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  • 1
    ISSN: 1432-1440
    Keywords: Apolipoprotein E ; Familial dysbetalipoproteinemia ; Gemfibrozil ; Simvastatin ; Type III hyperlipoproteinemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Nineteen adult patients with type III hyperlipoproteinemia (HLP) and homozygosity for apolipoprotein (apo) E2 were treated with the 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitor simvastatin (20 or 40 mg per day) alone or in combination with the fibrate derivative gemfibrozil (450 mg per day) during a 30-week outpatient study. With the 20-mg dose (n = 19) the mean plasma cholesterol level decreased from 13.24±8.04 8.04 at baseline to 8.04±4.19 mmol/l (mean reduction 39.3%; P〈0.05), and the mean plasma triglyceride level decreased from 13.47±19.22 to 7.84±7.71 mmol/l (−41.8%; NS); this was due to a decrease in very low density lipoprotein (VLDL) cholesterol from 8.95±8.64 to 4.94±4.24mmo1/l (−44.8%; NS), a decrease in low density lipoprotein (LDL) cholesterol from 3.54±0.93to 2.25 ± 0.59 mmol/l (−36.5%; P〈0.01), and an increase in high density lipoprotein (HDL) cholesterol from 0.72±0.28 to 0.85±0.34 (+18.1%; NS). Thirteen patients were treated with 40 mg simvastatin per day. Under this regimen there was a further significant decrease in LDL cholesterol from 2.33±0.62 to 1.81±0.49 mmol/l (−22.3%; P〈0.01). In six patients who remained hyperlipidemic on monotherapy combination drug therapy with simvastatin (40 mg per day) and gemfibrozil (450 mg per day) was given. Compared to simvastatin alone the addition of gemfibrozil further lowered plasma concentrations of total cholesterol by 14.9%, VLDL cholesterol by 23.5%, and triglycerides by 17.1%, although this was not statistically significant. No patient was discontinued from single or combination drug therapy, and no severe clinical or biochemical side effects were observed. The results of this study demonstrate the usefulness of simvastatin in the therapy of type III HLP and indicate that in individual patients who remain hyperlipidemic on monotherapy combination drug therapy with both of these drugs is effective in further reducing plasma concentrations of total cholesterol, VLDL cholesterol, and triglycerides. Although no patient in this investigation developed myopathy or rhabdomyolysis, combined fibrate-HMG CoA reductase inhibitor treatment should be considered only for severe forms of hyperlipidemia and for patients who do not respond sufficiently to mon-therapy of any of these drugs.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 70 (1992), S. 614-617 
    ISSN: 1432-1440
    Keywords: Apoliprotein E ; Bezafibrate therapy ; Familial dysbetalipoproteinemia ; Genetic polymorphism ; Type III hyperlipoproteinemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a preceding paper, we described the molecular biological defects in a patient with a severe form of the familial lipoprotein disorder type III hyperlipoproteinemia (HLP) and an unusual apolipoprotein (apo) El phenotype and ɛ1/“null” genotype. The index case was a 60-year-old white male of German ancestry who suffered from a myocardial infarction at age 50 years. He had distinctly elevated levels of plasma lipids (triglycerides 551 mg/dl and cholesterol 747 mg/dl, respectively) and typical clinical signs of this inborn error of lipoprotein metabolism. His mutant apo E1 was shown to be identical to a rare (already described) apo E1 (Gly127→Asp, Arg158→Cys) variant. A second independent defect at the molecular level was a nucleotide deletion of a guanosine (G) in the codon for amino acid 31 of the proband's apo ɛ3 allele. This single base deletion (not described before) changed his apo ɛ3 allele to a nonfunctional “null” allele devoid of a stable gene product. Here we describe the response to combined dietary and medical treatment of the patient with this unusual form of type III HLP. His response to therapy was excellent, similar to patients with “classical” type III HLP and homozygosity for apo E2. However, the correct diagnosis of this familial lipoprotein disorder seems to be necessary, even in patients without the expected apo E2/2 phenotype, in terms of the prompt and beneficial response to therapeutic interventions.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 68 (1990), S. 65-70 
    ISSN: 1432-1440
