Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Is heart failure an endocrine disease? Historically, congestive heart failure (CHF) has often been regarded as a mechanical and haemodynamic condition. However, there is now strong evidence that the activation of neuroendocrine systems, like the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, as well as the activation of natriuretic peptides, endothelin and vasopressin, play key roles in the progression of CHF. In this context, agents targeting neurohormones offer a highly rational approach to CHF management, with ACE inhibitors, aldosterone antagonists and beta-adrenergic blockade improving the prognosis for many patients. Although relevant improvements in clinical status and survival can be achieved with these drug classes, mortality rates for patients with CHF are still very high. Moreover, most patients do not receive these proven life-prolonging drugs, partially due to fear of adverse events, such as hypotension (with ACE inhibitors), gynaecomastia (with spironolactone) and fatigue (with beta-blockers). New agents that combine efficacy with better tolerability are therefore needed. The angiotensin II type 1 (AT(1))-receptor blockers have the potential to fulfil both these requirements, by blocking the deleterious cardiovascular and haemodynamic effects of angiotensin II while offering placebo-like tolerability. As shown with candesartan, AT(1)-receptor blockers also modulate the levels of other neurohormones, including aldosterone and atrial natriuretic peptide (ANP). Combined with its tight, long-lasting binding to AT(1)-receptors, this characteristic gives candesartan the potential for complete blockade of the RAAS-neurohormonal axis, along with the great potential to improve clinical outcomes.
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PMID:Neurohumoral blockade in CHF management. 1196 92

Cognitive dysfunction is a major cause of disability in patients with multiple sclerosis (MS). The prevalence of cognitive dysfunction is estimated at 45 to 65%. Natural history studies suggest that once cognitive dysfunction develops in a patient with MS, it is not likely to remit. Unlike physical disability in MS, cognitive disability correlates weakly with T2 lesion burden on brain magnetic resonance imaging (MRI). More robust correlations exist with magnetisation transfer imaging and MRI measures of brain atrophy. Patients with MS who have cognitive impairment most commonly display deficits in the cognitive domains of memory, learning, attention and information processing. In diagnosing cognitive dysfunction in a patient with MS, it is important first to recognise and treat the common comorbidities of fatigue and depression. The first step in the treatment of cognitive dysfunction is to delay disease progression, and there are currently five such disease-modifying agents approved for the treatment of MS (two preparations of interferon-beta-1a, interferon-beta-1b, glatiramer acetate and mitoxantrone). Nonpharmacological measures, such as cognitive rehabilitation, occupational therapy and psychotherapy, are the mainstays of symptomatic treatment. Pharmacological symptomatic therapy centres on the treatment of comorbid fatigue and depression. There are currently no effective pharmacological agents approved as symptomatic therapy of cognitive dysfunction in MS.
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PMID:Cognitive dysfunction in multiple sclerosis: natural history, pathophysiology and management. 1205 20

The first 600 cases of a 1200-case study of a monthly contraceptive pill at the Family Planning Clinic at Al-Azhar University Hospital in Cairo are described. The estrogen component, Quinestrol (17 alpha ethinyl estradiol-3-cyclopentyl ether) has prolonged activity. Quingestanol acetate (3 cyclopentyl ether derivative of norethindrone acetate), the progestogen component of the pill, induces withdrawal bleeding, and regulates the cycle. In Group A (96) the first pill was given on day 25 of the cycle to get withdrawal bleeding at the supposed date of the next flow; subsequent pills were given monthly on the same day of each calendar month. In Group B (504) the first pill was given on the first day of the menstrual flow and the second pill after 3 weeks; subsequent pills were given monthly on the same day of each calendar month. Follow-up was for 6 to 12 months. The total number of cycles was 3858. The flow began 6-15 days after taking the pill in 80.4% of the cycles. Treatment cycles were significantly longer than premedication cycles. During contraception the incidence of light flow decreased from 19.6 to 4.19% and the incidence of heavy flow increased from 10 to 12.4%. The mean duration of flow rose from 4.3 to 6.4 days. Percentages of cycles experiencing intermenstrual bleeding and amenorrhea were 5 and 2.6. Dysmenorrhea increased gradually to 20% at the ninth cycle. No significant changes were found in weight, libido, or breasts. Percentages of cycles getting various side effects were nausea and vomiting (6.95), headache (4.57), fatigue (4.05), and discharge (3.02). By the fourth cycle none of the 106 women originally lactating were still doing so. Ignoring pregnancies in the first cycle, when the pill is not yet effective, the pregnancy rate was 2.8/100 woman year. Endometrial biopsies indicated an anti-ovulatory effect after the first cycle. The drop-out rate was 21.3% in the first cycle, but no cases dropped out after the eighth cycle.
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PMID:Pill-a-month as an oral contraceptive. 1225 24

