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Background: Reports of the superiority of the antidepressant effect of ketamine during the conduct of electroconvulsive therapy (ECT) have been limited. We conducted an open-label trial of ketamine to determine whether ketamine as the anesthetic during ECT would provide a greater antidepressant effect than the antidepressant effect obtained with propofol., Methods: Between April 2006 and April 2007, 31 inpatients with treatment-resistant depression gave written consent for ECT and to participate in this study. An anesthesiologist who was unaware of the mental symptoms of the subjects assigned them to receive propofol or ketamine anesthetic according to the preferences of the patients, and the patients underwent 8 ECT sessions for 4 weeks. The Hamilton Depression Rating Scale (HDRS) was valuated before ECT and after the completion of the second, fourth, sixth, and eighth ECT sessions., Results: The HDRS scores improved earlier in the ketamine group, with decreases in HDRS scores that were significantly greater in the ketamine group., Conclusions: The results suggested that it is possible to improve symptoms of depression earlier by using ketamine anesthesia.

Context: Haloperidol is used commonly for the control of nausea and vomiting (N/V) in palliative care patients, but there is very little evidence to support its use., Objectives: To assess the efficacy of haloperidol as an antiemetic in patients with cancer and N/V not related to cancer treatment., Methods: Patients with an N/V score of at least 1 on a 4-point scale were prescribed either oral or subcutaneous haloperidol. N/V and toxicity were assessed daily for the duration of the study (maximum five days) by both the patient and an observer (health professional)., Results: At Day 2, 33 of 42 (79%) treated patients were assessable for response. Eight (24%; 95% confidence interval [CI]: 10%-39%) patients had complete control of N/V and 12 (36%; 95% CI: 20%-53%) had partial control, giving an overall response rate of 61% (95% CI: 44%-77%). At Day 5, 23 patients were assessable for response. The overall response rate was 17 of 23 (74%; 95% CI: 56%-92%). If all patients are included in the response analysis, the overall response rates at Days 2 and 5 were 47% and 40%, respectively., Conclusion: Haloperidol has some efficacy in the treatment of N/V in this patient group. The results from this uncontrolled study provide pilot data from which to plan future controlled trials of antiemetics in the palliative care population., (Copyright 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

The purposes of this prospective, longitudinal study were to examine the relationships between leptin, human chorionic gonadotropin (hCG), cortisol, and psychosocial stress and nausea and vomiting (NV) in women with mild-to-moderate NV throughout pregnancy. Participants comprised 91 pregnant women recruited from prenatal clinics in southern Taiwan. Data analysis using one-way analysis of variance (ANOVA) indicated that leptin, hCG, cortisol levels, and Index of Nausea, Vomiting, and Retching (INVR) scores, but not stress (measured with the Visual Analog Scale, VAS) scores, were significantly different among the three trimesters. The average INVR score and hCG level decreased from the first to third trimesters (p < .0001 for both). The average leptin and cortisol levels increased from the first to third trimesters (p = .001 and p < .0001, respectively). Analysis using mixed models indicated that the INVR scores decreased significantly in a progressive manner through the stages of pregnancy and were significantly lower in the second and third trimesters. Findings reveal that stress/VAS and hCG may both be significantly and independently associated with INVR scores. Future research should examine psychosocial reactions in addition to exploring other biochemical markers related to NV and stress.

Background: Refusal of appropriately indicated do-not-resuscitate (DNR) orders may cause harm and distress for patients, families, and the medical team. We conducted a retrospective study to determine the frequency and predictors of refusals of DNR in advanced cancer patients admitted to an acute palliative care unit., Methods: A total of 2538 consecutive admissions were reviewed. Demographic and clinical characteristics from 200 consecutive patients with DNR orders and 100 consecutive patients who refused DNR were collected, and differences between the groups were determined by multivariate regression and recursive partitioning analysis., Results: Of 2538 admissions, 2530 (99%) were appropriate for DNR discussion. Of the 2530 admissions, 2374 were unique patients, and 100 (4%) of 2374 refused DNR. Refusers had median (interquartile range, IQR) pain of 7 (4-9) versus 5 (3-8, P = .0005), nausea of 2 (0-7) versus 1 (0-4, P = .05), and dyspnea of 1 (0-5) versus 4 (0-7, P = .002) as compared with DNR nonrefusers, respectively. Patients with hematological malignancies and advance directives had a lower DNR refusal risk (odds ratio [OR], 0.38; P = .02, and OR, 0.36; P < .0001, respectively). Multivariate regression analysis revealed that patients with moderate-severe pain (OR, 3.19; P = .002) and with no advance directives (OR, 2.94; P < or = .001) had higher DNR refusal risk. There were more inpatient deaths among DNR nonrefusers (87 of 200 vs 1 of 100, P < .0001). Median (IQR) time from discharge to death was 18 (8-35) days for those with DNR orders and 85 (25-206) days for DNR refusers (P < or = .0001)., Conclusions: DNR refusal in patients admitted to the acute palliative care unit is low, more frequent in patients with more pain and nausea and no advance directives, and associated with longer survival. This study demonstrates possible predictors of complicated DNR discussions.

Introduction: We report a case of digoxin-like toxicity because of ingestion of foraged plants. This patient presented with nausea, vomiting, bradycardia, and hypotension after ingesting Veratrum viride (false hellebore). The patient's serum specimen demonstrated a positive digoxin level (0.38 ng/mL) measured by a clinical tubidimetric immunoassay. We hypothesize that steroidal alkaloid compounds contained in V. viride cross-react with the Multigent Digoxin immunoassay reagent antibodies., Results: Plant extracts from V. viride demonstrated cross-reactivity to Multigent reagent antibodies but did not bind therapeutic DigiFab antibodies. Gas chromatography/mass spectrometry analyses identified several steroidal alkaloid compounds present in the V. viride extracts: jervine, ribigirvine, solanidine, and veratraman., Conclusions: This study indicates that compounds extracted from V. viride can cross-react with a clinical Digoxin immunoassay. Yet these extracts did not bind DigiFab antibody fragments used for therapeutic intervention. Providers should not unnecessarily administer DigiFab fragments as an antidote in symptomatic V. viride toxic patients.

