Antiemetic efficacy of prophylactic dimenhydrinate (Dramamine) vs ondansetron (Zofran)

BACKGROUND: The prophylactic administration of dimenhydrinate (Dramamine) is as effective as the use of ondansetron (Zofran) in preventing postoperative nausea and vomiting (PONV) in patients undergoing elective laparoscopic cholecystectomy. A prospective double-blind randomized study was performed in a tertiary care referral center. METHODS: For this study, 128 American Society of Anesthesiology (ASA) physical statuses I, II, and III patients were randomly assigned to receive either ondansetron 4 mg intravenously (IV) at $17 per dose (group 1) or dimenhydrinate 50 mg IV at $2.50 per dose (group 2) before induction of anesthesia. The end points evaluated were frequency of PONV, need for rescue antiemetics, need for overnight hospitalization secondary to persistent nausea and vomiting, and frequency PONV 24 h after discharge. RESULTS: Chi-square tests and student's t-test were used to determine the significance of differences among groups. Of the 128 patients enrolled in this study, 20 were excluded: 15 patients received an additional antiemetic preoperative; 4 were converted to open cholecystectomies; and 1 procedure was aborted due to carcinomatosis. Of the 108 remaining participants, 50 received ondansetron (group 1) and 58 received dimenhydrinate (group 2). Both groups were well matched for demographics including gender, ASA class, and history of motion sickness. The need for rescue antiemetics occurred in 34% of group 1 and 29% of Group 2 (p = 0.376), postoperative vomiting in 6% of group 1 and 12% of group 2 (p = 0.228), and postoperative nausea in 42% of group 1 and 34% of group 2 (p = 0.422). One group 1 patient and two group 2 patients required overnight hospitalization for persistent nausea, a difference that was not significant. Rates of PONV 24 h after discharge were similar between groups 1 and 2 (10% vs 14%, p = 0.397 and 2% vs 5%, p = 0.375, respectively). CONCLUSIONS: Prophylactic administration of dimenhydrinate is as effective as the use of ondansetron in preventing PONV in patients undergoing elective laparoscopic cholecystectomy. Dimenhydrinate is the preferred drug because it is less expensive. With more than 500, 000 laparoscopic cholecystectomies performed in the United States each year, the potential drug cost savings from the prophylactic administration of dimenhydrinate instead of ondansetron exceed $7.25 million per year.     

Human sperm immobilization effect of Carica papaya seed extracts： an in vitro study

AIM: To examine if the seed extracts of Carica papaya, which showed antispermatogenic/sperm immobilization properties in animal models, could cause human sperm immobilization in vitro. METHODS: Chloroform extract, benzene chromatographic fraction of the chloroform extract, its methanol and ethyl acetate sub-fractions and the isolated compounds from the sub-fractions i.e., ECP 1 & 2 and MCP 1 &2, of the seeds of Carica papaya were used at concentrations of 0.1%, 0.5%, 1% and 2%. Sperm motility was assessed immediately after addition of extracts and every 5 minutes thereafter for 30 minutes. RESULTS: There were dose-dependent spermicidal effects showing an instant fall in the sperm motility to less than 20% at 2% concentration. Isolated compounds ECP 1 & 2 were more effective inducing a motility of less than 10%. Many of the spermatozoa became vibratory on the spot. Total inhibition of motility was observed within 20-25 min at all concentrations of all products. Scanning and transmission electron microscopy revealed deleterious changes in the plasma membrane of the head and mid-piece of spermatozoa. Sperm viability test and the number of abnormal spermatozoa after completion of incubation suggested that the spermatozoa were infertile. The effects were spermicidal but not spermiostatic as revealed by the sperm revival test. CONCLUSION: The results reveal spermicidal activity in vitro of the seed extracts of Carica papaya.     

