Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the results of clinical and endocrinological investigations performed on 10 children and adolescents (5 males and 5 females) with a primary central nervous system germinoma. Eight of 10 patients were between 10-20 yr of age at the time of initial presentation. Polyuria (7 of 10) and a decrease in or cessation of linear growth (5 of 10) were the most common presenting symptoms, while only 2 of 10 patients complained of visual problems. Two patients presented with the syndrome of polyuria, adipsia, hypernatremia, profound muscle weakness, and hyperlipidemia. Initial physical exam revealed abnormal eye findings in 60%, short stature (greater than or equal to 2.5 SD) in 50%, and abnormal pubertal development in 30% of the patients. The neoplasm was located in the suprasellar-hypothalamic region in 8, caudate nucleus in 1, and pineal region in 1. Biopsy performed in 7 patients revealed the classic two-cell germinoma in all cases. Assessment of endocrine function before radiotherapy documented pituitary deficits in all patients studied. Antidiuretic hormone was deficient in 8 of 10 patients and was associated with hypoadipsia in 4. GH was deficient in al patients tested (7 of 7). TSH (5 of 8), ACTH (3 of 7), and gonadotropin (1 of 1) deficiencies were also common before treatment. Plasma PRL concentrations were elevated in 5 of 8 patients, all with suprasellar tumors. The hCG values were elevated only in the patient with sexual precocity (1 of 10). Endocrine evaluation during the postirradiation period revealed additional instances of GH (1), ACTH (1), and gonadotropin (5) deficiencies. All 10 patients are alive without evidence of active disease 6 months to 10 yr after radiation therapy (4500-5100 R). Evidence of hypothalamic-pituitary dysfunction is an early and almost universal feature of central nervous system germ cell tumors. The importance of careful evaluation and follow-up of children with acquired anterior or combined anterior and posterior pituitary dysfunction for a suprasellar tumor is stressed.
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PMID:Hormonal and metabolic abnormalities associated with central nervous system germinoma in children and adolescents and the effect of therapy: report of 10 patients. 625 7

Induction by 7,12-dimethylbenz(a)anthracene of mammary tumors was studied in analbuminemic rats, a mutant strain established from Sprague-Dawley rats which are characterized by the absence of serum albumin and hyperlipidemia. Twenty-three weeks after carcinogen administration, the incidence and average number of mammary tumors and the tumor weight per tumor-bearing rat were respectively 35.0%, 1.7 +/- 0.2 (S.E.) and 8.9 +/- 0.5 g in analbuminemic rats and 69.2%, 2.3 +/- 0.2 and 12.2 +/- 2.8 g in the controls. Associated with this lower mammary tumorigenic response, analbuminemic rats had significantly lower plasma prolactin levels than controls during proestrus at 7-8 weeks of age when carcinogen was given (176 +/- 62 vs 308 +/- 52 ng/ml).
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PMID:Mammary tumor induction in analbuminemic rats by 7,12-dimethylbenz(a)anthracene. 642 89

A case of acute intestinal vascular necrosis in a 19-year-old user of oral contraceptives (OCs) is described, and hypotheses explaining the digestive complications of synthetic estrogens are reviewed. The patient had originally presented with a violent gastric pain that subsequently spread to the entire abdomen. An abrupt worsening of her condition involved cardiovascular collapse associated with a peritoneal syndrome, vomiting and dehydration, and hyperleukocytosis. Emergency opening of the peritoneum was followed by evacuation of a large quantity of fetid gas and alimentary debris, and observation of a completely necrosed stomach. A careful lavage of the entire intestinal cavity led to temporary improvement, but it became clear during an attempt at gastrectomy that further treatment would be unavailing and the patient died shortly thereafter. Estrogens were believed to be responsible for the digestive necrosis because it occurred in a young woman who had used an estrogen-rich OC for 3 years and who smoked; a hapatic biopsy confirmed the diagnosis. No traces of other risk factors such as hypertension, hyperlipidemia, diabetes, neoplasia, or obesity were observed. Recent publications indicate that OCs are responsible for a certain number of digestive problems, which may include acceleration of intestinal transit, severe diarrhea, rectorrhagia, ischemic or ulcerative colitis, intestinal infarct which is usually localized, and hepatocellular problems ranging from moderate hepatic insufficiency to malignant tumor and Budd-Chiari syndrome. OCs do not modify hemodynamic regimes, but they may cause elevation of fibrinogen and thrombin, diminution of antithrombin III acitivty, increased platelet adhesivity, and decreased fibrinolysis leading to hypercoagulability. These modifications in hemostasis occur in all OC users and are not statistically correlated with occurence of thrombotic accidents. OCs are probably responsible for parietal vascular lesions; experimental injection of synthetic estrogens is associated with both arterial and venous lesions. The most characteristic anomaly is at the level of the intima, with proliferation of smooth muscle cells and increased conjunctive tissue fibers associated with proliferation of the media or the endothelium. The absence of lipid deposits, the simultaneous appearance of arterial and venous lesions, and other evidence argues against and atheromatous origin of parietal lesions. A significant correlation has been found between high levels of anti-synthetic ethinyl estradiol antibodies and the presence of vascular lesions. It is hypothesized that these circulating immune complexes penetrate the vascular walls of OC users and produce lesions, which may depend on factors such as smoking.
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PMID:[Digestive complications of oral contraceptives: a case of extensive digestive necrosis in a young woman]. 647 54

