Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
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Repeatedly-bred, male and female Sprague-Dawley rats which develop hyperglycemia, hyperlipidemia, hypertension, and arteriosclerosis spontaneously were killed at sequential time intervals, i.e., when the females had completed 1, 2, 3 and 4 pregnancies. The control breeders received no treatment; the experimental animals were given 113 mg of clofibrate/100 g of b.w., subcutaneously, daily, 5 times per week. Clofibrate-treated breeders manifested reduction in blood pressure and in the incidence and severity of arterial disease characteristic of repeatedly-bred rats. The aortic lesions of the clofibrate-treated breeders showed attenuation of the usual severe ground substance alterations, the degenerative changes in connective tissue elements, e.g., fibrosis and elastosis, and absence of calcification and cartilaginous metaplasia. Clofibrate-treated breeders did not show any unusual elevation in serum enzymes, e.g., CPK, SGOT, SGPT and LDH, or significant reduction of their hyperlipidemia. They manifested a definite reduction in adrenocortical and medullary histopathology and their circulating corticosterone levels were subnormal compared to non-treated breeders. It is suggested that the protective effect of clofibrate was mediated through its ability to block normal adrenal steroidogenic pathways rather than through its antilipemic action.
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PMID:Clofibrate retardation of naturally-occurring arteriosclerosis in repeatedly-bred male and female rats. 66 83

A single s.c. injection (10 mg/100 g bw of alloxan) was given to nonarteriosclerotic, virgin, Sprague--Dawley rats and to breeder rats with preexisting arteriosclerosis, hyperlipidemia and hyperglycemia. All of the animals promptly developed severe diabetes with ketosis, hyperglycemia, and hyperlipidemia. Insulin therapy was deliberately withheld. Mortality was high. Seven days later one group was subjected to hypophysectomy and 30 days later, all of the animals were autopsied. The diabetes + hypophysectomy animals maintained their body weight better, did not have hypertrophied adrenal glands, showed the least elevation of serum enzymes, e.g., CPK, SGOT, SGPT and LDH, less hyperlipidemia and hyperglycemia and reduced corticosterone production than the animals with untreated severe diabetes. Despite the relative amelioration of metabolic derangements prognostic of cardiovascular degenerative changes, the diabetes + hypophysectomy animals manifested extensive renovascular damage and the breeder rats with pre-existing arteriosclerosis showed definite exacerbation of their arterial disease in response to the severe alloxan diabetes regardless of hypophysectomy. It is suggested that although hypophysectomy may alleviate certain metabolic derangements attributed to growth hormone, ACTH and adrenal steroids, the angiopathic damage proceeds inexorably.
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PMID:Effects of hypophysectomy on alloxan-diabetic, arteriosclerotic, breeder vs. non-arteriosclerotic, virgin rats. 98 94

We evaluated diagnostic utility of the hematological, biochemical and serological tests comprised in the "essential laboratory tests" advocated by the Japan Society of Clinical Pathology in 1,026 new patients visiting the outpatient unit of Comprehensive Medicine, National Defense Medical College. Of 750 evaluable patients, 52 showed anemia associated with such conditions as ulcer or cancer of digestive tract, inflammatory disease, or renal failure. Leukocytosis (greater than 9,000/microliters) was found only in 25 of 112 CRP-positive (greater than 0.3 mg/dl) patients, suggesting bacterial infection. Forty-four patients showed hypoproteinemia and/or hypoalbuminemia indicating chronic conditions including liver and inflammatory disease. Elevation of serum creatinine level was found in 4 patients subsequently diagnosed with renal failure, whereas 32 patients demonstrated elevated BUN. After application of the "essential laboratory tests", 97 patients were diagnosed with hyperlipidemia (total cholesterol greater than 230 mg/dl and/or triglyceride greater than 250 mg/dl). Determination of serum enzyme activity was useful not only for the diagnosis of liver dysfunction or biliary tract disease but also for those of hematological malignancies or myogenic disorders; however, in patients with abnormal values of LDH, gamma-GT and ALP, clinical significance was not clarified in 53%, 38% and 59%, respectively. These results indicate that the "essential laboratory tests" are useful in the following aspects of primary care medicine: for (1) estimation of the degree or nature of infection or inflammatory status; (2) classification of anemia and its relation to underlying diseases; (3) evaluation of patient general condition and protein-producible function of liver; (4) evaluation of renal function; (5) ambulatory screening for metabolic diseases such as hyperlipidemia; and (6) diagnosis of liver and biliary tract diseases.
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PMID:[Laboratory tests in primary care medicine: "essential laboratory tests" (2). Usefulness of hematological, biochemical and serological tests in diagnosis of new outpatients]. 159 65

