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Ziconotide intrathecal infusion was recently approved by the United States Food and Drug Administration for the treatment of intractable severe chronic pain. Patients with neuropathic pain make up a significant population among those who experience chronic pain for which there are less than optimal pharmacotherapeutic options. Published clinical trials provide a global view of ziconotide efficacy and safety. A subset of patients in clinical trials obtained complete pain relief, a remarkable finding given the history of drug treatment for neuropathic pain. To provide more information regarding those who respond to ziconotide therapy, we discuss three patients with neuropathic pain who received ziconotide infusion. Two patients with longstanding neuropathic pain, one with complex regional pain syndrome (formerly known as reflex sympathetic dystrophy) of the leg and one with lumbar radiculitis, achieved temporary but complete pain relief from single 5- and 10-microg epidural test doses. In the third case, a patient with longstanding bilateral leg and foot neuropathic pain from acquired immunodeficiency syndrome and antiretroviral drug therapy achieved considerable pain relief from a long-term continuous intrathecal infusion. The patients who received a single dose had mild central nervous system adverse effects such as sedation, somnolence, nausea, headache, and lightheadedness. The patient who received the intrathecal infusion experienced mild-to-severe adverse effects depending on the rate of infusion; these effects included sedation, confusion, memory impairment, slurred speech, and double vision. This patient could sense impending adverse effects and made rate adjustments or suspended infusion to avert untoward symptoms. In all three cases, patients achieved considerable pain relief that was long-lasting and persisted well after dose administration or suspension of infusion.
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PMID:Ziconotide infusion for severe chronic pain: case series of patients with neuropathic pain. 1650 20

An aversive tobacco abstinence syndrome, thought to reflect an underlying level of nicotine dependence, contributes to cigarette smokers' failed quit attempts. Nicotine replacement therapy (NRT) suppresses tobacco abstinence, but high relapse rates suggest room for improvement. Improving NRT's efficacy might begin with identifying factors that influence tobacco abstinence symptom suppression. Two such factors are smokers' gender and NRT dose. The purpose of this study was to determine the dose-related effects of transdermal nicotine (TN) on tobacco abstinence symptoms in 75 men and 53 women who regularly smoked cigarettes but who had abstained from smoking for at least 8-12 hr. Participants completed 4 double-blind, randomized 6.5-hr laboratory sessions that differed by TN dose (0, 7, 21, or 42 mg). Each session included blood sampling for plasma nicotine level, measurement of heart rate, participants' ratings of tobacco abstinence symptoms and effects of nicotine, and psychomotor performance. Increases in plasma nicotine level were related to TN dose and were independent of gender. TN-induced abstinence symptom suppression was dose-related for items assessing craving and urge to smoke and largely was independent of gender. TN increased heart rate and ratings of aversive side effects (e.g., nausea, lightheadedness) in a dose-related manner, and women were more sensitive at higher doses. Results from this laboratory study support the continued use of TN as a pharmacotherapy. Higher doses may ameliorate some abstinence symptoms, although the side effect profile, at least in the short term, may limit effectiveness, especially for women.
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PMID:Transdermal nicotine-induced tobacco abstinence symptom suppression: nicotine dose and smokers' gender. 1675 16

This paper will review the lumbosacral spine (L1-S5). Procedures performed in the lumbosacral spine include electromyography, spinal stimulator implants, spinal infusion implants for spasticity or pain medications, sacroiliac spine injections, facet blocks, and steroid injections. Complications from these procedures include iatrogenic paraplegia or paraplegia due to transverse myelitis, intravascular penetration, dural puncture, increased pain at the injection site, increased radicular pain, increased spine pain, lightheadedness, nausea, nonspecific headache, and vomiting. Long-term complications include implant infection, implant or catheter dislodgment/kinking, and device failure. This paper provides anatomically accurate schematics of innervations of the lumbosacral spine (L1-S5) that can be used to interpret magnetic resonance images of the muscles and nerves. Cross-sectional schematics of the lumbosacral spine were drawn as they appear on imaging projections. The relevant nerves were color coded. The muscles and skin surfaces were labeled and assigned the color of the appropriate nerves. An organized comprehensive map of the motor innervation of the lumbosacral spine allows the physician to increase the accuracy and efficacy of interventional procedures. This anatomical map could also assist the electromyographer in correlating the clinical and electrophysiological findings on magnetic resonance images.
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PMID:Sectional neuroanatomy of the lumbosacral spine (L1-S5). 1789

