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The ondansetron regimen was more effective and less toxic, but its cost was 20 times more than the metoclopramide regimen.
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Postoperative nausea and vomiting (PONV) is common in women undergoing dilatation and curettage under general anesthesia for pregnancy termination, and many studies suggest treating these women prophylactically for PONV.
We evaluated the clinical applicability of a 2-h test in which the prolactin (Prl) responses to thyrotrophin releasing hormone (TRH)(200 micrograms iv) and the dopamine antagonist, metoclopramide (MC; 10 mg iv) were studied successively, 1 h apart. Nine healthy women were studied with TRH-MC test and with another test in which MC alone was used or the drugs were given in opposite order. The preceding TRH injection did not affect the Prl responses to MC, nor did preceding MC affect the Prl response to TRH. With the TRH-MC test, Prl responses to TRH and MC were significantly lowered in amenorrhoea (N = 8) and hyperprolactinaemia (N = 15) regardless of whether or not treated with bromocriptine, and to MC only in oligomenorrhoea (n = 11). In normoprolactinaemic galactorrhoea (N = 7) the responses were similar as in healthy women. The ratio between Prl responses to TRH and MC was significantly higher in women with bromocriptine-treated hyperprolactinaemia (1.06 +/- 0.8, SD) than in healthy controls (0.34 +/- 0.13). The capacity of pituitary lactotrophs to secrete Prl in response TRH and MC can be evaluated with a 2-h test which has potential for investigation of pituitary Prl dynamics in gynaecological endocrine disorders, particularly in amenorrhoea and hyperprolactinaemia.
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Serum LH concentration.
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Prospective, randomized, double-blind study.
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Organophosphates are a class of highly toxic chemicals that includes many pesticides and chemical weapons. Exposure to organophosphates, either through accidents or acts of terrorism, poses a significant risk to human health and safety. Existing antidotes, in use for over 50 years, have modest efficacy and undesirable toxicities. Therefore, discovering new organophosphate antidotes is a high priority. Early life stage zebrafish exposed to organophosphates exhibit several phenotypes that parallel the human response to organophosphates, including behavioral deficits, paralysis, and eventual death. Here, we have developed a high-throughput zebrafish screen in a 96-well plate format to find new antidotes that counteract organophosphate-induced lethality. In a pilot screen of 1200 known drugs, we identified 16 compounds that suppress organophosphate toxicity in zebrafish. Several in vitro assays coupled with liquid chromatography/tandem mass spectrometry-based metabolite profiling enabled determination of mechanisms of action for several of the antidotes, including reversible acetylcholinesterase inhibition, cholinergic receptor antagonism, and inhibition of bioactivation. Therefore, the in vivo screen is capable of discovering organophosphate antidotes that intervene in distinct pathways. These findings suggest that zebrafish screens might be a broadly applicable approach for discovering compounds that counteract the toxic effects of accidental or malicious poisonous exposures.
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The combination group had a significantly higher complete response rate than the acustimulation group (73% vs.40%, P <0.01). In addition, fewer patients (8 vs. 18) in the combination (vs. acustimulation) group experienced subsequent emetic events (P < 0.03). However, there were no significant differences between the three groups with respect to patient satisfaction and quality of recovery scores.
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In this research psychic and somatic symptoms related to disturbances of hypothalamus-hypophysis-peripheral regulation which may occur in the schizophrenic process were analysed. Authors discussed the problem of relations between hypothalamus neuroregulation and pathogenesis of endocrine disturbances which suggest the organic cause of obesity, hirsutism and secondary amenorrhea among women diagnosed with paranoid schizophrenia. Actual antipsychotic pharmacological treatment, including some side-effects: the metabolic (obesity) and the endocrine (hyperprolactinemia) ones were considered. The authors conclude that endocrine disorders which are connected with hypothalamus disfunction (sleeping, eating and reproductive functions) may reach the psychotic symptoms and treating them influences at the same time some endocrine changes. The estimation of PRL release in a test of stimulation with metoclopramide can be a sensitive (though not specific) test of dopaminergic activity in tuberous--infundibulum pathway and may be used to control the treatment.