Background: A substantial number of individuals are at risk for the development of motion sickness induced nausea and vomiting (N&V) during road, air or sea travel. Motion sickness can be extremely stressful but the neurobiologic mechanisms leading to motion sickness are not clear. The endocannabinoid system (ECS) represents an important neuromodulator of stress and N&V. Inhibitory effects of the ECS on N&V are mediated by endocannabinoid-receptor activation., Methodology/principal Findings: We studied the activity of the ECS in human volunteers (n = 21) during parabolic flight maneuvers (PFs). During PFs, microgravity conditions (<10(-2) g) are generated for approximately 22 s which results in a profound kinetic stimulus. Blood endocannabinoids (anandamide and 2-arachidonoylglycerol, 2-AG) were measured from blood samples taken in-flight before start of the parabolic maneuvers, after 10, 20, and 30 parabolas, in-flight after termination of PFs and 24 h later. Volunteers who developed acute motion sickness (n = 7) showed significantly higher stress scores but lower endocannabinoid levels during PFs. After 20 parabolas, blood anandamide levels had dropped significantly in volunteers with motion sickness (from 0.39+/-0.40 to 0.22+/-0.25 ng/ml) but increased in participants without the condition (from 0.43+/-0.23 to 0.60+/-0.38 ng/ml) resulting in significantly higher anandamide levels in participants without motion sickness (p = 0.02). 2-AG levels in individuals with motion sickness were low and almost unchanged throughout the experiment but showed a robust increase in participants without motion sickness. Cannabinoid-receptor 1 (CB1) but not cannabinoid-receptor 2 (CB2) mRNA expression in leucocytes 4 h after the experiment was significantly lower in volunteers with motion sickness than in participants without N&V., Conclusions/significance: These findings demonstrate that stress and motion sickness in humans are associated with impaired endocannabinoid activity. Enhancing ECS signaling may represent an alternative therapeutic strategy for motion sickness in individuals who do not respond to currently available treatments.

Context: Research about clusters of symptoms in oncology is an emerging field of study. However, there is still conceptual confusion about clusters of symptoms and little agreement across studies., Objectives: The aim of the present study was to explore clusters of symptoms over time in a large heterogeneous group of patients with cancer and thereby contribute to the conceptual and methodological debate in this research area., Methods: A longitudinal design was used to assess symptoms in cancer patients over four time points during the first year after diagnosis using the Memorial Symptom Assessment Scale. The study recruited 143 patients from five U.K. cancer centers and provided 504 symptom assessments at the beginning of treatment and 3, 6, and 12 months later., Results: Six symptom clusters were identified at the first assessment, which were maintained across the assessment points with slight variations. These included gastrointestinal, hand/foot, body image, respiratory, nutritional, and emotional symptom clusters. The behavior of the clusters over time highlighted the complexities of symptom cluster assessment and the dynamic relationships between symptoms. Frequency, severity, and distress from symptoms were significantly higher (up to 75% higher) in patients who experienced a cluster of symptoms than in the overall sample, suggesting that symptom assessments in unselected patients underestimate the symptom burden in subgroups of patients., Conclusion: We propose attention to symptom clusters that are stable across time and include core or defining symptoms within the cluster, and we further discuss the usefulness and applicability of conceptual and methodological criteria used in this study for future symptom cluster research., (Copyright 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Hospital malnutrition is associated with increased morbidity and mortality, particularly among patients admitted to intensive care units (ICUs). The purpose of this observational study (August to November 2007) was to examine the adequacy of oral intake and to identify predictors of oral intake after ICU patients were removed from invasive mechanical ventilation. Patients aged > or = 18 years who required mechanical ventilation for at least 24 hours, advanced to an oral diet postextubation, and did not require supplemental enteral or parenteral nutrition were included. The first 7 days of oral intake after extubation were assessed via modified multiple-pass 24-hour recall and the numbers of days on therapeutic diets and reasons for decreased intake were collected. Oral intake <75% of daily requirements was considered inadequate. Descriptive statistics, chi2, Student t tests, and logistic regression analyses were conducted. Of the 64 patients who met eligibility criteria, 50 were included. Of these 50 patients, 54% were women and intubated for 5.2 days, with a mean age of 59.1 years, body mass index of 28.7, and Acute Physiology and Chronic Health Evaluation II score of 21.9. Subjective Global Assessment determined 44% were malnourished upon admission to the ICU. The average daily energy and protein intake failed to exceed 50% of daily requirements on all 7 days for the entire population. The majority of patients who consumed <75% of daily requirements were prescribed a therapeutic diet and/or identified "no appetite" and nausea/vomiting as the barriers to eating. Although more research is needed, these data call into question the use of restrictive oral diets and suggest that alternative medical nutrition therapies are needed to optimize nutrient intake in this unique patient population., (Copyright 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.)