Enhanced sympathetic activity causes an exaggerated heart rate response to standing in the postural tachycardia syndrome (POTS). All patients describe symptoms of orthostatic intolerance such as dizziness, blurred vision, shortness of breath, palpitations, tremulousness, chest discomfort, headache, lightheadedness and nausea, but only one third suffer loss of consciousness. We report four patients with POTS, who had long ventricular pauses (i.e. asystole) and syncope during head-up tilt test. This suggests that a subset of patients with POTS can have a surge in parasympathetic outflow that precedes vasovagal syncope.
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PMID:Postural tachycardia syndrome with asystole on head-up tilt. 1795 28

A substantial number of individuals evaluated for complaints of chest pain do not suffer from coronary heart disease (CHD). Studies show that many patients who complain of symptoms that might be caused by CHD, such as shortness of breath or chest pain, may actually have an anxiety disorder. Gender differences in how patients present with these symptoms have not been adequately explored. The purpose of this study was to explore possible gender differences in the presentation of patients with CHD-like symptoms. Two groups were examined, one comprising 6,381 individuals self-referred for electron beam tomography (EBT) studies and a subset of these individuals who defined a "low-risk" group based on the absence of risk factors for CHD and low coronary artery calcium (CAC) scores. We explored gender differences in symptom presentation in each group after controlling for relevant variables by using logistic regression models. These analyses showed that women were significantly more likely than men to endorse CHD symptoms that might also be caused by an anxiety disorder. Women in the low risk group reported CHD symptoms also referable to anxiety more often than men, but unlike men did not complain primarily of chest pain. Women were also more likely to have been prescribed antianxiety or antidepressant medication. In previous studies, non-cardiac chest pain has been considered a hallmark of anxiety in individuals seen in medical settings. This study suggests that in individuals with low risk for CHD chest pain was not related to gender, but other anxiety-related symptoms including heart flutter, lightheadedness, nausea, and shortness of breath were more likely to be reported in women than in men.
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PMID:Women and non-cardiac chest pain: gender differences in symptom presentation. 1859 45

Evidence of the effect of dehydration on physiological responses to hypoxia is limited. The purpose of this study was to determine the effect of hypohydration severity on physiological, renal hormonal and psychological responses to acute hypoxia. Eight males completed intermittent walking tests under normobaric hypoxic conditions (FI O(2) = 0.13) after completing four separate hypohydration protocols, causing change in body mass of approximately 0% (EU), -1% (H1), -2% (H2) and -3% (H3). Physiological and psychological markers were monitored throughout the 125 min test. Fluid controlling hormones were measured pre and post exposure. Heart rate, core temperature, peripheral arterial oxygen saturation (SpO(2)), minute ventilation and urine osmolality were found to be significantly different between hydration conditions and correlated with Lake Louise Questionnaire score (LLQ) (P < 0.05). LLQ score increased with hypohydration severity above H2 (EU 1.3 +/- 1; H1 1.2 +/- 1; H2 2.7 +/- 2; H3 3.9 +/- 2) (P < 0.001). Antidiuretic hormone and aldosterone increased over the test, but were not different between hydration conditions (P < 0.05). Atrial natriuretic peptide showed no change over time, or with conditions. Therefore, renal hormones are not influenced by hypohydration severity during moderate intensity hypoxic exercise. Hypohydration less than -2% induces greater physiological strain during hypoxic exercise and may cause rise in symptoms such as, fatigue, headache, nausea and lightheadedness.
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PMID:The effect of hypohydration severity on the physiological, psychological and renal hormonal responses to hypoxic exercise. 1919 72

