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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 16 (1974), S. 145-152 
    ISSN: 1432-0827
    Keywords: EHDP ; Bone ; Chemistry ; Serum ; Rabbits
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The effects of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on bone and serum chemistry were investigated in adult rabbits. EHDP was administered by subcutaneous injection at doses of 0.25, 2.5 and 10 mg/kg body weight/day for of 28 days. Blood samples were obtained weekly from each rabbit and serum levels of total calcium, ionized calcium, inorganic phosphate and alkaline phosphatase were determined. At the end of the treatment period all rabbits were sacrificed and the tibiae removed for chemical analysis and histological evaluation. The effect of EHDP administration on serum chemistry was both dose- and time-related. The highest of the three doses, 10 mg/kg/day, resulted in a time-related decrease in total serum calcium. This dose also caused a rapid but transient reduction in serum ionized calcium. The effect of EHDP on serum inorganic phosphate was biphasic. Administration of 2.5 mg/kg/day resulted in a time-related elevation in this parameter, whereas the 10 mg/kg/day dose resulted in a time-related hypophosphatemic response. There were no significant drug-related changes in tibial fat-free dry weight, ash weight, total calcium or total phosphorus values. However, administration of 2.5 and 10 mg/kg/day EHDP resulted in increased osteoid tissue as measured histologically. These results are compared with data from other EHDP studies, and discussed in relation to the maturity and growth-state of the experimental animals.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 14 (1974), S. 3-14 
    ISSN: 1432-0827
    Keywords: Hydroxyapatite ; Mineral ; Phase ; Chemistry ; Synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des diagrammes de phase d'équilibre ont été déterminés pour le système CaO-P2O5-H2O en utilisant des techniques de synthèse hydrothermique au cours de variatio nsde température allant de 300–600° et 2 Kb H2O de pression. De l'hydroxyapatite bien cristallisé a été synthétisé et caractérisé. De faibles variations de paramètres de la maille cristalline, liées à la température de synthèse et composition globale du matériel initial, ont été déterminées. Des conditions chimiques précises sont nécessaires pour obtenir de l'apatite, en tant que seule phase solide en équilibre dans la solution. Les résultats de diagramme de phase d'équilibre sont comparés avec ceux obtenus dans des milieux synthétiques.
    Abstract: Zusammenfassung Es wurden Gleichgewichts-Phasendiagramme für das System CaO-P2O5-H2O bestimmt, indem hydrothermale Synthese-Techniken im Temperaturbereich von 300–600° und bei einem Druck von 2 Kb H2O verwendet wurden. Es wurde gut-kristallisiertes Hydroxyapatit erzeugt und charakterisiert. Es wurden geringe Unterschiede in den Parametern der Zelleinheiten festgestellt, welche von der angewandten Temperatur und der Zusammensetzung des Startmaterials abhingen. Es waren genaue chemische Bedingungen nötig, um Apatit als die einzige feste Phase im Gleichgewicht mit der Lösung zu erhalten. Die Resultate der Gleichgewichts-Phasendiagramme werden mit früheren Untersuchungen mit der Synthesetechnik verglichen.
    Notes: Abstract Equilibrium phase diagrams have been determined for the system CaO-P2O5-H2 using hydrothermal synthesis techniques in the temperature range 300–600° and 2 Kb H2O pressure. Well-crystallized hydroxyapatite has been produced and characterized. Small variations in unit cell parameters dependent on temperature of synthesis and bulk composition of the starting materials have been determined. Precise chemical conditions were required to obtain apatite as the only solid phase in equilibrium with solution. Equilibrium phase diagram results are compared with previous synthetic investigations.
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  • 3
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    Calcified tissue international 7 (1971), S. 150-162 
    ISSN: 1432-0827
    Keywords: Uranium ; Bone ; Distribution ; Fission ; Chemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Une concentration moyenne de 2.4×10−8 g U/g de cendre a été obtenue à partir de l'os humain normal. La microdistribution de l'uranium dans l'os indique que cet élément est surtout limité à surface de l'endoste et, en particulier, aux surfaces de l'os lamellaire et aux parois des canaux de Havers, ouverts dans l'os corticol. Cette répartition suggère que l'uranium se présente sous une forme chimique impropre à son incorporation dans l'apatite osseux: il ne semble donc pas exister une distribution diffuse significative de l'uranium dans l'os.
    Abstract: Zusammenfassung Eine mittlere Konzentration von 2,4×10−8 g Uran/g Asche wurde in normalen menschlichen Knochen gefunden. Die Feinverteilung von Uran im Knochen zeigt, daß dieses Element hauptsächlich an der endostalen Oberfläche vorkommt, insbesondere an der Oberfläche des trabeculären Knochens und an den Wänden der offenen Haversschen Kanäle im kortikalen Knochen. Diese Verteilung läßt vermuten, daß Uran in einer chemischen Form vorliegt, welche sich für den Einbau in das Knochenapatit nicht eignet. Daraus folgt, daß keine signifikante diffuse Verteilung des Urans innerhalb des Knochens vorliegt.
    Notes: Abstract A mean concentration of 2.4×10−8 g U/g ash has been obtained for normal human bone The microdistribution of uranium in bone indicates that this element is mainly restricted to endosteal surfaces; in particular the surfaces of trabecular bone and the walls of open Haversian canals in cortical bone. This distribution suggests that uranium is present in a chemical form that is not acceptable for incorporation into bone apatite and consequently there does not appear to be a significant diffuse distribution of uranium throughout bone.