    Keywords: Apolipoprotein E ; Bezafibrate therapy ; Chronic hemodialysis ; Familial dysbetalipoproteinemia ; Type III hyperlipoproteinemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two patients with severe hyperlipidemia receiving long-term hemodialysis were classified as type III hyperlipoproteinemic subjects. They are homozygous for apolipoprotein E2 and have an elevated VLDL-cholesterol/plasma-triglyceride ratio. The dyslipoproteinemia was severely aggravated by the renal failure, but careful treatment with bezafibrate was able to effectively lower elevated serum lipids. Accurate diagnosis of lipid abnormalities in patients with chronic renal failure seems to be necessary to plan appropriate therapeutic interventions and to lower the risk for accelerated atherosclerosis.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 71 (1993), S. 362-366 
    ISSN: 1432-1440
    Keywords: Apolipoprotein E ; Atherosclerosis ; Familial dysbetalipoproteinemia ; Genetic polymorphism ; Type III hyperlipoproteinemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The clinical and biochemical characteristics of type III hyperlipoproteinemia are described in 64 patients (35 males and 29 females). Homozygosity for apolipoprotein E2, the presence of an abnormally cholesterol-rich very low density lipoprotein fraction (β-VLDL) and an elevated ratio of very low density lipoprotein cholesterol to plasma triglycerides (〉0.3; normal ratio about 0.2) were the basis for the diagnosis. Mean serum cholesterol and triglyceride concentrations at the first visit in the clinic were 426 ± 221 and 719 ±996 mg/dl, respectively. The mean age at diagnosis of the disorder was 49 years in males and 53 years in females. There was a high prevalence of obesity (72%), xanthomas (42%), and atherosclerosis (39%), especially peripheral vascular disease (31%). Early and correct diagnosis of this familial lipoprotein disorder seems necessary because of the prompt and beneficial response to therapeutic interventions.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1440
    Keywords: Calcitonin ; Carcinoembryonic antigen ; Medullary thyroid carcinoma in vitro ; Organ culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tissue cultures of four C-cell carcinomas (medullary thyroid carcinoma, MTC) were prepared to study the basal and stimulated calcitonin (CT) and carcinoembryonic antigen (CEA) release. Immunohistological staining of the explants for CT and CEA have been performed after various periods of culture. These MTC explants were able continuously to release CT and CEA for periods up to 157 days. The spontaneous CT and CEA release decreased sharply during the 1st week of culture, then remained nearly constant over the observation period. The CEA/CT secretion ratio slightly declined during long-term culture; CEA release seems to drop earlier than CT production. CT and CEA could be detected in the same cells by immunocytochemical technique. The septal tissue consisting of dense connective tissue and amyloid produced by tumor cells seemed to increase during long-term culture. CT, but not CEA, was stimulated by pentagastrin (10−5 M), glucagon (6×10−6 M), and dose related by calcium (2.5–20 mM) in vitro. The MTC explant organ long-term culture proved to be a useful model for studies of human CT and CEA secretion.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Research in experimental medicine 160 (1973), S. 152-165 
    ISSN: 1433-8580
    Keywords: Pancreatic secretion in man ; Secretin ; Cholecystokininpancreozymin ; Hypercalcemia ; Hypocalcemia ; Calcitonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influences of acute changes of the serum calcium and of calcitonin (CT) on the exocrine pancreatic function have been studied in man. During stimulation with secretin and cholecystokinin-pancreozymin (CCK-PZ) Ca++-glucolactobionate, Na2-EDTA, porcine and human synthetic CT were infused i.v. Hypercalcemia provoked an increase of enzyme secretion under unstimulated and secretin stimulated conditions; however, in the case of CCK-PZ administration enzyme output was not altered. EDTA-hypocalcemia inhibited pancreatic secretion during secretin as well as during CCK-PZ infusions. CT doses above 2 MRCU caused a decrease of enzyme secretion during simultanous secretin/CCK-PZ administration by about 70–80% of the initial value without decreasing serum Ca++; doses of 0.5 MRCU and less were without effect. In none of the experiments bicarbonate secretion was affected. The results show important changes of the pancreatic enzyme secretion during acute hyper- and hypocalcemia, while calcitonin exerts an inhibitory effect during normocalcemia.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1433-8580
    Keywords: Rat pancreas ; Hypercalcemia ; Hypocalcemia ; Calcitonin ; Rattenpankreas ; Hypercalciämie ; Hypocalciämie ; Calcitonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die stimulierte exokrine Pankreasfunktion der Ratte läßt sich durch akute Hypercalciämie, ÄDTA-Hypocalciämie oder Calcitoningabe nicht beeinflussen. Dieses Verhalten steht im Gegensatz zur Reaktion des Magens der Ratte auf Calciumreize.
