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Strabismus surgery is one of the most common pediatric ophthalmic procedures. The purpose of this continuing professional development module is to update physicians on the anesthetic considerations of pediatric patients undergoing strabismus surgery.
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Substituted benzamides such as metoclopramide, cisapride, zacopride, renzapride or BRL 20627, stimulate intestinal motility in various species. As they are antagonists at 5-HT3 and agonists at 5-HT4 receptors and as both mechanisms could potentially contribute to their gastrointestinal prokinetic effect, the underlying mechanism is unclear. To clarify this, the effect of some substituted benzamides on gut motility was investigated in the isolated guinea pig ileum using the Trendelenburg technique, in which pressure-induced peristaltic contractions are measured. All benzamides stimulated the peristaltic reflex with the rank order of potency: renzapride greater than cisapride greater than BRL 20627 greater than (+/-)-zacopride greater than metoclopramide. ICS 205-930, granisetron and 2-methyl-5-HT did not change the peristaltic response. 5-HT and 5-methoxytryptamine potently mimicked the effect of the benzamides. The effect of 5-HT was not blocked by ICS 205-930 (10(-7) M). These results indicate that the Trendelenburg preparation is suitable for the investigation of intestinal prokinetic effects of the substituted benzamides. Furthermore, the results suggest that the intestinal effect of benzamides results from activation of 5-HT4 receptors rather than from blockade of 5-HT3 receptors.
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Rectal indomethacin was compared with placebo in a randomised, double-blind study of 100 patients undergoing spinal surgery, in which postoperative pain scores, pethidine, diazepam and metoclopramide consumption, bleeding time, blood loss and oral fluid and food tolerance were measured. Side-effects of indomethacin and pethidine were compared in the two groups. In the indomethacin group, pain scores were significantly less for all measurements made during the first three postoperative days, pethidine and diazepam consumption were significantly less on all three days, bleeding time was significantly increased, although still within the clinically normal range, intraoperative and postoperative blood losses were not significantly affected, coagulation was not significantly impaired as assessed clinically, patients tolerated oral feeding significantly earlier, there was no significant increase in the incidence of gastro-intestinal side-effects except for diarrhoea, and there was no significant reduction in the incidence of side-effects associated with the use of pethidine.
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We reviewed our upper endoscopic records over a 27-month period, retrospectively for 23 months and prospectively for four months and identified patients with substantial bile reflux. Patients with prior gastrectomies were excluded. Of the remaining 36 patients, 23 had prior cholecystectomies. Bile reflux gastritis and esophagitis were found in the majority of patients with bile reflux and occurred more often than is generally appreciated. Patients were seen with a fairly consistent and protracted clinical pattern, usually with severe early postprandial epigastric pain, tenderness and frequent heartburn. Cholecystectomy appeared to be a most important predisposing factor. The correct diagnosis can only be made by upper gastrointestinal endoscopic inspection and biopsies. A pilot therapeutic trial of metoclopramide suggests beneficial effects of this drug in the majority of afflicted patients. A randomized controlled trial of metoclopramide is being prepared to define more clearly the role of this drug in bile reflux gastritis and esophagitis.
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The diagnosis of the female infertility is concentrated on five main points: monitoring of the female cycle, diagnosis of tubal, cervical, immunologic and psychosomatic factors. Outpointed is the endocrinological control in the female cycle and there disturbances. An important role in insufficiency of ovaries plays the hyperprolactinemic, the hyperandrogenemic and the thyroidogenic state. Also important for the diagnosis of female infertility are functional explorations like Metoclopramide and TRH tests.
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There is reason to believe that the dopaminergic system plays a role in the control of salt and water metabolism in the neonate. Therefore, we performed a series of studies designed to test this assumption and reveal the relationship between dopamine (DA) and other factors known to affect salt and water balance. The postnatal course of urinary dopamine excretion was assessed in a group of premature infants kept on low or high salt diet. A clear association between sodium depletion and increased DA excretion, and between reduction in DA excretion and restoration of salt balance was demonstrated. In premature infants with cardiopulmonary distress, DA therapy resulted in an increase in sodium and water diuresis, enhanced plasma renin activity (PRA) and decreased plasma prolactin level; the plasma aldosterone (pAldo) level remained stable. Metoclopramide (MTC), a specific DA antagonist given to premature infants to treat functional gastrointestinal disturbances, induced an increase in Na+ and water excretion which was associated with significant falls in plasma and urinary aldosterone, but left PRA unaltered. Arginine vasopressin excretion also fell after MTC, but this change was not associated with increased free water clearance. These results suggest that endogenous DA has no apparent influence on PRA and, contrary to findings in adults, it stimulates the secretion of aldosterone and vasopressin and thus tubular sodium and water reabsorption.