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  • 4
    ISSN: 1432-0827
    Keywords: Morphology ; Glycosaminoglycans ; Cartilage ; Chemistry ; Audioradiography ; Healing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Une perte de substance ostéo-cartilagineuse, de taille limitée et identique, est réalisée chez le lapin adulte et la cicatrisation est étudiée histologiquement et par autoradiographie après marquagein vitro au35S-sulfate. Une analyse microchimique est pratiquée pour le contenu et la composition en glycosaminoglycanes. 1. Entre la première semaine et la 4ème et 8ème semaine, un tissu conjonctif non-métachromatique se différencie en un cartilage métachromatique et la quantité de sulfate de chondroitine augmente de façon significative aux dépens des glycoprotéines. 2. Jusqu'à la 4ème semaine, la perte de substance est surtout comblée par de l'os néoformé: après cette période, la région est comblée au delà de la limite de la surface articulaire. 3. Le cartilage hyalin, ressemblant morphologiquement, autoradiographiquement et chimiquement au cartilage articulaire, en ce qui concerne la distribution en glycosaminoglycanes, constitute la surface articulaire de la perte de substance comblée dans un tiers des cas après 8 semaines. Le cartilage hyalin s'observe surtout dans les régions où de l'os néoformé a comblé la cavité médullaire. 4. Dans les deux tiers des cas, après 8 semaines, les surfaces articulaires des zones comblées comportent, non seulement du cartilage, mais aussi du tissu fibreux se formant essentiellement sur les parties latérales et dans les régions, où la cavité médullaire, fliant face, à la surface articulaire, n'a pas été comblée par du tissue osseux. La fraction glycoprotéique augmente par rapport à la fraction chondroitine sulfate. 5. Dans la majorité des cas, après 20 semaines, le cartilage néoformé subit des phénomènes dégénératifs, qui se traduisent par une diminution en chondroitine sulfate.
    Abstract: Zusammenfassung Bei ausgewachsenen Kaninchen wurde ein begrenzter, standardisierter, osteochondraler Defekt hervorgerufen, und das regenerierte Gewebe wurde histologisch und autoradiographisch durch Markierung in vitro mit35S-Sulfat und durch mikrochemische Bestimmung des Gehaltes und der Zusammensetzung der Glykosaminglykane untersucht. Die wichtigsten Befunde waren: 1. Zwischen 1 und 4–8 Wochen veränderte sich nichtmetachromatisches Bindegewebe zu metachromatisch gefärbtem Knorpel, und der Anteil an Chondroitin-Sulfat nahm auf Kosten der Glykoproteine signifikant zu. 2. Bis zu 4 Wochen war der Hauptteil des defekten Gebietes mit neugebildetem Knochen gefüllt; nach dieser Zeit lag dieser Bezirk oberhalb der Verknöcherungsgrenze in Richtung der Gelenkoberfläche. 3. Nach 8 Wochen bestand die Gelenkoberfläche des defekten Gebietes in einem Drittel der Fälle aus hyalinem Knorpel, der morphologisch, autoradiographisch und chemisch dem Gelenkknorpel in Bezug auf die Verteilung von Glykosaminoglykanen glich. Hyaliner Knorpel wurde hauptsächlich an Stellen beobachtet, wo neugebildeter Knochen die Markhöhle geschlossen hatte. 3. Nach 8 Wochen bestand die Gelenkoberfläche des defekten Gebietes in einem Drittel der Fälle aus hyalinem Knorpel, der morphologisch, autoradiographisch und chemisch dem Gelenkknorpel in Bezug auf die Verteilung von Glykosaminoglykanen glich. Hyaliner Knorpel wurde hauptsächlich an Stellen beobachtet, wo neugebildeter Knochen die Markhöhle geschlossen hatte. 4. Nach 8 Wochen bestanden Teile der Gelenkoberfläche des Defektes in zwei Dritteln der Fälle nicht nur aus Knorpel, sondern auch aus fibrösem Gewebe, welches vor allem in den seitlichen Teilen des Defektes und an Stellen vorlag, wo die Markhöhle gegenüber der Gelenkoberfläche nicht mit Knochengewebe verschlossen worden war. Die Glykoproteinfraktion nahm im Vergleich zur Chondroitin-Sulfatfraktion zu. 5. Nach 20 Wochen zeigten sich in den meisten Fällen bei neugebildetem Knorpel degenerative Veränderungen, welche durch eine gewisse Abnahme des Chondroitin-Sulfats wiedergegeben wurden.
    Notes: Abstract A limited, standardized osteochondral defect was created in adult rabbits and the regenerated tissue was examined histologically and autoradiographically after labellingin vitro with35S-sulphate, and microchemically for its content and composition of glycosaminoglycans. The principal findings were: 1. Between 1 week and 4 to 8 weeks, non-metachromatic connective tissue differentiated to metachromatically stained cartilage, and the proportion of the chondroitin sulphate increased significantly at the expense of the glycoproteins. 2. Up to 4 weeks, the major part of the defect area was filled with newly formed bone; after this time, the area lay above the level of the “tidemark”, towards the articular surface. 3. Hyaline cartilage with morphological, autoradiographic and chemical resemblance to the articular cartilage in terms of the distribution of glycosaminoglycans constituted the articular surface of the defect area in one-third of the cases at observation times after 8 weeks. Hyaline cartilage was observed mainly in areas where newly formed bone had closed the medullary cavity. 4. In two-thirds of the cases, after 8 weeks, parts of the articular surface of the defect consisted not only of cartilage but also of fibrous tissue, occurring mainly in the lateral parts of the defect and in areas where the medullary cavity facing the articular surface had not been sealed by bone tissue. The glycoprotein fraction increased relative to the chondroitin sulphate fraction. 5. In most cases after 20 weeks, newly-formed cartilage underwent degenerative changes, which were reflected in some reduction of the chondroitin sulphate.