    Notes: Summary In the rat, stimulated exocrine pancreatic secretion is not influenced by acute hypercalcemia, EDTA hypocalcemia or calcitonin administration. This unresponsiveness is in contrast to the reaction of the rat stomach to calcemic challenges.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 6 (1970), S. 143-150 
    ISSN: 1432-0827
    Keywords: Calcitonin ; Bone ; Atrophy ; Formation ; Tetracycline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La patte arrière gauche de trente rattes Sprague-Dawley a été immobilisée par une attelle plâtrée. Dix rattes témoins ont été utilisées (groupe A): les 30 rattes plâtrées ont été réparties en 4 groupes. Le groupe B n'a pas reçu de traitement. Le groupe C a reçu, par injection sous-cutanée quotidienne, 50 MRC mU de calcitonine (préparée par les auteurs) dans 5% de gélatine. Le groupe D a reçu 5% de gélatine. Le groupe E a reçu 50 MRC mU de calcitonine (Ciba), dans 5% de gélatine par jour, en sous-cutanée. Après 6 jours, les fémurs et tibias ont été pesés, radiographiés et étudiés histologiquement. Les os du groupe A sont normaux. Les os des groupes B, C, D et E présentent une ostéoporose d'immobilisation du coté gauche, avec diminution de l'os trabéculaire, sans traduction radiologique. Le traitement à la calcitonine n'a pas inhibé l'ostéoporose. La pression exercée par les attelles plâtrées a induit une apposition périostée, au niveau de quelques tibias. Après traitement à la calcitonine, une apposition augmentée a été observée au niveau des fémurs et tibias. La gélatine, seule, n'a pas eu d'effet. Bien que la calcitonine n'ait pas agi sur l'ostéoporose d'immobilisation, elle semble pourtant favoriser les processus ostéogéniques provoqués par d'autres mécanismes.
    Abstract: Zusammenfassung 30 weibliche Sprague-Dawley-Ratten erhielten zur Immobilisation der linken hinteren Extremität einen Gipsverband. Die Tiere wurden in folgende 4 Gruppen unterteilt: B) keine Therapie. C) 50 MRC mE Calcitonin (eigene Präparation) in 5% Gelatine täglich s.c. D) Lösungsmittel in 5% Gelatine täglich s.c. E) 50 MRC mE Calcitonin (Ciba) in 5% Gelatine täglich s.c. Zusätzlich diente eine Gruppe ohne Gipsverband sowie ohne Therapie als Kontrolle (A). Nach 6 Wochen Versuchsdauer wurden die Femora und Tibiae geröntgt, gewogen und histologisch untersucht. In der Kontrollgruppe(A) bestand kein Unterschied zwischen rechter und linker Seite. In den Gruppen B, C, D und E hatte sich eine deutliche Immobilisationsosteoporose entwickelt (Rarefizierung der Spongiosa des Femurhalses), die röntgenologisch nicht nachgewiesen werden konnte. Die Therapie mit Calcitonin konnte diese Immobilisationsatrophie nicht verhindern. Der mechanische Reiz des Gibsverbandes erzeugte eine periostale Apposition in einigen Tibiae der Gruppen B und D. Nach Gabe von Calcitonin entwickelte sich diese periostale Neubildung in allen Femora und Tibiae der Gruppen C und E. Außerdem war das Ausmaß der Apposition unter Calcitonintherapie wesentlich größer. Das Lösungs-mittel allein hatte keinen Einfluß auf die beschriebenen Veränderungen. Calcitonin konnte die Entwicklung einer Immobilisationsosteoporose nicht verhindern, die Knochenneubildung nach Auslösung durch mechanische Einflüsse wurde dagegen wesentlich verstärkt.
