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)

Radiographic contrast agents have undergone a tremendous evolution over the past several decades. The creation of contrast agents with greater iodine carrying capacity and lower osmolality has improved imaging quality and reduced complications, including nausea, vomiting, congestive heart failure, and cardiac rhythm abnormalities. Whether differences exist among agents in terms of thrombotic complications remains controversial. Several characteristics including potential complications, toxicity, and cost must factor into the decision to use a particular contrast agent in cardiac procedures.
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PMID:Contrast Agents for Cardiac Angiography: Osmolality and Contrast Complications. 1109 75

Levosimendan, a pyridazinone-dinitrile derivative, is a calcium sensitiser with additional action on adenosine triphosphate (ATP)-sensitive potassium channels. It is used intravenously (IV) for the treatment of decompensated cardiac failure. At therapeutic doses, levosimendan exhibits enhanced contractility with no increase in oxygen demands. It also produces antistunning effects without increasing myocardial intracellular calcium concentrations or prolonging myocardial relaxation. Levosimendan also causes coronary and systemic vasodilation. In patients with decompensated congestive heart failure (CHF), IV levosimendan significantly reduced the incidence of worsening CHF or death. IV levosimendan significantly increased cardiac output or cardiac index and decreased filling pressure in the acute treatment of stable or decompensated CHF in large, double-blind, randomised trials and after cardiac surgery in smaller trials. Levosimendan is well tolerated, with the most common adverse events (headache, hypotension, nausea) being secondary to vasodilation. It has not been shown to be arrhythmogenic. Levosimendan has shown no clinically important pharmacokinetic interactions with captopril, felodipine, beta-blockers, digoxin, warfarin, isosorbide-5-mononitrate, carvedilol, alcohol (ethanol) or itraconazole.
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PMID:Levosimendan. 1136 86

Gastrointestinal (GI) Adverse Drug Reactions (ADRs) from the NSAIDs are a major cause of morbidity and mortality in arthritic patients taking these drugs. The recent much heralded development of COX-2 selective drugs (celecoxib, rofecoxib), the objective of which has been to spare inhibition of the production of COX-1 derived mucosal protective prostaglandins, may have represented an advance in reducing the risk of serious ADRs--ulcers and bleeding--but does not appear to have reduced the incidence of symptomatic side-effects (nausea, vomiting, epigastric pain/heartburn, abdominal discomfort) which are a major reason for withdrawal from NSAID therapy, especially in the long term. The rationale of COX-2 selectivity from these newer drugs is controversial since there may be pharmacokinetic differences from established carboxylate-NSAIDs that accounts for their apparent lower ulcerogenicity. Moreover, concerns have been recently expressed that as COX-2 is important in ulcer healing, control of prostacyclin production and renal function that they may have adverse reactions from these effects. Indeed, recent reports of enhanced risk of congestive heart failure with rofecoxib are of importance and may relate to impaired prostacyclin production. Moreover, there are other therapeutic strategies that have yielded equally low ulcerogenic NSAIDs (e.g. the prodrug, nabumetone; the established COX-2 inhibitory drug, nimesulide) and even the well-established NSAIDs ibuprofen and diclofenac have relatively low upper GI ulcerogenicity and have been used as benchmark standards in comparative trials of the newer "Oxib" drugs (celecoxib, rofecoxib). Much research interest has centred on the nitric oxide-donating NSAIDs (NO-NSAIDs). The rationale for donating NSAIDs being to counteract the vasoconstriction effects of NSAIDs but this has yet to be fully evaluated. It is not certain that this "antidote" approach will be acceptable as there may also be systemic effects of the nitrobutoxyl--or other NO-donors that may have toxicological consequences. Another strategy is the development of mixed COX-5 lipoxygenase (LOX) inhibitors--the progenitors of which were benoxaprofen and BW-755C. The rationale of reducing the potential for lipoxygenase mediated actions in the stomach (e.g. vasoconstriction, leucocyte accumulation). Clearly, the need to develop newer NSAIDs with lower risks of ulcers and bleeding as well as symptomatic ADRs is still representing a major challenge.
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PMID:The ever-emerging anti-inflammatories. Have there been any real advances? 1159 13

