13-year-old girl with recurrent, episodic, persistent vomiting: out of the pot and into the fire.

Cyclic vomiting syndrome (CVS) is a well-established cause of recurrent vomiting in the pediatric population. Severe vomiting with chronic cannabis use, known as cannabinoid hyperemesis syndrome, has recently been more widely recognized as an etiology of persistent episodic vomiting. In turn, patients presenting with frequent episodes of CVS are now increasingly being screened for cannabinoid use. Because patients with persistent vomiting are also frequently prescribed a proton pump inhibitor (PPI) for their gastrointestinal symptoms, it is important to be aware of the potential for a PPI to cause an interaction that can lead to false-positive urine cannabinoid screening. We describe a case of a false-positive urine cannabinoid screen in a patient with CVS who received a dose of intravenous pantoprazole. The primary reference regarding drug screen interference from PPIs can be found in the pantoprazole package insert that refers to pre-Food and Drug Administration approval data. Although multiple sources on the Internet report the possibility of positive cannabinoid screens from pantoprazole, there are no known published reports of the phenomenon in the medical literature.

Bioanalytical investigation of asarone in connection with Acorus calamus oil intoxications.

Preparations of the plant Acorus calamus (calamus or sweet flag) (A. calamus) are available via internet trade and marketed as being hallucinogenic. In 2003-2006, the Swedish Poisons Information Centre received inquiries about 30 clinical cases of intentional intoxication with A. calamus products. The present investigation aimed to identify alpha- and beta-asarone, considered active components of A. calamus, and metabolites thereof in urine samples collected in seven of these cases. To further aid the identification of asarone biotransformation products, a calamus oil preparation was incubated with the fungus Cunninghamella elegans, which is used as a microbial model of mammalian drug metabolism. Using gas chromatography-mass spectrometry (GC-MS) analysis in selected ion monitoring mode, alpha-asarone was detected in five urine samples at concentrations ranging between approximately 11 and 1150 microg/L and beta-asarone in four of those at approximately 22-220 microg/L. A previously identified asarone metabolite, trans-2,4,5-trimethoxycinnamic acid (trans-TMC), was detected in the fungus broth by liquid chromatography-tandem mass spectrometry whereas cis-TMC was tentatively identified in the human urine samples. Using GC-MS, a hydroxylated asarone metabolite was identified both in fungus broth and urine samples. However, this study demonstrated no evidence for the presence of 2,4,5-trimethoxyamphetamine, claimed as a hallucinogenic component of A. calamus. The main clinical symptom reported by the patients was prolonged vomiting that sometimes lasted more than 15 h.

5-Hydroxyindoleacetic acid and substance P profiles in patients receiving emetogenic chemotherapy.

BACKGROUND: Even though direct cause and effect has not been proved, clinical evidence suggests serotonin and substance P (SP) are involved in the emetic response following chemotherapy. Because of several parallels, we hypothesized that SP release, like serotonin, may be propagated by chemotherapy and both substances can be measured in biological fluids, and correlated with a particular phase of emesis. METHODS: Urinary 5-hydroxyindoleacetic acid (5-HIAA) was assessed by HPLC; serum and urine SP were measured by immunoassay. In addition to construction of neurotransmitter profiles, all SP data were grouped according to cisplatin dosages, = or >75 mg/m(2) versus <75 mg/m(2), and phase of emesis, acute versus delayed. Analyses of these data were performed by repeated measures analysis of variance. RESULTS: Samples were collected over a 72-hour period from 26 adult patients who received cisplatin- (n = 13) or non-cisplatin-containing (n = 13) chemotherapy. Mean baseline 5-HIAA: creatinine ratios were 5.23 and 5.16 in females and males, respectively; mean baseline SP levels were 392 and 181 pg/mL in females and males, respectively. Comparisons between SP data stratified by cisplatin dosage and emetic phase were significantly different, P < 0.0001. CONCLUSIONS: Laboratory studies provide additional evidence that serotonin and SP are involved primarily, though not exclusively, in acute and delayed vomiting, respectively.

Symptoms in advanced cancer: relationship to endogenous cortisol levels.

We investigated a possible relationship between levels of endogenous cortisol and severity of different symptoms in patients with advanced cancer. Twenty-three patients with predominantly gastrointestinal cancer, recruited in a palliative care unit, entered the study. Urinary free cortisol (UFC) was measured together with demographic data, blood parameters, tumour burden, concurrent illness, medication, nutritional status and quality of life. Significant positive correlations were found between levels of endogenous cortisol and appetite loss, fatigue and nausea/vomiting. The findings support the view of a chronic stress condition in advanced cancer. Interaction between cytokines and the hypothalamic-pituitary-adrenal (HPA) axis may also be important in the interpretation of the results.

Urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion during multiple-day high-dose chemotherapy.