Purpose: This study was conducted to examine and compare clinical manifestations and predicting factors for treatment-seeking delay among patients <65 and > or = 65 yr with first-time acute coronary syndrome (ACS)., Methods: A total of 288 patients who were diagnosed with ACS were individually interviewed at C university hospital in G-city from November 2007 to December 2008., Results: Median pre-hospital delays for younger and older patients were 5 and 12 hr, respectively. Younger patients were more likely to be current smokers, heavy drinkers, obese, stressed, and have an unhealthy diet and family history, and to complain of chest pain, left shoulder and arm pain, perspiration, and nausea. Older patients were more likely to have hypertension and diabetes, and to complain syncope and dyspnea. Logistic regression analyses showed that after adjustment for age, gender and education, progressive onset of symptom and no attribution to cardiac problem significantly predicted pre-hospital delay >3 hr in both younger and older patients. Low perceived health status was a significant independent predictor in older patients only., Conclusion: Health care providers should be concerned with different manifestations between younger and older adults, and educate people at risk for heart attack about symptoms and actions to get immediate help.

Purpose: Evidence to support the routine use of local anaesthetic in the reversal of loop ileostomy is equivocal. This randomized control study looked at the use of peri-operative infiltration of stoma with 0.25% bupivacaine with 1/200,000 epinephrine on the ease of surgery and its effect on post-operative pain and nausea., Methods: Sixty patients were randomized to receive peri-stomal infiltration with either 0.25% bupivacaine with 1/200,000 epinephrine or normal saline. The surgeon graded the surgery as straightforward, intermediate or difficult, and the time for the operation was also recorded. Post-operatively, analgesia was provided via PCA for 24 h. Post-operative pain and nausea scores and total morphine usage median (inter-quartile range) were compared using the Mann-Whitney U test with p < 0.05 considered significant., Results: There was no difference between the local anaesthetic groups and controls with respect to opiate consumption (p = 0.4), post-operative pain (p = 0.72) or nausea (p = 0.78). Shorter total anaesthetic and operative times were noted in study group, but this was not significant (p = 0.55). However, surgery was found to be easier in the local anaesthetic group (p = 0.0046)., Conclusion: Peri-stomal infiltration with 0.25% bupivacaine with 1/200,000 epinephrine does not impact on post-operative pain and nausea scores or opiate analgesia use. However, its use is recommended as an aid to dissection in surgery.

With up to 80% of pregnant women experiencing nausea and vomiting of pregnancy (NVP), it is critical to have a graded scale of its severity as a guide for appropriate treatment. In 2002 we introduced the Pregnancy-Unique Quantification of Emesis (PUQE) scoring system, which assessed the severity of nausea and vomiting in pregnancy (NVP) based on three physical symptoms: nausea, vomiting, and retching over the previous 12 hours. We present here validation of an extension of the original PUQE, by assessing NVP over 24 hours. This extension is deemed more clinically relevant, because assessment of symptoms over only 12 hours may encompass sleeping hours and hence may not adequately capture the length and severity of the symptoms. In this study we assessed the external validity of the new PUQE-24 by examining its ability to evaluate several characteristics associated with NVP: (a) ability to take multivitamin supplements; (b) rates of hospitalization and emergency room visits for severe symptoms; (c) sleep patterns; (d) liquid intake; and (e) the woman's self-rated well-being scores. Data collected prospectively from 315 women counselled via the Motherisk NVP line were used for the validation. PUQE-24 showed strong correlation with all parameters examined except for sleep patterns and hydration status. The well-being score, however, correlated significantly with hydration status. Capturing 24 hours rather than 12 hours of symptoms may better direct management of NVP and predict its outcome.

Objectives: To investigate the relations among hot flashes, other menopausal symptoms, sleep quality and depressive symptoms in midlife women., Methods: A large population-based cross-sectional study of 639 women (ages 45-54 years) consisting of a questionnaire including the Center for Epidemiologic Studies-Depression (CES-D) Scale, demographics, health behaviors, menstrual history, and menopausal symptoms., Results: After controlling for menopausal status, physical activity level, smoking status and current self-reported health status elevated CES-D score is associated with frequent nocturnal hot flashes, frequent trouble sleeping, experiencing hot flashes, nausea, headaches, weakness, visual problems, vaginal discharge, irritability, muscle stiffness, and incontinence., Conclusions: The present study found significant links between depressive symptoms and several menopausal symptoms including hot flashes, sleep disturbance, irritability, muscle stiffness, and incontinence after controlling for covariates. These findings suggest that a potential mechanism in which bothersome menopausal symptoms may influence depressed mood during the midlife is through sleep disturbance.

Objectives: The pain-relieving efficacy of antagonists of histamine 1 (H1) receptors that are widely found in the ureter and that cause contractions in renal colic was presented in comparison with a placebo., Methods: Eighty-six patients who presented to the emergency service because of renal colic accompanied by nausea, and who had urinary system stones detected were included in the study. The patients were separated into 2 groups by double-blind, random assignment. The 45 patients in group 1 received 50 mg intramuscular (IM) dimenhydrinate. The 41 patients in group 2 received 2 mL IM saline solution as a placebo. The visual analogous scale (VAS) values were detected at referral of the patients and at 10, 20, and 30 minutes of therapy to detect the pain intensity. Verbal descriptive scale (VDS) was used for evaluation of nausea and vomiting before and after the therapy., Results: VAS values were statistically quite low in group 1 at 10, 20, and 30 minutes of therapy. VDS scores were also statistically significantly low in group 1 at 30 minutes of treatment., Conclusions: Dimenhydrinate, which is an ethanolamine group H1 receptor blocker, appeared to be effective compared with the placebo in relieving renal colic pain and nausea and vomiting symptoms in patients. Comparative studies with other analgesics will be useful for determining how to use this agent for analgesic purposes in renal colic.

To identify predictors of quality of life (QoL) in episodic migraine (EM) and chronic migraine (CM), 116 migraineurs were evaluated using the Headache Needs Assessment (HANA). QoL was significantly more impaired in patients with CM. Disability was a predictor of QoL in both EM and CM. Severity of depressive symptoms emerged as a predictor of QoL in CM. QoL was also poorer in women and in those with greater headache intensity and nausea associated with headache in the total sample. The present findings suggest a specific role for depressive symptoms in impaired QoL in CM sufferers.