Ziconotide is a conopeptide intrathecal (IT) analgesic which is approved by the US Food and Drug Administration (FDA) for the management of severe chronic pain. It is a synthetic equivalent of a naturally occurring conopeptide found in the venom of the fish-eating marine cone snail and provides analgesia via binding to N-type voltage-sensitive calcium channels in the spinal cord. As ziconotide is a peptide, it is expected to be completely degraded by endopeptidases and exopeptidases (Phase I hydrolytic enzymes) widely located throughout the body, and not by other Phase I biotransformation processes (including the cytochrome P450 system) or by Phase II conjugation reactions. Thus, IT administration, low plasma ziconotide concentrations, and metabolism by ubiquitous peptidases make metabolic interactions of other drugs with ziconotide unlikely. Side effects of ziconotide which tend to occur more commonly at higher doses may include: nausea, vomiting, confusion, postural hypotension, abnormal gait, urinary retention, nystagmus/amblyopia, drowsiness/somnolence (reduced level of consciousness), dizziness or lightheadedness, weakness, visual problems (eg, double vision), elevation of serum creatine kinase, or vestibular side effects. Initially, when ziconotide was first administered to human subjects, titration schedules were overly aggressive and led to an abundance of adverse effects. Subsequently, clinicians have gained appreciation for ziconotide's relatively narrow therapeutic window. With appropriate usage multiple studies have shown ziconotide to be a safe and effective intrathecal analgesic alone or in combination with other intrathecal analgesics.
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PMID:Safety and efficacy of intrathecal ziconotide in the management of severe chronic pain. 1970 62

Idiopathic intracranial hypertension is the syndrome of elevated intracranial pressure without clinical, laboratory, or imaging evidence of intracranial pathology. The classic symptoms include headache, nausea, and vomiting. It may also be associated with blurry vision, diplopia, stiff neck, increasing head size, photophobia, anorexia, retro-orbital pain, lightheadedness, myalgia, and head tilt. Sixth nerve palsy is documented in 10-40% of patients with pseudotumor cerebri, in most series, but third nerve palsy is very rarely associated with pseudotumor cerebri. Described here is the novel case of a pseudotumor cerebri patient who had bilateral partial oculomotor palsy with sparing of the pupillary fibers.
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PMID:Bilateral oculomotor palsy secondary to pseudotumor cerebri. 2011 53

This study evaluated the efficacy and safety of two fixed doses of aripiprazole (15 mg/day, n = 131 and 30 mg/day, n = 136) compared with placebo (n = 134) in acutely manic or mixed bipolar I hospitalized patients. The mean change from baseline to Week 3 in the YMRS Total Scores was -10.01 (95% CI: -11.92, -8.09) for aripiprazole 15 mg/day, -10.80 (95% CI: -12.71, -8.90) for aripiprazole 30 mg/day, and -10.12 (95% CI: -12.01, -8.24) for placebo. The most frequent adverse events (> or = 10% and greater than placebo) for either of the aripiprazole treatment groups were headache, nausea, dyspepsia, insomnia, agitation, constipation, akathisia, anxiety, lightheadedness, vomiting, diarrhea, asthenia and extremity pain. Aripiprazole 15 or 30 mg/day was not significantly more effective than placebo in the treatment of bipolar I disorder acute mania at endpoint (Week 3). A high placebo response rate may have accounted for the lack of separation between treatment groups.
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PMID:A comparison of two fixed doses of aripiprazole with placebo in acutely relapsed, hospitalized patients with bipolar disorder I (manic or mixed) in subpopulations (CN138-007). 2072 18

Milk-alkali syndrome is a rare cause of hypercalcemia characterized by the triad of hypercalcemia, renal insufficiency, and metabolic alkalosis that results from the overconsumption of calcium containing products. In the setting of pregnancy where there is a physiologic increase in calcium absorption, milk-alkali syndrome can be potentially life threatening. We report a case of a 26-year-old woman in her second trimester of pregnancy who presented with 2 weeks of flank pain, nausea, vomiting, anorexia, headache, and lightheadedness. The history revealed consumption of a large quantity of milk, calcium carbonate antacid, and calcium-containing prenatal vitamins. Her symptoms and hypercalcemia resolved with intravenous fluids and a loop diuretic. With the increased use of calcium carbonate for peptic ulcer disease, gastroesophageal reflux disease, and osteoporosis, milk-alkali syndrome has experienced a resurgence and must be considered in the differential diagnosis of hypercalcemia. In this clinical vignette we review the literature on milk-alkali syndrome in pregnancy and discuss important diagnostic and therapeutic considerations when managing the pregnant patient with hypercalcemia.
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PMID:Hypercalcemia in pregnancy: a case of milk-alkali syndrome. 2134 76


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