Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015674 (chronic fatigue syndrome)
 2,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-alpha (IFN-alpha) has a direct anti-tumour effect and is an immunomodulator. Somatostatin analogues, by contrast, when used to treat neuroendocrine tumours, control the secretion and peripheral effects of hormones, although at high doses they induce apoptosis. We have used IFN-alpha to treat > 350 patients with neuroendocrine tumours, and combining our and published data gives a median 44% biochemical response rate and 11% tumour response rate. Side-effects are mainly flu-like symptoms, then low-grade chronic fatigue syndrome. 15% may develop autoimmune reactions. The side-effects profile of somatostatin analogues is better but patients must take frequent injections and may have bile problems. We combined IFN-alpha and octreotide treatment in 24 patients with malignant carcinoid tumours who did not respond biochemically to high-dose (300 micrograms/day) octreotide alone. Biochemical response occurred in 77% but no significant anti-tumour effect was noted besides disease stabilisation in 4 cases. The combination therapy had an effect on clinical symptoms rather than tumour mass. Interferon was better tolerated when in the combination.
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PMID:Interferon-alpha versus somatostatin or the combination of both in gastro-enteropancreatic tumours. 881 77

A large body of data from a number of different laboratories worldwide has demonstrated a general tendency for reduced adrenocortical responsiveness in CFS. It is still not clear if this is secondary to CNS abnormalities leading to decreased activity of CRH- or AVP-producing hypothalamic neurons. Primary hypofunction of the CRH neurons has been described on the basis of genetic and environmental influences. Other pathways could secondarily influence HPA axis activity, however. For example, serotonergic and noradrenergic input acts to stimulate HPA axis activity. Deficient serotonergic activity in CFS has been suggested by some of the studies as reviewed here. In addition, hypofunction of sympathetic nervous system function has been described and could contribute to abnormalities of central components of the HPA axis. One could interpret the clinical trial of glucocorticoid replacement in patients with CFS as confirmation of adrenal insufficiency if one were convinced of a positive therapeutic effect. If patient symptoms were related to impaired activation of central components of the axis, replacing glucocorticoids would merely exacerbate symptoms caused by enhanced negative feedback. Further study of specific components of the HPA axis should ultimately clarify the reproducible abnormalities associated with a clinical picture of CFS. In contrast to CFS, the results of the different hormonal axes in FMS support the assumption that the distortion of the hormonal pattern observed can be attributed to hyperactivity of CRH neurons. This hyperactivity may be driven and sustained by stress exerted by chronic pain originating in the musculoskeletal system or by an alteration of the CNS mechanism of nociception. The elevated activity of CRH neurons also seems to cause alteration of the set point of other hormonal axes. In addition to its control of the adrenal hormones, CRH stimulates somatostatin secretion at the hypothalamic level, which, in turn, causes inhibition of growth hormone and thyroid-stimulating hormone at the pituitary level. The suppression of gonadal function may also be attributed to elevated CRH because of its ability to inhibit hypothalamic luteinizing hormone-releasing hormone release; however, a remote effect on the ovary by the inhibition of follicle-stimulating hormone-stimulated estrogen production must also be considered. Serotonin (5-HT) precursors such as tryptophan (5-HTP), drugs that release 5-HT, or drugs that act directly on 5-HT receptors stimulate the HPA axis, indicating a stimulatory effect of serotonergic input on HPA axis function. Hyperfunction of the HPA axis could also reflect an elevated serotonergic tonus in the CNS of FMS patients. The authors conclude that the observed pattern of hormonal deviations in patients with FMS is a CNS adjustment to chronic pain and stress, constitutes a specific entity of FMS, and is primarily evoked by activated CRH neurons.
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PMID:Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. 1108 55