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  • 5
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    Calcified tissue international 8 (1971), S. 228-236 
    ISSN: 1432-0827
    Keywords: Skin ; Calcinosis ; Keratin ; Chemistry ; X-ray diffraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des études histologiques antérieures ont montré que le follicle pileux est particulièrement susceptible de se calcifier, lorsque la peau de rats hypercalcémiques est lésée. Des analyses chimiques et par diffraction aux rayons X du follicule ont confirmé ce résultat. — En se basant sur l'augmentation du calcium et du phosphore, les calcifications débutent dans le tissue folliculaire 6–12 h après une blessure d'intensité moyenne de la peau de rats, ayant reçu du dihydrotachysterol (DHT), et 24–48 h après une blessure similaire chez des rats non injectés. Les diagrammes de diffraction aux rayons X sont diffus. Trois heures après la blessure, on note une augmentation du calcium du tissu folliculaire qui ne semble pas en rapport avec le DHT qui traduit probablement une liaison de calcium plutôt qu'un dépot minéral.
    Abstract: Zusammenfassung Frühere histologische Untersuchungen haben gezeigt, daß der Haarfollikel besonders anfällig für Verkalkungen ist, wenn die Haut von hypercalcämischen Ratten verletzt wird. Dieses Resultat wurde nun durch direkte chemische Bestimmungen und Röntgendiffraktions-analysen von Follikelgewebe bestätigt. Aufgrund der erhöhten Calcium- und Phosphatwerte kann gesagt werden, daß nach einer leichten Quetschung der Haut von Ratten, die mit Dihydrotachysterol (DHT) behandelt wurden, im Haarfollikelgewebe nach 6–12 Std Mineral-ablagerungen stattfanden, wogegen Kontrollratten mit der gleichen leichten Hautverletzung diese Ablagerungen erst nach 24–48 Std zeigten. Röntgendiffraktionsanalysen ergaben ein diffuses Apatit-Muster. Innerhalb 3 Std nach der Verletzung wurde ein Anstieg des Calcium-gehaltes im Follikelgewebe beobachtet, der nicht im Zusammenhang mit der DHT-Behandlung stand, also nicht eine Mineralablagerung, sondern eher eine Bindung von Calcium widerspiegelte.
    Notes: Abstract Previous histological investigations have shown that the hair follicle is particularly susceptible to mineralization when the skin of hypercalcaemic rats is injured. Direct chemical and X-ray diffraction analyses of follicle tissue have now confirmed this finding. As judged by increases in both calcium and phosphorus, mineral deposits began to form in hair follicle tissue 6–12 h after a mild crush injury to the skin of rats dosed with dihydrotachysterol (DHT), and 24–48 h after a similar injury to the skin of non-dosed rats. X-ray diffraction gave a diffuse apatite pattern. Within 3 h of injury there was a rise in the calcium content of follicle tissue which was not related to DHT-dosing and which was probably a reflection of calcium binding rather than mineral deposition.
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  • 6
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    Calcified tissue international 8 (1971), S. 304-319 
    ISSN: 1432-0827
    Keywords: Chemistry ; Calcium ; Phosphate ; Solubility ; Computer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Un programme d'ordinateur a été mis au point pour calculer les activités ioniques du calcium et l'orthophosphate dans un grand nombre de solutions. Dans le cas de solutions synthétiques, les calculs sont vérifiés en comparant les valeurs de pH, obtenues par ordinateur, avec celles observées expérimentalement. Des essais de ce type, avec des solutions possèdant des concentrations de calcium et d'orthophosphate trouvées dans les liquides biologiques et à des valeurs de pH variant de 3.00 à 10.00, indiquent que le programme est adapté pour des applications biologiques. Le programme n'est pas effectif pour des solutions, dans les lesquelles l'ion bromure est la source principale de la force ionique, sans doute, par manque d'équation étendue de Debye-Hückel dans ces circonstances. Aucune formation de complexe de phosphate de sodium n'a été notée à des concentrations biologiques normales.
    Abstract: Zusammenfassung Es wurde ein Computer-Programm ausgearbeitet, um die Ionenaktivitäten von Calcium und Orthophosphat in einer breiten Varietät von Lösungen zu berechnen. Die Berechnungen wurden bei synthetischen Lösungen durch Vergleiche zwischen den auf diese Weise errechneten pH-Werten und den experimentell gefundenen kontrolliert. Diese Art Kontrollen mit Calcium-und Orthophosphatkonzentrationen, wie sie in biologischen Flüssigkeiten gefunden werden, und mit pH-Werten zwischen 3,0 und 10,0 wies darauf hin, daß das Programm für biologische Anwendungen geeignet war. Das Programm konnte nicht benützt werden für solche Lösungen, bei welchen hauptsächlich das Bromidion zur Einstellung der Ionenstärke verwendet wurde, vermutlich weil die erweiterte Debye-Hückel-Gleichung unter diesen Umständen nicht anwendbar ist. Die Bildung eines Natriumphosphat-Komplexes unter normalen biologischen Konzentrationen konnte nicht nachgewiesen werden.
    Notes: Abstract A computer program has been designed to calculate the ionic activities of calcium and orthophosphate in a wide variety of solutions. In the case of synthetic solutions the calculations were checked by comparing the computed pH values with those observed experimentally. Tests of this type with solutions having the concentrations of calcium and orthophosphate found in biological fluids and with pH values ranging from pH 3.0–10.0 indicated that the program was suitable for biological applications. The program was not effective for solutions in which the bromide ion was a principal source of ionic strength probably because of the failure of the extended Debye-Hückel equation under those circumstances. No evidence for the formation of any sodium phosphate complex at normal biological concentrations could be found.