Highly emetogenic drugs such as cisplatin induce an increase in the urinary 5-hydroxyindoleacetic acid (5-HIAA) level, the main metabolite of serotonin (5-HT), within the first 24 h following a single infusion, thus providing a possible cause for acute emesis and an explanation for the action of 5-HT3 antagonists. No further excretion peaks have been observed, suggesting that additional or serotonin-independent mechanisms cause delayed emesis. Our aim was to study the mechanisms behind emesis seen during a highly emetogenic chemotherapy regimen given as a continuous infusion over several days. Seven women treated with a 4-day high-dose chemotherapy (HDCT) regimen for breast cancer entered the study. Pooled urine samples were collected prior to and during chemotherapy for determining 5-HIAA excretion. An excretion peak in the urinary 5-HIAA level was observed within the first 24 h with no further peaks thereafter. Thus, the mechanisms behind the emesis experienced during this highly emetogenic multiple-day chemotherapy regimen from days 2-3 onwards would appear to be at least partially serotonin independent and would not be expected to be completely relieved by 5-HT3 antagonists alone.

3-Hydroxyisobutyric aciduria in two brothers.

Two Japanese brothers with 3-hydroxyisobutyric aciduria (3HiB-uria) are studied. The elder brother died of a ketoacidotic episode at the age of 4 years; the younger brother also manifested repeated episodes of ketoacidosis after 1 year of age. He is diagnosed as having 3HiB-uria by gas chromatography/mass spectometry analysis, using the unique fragment ions of 3HiB. Magnetic resonance imaging reveals focal white matter abnormalities. Protein restriction is effective for preventing the ketoacidotic episodes, although carnitine therapy seems less effective.

5-Hydroxyindoleacetic acid (5-HIAA) and cortisol excretion as predictors of chemotherapy-induced emesis.

This study evaluated the relationship between prechemotherapy cortisol and 5-hydroxyindoleacetic acid (5-HIAA) excretion and chemotherapy-induced emesis. The urinary excretion of cortisol and the serotonin metabolite 5-HIAA in the night before chemotherapy administration were measured in 28 and 49 female patients receiving > 300 mg m-2 carboplatin. Vomiting and nausea were documented over a 3 day observation period. Lower basal cortisol excretion was significantly correlated with vomiting with or without nausea occurring within the observation period. 5-HIAA showed only a weak correlation with emesis on days 1-3, but low 5-HIAA excretion was correlated with a higher proportion of patients vomiting on days 2-3 following chemotherapy. Low basal cortisol excretion might be useful as a predictor for chemotherapy-induced emesis and therefore should be evaluated prospectively in future studies.

Treatment with para-chlorophenylalanine antagonises the emetic response and the serotonin-releasing actions of cisplatin in cancer patients.

To test the role of serotonin in chemotherapy-induced nausea and emesis, ten cancer patients were pretreated with the serotonin synthesis inhibitor para-chlorophenylalanine (PCPA). PCPA (2 g 8 hourly for 2 or 3 days prior to cisplatin) reduced the spontaneous urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), inhibited the increase in urinary 5-HIAA induced by cisplatin and markedly attenuated the acute period of nausea and vomiting associated with the cytotoxic drug. These results indicate that gastrointestinal serotonin mediates cisplatin-induced emesis and that the amount of serotonin released by cisplatin is a major factor in determining the severity of the acute period of emesis experienced by the patient.

Delayed chemotherapy-induced nausea is augmented by high levels of endogenous noradrenaline.

The relation between pretreatment night-time urinary catecholamine excretion and chemotherapy-induced nausea and vomiting was studied. The first cohort included 17 women and three men with various cancer forms receiving low or moderately emetogenic chemotherapy. The second cohort included 42 women receiving cisplatinum (50 mg m-2) for ovarian cancer and ondansetron as an antiemetic (8 mg i.v. x 3 at chemotherapy and 8 mg p.o. x 3 for 5 days). Relatively higher noradrenaline, but not adrenaline, excretion was associated with an increased intensity of delayed nausea following treatment. Vomiting was not consistently related to the excretion of either catecholamine. The results indicate that noradrenaline modulates delayed nausea resulting from chemotherapy.

Jamaican vomiting sickness in Toledo, Ohio.

The endemic illness of Jamaica known as ackee poisoning is reported for the first time in the United States. The toxic exposure resulted from the consumption of canned ackee. The epidemiology, diagnosis, theoretical mechanism, and possible therapy of this disease are discussed.

Urinary serotonin metabolite excretion during cisplatin chemotherapy.

BACKGROUND: Nausea and vomiting associated with cisplatin chemotherapy is a source of major morbidity that remains difficult to control. Acute phase (0-24 hours after induction of chemotherapy) nausea and vomiting parallels plasma serotonin release, which explains the effectiveness of 5HT3 antagonists; serotonin release in the delayed phase (24-48 hours after induction), during which consistent antiemetic control remains elusive, has not been investigated. The effect of propofol, a recent addition to the antiemetic armamentarium, on this serotonin release has not been studied. METHODS: Ten women with nausea and vomiting refractory to ondansetron and dexamethasone prophylaxis in their first cisplatin chemotherapy cycle were studied. Serial urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were determined during a 48-hour period in 30 subsequent cycles, conducted under ondansetron/dexamethasone prophylaxis together with a propofol infusion. RESULTS: There was a significant urinary 5-HIAA peak 6 hours after induction of chemotherapy, with no peaks thereafter. Propofol did not inhibit serotonin release. CONCLUSIONS: Cisplatin chemotherapy is associated with serotonin release in the acute phase. There is no serotonin release during the delayed phase. Thus the use of 5HT3 antagonists for delayed-phase nausea and vomiting would appear questionable.