Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
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A brief survey of the literature on the side effects of oral contraceptives is given. Of the many influences on laboratory results those related to (reversible) cholestasis or to a change in protein synthesis are the most important ones. A decrease of the tolerance for glucose is sometimes observed. Few of the clinical side effects attributed to oral contraceptives can be directly correlated with the pharmaceutical action of these drugs. Many so-called side effects of the pill are due to other factors such as altered psychosociological or sexual behavior, etc. However, among users of oral contraceptives there is a significant decrease in the number of benign tumors, particularly of the breast, the uterus and the ovaries. It is still an open question if this also signifies protection against cancer. Anemias due to iron deficiency are less frequent among users of the pill. According to recent studies arterial hypertension and cholecystopathies are probably directly related to oral contraceptives, but a causal relation has not been proven for migraine, headaches, depression etc. An elevated risk for vascular complications seems to be well established: there is a 4-6-fold increase of the estimated risk for venous thrombo-embolism and a 4-9-fold increase for cerebrovascular accidents among users of oral contraceptives when compared with nonpregnant women of the same age not using the pill. Oral contraceptives act as a supplementary factor of risk which may cumulate with other similar factors, such as arterial hypertension, hyperlipidemia, overweight, smoking etc. Mortality due to oral contraceptives is very much 10-50 x) inferior to the one caused by delivery and the post partum state. Since the number of failures in prevention of pregnancies is less for oral contraceptives than for any other method of contraception, the overall risk of death under oral contraceptives in this age group of women is least.
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PMID:[Real and seeming side-effects of oral contraceptives with an emphasis on medical and haematological problems. Review of literature (author's transl)]. 79 Mar 74

Report of a 10-year-old boy with congenital hypoplasia of the intrahepatic bile ducts, the socalled MacMahon-Thannhauser-Syndrome. The patient had been suffering from a varying degree of jaundice since his 2nd day of life and from pruritus since his 21st month of life. Furthermore, he had hepatomegaly, a systolic cardiac murmur, hypogenitalism, retarded growth, and finally hypertension. Transitory xanthomas existed between 1 3/4 and 2 3/4 years of age. Signs of persistent intrahepatic cholestasis was manifested by increased levels of bilirubin and bile acids in serum as well as raised activities of leucine aminopeptidase, gamma-glutamyl transpeptidase and alkaline phosphatase. Pathological values of serum glutamic dehydrogenase pointed to a persistent destruction of liver cells. Without treatment, the activities of vitamin K dependent clotting factors were decreased. Cholesterol, phosphatides and triglycerides in serum were increased and lipoprotein-X was detectable. Aortography revealed stenosis of both renal arteries. An exploratory laparotomy and 5 liver biopsies led to the diagnosis of hypoplasia of the intrahepatic bile ducts. Therapeutic trials with steroids and the anion exchange resin "cholestyramine" were ineffective. Phenobarbital relieved the pruritus. Parenteral administration of fat soluble vitamins restored the activity of vitamin K dependent clotting factors to normal. The high blood pressure fell significantly due to treatment with adelphan. The etiology of hypoplasia of the intrahepatic bile ducts is unknown. It may be a malformation or an obliteration secondary to inflammation. In our patient, narrowing of the renal arteries, increase of plasma-renin activity and hypertension were probably secondary to hyperlipidemia. It has been suggested that hyperlipemia secondary to cholestasis may be due to a disturbance of lipoprotein metabolism. A review of reports on 118 patients suffering from intrahepatic bile ducts hypoplasia is included.
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PMID:[Hypertension and bilateral stenosis of the renal artery associated with congenital hypoplasia of the intrahepatic bile ducts (author's transl)]. 124 84

