Poor prognostic factors for midgut carcinoid patients were multiple liver metastases, presence of carcinoid syndrome and high levels of the tumor markers studied. In this study the only independent predictors of bad prognosis in midgut, carcinoid patients were advanced age, which however is inherently related to overall survival, and plasma chromogranin A > 5000 micrograms/l. Thus, chromogranin A may prove to be an important prognostic marker for patients with carcinoid tumors.

Nerve growth factor (NGF) is important for the survival and maintenance of central cholinergic neurons, a signalling system impaired in Alzheimer’s disease. We have treated 3 patients with Alzheimer’s disease with a total of 6.6 mg NGF administered continuously into the lateral cerebral ventricle for 3 months in the first 2 patients and a total of 0.55 mg for 3 shorter periods in the third patient. The patients were extensively evaluated with clinical, neuropsychological, neurophysiological and neuroradiological techniques. Three months after the NGF treatment ended, a significant increase in nicotine binding was found in several brain areas in the first 2 patients and in the hippocampus in the third patient as studied by positron emission tomography. A clear cognitive amelioration could not be demonstrated, although a few neuropsychology tests showed slight improvements. The amount of slow-wave cortical activity as studied by electroencephalography was reduced in the first 2 patients. Two negative side effects occurred with NGF treatment: first, a dull, constant back pain was observed in all 3 patients, which in 1 patient was aggravated by axial loading resulting in sharp, shooting pain of short duration. When stopping the NGF infusion, the pain disappeared within a couple of days. Reducing the dose of NGF lessened the pain. Secondly, a marked weight reduction during the infusion with a clear weight gain after ending the infusion was seen in the first 2 patients. We conclude from this limited trial that, while long-term intracerebroventricular NGF administration may cause certain potentially beneficial effects, the intraventricular route of administration is also associated with negative side effects that appear to outweigh the positive effects of the present protocol. Alternative routes of administration, and/or lower doses of NGF, perhaps combined with low doses of other neurotrophic factors, may shift this balance in favor of positive effects.

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Objectives5-HT storing enterochromaffin (EC) cells are believed to respond to nutrient and gut microbial components, and 5-HT receptor-expressing afferent vagal neurons have been described to be the major sensors of nutrients in the GI-tract. However, the molecular mechanism through which EC cells sense nutrients and gut microbiota is still unclear.Methods and resultsTPH1, the 5-HT generating enzyme, and chromogranin A, an acidic protein responsible for secretory granule storage of 5-HT, were highly enriched in FACS-purified EC cells from both small intestine and colon using a 5-HT antibody-based method. Surprisingly, EC cells from the small intestine did not express GPCR sensors for lipid and protein metabolites, such as FFAR1, GPR119, GPBAR1 (TGR5), CaSR, and GPR142, in contrast to the neighboring GLP-1 storing enteroendocrine cell. However, the GLP-1 receptor was particularly highly expressed and enriched in EC cells as judged both by qPCR and by immunohistochemistry using a receptor antibody. GLP-1 receptor agonists robustly stimulated 5-HT secretion from intestinal preparations using both HPLC and a specific amperometric method. Colonic EC cells expressed many different types of known and potential GPCR sensors of microbial metabolites including three receptors for SCFAs, i.e. FFAR2, OLF78, and OLF558 and receptors for aromatic acids, GPR35; secondary bile acids GPBAR1; and acyl-amides and lactate, GPR132.ConclusionNutrient metabolites apparently do not stimulate EC cells of the small intestine directly but through a paracrine mechanism involving GLP-1 secreted from neighboring enteroendocrine cells. In contrast, colonic EC cells are able to sense a multitude of different metabolites generated by the gut microbiota as well as gut hormones, including GLP-1.

Our results lend additional support to the value of skin-to-skin care in neonatal intensive care. Variable stress responses in preterm infants favor the need for individualized care. The mothers' need for support seem to be more pronounced in the first skin-to-skin session as our results show a higher degree of stress as compared with later skin-to-skin care.

BackgroundStress as a cause of illness has been firmly established. In public health and stress research a retrospective biomarker of extended stress would be an indispensible aid. The objective of this pilot study was to investigate whether concentrations of cortisol in hair correlate with perceived stress, experiences of serious life events, and perceived health in young adults.MethodsHair samples were cut from the posterior vertex area of (n = 99) university students who also answered a questionnaire covering experiences of serious life events, perceived Stress Scale and perceived health during the last three months. Cortisol was measured using a competitive radioimmunoassay in methanol extracts of hair samples frozen in liquid nitrogen and mechanically pulverised.ResultsMean cortisol levels were significantly related to serious life events (p = 0.045), weakly negatively correlated to perceived stress (p = 0.025, r = -0.061) but nor affected by sex, coloured/permed hair, intake of pharmaceuticals or self-reported health. In a multiple regression model, only the indicator of serious life events had an independent (p = 0.041) explanation of increased levels of cortisol in hair. Out of four outliers with extremely high cortisol levels two could be contacted, both reported serious psychological problems.ConclusionsThese findings suggest that measurement of cortisol in hair could serve as a retrospective biomarker of increased cortisol production reflecting exposure to major life stressors and possibly extended psychological illness with important implications for research, clinical practice and public health. Experience of serious life events seems to be more important in raising cortisol levels in hair than perceived stress.

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WHAT'S KNOWN ON THIS SUBJECT: Stress affects health of children, potentially persisting as a trajectory into adulthood. Earlier biological markers assess only momentary stress, making it difficult to investigate stress over longer periods of time. Cortisol in hair is a new biomarker of prolonged stress. WHAT THIS STUDY ADDS:Mother and child hair cortisol association suggests a heritable part or maternal calibration. Cortisol output gradually stabilizes, has a stable trait, and is positively correlated to birth weight. Hair cortisol is a promising noninvasive biomarker of prolonged stress, especially applicable for children. abstract OBJECTIVE: To investigate cortisol concentrations in hair as biomarker of prolonged stress in young children and their mothers and the relation to perinatal and sociodemographic factors.METHODS: Prospective cohort study of 100 All Babies In Southeast Sweden study participants with repeated measures at 1, 3, 5, and 8 years and their mothers during pregnancy. Prolonged stress levels were assessed through cortisol in hair. A questionnaire covered perinatal and sociodemographic factors during the child' s first year of life. RESULTS:Maternal hair cortisol during the second and third trimester and child hair cortisol at year 1 and 3 correlated. Child cortisol in hair levels decreased over time and correlated to each succeeding age, between years 1 and 3 (r = 0.30, P = .002), 3 and 5 (r = 0.39, P , .001), and 5 and 8 (r = 0.44, P , .001). Repeated measures gave a significant linear association over time (P , .001). There was an association between high levels of hair cortisol and birth weight (b = .224, P = .020), nonappropriate size for gestational age (b = .231, P = .017), and living in an apartment compared with a house (b = .200, P = .049). In addition, we found high levels of cortisol in hair related to other factors associated with psychosocial stress exposure. CONCLUSIONS:Correlation between hair cortisol levels in mothers and their children suggests a heritable trait or maternal calibration of the child' s hypothalamic-pituitary-adrenocortical axis. Cortisol output gradually stabilizes and seems to have a stable trait. Cortisol concentration in hair has the potential to become a biomarker of prolonged stress, especially applicable as a noninvasive method when studying how stress influences children' s health. Pediatrics 2013;132:e1333-e1340