present in 20 ACLA-negative (ACLA neg.) subjects (P<.001). Indirect testing revealed 10/12 cases of platelet microaggregation and none in the ACLA neg. subjects. In addition, immunofluorescent studies showed that platelet antibody complex binding occurred in 8/12 cases tested directly and in 11/12 cases in indirect testing, as compared to 1 out of 20 binding in ACLA neg. subjects (P<.001). Antibody complex binding was inhibited in two cases by prior extraction of phospholipids. Platelet aggregation could be demonstrated in two ACLA neg. individuals by the addition of exogenous ACLA to platelets in EDTA-plasma. We therefore propose a mechanism for immune-mediated thrombosis in APLS in which calcium-independent platelet aggregation, or thromboagglutination, is initiated by an ACLA-phospholipid complex present in the patients' plasma. Following the antibody complex-induced platelet agglutination, thrombosis proceeds by release, recruitment, and fibrin formation. The mechanism should have important implications in the diagnosis, management, and monitoring of APLS.

Adolescent↗
PubMed2001

[Thoracic pain from the viewpoint of the gastroenterologist: diagnosis and therapy].

Non-cardiac-chest-pain is frequently associated with esophageal diseases. Gastroesophageal reflux disease (GERD) is present in 60%, esophageal motility disorder in 40-50%, tumours in 5-10% and achalasia in 5% of such cases. Diagnosis is based on endoscopy and in patients with no endoscopy findings on 24-h esophageal pH-monitoring. GERD can present with various symptoms and can best be managed with proton pump inhibitors (PPI). Considering increased mortality and morbidity operation should only be performed in special situations. Esophageal motility disorders most frequently produce retrosternal pain. Pain in achalasia may not respond to standard therapy. Motility disorders and achalasia are diagnosed by perfusion manometry and videofluoroscopy. If a tumour is suspected diagnosis is made by endoscopy (biopsy, endosonography) and radiology.

Chest Pain↗
PubMed2001

Helicobacter pylori and symptomatic relapse of gastro-oesophageal reflux disease: a randomised controlled trial.

BACKGROUND: There is little information on the effects of Helicobacter pylori eradication in patients with a primary diagnosis of gastro-oesophageal reflux disease (GORD). Our aim was to investigate the effect of H pylori eradication in this group of patients. METHODS: We did a double-blind, randomised, placebo-controlled study in 70 patients with GORD. We assigned individuals to three groups. All patients received lansoprazole 30 mg twice daily for 10 days, followed by 30 mg once daily for 8 weeks. Patients infected with H pylori received either antibiotics (clarithromycin 500 mg and amoxicillin 1000 mg twice daily) or placebo for the first 10 days. Controls were patients not infected with H pylori. Patients were followed up for 6 months at 2-week intervals for GORD symptoms. At the end of the study we repeated endoscopy and oesophageal and gastric 24 h-pH monitoring. FINDINGS: 58 of 70 patients completed our study. At the end of the study 16 of these patients were H pylori-positive (14 placebo and two eradication failures), 13 were negative because of successful H pylori eradication, and 29 were controls. H pylori-positive patients relapsed earlier (54 days) than did those in whom H pylori was eradicated (100 days) (p=0.046). The H pylori-negative control group relapsed after the longest period (110 days). However, time to relapse was also affected by oesophagitis grade (no oesophagitis 127 days, grade III or IV oesophagitis 18 days). When results were corrected for the affect of oesophagitis grade, H pylori-positive patients relapsed earlier (p=0.086) than H pylori-eradiated patients and controls (p=0.001). INTERPRETATION: H pylori infection positively affects the relapse rate of GORD. Eradication of H pylori could, therefore, help to prolong disease-free interval in patients with GORD.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Relationship between APC genotype, polyp distribution, and oral sulindac treatment in the colon and rectum of patients with familial adenomatous polyposis.