Hyperlipidemia occurs in animals bearing tumors but the mechanism of its development is uncertain. We have measured triacylglycerol clearance and production rate in rats bearing a transplantable sarcoma. The plasma content of very-low-density lipoprotein triacylglycerol was increased in these tumor-bearing rats but our data excluded a primary clearance defect because the rate of triacylglycerol accumulation (mg/min) after Triton injection was equal to or greater than in normal control rats, except in cachectic rats with very large tumors. The fractional clearance of injected radioactive triacylglycerols was less in tumor-bearing rats than in controls, but the turnover (mg/min) was probably not decreased in the tumor-bearing rats because of their expanded plasma pool. Also inconsistent with a decreased turnover was our finding of a greater production of radioactive plasma triacylglycerols after injection of a tracer dose of radioactive free fatty acid, and unchanged production in Triton-treated rats. Therefore, in the fasted state, the hyperlipidemia of the tumor-bearing rats was associated with an unchanged or possibly an increased flux of hepatic triacylglycerols and a primary clearance defect was excluded. After fat-feeding, rats with tumors developed a higher post-prandial hyperlipidemia than control rats. Therefore, the clearance mechanism for the plasma triacylglycerols was close to saturation in the fasted state, and the added influx of exogenous triacylglycerols was removed less efficiently in the tumor-bearing rats.
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PMID:Hyperlipidemia in tumor-bearing rats. 647 46

Low dose estrogen tablets, containing less than 50 mcg of ethinyl estradiol, were formulated because of the recognized dose response relationship with the steroid content of the tablet and side effects. These new oral contraceptives (OCs) are as effective as the older high-dose OCs, and available evidence reports fewer side effects. This discussion reviews pharmacology of these new OCs, the mechanism of action, contraindications, side effects, and problems with the low-dose estrogen OC. Ethinyl estradiol is the only estrogen used in the low-dose combination OC. There are several synthetic progestins: norethindrone, norethindrone acetate, norgestrel, levonorgestrel, and ethynodiol diacetate. These progestins have different potencies so the pharmacologic activity cannot be accurately predicted based on the amount present in the tablet. The synthetic steroids in OCs are absorbed in the small intestine, metabolized in the liver, excreted in the bile and feces with a half-life of 24 hours. The low-dose estrogen combination preparation is taken 3 out of every 4 weeks. Its contraceptive effect is primarily a result of hypothalamic mediated gonadotropin suppression with subsequent inhibition of ovulation. Contraindications to taking the low-dose OC are the same as for the higher dose OC: thromboembolic or cardiovascular disease, estrogen dependent neoplasia, markedly impaired liver function, undiagnosed genital bleeding, congenital hyperlipidemia, pregnancy, and women over age 30 who smoke. Relative contraindications include hypertension, diabetes mellitus, migraine headaches, uterine myomas, and epilepsy. The often quoted 2-5-fold increased incidence of thromboembolic disease, myocardial infarction, and stroke is based on large epidemiologic studies involving patients taking the older higher dose OCs. Current data from patients taking the newer low-dose medication demonstrate minimal if any increased incidence of these problems in young women who do not smoke. The low-dose estrogen OCs have minimal effect on lipid levels. Early reports of patients using the low-dose OC have shown little if any increased incidence of hypertension. The low-dose contraceptives have little effect on glucose tolerance, and there is no evidence to show an increased incidence of overt diabetes in OC users. There is no evidence that use of the combination OC causes an increase in cancer of the cervix, uterus, or ovaries. Clinical complaints of nausea, breast discomfort, chloasma, weight changes, and depression are reduced with the low-dose estrogen preparation. Hypomenorrhea while taking the OC occasionally occurs because the lower dose of estrogen is insufficient to stimulate the endometrial growth in face of the predominant progestin-atrophy effect.
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PMID:Oral contraceptives in 1984. 649 Mar 38

