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Klinefelter's syndrome (KS) concerns men and is usually characterized by tallness, underdeveloped testes and sterility. It is generally due to the 47,XXY genotype, ie one extra X chromosome in each cell. Its estimated frequency among newborn boys is 1/500 to 1/700. It seems that 64% KS would be undiagnosed. Abnormally low levels of testosterone blood values are very common in this syndrome. In this case, replacement androgen therapy should be initiated (ideally at the age of 11-15) which prevents osteoporosis and enhances secondary sexual features. Case report - Since early childhood, Mr X has been shy, passive with few friends. When he was 13 years old, the school physician noted a delay of puberty and referred him to an endocrinologist who diagnosed KS. Androgen therapy was introduced but rapidly stopped, because the boy and his parents thought it was useless. Mr X consulted a psychiatrist at the age of 21. He presented a schizo-affective disorder with influence syndrome, auditory and visual hallucinations, labile mood with disinhibited and depressive periods. He was admitted in a psychiatry ward of a general hospital. An endocrinologist confirmed the diagnosis of KS and found very low blood testosterone levels. Besides lithium and risperidone which had already been introduced before the hospitalization, androgens (testosterone undecanoate) were very progressively given to Mr X with a daily psychiatric evaluation. One month after discharge, a major depressive episode led to the adjunction of citalopram. After one year of follow-up, Mr X shows increased social adjustment and enhanced interest; the influence syndrome has partially regressed and his mood is more stable. Discussion - In the years '60 and '70, systematic screenings in psychiatric hospitals have detected 1.3% KS among hospitalized boys, ie 10 times more than in the general population, and 0.6 to 1% KS among hospitalized men. A large variety of psychiatric disorders have been described. Boys presenting KS are usually described as shy, with little energy and initiative, and few friends. They cry more often than compares. Neuropsychological studies demonstrate significantly lower verbal IQ than controls, while performance IQ is generally normal and global IQ is in the normal range with large individual variations. Language acquisition is always delayed. However, agressiveness is not increased. In his follow-up study of 20 years, Nielsen at al found more psychiatric disorders among KS patients, compared to a group of hypogonadal patients at first examination (mean age=27 years). After 20 years follow-up, however, no significant difference remained between the two cohorts concerning the frequency of psychiatric hospitalizations or mental diseases. Several hypotheses have been proposed to explain psychological aspects of KS such as low levels of androgens during foetal and child development, personality disorder related to hypogonadism, delay of mitosis of cells with an extra X chromosome, but none of them is able to explain the specificity of psychological problems associated with KS. Concerning therapeutic aspects, specialists prone substitutive androgen therapy in case of too low testosterone blood levels, from the time of increase in FSH (around the age of 11-15). It prevents osteoporosis, backache and excessive tiredness often found in males with KS; testosterone also improves social drive, mood, concentration and ability at work. If KS diagnosis is made at adult age, androgen therapy has also shown some efficacy, though less than if started earlier. Due to the oral and written language problems of KS boys between 5 and 12 years of age, Graham et al. recommend anticipatory guidance for these boys. In addition, they insist on the importance of the information of the parents, language therapy, the reduction of the length of the instructions given by schoolmasters and specially stimulating and stable childhood conditions. Though it is generally thought that androgens increase agressiveness, we found no consistent data in litterature proving that the restoration of physiological androgen blood levels increases crimes nor aggressiveness. In the contrary, Miller and Sulkes described four cases of KS men presenting chronic fire-setting behaviors. Testosterone was introduced. For three of them, follow-up was available: their behavior seemed improved and none of them recurred. However, the initiation of androgen therapy for patients with severe psychiatric illness should be done very carefully. Conclusion - The Klinefelter's syndrome is frequent and, if not diagnosed (which seems to be the most common case), these men have higher risks to develop psychiatric disorders. Therefore, child psychiatrists and psychiatrists should evoke that diagnosis when they examine boys or men who present typical physical traits of KS (tallness, underdevelopped testes) associated to school problems and/or psychiatric disorders. Indeed, if the diagnosis is confirmed by an endocrinologist and a genetic testing, psychological follow-up and testosterone undecanoate treatment (in case of abnormal testosterone blood levels) should be initiated. This therapy generally improves physical well-being and improves mood, concentration, capacity at work. There is no consistent data in the litterature proving that restoring physiological testosterone blood levels would be dangerous for KS men presenting severe psychiatric troubles. However, this should be discussed in each situation with caution, and androgens should be introduced very progressively.
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PMID:[What is the interest of Klinefelter's syndrome for (child) psychiatrists?]. 1209 88