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  • 7
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    Calcified tissue international 8 (1971), S. 197-210 
    ISSN: 1432-0827
    Keywords: Fluorescence ; Calcium ; Collagen ; Chemistry ; Bone ; Dentine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Des composants fluorescents de l'os et la dentine sont séparés des hydrolysats alcalins de leur marice sur des colonnes Sephadex C25 CM d'échange cationique. Les concentrations en fluorescence et le spectre d'excitation (λ max 330 nm) et d'émission (λ max 395 nm) sont les mêmes que ceux observés au niveau des matrices intactes et gélatinisées. Les paramètres de fluorescence ne sont pas altérés par hydrolyse. La filtration sur gel à l'aide de colonnes Sephadex G 10 perment de différencier le matériel isolé en deux composants, ayant la même fluorescence et la même absorption UV. La fluorescence est indépendante de pH de 3.5–9.5. Des études de dialyse et de filtration sur gel de matrices gélatinisées indiquent une association étroite du matériel fluorescent avec les chaines polypeptidiques de collagène.
    Abstract: Zusammenfassung Fluorescierende Bestandteile aus Knochen und Dentin wurden in Sephadex C25 CM Kationen-Austauschersäulen von alkalischen Hydrolysaten ihrer Matrices getrennt. Die Fluorescenzintensitäten sowie die Erregungs- (λ max 330 nm) und Emissions- (λ max 395 nm) Spektren waren dieselben wie bei intakten und gelatinisierten Matrices. Die Fluorescenzparameter wurden durch die Hydrolyse nicht verändert. Eine Gelfiltration über Sephadex-G10-Säulen trennte das isolierte Material in 2 Komponenten auf, welche gleiche Fluorescenz- und UV-Absorptionseigenschaften zeigten. Im pH-Bereich zwischen 3,5 und 9,5 war die Fluorescenz unabhängig vom pH. Dialysierversuche sowie Gelfiltrationsexperimente mitden gelatinisierten Matrices zeigten eine starkgefügte Bindung des fluorescierenden Materials mit den Polypeptidketten des Kollagens.
    Notes: Abstract Fluorescent components in bone and dentine were separated from alkaline hydrolysates of their matrices on Sephadex C25 CM cationic exchange columns. The fluorescence levels, and the excitation (λ max 330 nm) and emission (λ max 395 nm) spectra, were the same as those observed in the intact and gelatinised matrices. The fluorescence parameters were unaltered by the hydrolysis procedure. Gel filtration on Sephadex G. 10 columns further resolved the isolated material into two components with the same fluorescence and UV absorption properties. The fluorescence was independent of pH over the range 3.5–9.5. Dialysis and gel filtration studies on the gelatinised matrices indicated a firmly-bonded association of the fluorescent material with the collagen polypeptide chains.
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  • 8
    ISSN: 1432-1041
    Keywords: Chlorthalidone ; spironolactone ; hypertension ; potassium deficiency ; diuretic ; Kühns' test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Kühns' oral test for potassium deficiency (KDT) has been used to evaluate potassium balance after treatment with diuretics. The test was first standardised in 23 patients, both with and without known potassium deficiency. Subsequently, 18 patients with essential hypertension were investigated before and after the use of 3 different diuretics, each for a period of 6 weeks; all patients received all three forms of treatment but in different sequence. Before treatment the patients excreted an average of 121 mEq potassium a day in urine after oral administration of potassium 127 mEq (citrate). After treatment with chlorthalidone (Hygroton®), 50 mg a day, the excretion of potassium decreased significantly to 83 mEq, suggesting an intracellular deficit of it. Treatment with chlorthalidone 50 mg and potassium chloride 2 g daily (Hygroton — K®), led to potassium excretion of 100 mEq after loading, which was distinctly, but not significantly, larger than in the period of treatment with chlorthalidone alone. After chlorthalidone 50 mg daily and spironolactone (Aldactone “Searle”®), 25 mg q. i. d., the excretion of potassium was 121 mEq, which was the same as before treatment. The mean serum potassium before treatment was 4.4 mEq/l, after chlorthalidone 3.8 mEq/l, after chlorthalidone plus potassium chloride 3.9 mEq/l, after chlorthalidone combined with spironolactone 3.9 mEq/l. The results were in agreement with previously published investigations of “exchangeable potassium” after similar treatments. As the test for potassium deficiency gave better information about the amount of intracellular potassium in the body than analysis of serum potassium, it is suitable for the evaluation of potassium deficiency associated with diuretic therapy.
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  • 9
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    European journal of clinical pharmacology 26 (1984), S. 309-313 
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; therapeutic window ; steady state concentration ; pharmacokinetics ; cardiovascular effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonidine was given orally as monotherapy in increasing daily doses from 3.1 to 25.7 µg/kg to patients with essential hypertension (n=6). When a steady state concentration in plasma was reached at each dose level, the blood pressure (BP) and heart rate were measured during a dosage interval. Effect time — plasma concentration data were submitted to nonlinear regression analysis, which showed that the observed BP effects could be dissociated into depressor and pressor components. A window for the antihypertensive effect was established. At a plasma clonidine concentration of 0.65±0.07 ng/ml 50% of the maximal depressor effect was found, and it was only separated by a factor of 2 from the half maximal pure pressor concentration in plasma. No relationship between the change in heart rate and the plasma clonidine was observed. The findings strengthen the importance of close monitoring of clonidine therapy.
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  • 10
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    European journal of clinical pharmacology 26 (1984), S. 331-334 
    ISSN: 1432-1041
    Keywords: metoprolol ; oxprenolol ; hypertension ; beta-blockers ; HDL-cholesterol ; intrinsic sympathomimetic activity ; cardioselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the present study was to evaluate whether a reduction in HDL-cholesterol is peculiar to non cardioselective beta blockers or whether it is also produced by cardioselective beta1-blockers. 16 patients with primary arterial hypertension on a balanced isocaloric diet were given oxprenolol 120 to 240 mg/day or metoprolol 100 to 200 mg/day in a random cross-over study. No significant change was observed after either treatment in fasting blood glucose, serum total cholesterol and triglycerides. HDL-cholesterol concentration was significantly decreased on metoprolol, from 41 to 36 mg/dl (p〈0.05), while oxprenolol did not affect it at all. The difference might depend on intrinsic sympathomimetic activity which is possessed by oxprenolol and which metoprolol lacks.