Lipid content and lipoprotein lipase activity (LPLA) of serum and various tissues of mice bearing Ehrlich ascites tumor have been studied. The growing tumor caused hyperlipidemia, depletion of adipose tissue, a slight increase of heart lipid content, lipid accretion in the tumor cells and a relative increase of free fatty acids and cholesterol in the ascites fluid. LPLA of the post-heparin plasma was higher in tumorous than in control mice. Tumor growth led to a marked decline of LPLA in the adipose tissue and an elevation in the heart. It declined slightly in the older tumor cells and increased in the ascites plasma of the same. It has been concluded that: a) decline in adipose tissue LPLA may play an important part in the development of hyperlipidemia and loss of body fat; b) increase of the heart LPLA proves insufficient for elimination of the piled up blood lipids during progression; c) LPLA in the ascites fluid may favour the hydrolysis of triglycerides entering the ascites fluid, which might account at least in part for the fatty acids made available to the tumor; d) LPLA detected in the tumor cells might also facilitate the assimilation of lipids by the tumor cells.
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PMID:Changes in lipoprotein lipase activity (LPLA) in tumor cells and tissues in mice bearing Ehrlich ascites tumor. 652 66

Cancer patients have increased insulin resistance in skeletal muscles and probably also in the liver. The insulin production in response to a glucose challenge is decreased. This is associated with decreased glucose uptake in peripheral tissues and increased gluconeogenesis from amino acids, lactate, and glycerol. The correlation between the insulin response to a glucose challenge and the activities of glycolytic and oxidative rate-limiting enzymes in muscle tissue suggests a common denominator for these metabolic alterations. The most prominent feature in alteration of lipid metabolism is a reduction of body fat, probably dependent on increased lipolysis. The released fatty acids are oxidized outside the tumor mass. Species characteristics may be important for the degree of hyperlipidemia. Wasting of the skeletal muscle mass is caused by decreased protein synthesis and probably increased degradation. Anorexia can induce but not entirely explain this altered protein metabolism. Decreased physical activity may be another important factor for the depressed protein synthesis. Total parenteral nutrition (TPN) improves the muscle protein synthesis. The mechanism behind increased fractional degradation of muscle proteins in vitro is not clear, but it may be coupled to increased cathepsin D activity.
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PMID:Metabolism in peripheral tissues in cancer patients. 680 27

The author presents a hypothesis that the complex of endocrine and metabolic disturbances arising long before the development of endometrial carcinoma determines the biological peculiarities of the tumor, its clinical course, and the prognosis of the disease. On the basis of a prospective study of 366 patients with endometrial carcinoma, the author postulates that there are two different pathogenetic types of endometrial carcinoma. The first pathogenetic type of the disease arises in women with obesity, hyperlipidemia, and signs of hyperestrogenism: anovulatory uterine bleeding, infertility, late onset of the menopause, and hyperplasia of the stroma of the ovaries and endometrium. The second pathogenetic type of the disease arises in women who have no signs stated above or these signs are not clearly defined. The frequency of the first pathogenetic type in the studied group of women was 65%, whereas the frequency of the second type was 35%. The peculiarities outlined above which are characteristic of the first pathogenetic type of the disease determine the development of highly and moderately differentiated tumors (82.3% G1 and G2), superficial invasion of the myometrium (69.4%), high sensitivity to progestogens (80.2%), and favorable prognosis (85.6% 5-year survival rate). In patients who have the second pathogenetic type of endometrial cancer when endocrine and metabolic disturbances are absent or occult, poorly differentiated tumors arise (62.5% G3), a tendency to deep invasion of tumor into the myometrium is observed (65.7%); high frequency of metastatic spread into the pelvic lymph nodes (27.8%); decrease of sensitivity to progestogens (42.5%); and doubtful prognosis (58.8% 5-year survival rate) are noted.
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PMID:Two pathogenetic types of endometrial carcinoma. 682 61

