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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heart transplantation (HTx) has now become an accepted treatment modality for end-stage heart disease. The limited supply of suitable donor organs imposes constraints upon the decision of who should be selected for transplantation. Usually patients are candidates for HTx, who remain NYHA functional class III or IV despite maximal medical therapy. Further criteria are low left ventricular ejection fraction (less than 20%) with heart rhythm disturbances class IIIA-V (LOWN), which are associated with poor prognosis. Additionally, the suffering of the patient and also the course of heart failure are essential for judging the urgency of HTx. Contraindications are absolute in patients with untreated infections, fixed pulmonary vascular resistance (PVR) above 8 WOOD-degrees, severe irreversible kidney and liver disease, active ventricular or duodenal ulcers and acute, psychiatric illness. HTx is relatively contraindicated in patients with diabetes mellitus, age over 60 years, PVR above 6 WOOD-degrees and an unstable psychosocial situation. To prevent rejection of the transplant heart, live-long immunosuppressive therapy is needed. Most immunosuppressive regimes consist of Cyclosporine A and Azathioprine (double drug therapy) or in combination (tripple drug therapy) with Prednisolone. For monitoring of this therapy, control of hole blood cyclosporine A level and white blood count is needed. Rejection episodes can be suspected if there is a greater than 20 mmHg decrease of systolic blood pressure, elevated body temperature, malaise, tachycardia or heart rhythm disturbance. The diagnosis of cardiac rejection can be established by endomyocardial biopsy. Measurement of the voltage of either the surface or intramyocardial ECG, echocardiography with special consideration to early left ventricular filling time as well as immunological methods are additionally used tools. Graft sclerosis as the main risk factor of the late transplant period remains an unsolved problem.
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PMID:[Therapy of terminal heart failure using heart transplantation]. 192 Dec 33

Captopril has attained widespread use as an effective agent in the treatment of heart failure and hypertension. Dermatological, renal and haematological toxicity associated with its use has been widely described and is usually well recognized. There have been comparatively few reports implicating it as causing hepatic drug reactions. Most descriptions have emphasized strongly cholestatic features, although a mixed hepatocellular cholestatic picture and predominant hepatocellular reactions have been reported. Between November 1972 and June 1990 only five cases of possible Captopril-associated hepatic dysfunction were reported to the Australian Adverse Drug Reaction Advisory Committee. Cases reported suggest equal sex distribution, latent period to development of abnormality between 1 week and 20 months, with slow resolution of jaundice and biochemical abnormality from 1 week to 6 months after withdrawal of the drug. One case of hepatic coma and death with massive acute hepatic necrosis on biopsy has been reported. Not uncommonly the accompanying systemic features suggest a syndrome of drug hypersensitivity. We report a case of Captopril-induced cholestatic jaundice in which the abnormality occurred 2 weeks after commencement of the drug and resolved slowly upon discontinuation. The case illustrates two important points: first, the importance of taking a full history, obtaining detailed information about previous drug administration in patients admitted with jaundice; and second, in the case of Captopril-induced liver disease, the jaundice may persist for many weeks after drug withdrawal.
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PMID:Cholestatic jaundice associated with captopril therapy. 193 74

Postoperative use of as-needed intramuscular narcotics is potentially hazardous in frail elderly patients. Patient-controlled analgesia (PCA) allows patients to self-administer small boluses of narcotic, allowing better dose titration, enhanced responsiveness to variability in narcotic requirements, and reduction in serum narcotic level fluctuation. Although theoretically useful, this method has not bee well studied in the elderly or medically ill. A prospective controlled trial among 83 higher-risk elderly men after major elective surgery compared PCA containing morphine sulfate with intramuscular morphine injections as needed (mean [+/- SD] age, 67.4 +/- 5.6 vs 67.0 +/- 6.3 years). Subjects had a variety of medical illnesses, including chronic lung disease (57%), coronary artery disease (43%), heart failure (13%), and liver disease (12%). Preoperative and postoperative assessments included chest roentgenograms; daily mental status and pulmonary function testing; twice-daily serum morphine levels; and oxygen saturation values, linear analogue pain and sedation scores, and vital signs every 2 hours. Care was taken to optimize narcotic administration in control subjects as well as PCA subjects. Analgesia was significantly improved by PCA (3-day mean pain score, 40.5 +/- 18.0 vs 32.5 +/- 15.0), without an increase in sedation. Significant postoperative confusion (18% vs 2.3%) and severe pulmonary complications (10% vs 0%) occurred significantly more frequently in intramuscular-treated controls. Patient-controlled analgesia was quickly mastered by most patients; no major problems referable to its use occurred. Patients who had previously received intramuscular injections reported that PCA was easier to use and provided better analgesia. Serum morphine levels showed significantly less variability on postoperative day 1 with PCA, compared with intramuscular injections. We conclude that PCA is an improved method of postoperative analgesia in high-risk elderly men with normal mental status, compared with as-needed intramuscular injections.
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PMID:Randomized trial of postoperative patient-controlled analgesia vs intramuscular narcotics in frail elderly men. 197 90