A total of 108 patients with myocarditis and cardiomyopathies and 25 with chronic coronary disease (CCD) were investigated. The most informative diagnostic criteria were identified for the differentiation between noncoronarogenic myocardial disease (NMD) and CCD. Bicycle ergometry was positive in all CCD patients, whereas in those with NMD it was negative or had to be discontinued because of fatigue. NMD was associated with increased activity of transaminases, LDH and its isonenzymes (first and second fractions) and normal lipid spectrum. In CCD patients, enzyme activity was normal, and hyperlipidemia was detected in 88%. Coxsackie virus B2 was found in 24 of 58 NMD patients and only 3 of 25 patients with CCD. Echocardiography was effective in the diagnosis of cardiomyopathies. The diagnostic value of the patient's medical history is emphasized.
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PMID:[Differential diagnosis of myocarditis, cardiomyopathy and chronic ischemic heart disease]. 631 18

The effect of a four-week experiment on ten fa/fa Zucker rats (aged seven weeks at the beginning) fed on a lipid-rich diet (HL: 31 per cent w/w lipids, 45.6 per cent starch) was compared to that of a control diet (C: 10 per cent lipids, 66 per cent starch) on control Fa/- rats using a special pair-feeding apparatus that made it possible to obtain an identical intake rhythm. Energy level of the intake was significantly higher for the HL diet than for the C diet. At the end of the experiment, fa/fa rats remained obese and hyperlipemic, and still showed liver steatosis. With equal energy levels ingested, the obesity of fa/fa rats was comparable for both diets; hypertriglyceridemia and hypercholesterolemia were identical for both diets. When compared to the C diet, the HL diet modified neither their obesity nor their hyperlipemia. Obese rat liver on the HL diet showed lower levels for triacylglycerols, cholesterol, GGT, ALT, LDH and aldolase activities, while hepatic glycerol kinase and AST activities were higher than and comparable to, respectively, the C diet. Thus the HL diet led to a decreased liver steatosis for fa/fa rats as compared to the C diet.
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PMID:Influence of diet composition on obesity, hyperlipemia and liver steatosis in Zucker fa/fa rats pair-fed with Zucker Fa/- rats. 637 17

Virgin and breeder, spontaneously hypertensive and stroke prone rats (SHR/SP) were observed from weaning until 130 +/- 10 days of age. Blood pressure rose rapidly, reaching 230--240 mm Hg. After the birth of the second litter of pups, male and female breeders began to die suddenly, due to myocardial necrosis and congestive heart failure. At autopsy, the brains of virgin and breeder SHR/SP were swollen but were free of any pathologic changes. There were no significant alterations in the blood chemistry of virgin rats but breeder SHR/SP had super-normal enzyme levels, CPK, SGOT, SGPT and LDH, hyperglycemia, hyperlipidemia, and hypersecretion of corticosterone. Breeder SHR/SP developed PAN-like lesions of the mesenteric arcades and adrenal cortex along with severe fibrino-hyalin lesions of the testicular and ovarian arteries. It is suggested that alterations in hypothalamic-pituitary-adrenal function associated with the reproductive effort conditioned these SHR/SP to develop myocardial necrosis rather than stroke and the development of unusual hypertensive arteriopathy.
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PMID:Myocardial necrosis induced by breeding in stroke-prone/SHR. 721 76

A genetic variant of the spontaneously hypertensive rat (SHR) has been produced which becomes markedly obese as well as hypertensive, i.e. Obese/SHR weigh 800 g as against 300 g for non-obese cohorts. Serum enzymes (CPK, SGOT, SGPT and LDH) are frequently abnormally elevated, concomitantly with a high incidence of myocardial necrosis. Obese/SHR are hyperlipidaemic with severe fatty infiltration of the liver; they are hyperglycaemic with enormous islets of Langerhans and extensive beta-cell degranulation; despite elevated blood urea nitrogen (BUN) levels, they manifest little or no renal damage. Measurement of corticosterone, deoxycorticosterone (DOC) and aldosterone in Obese/SHR demonstrate marked hyper-responsiveness to moderate stress. Circulating prolactin levels are lower in Obese and non-obese/SHR compared to SHR, but Obese/SHR manifest unusually high increases incirculating prolactin levels in response to stress. Obese/SHR are hyperinsulinaemic and have subnormal growth-hormone levels. Desite mild hypertension, hyperglycaemia and hyperlipidaemia, Obese/SHR show no evidence of atheromatous change but do develop early polyarteritis nodosa. It is believed that the genetically programmed hypertension and hyperglycaemia is mediated by increased DOC, aldosterone and corticosterone production respectively, and that the obesity, hypertension, and diabetes in Obese/SHR may be likened to human Cushing's disease.
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PMID:Pathophysiological differences between obese and non-obese spontaneously hypertensive rats. 742 76