A mammotropic pituitary tumor, MtT-F4, was implanted into male Fisher 344 rats for a period of 4 weeks. This tumor induced growth retardation, hyperlipidemia, hepatic hypertrophy and adrenal hyperplasia. Lipids were extracted from various tissues. In tumor-bearing rats, phospholipid concentration was found to be increased in plasma, spleen and testis. Distribution among the various phospholipid classes was similar to that of controls except in liver and heart, where phosphatidylcholine was increased at the expense of phosphatidylinositol and phosphatidylserine. The main difference was in the fatty acid composition of major phospholipids. The proportion of omega 6 fatty acids was lower and that of docosahexaenoic acid of the omega 3 series (22:6 omega 3) was higher in most tissues, especially in plasma, liver, heart and kidney. Concurrently, the urinary excretion of two endogenous metabolites of PGI2 (2,3-dinor-6-keto-PGF1 alpha and 6,15-diketo-13,14-dihydro-2,3-dinor-PGF1 alpha) was found to be increased significantly in tumor-bearing rats. The results raise the hypothesis that hormonal changes induced by the MtT-F4 tumor accelerate the conversion of arachidonic acid (20:4 omega 6) to prostaglandins. This effect, perhaps coupled with a diversion of linoleic acid (18:2 omega 6) towards other metabolic processes, would account for a partial depletion of membrane phospholipids in 18:2 omega 6 and for the reduced production of longer chain omega 6 unsaturated acids from 20:4 omega 6, creating a state of "relative essential fatty acid deficiency." As a result, the metabolism of omega 3 fatty acids is altered towards an enhanced production of 22:6 omega 3 which accumulates in the lipids of cell membranes to compensate for the depletion of unsaturated acids of the omega 6 series.
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PMID:Fatty acid composition of tissue phospholipids and prostaglandin excretion in hyperlipidemia induced in rats by implantation of the mammotropic pituitary tumor MtT-F4. 687 47

OC (oral contraception) can cause hypertension in a small minority, about 5%, of users. There does not seem to be a relationship between estrogen dosage and hypertension, while a relationship between progesterone and hypertension seems more possible. Hypertensive reaction to OC has been primarily seen in patients over 30; length of use is another important factor; the incidence after the 5th year of use is reputed to be 2.5-3 times higher than for the first year. Almost all women who develop hypertension with OC use will return to normal levels after OC termination. Several studies indicate a 4-fold to 6-fold increase in the risk of thrombosis and of thrombophlebitis among OC users and especially among woman over 35. OCs containing 50 mcg or less of estrogen can decrease the incidence of thromboembolic diseases by as much as 25%. It has also been reported that OC use before a surgical procedure increases the risk of postsurgical thromboembolism. Frequency of cerebral thrombosis, however rare, also seems to be higher in OC users, especially smokers. Risk of myocardial infarction is also higher among OC users especially in relation to age and smoking. A British study found that mortality rates among smokers were 10.2/100,000 pill users, versus 2.6 in nonusers in the age group 30-39; rates were 62.0 and 15.9 respectively in women over 40; duration of OC use is also a relevant factor. Absolute contraindications to OC use include any precedent of history of cardiovascular or cerebrovascular disease, impaired liver functions, any known or suspected form of neoplasia, genital bleeding, congenital hyperlipidemia, and obviously pregnancy. Relative contraindications include hypertension, migraine, epilepsy, varicose veins, diabetes, uterine leiomyomas, age over 35, and elective surgery. Potential OC users should be carefully screened to minimize possible risks. Age, health history, and smoking are extremely important. Starting OC with a dose lower than 50 mcg of estrogen is also advisable. A woman on OC should be seen every 6 months. Despite side effects and complications, OCs are the most effective and safest method of contraception a physician can offer.
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PMID:Complications and contraindications of oral contraception. 702 10


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