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  • 11
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    European journal of clinical pharmacology 26 (1984), S. 549-553 
    ISSN: 1432-1041
    Keywords: pafenolol ; hypertension ; antihypertensive therapy ; beta1-blocking agent ; exercise tests ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pafenolol, a new selective adrenergic beta1-blocking agent, has been tested for the first time in 6 hypertensive patients. After single oral doses of pafenolol 25 to 100 mg, there was a marked reduction in heart rate and systolic blood pressure during exercise tests. These effects were dose dependent. A significant positive correlation was found between the reduction in heart rate during exercise and the plasma level of pafenolol 5 hours after drug intake (correlation coefficient r=0.94). Side effects were mild and seemed to be dose dependent. It is concluded that this new beta1-blocking agent was effective in reducing blood pressure and was well tolerated.
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  • 12
    ISSN: 1432-1041
    Keywords: etozolin ; ozolinone ; furosemide ; hypertension ; renin ; catecholamines ; chronic renal failure ; steady state kinetics ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect on urinary electrolyte excretion, renin release and plasma norepinephrine of single oral doses of 400 mg etozolin (E) and of 40 mg furosemide (F) were studied in hypertensive patients with normal (n=6) and impaired kidney function (n=6). E caused a marked saluresis up to 24 hours, showing its long duration of action. F, however, displayed a brief, brisk peak diuresis, followed by a rebound from the 4th to the 24th hours. The brisk peak diuresis induced by F was associated with pronounced release of renin, almost twice that induced by E. In chronic renal failure the renin release in relation to the magnitude of the diuresis was increased, i.e. the sensitivity of these patients to changes in water homeostasis was increased. E and F stimulated the sympathetic system to roughly the same extent. Patients with essential hypertension had higher plasma levels of norepinephrine than hypertensive patients with chronic renal failure. In addition, hypertensive patients with normal renal function (n=4) and varying degrees of renal impairment (n=11) were also given 400 mg daily for 2 weeks. Effects on blood pressure and electrolyte homeostasis were monitored, as well as the plasma kinetics of metabolite I, ozolinone. At the end of the 2 week treatment E had significantly lowered systolic (−12 mm Hg) and diastolic (−9 mm Hg) blood pressure, and had produced a significant loss of body weight, without altering plasma electrolytes or blood chemistry. There was no accumulation of the effective metabolite ozolinone under conditions of severe impairment of kidney function. It is concluded that E can effectively control high blood pressure in patients with normal and impaired kidney function. Its effective metabolite ozolinone did not accumulate in chronic renal failure.
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  • 13
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    European journal of clinical pharmacology 27 (1984), S. 397-405 
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; cardiovascular reflexes ; diuretic effect ; blood pressure variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine elderly and 11 young hypertensives underwent continuous ambulatory monitoring of blood pressure (BP), assessment of cardiovascular reflexes and M-mode echocardiography as hospital in-patients prior to treatment with once-daily indapamide (2.5 mg). They were followed as out-patients for 4 months during which time casual BP was measured at monthly intervals. The patients were then readmitted to hospital and studied using the same protocol under similar standardised conditions. The results showed that indapamide reduced casual and ambulatory BP in both young and elderly although the most marked effect was seen on systolic BP. Assessment of cardiovascular reflexes indicates that at least part of the hypotensive action of indapamide is due to a diuretic effect. Treatment with indapamide has comparable results on both young and elderly.
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  • 14
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    European journal of clinical pharmacology 26 (1984), S. 315-323 
    ISSN: 1432-1041
    Keywords: captopril ; hypertension ; glomerular filtration ; para-aminohippuric acid ; renal function ; severe drug reaction ; nephrotic syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of captopril up to 450 mg/day on blood pressure and renal function were investigated during sustained treatment of 10 patients whose severe hypertension had not responded to previous therapy. All the patients were kept on diuretics and most of them on β-blockers, too. A control determination of glomerular filtration rate (GFR) and para-aminohippuric acid clearance (CPAH) was performed during the prior treatment. The effect of the addition (or substitution) of captopril were assessed after an average of 25 days (short-term) and 26 weeks (long-term). Short-term treatment produced a 15.5% decrease in mean blood pressure and interindividually variable effects on renal function. On average GFR was somewhat lower and CPAH slightly higher than the control values (not significant). This pattern is quite similar to the effects of most other antihypertensive drugs. On long-term therapy GFR rose by a mean of 9% (NS) and CPAH by 17% (p〈0.02). However, in a patient who developed a captopril-induced nephrotic syndrome, GFR dropped to 56% and CPAH to 50% of the control values. In another patient a transient rise in serum creatinine accompanied a severe drug reaction.
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  • 15
    ISSN: 1432-1041
    Keywords: beta-blocking drugs ; insulin sensitivity ; pancreatic beta-cell function ; hypertension ; propranolol ; atenolol ; insulin secretion ; plasma GIP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of two beta-blocking drugs on endogenous insulin secretion and insulin sensitivity were investigated in a double blind cross-over study in 13 hypertensive patients. The patients were randomly allocated to each of three 2-week treatment periods with propranolol 80 mg b.i.d., atenolol 50 mg b.i.d. and placebo b.i.d. Endogenous insulin secretion was assessed by measuring serum insulin and C-peptide before and 6 min after iv administration of glucagon; insulin sensitivity was determined by measuring insulin binding to erythrocytes, and as the glucose disappearance rate (KITT) after i.v. insulin. Fasting concentrations of serum free fatty acids (S-FFA) and plasma gastric inhibitory polypeptide (P-GIP) were also recorded during the three study periods. Both propranolol and atenolol reduced blood pressure, heart rate and S-FFA concentrations compared to placebo, and all patients showed measurable plasma concentrations of propranolol and atenolol. The results can be considered representative, therefore, of clinical beta-blockade. The two drugs did not significantly influence the fasting blood glucose level. There was an increase in fasting and glucagon-stimulated serum C-peptide concentration during propranolol therapy compared with placebo (p=0.037 and p=0.030, respectively), although this was not reflected by a significant change in serum insulin. Propranolol and atenolol did not significantly influence insulin binding to erythrocytes, but they clearly reduced the glucose disappearance rate KITT was compared to placebo (p=0.0036 and p=0.0003, respectively). The findings support the view that beta-blocking drugs can influence glucose metabolism by mechanisms other than inhibition of endogenous insulin secretion.