Tc-99m and Re-186 complexes of tetraphosphonate ligands and their biodistribution pattern in animal models

The syntheses of four alpha-aminomethyl phosphonates and their complexation studies with (99m)Tc and (186/188)Re are reported. Complexation conditions were standardized to give maximum yields, which ranged from 90-97%. The yields of complexation were estimated by paper chromatography. The (99m)Tc complexes were stable for more than 4 h, while the (186/188)Re complexes were stable for 3-8 days when stored at 4 degrees C. Biodistribution of these complexes in Wistar rats were carried out, and the uptake in bone and other soft tissue are detailed. Bone uptake of the (99m)Tc complexes varied from 40-60% at 30 min postinjection depending on the ligands. The uptake in soft tissue was minimum with all the complexes. A comparison of the biodistribution studies of the (99m)Tc complexes with that of the well-established radiopharmaceutical (99m)Tc-MDP was carried out for the purpose of evaluating the efficacy of the radiopharmaceutical preparation with the complexes of these ligands. The bone uptake of the (186/188)Re complexes varied from 19-28% corresponding to 1.6-3% per g at 3 h postinjection. The residual activity in both (99m)Tc and (186/188)Re complexes showed renal clearance.     

186Re-1,4,8,11-tetraaza cyclotetradecyl-1,4,8,11-tetramethylene phosphonic acid: a novel agent for possible use in metastatic bone-pain palliation

In connection with our work on the development of 186Re-tetra-phosphonates with optimum properties for use in bone pain palliation, a novel cyclic tetraphosphonate derivative, has been synthesized, complexed with 186Re and evaluated with promising results. The ligand, which consists of a cyclic array of tetra-aminomethylphosphonate groups, was synthesized using orthophosphorus acid, 1,4,8,11-tetraazacyclotetradecane and formaldehyde. The labeling conditions with 186Re have been standardized under varying reaction conditions to give maximum yield. In a reaction volume of 1 mL, maximum complexation yield of 98% was observed at pH 2 using 0.1 mg Re (37-370 MBq) for a ligand concentration at 9 x 10(-2) M/L, under heating at 100 degrees C for 30 min with 2 mg of stannous chloride. The complex was found to be stable for 6 days with RC purity remaining approximately 97%. The complex was characterized by paper chromatography in saline and acetone, wherein the R(f) exhibited were 0.9 and 0, respectively. Biodistribution studies of the complex were performed in male Wistar rats. Activity in femur which was observed to be 1.8%/g (equivalent to about 23% of the injected activity in skeleton) at 3 h post injection remained almost constant up to 48 h. Minimum activity was observed in blood and other soft tissues. The complex showed major renal clearance. Scintigraphic images in rabbits after injecting 70-100 MBq of 186Re-CTMP and using a dual head gamma camera were observed to be superior to 186Re-HEDP, prepared by a procedure standardized by us. Insignificant activity was observed in other vital organs. The results suggest the suitability of the complex for further evaluation in higher animals for bone pain palliation.     

Esophageal atresia and tracheoesophageal fistula: a review of 25 years' experience

During a 25-year period (1972–1996), 585 patients with esophageal atresia with or without tracheoesophageal fistula were treated at the Department of Pediatric Surgery, SMS Medical College, Jaipur, India. Increasing awareness of the anomaly has led to early detection and referral with fewer pulmonary complications. For purposes of analysis the period has been divided into five phases, with a steady decline in overall mortality observed from 95.4% in phase 1 to 41% in phase V. Although postoperative complications have also shown a declining trend, delay in diagnosis, prematurity, low birth weight, delayed arrival at the surgical centers, sepsis, pulmonary complications including pnuemonitis, and inadequate nursing care all continue to contribute substantially to lower the survival in developing countries such as ours. Accepted: 27 September 1999     

Evidence for endogenous formation of tobacco-specific nitrosamines in rats treated with tobacco alkaloids and sodium nitrite