Liver disorders characterized by prolonged bile stasis are often associated with the accumulation of an abnormal lipoprotein, lipoprotein-X (LP-X), in plasma. LP-X is separated in the low-density lipoprotein (LDL) density range, but lacks apolipoprotein B and does not interact with the LDL receptor; LP-X can cause hyperlipidemia, cutaneous xanthomas, and worsening of arterial disease. We report the case of a patient with severe cholestasis, markedly elevated plasma cholesterol levels (26.8 to 31.5 mmol/L), mainly due to a massive accumulation of LP-X in plasma, and diffuse xanthomas. To reduce the elevated cholesterol levels, the patient was given extracorporeal treatment aimed at removing atherogenic lipoprotein (LDL-apheresis). LDL-apheresis was performed at weekly or bi-weekly intervals, either by a semi-selective technique using filters with a defined pore diameter (double filtration, DF) or by a more selective technique using dextran-sulfate-cellulose (DSC) columns able to bind LDL. The semi-selective DF technique proved more effective than DSC, removing 48% of total cholesterol (compared to 30% with DSC), and lowering cholesterol levels to 11.1 mmol/L in 6 weeks. DF removed both LDL and LP-X from plasma, whereas DSC selectively decreased the LDL content. The reduction of plasma cholesterol levels was associated with a complete regression of the xanthomas, supporting DF apheresis as a first-choice treatment for patients with massive LP-X accumulation due to cholestasis.
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PMID:Management of lipoprotein-X accumulation in severe cholestasis by semi-selective LDL-apheresis. 202 22

Hepatic diseases differ from most other causes of secondary dyslipidaemia in that the circulating lipoproteins are not only present in abnormal amounts but they frequently also have abnormal composition, electrophoretic mobility and appearance. Pre-beta and alpha bands can be absent on electrophoresis in all types of liver disease although material in the VLDL and HDL ranges can be isolated in the ultracentrifuge. Cholestatic liver disease has been the most extensively studied and the hyperlipidaemia can be extreme with marked elevations of free cholesterol and phospholipids. This results largely from the presence of LP-X, an abnormal LDL, with a vesicular structure that appears in rouleaux formation under the electron microscope. It is virtually specific for cholestasis and familial LCAT deficiency. The LDL, however, is heterogeneous and may also contain a large triglyceride-rich particle (LP-Y) as well as more normal-looking particles, which are none the less depleted in cholesteryl esters and rich in triglycerides. Indeed, when patients with cholestasis are hypertriglyceridaemic the excess triglyceride is to be found predominantly in these two LDL fractions rather than in VLDL. HDL in cholestasis may contain disc-like particles, similar to those newly secreted by the liver and intestine, as well as more normal-looking spherical particles. In extrahepatic obstruction concentrations of HDL and its major apolipoproteins, apoAI and apoAII, are frequently reduced, although a subfraction rich in apoE is often found. In all but the latest stages of chronic intrahepatic cholestasis due to primary biliary cirrhosis, however, HDL, especially HDL2, concentrations are increased, probably due to the presence of a circulating inhibitor of HL. Many of these lipoprotein changes found in cholestasis resemble those of familial LCAT deficiency, although the hyperlipidaemia is not usually so severe in the latter condition. Indeed, in patients with cholestasis but well-preserved LCAT activity many of the characteristic lipoprotein changes, such as LP-X, LP-Y and discoidal HDL, may not be seen. In acute hepatocellular disease, such as alcoholic or viral hepatitis, it is not unusual for the patient to go through a cholestatic phase and many of the same lipoprotein changes may be seen. In cirrhosis without cholestasis the patients are not usually significantly hyperlipidaemic and in advanced cases cholesterol and apoB levels may be reduced. Although LCAT activity and the proportion of plasma cholesterol esterified may also be markedly reduced, LP-X is not usually seen, possibly because the flux of free cholesterol and phospholipid (lecithin), the LCAT substrates, is relatively low. Discoidal HDLs are often present.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dyslipoproteinaemia of liver disease. 208 7

We have previously shown that bile duct ligation inhibits the hepatic uptake of chylomicron remnants in rats. In the present study we have investigated different possible causes of this inhibition. Intravenous infusion of bile or sodium taurocholate reduced the hepatic chylomicron remnant uptake. Perfused livers from bile duct-ligated rats metabolized chylomicron remnants at a reduced rate. Rat hepatocyte monolayer cultures metabolized remnants formed in cholestatic rats and those formed in hepatectomized animals equally well, but serum from cholestatic rats inhibited remnant uptake more strongly than control serum. Bile duct ligation did not influence the clearance from plasma of human low-density lipoprotein, and the inhibition of hepatic remnant uptake was not affected by treatment of cholestatic rats with ethinylestradiol. The clearance of 125I-labeled asialofetuin was only slightly impaired by cholestasis, indicating that no strong inhibition of all endocytic processes of the hepatocytes occurred. The reduced hepatic uptake of chylomicron remnants in the cholestatic rat is thus not due to formation of abnormal remnant particles. An increased plasma bile acid concentration rapidly reduced the hepatic remnant uptake without causing any significant hyperlipidemia. However, the pathological lipoproteins accumulating in the cholestatic rat aggravated the hepatic uptake defect even further.
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PMID:Factors affecting the impaired hepatic uptake of chylomicron remnants in the cholestatic rat. 243 46