It is well described that quality of life (QoL) improved after liver transplantation. The aim of the present study was to investigate how psychosocial parameters develop after liver transplantation (LTX) and whether post-operative complaints are the result of osteoporosis or patient somatization. The prospective study looks into biomedical and psychosocial parameters of 82 LTX patients before, 1 and 3 yrs after transplantation. Osteoporosis was measured by bone mineral density (BMD) and psychosocial parameters were assessed with validated questionnaires measuring complaints, mood and overall QoL. Overall QoL and mood improved after liver transplantation, while back and limb pain increased continuously. Back and limb pain were highly correlated with reduced bone density and high values for tiredness and depressive anxiety. Back and limb pain of patients following liver transplantation may indicate the development of a post-operative depression in some cases. The treatment offered by an essentially biologically based medicine may promote the manifestation of this depression as a somatization disorder.
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PMID:Psychosomatic interrelations following liver transplantation. 1209 88

The diet of many athletes is inadequate due to overly restrictive habits and an obsession with losing weight in order to maintain a particular level of body weight. Many female athletes, particularly those who participate in sports that emphasize leanness (gymnastics, distance running, diving, figure skating and classical ballet), have suboptimal energy and nutrient intakes and are at risk of compromised nutritional status, including fatigue, dehydration, nutrient inadequacies, delayed growth and an impaired immunocompetence. It is very well known that active women and girls who are driven to excel in sports may develop the so-called female athlete triad in which malnutrition, amenorrhoea and osteoporosis appear as typical signs of medical complications, frequently linked to serious psychological alterations. This outcome is mainly related to that found in eating disorders-syndromes in which athletes have been defined to be at increased risk. As a consequence of all these alterations, the immune system may be affected in athletes, and subsequently they might be more prone to infections. As there is a lack of knowledge about how the immune system may be affected in basal conditions of athletes, the study of immunocompetence as an index of the nutritional status is reviewed. In summary, it is necessary to encourage all professionals surrounding athletes to be aware of the importance of taking care of their nutritional status in order not only to avoid physical and psychological complications but also to improve performance and, thus, to achieve sporting goals.
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PMID:The implication of the binomial nutrition-immunity on sportswomen's health. 1214 60

In the Dutch College of General Practitioners' practice guideline 'The menopause', the menopause is viewed as a physiological phase of life with its associated discomforts, which sometimes require treatment. The GP should inform women with menopausal symptoms about the extent to which oestrogens can diminish vasomotor symptoms and about the benefits and risks of hormonal therapy on various organ systems. Oestrogens can be used when vasomotor symptoms cause serious limitations in daily life. First choice is a sequential combination of oestrogen and progestagen hormones, in which progestagens are given at least ten days per month. When urogenital complaints need to be treated, vaginally applied oestrogens can be prescribed. Depressive symptoms, fatigue, myalgia or arthralgia should not be treated with hormonal therapy. Nor are oestrogens recommended for the prevention of osteoporosis and cardiovascular diseases.
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PMID:[Summary of the Dutch College of General Practitioners practice guideline 'The menopause']. 1214 16

