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Query: UMLS:C0020473 (hyperlipidemia)
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Univariate and bivariate analyses of cholesterol and triglycerides are performed after appropriate age adjustment on 247 individuals in 33 families where the probands have elevations of cholesterol, low density lipoprotein and triglycerides, and type IIb lipoprotein phenotype. Mixture of lognormal distributions are fitted by maximum likelihood to the data. Best fitting single and mixtures of lognormal distributions are compared with empirical cumulative plots, and the likelihood-ratio criterion is used to test for significance. A mixture of two lognormal distributions fits significantly better than one lognormal distribution for cholesterol but not for triglycerides. When a mixture of bivariate lognormals is fitted to the data, only one local maximum is found, suggesting action of a single genetic determinant in this sample. The best cutoff line is almost parallel to the triglyceride axis, indicating the relatively high involvement of cholesterol compared to triglycerides in separating the normal and abnormal groups. Using the best linear function, the difference in the two bivariate means is found to account for 61% of the total variation in log cholesterol and log triglycerides. To determine if the results are due to enrichment of the sample with familial hypercholesterolemia syndrome, seven families where the proband and/or any relative has tendon xanthomas are removed and the analyses repeated on the remaining 26 kindreds. The results of these analyses are virtually the same as those of the total sample. Also, a subsample of 21 families in which the proband and at least one additional kindred member are affected is analyzed in the same manner with similar results. For comparison, data from a study of families with combined hyperlipidemia [1] are analyzed in an analogous manner, bearing in mind that the populations sampled are probably different. Fitting a mixture of two bivariate distributions and finding the best cutoff to these data indicate that triglycerides are more involved in separating the two groups. Probably because of major differences in ascertainment, the distribution of lipid levels in oour patient group is practically indistinguishable from that of hypercholesterolemia, and the Seattle data [1] are more nearly similar to hypertriglyceridemia. It may be premature to consider familial combined hyperlipidemia as an entity distinct from both hypercholesterolemia and hypertriglyceridemia. We hope it will eventually be possible to analyze these data using a refined genetic model that includes both major gene and polygenic effects and to combine this form of analysis with quantitative tissue culture methods.
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PMID:Bivariate analyses of cholesterol and triglyceride levels in families in which probands have type IIb lipoprotein phenotype. 16 68

A general linear model is presented here for biological and cultural inheritance involving ten parameters to be estimated from 16 correlations in nuclear families, providing ample degrees of freedom to test goodness of fit. Applied to six lipoprotein traits the model fits acceptably to all, although there is evidence of transient maternal effects for cholesterol and lipemia. Genetic heritability in children ranges from 0.175 for triglyceride to 0.562 for total cholesterol. Cultural heritability in children ranges from 0.012 for VLDL to 0.149 for HDL-cholesterol.
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PMID:Cultural and biological determinants of lipoprotein concentrations. 47 34

Diabetes mellitus occurs in many animals species. However, only a few have been utilized in systematic studies designed to answer unsolved problems associated with the disorder in man such as molecular basis, pathogenesis of the vascular and neural lesions, and the roles of diet, exercise and obesity. Among the animal models available, rodents have been studied most thoroughly for a number of reasons: a) short generation time (sexually mature at about 3 mo of age, gestation time 21 days) and life-span is approximately 3 yr; b) hyperglycemia and/or obesity is known to be inherited in several species; c) environmental factors can be controlled easily in the laboratory because of small size; and d) economic considerations. The better-known rodent diabetes/obesity syndromes may be categorized as follows: 1) hyperglycemic with ketoacidosis, nonobese (Chinese hamster, South African hamster); 2) hyperglycemic with insulin hypersecretion, moderate obesity and may develop ketoacidosis (diabetic mouse (db/db), spiny mouse, sand rat); and 3) less pronounced hyperglycemia with hyperinsulinemia, insulin "resistance" and marked obesity (obese (ob/ob), yellow (Ay) and New Zealand obese (NZO) mice, and the Zucker "fatty" rat). The PBB/Ld mouse, described here in detail for the first time, is a new strain of mouse that also fits into the latter category. Members of this strain following maturity develop an obesity that is characterized by increasing cellularity of adipose tissue, increased serum immunoreactive insulin, reduced glucose tolerance, fatty liver, and hyperlipidemia. Therefore, this strain of mouse represents another model for study of adult onset obesity.
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PMID:Animal models of diabetes and obesity, including the PBB/Ld mouse. 77 Jan 97