In the 1974-86 period, gossypol acetate was taken as an antifertility measure by 16 men. The initial dose was 20 mg/day, with a maintenance dose of 40 mg/week. Antifertility efficacy was obtained in all 16 cases. Azoospermia persisted in 1 case where the gossypol had been taken for 8 years and discontinued for the past 2 1/2 years. Symptoms experienced in the first 2 weeks of gossypol acetate administration included dizziness, anorexia, nausea, fatigue, and stomach discomfort. Results of examinations of blood and urine; functions of the heart, liver, lung, and liver; electrolytes; external genitalia; and sexual performance were all in the normal range. Measurements of semen, plasma biochemistry, and endocrine changes also were within normal limits. However, in the 9 cases in which the average value of plasma testosterone was near the lower limit of normal, the average value of follicle-stimulating hormone was higher than normal and the testosterone/luteinizing hormone ratio was unusually low. Testis biopsy indicated that long-term gossypol treatment affected both germ cells and Sertoli cells. Leydig cells also demonstrated some damage. Gossypol acetate is, in general, considered an ideal male contraceptive because of its long-term effectiveness, reversibility, and lack of severe toxic side effects.
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PMID:Antifertility treating with long term gossypol. 1226 55

The injectable contraceptive depot-medroxyprogesterone acetate (DMPA) dissolves slowly and is released over 3 months to suppress ovulation. It is more than 99% effective at preventing pregnancy. More than 30 million women in 90 countries have used DMPA and none have died from using it. A World Health Organization [WHO] study showed that DMPA did not significantly increase the risk of breast cancer or other cancers. One study points to a small reduction in bone density with DMPA use, but the reduction did not become larger with long-term use and may even be reversible. The US Food and Drug Administration (FDA) thoroughly reviewed these studies and the experiences of DMPA users. This review resulted in the FDA's approving DMPA as a contraceptive in October, 1992. Almost all DMPA users experience menstrual changes with irregular bleeding and spotting occurring during the 1st few months. After 12 months, at least 50% of DMPA users experience amenorrhea, which some women consider a benefit. Other possible but rare side effects are weight gain, headache, breast tenderness, loss of libido, depression, nervousness, and fatigue. It takes longer for past DMPA users to conceive after stopping DMPA use than users of other contraceptive methods, but by 18 months more than 90% of past DMPA users who wanted to become pregnant conceived. DMPA does not protect users from sexually transmitted diseases (STDs) or HIV/AIDS. They need to use latex condoms to prevent STD/HIV transmission. DMPA users must return to their health care provider every 3 months for another injection. DMPA is a viable contraceptive for women wanting a safe, reliable, long-term, reversible contraceptive. Any woman wanting to use DMPA should discuss it with her provider.
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PMID:Facts about injectable contraception. 1228 37