Pruritus, fatigue and metabolic bone disease represent three major extrahepatic manifestations of chronic cholestatic liver disease that considerably affect the patient's quality of life. The present article reviews pathogenetic aspects of and current therapeutic approaches to extrahepatic manifestations of cholestatic liver disease. Pathogenesis of pruritus of cholestasis remains poorly understood. The involvement of putative peripherally acting pruritogens, such as bile acids or endogenous opioids, is being discussed. More recently, central mechanisms, including an increased central opioidergic tone and pertubations in the serotonergic system have been proposed. Treatment of the underlying disease is beneficial also for the control of cholestasis-associated pruritus. Current therapeutic recommendations include ursodeoxycholic acid, cholestyramine, rifampicin and opioid antagonists. Liver transplantation may be indicated when severe pruritus is refractory to medical treatment. Fatigue is being recognized as the most frequent and one of the most disabling complaints in chronic cholestasis. Fatigue is presumably of central origin and its association with other neuropsychiatric disorders (e.g. depression, obsessive-compulsive disorders) is consistent with defective central neurotransmission. No specific therapies are currently available and a healthy lifestyle, regular sleep and avoidance of unnecessary stress and other precipiting factors are recommended. Antidepressant therapy may be warranted in selected patients. Osteopenia and osteoporosis are common in chronic cholestatic liver disease, whereas osteomalacia is rare. The pathophysiology of cholestasis-associated metabolic bone disease is regarded as multifactorial. Therapeutic recommendations include regular exercise, calcium and vitamin D supplementation in late stage disease, hormone replacement therapy in postmenopausal women and bisphosphonates.
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PMID:Extrahepatic manifestations of cholestasis. 1216 13

We describe a case of multiple pathologic fractures in a woman with Cushing's syndrome during pregnancy. Pathologic fractures were seen in the pubic and ischial bones and in T12 and L1 of the vertebral body. These findings, accompanied by easy fatigue, amenorrhea without nursing, psychological disorder, and premature birth, were retrospectively compatible with those of Cushing's syndrome, not pregnancy-associated osteoporosis. After adrenalectomy, the pain in her groin and back ceased. Plain radiographs showed healing of the fractures and increased mineralization. This case demonstrates the need to be alert to the possible presence of metabolic bone disease, including Cushing's syndrome, when we encounter multiple pathologic fractures with osteoporosis in young patients, even if the patient is pregnant.
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PMID:Case report of a Cushing's syndrome patient with multiple pathologic fractures during pregnancy. 1218 67

Many patients with prostate cancer for whom hormonal therapy is indicated are still physically and sexually active; quality of life is therefore a vital issue when considering treatment options. Traditional castration-based therapies, although effective, have implications with respect to quality of life, causing loss of libido, impotence, fatigue, and reduced bone mineral density. Monotherapy with a nonsteroidal antiandrogen is an attractive therapeutic alternative to castration, offering effective therapy with potential quality-of-life benefits. Of the available nonsteroidal antiandrogens, bicalutamide has been most extensively evaluated in the monotherapy setting. Mature combined data (56% mortality) from 2 large randomized studies show no statistically significant difference in overall survival between bicalutamide 150-mg monotherapy and castration in patients with locally advanced, nonmetastatic (stage M0) disease. Survival outcome in patients with metastatic (stage M1) disease (43% mortality) favored castration, although the difference in median survival between the groups was only 6 weeks. Bicalutamide 150-mg monotherapy was associated with significant advantages compared with castration, in terms of sexual interest and physical capacity, in patients with either M0 and M1 stage disease. Data from a small subgroup of patients with stage M0 disease suggest that bicalutamide may also reduce the risk of osteoporosis compared with castration. Long-term therapy with bicalutamide 150-mg monotherapy is generally well tolerated, with a predictable side-effect profile. The most common side effects are male breast pain and gynecomastia. Emerging evidence also supports the use of bicalutamide 150 mg, both as immediate monotherapy and as adjuvant therapy in early stage (localized or locally advanced) prostate cancer.
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PMID:Antiandrogen monotherapy: indications and results. 1223 Oct 53