Twenty-six patients under 20 years of age having cerebrovascular disease were studied from 1968 to 1972. Common risk factors such as hypertension, diabetes mellitus, hyperlipidemia and heart disease were not present. Angiographical study showed a variety of abnormalities. No consistent defect was present. There was a high incidence of pyrexia and convulsions in the early stages of stroke and it appears possible that some form of arteritis might have been important in the production of the cerebral infarction.
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PMID:Stoke in the young: a four-year study, 1968 to 1972. 115 68

36 original cases, 24 from the Hopital de Sainte-Anne in Paris and 12 from the surrounding region, of ischemic (30) or hemorrhagic (6) strokes in women taking oral contraceptives are reported. The patients were 20-55 years, half under 30; took various types of pills from 10 weeks to 10 years, mean 28 months; 30 of them for contraception but other for migraine, Reclus disease, amenorrhea, sterility, and endometri osis. 27 women had related history: ischemic vascular accident (5), hyp ertension (5), thromboembolism (4), Basedow disease (3), heavy smoking (3), essential comitiality (2), migraine (1), essential hyperlipidemia (1). The women with ischemic strokes were younger, 61% under 30. A 3rd had premonitory symptoms like headache, progressing rapidly to massive hemiplegia in 17, discrete hemiplegia in 11, loss of consciousness in 6, and convulsions in 3. The cerebrospinal fluid was clear in 11 cases tested. Angiography revealed lesions in the internal carotid in 4, sylvian arteries in 9, posterior cerebral in 1, but no anomaly in 8. Only 5 recovered completely: 3 died and 7 retained major neurologic dysfunction. 6 women had hemorrhagic strokes, 2 intracerebral hematomas, and 4 cerebromeningeal hemorrhages. 5 were operated on, 3 with good results and 2 were left with severe neurologic sequelae. The authors insisted that none of these women had been given any preliminary tests or followed with any attention to their related history while taki ng oral contraceptives.
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PMID:[Cerebrovascular accidents and oral contraceptives (reflections a propos of 36 observations)]. 121 91

We report the results of 510 periodical health examinations in adults aged 16-60 years (43% males and 57% females), carried out by the nursing staff in our center (belonging to the PAPPS of the SEMFyC). In the results there was a remarkably high rate of risk factors: 46.6% of obesity, 46% of smokers, 40% of sedentarism, 20% of hyperlipidemia, and 5.1% of hypertension. There was a higher prevalence of smokers among the female population between 15-44 years of age; 6.3% of the surveyed population consumed more than 50 g of alcohol/day, 3.7% had abnormal urine reactive strips and 1.6% had abnormal carbohydrate metabolism. In our experience, the periodical health examination perfectly fits the role of nurses and is well accepted by the population.
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PMID:[Results of periodic health examinations in an adult population aged 15-60 years]. 188 63

Dementias which are either reversible or avoidable are discussed in the light of the literature. The frequency is between 6 and 32%. The most important etiological groups are immunological vasculopathies, hyperlipidemia, some types of encephalitis and, mainly, progressive dementia of the insane, benign tumors and in particular meningioma, low pressure hydrocephalus, intoxications due to drugs, industrial products and alcohol, metabolic disturbances, encephalopathy in dialysed patients, ileo-jejunal-bypass encephalopathy and encephalopathy due to neoplasms. Dementias are also seen in endocrinological disturbances and particularly in hypothyroidism. Vitamin B12 and folate deficiency, as well as epilepsy, may be causes of dementia. Depression may mimic a state of dementia. Some features of reversible dementias are listed, including in particular the somewhat more rapid onset, the younger age of patients, and accompanying neurological symptoms such as headache, gait disturbances, ataxia, polyneuropathy, myoclonus or epileptic fits.
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PMID:[Reversible and preventable dementias]. 361 87