In its simplest and most succinct definition, heart failure can be defined as an inability of the heart to meet the metabolic demands of the body. Despite the diverse etiologies of heart failure in the pediatric population, the presentation of heart failure represents a common constellation of symptoms, signs, and physical findings. In infants, an inability to maintain growth either secondary to decreased nutritional intake or an increased catabolic state is a hallmark of heart failure. Infants exhibit increased sympathetic tone with excessive diaphoresis and increased heart rate. Physical findings in the infants with congestive heart failure (CHF) include increased work of breathing, tachypnea and hepatomegaly. In older children, in contrast, new onset heart failure may be less overtly symptomatic. Malaise, decrease in the level of daily activity, and weight loss may be present. Symptoms of abdominal pain and nausea and anorexia can be present and sometimes divert attention from the real etiology. Physical findings include rales and peripheral edema. If there is hepatomegaly, there will likely be hepatic tenderness as well. A gallop rhythm and tachycardia are commonly present. The long-term treatment of CHF in children includes digoxin, diuretics and afterload reduction with angiotensin-converting enzyme (ACE) inhibitors. Digoxin decreases sympathetic tone and improves growth in infants. Diuretics should be used to relieve symptoms but may not be necessary in all children. ACE inhibitors are increasingly valuable in maintaining cardiac function long term. New uses of medications include the addition of spironalactone (Aldactone, G. D. Searle & Co., Chicago, IL) which, in adults, has been shown to significantly decrease both the death rate from CHF and the need for hospitalization. Beta-Blockers have been used in children in limited studies and may have a role in the treatment of patients with idiopathic dilated cardiomyopathy. Surgical treatment, such as partial vectriculectomy, has shown short-term benefit and has been used sparingly in infants.
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PMID:Treatment of heart failure in infants and children. 1172 82

Based on the recommended phase II doses for doxorubicin (60 mg/m2) and docetaxel (60 mg/m2) and the National Surgical Adjuvant Breast and Bowel Project's (NSABP) experience with doxorubicin and cyclophosphamide (cyclophosphamide 600 mg/m2), we conducted a phase II trial at 18 institutions using doxorubicin/docetaxel/cyclophosphamide (ATC) given every 21 days, in preparation for a major adjuvant breast cancer study (NSABP B-30), in which ATC would be used. Eligibility requirements included measurable stage IIIB/IV breast cancer, performance status 0-2, normal left ventricular ejection fraction, and no prior chemotherapy for metastatic disease (nontaxane adjuvant chemotherapy was allowed if completed > 12 months before entry and if the cumulative dose of doxorubicin was =240 mg/m2). Eighty-nine patients were entered who ranged in age from 30-78 years (38.2% < 50 years; 61.8% =50 years). A total of 33.7% of patients had stage IIIB disease, and 66.3% had stage IV disease. Among the stage IV patients, 20.3% had received prior adjuvant chemotherapy. Dexamethasone premedication (8 mg p.o. b.i.d. for 3 days) and prophylactic ciprofloxacin (500 mg p.o. b.i.d. days 5-15) were used. Colony-stimulating growth factors were reserved for secondary prophylaxis after prolonged or febrile neutropenia (FN) or documented severe infection in a prior cycle. After a cumulative dose of doxorubicin 480 mg/m2, patients could continue with docetaxel/cyclophosphamide alone. Eighty-nine patients and 577 courses were evaluable for toxicity. Median time on study as of May 2002 was 36.5 months (range, 28-47 months). Febrile neutropenia occurred in 34 patients (38%); 8 developed FN in the absence of prior prophylactic growth factor support; 26 developed FN despite prior growth factor support (for one patient this information was unavailable). There were no septic deaths. One patient died from pulmonary embolism. Other grade 3/4 adverse events included: nausea (9%), vomiting (7%), stomatitis (6%), diarrhea (4%), arthralgia/myalgia (3%), and neurotoxicity (1%). Clinical congestive heart failure was seen in 3 patients (3.4%). Seventy-seven patients were evaluable for best response within 6 cycles of therapy. Thirteen patients (16.9%) had a complete response, 43 (55.8%) had a partial response, for an overall response rate of 72.7%. The median response duration was 23.8 months (95% CI, 16.2-37.8 months), and the median time to progression or death was 23.5 months (95% CI, 16.3-38.7 months). The median survival time was 35.6 months (95% CI, 26.6-39.4 months). The administration of ATC with primary ciprofloxacin and secondary colony-stimulating factor prophylaxis is feasible and active. Its value in the adjuvant setting is currently under investigation.
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PMID:Phase II trial of doxorubicin/docetaxel/cyclophosphamide for locally advanced and metastatic breast cancer: results from NSABP trial BP-58. 1253 63