The stress system coordinates the adaptive responses of the organism to stressors of any kind.(1). The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic beta-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholaminergic input. The end-hormones of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LC/NE and beta-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5' deiodinase, which converts the relatively inactive tetraiodothyronine (T(4)) to triiodothyronine (T(3)), contributing further to the suppression of reproductive, growth and thyroid functions. They also have direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome X) and direct effects on the bone, causing "low turnover" osteoporosis. Central CRH, via glucocorticoids and catecholamines, inhibits the inflammatory reaction, while directly secreted by peripheral nerves CRH stimulates local inflammation (immune CRH). CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above. Conversely, potentiators of CRH secretion/action may be useful to treat atypical depression, postpartum depression and the fibromyalgia/chronic fatigue syndromes, all characterized by low HPA axis and LC/NE activity, fatigue, depressive symptomatology, hyperalgesia and increased immune/inflammatory responses to stimuli.
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PMID:Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. 1237 95

Gluten-sensitive enteropathy or, as it is more commonly called, celiac disease, is an autoimmune inflammatory disease of the small intestine that is precipitated by the ingestion of gluten, a component of wheat protein, in genetically susceptible persons. Exclusion of dietary gluten results in healing of the mucosa, resolution of the malabsorptive state, and reversal of most, if not all, effects of celiac disease. Recent studies in the United States suggest that the prevalence of celiac disease is approximately one case per 250 persons. Gluten-sensitive enteropathy commonly manifests as "silent" celiac disease (i.e., minimal or no symptoms). Serologic tests for antibodies against endomysium, transglutaminase, and gliadin identify most patients with the disease. Serologic testing should be considered in patients who are at increased genetic risk for gluten-sensitive enteropathy (i.e., family history of celiac disease or personal history of type I diabetes) and in patients who have chronic diarrhea, unexplained anemia, chronic fatigue, or unexplained weight loss. Early diagnosis and management are important to forestall serious consequences of malabsorption, such as osteoporosis and anemia.
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PMID:Gluten-sensitive enteropathy (celiac disease): more common than you think. 1250 63

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic cholestatic liver diseases that affect 0.5 to 40 per 100,000 and 1 to 6 per 100,000 Americans, respectively. Prompt recognition and management of the clinical manifestations of these diseases is essential for the patients' well-being and ultimate outcome. Ursodeoxycholic acid (UDCA), 13 to 15 mg/kg per day, is the standard therapy for PBC and should be offered to every patient. It has been shown to slow progression of the disease and prevent the need for liver transplantation, which is the last recourse for patients with end-stage disease. However, there is no effective therapy for PSC yet. Patients are managed symptomatically, with surgical or endoscopic interventions as needed in cases of significant biliary obstruction. Complications of chronic cholestasis are seen in both PBC and PSC, with pruritus and fatigue being the most common complaints. The first choice for the treatment of pruritus is still cholestyramine, starting at 4 g/d. The pathogenesis of fatigue is poorly understood in this population; unrecognized hypothyroidism should be excluded. The use of antidepressants is currently under evaluation, but there is no specific therapy for fatigue as of yet. For prevention of severe osteoporosis, we recommend supplementation with 800 IU vitamin D and 1500 mg calcium/d. In patients with PBC and established osteoporosis, the use of alendronate and vitamin K appears to cause an increase in bone mineral density. Further studies are necessary before either of these drugs is routinely recommended. Finally, fat-soluble vitamin deficiencies are noted with more advanced disease. We recommend that serum levels be checked in high-risk patients, and that vitamins are replaced as appropriate with water-soluble supplements. However, other causes of malabsorption must be ruled out, including pancreatic insufficiency and celiac sprue.
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PMID:Treatment Options for Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis. 1262 68


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