Cyclic Vomiting Syndrome in 41 adults: the illness, the patients, and problems of management

BACKGROUND: Cyclic Vomiting Syndrome (CVS) is a disorder characterized by recurrent, stereotypic episodes of incapacitating nausea, vomiting and other symptoms, separated by intervals of comparative wellness. This report describes the clinical features, co-morbidities and problems encountered in management of 41 adult patients who met the diagnostic criteria for CVS. METHODS: This is a retrospective study of adults with CVS seen between 1994 and 2003. Follow-up data were obtained by mailed questionnaires. RESULTS: Age of onset ranged from 2 to 49 years. The duration of CVS at the time of consultation ranged from less than 1 year to 49 years. CVS episodes were stereotypic in respect of their hours of onset, symptomatology and length. Ninety-three percent of patients had recognizable prodromes. Half of the patients experienced a constellation of symptoms consisting of CVS episodes, migraine diathesis, inter-episodic dyspeptic nausea and a history of panic attacks. Deterioration in the course of CVS is indicated by coalescence of episodes in time. The prognosis of CVS is favorable in the majority of patients. CONCLUSION: CVS is a disabling disorder affecting adults as well as children. Because its occurrence in adults is little known, patients experience delayed or mis-diagnosis and ineffectual, sometimes inappropriately invasive management

Deletion of Running-Induced Hippocampal Neurogenesis by Irradiation Prevents Development of an Anxious Phenotype in Mice

Recent evidence postulates a role of hippocampal neurogenesis in anxiety behavior. Here we report that elevated levels of neurogenesis elicit increased anxiety in rodents. Mice performing voluntary wheel running displayed both highly elevated levels of neurogenesis and increased anxiety in three different anxiety-like paradigms: the open field, elevated O-maze, and dark-light box. Reducing neurogenesis by focalized irradiation of the hippocampus abolished this exercise-induced increase of anxiety, suggesting a direct implication of hippocampal neurogenesis in this phenotype. On the other hand, irradiated mice explored less frequently the lit compartment of the dark-light box test irrespective of wheel running, suggesting that irradiation per se induced anxiety as well. Thus, our data suggest that intermediate levels of neurogenesis are related to the lowest levels of anxiety. Moreover, using c-Fos immunocytochemistry as cellular activity marker, we observed significantly different induction patterns between runners and sedentary controls when exposed to a strong anxiogenic stimulus. Again, this effect was altered by irradiation. In contrast, the well-known induction of brain-derived neurotrophic factor (BDNF) by voluntary exercise was not disrupted by focal irradiation, indicating that hippocampal BDNF levels were not correlated with anxiety under our experimental conditions. In summary, our data demonstrate to our knowledge for the first time that increased neurogenesis has a causative implication in the induction of anxiety

Gene-Trap Mutagenesis Identifies Mammalian Genes Contributing to Intoxication by Clostridium perfringens ε-Toxin

The Clostridium perfringens ε-toxin is an extremely potent toxin associated with lethal toxemias in domesticated ruminants and may be toxic to humans. Intoxication results in fluid accumulation in various tissues, most notably in the brain and kidneys. Previous studies suggest that the toxin is a pore-forming toxin, leading to dysregulated ion homeostasis and ultimately cell death. However, mammalian host factors that likely contribute to ε-toxin-induced cytotoxicity are poorly understood. A library of insertional mutant Madin Darby canine kidney (MDCK) cells, which are highly susceptible to the lethal affects of ε-toxin, was used to select clones of cells resistant to ε-toxin-induced cytotoxicity. The genes mutated in 9 surviving resistant cell clones were identified. We focused additional experiments on one of the identified genes as a means of validating the experimental approach. Gene expression microarray analysis revealed that one of the identified genes, hepatitis A virus cellular receptor 1 (HAVCR1, KIM-1, TIM1), is more abundantly expressed in human kidney cell lines than it is expressed in human cells known to be resistant to ε-toxin. One human kidney cell line, ACHN, was found to be sensitive to the toxin and expresses a larger isoform of the HAVCR1 protein than the HAVCR1 protein expressed by other, toxin-resistant human kidney cell lines. RNA interference studies in MDCK and in ACHN cells confirmed that HAVCR1 contributes to ε-toxin-induced cytotoxicity. Additionally, ε-toxin was shown to bind to HAVCR1 in vitro. The results of this study indicate that HAVCR1 and the other genes identified through the use of gene-trap mutagenesis and RNA interference strategies represent important targets for investigation of the process by which ε-toxin induces cell death and new targets for potential therapeutic intervention