Thirty-seven patients with advanced malignancies, who received cis-platinum-based combination chemotherapy, were evaluated for the antiemetic efficacy of high-dose metoclopramide. Most of the patients suffered from ovarian carcinoma. The dose of metoclopramide was 7.5 or 10 mg/kg per course. A total of 69 courses were given to 37 patients and in 22% of the courses, nausea and vomiting were eliminated altogether. In an additional 48% of the courses, a partial protection from chemotherapy-induced emesis was evident. No serious side effects were observed. The administration of high-dose metoclopramide is recommended for prevention of cis-platinum chemotherapy-induced emesis.
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To compare the effects of midazolam, which is a fast and short-acting benzodiazepine, and diphenhydramine, which is a widely used anticholinergic agent, in clinical practice for the treatment of metoclopramide-induced akathisia.
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We describe a case of neurological symptoms after the intrathecal use of an opioid. These symptoms were not reversible by the use of an opioid-antagonist.
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1. Fast cyclic voltammetry at carbon fibre microelectrodes was used to study the effects of several dopamine antagonists upon stimulated dopamine release in the rat striatum and nucleus accumbens. 2. In both nuclei, stimulated dopamine release was increased by D2-receptor-selective and mixed D1/D2-receptor antagonists. The D1-selective antagonist SCH 23390 had no effect. 3. Striatal and limbic dopamine release were elevated by cis- but not trans-flupenthixol. 4. The 'atypical' neuroleptics (clozapine and thioridazine) did not cause a selective elevation of dopamine release in the limbic terminal region, whereas the non-antipsychotic drug metoclopramide increased dopamine release more in striatum than nucleus accumbens. 5. We conclude from this study that striatal and limbic dopamine release are under the control of a stereoselective dopamine D2-autoreceptor on the nerve terminal and that atypical neuroleptics do not show a limbic-selective effect at this receptor after acute administration.
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As a first step in an extensive project planned to determine serum PRL levels in response to oral metoclopramide in women with a diverse gyneco-obstetric history, it was decided to study 51 clinically healthy nulliparous women, aged 15.8 to 48.2 years, with history of regular menses at least one year before the study (except the three postmenopausal women), with no regular drug ingestion during the last six months. Women were studied on days 18 to 22 of menstrual period, after a 30 minute rest on basal conditions (3 samples) at 60, 90, and 120 minutes after a single 10 mg. oral dose of metoclopramide. Duplicate PRL determinations were performed in all samples and progesterone(P) only in a pool of the three basal samples by radioimmunoanalysis. All women had serum P levels > or = 4.0 ng/ml. A significant linear positive correlation (r > or = 0.6795, p < 0.001) was observed between chronologic age (CA) and serum PRL levels, regardless the way they were expressed. Considering the individual responses it was decided to divide the group according to CA and it was observed that serum PRL levels--expressed in any form were always significantly greater in women aged > 25 years (Group 2) in contrast with women aged < or = 25 years (Group 1). Since differences were evident, percentiles 3, 50 and 97 for serum PRL levels were calculated during each test time for both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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Progressive systemic sclerosis (PSS) is a chronic multisystem disease characterized by excess deposition of connective tissue in skin and internal organs, associated with microvasculature changes and immunologic abnormalities. Involvement of the gastrointestinal tract may occur in 2 stages, a neuropathic disorder followed by a myopathy. Gastric emptying is delayed in 10% to 75% of patients and correlates with symptoms of early satiety, bloating, and emesis. Compliance of the fundus is increased although perception of fullness is normal. Myoelectric abnormalities have been found in some studies. Treatments include metoclopramide, cisapride, and erythromycin. Bleeding from telangiectasias and watermelon stomach is treated endoscopically. Small bowel involvement in PSS occurs in 17% to 57% of patients. The migrating motor complexes are reduced or absent, predisposing to bacterial overgrowth. Malabsorption may also be due to pancreatic insufficiency. Barium enemas demonstrate pancolonic involvement in 10% to 50% of patients with PSS. Wide-mouthed diverticuli, involving all layers of the intestinal wall, are characteristic. Pseudoobstruction may respond to octreotide or prucalopride therapy. Complications include pneumatosis cystoides intestinalis, stercoral ulcerations, and perforation. Fecal incontinence may be due to dysfunction of the internal anal sphincter, a smooth muscle responsible for most of the resting anal sphincter pressure. Anal manometry may show a reduction or loss of the rectoanal inhibitory reflex. Treatments include biofeedback, sacral nerve stimulation, and surgery. PSS involves the gastrointestinal tract from the mouth to the anus. Studies are needed to define effective treatments in these diseases, which cause great morbidity.
