Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to evaluate the effectiveness and side-effects of intrapericardial administration of cisplatin (IAC), in cases of abundant malignant pericardial effusion (MPE) and/or cardiac tamponade occurring in the course of adenocarcinoma of the lung (AL). Fifteen consecutive patients with abundant MPE and AL (4 females and 11 males; mean age 54 yrs) entered this prospective study. Following pericardiocentesis and insertion of a polyurethane catheter, the pericardial fluid was drained. Malignant aetiology of the pericardial fluid was confirmed by cytological examination. After confirmation of MPE, cisplatin (10 mg in 20 mL normal saline) was instilled directly into the pericardial space, over a period of 5 min for 3-5 consecutive days. Treatment was considered successful (response) if the patient survived 30 days without recurrence of symptoms of abundant MPE, and no other interventions directed to the pericardium were required. Response was achieved in 10 patients (67%). The mean (+/-SEM) dose of cisplatin was 56 (+/-18.9) mg. There were no complications related to the pericardiocentesis. Transient atrial fibrillation was detected in one patient. Mild nausea also occurred in one case. No hypotension or retrosternal pain was observed. Sclerotization of the pericardium and pericarditis constrictiva were detected after IAC in only one case. Cisplatin administered directly into pericardial space is effective and safe. Intraperitoneal administration of cisplatin appears to be the method of choice in the treatment of recurrent malignant pleural effusion in patients with primary adenocarcinoma of the lung. Sclerosis of the pericardial space is a very rare complication observed after intraperitoneal administration of cisplatin therapy.
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PMID:Intrapericardial administration of cisplatin in treatment of metastatic pericardial involvement in adenocarcinoma of the lung. 927 Feb 45

Inadequate training of physicians contributes to the undertreatment of cancer pain. To address these concerns, the University of Kentucky has introduced a 4-week course for final-year medical students that teaches the principles of clinical pharmacology and pain management. The purposes of this study are to assess the knowledge deficits of final-year medical students about the use of morphine for cancer pain and to assess the efficacy of a short course on cancer pain management. Eighty-six final-year medical students completed a 22-item questionnaire assessing their knowledge and attitudes toward the use of morphine for cancer pain. Students indicated their agreement with each statement on a four-point scale (one, strongly disagree; four, strongly agree). All students then completed a compulsory short course on pain management. The course content included a 1-hr lecture on chronic nonmalignant pain, a 1-hr lecture on acute pain management, and a 1-hr lecture on cancer pain management. In addition, students completed small-group, problem-based learning modules on several aspects of pain management. After the course, all students completed the same 22-item survey. The alpha reliability score of the pretest instrument was 0.55, and the posttest reliability was 0.86. Upon course completion, students agreed most strongly (mean +/- SEM) that morphine should be given on a regular schedule for cancer pain (3.41 +/- 0.08), that cancer pain management frequently requires co-analgesics (3.36 +/- 0.06), and that patients with good pain relief function better than those with continuing pain (3.39 +/- 0.08). A comparison of pretest and posttest means on specific items suggested that the greatest amount of learning took place in the following content areas: morphine is a good oral analgesic; increases in cancer pain should be treated by increasing the morphine dose; respiratory depression is not a concern for cancer pain patients; and morphine can be used over a wide range of doses. The regular use of morphine was recognized as the treatment drug of choice for cancer pain. The students showed improved knowledge scores on ten of the 22 items on the posttest survey. A significant increase in learning occurred on six knowledge and attitude items. On only one item (nausea as a side effect of morphine) did the knowledge scores decrease on the posttest. A significant minority (40%) of senior medical students had deficits in knowledge about the use of morphine for cancer pain. The risk of addiction, respiratory depression, and tolerance were misunderstood by a significant minority (25%) of students.
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PMID:Medical student knowledge of morphine for the management of cancer pain. 967 Jun 36

