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)

Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly effective treatment for erectile dysfunction. The mechanism of action of sildenafil depends on activation of the nitric oxide (NO)-cGMP pathway during sexual stimulation, which results in corpus cavernosal smooth muscle relaxation and penile erection. Endogenously derived NO is also involved in blood pressure regulation through its effect on basal vascular tone, which is mediated by cGMP levels. Organic nitrates and NO donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO. Since both sildenafil and organic nitrates exert their pharmacologic effects via increases in cGMP concentrations, a double-blind, placebo-controlled, crossover study was undertaken to investigate the effects of sildenafil coadministered with glyceryl trinitrate on blood pressure and heart rate in healthy male subjects. The hemodynamic effects of sildenafil were also evaluated in a second placebo-controlled crossover study in men with hypertension who were taking the calcium antagonist amlodipine, which has a mechanism of action that does not involve the cGMP pathway. In the first crossover study, subjects were treated with oral sildenafil (25 mg, 3 times a day for 4 days) or placebo and then challenged on day 4 with a 40-minute, stepwise, intravenous infusion of glyceryl trinitrate (0.5 mg/mL in 5% dextrose at an initial infusion rate of 2.5 microg/min and doubling every 5 minutes to a maximum rate of 40 microg/min) 1 hour after taking sildenafil or placebo. On day 5, subjects received a sublingual glyceryl trinitrate tablet (500 microg) 1 hour after taking 25 mg of sildenafil or placebo. During sildenafil treatment, the subjects were significantly less tolerant of intravenously administered glyceryl trinitrate than during placebo treatment, based on the occurrence of a >25 mm Hg decrease in blood pressure or the incidence of symptomatic hypotension (p <0.01). When a sublingual glyceryl trinitrate tablet was administered on day 5, a 4-fold greater decrease in systolic blood pressure was observed for the subjects during the sildenafil treatment period than during the placebo treatment period. The changes in heart rate were negligible during both glyceryl trinitrate challenges. In conclusion, sildenafil potentiated the hypotensive effects of glyceryl trinitrate, an organic nitrate. Thus, sildenafil administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is contraindicated. In the second crossover study, men with hypertension, who were taking 5 or 10 mg/day of amlodipine, received a single oral dose of 100 mg sildenafil or placebo. Coadministration of sildenafil did not significantly affect the pharmacokinetics of amlodipine. In the 4 hours after dosing, differences in the mean maximum change from baseline in supine systolic and diastolic blood pressures between the sildenafil plus amlodipine and the placebo plus amlodipine treatment periods were -8 mm Hg and -7 mm Hg, respectively (p < or =0.002). The mean maximum supine heart rate increased 2.1 beats/min during sildenafil plus amlodipine treatment and decreased 1.5 beats/min during placebo plus amlodipine treatment (p <0.02). The adverse events in this study were predominantly mild or moderate and did not cause discontinuation of treatment. Adverse events considered to be related to sildenafil treatment included headache, nausea, and dyspepsia. In patients with hypertension who were taking amlodipine therapy, sildenafil produced additive, but not synergistic, reductions in blood pressure. The difference in the mean maximum change from baseline in blood pressure between sildenafil plus amlodipine and placebo plus amlodipine was comparable to the decrease in blood pressure reported for healthy men taking sildenafil alone. (ABSTRACT TRUNCATED)
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PMID:Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. 1007 39

There is a controversy whether central pontine myelinolysis can complicate either hyponatremia or its rapid correction. We report a 69 years old woman with a history of one month of vertigo, nausea, vomiting and diarrhea. She was admitted dehydrated ad stuporous, and initial laboratory values showed a serum sodium of 96 mEq/L. She was treated with dextrose 5% and 3% NaCl. Serum sodium raised to 120 mEq/L at the next day and the level of consciousness improved. At the 4th day of admission, the patient was again stuporous and with spastic quadriplegia. A magnetic resonance imaging showed a central and symmetrical pontine lesion on T1 and T2 weighed images. Thereafter, the patient experienced a progressive improvement of her neurological condition and was discharged three months later, moving her lower limbs. Nine month later she was able to walk.
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PMID:[Central pontine myelinolysis and hyponatremia. Clinical case]. 1141 96