PURPOSE: Familial adenomatous polyposis is an inherited colorectal cancer syndrome characterized by the presence of multiple adenomatous colorectal polyps. Molecular studies have revealed that germline mutations in the APC gene are the underlying cause of the disease. The nonsteroidal anti-inflammatory agent sulindac has been shown to reduce the number of colorectal adenomas. Most sulindac trials in the large bowel have focused on the distal colon and relatively little is known about its effect on the proximal colon. Moreover, it is unknown whether the site of the APC mutation affects the efficacy of sulindac. METHODS: This study investigated whether there were regional differences in the effect of sulindac on the colon and whether response to sulindac was dependent on the site of mutation in the APC gene. In an open prospective study 17 patients with familial adenomatous polyposis were treated with 300 mg oral sulindac daily for four months followed by a washout phase of six months. Ten of the patients had an intact colon and seven had rectal stumps only. The number, size, and the degree of dysplasia of the adenomas were evaluated by colonoscopy at entry, end of treatment and end of the study. RESULTS: Overall, a statistically significant decrease in the number of adenomas was observed (120 +/- 112 to 28 +/- 64, P = 0.007). After cessation of sulindac treatment the number of adenomas increased to 48 +/- 44.5, but remained significantly lower than the values observed at baseline. In the ten patients with intact colons, adenomas decreased by sevenfold in the proximal colon (103 +/- 73 to 15.1 +/- 47.4, P = 0.011) and twofold in the distal colon (80 +/- 52 to 29.6 +/- 37.2, P = 0.005). The size of adenomas and the grade of dysplasia also decreased. No correlation could be seen between the APC mutation site and the response to treatment. CONCLUSION: These data indicate that sulindac reduces the number of adenomas in the entire colon and that the effect seems to be more pronounced in the proximal colon.

Adenomatous Polyposis Coli↗
PubMed2001

Monitoring the intragastric distribution of a colloidal drug carrier model by magnetic resonance imaging460.

PURPOSE: Monitoring the distribution of drugs or drug delivery systems in the human gastrointestinal tract is an important prerequisite for the design of orally administered drugs. We investigated the intragastric distribution of a colloidal drug delivery system (liposomes containing the contrast agent Gd-DOTA) by magnetic resonance imaging. METHODS: Following ingestion of a liquid or a solid meal, gastric distribution of liposomes released from a capsule and the fat component of the solid meal were tracked in 7 healthy subjects for 90 min. Liposomes were identified in gastric content by the increased signal intensity provided by the encapsulated Gd-DOTA. RESULTS: With the liquid meal, liposomes initially formed a layer on the surface before distributing in 86 +/- 2% of gastric content (maximum distribution volume) within 42 +/- 6 min. With the solid meal, maximum distribution (7 +/- 1%, reached within 24 +/- 6 min) was confined to a small volume in the fundus without forming a layer, suggesting that distribution was related to the accessible liquid compartment. Fat distribution was inhomogeneous and concentrated in the fundus. CONCLUSIONS: Intragastric distribution of a colloidal drug carrier model, such as Gd-DOTA-filled liposomes, varies between meals of different composition. These differences can be monitored in three dimensions in humans by MRI.

Adult↗
PubMed2001

Fat digestion modulates gastrointestinal sensations induced by gastric distention and duodenal lipid in humans.

BACKGROUND AND AIMS: It is unclear whether fat digestion is required for the induction of gastrointestinal sensations and whether different fats have different effects. We investigated the effect of fat digestion and of medium-chain triglycerides (MCTs; C < 12) and long-chain triglycerides (LCTs; C > 16) on gastrointestinal sensations. METHODS: In a double-blind study, 15 healthy subjects were studied on 5 occasions during which LCT or MCT emulsions (2 kcal/min), with or without 120 mg tetrahydrolipstatin (THL, lipase inhibitor), or sucrose polyester (SPE, nondigestible fat) were infused intraduodenally in randomized order. After 30 minutes, the proximal stomach was distended in 1 mm Hg steps/min. Intensity of gastrointestinal sensations (on a 0-10 visual analog scale), plasma cholecystokinin (CCK) levels, and gastric volumes were assessed throughout. RESULTS: LCT and MCT increased gastric volume at baseline pressure compared with SPE, and LCT more than MCT. THL entirely abolished this effect (volumes [mL]: LCT, 213 +/- 19; LCT-THL, 39 +/- 3; MCT, 155 +/- 12; MCT-THL, 43 +/- 5; SPE, 44 +/- 5). Only LCT increased plasma CCK levels (pmol/L per 30 minutes: LCT, 21 +/- 2; LCT-THL, 9 +/- 1; MCT, 9 +/- 1; MCT-THL, 11 +/- 1; SPE, 9 +/- 1). During distentions, intragastric volumes were greater during infusion of LCT and MCT than during the respective THL conditions or SPE, but plasma CCK levels did not change. The intensity of sensations increased (hunger decreased) more with LCT than with MCT. During infusion of THL or SPE, the effects were smaller than during LCT or MCT. CONCLUSIONS: Fat digestion is required for the modulation of gastrointestinal sensations during gastric distention. The effects of fat depend on the fatty acid chain length and are not entirely explained by release of CCK.

Adult↗
PubMed2001

Hepatic uptake of cholecystokinin octapeptide by organic anion-transporting polypeptides OATP4 and OATP8 of rat and human liver.