(1) In June 2006 the French National Cancer Institute published the results of a survey of eating difficulties among 1843 patients receiving cancer chemotherapy; (2) More than one-third of patients said they had less appetite than before ("far less" in 13% of cases). About half of patients said they had noticed a change in their sensation of thirst; (3) Half of patients who had been receiving treatment for at least 6 months said they had lost weight; (4) Half of patients found food tasted different. 43% of patients found certain odours unbearable, especially perfumes and tobacco. One-third of patients said the smell of the treatment room made them nauseous. Many patients found mealtimes unpleasant, sometimes even a source of anxiety; (5) In practice, these eating difficulties should be taken into account when assessing the risk-benefit balance of cancer treatments. When a treatment needs to be pursued, patients should be helped to find ways of making food more palatable, the treatment room should be well ventilated, and perfumes should not be used.

Background: Few population-based studies have examined comorbidity in relation to gastro-oesophageal reflux disease (GERD)., Aim: To study the association between cardiovascular disease, diabetes, gastrointestinal symptoms and GERD., Methods: Population-based, cross-sectional, case-control study based on a large Norwegian health survey conducted in 1995-97. Among 65,333 participants, 3153 persons reporting severe reflux symptoms were defined as cases, and 40,210 persons without such symptoms were defined as controls. Data on cardiovascular disease, diabetes, gastrointestinal symptoms and potential confounders were collected through questionnaires. Odds ratios (OR) with 95% confidence intervals (CI) were estimated using unconditional logistic regression, in crude and adjusted models., Results: In the crude models, positive associations were observed between myocardial infarction (OR 1.7, 95% CI 1.4-2.1), angina pectoris (OR 2.5, 95% CI 2.1-2.9) and stroke (OR 1.6, 95% CI 1.2-2.1) and risk of GERD. The associations were attenuated in the adjusted models, but remained significant for angina pectoris (OR 1.9, 95% CI 1.6-2.2). No association was observed between diabetes and GERD. Strong positive associations were seen between all studied gastrointestinal symptoms, i.e. nausea, diarrhoea and constipation, and risk of GERD., Conclusions: This population-based study indicates that myocardial infarction, angina pectoris, stroke and symptoms of nausea, diarrhoea and constipation are associated with GERD.

Thirty to forty percent of migraineurs do not respond to any given triptan treatment. We identified clinical variables that significantly predict therapeutic non-response and evaluated the efficacy of eletriptan (20, 40 and 80 mg) and sumatriptan (100 mg) vs. placebo in a subgroup of patients with all predictor variables. First-attack data were pooled from 10 randomized, double-blind, placebo-controlled migraine trials (n = 8473). Multivariate regression analyses identified three significant baseline predictors of failure to achieve 2-h pain-free response: severe headache pain, presence of photophobia/phonophobia and presence of nausea. Time of dosing following headache onset did not influence 2-h pain-free response. Among patients with all three risk factors (n = 2010; 24% of total sample), 2-h pain-free response was significantly higher in patients receiving all three doses of eletriptan or sumatriptan vs. placebo (all P < 0.01). Thus, eletriptan and sumatriptan are efficacious in difficult-to-treat patients at high risk for non-response to triptans.

Nausea and vomiting is a common and distressing symptom complex in patients with far-advanced cancer, affecting up to 60% of individuals at some stage of their illness. The current approach to the palliative care of patients with nausea and vomiting is based on identifying the cause, understanding its pathophysiology and knowing the pharmacology of the drugs available for its amelioration. The following six main syndromes are identified: gastric stasis, biochemical, raised intracranial pressure, vestibular, mechanical bowel obstruction and ileus. A careful history, focused physical examination and appropriate investigations are needed to elucidate the syndrome and its cause, so that therapy is rational. Drugs are the mainstay of treatment in terminal cancer, and the main classes of antiemetic agents are prokinetics, dopamine antagonists, antihistamines, anticholinergics and serotonin antagonists. Dexamethasone and octreotide are also used, especially in bowel obstruction. Non-drug measures are important in relieving the associated distress. Patients should be able to die comfortably, without tubes. Despite decades of practice affirming this approach, the evidence base is weak and well designed studies are urgently needed.

Background: Sphincter of Oddi (SO) dysfunction has not been reported as a cause of recurrent abdominal pain (RAP) in children. We present a 5-year follow-up of a group of children with RAP and manometry proven SO dysfunction., Methods: Retrospective chart review of children who underwent SO manometry and endoscopic sphincterotomy (ES) for recurrent abdominal pain. Long-term follow-up was obtained by telephone survey., Results: Eleven of the 12 children had abdominal pain; one had reproducible postprandial discomfort. Five children localized the pain to the upper abdomen. The same number of children had associated nausea or vomiting. On hepatobiliary scintigraphy study, three children had SO dysfunction type curve, four had low ejection fraction and nine had reproduction of symptoms on cholecystokinin (CCK) infusion. SO manometry revealed elevated pressure in 11 children. The remaining child had paradoxical contraction of the SO. On short-term follow-up, eight children had resolution of symptoms after ES, three did not respond and one had recurrence of symptom in 6 months. Children symptomatic for less than 1 year were more likely to respond to ES (P < 0.01). All children with upper abdominal pain with nausea and/or vomiting, postprandial pain and SO type scintiscan curve responded to ES. On long-term follow-up, seven of the eight responders to ES remained symptom free, one recurred with irritable bowel syndrome-like symptoms. One child with recurrent symptoms had resolution after cholecystectomy and another non-responder improved after an appendectomy., Conclusion: SO dysfunction is an uncommon but treatable cause of RAP in children. Awareness of this condition may help a segment of children with RAP.