A new non-linear mathematical model was constructed in order to perform in vivo quantification of the RES phagocytic function. This method is based on the same technical facilities as used for the routine liver-spleen scintigraphy with radiocolloids [1, 2]. But kinetic modeling of dynamic Tc-99m-sulfur colloid data produced estimations of the functional RE-parameters: the clearance rate of the colloidal particles, the rate of phagocytosis, and the RES functional volume, which can not be obtained by classical approaches. This non-linear model was designed on the basis of the principal characteristics of particulate material interaction with macrophages (attachment, phagocytosis, digestion) [3, 4, 5]. The theoretically examined behavior of this in vivo mathematical model corresponds with the experimental behavior of the RES. The mathematical expression of the dynamics is the system of non-linear differential equations with constant coefficients that have no analytical solution. Fitting of the normalized heart blood time-activity curve was obtained to identify the unknown model parameters via non-linear regression. For this purpose general interactive PASCAL procedure IDPAR for a PDP-11/34 computer was used (an IBM PC version is also available). Two to three iterations were needed to estimate the set of unknown parameters for any patient study (1-1.5 min). A very good fitting was obtained between experimental and model curves in every case of different pathologies (error of the approximation is about 2-3%). Studies were performed using an in vivo bolus injection of 3.6 mg/80 kg commercially available colloid KOREN labeled with 3m-Ci 99m-Tc (analog of TCK-1). Our method was used to determine the RES functional parameters for patient groups with different levels of the RES dysfunction. Obtained results illustrate the possibilities of our technique to quantitatively estimate not only great pathology (portal cirrhosis), but also small changes of the RE-function (case of hyperlipidemia and ulcer gaster). In all patient groups marked changes of Tc-99m-sulfur colloid turnover were observed. In general, tracer clearance from the circulation was decreased, and the rate of phagocytosis and the RES volume were diminished compared with controls. The effect of a reduction of phagocytosis increases when the RES dysfunction becomes stronger. It can be shown that a non-parametric Wilcoxon-Mann-Whitney test gives a significant difference (P95%) for these patient groups. Further, we represent the possibility of using the model for monitoring changes of the RES-function parameters during and after therapy. The quantitative test of the RES function can significantly enhance the diagnosis and management of different diseases. Serial colloidal studies may document changes in the RES-function for the tumors, cirrhosis, hyperlipidemia, reticulosis, hepatitis, thrombosis, infection, AIDS, burn injury, shock and trauma patients. The technique may be useful for the different RES investigations with laboratory animals. Created computer software can be used as a tool for kinetic models, simulation, and unknown parameters identification.
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PMID:A non-linear mathematical model for the in vivo evaluation of the RES phagocytic function. 859 76