Regular drug treatment in mild hypertension (diastolic blood pressure 90-104 mm Hg) reduces death from stroke, and other non-coronary vascular events. The optimum strategy remains sequential monotherapy with the lowest effective dose, with drug combinations as an option. A beta-adrenoceptor blocker or low-dose thiazide is good value treatment for many patients. beta-Blockers are good for young (under 50 years), anxious non-smoking men, men after myocardial infarction, and renal failure patients. Older persons over about 65 years, women, smokers, stroke victims, and liver disease patients should generally take a thiazide or calcium ion-channel blocker. Pregnant women and untreated gouty patients should avoid diuretics. Calcium blockers and angiotensin-converting enzyme inhibitors are preferable in severe or insulin-dependent diabetes and renal failure, and angiotensin manipulators or thiazides in heart failure or peripheral vessel disease. Hyperlipidaemia should not generally exclude thiazides or beta-blockers. Some hypertensive stroke patients without encephalopathy may not need antihypertensive drug treatment for the first 24-48 hours. Drug treatment should be tailored to individuals according to their general condition, physiological age, and any concurrent disease or medication. Unwanted drug reactions should not deter patients from fulfilling social and economic goals. The desired treatment end-point is a diastolic pressure of 85-89 mm Hg, but a compromise is usual in poorly motivated young men, and the elderly.
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PMID:Optimising drug management of individuals with cryptogenic hypertension. 202 55

Cardiac scintigraphy has been performed in 60 beta-thalassaemia major patients aged 8-35 years who received regular blood transfusions and subcutaneous desferrioxamine (DFX) chelation. Fifty-seven showed no clinical, radiological or electrocardiographic evidence of heart disease and 3 had clinically apparent cardiac failure. Twenty-two patients (37%) showed severe cardiac functional impairment defined by a resting left ventricular ejection fraction (LVEF) less than 45% and/or a drop of greater than 12% on stress, while 19 were normal and 19 had a mild abnormality. There was no significant correlation between abnormality of LVEF and age, serum ferritin, number of units transfused, dose and duration of subcutaneous DFX therapy, liver disease or sexual maturation. Non-compliant patients (defined as the use of subcutaneous DFX less than 4 times weekly) generally showed worse cardiac function. Repeat study on 17 patients after 6-28 months of better compliance with subcutaneous or intravenous DFX (using an indwelling catheter) showed a significant overall improvement in LVEF associated with a significant drop in serum ferritin. We conclude that cardiac scintigraphy uncovers a high incidence of cardiac functional abnormality in asymptomatic, well-transfused thalassaemia patients, particularly those poorly compliant with chelation. Those with poor LVEF results should be offered intensive chelation therapy to improve cardiac function.
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PMID:High incidence of cardiomyopathy in beta-thalassaemia patients receiving regular transfusion and iron chelation: reversal by intensified chelation. 212 60

Mexiletine is a type I antiarrhythmic drug that is structurally similar to lidocaine. Mexiletine has considerable potential for causing neurologic, cardiac, or gastrointestinal side effects. However, mexiletine does not undergo clinically significant first-pass metabolism and, thus, has good oral bioavailability. Mexiletine has a large and variable volume of distribution and an elimination half-life ranging from 6 to 12 hours. Mexiletine disposition is probably altered in patients with heart failure, liver disease, and severe renal dysfunction. Efficacy and toxicity are not well correlated with mexiletine serum concentrations. Mexiletine is as effective as traditional antiarrhythmics in the treatment of premature ventricular contractions. However, in patients with drug-refractory inducible ventricular tachycardia, mexiletine is usually ineffective when used alone. When mexiletine is combined with other antiarrhythmic agents, a significantly higher percentage of patients with this difficult arrhythmia have a good response. Mexiletine is a potentially important addition to the existing antiarrhythmic drugs currently available, but its place in the clinical setting and in therapeutic drug monitoring is not well defined at this time.
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PMID:Mexiletine: a new type I antiarrhythmic agent. 242 92