Many of those involved in palliative care have justifiable objections to the introduction of intravenous hydration in patients with dehydration-associated symptoms and advanced cancer. Researchers from the University of Buenos Aires carried out a randomized, comparative and prospective trail to determine the usefulness of hypodermoclysis in the control of thirst, chronic nausea and delirium. Forty-two patients were randomized into two groups. Both groups received drugs subcutaneously (haloperidol 2.5 mg every 4 hours to control delirium and/or metoclopramide 10 mg every 4 hours to control chronic nausea). The study group also received 1000 ml 5% dextrose in water infusion plus 140 milliequivalent per litre (mEq/L) sodium chloride, at a rate of 42 ml/hour per day. Both groups showed significant and equal improvements in relief of thirst and chronic nausea at 24 hours. After 48 hours, this improvement was maintained in the group that received hydration, but only for the relief of chronic nausea. Delirium did not improve significantly in either group during the 48-hour trial period. Current data suggest that decisions on rehydration of patients with terminal-phase cancer should be based more on the patient's comfort than on providing optimal hydration.
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PMID:Hypodermoclysis for control of dehydration in terminal-stage cancer. 1241 47

Conscious intravenous sedation is a safe alternative method to general anaesthesia. We have used a technique of continuously titrated, as opposed to incremental boluses of, intravenous or intramuscular midazolam for conscious sedation, with tumescent adrenaline-lignocaine solution for local anaesthesia, routinely in 421 plastic surgical procedures between 1997 and 2000. All patients were American Society of Anesthesiologists (ASA) class I or II. Conscious sedation was administered through our protocol of continuously titrated doses of midazolam in dextrose saline. The operative field was injected subcutaneously with varying volumes of diluted lignocaine and adrenaline, depending on the anatomical region. Preoperative sedation was administered 1 h before the procedure in the form of an intramuscular injection of pethidine and promethazine (Phenergan). Intraoperatively, a subset of patients received up to four divided diluted doses of pethidine. A preoperative 4 h starvation period pronounced the effect of the sedative. No intraoperative conversions to general anaesthesia were needed, and no sedation complications occurred. No unplanned re-admissions secondary to nausea, prolonged drowsiness or pain were required. All patients who were treated using this technique had an uneventful postoperative course. Hospital stay was substantially shorter than following general anaesthesia, which provided a significant reduction in medical-care expenses and a faster return to work. In conclusion, conscious sedation administered by titrated intravenous midazolam is a well-tolerated, safe, consistent, predictable and effective anaesthetic choice for a variety of plastic surgical procedures, many of which would commonly be performed under general anaesthesia.
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PMID:Continuous intravenous versus bolus parenteral midazolam: a safe technique for conscious sedation in plastic surgery. 1285 24

The purpose of this report is to summarize information on oxaliplatin, a drug recently approved by the U.S. Food and Drug Administration. Information provided includes regulatory history, study design, efficacy and safety results, and pertinent literature references. A single, multicenter, randomized trial, enrolling 463 patients with metastatic colorectal carcinoma whose disease had recurred or progressed during or within 6 months of completion of therapy with the combination of bolus 5-fluorouracil (FU)/leucovorin (LV) and irinotecan, was submitted. Study arms included infusional 5-FU/LV alone (arm A), oxaliplatin alone (arm B), and the combination of oxaliplatin and infusional 5-FU/LV(arm C). Oxaliplatin, at a dose of 85 mg/m2, was administered to patients in arms B and C intravenously over 2 hours in 250-500 ml of dextrose 5% in water (D5W) on day 1 only. A 200-mg/m2 dose of LV was administered simultaneously to arm C patients, in a separate bag using a Y-line, or alone to arm A patients, by i.v. infusion, over 2 hours. 5-FU was then administered to arms A and C patients, first as a bolus injection over 2-4 minutes at a dose of 400 mg/m2, then as a continuous infusion in 500 ml of D5W over 22 hours at a dose of 600 mg/m2. LV was repeated on day 2 of the cycle (arms A and C) followed by a 400-mg/m2 5-FU bolus and a 600-mg/m2 22-hour infusion. Treatment was repeated every 2 weeks. Response rate was the prespecified end point for accelerated approval. Time to progression (TTP) was a secondary end point. The prespecified primary comparison was between the 5-FU/LV regimen and the 5-FU/LV/ oxaliplatin combination regimen. The three arms were well balanced for patient prognostic factors. There were no complete responders. The partial response rates were 0%, 1%, and 9% for the 5-FU/LV, oxaliplatin, and oxaliplatin plus 5-FU/LV treatments, respectively (p = 0.0002, arm C versus arm A). The median times to radiographic tumor progression, based on available radiographs, were 2.7 months, 1.6 months, and 4.6 months, respectively (p < 0.0001, arm C versus arm A). Common adverse events associated with the combination treatment included peripheral neuropathy, fatigue, diarrhea, nausea, vomiting, stomatitis, and abdominal pain. Neutropenia was the major hematologic toxicity. Adverse events were similar in men and women and in patients <65 and > or =65 years of age, but older patients may have been more susceptible to dehydration, diarrhea, hypokalemia, and fatigue. Oxaliplatin in combination with infusional 5-FU/LV was approved for the treatment of patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed during or within 6 months of completion of first-line therapy with the combination of bolus 5-FU/LV and irinotecan. Approval was based on response rate and on an interim analysis of TTP. No results are available, at this time, that demonstrate a clinical benefit, such as improvement in disease-related symptoms or survival.
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PMID:FDA drug approval summaries: oxaliplatin. 1475 10