Psychiatric manifestations of primary hyperparathyroidism are mediated by hypercalcemia. To date, most evidence indicates that hypercalcemia and increased cerebrospinal-fluid calcium levels produce depression symptoms. Presented here is a case report of a 52-year-old woman in a manic state. She had no psychiatric history but had substantially elevated parathyroid hormone levels and hypercalcemia. On the basis of emerging evidence that calcium channel-blockers effectively treat mania, the authors propose that elevated calcium levels may act through multiple mechanisms or on various regions of the brain to produce a spectrum of psychiatric symptoms that should now include mania as a possibility.

Background: Studies of exposure to environmental tobacco smoke (ETS) and risk of spontaneous abortion are limited to a few studies of self-reported exposure, and the results have been inconsistent. The aim of this study was to investigate risk of early spontaneous abortion related to ETS and active smoking as defined by plasma cotinine levels., Methods: We conducted a population-based case-control study in Uppsala County, Sweden, between January 1996 and December 1998. Cases were 463 women with spontaneous abortion at 6 to 12 completed weeks of gestation, and controls were 864 pregnant women matched to cases according to the week of gestation. Exposure status was defined by plasma cotinine concentrations: nonexposed, <0.1 ng/mL; ETS-exposed, 0.1-15 ng/mL; and exposed to active smoking, >15 ng/mL. Multivariable analysis was used to estimate the relative risk of spontaneous abortion associated with exposure to ETS and active smoking., Results: Nineteen percent of controls and 24% of cases were classified as having been exposed to ETS. Compared with nonexposed women, risk of spontaneous abortion was increased among both ETS-exposed women (adjusted odds ratio = 1.67; 95% confidence interval = 1.17-2.38) and active smokers (2.11; 1.36-3.27). We could not show a differential effect of exposure to ETS or active smoking between normal and abnormal fetal karyotype abortions., Conclusions: Nonsmoking pregnant women exposed to ETS may be at increased risk of spontaneous abortion. Given the high prevalence of ETS exposure, the public health consequences of passive smoking regarding early fetal loss may be substantial.

Gastroparesis is a condition of abnormal gastric motility characterized by delayed gastric emptying without evidence of mechanical outlet obstruction. The authors describe complete remission of recurrent postprandial discomfort, nausea, and vomiting within 1 week of starting mirtazapine in a gastroparetic patient who had failed to respond, in 7 months, to conventional prokinetics (erythromycin, metoclopramide, domperidone, perphenazine, itopride, bethanechol, and/or tegaserod) and pyloric injection of botulinum toxin. This is the first report to show that mirtazapine may be an effective alternative when gastroparesis is refractory to conventional measures.

Dyspepsia itself is not a diagnosis but stands for a constellation of symptoms referable to the upper gastrointestinal tract. It consists of a variable combination of symptoms including abdominal pain or discomfort, postprandial fullness, abdominal bloating, early satiety, nausea, vomiting, heartburn and acid regurgitation. Patients with heartburn and acid regurgitation invariably have gastroesophageal reflux disease and should be distinguished from those with dyspepsia. There is a substantial group of patients who do not have a definite structural or biochemical cause for their symptoms and are considered to be suffering from functional dyspepsia (FD). Gastrointestinal motor abnormalities, altered visceral sensation, dysfunctional central nervous system-enteral nervous system (CNS-ENS) integration and psychosocial factors have all being identified as important pathophysiological correlates. It can be considered as a biopsychosocial disorder with dysregulation of the brain-gut axis being central in origin of disease. FD can be categorized into different subgroups based on the predominant single symptom identified by the patient. This subgroup classification can assist us in deciding the appropriate symptomatic treatment for the patient.

Migraine is the most common cause of vascular headache and a highly prevalent illness. In the last 20 years, the discovery of new agents has increased clinical research on migraine. In most of clinical trials that have been conducted, the efficacy was established using a placebo as a control treatment. The objective of the study reported here was to analyse the response rate in patients who received a placebo as well as to determine how a number of the methodological factors may affect the effect of the placebo in clinical trials of acute migraine. Computer-based information searches were conducted on the Medline database. Data analysis included the outcomes 'pain relief', 'pain-free', 'associated symptoms', 'recurrence', 'patients' opinion' about pain relief and 'adverse events'. Administration route, study design and country in which the study was carried out were the methodological factors that were analyzed. Meta-analysis was computed using Mantel-Haenszel, and a total of 98 papers were considered in the final analysis. After 2 h, 28.6% of the patients of the placebo group improved and 8.8% were pain-free. The percentage of pain-free patients was the highest in the placebo and active drug groups in which the placebo or drug had been administered subcutaneously, in parallel design studies (vs. cross-over trials) and in studies performed in Europe (vs. North America). Adverse events in the placebo group were significantly higher in studies performed in North America. These data reinforce the need for knowing the magnitude of the placebo response in each specific situation during the planning of clinical trials on acute migraine.

Malnutrition is common in patients with advanced cancer and is associated with worse prognosis. The aim of this study was to follow-up the nutritional status of elderly patients with advanced cancer in comparison with that of younger ones, in the course of hospitalization. Eighty-eight (44 males and 44 females) patients with advanced cancer entered the study. Two groups were defined according to age : superior 70 y (n = 45) and < 70 y (n = 43). Nutritional status by means of anthropometric variables and daily intake were assessed on Day 0, Day 30 and Day 60. A blood sample was collected on Day 0 for determination of serum proteins. The two groups of patients did not differ in terms of anthropometry and biological variables on admission to our department ; only bicipital skinfold thickness and energy intake were lower in the elderly patients. After one month hospitalization, tricipital skinfold thickness and fat mass decreased in these patients. After two months, mid-arm circumference also decreased. Unlike the older group, the younger patients increased their daily energy and protein intakes. During hospitalization, older persons with advanced cancer cannot improve their energy intake and therefore, are at particular risk of aggravating their nutritional status.