Since most of the toxicity associated with class 1B antiarrhythmic drugs is dose-related, this review examines adverse effects seen in both therapeutic practice and accidental or premeditated overdose. Toxicity is very common with these agents and can be life-threatening. A high percentage of patients must discontinue therapy because of adverse effects. Mexiletine and tocainide are structural analogues of lignocaine (lidocaine) and toxicity is similar with all 3 drugs. With gradual intoxication (the most common form) central nervous system effects such as lightheadedness, dizziness, drowsiness and confusion are seen first. Seizures and respiratory arrest can occur. Cardiovascular toxicity is manifested by progressive heart block, reduced cardiac contraction, hypotension and asystole. Both mexiletine and tocainide may have proarrhythmic effects. Gastrointestinal toxicity is also common. Shock, hypotension, cardiac failure and beta-blocker therapy reduce lignocaine clearance and enhance the risk of intoxication during routine therapy. Both lignocaine and mexiletine elimination is impaired in severe liver disease while tocainide clearance is reduced in renal failure. Management of toxicity is largely supportive and symptomatic. Lignocaine infusion must be discontinued and decontamination of the gut in the case of oral preparations is recommended. Serious intoxication requires intensive care unit admission. Haemodialysis or haemoperfusion may be helpful in serious lignocaine and tocainide poisoning. In institutions where extracorporeal circulatory assistance is available, massive lignocaine poisoning has been successfully treated with this intervention. In the therapeutic setting serious toxicity can be prevented by close clinical surveillance and appropriate dose reduction in patients with reduced drug clearance. Because of the large interindividual variation in lignocaine pharmacokinetic parameters, therapeutic drug monitoring is recommended if results can be reported quickly. Mexiletine and tocainide have stereoselective metabolism and assays do not distinguish the more active isomers. Therapeutic drug monitoring is less useful in this situation.
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PMID:Poisoning due to class 1B antiarrhythmic drugs. Lignocaine, mexiletine and tocainide. 251 64

The pharmacokinetics of xamoterol, a beta 1-adrenoceptor partial agonist, have been studied in patients with liver disease and a group of age- and sex-matched normal controls. No significant differences were observed after the oral administration of xamoterol 200 mg. The low bioavailability of xamoterol was confirmed (6.1% in patients, 6.9% in controls). After i.v. xamoterol 0.2 mg kg-1, no significant differences between the groups were observed. A small increase in the terminal plasma elimination half-life (t1/2) was observed in patients when compared with controls (15.3 +/- 6.4 vs 8.4 +/- 2.8 h, mean +/- s.d., P = 0.08). Renal clearance accounted for about 50% of total clearance in patients and about 30% in controls. It is suggested that in patients with heart failure, hepatic dysfunction would probably not influence xamoterol disposition.
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PMID:The pharmacokinetics of xamoterol in liver disease. 253 23

The inter-relationship between the pharmacokinetic and pharmacodynamic behaviour of ACE inhibitors is reviewed. First, some of the methods which have been used to assess the pharmacodynamics of ACE inhibitors in humans are presented. They include humoral assays (e.g. ACE activity in plasma, renin activity, etc.), haemodynamic changes (blood pressure, total peripheral resistance, etc.) and agonist challenges (angiotensin I infusions). Subsequently a pharmacokinetic-dynamic model is described, based on biochemical processes obtained after ACE inhibition, which seems to be useful for the interpretation of the complex processes. The various correlations between plasma drug concentration on the one hand and plasma ACE activity, angiotensin II concentration in plasma or blood pressure on the other, are discussed on the basis of this model. From the model obtained it becomes obvious that under many circumstances the release of the inhibitor from ACE binding is the step which in fact determines the pharmacodynamically relevant elimination rate of the drug at low concentrations, whereas at high concentrations the elimination of the drug is mainly dependent on kidney (and/or liver) elimination rate. The dynamic-kinetic correlations are then presented for some ACE inhibitors in various disease states: arterial hypertension, heart failure, old age, renal failure, liver disease. In a final section the kinetic and dynamic relevance of interactions of ACE inhibitors with food and other drugs is described (e.g. prostaglandin inhibitors, diuretics, digoxin and cimetidine). Despite the great body of literature which deals with the kinetic and/or dynamic properties of ACE inhibitors, precise knowledge of the relationship between their kinetic and dynamic behaviour is rather limited and there is a clear need for further studies to elucidate this complex topic, thereby improving therapeutic possibilities with these useful new compounds.
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PMID:Angiotensin-converting enzyme inhibitors. Relationship between pharmacodynamics and pharmacokinetics. 284 18

The mucopolysaccharidoses are a group of clinically progressive, heritable, lysosomal storage disorders. Many organ systems are affected due to widespread accumulation of incompletely degraded mucopolysaccharide. The novel finding of hepatic fibrosis in each of six cases of mucopolysaccharidosis examined at autopsy (including examples of Hurler syndrome, Hunter syndrome, and Sanfilippo syndrome) is described. In each instance, the liver was diffusely involved by fibrosis that outlined the lobules, and there was extensive hepatocyte and Kupffer cell vacuolization. The pattern of hepatic fibrosis is not explained by either cardiac failure or drug toxicity. It is hypothesized that the hepatic fibrosis is due to the abnormal accumulation of a hepatotoxic metabolite. The frequency and severity of liver disease in the mucopolysaccharidoses deserve further study. In particular, with the advent of bone marrow transplantation as therapy for some of the mucopolysaccharidoses, the question of whether cirrhosis develops in these patients and, if so, what its rate of progression is, should be addressed.
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PMID:Hepatic fibrosis in the mucopolysaccharidoses. 309 34


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