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Query: UMLS:C0015672 (fatigue)
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Prolactin is an important physiological regulator of prostate development and growth in preclinical models. In prostate cancer there is strong evidence that prolactin exerts a trophic effect independent of testosterone. In addition, patients with prostate cancer that have an elevated prolactin level correlated with a poorer prognosis. Based on these data, we evaluated the clinical effect of prolactin suppression using bromocriptine in patients with androgen-independent prostate cancer. We conducted an open-label phase II trial of bromocriptine in patients with progressive metastatic prostate cancer. Basal and thyrotropin releasing hormone (TRH)-stimulated prolactin levels were utilized as biological endpoints for determining the dose of bromocriptine. All patients continued to receive complete androgen blockade. Thirteen patients were enrolled (median age 69.5 years). There were no complete or partial responses associated with bromocriptine in 11 of the evaluable patients. The mean duration of bromocriptine treatment was 8.2 weeks (2-14 weeks). One patient had a clinically insignificant decrease in prostate-specific antigen (PSA) and another patient had a 19.9% decrease in PSA with progression of a soft tissue mass. The vast majority of patients (10 of 11) had suppression of prolactin with a bromocriptine dose of 2.5 mg three times a day. One patient required a dose adjustment due to inadequate suppression, with a final maintenance dose of bromocriptine 12.5 mg per day resulting in complete suppression. No serious treatment-related toxicities were observed. The most common complications noted were nausea, headaches, dizziness, and fatigue. Our data showed that 2.5 mg three times per day of bromocriptine suppressed prolactin in 90% of the patients. Furthermore, this dose appears to be well tolerated.
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PMID:A phase II study of bromocriptine in patients with androgen-independent prostate cancer. 962 40

We hypothesized that central fatigue may have a role in limiting the endurance capacity of horses. Therefore, we tested the effect of infusing tryptophan and/or glucose on endurance time and plasma concentrations of free tryptophan and other substrates thought to affect tryptophan uptake into the brain of seven mares (3-4 yr of age, 353-435 kg) that ran on a treadmill at 50% of maximal O2 consumption to fatigue. With use of a counterbalanced crossover design, the horses were infused with tryptophan (100 mg/kg in saline solution) or a similar volume of saline solution (placebo) before exercise. During exercise, horses received infusions of glucose (2 g/min, 50% wt/vol) or a similar volume of saline. Thus the treatments were 1) tryptophan and glucose (T & G), 2) tryptophan and placebo (T & P), 3) placebo and glucose (P & G), and 4) placebo and placebo (P & P). Mean heart rate, hematocrit, and concentration of plasma total solids before and during exercise were similar for all trials. Mean time to exhaustion was reduced (P < 0.05) for T & P and T & G compared with P & P [86.1 +/- 6.9 and 87.1 +/- 6.8 vs. 102.3 +/- 10.3 (SE) min], whereas endurance for P & G (122.4 +/- 11.9 min) was greater than for all other trials (P < 0.05). Compared with nontryptophan trials, during the tryptophan trials plasma prolactin increased (P < 0.05) nearly threefold before exercise and almost twofold early in exercise. Muscle glycogen concentrations were reduced (P < 0.05) below preexercise values in the P & G and P & P trials only. However, glucose infusions (P & G) did not affect (P > 0.05) concentrations of plasma free fatty acids or ratios of branched-chain amino acids to free tryptophan. In conclusion, tryptophan infusion reduced endurance time, which was consistent with the central fatigue hypothesis. The failure of glucose infusion to alleviate the effects of tryptophan and the absence of significant muscle glycogen reduction in the tryptophan trials suggest that the early onset of fatigue in the tryptophan trials is not due to a lack of readily available substrate.
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PMID:Effect of tryptophan and of glucose on exercise capacity of horses. 972 51