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In squirrel monkeys that had undergone repeated treatment with haloperidol at intervals of 7--14 days, subsequent acute administration of haloperidol induced dystonia and dyskinesias. This acute effect of haloperidol was dose-related and occurred at the same doses that impaired Sidman avoidance performance. Chlorpromazine, fluphenazine, metoclopramide, tetrabenazine, and Su-23397, all of which have been associated with extrapyramidal side effects, reliably elicited dyskinesias in these monkeys. Dyskinesias were less mared after thioridazine and absent after clozapine, corresponding to the reported lower incidence of extrapyramidal side effects in the clinic. The non-neuroleptics, baclofen, and diazepam, failed to elicit dyskinesias. In contrast to the dyskinetic syndrome, the incidence of catalepsy or tremor did not accurately predict propensity to elicit extrapyramidal symptomatology. The acute dyskinetic syndrome in squirrel monkeys may therefore serve as an animal model for predicting the ability of antipsychotics to cause extrapyramidal dysfunction, and may yield insight into the mechanisms of these drug-induced motor disorders.
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Progressive systemic sclerosis alters smooth muscle function throughout the gastrointestinal tract. In 10 consecutive patients with the disease, colonic spike activity and contractile activity were measured after a 1000-kcal meal, intramuscular injection of neostigmine, or intravenous injection of metoclopramide. The 1000-kcal meal stimulated a significant increase in spike and contractile activity in normal subjects. Nine of the 10 patients had no increase in motility after eating. Neostigmine or metoclopramide stimulated colonic spike (p less than 0.01) and contractile (p less than 0.02) activity in normal subjects and stimulated colonic motility (p less than 0.01) in four of 10 patients with less severe systemic manifestations of the disease (Group 1). The drugs had no effect on patients with severe progressive systemic sclerosis (Group II). The patients with severe scleroderma had significant gastrointestinal roentgenographic abnormalities and severe cardiac, renal, or pulmonary dysfunction. Four of six Group II patients died from the disease; all four had marked smooth muscle atrophy in the colonic wall. These findings suggest that the gastrocolonic response is absent early in the disease process and that the smooth muscle atrophy occurring with progression of the disease may lead to a more severe colonic motor disturbance.
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A prospective randomized study was performed to assess the value of some individual risk factors for postoperative nausea and vomiting (PONV), and to compare the efficacy of ondansetron, metoclopramide, dexamethason, and combinations of these antiemetics in preventing PONV in patients after laparoscopic cholecystectomy.
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From 2011 to 2014, patients at 2 large hospitals were randomized after radical cystectomy to receive access to liquids and then a regular diet on postoperative days 1 and 2 or conventional care with introduction of a liquid diet after return of bowel activity, typically days 3-5. Early ambulation, use of metoclopramide, and no nasogastric tube were standard for all patients. The study was powered to detect a 50% decrease in 90-day complication rate with secondary end points of length of stay, time to bowel activity, and time to diet tolerance. The study was terminated early due to slow accrual (102 of 328).
There was no difference between groups in relation to clinical outcome. Two animals in the study group had blocked anastomotic leakage. The animals that received bromopride had the number of intracavitary adhesions and adhesions to the anastomosis similar to the control group. The anastomoses from the group E3 animals showed lower resistance to rupture the one from the C3 group (p = 0.04). This effect did not occur on the seventh postoperative day (p = 0.37). There was no significant difference between groups in relation to histopathology and hydroxyproline concentration in the anastomoses.
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Nephrotoxicity was studied in 47 patients who received combined chemotherapy with cisplatin (DDP, 50-100 mg/m2) as the chief agent. The treatment was given every 3-4 weeks with vigorous hydration and forced diuresis. The renal tubular toxicity was evaluated by urinary beta 2 microglobulin (beta 2-MG). It was found that the nephrotoxicity secondary to DDP was dose-dependent. Hypertonic saline was able to decrease the renal damage without any significant difference among the first, second and third course. The nephrotoxicity of DDP administered in one day was more severe than that given in two days. beta 2-MG was a good parameter of DDP nephrotoxicity. By multivariate statistical analysis, metoclopramid and chlorpromazine were found to alleviate DDP nephrotoxicity. Classification, examination and management of DDP nephrotoxicity is proposed.