Eptastigmine is a new acetylcholinesterase (AChE) inhibitor currently under development for the symptomatic treatment of Alzheimer disease. This study was conducted to establish the maximum tolerated dose and the pharmacodynamics of eptastigmine in nine healthy elderly volunteers. Subjects received single oral doses of 8 mg, 20 mg, 32 mg, and 40 mg eptastigmine and placebo according to a double-blind, randomized, rising-dose, five-way crossover design. Adverse events, blood pressure, heart rate, body temperature, forced expiratory volume, salivary flow, and pupilar activity were closely monitored during treatment. Pharmacodynamic activity of eptastigmine was evaluated with an assay of AChE activity in red blood cells. Eptastigmine doses of 8 mg, 20 mg, and 32 mg were well tolerated. Two of four subjects receiving the 40-mg dose developed profound AChE inhibition (58-59%) and reported severe adverse events (nausea, vomiting, syncope, and bradycardia), precluding further administration in the remaining subjects. Eptastigmine administration produced a weak effect on supine heart rate, body temperature, and pupil diameter. There were no effects on blood pressure, forced expiratory volume, salivary flow, and near point of focus. Acetylcholinesterase activity was inhibited in a dose-related fashion according to a sigmoidal (logistic) function. The mean (+/- SEM) maximum inhibition of AChE activity (Imax) was 14.5+/-3.3%, 20.4+/-2.3%, 28.7+/-2.9%, 45.2+/-1.3% and 53.6+/-2.9% after placebo, 8 mg, 20 mg, 32 mg, and 40 mg of eptastigmine, respectively. The theoretical maximum response (Emax) was 72.9%, and the dose that produced half of the maximum response (ED50) was 29.5 mg. At 24 hours, residual AChE inhibition ranged from 9% to 15%, with a half-life of recovery of the enzyme of approximately 10 hours. The maximum tolerated dose of eptastigmine after single-dose oral administration in healthy elderly subjects is 32 mg. Single oral doses of eptastigmine produce sustained, dose-related inhibition of AChE activity. Adverse events are related to the degree of AChE inhibition.
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PMID:Maximum tolerated dose and pharmacodynamics of eptastigmine in elderly healthy volunteers. 970 45

Fentanyl has been incorporated into a transdermal therapeutic system (TTS) containing a rate-limiting membrane that provides constant release of the opioid. TTS fentanyl provides continuous opioid delivery for up to 72 hr without the need for special equipment. After Institutional Review Board approval, 53 patients with cancer pain requiring 45 mg or more of oral morphine daily were admitted into an open-label, prospective, multicenter evaluation of TTS fentanyl for the relief of pain. After a 1-week stabilization on oral morphine, patients were transferred from morphine to an appropriate dose of TTS-fentanyl (25, 50, 75, or 100 micrograms/hr) administered as a transdermal patch every 3 days. TTS fentanyl was titrated to pain relief, and patients were followed up for as long as 3 months. Pain relief and the side effects of the medications were assessed daily. Twenty-six men and 27 women with a mean (+/- SD) age of 61 (+/- 12) years entered the study; 23 patients completed the full 84-day study. The mean duration of TTS fentanyl use was 58 +/- 32 days. The mean (+/- SEM) daily morphine dose during the last 2 days of stabilization was 189 (+/- 20) mg, and the mean initial fentanyl patch dose was 58 (+/- 6) micrograms/hr. The mean daily morphine dose taken "as needed" for breakthrough pain at study completion was 35 mg. The mean final fentanyl dosage at study completion was 169 (+/- 29) micrograms/hr. Pain relief was rated as good or excellent by 82% of patients during the treatment period. When asked to compare pain relief during the first month of TTS-fentanyl use to that provided by their last analgesic before study entry, 63% preferred TTS fentanyl. Side effects considered related to the fentanyl patch were nausea (13%), vomiting (8%), skin rash (8%), and drowsiness (4%). Thirty percent of patients reported adverse experiences related to the fentanyl patch, and 17% had to be discontinued from the study. We conclude that TTS fentanyl administered every 3 days for the treatment of cancer pain is effective, safe, and well tolerated by most patients.
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PMID:A clinical evaluation of transdermal therapeutic system fentanyl for the treatment of cancer pain. 973 1