Since the last in a series of childbirth education classes discusses contraception, educators must know about various family planning methods. Oral contraceptives (OCs) comprise combined OCs, phasic OCs, and minipills. Combined OCs inhibit secretion of gonadotropin-releasing hormone, which in turn keeps the follicle-stimulating hormone from inducing the ovarian follicle to grow and keeps luteinizing hormones from activating ovulation. They also thicken cervical mucus. Minipills also thicken cervical mucus and render the endometrium unreceptive to fertilized egg implantation. They do not always inhibit ovulation, however. OCs can induce side effects, such as nausea, hypertension, increased risk of atherosclerosis, and fatigue. The IUD prevents pregnancy either by inhibiting implantation of a fertilized egg or by an inflammatory reaction of the endometrium resulting in a release of macrophages which may destroy sperm. The no-longer-produced Dalkon Shield IUD increased the risk of pelvic inflammatory disease and damaged the reputation of other IUDs. Rare IUD complications are uterine perforation, salpingitis, tubal scarring, pelvic inflammatory disease, and infertility. Diaphragms, cervical film, and condoms serve as barriers between the egg and sperm. The main problem with barrier methods is the increased risk of developing toxic shock syndrome. Spermicide increase the effectiveness of diaphragms, cervical caps, and condoms. Vasectomy keeps sperm from arriving at storage sites. Shortterm side effects are swelling, discomfort, and occasional rejoining of the cut ends of the vas. Research hints at a link between vasectomy and prostate cancer. Some complications of tubal ligation are urinary tract infections, accidental electrical burns, and pelvic infections. Natural family planning methods include withdrawal, the rhythm method, and the sypto-thermal method. Controversial injectable contraceptives are Depo-Provera (medroxyprogesterone acetate) and Noristerate (norethisterone enanthate).
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PMID:Birth control update for childbirth educators. 1234 29

Bisoprolol is a highly selective beta(1)-adrenoceptor antagonist. Administration of bisoprolol to patients with chronic heart failure is associated with increases in left ventricular function and reductions in heart rate; increases in heart rate variability are also seen. Two major randomised, double-blind, placebo-controlled, multicentre trials have examined the clinical efficacy of bisoprolol in combination with ACE inhibitors and diuretics in patients with stable chronic heart failure (New York Heart Association class III or IV): the Cardiac Insufficiency Bisoprolol Study (CIBIS; n = 641) and CIBIS II (n = 2 647). All-cause mortality (primary endpoint) was significantly lower in bisoprolol than in placebo recipients in CIBIS II (11.8 vs 17.3%) and was reduced by bisoprolol regardless of dosage. All-cause mortality was also lower in CIBIS (16.6 vs 20.9%) although the difference did not achieve statistical significance. In a meta-analysis of CIBIS and CIBIS II (n = 3 288), a relative reduction of 29% in the incidence of all-cause mortality was seen in bisoprolol versus placebo recipients; this analysis also demonstrated that bisoprolol reduces mortality in patients with chronic heart failure regardless of aetiology or severity. In CIBIS II, there were significantly fewer cardiovascular deaths, admissions to hospital for any reason, or cardiovascular deaths or cardiovascular hospitalisations (combined endpoint) in bisoprolol, compared with placebo, recipients (secondary endpoints). Compared with standard treatment alone, the addition of bisoprolol was a cost-effective option in chronic heart failure in UK, French, German and Swedish pharmacoeconomic studies. Bisoprolol is generally well tolerated in patients with chronic heart failure. In CIBIS II, adverse events occurring more commonly in bisoprolol than placebo recipients, regardless of causal relationship with the study medication, included dizziness, bradycardia, hypotension and fatigue. Bisoprolol recipients were less likely than placebo recipients to experience worsening of heart failure, dyspnoea or tachycardia. In both CIBIS and CIBIS II there was no significant difference between bisoprolol and placebo recipients in the incidence of permanent treatment withdrawal. In conclusion, adding the highly selective beta(1)-blocker bisoprolol to a treatment regimen comprising an ACE inhibitor and a diuretic significantly improves survival in patients with stable chronic heart failure and reduces the need for hospitalisation. The use of bisoprolol in this disorder is generally well tolerated and is cost effective. Thus, bisoprolol should be considered a standard treatment option when selecting a beta-blocker for use in combination with ACE inhibitors and diuretics in patients with stable, moderate to severe chronic heart failure.
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PMID:Bisoprolol: a review of its use in chronic heart failure. 1246 13