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Today's physician has many useful medication options available for acute migraine treatment. There is a wide cost range among these drugs and today's health care environment demands that cost be factored into the decision process. Effective migraine abortive treatment decreases the costs of repeat dosing and disability. Early use of migraine abortive medication can increase its rapidity of action and effectiveness. Adjunctive medication such as metoclopramide ($0.10) is inexpensive and may improve the effectiveness of the primary abortive medication. Over-the-counter medications such as aspirin ($0.02/325 mg), Excedrin ($0.09/tablet), ibuprofen ($0.04/200 mg), or naproxen sodium ($0.09/220 mg) are inexpensive and effective. "Triple therapy" combining metoclopramide, a nonsteroidal anti-inflammatory agent, and an ergotamine preparation may improve tolerance and effectiveness of the ergot. Locally compounded dihydroergotamine nasal spray is inexpensive ($0.78/1 mg spray). The cost of using oral sumatriptan can be almost halved by prescribing half of a 50-mg tablet. Emergency department services are expensive. Huge cost savings occur through self-controlled administration of oral, rectal, or even intramuscular narcotic medications. Oral narcotic agents such as hydromorphone ($0.42/4 mg) and meperidine ($0.92/200 mg) are generally used in inadequate doses to be effective for severe migraine. Guidelines are give for more effective use of these agents. Sophisticated comparative studies are needed to evaluate, not only the direct costs of medications, but all costs of treatment of an acute migraine attack, as well as indirect costs to the patient, family, and society.
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The combination of Fourier transform infrared (FT-IR) microspectroscopy with a thermal analyzer was applied to quickly investigate the solid-state ion-exchange reaction of metoclopramide HCl monohydrate (MCP H(2)O) by clipping MCP H(2)O powder between two KBr or KCl pellets. The physical and ground mixtures of MCP H(2)O or 150 °C-preheated MCP powder and KBr or KCl powders with a weight ratio of 1 : 100 were also prepared and determined by FT-IR microspectroscopy. The samples of MCP H(2)O or 150 °C-preheated MCP were identified by using differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis. The results of present study indicate that the ion-exchange reaction was easily induced between MCP H(2)O and KBr by grinding and heating processes. The possible mechanism of ion-exchange reaction may take place between the HCl salt of MCP H(2)O and a KBr matrix by grinding or heating to yield a mixture of HCl and HBr salts of the MCP sample in the presence of hydrated water. The crystal hydrate played an important role to improve this ion-exchange reaction between MCP H(2)O and KBr. However, no ion-exchange reaction occurred between MCP H(2)O and KCl or between 150 °C-preheated MCP and KBr. The solid-state ion-exchange reaction was more easily determined by this novel thermal FT-IR microspectroscopy than other conventional methods.
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To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared with placebo and other active interventions in the treatment of acute migraine in adults.
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In a randomised, placebo-controlled, double-blind trial, the efficacy of 12.5 mg dolasetron i.v. and 1.25 mg DHB was evaluated in preventing PONV in 83 patients undergoing surgery for prognathism. Patients were allocated randomly to one of three groups: group A (n=27) received 12.5 mg dolasetron intravenously (i.v.), group B (n=27) received 1.25 mg DHB i.v. and placebo group C (n=29) received saline 0.9%. If patients complained of retching or vomiting or if patients demanded antiemetics, 20mg metoclopramide (MCP) i.v. was given. Postoperative nausea, postoperative vomiting, or nausea and vomiting was assessed in the postoperative period at 0-4 h and overall between 0 and 24 h.
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A new group of selective 5HT3 antagonists are proving to be effective anti-emetics for cytotoxic and radiation induced vomiting in both animal models and man. Current anti-emetic regimens often benefit from combination therapy, in particular the efficacy of metoclopramide (which can be a weak 5HT3 antagonist), can be improved by combination with dexamethasone, another anti-emetic. Hence it was of interest to evaluate whether a 5HT3 receptor antagonist GR38032F could be improved by combination with dexamethasone. Vomiting induced by cyclophosphamide in the ferret was observed after pre-treatment with dexamethasone alone or in combination with GR38032F. Animals were also observed for signs of 'nausea'. Dexamethasone alone proved a weak anti-emetic in this system but did have significant effects on 'nausea'. GR38032F has previously been shown to be capable of totally controlling emesis due to cyclophosphamide in the ferret. Here a dose of GR38032F that is not 100% effective was employed; this was shown to have effects on 'nausea' but most interestingly its anti-emetic action was increased by combination with dexamethasone. This may be important for the minority of patients whose vomiting is not completely controlled by GR38032F alone.