Atherogenesis is a disease of middle-sized and large-caliber blood vessels that can be divided into three major phases. The initial lesions of early atherosclerosis are characterized by the adhesion and subendothelial emigration of blood-borne monocytes, which differentiate into macrophages and provide the morphologic basis for the formation of foam cells and fatty streak lesions. These lesions are found in most children and teenagers in industrialized nations. The next key event in atherogenesis is the proliferation of smooth muscle cells within the intima and media, resulting in the gradual compromise of the vessel lumen. Myofibroblastic cells also contribute to lesion growth through the production of excessive amounts of extracellular matrix. Such lesions are clinically silent unless progression to the next phase continues: the lesions degenerate, forming a mostly necrotic "lipid core" consisting of extracellular lipid, cholesterol crystals, inflammatory cells and necrotic debris. A fibrous cap is formed which prevents the interaction of blood cells, particularly of platelets with the highly proaggregatory material found in the lipid core. However, continuous inflammatory activity and/or heightened mechanical stress (i.e., in hypertension) tends to weaken the fibrous caps. Eventually, plaque rupture ensues, platelets aggregate, and the lesions become clinically manifest in such dramatic events as myocardial infarction, stroke, or mesenteric ischemia. Research into lesion formation and progression is limited by the fact that lesions develop in silence over many decades and that animal models only incompletely model the situation in humans. Most currently debated concepts accept the "response to injury" hypothesis formulated by the late Russell Ross and the multi-factorial nature of atherogenesis. The discussion today circles around the relative contributions of low density lipoproteins (oxidized or enzymatically modified LDL?), the immune response (adaptive or innate?), infectious agents (CMV, Chlamydia pneumoniae?), and/or hereditary factors, to name only a few of the most widely debated concepts. Irrespective of the outcome of this pathomechanistic discussion, the knowledge of established risk factors (hypercholesterolemia, hypertension, diabetes, smoking, etc.) and protective interventions (lifestyle changes, physical exercise, "healthy" diets, effective dietary and pharmacologic control of hyperglycemia, blood pressure or hyperlipidemia) has helped to define atherosclerosis as a "new entity" that has little to do with the archaic concept of a "degenerative" vessel disease. The new concept takes us into the responsibility--puts us in charge of our own and our patients' cardiovascular risk--whether we like it or not. The smoking obese doctor no longer fits into the modern medical landscape.
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PMID:[Atherosclerosis--progression by nonspecific activation of the immune system]. 1197 79

PCOS is a metabolic syndrome that exists throughout the world with much clinical heterogeneity. PCOS is now appreciated as encompassing two interrelated metabolic phenomena--insulin resistance and hyperandrogenism. Patients present with oligo-amenorrhea and clinical hyperandrogenism, and the diagnosis is based on clinical grounds with few laboratory tests necessary. Because patients are at higher than normal risk for diabetes, glucose intolerance, and hyperlipidemia, and perhaps at higher risk for coronary heart disease, newly diagnosed patients with PCOS should be evaluated for glucose intolerance and hyperlipidemia. The cornerstone of therapy today includes weight management, and further therapeutic intervention is focused on reproductive and cardiovascular health and treatment of insulin resistance. Clinical case continued The 17-year-old mentioned in the beginning of this article probably does have PCOS. She fits the clinical criteria: oligo-ovulation and hyper-androgenism (the acne and hirsutism). In addition, she is obese, which is also associated with PCOS. Her TSH and prolactin were normal, and as her presentation was not suggestive of an adrenal tumor or congenital adrenal hyperplasia (she had mild hirsutism, and those diagnoses are associated with more severe hyperandrogenism), no further laboratory evaluation was deemed necessary. Once the diagnosis was made, she was screened for lipid abnormalities and for glucose intolerance. Her LDL was 150, HDL 35; oral glucose tolerance test (OGTT) was normal. A pregnancy test was negative, and she was started on OCPs. Devoting herself to exercise and dietary change, she lost 10 pounds in her first 3 months after diagnosis. Her hirsutism and acne have improved with the OCPs and weight loss, and her menses are regular. She has elected to defer oral insulin sensitizers until her weight loss has stabilized. Findings PCOS is common in reproductive-aged women. Diagnosis is clinical and is supported by lab findings; there is significant clinical heterogeneity. Insulin resistance is likely central to the pathophysiology along with androgen excess. Health implications include infertility, diabetes, endometrial cancer, hyperlipidemia, and possibly coronary heart disease. Treatment is evolving and includes weight loss, OCPs, and insulin sensitizers.
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PMID:Polycystic ovary syndrome: a review for primary providers. 1502 92


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