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  • 16
    ISSN: 1432-1041
    Keywords: acetylator phenotype ; hydralazine response ; hypertension ; blood pressure control ; lupus syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of acetylator phenotype in determining the response to hydralazine when it was added to diuretic and β-blocker at doses not exceeding 200 mg daily was examined in 57 hypertensive patients. 81% of rapid acetylators needed 200 mg hydralazine daily compared to 38% of slow acetylators (p〈0.01). Despite higher doses of hydralazine the blood pressure was controlled in only 27% of rapid acetylators compared to 65% of slow acetylators (p〈0.02). The relation of acetylator phenotype to blood pressure response was statistically independent of initial blood pressure, age, sex, body weight and serum creatinine (p〈0.005). Current recommendations on hydralazine dosage are unsatisfactory for the 40% of hypertensive patients who are rapid acetylators. We suggest measurement of the acetylator phenotype in patients who respond incompletely to 200 mg hydralazine daily. About 70% of these patients will be rapid acetylators in whom the dose of hydralazine can be increased safely.
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  • 17
    ISSN: 1432-1041
    Keywords: Tobanum® ; beta-blocker ; chloranolol ; hypertension ; angina pectoris ; arrhythmia ; detection methods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The incidence of side-effects on administration of chloranolol (Tobanum®), a beta-adrenergic receptor blocking drug, to 2066 patients with hypertension, angina pectoris or arrhythmias was measured by three different methods. In 600 patients in an efficacy trial (Group 1) both spontaneously reported complaints and objective signs were tabulated. A side effect — directed method, utilising a questionnaire containing a list of possible side-effects was also used, with the questionnaire being completed by the physician. 35 questions referred to anticipated and other side-effects. The trial was performed in two groups: in 537 patients a placebo was also given (Group 2), and in another set of 929 patients (Group 3) the questionnaire inquiry was performed uncontrolled, without placebo. All three groups were comparable in their distribution of sexes, ages and diagnoses, the mean daily dose of chloranolol its use alone or in combination, and in a similar duration of treatment. 55% of all patients received chloranolol therapy for a period of more than 3 months. The ratio of in- and outpatients was 1:5. The side-effect incidence was independent of the age and sex of the patients and of the dose of chloranolol. The incidence was also unaffected whether chloranolol was used alone or in combination. The number of side-effects differed markedly between the three groups, their ratio was 1:10:24 in Groups 1, 2 and 3. Two-thirds of the side-effects subsided spontaneously within 1 month of their onset. The duration of the side-effects varied according to their character: cardiorespiratory side-effects were of the shortest duration and those affecting the central nervous system were the most enduring. The appreciable differences in incidence could be attributed to the methods of collection of the data. It has been stated that placebo controlled trials using a detailed questionnaire are the most suitable for estimating the incidence of side-effects; recording side-effects spontaneously reported by patients are insufficiently sensitive, and uncontrolled trials using a questionnaire have been shown to be too sensitive. The revealed incidence of side effects leading to interruption of treatment is less affected by the method chosen. In 100 patients (4.8%) therapy had to be suspended because of the side-effects of chloranolol (Group 1: 1%, Group 2: 6.20%, Group 3: 6.6%). Comparison of the incidence of cessation of therapy due to side-effects did not show an appreciable difference between the various beta-adrenergic receptor blocking agents, including chloranolol.
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  • 18
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    European journal of clinical pharmacology 26 (1984), S. 1-6 
    ISSN: 1432-1041
    Keywords: hypertension ; beta-blockers ; propranolol ; metoprolol ; labetalol ; exercise ; heart rate ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double blind, within patient investigation of twenty-four patients (nineteen males and five females) with a mean age of 46.3 years (SD 10.9 years) with mild to moderate essential hypertension a comparison between equipotent beta-blocking doses of propranolol, metoprolol and labetalol was carried out. Blood pressure and pulse rate were measured in lying, sitting and standing positions and before, during and after isometric and dynamic exercise. Peak expiratory flow was recorded before and during dynamic exercise. All the active treatments were better than placebo in reducing blood pressure and heart rate. Comparing the effects of treatment, labetalol lowered sitting diastolic pressure significantly more than propranolol and standing diastolic pressure than both propranolol and metoprolol. Metoprolol and propranolol were more effective in reducing heart rate. Propranolol significantly reduced peak flow rate compared to labetalol. During the exercise, both isometric and dynamic, the heart rate and the blood pressure, both systolic and diastolic, of the treated patients were lower than those on placebo. There was little difference between the drugs in the influence on blood pressure, but metoprolol and propranolol were significantly more effective than labetalol in lowering the heart rate.
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  • 19
    ISSN: 1432-1041
    Keywords: alpha-methyldopa ; propranolol ; hypertension ; side effects ; blood pressure control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A multicentre study of 6–10 weeks duration was performed in 60 ambulant hypertensive patients aged over 60 years to compare the efficacy of methyldopa and propranolol with particular reference to the occurrence of cold extremities and sleep disturbances. Blood pressure was effectively controlled by both drugs being reduced from a mean of 180/108 mmHg to 161/93 with methyldopa and 180/108 to 162/94 with propranolol. More patients treated with methyldopa (74%) achieved the target diastolic blood pressure of 95 mmHg or below compared with those treated with propranolol (58%). Side effects were more frequent in the propranolol group necessitating the withdrawal of four patients from the study. Only one patient on methyldopa was withdrawn. The incidence of cold extremities was significantly greater with propranolol. The occurrence of sleep disturbances was similar in both groups. In this group of elderly patients methyldopa was better tolerated than propranolol.