Menorrhagia--menstrual periods lasting longer than 7 days and totaling blood losses greater than 80mL--affects 9%-14% of otherwise healthy women, and it can signal cancer, an endocrinologic disorder, or gynecologic disease. Blood loss can be high enough to result in anemia, fatigue, and syncope. Most often, abnormal uterine bleeding such as menorrhagia involves a disruption in the hypothalamic-pituitary axis, the ovary, and/or the uterus. Other identified causes include medications (especially psychotropics) that cross the blood-brain barrier; chronic diseases such as cancer, diabetes, and liver and kidney dysfunction; endocrine disorders, perimenopausal anovulation, polycystic ovary disease, pituitary tumors, and abnormal estrogen cycling caused by morbid obesity; and anatomic abnormalities of the uterus. Routine tests include hematocrit or hemoglobin to detect and evaluate anemia, thyroid stimulating hormone (TSH) level to evaluate thyroid function as a possible cause, and a pregnancy test to rule out an incomplete, spontaneous abortion as a cause. A Pap test is recommended to screen for dysplasia that can suggest a gynecologic cancer cause. Additional screening for endocrine disorders that may be causing menorrhagia include tests of thyroid, liver, and kidney function, and tests of follicle stimulating hormone (FSH), prolactin, and cortisol levels. Treatment can be medical or surgical. Medical treatment includes prostaglandin inhibitors, specifically nonsteroidal antiinflammatory drugs (NSAIDs), and hormonal therapy with estrogen, progesterone, gonadotropin-releasing hormone agonists, or oral contraceptives such as medroxyprogesterone (Depo-Provera). Surgical treatment includes hysteroscopic endometrial ablation by physical agents, laser electrodiathermy, and "roller ball," or surgical, resection. Hysterectomy is the treatment of last resort.
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PMID:Treatment Decisions in the Management of Menorrhagia. 974 72

Fatigue is the most commonly reported and most debilitating of post-polio sequelae affecting the >1.8 million North American polio survivors. Post-polio fatigue is characterized by subjective reports of difficulty with attention, cognition, and maintaining wakefulness. These symptoms resemble those reported in nearly 2 dozen outbreaks of post-viral fatigue syndromes (PVFS) that have recurred during this century and that are related clinically, historically, anatomically, or physiologically to poliovirus infections. This article reviews recent studies that relate the symptoms of post-polio fatigue and chronic fatigue syndrome (CFS) to clinically significant deficits on neuropsychologic tests of attention, histopathologic and neuroradiologic evidence of brain lesions, impaired activation of the hypothalamic-pituitary-adrenal axis, increased prolactin secretion, and electroencephalogram (EEG) slow-wave activity. A possible common pathophysiology for post-polio fatigue and CFS, based on the Brain Fatigue Generator Model of PVFS, and a possible pharmacotherapy for PVFS based on replacement of depleted brain dopamine, will be described.
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PMID:Parallels between post-polio fatigue and chronic fatigue syndrome: a common pathophysiology? 979 Apr 85

(+/-)3,4-Methylene-dioxymethamphetamine (MDMA, or 'Ecstasy') effects on serotonin system function and behaviour in humans are unclear. Fifteen MDMA users, who did not have other drug dependencies or alcohol abuse, and had not used other drugs for prolonged periods, and 15 control individuals were included in a study to assess the biological and psychological changes after chronic use of MDMA. Prolactin and cortisol responses to D-fenfluramine challenge, clinical psychobehavioural changes, personality characteristics, including mood, aggressiveness and temperamental aspects, were evaluated 3 weeks after MDMA discontinuation. MDMA users had significantly reduced prolactin and cortisol responses in comparison with control individuals (p < 0.001 and p < 0.005, respectively). Dysphoria and mood changes were exhibited in seven individuals, tiredness in five and sensation-seeking behaviour in twelve at the clinical evaluation. Significantly higher scores were found in MDMA individuals than in control individuals for Minnesota Multiphasic Personality Inventory subscale for Depression, for Buss Durkee Hostility Inventory direct and guilt subscales, for Hamilton Depression Rating Scale and for novelty-seeking Tridimensional Personality Questionnaire subscale. Prolactin responses to D-fenfluramine stimulation area under the curve among MDMA users were negatively correlated with direct aggressiveness scores for Buss Durkee Hostility Inventory; a negative correlation between prolactin responses and novelty-seeking scores was also evidenced among MDMA users. These data suggest an association between serotonin system impairment and MDMA use in humans; in interpretation of these results, the possibility that serotonin deficit in MDMA individuals was partially related to a premorbid condition, in relationship with novelty-seeking behaviour and mood disorders, can not be excluded.
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PMID:Serotonergic function after (+/-)3,4-methylene-dioxymethamphetamine ('Ecstasy') in humans. 998 61