The objective of this study was to evaluate the safety, tolerability, maximum tolerated dose, pharmacokinetics, and pharmacodynamics of five fixed doses of ganstigmine (CHF 2819) in patients with probable Alzheimer's disease (AD). This randomized, double-blind, placebo-controlled trial evaluated five dose levels (5, 7.5, 10, 12.5, and 15 mg) administered orally once daily for 7 days. Adverse events and continuous telemetry were collected on successive panels of six patients (five active, one placebo). Acetylcholinesterase, butyrylcholinesterase, and plasma drug levels were measured. A total of 29 patients were randomized and 18 completed the study. A total of seven patients, including five of five in the 12.5-mg panel, discontinued because of adverse events. Four patients were withdrawn administratively from the first panel while an episode of atrial fibrillation (the only serious adverse event) was investigated. This panel was then repeated. Mild, transient headache or nausea were the most commonly reported adverse events. Multiple moderate adverse events in the 12.5-mg panel (including nausea, vomiting, and anorexia) led to the decision not to proceed with a 15-mg panel. Ten milligrams was determined to be the maximum tolerated dose. Ganstigmine exhibited nonlinear pharmacokinetics, was absorbed rapidly, and reached peak concentrations within 1 hour. Acetylcholinesterase inhibition was dose dependent and lasted as long as 24 hours. Ganstigmine, a novel cholinesterase inhibitor, was well tolerated within a dosing range of 5 to 10 mg. Once-daily dosing is supported by data on acetylcholinesterase inhibition.
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PMID:First clinical evaluation of ganstigmine in patients with probable Alzheimer's disease. 1278 20

The Rainey Hospice House, South Carolina's first stand-alone inpatient facility opened in September 1998. During the year 2000, 220 inpatients were served in the house. Patients ranged in age from 23 to 107 years old (average age 73). Cancer was the most common hospice diagnosis, followed by congestive heart failure, cardiovascular disease and cerebrovascular disease, dementia, cirrhosis, renal failure, and COPD. Thirty-three percent of patients were in the program less than ten days. Over 98 percent of deaths under hospice care were described as peaceful. During 2000, our outpatients and our inpatients were similar in age, insurance coverage, diagnoses, and time in the program. Inpatient hospice is highly valued by families and patients alike. It is especially useful for the following patients: those with uncontrolled symptoms, those with exhausted care givers, those with no caregivers, those who require total care, and those very close to death. The symptoms most likely to precipitate inpatient admission include pain, nausea, confusion, and agitation. Given the graying of South Carolina's population and the increase in outpatient hospice care, more areas of the state will need inpatient facilities in the future.
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PMID:Comfort always. The Rainey Hospice House: South Carolina's first inpatient hospice. 1450 98

The records of 38 elderly patients with hip fracture admitted to our hospital between January and December 2002 were retrospectively reviewed to determine the incidence and outcomes of medical complications. The mean age was 84.5 +/- 6.83 years old, 32 women and 6 men. 27 patients (71%) suffered from dementia. Of the 38 patients, 33 (86.8%) had one and more underlying diseases: hypertension 29, cerebrovascular episode 7, congestive heart failure 5, diabetes mellitus 4, gastric ulcer or chronic gastritis 3, ischemic heart disease 4, depression 2. Three patients had a past history of hip fracture. Fourteen patients (37%) developed medical complications after hip fracture, most frequently pneumonia (64%). Other complications were dizziness, nausea, congestive heart failure, choledocholithiasis, and GI tract bleeding. Eight patients who suffered pneumonia cancelled elective surgery. Severity of pneumonia was mild in 2, moderate in 5, and severe in 2. Both cases with severe pneumonia died in hospital. Patients with pneumonia (pneumonia group) were significantly older and had more severe dementia than patients without pneumonia (non-pneumonia group). Although there were no significant differences in physical ability between the two groups before admission, physical ability on discharge was lower in the pneumonia group. The pneumonia group had a significantly longer mean hospital stay than the non-pneumonia group. Our results suggest that the prevention of pneumonia is necessary to improve the outcome of hip fracture.
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PMID:[Effect of pneumonia on clinical course and prognosis after hip fracture]. 1468 54