The objective of the study was to investigate the possible association between nausea and vomiting in early pregnancy and congenital abnormalities. The prevalence of medically-recorded severe nausea and vomiting in early pregnancy in cases with congenital abnormalities and their available matched population controls without any defect was compared in the population-based large data set of the Hungarian Case-Control Surveillance System of congenital abnormalities, 1980-1996. Of 22,843 cases with as 25 different congenital abnormality groups, 1,713 (7.5%) cases had mothers with medically recorded and treated severe nausea and vomiting during pregnancy. Of 38,151 matched population controls, 3,777 (9.9%) had mothers with severe nausea and vomiting (adjusted prevalence odds ratio (POR) with 95% CI: 0.74, 0.68-0.79). Five congenital abnormality groups: cleft lip with or without cleft palate (0.50, 0.37-0.70), posterior cleft palate (0.53, 0.32-0.89), renal a/dysgenesis (0.23, 0.06-0.96), obstructive defects of urinary tract (0.32, 0.18-0.58), and cardiovascular malformations (0.68, 0.57-0.81) had mothers with a lower prevalence of severe nausea and vomiting in pregnancy (adjusted PORs with 95% CI included in parentheses). Of 25 congenital abnormality groups, 22 had POR lower than 1. Thus in this study the mothers of cases with congenital abnormalities were 26% less likely to have had severe nausea and vomiting in early pregnancy than the mothers of population controls without congenital abnormalities.

The immunosuppressive drug mycophenolate mofetil (MMF) is used after nonmyeloablative hematopoietic cell transplantation (HCT); however, limited pharmacodynamic data are available. We evaluated plasma concentrations of mycophenolic acid (MPA), the active metabolite of MMF, and outcomes in 85 patients with hematologic malignancies conditioned with fludarabine and 2 Gy total body irradiation followed by HLA-matched unrelated-donor HCT and postgrafting cyclosporine and MMF. The first 38 patients received MMF 15 mg/kg twice daily; the next 47 patients received MMF 3 times daily. MPA pharmacokinetics were determined on days 7 and 21. Comparing the twice-daily and 3-times-daily MMF groups, the mean total MPA concentration steady state (Css) was 1.9 and 3.1 microg/mL; the unbound Css was 18 and 36 ng/mL, respectively (P < .001). Sixteen patients with a total MPA Css less than 3 microg/mL had low (< 50%) donor T-cell chimerism (P = .03), and 6 patients with MPA Css less than 2.5 microg/mL had graft rejection. An elevated unbound Css was associated with cytomegalovirus reactivation (P = .03). There were no significant associations between MPA pharmacokinetics and acute graft-versus-host disease (GVHD) or relapse. We conclude that increased MPA Css's predicted higher degrees of donor T-cell chimerism after unrelated donor nonmyeloablative HCT and suggest that targeting MPA Css's greater than 2.5 microg/mL could prevent graft rejection.

Objective: To describe the characteristics of headache related to lacunar stroke based on data collected from a prospective hospital-based stroke registry over a 12-year period. Demographics, clinical variables, and prognostic features of lacunar stroke in patients with and without headache are compared., Background: Stroke-related headache has been largely investigated, but there is little clinical data on headache in individualized stroke subtypes., Methods: The cohort of 484 patients with lacunar infarction was selected. Forty-five (9.3%) presented headache within a 72-hour interval of stroke onset. Predictors of lacunar infarction with headache were assessed by logistic regression analysis., Results: The intensity of headache was mild in severity and poorly localized (diffuse or bilateral headache). Tension-type headache was present in 36 patients (80%) and 9 patients (20%) presented nausea or vomiting while experiencing mild pulsating pain. The frequency of headache was 17% in patients with atypical lacunar syndrome, 12% in dysarthria-clumsy hand, 11.5% in pure sensory stroke, 9.4% in sensorimotor stroke, and 7.1% in pure motor hemiparesis. When patients with lacunar infarction with and without headache were compared, female sex, diabetes mellitus, nausea and vomiting, and mesencephalic topography were significantly more frequent and dysarthria and frequency of symptom free at discharge were less frequent in the headache group. In the multivariate analysis, mesencephalic topography (odds ratio [OR] 16.62), nausea and vomiting (OR 13.27), sex female (OR 2.29), diabetes mellitus (OR 1.96), and age (OR 0.95) were predictors of lacunar infarction with headache., Conclusions: Headache at the onset of a lacunar infarction is uncommon. Mesencephalic topography, nausea and vomiting, female sex, diabetes, and age were independent variables significantly associated with lacunar infarction with headache. These findings contribute to knowledge of stroke-related headache in patients with lacunes.

The effectiveness of ramosetron tablets and granisetron injection was compared for reducing the frequency of nausea, vomiting, and anorexia in patients with malignant glioma undergoing ACNU chemotherapy. Patients with malignant glioma to be treated with ACNU chemotherapy were randomly assigned to receive oral ramosetron (20 patients) or intravenous granisetron (19 patients) prior to ACNU injection. Gastrointestinal toxicity within 48 hours of ACNU injection was compared to that in patients who had received ACNU chemotherapy with dopamine D2 receptor-blocker as a historical control group. Within 24 hours of the administration of ACNU, 15 of the 20 patients treated with ramosetron and 16 of the 19 treated with granisetron were nausea-free, and 14 of the former and 14 of the latter regained their normal appetite. There was no significant difference in the anti-emetic effects. Ten of the 17 controls experienced no vomiting within 6 hours of the injection of ACNU, five were nausea-free within 24 hours, and two retained their normal appetite within 24 hours. Oral ramosetron has the same anti-anorectic and anti-emetic effects as intravenous granisetron. Ramosetron tablets are less expensive and are easy to take, so should be on the list of first-choice anti-emetic drugs for patients treated with ACNU chemotherapy.

