Intrapyloric Botulinum Toxin Injection for Refractory Nausea and Vomiting in Pediatric Patients.

OBJECTIVES: Chronic nausea and vomiting may be associated with gastroparesis or other conditions. Poor mechanistic understanding of symptoms often precludes targeted therapy. Numerous case series suggest that intrapyloric botulinum toxin injection (IPBI) may be beneficial in treating gastroparesis and dyspepsia in children. We hypothesized that nausea, vomiting, and other symptoms, independent of gastroparesis, may improve with IPBI. We sought to identify gastric emptying (GE) and manometric patterns in IPBI responders versus nonresponders. METHODS: Electronic records of 25 pediatric patients who received IPBI for refractory nausea, vomiting, or both were retrospectively reviewed. We assessed symptom improvement post-IPBI and compared symptoms, GE, and antroduodenal manometry (ADM) findings between IPBI responders and nonresponders. RESULTS: At least one major symptom improved in 19 patients (76%) after IPBI. Of 22 patients completing a GE study, 14 had delayed GE with no significant difference between IPBI responders and nonresponders. Of 22 patients who underwent ADM, 18 had normal fasting peristalsis, 5 had postprandial antral hypomotility, 4 had neuropathic findings, and 19 had pylorospasm. IPBI responders, compared to nonresponders, demonstrated higher antral pressures with feeding ( P < 0.0001) and shorter duration of pylorospasm ( P = 0.0036). Antral pressures did not differ significantly with fasting or following motilin agonists. CONCLUSIONS: Our findings suggest that IPBI may have therapeutic benefit in pediatric patients with chronic nausea and/or vomiting, independent of gastroparesis. ADM findings of intact antral peristalsis and elevated antral pressures, in conjunction with efficacy of IPBI, support pyloric non-relaxation as a potential contributor to nausea and/or vomiting in pediatric patients.

Use of Cluster Analysis to Identify Subtypes of Pediatric Functional Nausea.

OBJECTIVE: The aim of the study was to evaluate whether there are clinical subtypes in children with functional nausea based on comorbidities and responses to the Nausea Profile questionnaire. METHODS: Patients from the Neurointestinal and Motility Program clinical registry at Lurie Children's Hospital were included if they met Rome IV criteria for functional nausea. Patients completed the Nausea Profile, a multidimensional measure of nausea with gastrointestinal, emotional, and somatic subscales. Comorbidities were assessed by chart review and self-report measures. Latent class analysis was used to identify patient groups based on comorbidities. To assess if model-identified groups were predictive of differences in nausea quality, Nausea Profile subscale means were compared between groups and used to predict group membership. Conversely, k-means analysis was used to divide the sample into groups based upon Nausea Profile subscale scores, to determine if identified groups had different comorbidities. RESULTS: Seventy-two patients (n = 53 girls) with a mean age (±SD) 14.5 ±â€Š2.9 were included. Two clinical subtypes were identified based on comorbidities, with responses on the emotional subscale of the Nausea Profile predicting group membership (P < 0.04). When patients were grouped by nausea quality, the resulting clusters differed on psychiatric comorbidities (P < 0.001). CONCLUSIONS: Our findings support the existence of nausea subtypes within the broad diagnosis of functional nausea. One such subtype is an emotional predominant nausea supporting the notion that anxiety and depression constitute a subset of patients with nausea. Thus, patients may benefit from a treatment approach that integrates both GI assessment and psychiatric support in their care.

Children with Functional Nausea-Comorbidities outside the Gastrointestinal Tract.

OBJECTIVE: To detail common comorbidities and procedures performed to evaluate functional nausea in children. STUDY DESIGN: In total, 63 children age 7-18 years seen in a tertiary care pediatric clinic who met Rome IV criteria for functional nausea prospectively completed an Intake Questionnaire, the Pediatric and Parent-Proxy PROMIS-25 Profile v 2.0, the Pediatric and Parent-Proxy Pediatric Sleep Disturbance-Short Form 4a, and the COMPASS 31 orthostatic intolerance scale to assess comorbidities. Medical records were reviewed for diagnostic tests performed to evaluate nausea and for additional comorbidities. Summary statistics were used to determine the most common comorbidities and diagnostic yield of the procedures. Intraclass correlation coefficients assessed agreement between parent and child reports on the PROMIS scales. RESULTS: Patients with functional nausea experienced multisystem comorbidities. A majority reported abdominal pain, headache, orthostatic intolerance, fatigue, disturbed sleep, anxiety, constipation, allergies, and vomiting. Agreement between parent-proxy and child report of symptoms on PROMIS scales was good to excellent (intraclass correlation coefficients = .78-.83; all P < .001). Patients underwent extensive diagnostic testing: 96 endoscopic procedures, 199 radiologic tests, and 4 cholecystectomies. Most of the procedures were not diagnostically informative. CONCLUSIONS: Children with functional nausea have comorbidities outside the gastrointestinal tract that warrant evaluation. Gastrointestinal diagnostic tests were of low-yield in identifying a cause. Understanding the relationship with comorbidities may provide insight into etiologies for the nausea and define clinical phenotypes to better tailor care.