Among the potential hazards of laparoscopic surgery using electrocautery is the release of chemical by-products of incomplete tissue combustion into the pneumoperitoneum with subsequent transperitoneal absorption into the bloodstream and/or release into the operating room. The purpose of this study of patients undergoing laparoscopic cholecystectomy (LC) was twofold: (1) to assess the relationship between intraperitoneal concentration of carbon monoxide (CO) and blood levels of carboxyhemoglobin (COHb) and methemoglobin (MetHb), and (2) to assess the surgeon's inhalation of CO resulting from ambient smoke exposure. During LC with monopolar electrocautery, 21 patients were evaluated intraoperatively for intraperitoneal [CO] by sampling gas from a trocar, whereas arterial [COHb) and [MetHb] were determined perioperatively. The surgeon's venous blood was drawn pre- and postoperatively to assay [COHb] and [MetHb]. Patients completed visual analogue questionnaires 6 hours and 24 hours postoperatively to assess for adverse symptoms. Mean (+/- SEM) patient age and weight were 45 +/- 3 years and 84 +/- 4 kg, respectively. Mean duration of the operation was 69 +/- 5 minutes, and electrocautery was used for 3.0 +/- 0.3 minutes. Intraperitoneal [CO] rose to peak levels of 209 +/- 19 ppm at 50 minutes, whereas systemic [COHb] and [MetHb] were unchanged. The surgeon's systemic [COHb] and [MetHb] did not increase postoperatively. Nausea, abdominal pain, and fatigue scores decreased significantly between 6 and 24 hours postoperatively; however, there were no correlations between these symptoms and peak intraperitoneal [CO]. Although LC using electrocautery increases intraperitoneal [CO] to "hazardous" levels, systemic [COHb] and [MetHb] are not elevated by generation of intraperitoneal smoke. The surgeon's exposure to CO by the evacuation of smoke through laparoscopic ports is negligible. Production of smoke during LC using monopolar electrocautery, therefore, does not appear to pose a threat to either the patient or the surgeon.
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PMID:Production and systemic absorption of toxic byproducts of tissue combustion during laparoscopic cholecystectomy. 984 98

The feasibility of performing hysteroscopic endomyometrial resection using isotonic 2.2% glycine as distension medium was studied in 181 consecutive operations. A standard continuous flow loop-resectoscope was used. Distension was achieved by means of a gravity-fed system and glycine flowed out under its own pressure. The mean (+/-SEM) glycine deficit was 160+/-20 ml and in only 7 patients was it >1 liter (maximum 1,800 ml). Only in patients with >1 liter glycine absorption was there a significant decrease in serum sodium level (mean 9 mmol/l), while serum osmolality remained normal. Apart from 1 case of transient nausea, these patients had no sequelae. We experienced isotonic 2.2% glycine as a useful and safe distending medium for operative hysteroscopy.
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PMID:Experience with isotonic 2.2% glycine as distension medium for hysteroscopic endomyometrial resection. 1035 90

Objectives: To assess the long-term efficacy and safety of modafinil in patients with excessive daytime sleepiness (EDS) associated with narcolepsy.Background: Modafinil has been shown to be effective and well tolerated for treating EDS associated with narcolepsy in two large-scale, well-controlled, 9-week clinical trials.Methods: Four hundred and seventy eight adult patients with a diagnosis of narcolepsy who had completed one of two 9-week, double-blind, placebo-controlled, multicenter, clinical trials of modafinil were enrolled in two 40-week, open-label, extension studies. A flexible-dose regimen (i.e. 200, 300, or 400 mg daily) was followed in one study. In the second study, patients received 200 mg/day for 1 week, followed by 400 mg/day for 1 week. Investigators then prescribed either 200- or 400-mg doses for the duration of the study. Efficacy was evaluated using Clinical Global Impression of Change (CGI-C) scores, the Epworth Sleepiness Scale (ESS), and the 36-item Medical Outcomes Study health survey (SF-36). Adverse events were recorded. Data from the two studies were combined.Results: The majority of patients ( approximately 75%) received 400 mg of modafinil daily. Disease severity improved in >80% of patients throughout the 40-week study. At weeks 2, 8, 24, and 40, disease severity was 'much improved' or 'very much improved' in 49, 58, 59, and 58% of patients, respectively. The mean (+/-SEM) ESS score improved significantly from 16.5+/-0.2 at open-label baseline to 12.4+/-0.2 at week 2 and remained at that level through week 40 (P<0.001). Quality of life scores at weeks 4, 8, 24, and 40 were significantly improved versus open-label baseline scores for six of the eight SF-36 domains (P<0.001). The most common treatment-related adverse events were headache (13%), nervousness (8%), and nausea (5%). Most adverse events were mild to moderate in nature. A total of 341 patients (71%) completed the studies. Forty-three patients (9.0%) discontinued treatment because of adverse events.Conclusions: Modafinil is effective for the long-term treatment of EDS associated with narcolepsy and significantly improves perceptions of general health. Modafinil is well tolerated, with no evidence of tolerance developing during 40 weeks of treatment.
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PMID:Long-term efficacy and safety of modafinil (PROVIGIL((R))) for the treatment of excessive daytime sleepiness associated with narcolepsy. 1082 34