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The occurrence of nausea and vomiting appeared more frequently during 6 to 24 hours following the administration of epidural morphine. The total frequency of nausea and vomiting in the dexamethasone group was significantly lower than that of the metoclopramide and saline groups during this period, with reporting frequencies of 21%, 49%, and 53%, respectively (p <.05 each). However, the difference between metoclopramide and saline did not reach statistical significance.
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This randomised, double-blind, parallel-group study was carried out to compare the efficacy and safety profile of ondansetron plus dexamethasone and metoclopramide plus dexamethasone in patients receiving fractionated cisplatin (20-25 mg/m2/day) chemotherapy for the treatment of testicular cancer. An interim analysis of 95 patients showed that the ondansetron regimen was significantly superior compared to the metoclopramide regimen (p < 0.001). According to the study protocol the study was terminated at this stage. At the time the decision to stop the study was taken, a total of 113 patients had been enrolled and were evaluable on an 'intention to treat' basis. Fifty-six of these had received ondansetron (32 mg i.v. single dose/day) plus dexamethasone (20 mg i.v. single dose/day) and 57 were given metoclopramide (2 mg/kg or 1 mg/kg i.v. twice a day) plus dexamethasone (20 mg i.v. single dose/day). The ondansetron regimen was significantly superior in the control of emesis and nausea. Seventy-one percent of patients experienced 2 or fewer emetic episodes over the entire 5-day study period compared with 26% of patients given metoclopramide (p < 0.001). Seventy-nine percent of patients in the ondansetron group experienced 'none' or only 'mild' nausea compared with 39% of patients in the metoclopramide group (p < 0.001). The dose of metoclopramide had to be reduced during the study from 2 mg/kg i.v. twice daily to 1 mg/kg i.v. twice daily because 4 of the first 8 patients randomised to this treatment experienced extrapyramidal reactions. Ondansetron was well tolerated and it did not induce any extrapyramidal reactions. The results of this study show that ondansetron plus dexamethasone represents a very effective treatment option for patients receiving fractionated cisplatin chemotherapy for testicular cancer.
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The results suggest that a combination of intravenous Met and epidural pain control may be required to achieve a considerable decrease in time to resumption of oral soft diet in advanced gastric cancer patients who underwent gastrectomy and IPC. Furthermore, the administration of Met did not increase anastomotic leakage. Met has a role in the prevention of prolonged post-operative ileus.
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Our study showed that the onset times for sensory and motor block were significantly shorter in Group LM compared with Group L and Group IM (4.5 ± 0.7 vs. 5.0 ± 0.7 and 5.0 ± 0.6, respectively, P = 0.006 for sensory block; 6.3 ± 0.7 vs. 5.1 ± 0.9 and 5.9 ± 0.6 respectively, P = 0.000 for motor block). The postoperative VAS scores were significantly less at 1, 5, 10, 15, and 30 minutes after tourniquet release in Group LM compared with Group L and Group IM (P < 0.05).
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1. 5-Hydroxytryptamine (5-HT) stimulated a biphasic increase in short-circuit current (SCC) in guinea-pig isolated ileal mucosa. The initial 'spike' response to 5-HT was inhibited by tetrodotoxin (0.3 microM). We have investigated the 5-HT receptor mechanism(s) controlling the second 'maintained' component of the response which remained after treatment with tetrodotoxin. 2. 5-HT stimulated concentration-related increases in SCC with an EC50 value of 5.4 microM. Isobutyl-methylxanthine (IBMX, 10 microM) produced a six fold leftward shift of this concentration-response curve, suggesting the involvement of a cyclic nucleotide(s) in these responses. 3. In the presence of IBMX, 5-HT stimulated reproducible increases in SCC with an EC50 value of 0.9 microM. The rank order of potency of indole agonists in these tests was 5-HT greater than or equal to 5-methoxytryptamine greater than 5-carboxamidotryptamine = alpha-methyl-5-HT much greater than 2-methyl-5-HT. 4. The substituted benzamides were partial agonists. Metoclopramide and cisapride produced approximately 20% of the 5-HT maximum, and renzapride and R,S-zacopride produced approximately 50% of the 5-HT maximum. Metoclopramide and cisapride inhibited the SCC responses to 5-HT with apparent pKB values of 4.8 and 7.0 respectively. 5. The SCC responses to 5-HT were not inhibited by antagonists selective for 5-HT1 (methysergide, methiothepin), 5-HT2 (ketanserin) or 5-HT3 (ondansetron, ICS205-930) receptors. 6. The SCC responses to 5-methoxytryptamine, 5-carboxamidotryptamine, alpha-methyl-5-HT and R,S-zacopride, but not 5-HT, were selectively inhibited by high concentrations of ICS205-930 with apparent pKB values of approximately 6.7. A possible interpretation of these results is that the 'maintained' SCC response to 5-HT is mediated by a heterogeneous population of 5-HT receptors. One of these receptors exhibits the characteristics of the putative 5-HT4 receptor.