Serotonin transporter genotype modulates HPA axis output during stress: effect of stress, dexamethasone test and ACTH challenge.

BACKGROUND: Studies show that the hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in depression. Some studies suggest that variation in the serotonin transporter genotype (hereafter 5HTT) modulates both risk for depression and psychopathological HPA axis responsiveness. Rhesus monkeys are well suited to model such relationships. Rhesus macaque models of human psychopathology have assessed the effect of the serotonin transporter (rh5HTT) on levels of cortisol in stressed subjects. These studies show that that under conditions of stress, heterozygous females (Ls) reared under adversity exhibit high levels of cortisol. Studies have not to our knowledge, however, assessed the potential additive effect on the cortisol response in a number of macaque subjects homozygous for the serotonin transporter short allele (ss). Moreover, little is known about the level of the central or peripheral nervous system at which the 5HTT genotype acts to modulate the cortisol response. METHODS: This study assesses a relatively large number of subjects homozygous and heterozygous for the rh5HTT short and long alleles (a) during stress; (b) following a dexamethasone suppression test; and (c) following an adrenocorticotropic hormone (ACTH) challenge. Subjects included 190 infant rhesus macaques (Macaca mulatta - 84 males and 106 females; 118 LL, 60 Ls, and 12 ss subjects), obtaining two blood plasma samples during the stress of separation from their mothers. Then on the following day, we obtained a blood sample following a dexamethasone test, and later that day we obtained a blood sample after an ACTH challenge test. Subjects ranged in age between 90 and 128 days, with a mean age of 107 days. RESULTS: Subjects homozygous for the short allele had significantly higher levels of cortisol across all test conditions, when compared to those homozygous for the long allele, or those heterozygous with Ls alleles. Subsequent analyses showed a high correlation between individual cortisol levels across the three different tests. CONCLUSIONS: These data suggest that subjects homozygous for the short allele are more likely to show dysregulated cortisol levels in response to stress. Given the correlation in individual responses of the HPA axis across the different tests, our data suggest that the effect of the 5HTT genotype shows some commonality in its regulation of stress, feedback, and ACTH-stimulated cortisol output. Our data suggest that under conditions of stress, the serotonin transporter may modulate HPA axis psychopathology.

Fish consumption and advisory awareness among the Philadelphia Asian community: a pilot study.

Difficulties in the risk communication of fish consumption arise from the concept that this consumption can have both harmful and beneficial effects. This is particularly an issue among populations for which seafood is a major dietary and cultural component. Fish advisories are an important tool in preventing overconsumption of fish that have elevated concentrations of toxic contaminants. The exploratory pilot study described in this article examined fish consumption patterns and knowledge of the potential health risks associated with overconsumption of mercury-contaminated fish within a limited (N = 34) sample of the Philadelphia Asian-American population. Study data were used to evaluate the efficacy of state-issued advisories designed to encourage safe levels of fish consumption within the study population. Results indicate that while advisory awareness levels among study participants were greater than previously observed in Asian-American populations, consumption levels remained high. The limited findings of the authors' study, in combination with existing evidence, suggest the need for the development of more effective methods of disseminating advisory information.

Similarity in temperament between mother and offspring rhesus monkeys: sex differences and the role of monoamine oxidase-a and serotonin transporter promoter polymorphism genotypes.

Temperament is usually considered biologically based and largely inherited, however, the environment can shape the development of temperament. Allelic variation may confer differential sensitivity to early environment resulting in variations in temperament. Here we explore the relationship between measures of temperament in mothers and their first-born offspring and the role of genetic sensitivity in establishing the strength of these associations. Temperament ratings were conducted on 3- to 4-month-old rhesus monkeys after a 25-hr biobehavioral assessment. Factor analysis revealed a four-factor structure of temperament. Females assessed as infants have reproduced and their offspring have also been evaluated through the standardized testing paradigm. Canonical correlation analysis revealed statistically significant associations between factor scores of mothers and sons, but not mothers and daughters. Further, offspring possessing the high activity, "low risk," alleles of the rhMAOA-LPR or rh5-HTTLPR showed statistically significant canonical correlations, whereas those possessing other alleles did not, suggesting differential genetic sensitivity to the normative early experience of maternal temperament.

Cortisol concentrations in the milk of rhesus monkey mothers are associated with confident temperament in sons, but not daughters.

One pathway by which infant mammals gain information about their environment is through ingestion of milk. We assessed the relationship between stress-induced cortisol concentrations in milk, maternal and offspring plasma, and offspring temperament in rhesus monkeys. Milk was collected from mothers after a brief separation from their infants at 3-4 months postpartum, and blood was drawn at this time for both mothers and infants. Offspring temperament was measured at the end of a 25-hr assessment. Cortisol concentrations in milk were in a range comparable to those found in saliva, and were positively correlated with maternal plasma levels. Mothers of males had higher cortisol concentrations in milk than did mothers of females, and cortisol concentrations in maternal milk were related to a Confident temperament factor in sons, but not daughters. This study provides the first evidence that naturally occurring variation in endogenous glucocorticoid concentrations in milk are associated with infant temperament.