Feeding diets with fodder beet decreased methane emissions from dry and lactating dairy cows in grazing systems

Fodder beet (Beta vulgaris L.) has a very high readily fermentable carbohydrate concentration, which could affect rumen fermentation and reduce enteric methane (CH₄) emissions. The objective of the current study was to estimate CH₄ emissions from dry dairy cows grazing either fodder beet supplemented with perennial ryegrass (Lolium perenne L.)-dominated pasture silage (6 kg DM/cow/day; FB+Sil) or forage kale (Brassica oleracea L.) supplemented with barley (Hordeum vulgare L.) straw (3 kg DM/cow/day; kale+Str; dry cows, Experiment 1), and from dairy cows in early lactation grazing perennial ryegrass-dominated pasture alone (pasture) or supplemented with fodder beet bulbs (3 kg DM/cow/day; past+FB; lactating cows; Experiment 2). Methane measurements were performed using GreenFeed units (C-Lock Inc., Rapid City, SD, USA) for 40 days in August-September 2015 (Experiment 1) and for 22 days in November-December 2015 (Experiment 2), from 45 and 31 Holstein-Friesian × Jersey dairy cows in Experiments 1 and 2, respectively. Dry cows grazing FB+Sil in Experiment 1 produced 18% less CH₄ (g/day) and had 28% lower CH₄ yield (g/kg DM intake; P < 0.001) than did cows grazing kale+Str. Lactating cows grazing past+FB in Experiment 2 produced 18% less CH₄ and had 16% lower CH₄ intensity (g/kg fat and protein-corrected milk production; P < 0.01) than did cows grazing pasture alone, while milk production and composition were similar for the two groups. In conclusion, feeding fodder beet at ∼50% and 20% of the diet of dry and lactating dairy cows in pastoral systems can mitigate CH₄ emissions

Methane and carbon dioxide emissions from lactating dairy cows grazing mature ryegrass/white clover or a diverse pasture comprising ryegrass, legumes and herbs

There is a growing interest in forage mixtures (Diverse pasture; e.g. containing grasses, legumes and herbs), especially those with a greater tolerance of dry conditions and a decreased nitrogen (N) content (reducing N losses), compared with ryegrass (Lolium perenne L and Lolium multiflorum L)/white clover (Trifolium repens L) pastures (RyeWC), which dominate New Zealand pastoral systems for dairy production. However, the effect of alternative forages on enteric methane (CH₄) emissions is not known. The objective of the present trial was to compare CH₄ emissions and milk production from dairy cows grazing either mature RyeWC or mature Diverse pasture (both approximately with pasture mass of 5600 kg DM/ha). The Diverse mixture comprised ryegrass, white clover, lucerne (Medicago sativa L), chicory (Cichorium intybus L) and plantain (Plantago lanceolata L). Milk production, measured from cows commencing at ∼162 days of lactation, was less when cows grazed RyeWC than Diverse pastures (15.4 vs 16.7 kg/day; P < 0.001), whereas CH₄ production (g/day) was similar for the respective treatments (411 g/day; P = 0.16). Milk composition was not affected by diet and CH₄ intensity was similar for both diets (22 g/kg fat-and protein-corrected milk; P = 0.31). Methane yield [g/kg predicted dry matter intake (DMI)] averaged 22.6 and 24.9 for cows grazing RyeWC and Diverse pastures, respectively (P = 0.006). In conclusion, although the CH₄ yield was greater when Diverse pasture was grazed, relative to RyeWC, there were no differences in emissions intensity or total CH₄ emissions