Over the past decade, national and international guidelines have proposed beta-blockers to be used on an equal footing with diuretics for initial therapy of hypertension. This preferred status was supposedly based on evidence documenting a reduction in morbidity and mortality with beta-blocker therapy in hypertension. We systematically analyzed all available outcome studies and found no evidence that beta-blocker based therapy, despite lowering blood pressure, reduced the risk of heart attacks or strokes. Despite the inefficacy of beta-blockers, the incidence of adverse effects is substantial. In the MRC study, for every heart attack or stroke prevented, three patients withdrew from atenolol because of impotence, and another seven withdrew because of fatigue. Thus the risk/benefit ratio of beta-blockers is characterized by lack of efficacy and multiple adverse effects. Given that many thorough, prospective, randomized trials attest to efficacy and safety of diuretics, calcium antagonists, ACE inhibitors, and angiotensin receptor inhibitors, the time has come to admit that beta-blockers should no longer be considered appropriate for first-line therapy in uncomplicated hypertension.
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PMID:beta-Blockers in hypertension-the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension. 1455 68

The aim of this work was to determine the concentration of total and ionized magnesium in hair and blood of patients with primary hypertension and the influence of oral magnesium supplementation (Slow-Mag B6) on clinical parameters and blood pressure values. 92 patients were recruited from the Family Care Unit, Pomeranian Academy of Medicine in Szczecin. Each patient was treated during at least 6 months preceding the study with a single antihypertensive agent from one of the following groups: ACE inhibitors, beta-receptor inhibitors, Ca channel blockers, diuretics. The control group included patients with hypertension not treated pharmacologically. Changes in ionized magnesium concentration before and after oral magnesium supplementation were studied in relation to total cholesterol, triglycerides, and other parameters of importance in hypertension. Significantly lower total magnesium concentrations were demonstrated in hair of patients receiving ACE inhibitors and diuretics in comparison to controls. Ionized magnesium concentrations in serum of hypertensive patients were significantly reduced as compared with controls. A highly significant increase in these levels was noted after magnesium supplementation. Blood pressure values after magnesium supplementation were reduced in the study group by an average of 15-20 mmHg for systolic and 5-9 mmHg for diastolic blood pressure. Correlations between ionized magnesium and triglyceride concentrations in patients treated with Ca channel blockers before oral Mg supplementation were found. Patients treated with diuretics demonstrated correlations between total magnesium and total cholesterol concentrations. Following oral magnesium supplementation with Slow-Mag B6 at 320 mg/day, the frequency of complaints reported by patients, including irregular heart beat, pricking heart pain, nervousness, sleep disorders, irritability/tearfulness was reduced. There was no effect on other complaints, such as mental and physical fatigue, constipation/diarrhea, and anxiety.
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PMID:[Level of total and ionized magnesium fraction based on biochemical analysis of blood and hair and effect of supplemented magnesium (Slow Mag B6) on selected parameters in hypertension of patients treated with various groups of drugs]. 1460 71

Addison's disease or primary adrenal insufficiency is a rare disease, which is usually caused by autoimmune destruction of the adrenal cortex. The clinical picture is caused by deficiency of cortisol and aldosterone. These deficiencies are accompanied by adrenal androgen depletion of yet unknown significance. The current therapy is the replacement of glucocorticoids and mineralocorticoids, but the available drugs do not restore the normal diurnal variations in serum hormone levels. The clinical consequences of the grossly unphysiological replacement therapy are largely unknown. Many patients with Addison's disease on standard replacement therapy complain of fatigue, weariness, and reduced stress tolerance. One particular concern has been negative effects on both bone metabolism due to over-replacement of glucocorticoids and androgen depletion. This review discusses the evidence for the current drug and dosage recommendations. Current recommended daily starting dose for hydrocortisone and cortisone acetate are 20 and 25 mg, respectively, divided into two or preferably three doses. The mineralocorticoid depletion should be treated with fludrocortisone 0.05-2.0 mg/day [DOSAGE ERROR CORRECTED]. Replacement of dehydroepiandrosterone 20-50 mg has been advocated in adrenal failure, but the evidence for benefit is weak.
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PMID:Replacement therapy in Addison's disease. 1464 Sep 13


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