    Notes: Abstract In thirty female Sprague-Dawley rats the left hind leg was immobilized with plaster casts. According to treatment they were divided into the following groups: A) Control, no casts. B) No treatment. C) 50 MRC mU calcitonin (own preparation) in 5% gelatin subcutaneously per day. D) Vehicle alone subcutaneously. E) 50 MRC mU calcitonin (Ciba) in 5% gelatin subcutaneously per day. In addition, untreated rats without casts served as control (group A). After 6 weeks the femora and tibiae were X-rayed, weighed and examined histologically. The bones of the left and right legs did not differ in control group A. In groups B, C, D, and E a disuse osteoporosis had developed in the left legs (rarefication of trabecular bone volume of femur neck) which could not be seen in X-rays. Calcitonin treatment did not prevent the development of the bone atrophy. However, the pressure of the plaster casts had induced a periosteal apposition in some tibiae, and under calcitonin treatment the extent of this new formation in all femora and tibiae was markedly increased. The vehicle alone was ineffective. It can be concluded that whereas calcitonin is without effect on disuse osteoporosis, it probably favours new bone formation which is induced by other mechanisms.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 133 (1980), S. 151-156 
    ISSN: 1432-1076
    Keywords: Calcitonin ; Parathyroid hormone ; Anticonvulsant bone disease ; Urinary cyclic AMP ; Urinary hydroxyproline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serum calcitonin (CT) levels and other aspects of calcium metabolism were investigated in 40 epileptic children receiving long-term treatment with phenytoin and/or other anticonvulsant drugs, and in 38 age-matched controls. In the patients CT levels were significantly lower. Immunoreactive parathyroid hormone (iPTH) was significantly elevated exceeding the upper limit of controls in 11 patients. We also observed a highly significant correlation between iPTH and urinary cyclic AMP (cAMP) excretion but a lack of such a correlation with the renal handling of phosphate; this indicates to us a dissociation between cAMP production and phosphaturia. A significant correlation between iPTH levels and urinary hydroxyproline excretion points to a normal action of PTH on bone in the patients. The low CT levels are not due to hypocalcemia and may be directly attributed to the effects of anticonvulsant drugs. As the primary effect of CT is a direct inhibition of PTH induced calcium loss from bone, the drug-related low CT levels in association with secondary hyperparathyroidism possibly is an additional factor in anticonvulsant bone disease.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 143 (1984), S. 112-116 
    ISSN: 1432-1076
    Keywords: C-cell-carcinoma ; Pheochromocytoma ; Neuroma ; Calcitonin ; Carcinoembryonic antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three patients with a sporadic form of multiple endocrine neoplasia (MEN) IIb are presented. MEN IIb is the association of medullary carcinoma of the thyroid (MTC), pheochromocytoma and multiple mucosal neuromata. The age at diagnosis and primary therapy of MTC was relatively late (8, 16, 18 years) although thyroid enlargement (two cases), typical marfanoid habitus (two cases) or multiple mucosal neuromata (one case) had been evident since early childhood. The diagnosis was confirmed by measurements of tumour markers like calcitonin (CT) and carcinoembryonic antigen (CEA) for MTC, measurements of vanillylmandelic acid for pheochromocytoma, evaluation of the thyroid gland by sonography, scintigraphy and fine needle biopsy, and investigation of the adrenals by computer tomography and meta-(I-131) iodobenzylguanidine (I-131-MIBG) scintigraphy. After surgical treatment determinations of tumour markers confirmed relapses of MTC in all cases. Early diagnosis of MEN IIb, which could be made by recognition of the typical clinical appearance, is of special importance because of the poor prognosis of MTC.
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