Polymerized hemoglobin solutions (Hb-based oxygen carriers; HBOCs) and a second-generation perfluorocarbon (PFC) emulsion (Perflubron) are in clinical trials as temporary oxygen carriers ("blood substitutes"). Plasma and serum samples from patients receiving HBOCs look markedly red, whereas those from patients receiving PFC appear to be lipemic. Because hemolysis and lipemia are well-known interferents in many assays, we examined the effects of these substances on clinical chemistry, immunoassay, therapeutic drug, and coagulation tests. HBOC concentrations up to 50 g/L caused essentially no interference for Na, K, Cl, urea, total CO2, P, uric acid, Mg, creatinine, and glucose values determined by the Hitachi 747 or Vitros 750 analyzers (or both) or for immunoassays of lidocaine, N-acetylprocainamide, procainamide, digoxin, phenytoin, quinidine, or theophylline performed on the Abbott AxSym or TDx. Gentamycin and vancomycin assays on the AxSym exhibited a significant positive and negative interference, respectively. Immunoassays for TSH on the Abbott IMx and for troponin I on the Dade Stratus were unaffected by HBOC at this concentration. Tests for total protein, albumin, LDH, AST, ALT, GGT, amylase, lipase, and cholesterol were significantly affected to various extents at different HBOC concentrations on the Hitachi 747 and Vitros 750. The CK-MB assay on the Stratus exhibited a negative interference at 5 g/L HBOC. HBOC interference in coagulation tests was method-dependent-fibrometer-based methods on the BBL Fibro System were free from interference, but optical-based methods on the MLA 1000C exhibited interferences at 20 g/L HBOC. A 1:20 dilution of the PFC-based oxygen carrier (600 g/L) caused no interference on any of these chemistry or immunoassay tests except for amylase and ammonia on the Vitros 750 and plasma iron on the Hitachi 747.
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PMID:Effect of hemoglobin- and Perflubron-based oxygen carriers on common clinical laboratory tests. 929 68

A 7-year-old previously healthy Czech boy was admitted due to fever, hepatosplenomegaly and pancytopenia. Aspiration of bone marrow revealed no signs of hemoblastosis (nor hemophagocytosis). He was treated with antibiotics and virostatics without effect. Progression of hepatosplenomegaly and pancytopenia induced suspicion of hemophagocytic lymphohistiocytosis (HLH). Five weeks later, bone marrow hemophagocytosis of erythrocytes, nuclear elements and platelets was detected. He was given corticoids and intravenous immunoglobulins and transferred to our haematology department. Laboratory findings of mild pancytopenia, hypofibrinogenaemia, hyperlipidaemia and elevated levels of ferritin, LDH and immunoglobulins were compatible to the diagnosis of HLH. Immunologic evaluation revealed T-lymphocyte activation. Appropriate immunosuppressive treatment with Dexamethasone, etoposide and Cyclosporine A was launched, followed by transient subside of fever and improvement of peripheral blood count, but not regression of hepatosplenomegaly. Four weeks later, relapse of fever and deterioration of blood count led to intensification of immunosuppression. However, no effect was evident. Moreover, hypertrophic cardiomyopathy with ventricular arrhythmia occurred. Treatment with antilymphocytic globulin for resistant course of HLH was planned. Before that, a fifth bone marrow aspiration was performed. Surprisingly, many Leishmania amastigotes were observed within marrow macrophages. Leishmania infection was confirmed by positive serology. Immunosuppressive treatment was withdrawn and changed for causal treatment with liposomal Amphotericin B. Positive clinical effect with subside of fever was evident in ten days, splenomegaly gradually resolved during three weeks, restoration of normal blood count lasted six weeks. No relapses of HLH nor leishmaniasis occurred. In control bone marrow aspirate performed three months later, the parasites were not detected. Ten months after the event, the patient is in complete remission of HLH with normal immunologic parameters. Most probably, he contracted visceral leishmaniasis during a visit of a Neapol area in Italy 3 months before the onset of the disease.
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PMID:[Hemophagocytic lymphohistiocytosis as a manifestation of visceral leishmaniasis]. 1242 69

A retrospective survey was performed to establish patient and graft outcome for all 41 patients at our centre receiving sirolimus (SRL) in combination with calcineurin inhibition (CNI) as primary therapy for the 6 years prior to March 2002. Patient mortality [12%; n = 5 (TTP, lymphoma, mucormycosis, and small bowel perforation] was significantly higher at 3 months compared with those not receiving SRL, but not thereafter. 12.8% had delayed graft function and 33% had one or more episodes of rejection in the first 6 months. Mean GFR at 12 months was significantly lower (47.3 mL/min) in the SRL group compared with those not receiving SRL (51.3 mL/min). Twenty-two patients had a 12-month protocol biopsy; CNI toxicity was present in 36%. SRL was associated with significant hyperlipidaemia (serum cholesterol, 5.2 +/- 1.4 at baseline vs 7.3 +/- 1.7 mmol/L at 3 months, P <.001; triglycerides, 2.3 +/- 1.4 at baseline vs 2.7 +/- 1.1 mmol/L at 3 months, P <.05). Mild thrombocytopenia occurred in 23% but was not associated with haemorrhagic events. LDH increased by 62%, remaining elevated out to 2 years post engraftment. Seven patients developed insulin requiring diabetes mellitus, similar to the rate observed in our general transplant population.Thus, in this early experience, SRL in combination with CNI was associated with significant mortality and morbidity including CNI toxicity, presumably a reflection of a heavy burden of immunosuppression. However, 1-year graft survival on SRL was similar to the mean Australia-wide graft survival regardless of immunosuppression. The future use of SRL may center around CNI sparing and avoidance type protocols.
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PMID:Sirolimus: a single center experience in combination with calcineurin inhibitors. 1274 76


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