Background: Documentation of concurrent and late side effects of medical interventions to prevent and treat breast cancer is important in research and clinical practice. We used the Breast Cancer Prevention Trial (BCPT) Symptom Checklist to develop an instrument (BCPT Symptom Scales) that could be used to assess side effects and to examine correlates of the derived symptom dimensions among patient populations., Methods: Exploratory and confirmatory factor analyses were conducted using data from the 42-item BCPT Symptom Checklist completed by four distinct patient populations (N = 2208) who had previously been diagnosed with breast cancer or were at risk for the disease. We examined associations among the resulting BCPT Symptom Scales and demographic and cancer-related variables and a widely used measure of health-related quality of life., Results: Exploratory and confirmatory factor analyses revealed eight factors corresponding to physical symptoms associated with cancer treatment, chemoprevention, menopause, and normal aging: hot flashes, nausea, bladder control, vaginal problems, musculoskeletal pain, cognitive problems, weight problems, and arm problems. On the derived BCPT Symptom Scales, women reported somewhat higher mean scores on scales for hot flashes, pain, and weight problems than on scales for the other symptoms. Demographic and cancer-related variables accounted for up to 15% of the interindividual variance in how women responded to the symptom scales. The most consistent predictors of reporting greater symptoms included lower education level and previous receipt of chemotherapy., Conclusions: Meaningful symptom dimensions, identified across four samples of women, were associated with demographic and breast cancer-related variables. The BCPT Symptom Scales offer a valuable refinement of the original BCPT Symptom Checklist to assess side effects associated with the treatment and prevention of breast cancer.

This study assesses the nutritional status of tuberculosis (TB) patients in Sri Lanka and differences in the nutritional presentation between males and females. In May-June 2002, cases from Colombo hospitals and controls from both the Sri Lankan Air Force Base and audience members at a 'better health' presentation in Colombo were assessed for nutritional status using a modified Standard Global Assessment. Fifty cases and 49 controls were recruited. Nutritional examinations revealed the cases to have significantly lower nutritional values than the controls (body mass index 16.2 vs. 24.0 kg/m(2); arm circumference 20.7 vs. 28.4 cm; muscle wasting [temple 56% vs. 0%; shoulder 46% vs. 0%]). The nutritional history revealed the cases to have higher levels of anorexia, vomiting, nausea and diarrhoea within the preceding fortnight. Differences between the genders were minimal other than an increase of 23 and 19% in the frequency of female cases having suffered with vomiting and nausea respectively. Consequently, both male and female TB patients in Sri Lanka are significantly malnourished. It is recommended that patients receive nutritional support during their treatment, with studies of the exact nutritional deficiencies at the micronutrient level and their effect on the immune system being required.

Background: Nausea and vomiting are preventable side effects of cancer chemotherapy for children. Antiemetics are essential, especially as treatment becomes more intensive. Many drugs are available, but adequate evidence-based recommendations are lacking. We aimed (1) to consider an evidence-based approach for pharmacological prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in children, and (2) to compare this approach with antiemetic prescribing in two paediatric oncology centres., Procedure: Relevant publications (Medline, Embase, CancerLit:1966-2002) were critically evaluated using pre-defined criteria. Evidence-based statements summarising their findings were formulated, and evidence basis proposed. Current prescribing practice was then compared with this evidence basis in Welsh children under 16 receiving chemotherapy at Llandough Hospital, Cardiff or Alder Hey Children's Hospital, Liverpool between 1 January 2001 and 31 December 2001., Results: Of 213 studies retrieved, 82 provided evidence. Our evidence basis recommends combination 5HT3-antagonist/corticosteroid for highly emetogenic chemotherapy, 5HT3-antagonist alone for moderate emetogenicity, and no antiemetic for other chemotherapy. Forty-four children in Cardiff (0.6-16.9 yrs) and 14 in Liverpool (0.8-16.2 yrs) were included in the audit. Differences in prescribing practice between the centres were not significant. In 109/159 (69%) of chemotherapy courses (35, 87 and 100% of high, moderate and low emetogenicity, respectively), antiemetics were selected in accordance with evidence basis. Seventy percent of prescribed doses were as evidence basis recommended., Conclusions: We present an evidence basis for prescribing prophylactic antiemetics to children undergoing chemotherapy. Prescribing practices in these two centres treating Welsh children were similar. Both differed from the evidence basis we propose. Deviations were greatest for regimens of high emetogenicity, where effective emetic control is most crucial., ((c) 2004 Wiley-Liss, Inc.)

Goals of Work: The aim of this study was to evaluate the occurrence of chemotherapy-induced nausea and vomiting (CINV) and its effect on patients' ability to carry out daily life activities following moderately to highly emetogenic, first-cycle chemotherapy in routine practice in cancer centers of four different European countries., Patients and Methods: This was a prospective, cross-sectional, nonrandomized, self-assessment study in 249 patients enrolled from cancer centers in Spain, Austria, Germany, and Switzerland. The study population consisted of 78% women, with a mean age of 54. Breast, lung, and ovarian cancers made up 75% of all cancers in the study. Patients received a mean of 2.0 chemotherapy agents and 2.5 antiemetic drugs., Main Results: A total of 450 emetic episodes experienced by 243 patients was recorded over 5 days following chemotherapy, with an average of 1.8 episodes per patient (range: 0-28). A higher percentage of patients (38%) suffered from delayed compared to acute emesis (13%). Between 42% and 52% of all patients suffered from nausea (visual analogue scale > or = 5 mm) on any one day, peaking at day 3. Using the Functional Living Index for Emesis (FLIE) questionnaire, 75% of patients with nausea and 50% with vomiting reported a negative impact of these conditions on performance of daily living., Conclusions: CINV remains a significant problem in routine practice, particularly in the delayed phase posttreatment. Overall, CINV had a negative impact on patients' daily life.