In contrast to deficiencies of vitamins A, D and K, little is known of the prevalence, clinical manifestations and mechanisms of vitamin E deficiency in adult patients with cholestasis. We measured serum vitamin E levels in 45 patients with primary biliary cirrhosis, 20 with primary sclerosing cholangitis, 9 with cryptogenic cirrhosis and 12 with alcoholic cirrhosis. To correct for the hyperlipidemia often found in patients with primary biliary cirrhosis and primary sclerosing cholangitis, total serum lipids were measured and vitamin E levels were expressed as the vitamin E/total serum lipid ratio. Serum vitamin A and D levels and prothrombin time were also determined. Six of 45 patients with primary biliary cirrhosis (13%) but none of the patients with sclerosing cholangitis, cryptogenic cirrhosis or alcoholic cirrhosis and subnormal vitamin E/total serum lipids ratios. Vitamin E deficiency was found in two of eight patients with asymptomatic primary biliary cirrhosis. There was no correlation between standard liver biochemical tests, fasting serum cholylglycine and vitamin E levels. Patients with primary biliary cirrhosis and primary sclerosing cholangitis had significantly lower vitamin E/total serum lipids ratios than patients with either cryptogenic or alcoholic cirrhosis. Twenty-three percent of patients with primary biliary cirrhosis were vitamin D deficient and 14% had low vitamin A levels. Two of the six patients with vitamin E deficiency were also deficient in vitamin D, only one was vitamin A deficient and none had prolonged prothrombin time. We also investigated the gastrointestinal absorption of vitamin E in nine patients with primary biliary cirrhosis and normal vitamin E levels as well as in six normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vitamin E deficiency in primary biliary cirrhosis: gastrointestinal malabsorption, frequency and relationship to other lipid-soluble vitamins. 292 55

A 52-year-old man, having been treated for 4 months with chlorpropamide for diabetes mellitus type II, developed severe cholestatic hepatitis following a short course of erythromycin ethylsuccinate. Despite prompt withdrawal of both drugs, the cholestatic picture worsened and was associated with morphological evidence of disappearing interlobular bile ducts. After a 2-year course of profound cholestasis complicated by steatorrhea and striking hyperlipidemia, the patient died of ischemic cardiomyopathy. It is believed that this is the first published case of irreversible cholestasis with disappearance of ducts potentially related to a metabolic interaction between erythromycin ethylsuccinate and chlorpropamide.
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PMID:Prolonged cholestasis and disappearance of interlobular bile ducts following chlorpropamide and erythromycin ethylsuccinate. Case of drug interaction? 326 70

Primary biliary cirrhosis (PBC) is a chronic nonsuppurative, destructive cholangitis, whose etiology is unknown. Morbidity arises early from pruritus and later from hypercholesterolemia with xanthoma formation. Therapy is supportive and directed at the complications of cholestasis. Plasmapheresis has been reported to benefit patients with hyperlipidemia and PBC; thus a pilot study of plasmapheresis utilizing the Haemonetics Model 30 with replacement by albumin and saline was conducted. Five patients (four female and one male) with a mean age of 43 (range 29-58) and a mean duration of illness of 9.5 years (range 6-21) with marked jaundice, xanthomas, xanthelasma, hepatomegaly, fatigability, anorexia, and pruritus, as well as mild nausea were studied. Peripheral neuropathy was present in two patients. Two patients had splenomegaly. Two patients had an associated Sjogren syndrome. All patients had high serum bilirubin, alkaline phosphatase, and cholesterol levels and mild elevations in aspartate amino transferase and alanine amino transferase activities. Immune complexes measured in four patients were present. Antimitochondrial antibody titers were significant in all patients. Patients underwent a mean of 63 plasmapheresis procedures over a mean of 112 weeks removing a mean of 94.7 liters of plasma. No serious toxicity was seen. All patients showed a reduction in pruritus, xanthomas, xanthelasmas, and serum cholesterol values. The two patients who had evidence of Sjogren syndrome noted subjective improvement. All patients who had fatigue, anorexia and nausea also noted moderate improvement. There was no change in hepatomegaly or splenomegaly in patients demonstrating such organomegaly. Liver function did not change significantly. Overall, four patients had improvement in their condition and one patient achieved stability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The clinical effectiveness and safety of chronic plasmapheresis in patients with primary biliary cirrhosis. 403 Jul 9