In patients with advanced breast cancer, treatment with paclitaxel and doxorubicin has been shown to produce impressive overall response rates (up to 94%) and to prolong overall survival significantly over a combination of fluorouracil (5-FU), doxorubicin, and cyclophosphamide (Cytoxan, Neosar) in one prospective phase III clinical study. These results have been challenged, however, by other data demonstrating no survival advantage for taxane-based therapies. In addition, the combination of paclitaxel and doxorubicin has repeatedly been shown to be complicated by the development of treatment-related congestive heart failure, when cumulative doxorubicin doses exceed 300-360 mg/m2. Consequently, attempts have been made to increase the complete remission rate and overall survival resulting from first-line treatment of metastatic breast cancer without compromising patient safety. Gemcitabine (Gemzar)--a relatively effective, well-tolerated and partially non-cross-resistant antitumor compound with limited toxicity--represents an attractive alternative to paclitaxel/anthracycline combinations. Initial studies of combination therapy with gemcitabine and paclitaxel have produced an average response rate of 52%, with time to progression ranging between 7.0 and 14.5 months. Three-drug regimens containing gemcitabine, an anthracycline, and paclitaxel have been tested in phase II studies and have produced impressive response rates of 82.9% with gemcitabine, doxorubicin, and paclitaxel and 92% with gemcitabine, epirubicin (Ellence), and paclitaxel (GET). The Central European Cooperative Oncology Group has evaluated the GET regimen vs a regimen containing 5-FU, epirubicin, and cyclophosphamide (FEC) in a randomized, prospective phase III study. Interim toxicity analysis showed that the GET regimen was well tolerated but produced more grade 4 neutropenia (64% vs 42%, P = .084) and significantly more grade 4 thrombocytopenia (12% vs 0%; P < .001) than FEC. Anaphylactic/allergic reactions, peripheral polyneuropathy, nausea, and cardiotoxicity constituted rare events and did not exceed grade 1 or 2 in severity. Although final data from this phase III trial are not yet available, preliminary analysis suggests the GET regimen represents an attractive option for patients with advanced breast cancer.
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PMID:Gemcitabine, anthracycline, and taxane combinations for advanced breast cancer. 1476 4

We evaluated the efficacy and toxicity of trastuzumab plus gemcitabine in patients with HER2-positive metastatic breast cancer (MBC). Sixty-four patients were enrolled, the majority of whom (95%) had been treated with an anthracycline and a taxane before study enrollment. Eligible women were treated with gemcitabine (1200 mg/m(2) weekly for 2 weeks with the third week off on a 21-day cycle) plus weekly doses of trastuzumab (4-mg/kg loading dose; 2 mg/kg thereafter) until disease progression. The median patient age was 55 years, and the median number of previously administered (including adjuvant) chemotherapy regimens was 3. Twenty-two patients were scored as 2+ for HER2 expression by immunohistochemistry; 39 patients scored 3+. Three patients were assessed as HER2-negative on central pathology review and were ineligible for evaluation. Fifty-nine of the 61 patients remained evaluable for response. The objective response rates were 38% in the intent-to-treat population (23 of 61) and 44% among the 39 patients with HER2 3+ expression. The median response duration was 5.8 months, median overall survival was 14.7 months, and median time to disease progression was 5.8 months. Trastuzumab plus gemcitabine was well tolerated. No cases of clinical congestive heart failure occurred. Grade 3/4 toxicities included asthenia in 4 patients, fever in 4, neutropenia in 18, dyspnea in 6, abdominal or back pain in 3, and edema and nausea in 1 patient each. The combination of trastuzumab plus gemcitabine appears to be well tolerated and effective for patients with HER2-positive MBC previously treated with chemotherapy.
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PMID:Phase II study of trastuzumab plus gemcitabine in chemotherapy-pretreated patients with metastatic breast cancer. 1524 19


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