Trofosfamide (Ixoten; Baxter Oncology, Germany) is an alkylating agent that, as with other oxazaphosphorine derivatives, has to be activated by hepatic cytochrome P450 oxidases. The bioavailability is nearly 100% after oral application, and the main metabolites are 4-hydroxytrofosfamide, and 4-hydroxyifosfamide. The main side-chain metabolites ifosfamide and cyclophosphamide can be further activated by oxidation and formation of their respective phosphoramide mustards. Oral continuous low-dose therapy has been the most widely used schedule. The toxicity profile consists mainly of dose-dependent hematotoxicity and, rarely, hemorrhagic cystitis. Nausea and vomiting are infrequently seen. Higher grades of nephrotoxicity or neurotoxicity--side-effects that typically limit the use of ifosfamide-have not been reported with low-dose continuous trofosfamide treatment. We report herein a case of a 83-year-old female patient with a disseminated malignant peripheral nerve sheath tumor treated with trofosfamide developing pulmonal toxicity. To our knowledge, this is the first reported case of exogenous allergic alveolitis after exposure to this drug.

The objective of this study was to define the maximally tolerated dose (MTD) and response rate of a combination of two topoisomerase I inhibitors, topotecan and irinotecan, in patients with metastatic colon cancer. Eleven patients, the majority with previously progressive disease on 5-fluorouracil-based regimens, were enrolled onto a phase I/II dose escalation trial utilizing continuous infusion topotecan for 2 weeks and weekly irinotecan x 3 with cycles repeated every 28 days. Dosages of topotecan utilized included 0.2 and 0.25mg/m2/day. Irinotecan was administered at a dose of 62 mg/m2 by i.v. bolus. Patients were followed for toxicity and response. The MTD of the combination of agents was found to be 0.25mg/m2/day for topotecan and 62 mg/m2 for irinotecan. The most common serious toxicities were diarrhea and nausea/vomiting. Only one patient experienced grade III neutropenia. There were no complete or partial responses. However, four patients had prolonged disease stabilization (SD) of up to 324 days and this group remained on protocol therapy for an average of 227 days (p=0.0005 versus patients not achieving SD). We concluded that the MTD for this combination of topoisomerase I inhibitors, given on this particular schedule, has been defined. This combination cannot be recommended as a first- or second-line therapy for patients with metastatic colon cancer based on the responses observed. However, approximately one-third of patients achieved prolonged disease stabilization. Topotecan with irinotecan may be useful as a palliative regimen for a subgroup of colon cancer patients.

Background & Objectives: Severe invasive infections caused by group A Streptococcus (GAS) are often associated with shock and organ failure. We describe epidemiological and disease related data from the national surveillance of invasive GAS infection in Denmark in addition to three fatal cases that occurred in Denmark in 2002 with gastrointestinal (GI) symptoms as the dominating preliminary signs., Methods: As the National Streptococcal Reference Centre The Streptococcus Unit, Statens Serum Institut (SSI) receives the vast majority of the invasive GAS isolates from patients admitted to all the hospitals in Denmark. The isolates were T-typed by slide agglutination test emm-squencing and pulsed field gel electrophoresis (PFGE) were also performed., Results: During January 2002 three patients died at home and GAS were found at autopsy. Cases 1 (12 yr) and 3 (25 yr) had been ill for less than two days with nausea, diarrhoea and vomiting. Case 2 (25 yr) had the same symptoms for two weeks. None of the three had any underlying diseases. The GAS isolates from cases 1 and 2 were T-type 3-13-B3264, emm89 and SpeA-, SpeC-. The third isolate was Ttype 1, emm1 and SpeA+, SpeC-. PFGE could not discriminate between the two isolates with T-type 3-13-B3264. The PFGE patterns of the three isolates were similar to those identified from GAS isolated elsewhere in Denmark at different times and from non-fatal cases. In 1999-2002, SSI received 409 isolates from patients with invasive GAS infection, and the mortality rate was 18 per cent. In 40 patients the primary symptoms were gastrointestinal, and in 30 per cent of these the outcome was fatal., Interpretation & Conclusion: The various early clinical manifestations of severe GAS infections are still a major challenge for clinicians because of the importance of a fast and appropriate diagnosis and immediate start of treatment.

To determine if droperidol i.v. is as effective as prochlorperazine i.v. in the emergency department (ED) treatment of uncomplicated headache, a randomized, controlled, blinded study was conducted in the Emergency Departments of two urban teaching hospitals. Patients >or= 18 years old with crescendo-onset headache were eligible for inclusion. Ninety-six patients (48 in each group) were randomized to receive droperidol 2.5 mg i.v. or prochlorperazine 10 mg i.v. Baseline characteristics were similar between the two study groups. For the main study outcome, 83.3% in the droperidol group and 72.3% in the prochlorperazine group reported 50% pain reduction at 30 min (p <.01; one-sided test of equivalence). The mean decrease in headache intensity was 79.1% (SD 28.5%) in the droperidol group and 72.1% (SD 28.0%) in the prochlorperazine group (p =.23). It is concluded that droperidol i.v. provided a similar reduction of headache as achieved with prochlorperazine i.v. with a similar incidence of akathisia.