Severe traumatic head injury has been recognized to be associated with hypothalamo-hypophyseal impairment and subsequent abnormalities in hormone secretion, which can contribute to a prolonged clinical course and to hampered recovery in many head-injured patients. Most of the data on the growth hormone/insulin-like growth factor -1 (GH/IGF-1) axis function have been obtained early after head injury, whereas GH secretory pattern has not been fully elucidated after patients had left the intensive care unit. We examined the activity of the GH/IGF-1 axis in 16 severely closed head-injured (CHI) patients (14 males; age range, 17 to 47 years; body mass index [BMI], 21.4 +/- 0.8 kg/m(2)) during the rehabilitation period at least 1 month after leaving the intensive care unit and in 12 sex-, age-, and weight-matched healthy controls. The severity of trauma was assessed by the Glasgow Coma Scale (GCS) score (8 or less), posttraumatic amnesia (PTA, more than 24 hours), and initial computed tomography (CT) scan. The clinical picture at time of the study was evaluated by the Rancho Los Amigos Scale of Cognitive Functioning (CFS) and the Functional Independence Measure (FIM). In all subjects, we evaluated basal levels of anterior pituitary hormones, IGF-1, insulin-like growth factor-binding protein (IGFBP)-3, and IGFBP-1, as well as the GH responses to intravenous (IV) infusion of growth hormone-releasing hormone (GHRH) alone, GHRH plus arginine (ARG), and the GH release evoked by somatostatin (SRIH) infusion withdrawal, which is related to endogenous GHRH tone. In all subjects, nutritional parameters and nitrogen balance were normal. Basal plasma concentrations of GH, IGF-1, IGFBP-3, and IGFBP-1 did not significantly differ between CHI patients and controls. The GH responses to GHRH and GHRH plus ARG did not significantly differ between CHI patients (GH peak, 10.7 +/- 3.0 microg/L; area under the curve [AUC], 5.9 +/- 1.5 microg/L. min; and GH peak, 34.7 +/- 6.1 microg/L; AUC, 20.25 +/- 3.3 microg/L. min, respectively) and normal subjects (GH peak at 30 minutes, 7.23 +/- 1.35 microg/L; AUC, 4.7 +/- 0.8 microg/L. min; and GH peak at 60 minutes, 41.0 +/- 5.1 microg/L; AUC, 24.3 +/- 1.7 microg/L. min, respectively). SRIH withdrawal resulted in an unequivocal increase in plasma GH concentrations both in CHI patients and in controls, without any significant difference between the 2 groups. A negative correlation was found between the GH response (deltaGH peak) to SRIH withdrawal and CFS (r = -.615, P <.005). In conclusion, our study indicates that patients receiving rehabilitation after leaving the intensive care unit for severe traumatic head injury have no significant changes of GH secretion with normal central regulation of the GH-IGF-1 axis.
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PMID:Evidence for integrity of the growth hormone/insulin-like growth factor-1 axis in patients with severe head trauma during rehabilitation. 1237 Aug 60

An important principle of psychoneuroimmunologic interaction is that immunocytes act as if they were mobile sensitive organs for the central nervous system, producing local and systemic neuropeptides and immunological transmitters with appropriate stimulation. They inform the brain of local damage and mobilize the neuroendocrine system for protection. Their list is long and continues to grow. It includes: somatostatin, vasoactive intestinal peptide, thyroid stimulating hormone, human chorionic gonadotropin, follicle stimulating hormone, luteinizing hormone and other neurotransmitters and hormones, having immunomodulating properties. This may indicate to close interaction between the immune and neuroendocrine systems, which may be involved into the disease process. A bright example of this may be a disease that has not been closely studied in our country, but is widespread throughout the world. This is the chronic fatigue syndrome, at the base of which lie disturbances of the central nervous, endocrine and immune systems. The idea that the chronic fatigue syndrome is a disturbance of the production of cytokines is related to a number of disturbances in the T system of immunity. It was found back in 1987-1988 that there is an increase in the level of HLA DR and IL-2 receptors and an increase in the ratio CD4/CD8 in patients suffering from this syndrome.
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PMID:Immunity Impairment as a Result of Neurohormonal Disorders. 1268 53