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In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupressure; acupuncture; corticosteroids; ginger; metoclopramide; ondansetron; prochlorperazine; promethazine; and pyridoxine (vitamin B6).
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Reflux esophagitis is a common disorder in which esophageal inflammation is caused by the reflux of gastric contents. The diagnostic approach includes documentation that reflux is present, that the patient's symptoms are caused by the reflux, and that esophageal mucosal damage has occurred. Therapy is guided by the current multifactorial pathophysiology model, which includes efficacy of the antireflux mechanism, volume of gastric fluid, potency of refluxed material, esophageal clearance, and tissue resistance factors. Although recurrences are common, treatment with life style changes supplemented with combinations of liquid antacids, H2 blockers, sucralfate, bethanechol, and metoclopramide is usually effective.
Intradermal tramadol or metoclopramide can produce local anesthetic effect.
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Blockade of dopaminergic pathways increases aldosterone levels by mechanisms that are not well delineated. Since both prolactin (PRL) and plasma renin activity (PRA) also increase after administration of dopaminergic antagonists, the aldosterone increments may be secondary to these changes. To address these questions, the relationship between plasma aldosterone (PA) and PRL responses to 2 different dopamine receptor antagonists, haloperidol and metoclopramide (MCP) was examined in rats. The PA response to MCP was compared before and after blockade of the renin-angiotensin system with saralasin and after pre-administration of L-dopa. MCP administration produced significant and parallel increments in PA and PRL whereas haloperidol increased PRL without any change in PA or PRA. L-dopa pre-treatment suppressed the early PA response to MCP. Hypophysectomy prior to MCP administration eliminated the PRL response but did not significantly alter the PA response to MCP. Our findings suggest that dopamine has an inhibitory action on the adrenal gland production of aldosterone acting independently of changes in PRL and the renin-angiotensin system.
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Early postoperative feeding protocol consisting of clear liquids on the evening of postoperative day 2, regular diet on postoperative day 3, and discharged home as tolerated. A subgroup of patients was treated with metoclopramide.
Eighty-three adult inpatients scheduled to receive general anesthesia for elective surgery.
Simple migraine attacks are usually controlled by rest and an analgesic (acetylsalicylic acid or paracetamol), eventually associated with metoclopramide. More severe cases with failure of these measures may benefit from antimigraine medications such as ergotamine derivatives. Preventive treatment is only indicated in case of frequent (> or = 3 per month) and complicated attacks.
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Studies were performed in 12 conscious sheep of both sexes to determine if a brain dopaminergic pathway is involved in modulating the central actions of angiotensin II (Ang II) in regulating body temperature and plasma renin activity (PRA). Previous data showed that intracerebroventricular (ICV) infusion of Ang II significantly decreased PRA and body temperature. In contrast, converting enzyme inhibitor SQ 20881 (SQ) or dopamine (DA) significantly increased PRA and body temperature of sheep. In the present study, ICV infusion of the DA antagonist metoclopramide (MCP) (20 micrograms/min) significantly decreased PRA to 68 +/- 5% of the basal level. When sheep were pretreated with ICV MCP (20 micrograms/min) for 2 hr and then infused ICV with MCP (20 micrograms/min) plus DA (20 micrograms/min), Ang II (25 ng/min), or SQ (1 microgram/min), the PRA and temperature responses to DA, Ang II, or SQ were all abolished or attenuated significantly. The converse did not hold. Sheep pretreated with SQ (1 microgram/min) still showed a significant increase in body temperature (0.43 +/- 0.05 degree C) when infused with DA (20 micrograms/min). These results support the hypothesis that a central DA pathway is involved in the modulation of the actions of centrally administered Ang II on temperature and PRA.
Prolactin (PRL) may be a tumor growth factor, mainly for breast cancer. The antidopaminergic drugs commonly used in the treatment of chemotherapy-induced vomiting stimulate PRL release, and this finding could represent a potentially negative biologic event for cancer patients. This study was performed to analyze PRL response to the serotonin-type 3 receptor antagonist ondansetron, a new active drug in the treatment of vomiting due to chemotherapy, in cancer patients.