Oral contrceptives (OCs), usd by over 30% of reproductive aged women in Belgium, are by far the most widely used contraceptive in that country. The various types of OCs include monophasic, biphasic, and triphasic combinations of an estrogen and a progestin, sequentials containing estrogen only for 7-14 days followed by a progestin through the 21st day; macrodose or microdose progestin only formulations, 3-month injectable progestins, and the morning after pill. Side effects of OCs are mainly due to metabolic effects on coagulation factors, the renin-angiotensin system, glucose tolerance, or the lipid profile. Users of OCs face increased risks of cholelithiases, thrombophlebitis, thromboembolism, cerebrovascular accidents, myocardial infarcts (among smokers over 35 years of age), and hepatic adenomas. The most troubling secondary effect is the excess cardiovascular morbidity and mortality show by contraceptive users, not just those who are obese, hypertensive, or who have histories of vascular pathology, but also those over 40 years of age and smokers. Lenght of use of OCs does not increase vascular risks. Epidemiologic studies demonstrate that vascular risks are reduced in lower dose formulations. Absolute contraindications to OC use include serious cardiovascular problems, severe hepatic pathology, estrogen-dependent tumors, pregnancy and undiagnosed gynecologic problems, and significant hyperlipidemia. Relative contraindications include severe headaches, cholelithiase, previous cholestasis of pregnancy, severe renal disease, fibromyomas, benign breast disease, age over 40 years, smoking, surgery anticipated within 4 weeks, infectious mononucleosis, falciform anemia, and immediate postpartum and lactation. Epilepsy, diabetes, depression, and varicose veins are not strictly speaking contraindications but require additonal surveillance. Lower dose formulations should be prescribed if possible. OC users should be followed up every 6-12 months. Among other steroidal contraceptive methods, sequential OCs and high dose progestin-only formulations are used for short-term treatment of specific conditions. Progestin-only minipills are used when an OC is desired but estrogens are contraindicated. Injectable progestins should be reserved for patients who for cultural or medical reasons can use no other type of contraceptive. Morning-after pills should not be considered a regular form of contraception. If OCs are used in adolescents, a low dose pill is indicated. Low dose OCs may be indicated for diabetics because of the danger of infection with IUDs and the lesser efficacy of barrier methods. If OCs are used in epileptics, they should be regular dosed because of the danger of drug interactions. Only low-dose formulations and progestin-only minipills should be used by women over 40.
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PMID:[The choice of oral contraception in 1984: general indications and specific cases]. 672 93

In this review we have endeavored to emphasize the central role of the liver in normal lipoprotein metabolism and to demonstrate how derangements in these metabolic processes can lead to abnormalities characteristic of liver disease. Since changes in the concentration and composition of plasma lipids and lipoproteins occur frequently in liver disease, these findings may be useful in following the clinical course of patients with liver disease of various causes. It should be emphasized that elevated plasma triglycerides and cholesterol are due to underlying defects in lipoprotein metabolism and should not be confused with primary hyperlipidemia. Impaired cholesterol esterification, abnormal lipoprotein electrophoretic patterns and lipoprotein compositional changes, all reflect abnormalities of lipoprotein metabolism that are secondary to hepatocellular injury or cholestasis. These abnormalities are very sensitive indicators of fundamental metabolic defects that are related in part to LCAT and apoprotein activator deficiencies, impaired H-TGL and LPL activity and, perhaps, defective remnant lipoprotein clearance by the liver. Since these abnormalities tend to improve with clinical recovery they have proved to be reliable and sensitive indicators of hepatic function and thus, are useful in the assessment of liver disease.
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PMID:Lipoprotein metabolism in liver disease. 698 38


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