Healthy women who underwent caesarean section under spinal anaesthesia were studied to determine the extent of postoperative analgesia and side-effects produced by low doses of intrathecal morphine. Patients were randomly allocated to receive, in double-blind fashion, 0 mg (group 1: control group), 0.05 mg (group 2), 0.1 mg (group 3), or 0.2 mg (group 4) of morphine, with 10 mg tetracaine in 10% dextrose 2.5 ml. (n = 20 x 4 groups). The effect of intrathecal morphine was examined in terms of the duration until the first supplemental analgesic was needed and the numbers of the doses within the first postoperative 48 h. Pain relief was significantly greater in groups 3 and 4 than in group 1. The incidence of nausea, vomiting and pruritus increased in a dose-dependent manner. No patient developed respiratory depression. Our results suggest that postoperative analgesia lasts more than 24 h with 0.1 mg or 0.2 mg of intrathecal morphine. Since the incidence of side-effects was higher at 0.2 mg, 0.1 mg may be the optimum dose for caesarean section.
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PMID:Low dose intrathecal morphine and pain relief following caesarean section. 1563 59

Active Hexose Correlated Compound (AHCC) is an extract of Lentinula edodes of the basidiomycete family of fungi rich in alpha glucans. AHCC has been used for many years as a dietary supplement to enhance the immune system and in clinical trials as an adjunctive treatment in Hepatocellular cancer. This multiple dose, Phase I trial, using FDA guidelines, directly investigates the clinical safety and tolerability of AHCC in healthy subjects. Its safety has been based previously on anecdotal reports and its use in clinical practice. Twenty-six healthy male or female subjects between the ages of 18 and 61 were recruited from the community and gave their consent to participate in the trial. The subjects were given 9 g of AHCC (150 mL of the currently available liquid AHCC) PO daily for 14 d. Laboratory data was obtained at baseline and after 14 d of exposure to AHCC and adverse events were monitored by a non-directed review of systems questionnaire three times during the trial. At each visit the vital signs and adverse events were recorded. Two subjects (7%) dropped out because of nausea and intolerance of the liquid. Adverse effects of nausea, diarrhea, bloating, headache, fatigue, and foot cramps occurred in a total of 6 subjects (20%) but were mild and transient. There were no laboratory abnormalities. When used in high dose in healthy subjects, AHCC causes no significant abnormality in laboratory parameters. The adverse effects of 9 g of liquid AHCC per day, a higher dose than used in routine clinical applications, are minimal and the dose was tolerated by 85% of the subjects.
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PMID:A Phase I study of the safety of the nutritional supplement, active hexose correlated compound, AHCC, in healthy volunteers. 1820 43