It is widely accepted that glucagon stimulates GH, ACTH and cortisol release in humans, though the mechanisms underlying these effects are unclear. Aim of the present study was to evaluate the stimulatory effect of intramuscolar (i.m.) and intravenous (i.v.) glucagon (GLU) administration on ACTH, cortisol (F) and GH release in normal adult subjects and to compare its effect on hypothalamo-pituitary adrenal (HPA) axis with that of hCRH. To this goal, in 6 normal young women (26-32 yrs, 50-58 kg) we studied the ACTH and F responses to either i.m. or i.v. GLU (1 mg, approximately 0.017 mg/kg in subjects of 54.1 +/- 1.6 kg) administration as well as to i.v. hCRH (2.0 micrograms/kg) or placebo administration. The GH and glucose variations after GLU administration were also studied. I.v. GLU did not modify the spontaneous decrease of ACTH and cortisol levels observed after placebo. Conversely, i.m. GLU elicited clear-cut ACTH and F responses (peak vs baseline, mean +/- SEM: 53.0 +/- 15.2 vs 19.0 +/- 1.5 pg/ml, p < 0.05 and 222.3 +/- 23.8 vs 158.3 +/- 7.0 micrograms/l, p < 0.05) which were higher than those recorded after hCRH (28.1 +/- 4.6 vs 17.4 +/- 3.1 pg/ml, p < 0.02 and 182.7 +/- 22.8 vs 114.8 +/- 12.3 micrograms/l p < 0.02), though this difference did not attain statistical significance. Also GH rise was recorded after i.m. but not after i.v. GLU administration (11.6 +/- 3.4 vs 3.3 +/- 0.7 micrograms/l, p < 0.05). Thirty min after both i.v. and i.m. GLU administration glucose levels showed a similar increase followed by similar decrease. The intramuscular administration of GLU induced negligible side-effects in some subject (mild and transient nausea) which, on the contrary, were clear in all subjects after its intravenous administration (nausea, vomiting, tachycardia). In conclusion, glucagon "per se" is not an ACTH, cortisol and GH secretagogue. After intramuscular administration glucagon is a stimulus of HPA axis at least as effective as hCRH. The mechanisms underlying the ACTH, cortisol and GH responses to i.m. glucagon unlikely include glucose variations or stress.
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PMID:Glucagon is an ACTH secretagogue as effective as hCRH after intramuscolar administration while it is ineffective when given intravenously in normal subjects. 1138 81

N-methyl-aspartate (NMDA) receptor antagonists have been shown to improve opioid analgesia in the animal model. The cough suppressant dextromethorphan is a clinically available NMDA-receptor antagonist. In this randomised, double-blind, placebo-controlled study 20 patients with chronic pain of several years duration were given 100 mg of oral dextromethorphan or matching placebo 4 h prior to an intravenous infusion of morphine 15 mg. Pain intensity and adverse effects were assessed at 0, 4, 5 and 7 h. Dextromethorphan had no effect on morphine analgesia: the mean (+/-SEM) visual analogue scores for pain relief (VAS, 0-100 mm) at the end of the morphine infusion were 38 (+/-6) for dextromethorphan+morphine and 38 (+/-7) for placebo+morphine. VAS scores for pain intensity were comparable both at rest and at movement at all time points. The most common adverse effects reported were dizziness, nausea and sedation. There were no significant differences in either the incidence or severity of adverse effects. In conclusion, oral dextromethorphan 100 mg had no effect on pain relief by intravenous morphine 15 mg in patients with chronic pain.
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PMID:Analgesic effects of dextromethorphan and morphine in patients with chronic pain. 1197 98

Desferrioxamine (DFX) alone (40-50 mg/kg/d s.c. over 8-12 h, five times weekly) was compared with combined DFX twice weekly and deferiprone (75 mg/kg/d) over 12 months in previously poorly chelated thalassaemia patients. Serum ferritin fell from 5506 +/- 635 microg/l (mean +/- SEM) to 3998 +/- 604 microg/l (P < 0.001; n = 14) in the DFX group and from 4153 +/- 517 microg/l to 2805 +/- 327 microg/l in the combined group (P < 0.01; n = 11). Deferiprone plus DFX produced a greater mean urine iron excretion (1.01 mg/kg/24 h) than iron intake from blood transfusion in each patient. Main side-effects were skin reactions (DFX alone), nausea and arthralgia (combined therapy). As chelation therapy, the combined protocol was as effective as DFX five times weekly.
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PMID:Comparison between desferrioxamine and combined therapy with desferrioxamine and deferiprone in iron overloaded thalassaemia patients. 1267 Mar 52


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