BACKGROUND & AIMS: Cholecystokinin (CCK) is a major gastrointestinal peptide hormone that is released postprandially from the small intestine and exerts marked effects on gallbladder and gastrointestinal motility. The smaller isoforms CCK-8 and CCK-4 are rapidly taken up into hepatocytes, metabolized, and excreted into bile. Our aim was to identify and characterize the hepatocellular CCK-8 uptake system. METHODS: CCK-8 uptake was measured in Xenopus laevis oocytes expressing the organic anion-transporting polypeptides of rat liver (Oatp1, Oatp2, Oatp3, or Oatp4) and of human liver (OATP-A, OATP-B, OATP-C, or OATP8) and in primary cultured rat hepatocytes. RESULTS: Rat Oatp4 and human OATP8 efficiently mediated CCK-8 uptake in oocytes, with Michaelis constant (Km) values of 14.9 +/- 2.9 micromol/L and 11.1 +/- 2.9 micromol/L, respectively. CCK-8 uptake by hepatocytes was also saturable, with a Km of 6.7 +/- 2.1 micromol/L. The Km value in rat hepatocytes is consistent with Oatp4-mediated transport. CONCLUSIONS: CCK-8 is selectively transported by rat Oatp4 and human OATP8, both of which are exclusively expressed at the basolateral membrane of hepatocytes. These 2 transporters are the first and probably the predominant hepatic uptake systems for CCK-8 and may be critical for the rapid clearance of this hormone from the circulation.

Animals↗
PubMed2001

Is histological investigation of polyps always necessary?

BACKGROUND AND STUDY AIMS: To assess whether polyp histological type can be predicted by patient characteristics and endoscopic polyp findings. PATIENTS AND METHODS: 1681 polyps in 494 patients were categorized as advanced adenomas (villous component or severe dysplasia or early cancer) or insignificant polyps. Chi-squared tests were used to analyze whether polyp histological type could be predicted based on patient age (< 60 vs. > or = 60 years), gender, family history of colon polyps or cancer, presence of anemia, polyp size (< or = 5 mm vs. > 10 mm), and location (left- vs. right-sided). RESULTS: Insignificant polyp histology (n = 1337) correlated with patient age < 60 years (P = 0.0026), lack of anemia (P< 0.0001), polyp size < or = 5 mm (P < 0.0001), and right-sided location (P= 0.0058). Stepwise inclusion of these parameters demonstrated that the association of a < or = 5 mm right-sided polyp in a patient < 60 years yielded the highest combined predictive value (96.2%) for an insignificant polyp. Conversely, age > or = 60 years, presence of anemia, polyp size > 10 mm, or left-sided location, as single or combined parameters, demonstrated a maximum predictive value of only 75.4% for an advanced adenoma. CONCLUSIONS: A small right-sided polyp in a young patient is associated with a small risk (3.8 %) for advanced adenomatous tissue, indicating that histological investigation of such a polyp might not always be necessary. However, the recent recognition of flat adenomas and "mini" de novo colon carcinomas in the European population also may limit the usefulness of small polyp diameters in the exclusion of severe polyp histology.

Adenoma↗
PubMed2001

Safer colonoscopy with patient-controlled analgesia and sedation with propofol and alfentanil.

BACKGROUND: The aim of this study was to assess the efficacy of patient-controlled analgesia and sedation with propofol/alfentanil for colonoscopy compared with continuous drug infusion and conventional nurse-administered medication. METHODS: One hundred fifty patients undergoing colonoscopy on an outpatient basis were randomly assigned to 1 of 3 medication regimens. To maintain blinding, all patients were connected to an infusion pump. Group I patients could self-administer boluses of 4.8 mg propofol and 125 microg alfentanil without restriction. Group II patients received a continuous infusion with 0.048 mg/kg propofol and 0.12 microg/kg alfentanil per minute. Group III patients received intravenous premedication with 0.035 mg/kg midazolam and 0.35 mg/kg meperidine. RESULTS: There were no differences between the groups with respect to pain (visual analogue scale) and procedure time. Patient-controlled analgesia and sedation with propofol/alfentanil (group I) resulted in less of an increase in the transcutaneous partial pressure of carbon dioxide (p = 0.0004) during colonoscopy and less of a decrease in mean arterial blood pressure (p = 0.0021) during recovery, as well as more complete recovery (p = 0.0019) after 45 minutes compared with conventional administration of midazolam/meperidine. Furthermore, patient-controlled analgesia and sedation yielded a higher degree of patient satisfaction than continuous infusion of propofol/alfentanil (p = 0.0033) or nurse-administered midazolam/meperidine (p = 0.0094). CONCLUSIONS: Patient-controlled administration of propofol and alfentanil for colonoscopy may provide a better margin of safety than conventional administration of midazolam and meperidine and results in a higher level of patient satisfaction and shorter recovery.

Alfentanil↗