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been shown to modulate various physiological and psychological functions such as fatigue. Altered regulation of the serotonergic system has been suggested to play a role in response to exercise stress. In the present study, the influence was investigated of acute endurance exercise and short-term increase in the amount of training on the concentrations of the 5-HT precursor tryptophan (TRP), of prolactin (PRL) and of branched-chain amino acids (BCAA) in the blood, as well as on the binding of [3H]ketanserin to the serotonin-2A (5-HT2A) receptors on platelets. Nine healthy endurance-trained men were tested the day before (I) and after (II) a 9-day training programme. Samples of venous blood were drawn after an overnight fast and following 5 h of cycling. Fasted and post-exercise plasma concentrations of free TRP, BCAA and free TRP:BCAA ratio did not differ between I and II. A significant decrease of plasma BCAA (P < 0.01) and significant augmentations of plasma free TRP, free TRP:BCAA ratio and PRL (P < 0.01) were found post-exercise. The increase in plasma PRL was smaller in II compared with I. Acute endurance exercise reduced the density of platelet 5-HT2A receptor [3H]ketanserin binding sites at I and II (P < 0.05). The basal density of the binding sites and the affinity of [3H]ketanserin for these binding sites were unaffected by an increase in the amount of training. The present results support the hypothesis that acute endurance exercise may increase 5-HT availability. This was reflected in the periphery by increased concentration of the 5-HT precursor free TRP, by increased plasma PRL concentration, and by a reduction of 5-HT2A receptors on platelets. It remains to be resolved whether these alterations in the periphery occur in parallel with an increase in the availability of 5-HT in the brain.
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PMID:Effect of acute and chronic exercise on plasma amino acids and prolactin concentrations and on [3H]ketanserin binding to serotonin2A receptors on human platelets. 1009 Jun 30

The acoustic startle response (ASR) and a range of psychophysiological parameters were evaluated during a continuous intravenous administration of cholecystokinin-tetrapeptide (CCK-4) in healthy volunteers. Subjects (n=28) were randomly assigned to double-blind infusion of either CCK-4 (0.5 mg/60 min) or placebo. The ASR sessions were performed prior to infusion and at 20 min and 50 min after the onset of infusion by recording eye-blink response to a series of acoustic stimuli (110 dB, 40 ms). An effect of CCK-4 on the eye-blink startle was observed in the first half of infusion. CCK-4 produced an increase of eye-blink startle amplitude from baseline values in contrast to the decrease observed at this time point with placebo. A mild increase in anxiety and heart rate followed by fatigue was reported with CCK-4. Administration of CCK-4 produced increases in plasma concentrations of adrenocorticotropic hormone, cortisol, prolactin and growth hormone. The results of this study show that a prolonged intravenous administration of CCK-4 may be a useful challenge method for further studies on the role of CCK system in the modulation of human anxiety and stress response.
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PMID:Effects of CCK-4 infusion on the acoustic eye-blink startle and psychophysiological measures in healthy volunteers. 1066 15

Stressful experiences may influence neuroendocrine, immune and cytokine functioning, as well as physical and psychological well being. The present prospective investigation assessed physiological and behavioral variations in anticipation of a critical oral academic examination among graduate students (i.e. related to a dissertation or comprehensive defense). Relative to matched control subjects, plasma cortisol levels were elevated among graduate students, especially females, 1 h prior to the oral examination, but not 6-8 weeks earlier (at about the time of the submission of the written document). In contrast, mitogen-stimulated (Con-A) lymphocyte proliferation was only reduced 6-8 weeks before the examination. Neither adrenocorticotrophic hormone (ACTH), prolactin, serum interleukin-1beta (IL-1beta) nor mitogen stimulated IL-1beta production was influenced at any time. Although, graduate students did not differ from controls with respect to perceived stress and feelings of mastery, they reported more frequent malaise (e.g. headaches, sore throat, fatigue) than did controls. The present findings suggest that during the course of lengthy anticipatory periods preceding a scheduled stressor, different stress-sensitive, situation-dependent biological processes may be engendered. It is further suggested that cortisol release is most closely aligned with immediate threats, while the immune alterations are sensitive to more distal events, or are subject to adaptation in response to a protracted stressor.
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PMID:A prospective study of neuroendocrine and immune alterations associated with the stress of an oral academic examination among graduate students. 1072 11