Carcinogenic tobacco-specific nitrosamines are present in tobacco products and are believed to play a significant role in human cancers associated with tobacco use. Additional amounts of tobacco-specific nitrosamines could be formed endogenously. We tested this hypothesis by treating rats with nicotine and sodium nitrite and analyzing their urine. Initially, we treated groups of rats with (S)-nicotine (60 micromol/kg) and NaNO2 (180 micromol/kg), (S)-nicotine alone, NaNO2 alone or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 12 nmol/kg) by gavage twice daily for 4 days. We collected urine and analyzed for two metabolites of NNK; 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanol and its glucuronide. We did not detect these metabolites in the urine of rats treated with nicotine alone or nicotine plus NaNO2, indicating that endogenous conversion of nicotine to NNK did not occur. However, the urine did contain N'- nitrosonornicotine (NNN), N'-nitrosoanabasine (NAB) and N'- nitrosoanatabine (NAT). Analysis of the (S)-nicotine used in this experiment demonstrated that it contained trace amounts of nornicotine, anabasine and anatabine. In a second experiment, we used an identical protocol to compare the endogenous nitrosation of this (S)-nicotine with that of synthetic (R,S)-nicotine, which did not contain detectable amounts of nornicotine, anabasine or anatabine. NNN (0.53 x 10(-3)% of nicotine dose), NAB (0.68%) and NAT (2.1%) were detected in the urine of the rats treated with the (S)-nicotine and NaNO2. NNN (0.47 x 10(- 3)% of dose), but not NAB or NAT, was present in the urine of the rats treated with synthetic (R,S)-nicotine and NaNO2. NNN probably formed via nitrosation of metabolically formed nornicotine. These results demonstrate for the first time that endogenous formation of tobacco- specific nitrosamines occurs in rats treated with tobacco alkaloids and NaNO2. The potential significance of the results with respect to nitrosamine formation in people who use tobacco products or nicotine replacement therapy is discussed.      

Expression of differential nitric oxide synthase isoforms in human normal gastric mucosa and gastric cancer tissue

The present study investigated the expression and distribution of three isoforms of nitric oxide synthase (NOS) in different anatomical regions of the human stomach and in gastric neoplastic tissues by immunohistochemistry using specific antibodies. Intracellular localization of individual isoenzymes of NOS was detected in normal gastric mucosa. Gastric cancer tissues had a marked reduction of all three NOS isoforms expression. The expression of the endothelial NOS, neuronal NOS and inducible NOS in the tumor tissue was significantly lower than in normal gastric mucosa (P = 0.01, P = 0.02, P < 0.01, respectively). In the tumor tissue the expression of inducible NOS was significantly lower than the expression of both constitutive forms of NOS (P < 0.01). There was a tendency to higher expression of both constitutive forms of NOS in earlier stages T2 of the tumor compared to advanced T4 tumor. In contrast, the expression of inducible NOS was higher than in the advanced T4 tumor than in the earlier stages T2 of the tumor. The mapping of the expression of endothelial NOS, neuronal NOS and inducible NOS in human stomach showed higher expression of NOS isoforms in the distal third than in the proximal third of the stomach (P = 0.03, P = 0.04, P = 0.01, respectively). We conclude that there is greater expression of NOS in the stomach corpus and in antrum than in the proximal third of the normal human stomach mirroring the anatomical predilection of common pathological changes in this part of the human stomach. Furthermore, there was loss of the expression of individual isoenzymes in gastric neoplasms.      

Absolute configuration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol formed metabolically from 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is an important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone (NNK). Using the chiral derivatizing agent, (R)- (+)-alpha-methylbenzyl isocyanate [(R)-(+)-MBIC], previous work has shown that the enantiomeric ratio of metabolically formed NNAL and its glucuronide derivative may be species dependent. However, the absolute configuration of such NNAL has not been previously reported. Synthetically prepared racemic NNAL was converted to diastereomeric esters by reaction with (R)-(+)- and (S)-(-)-alpha-methoxy-alpha- (trifluoromethyl)phenylacetic acid (MTPA) chloride (Mosher's reagent) and the products were characterized by 1H-NMR. Based on chemical shift data, the absolute configuration of NNAL in each diastereomeric ester was assigned. Hydrolysis of (R)-NNAL-(R)-MTPA gave (R)-NNAL. This was converted to the corresponding carbamate by reaction with (R)-(+)-alpha- MBIC and the absolute configurations of the diastereomeric carbamates formed by reaction of (R)- and (S)-NNAL with (R)-(+)-MBIC were thereby assigned. Conversion of metabolically produced NNAL to the same carbamates allowed us to assign the NNAL formed from NNK by rat liver microsomes as (R)-NNAL. The major and minor NNAL-glucuronide diastereomers found in the urine of patas monkeys and humans exposed to NNK were similarly assigned; they were formed from (R)-NNAL and (S)- NNAL, respectively.