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Nausea was significantly lower in the TROP group as compared with the MET group (median: 0.14 vs. 1.32; P = 0.03). Thirty percent of all patients experienced vomiting. In the TROP group one patient had a mean number of emetic events > 0 as compared with 6 patients in the MET group (P = 0.07). Two patients in the TROP group and one in the MET group discontinued therapy due to lacking control of emesis. In two further patients the doubling of the metoclopramide resulted in acceptable control of nausea/vomiting. Both drugs were generally well tolerated.
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Postoperative ileus is characterized by decreased gastrointestinal myoelectric activity and motility. Metoclopramide was used to treat experimentally induced postoperative ileus in six dogs. Contractile activity was monitored by extraluminal strain gages on the pyloric antrum and proximal segment of the duodenum, and myoelectric activity was measured by recording bipolar electromyograms (EMGs) at the pyloric antrum, pyloric canal, proximal segment of the duodenum, proximal and distal parts of the jejunum, and ileum. Measurements were obtained from animals without ileus (baseline) and those with ileus that were either untreated or treated with metoclopramide. Adynamic ileus was induced by rubbing a 50 cm segment of jejunum with a dry sponge for 5 minutes and exposing the bowel to the air for 30 minutes. Treated dogs received metoclopramide (0.4 mg/kg 4 times daily [QID] intravenously [IV]), whereas untreated dogs received a saline placebo, starting 1 hour after celiotomy closure. Recordings were made for 26 hours after induction of ileus. The phases of the migrating myoelectric complex (MMC) were identified and motility index values were determined. During ileus, the MMC phase II duration was increased at the duodenum and phase III duration was decreased at the antrum, pylorus, duodenum, and proximal segment of the jejunum (p less than 0.05). Motility index values were decreased at the antrum and duodenum during ileus (p less than 0.05). Treatment with metoclopramide reversed the MMC phase III inhibition at the antrum and pylorus, and partially reversed the inhibition at the duodenum and jejunum (p less than 0.05). Motility index values were restored to preoperative baseline values with metoclopramide treatment (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Drug-induced depression which is classified as DSM-III-R is difficult for clinicians to diagnose because the cause is not easily distinguishable from adjustment disorders or nonorganic mood disorders. This review summarizes the few articles published within 20 years as searched in the Index Medicus about the clinical manifestations of organic mood syndromes from oral contraceptives (OCs), beta blockers, alcohol and sedative-hypnotic drugs, and other medications. There was a noticeable lack of articles and specific clinical features which would help differentiate causes. Oral contraception may cause depression by inducing hepatic tryptophan oxidase, which may lead to a deficiency of vitamin B6. The most common reason for discontinuing OCs is depression, i.e., there are reports of a rate of 70/1000 woman years during the 1st year of OC use. However, the rate among females examined in a catchment study was similar at 6.6%. There is some indication that depression may be dose related, i.e., low dose is related to the same prevalence as in the control group. A basic requirement of DSM-III-R is severe and persistent depression; OC-related depression does not exhibit sleep or appetite disturbances. The relationship between beta blockers and depression indicates that the prevalence and the nature of the relationship are not consistently confirmed. Depressive episodes (14) reported in 8 studies showed major depression and suicidal thoughts or attempts just after initiation of propranolol and resolution when the drug was discontinued; timing of the symptoms may be the best basis upon which to make a clinical judgement. Alcohol use is usually seen as associated with depression, but the extent to which alcohol induces depression is unknown. Symptoms are transitory and appear during bouts of heavy drinking. Studies on benzodiazepine use and depression are reported to be confounded by other factors. Other depression-causing agents for which information was unavailable are identified as psychostimulants, metoclopramide, H-2 blockers, methyldopa, and steroids.
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To investigate whether exogenous hypercalcemia influences the release of TSH from the anterior pituitary, 25 microgram TRH were injected iv in six healthy subjects who were pretreated orally with either 10 mg metoclopramide or placebo and infused iv with either calcium or saline. Under normocalcemic conditions, TRH raised the serum TSH level from 1.1 +/- 0.1 to 8.0 +/- 3.3 microU/ml (P less than 0.01). Exogenous hypercalcemia reduced this TSH response to TRH by 37 +/- 11% (P less than 0.02). Although metoclopramide was without effect on basal TSH release in an additional five healthy subjects and also left TRH-stimulated TSH release unaffected under normocalcemic conditions, oral pretreatment with the drug counteracted the inhibitory effect of hypercalcemia and restored a normal TSH response to TRH in hypercalcemic subjects. These results indicate that exogenous hypercalcemia may potentiate dopaminergic TSH inhibition in normal individuals.
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While aprepitant significantly reduced the incidence of PONV compared with a multimodal antiemetic regime, used alone it did not eliminate PONV.