In a prospective, multicentre trial the efficacy of an Vitex agnus castus L extract Ze 440 was investigated in 50 patients with pre-menstrual syndrome (PMS). The patients were treated daily with one tablet (20 mg native extract) during three menstrual cycles. 43 patients completed the study protocol which encompassed 8 menstrual cycles (2 baseline, 3 treatment and 3 post-treatment). 13/43 patients were receiving concomitant oral contraceptives. 6 patients did not complete the study for reasons not related to study medication, and one patient complained of fatigue possibly related to study medication. All evaluated patients took at least 85% of the prescribed medication. The main effect parameter was the validated Moos' menstrual distress questionnaire (MMDQ), and secondary parameters were a visual analogue scale (VAS; self-assessment) and a global impression scale (GI, self-assessment). The study population was homogenous in age (31.3+/-7.7 years) weight (58.9+/-6.9 kg) and cycle length (28.4+/-0.3 d). The diagnosis was according to DMS-III. At the end of the study, PMS-related symptoms were reduced by treatment. There was a significant score reduction (42.5%) of the MMDQ as the main effect parameter (p<0.001). Symptoms gradually returned after treatment cessation. However, a difference from baseline remained (20%; p<0.001) up to 3 cycles thereafter. 20/43 patients were considered "responders", with a reduction in MMDQ score by at least 50% relative to baseline. At baseline, the VAS score was elevated in the late luteal phase and low at the follicular phase, as expected. During treatment, VAS score decreased in the late luteal phase (47.2%; p<0.01) and remained 21.7% (p<0.001) below baseline after 3 cycles post-cessation of treatment. The low VAS score within the follicular phase remained unchanged over the whole observation period. 38 patients judged the global efficacy moderate to excellent, 5 patients indicated no global efficacy. The number of days patients sustained PMS symptoms was reduced slightly from 7.5 to 6. Resting levels of blood prolactin remained within the physiological range throughout. No differences were seen between patients on or off oral contraceptives. 20 patients reported 37 adverse events (AE). No serious AE were reported. One patint withdrew after four days of treatment due to fatigue and headache. Laboratory safety control parameters were not affected. In conclusion, patients with PMS can be treated successfully with Vitex agnus-castus extract Ze 440, as indicated by clear improvement in the main effect parameter during treatment and the gradual return after cessation of treatment. The main response to treatment seems related to symptomatic relief rather than to the duration of the syndrome.
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PMID:Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS). 1112 15

A cross sectional field study was planned to assess neurotoxic effects caused by low-level occupational lead exposure. Two groups of 66 workers and 86 controls were examined with a battery including a questionnaire on neurotoxic symptoms, the measure of performance at neurobehavioral testing, the detection of visual contrast sensitivity, and the dosage of serum prolactin. Both current and cumulative exposure to lead were defined. The average PbB was 27.50 +/- 28 microg/dl (median 28, range 6-61) in the exposed and 8.11 +/- 4.47 microg/dl (median 7, range 2-21). The test results were controlled for possible confounders including age, schooling, alcohol and coffee intake. Significant differences were observed between exposed and controls regarding neurotoxic symptoms reporting, the exposed reporting more frequently mood changes and abnormal fatigue. The exposed subjects showed a decreased visual contrast sensitivity, and a marked increase of prolactin secretion. No changes emerged regarding neurobehavioral testing. The alterations observed resulted associated to the current lead exposure and not to the cumulative indices. A safe exposure level was calculated on the basis of dose-response relationship with prolactin alteration, yielding a PbB value of 10 microg/dl.
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PMID:Assessment of neurobehavioral performance as a function of current and cumulative occupational lead exposure. 1113 Feb 86


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