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  • 20
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    European journal of clinical pharmacology 26 (1984), S. 543-547 
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; glomerular filtration ; arginine vasopressin ; free water clearance ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Renal plasma flow (RPF), glomerular filtration rate (GFR), arginine vasopressin in plasma (AVP), free water clearance ( $${\text{C}}_{{\text{H}}_{\text{2}} {\text{O}}}$$ ) and blood pressure (BP) were determined in 11 patients with essential hypertension at the end of 3 consecutive periods of observation each of 6 of weeks duration; indapamide 2.5 mg daily was given in period 2 and placebo in periods 1 and 3. RPF and GFR were reduced by 9% and BP by 9%/14% supine and 14%/12% standing during indapamide treatment. Changes in renal haemodynamics were not correlated with those in BP. AVP was not significantly altered by indapamide and was not correlated with BP. Indapamide reduced $${\text{C}}_{{\text{H}}_{\text{2}} {\text{O}}}$$ possibly due to the reduction in GFR. It is concluded that indapamide evidently induces redistribution of the cardiac output, with enhanced muscle blood flow and reduced renal perfussion, and that AVP does not seem to be involved in blood pressure regulation in mild to moderate essential hypertension under basal conditions.
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  • 21
    ISSN: 1432-1041
    Keywords: beta-blockers ; hypertension ; ISA ; CS ; cold extremities
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Patients with essential hypertension were interviewed prior to entering therapeutic studies in general practice. Patients' age, sex and details of antihypertensive therapy (if any) were noted, as were their spontaneously reported symptoms. Complaints of cold extremities were highest in those taking a beta-blocker (4.1%). Those untreated or taking other therapies complained less often. Those patients taking a beta-blocker with ISA complained less often (3.1%) of cold extremities than those taking a beta-blocker without ISA (5.2%).
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  • 22
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    European journal of clinical pharmacology 27 (1984), S. 13-17 
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; blood pressure decrease ; drug combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The medication of patients receiving hydralazine, captopril and minoxidil was replaced by a new galenical form, long-acting nifedipine. An additional decrease in blood pressure was observed in most of the patients. Renal function was maintained in all of them. Adverse reactions may be reduced by the use of long-acting nifedipine, which would permit a reduction in the dosage of captopril and minoxidil.
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  • 23
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    European journal of clinical pharmacology 27 (1984), S. 23-27 
    ISSN: 1432-1041
    Keywords: hypertension ; alpha2-adrenoceptors ; blood pressure ; clonidine ; guanfacine ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time courses of the changes in plasma growth hormone and noradrenaline concentrations in response to 15 min infusions of clonidine 0.2 mgs and guanfacine 2 mgs, were studied in six normal volunteers, in a double-blind, randomised, crossover study. Plasma noradrenaline fell within 15 min of the commencement of drug administration, by 36±14% after clonidine (p〈0.05) and by 32±11% (p〈0.05) after guanfacine. Plasma growth hormone was not significantly elevated until the 30th minute to 12.0±4.7 lU/ml (p〈0.05) after clonidine and 14.7±11.5 lU/ml (p〈0.05) after guanfacine, having been undetectable prior to both drugs. The reduction in plasma noradrenaline by these α2-adrenergic agonists, prior to activation of central adrenoceptors as detected by changes in plasma growth hormone, is evidence for a peripheral component in their sympatholytic effect.
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  • 24
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    European journal of clinical pharmacology 27 (1984), S. 147-152 
    ISSN: 1432-1041
    Keywords: moxonidine ; clonidine ; hypertension ; double-blind crossover ; side-effects ; withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of moxonidine·HCl·H2O (MOX) was compared with that of clonidine·HCl (CLON) in a randomized double-blind crossover study in 20 hypertensive outpatients (BP range 154–178/96–108 mmHg). After 2 weeks without antihypertensive medication, either MOX 0.2 mg daily or CLON 0.2 mg daily was given and the dose was titrated until the diastolic blood pressure fell below 90 mmHg. The first treatment period was continued for 2 weeks and, after crossover without a wash-out period, it was followed by the second treatment for a further 2 weeks. Within the first 4 days of administration 0.2–0.4 mg of either agent caused a significant decrease in BP (p〈0.001) from a mean of 166/100 mmHg to 149/86 mmHg after CLON (approx. −10/−14%), and 163/99 mmHg to 146/84 mmHg after MOX (approx. −10/−15%). No significant difference in the fall in BP or pulse rate was detected between the two drugs. In the mean daily dose of 0.3 mg both drugs showed the same antihypertensive activity, but on CLON a higher incidence of side effects (p=0.003) was noted, and after discontinuation of therapy a more rapid rise in BP (systolic BP p〈0.01, diastolic BP p〈0.02) was found. 17 patients on CLON complained of side effects, especially tiredness and dry mouth, whilst only 6 patients on MOX were affected (p=0.003).