Fungal peritonitis is a relatively uncommon complication of peritoneal dialysis that contributes significantly to morbidity, drop out from the continuous ambulatory peritoneal dialysis (CAPD) program, and mortality. Candida sake infections were rarely published in literature. We present the first case of peritonitis due to C. sake. A 41-year-old man was admitted to our hospital with abdominal pain, nausea, vomiting, fever, weakness. Abdominal ultrasonography demonstrated a fistula tract, which has an opening at inferolateral of the umbilicus extending 5 cm from the skin into the abdominal cavity with a foreign body (11 x 10 mm length) inside the fistula. The foreign body was removed by surgery being apparently a part of a previously inserted peritoneal catheter. Postoperative specimens revealed polymorph leucocytes and yeast cells in Gram stain, and culture on Sabouraud dextrose agar (SDA) yielded a growth of a fungus, subsequently identified as C. sake with Api ID 32C. Fluconazole (200 mg/day) therapy was started. He recovered after two weeks of therapy. In conclusion, C. sake, a rare type of Candida species, should be considered as a probable peritoneal pathogen in patients with multiple episodes of bacterial peritonitis, previous broad-spectrum antibiotic therapy and diabetes mellitus.
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PMID:First case of continuous ambulatory peritoneal dialysis peritonitis due to Candida sake. 1862 71

Higher rates of glucose usage generally correlate with poor prognosis in several types of malignant tumours. Experimental studies (both in vitro and in vivo) have shown that 2-deoxy-D-glucose (2-DG), a glucose analog and glycolytic inhibitor, enhances radiation-induced damage selectively in tumor cells while protecting normal cells, thereby suggesting that 2-DG can be used as a differential radiomodifier to improve the efficacy of radiotherapy. Clinical trials undertaken to study the feasibility, safety, and validity of this suggested approach will be described. Based on 2-DG-induced radiosensitization observed in primary organ cultures of cerebral glioma tissues, clinical trials were designed taking into consideration the radiobiology of gliomas and pharmacokinetics of 2-DG. Phase I/II clinical trials have unequivocally demonstrated that a combination of 2-DG (200-300 mg 2-DG per kg body weight orally administered after overnight fasting, 20 min before irradiation) with large weekly fractions (5 Gy/fraction) of low-LET radiotherapy is well tolerated without any acute toxicity or late radiation damage to the normal brain tissue. Nonserious transient side effects similar to hypoglycemia induced disturbances like restlessness, nausea, and vomiting were observed at the 2-DG doses used. Data from these trials involving more than 100 patients have clearly indicated a moderate increase in the survival, with a significant improvement in the quality of life with clinicopathological evidence of protection of normal brain tissue. A phase III multicentric trial to evaluate the efficacy of the combined treatment is in progress. Directions for future studies are discussed.
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PMID:Clinical studies for improving radiotherapy with 2-deoxy-D-glucose: present status and future prospects. 2000 89

We report a case of a 50-year-old malnourished African American male with hiccups, nausea and vomiting who was brought to the Emergency Department after repeated seizures at home. Laboratory evaluations revealed sodium (Na(+)) 107 mmol/L, unmeasurably low potassium, chloride < 60 mmol/L, bicarbonate of 38 mmol/L and serum osmolality 217 mOsm/kg. Seizures were controlled with 3% saline IV. Once nausea was controlled with iv antiemetics, he developed large volume free water diuresis with 6 L of dilute urine in 8 h (urine osmolality 40-60 mOsm/kg) and serum sodium rapidly rose to 126 mmol/L in 12 h. Both intravenous desmopressin and 5% dextrose in water was given to achieve a concentrated urine and to temporarily reverse the acute rise of sodium, respectively. Serum Na(+) was gradually re-corrected in 2-3 mmol/L daily increments from 118 mmol/L until 130 mmol/L. Hypokalemia was slowly corrected with resultant auto-correction of metabolic alkalosis. The patient discharged home with no neurologic sequaele on the 11(th) hospital day. In euvolemic hyponatremic patients, controlling nausea may contribute to unpredictable free water diuresis. The addition of an antidiuretic hormone analog, such as desmopressin can limit urine output and prevent an unpredictable rise of the serum sodium.
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PMID:Desmopression is an effective adjunct treatment for reversing excessive hyponatremia overcorrection. 2430 90


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