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  • 25
    ISSN: 1432-1041
    Keywords: guanfacine ; hydrallazine ; hypertension ; sympathetic nervous activity ; plasma renin activity ; cardiac and systemic haemodynamics ; blood pressure ; limb blood flow ; limb vascular resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of guanfacine and hydrallazine on cardiovascular haemodynamics and on sympathetic nervous activity has been studied in 16 patients with essential hypertension. Two groups of patients were investigated: in Group A guanfacine brought the blood pressure back to normal (diastolic blood pressure ⩽90 mmHg), and in Group B diastolic blood pressure was 〉 90 mmHg and required the addition of hydrallazine. Guanfacine significantly decreased heart rate, plasma renin activity and urinary excretion of noradrenaline, without altering cardiac contractility. In Group B, guanfacine 2 to 6 mg/day produced a significant decrease in blood pressure from 178.7/112.4 to 164.4/102.9 mmHg and in heart rate from 77.1 to 62.7 beats/min after 4 weeks of treatment. Guanfacine did not significantly alter preejection period, cardiac output or total peripheral resistance. Hydrallazine 50 to 300 mg/day caused a further reduction in blood pressure from 164.4/102.9 to 150.7/90.2 mmHg and an increase in heart rate from 62.7 to 72.1 beats/min. Limb blood flow was increased from 4.55 to 5.93 ml/100 g/min and limb vascular resistance was decreased from 39.55 to 23.6 mmHg 100 g·min/ml. Hydrallazine also caused a slight increase in plasma renin activity and urinary excretion of noradrenaline. It is concluded that guanfacine is a useful agent to block a hydrallazine-induced increase in sympathetic nervous activity.
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  • 26
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    European journal of clinical pharmacology 27 (1984), S. 407-414 
    ISSN: 1432-1041
    Keywords: piretanide ; hypertension ; triamterene ; double blind comparison ; potassium ; magnesium ; side-effects ; serum electrolytes ; serum parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a randomized, double blind, parallel group study in out patients with mild to moderate essential hypertension the effects of piretanide on serum electrolytes and on blood pressure were compared with those of triamterene alone and the combination piretanide + triamterene. 136 patients entered the study; 18 patients did not fulfill the inclusion criteria (RRdiast was below 95 mmHg or above 120 mmHg) at the end of the placebo period, 6 dropped out due to side effects, and 1 due to lack of efficacy. Data from 1 patient were not evaluated because the patient did not come regularly for checkups. The results for 110 patients were analyzed. Piretanide 6 mg b.d. and piretanide 6 mg + triamterene 50 mg b.d. produced a significant reduction both in supine and erect blood pressure, which was evident at 2 weeks and which increased over the ensuing 12 week trial period. A mean maximal fall of 16.5% was noted in the piretanide group and 15% in the piretanide + triamterene group. Triamterene alone (50 mg b.d.) also reduced diastolic and systolic blood pressures but the reduction was significantly less (diastolic blood pressure) than in both the piretanide groups, and it showed a more rapid return to pretreatment level during a placebo washout phase at the end of the study. A reduction in standing diastolic blood pressure below 95 mmHg was attained in 84% of patients in the piretanide group, 82% in the piretanide + triamterene group and in only 58% of the triamterene group. There were no significant changes within groups nor differences between the three groups in serum potassium or magnesium. 7 patients were withdrawn from the study because of side-effects due to too marked a clinical action (polyuria, orthostatic disorders and hypotension), one from the piretanide group, and the others in the piretanide + triamterene group. One patient in the triamterene group left the study prematurely due to the lack of effect.
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  • 27
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    European journal of clinical pharmacology 27 (1984), S. 529-534 
    ISSN: 1432-1041
    Keywords: beta-adrenoceptor blocking agents ; hypertension ; adverse reactions ; atenolol ; bopindolol ; pindolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy of once-daily bopindolol, a nonselectiveβ-adrenoceptor blocking agent with partial agonist activity, and of pindolol and atenolol in the treatment of essential hypertension has been compared. 369 patients were investigated in a double-blind parallel-group study. The treatment period was 10 weeks. Blood pressure normalisation (diastolic BP equal to or less than 90 mmHg) was to be achieved by a stepwise increase in the dose of the test drugs, and, if required, by addition of a diuretic. Normalisation of blood pressure was achieved in 71 to 76% of the subjects, with no significant differences between bopindolol, pindolol, and atenolol. Special attention was given to evaluation of side effects by using two methods for registration of all adverse events during the study. A low incidence of drug-induced side effects was observed, with no significant difference between bopindolol, pindolol, and atenolol. There was no evidence of unsuspected adverse reactions due to bopindolol.
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  • 28
    ISSN: 1432-1041
    Keywords: hypertension ; hydrochlorothiazide ; atenolol ; side effects ; therapeutic efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After screening a local population in the northern part of The Netherlands for hypertension, 119 patients with a diastolic pressure (DP) between 95 and 120 mmHg were randomised and treated either with 50 mg hydrochlorothiazide (n=59) or 100 mg atenolol (n=60). After 1 month of treatment 6 patients in the hydrochlorothiazide group and 24 patients in the atenolol group had reached a DP⩽90 mmHg (p〈0.001). 43 of the 50 non-responders to hydrochlorothiazide were switched to atenolol and 30 of the 35 non-responders to atenolol were changed to hydrochlorothiazide. One month after the switch 19 patients in the atenolol group and 2 patients in the hydrochlorothiazide group had reached a DP⩽90 mmHg (p〈0.001). After 6 months of treatment 32 of the 43 atenolol responders and 7 of the 8 hydrochlorothiazide responders were still receiving the same medication, as their DP was still⩽90 mmHg. Non-responders to either medication were given the combination (n=46). 21 patients now became normotensive as did a further 10 after increasing the dose of atenolol to 200 mg. Thus, in all 70 patients had a blood pressure ⩽90 mmHg after treatment for 4 months. Both drugs induced a significant reduction in the total of number of complaints after 1 month of treatment. They did not differ from each other. The reduction was seen both in responders and non-responders and persisted during treatment for 6 months. It is concluded that in terms of short-term efficacy the cardioselective, hydrophilic beta adrenoceptor-blocking drug atenolol is preferable to hydrochlorothiazide in the treatment of uncomplicated hypertension.
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  • 29
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    European journal of clinical pharmacology 26 (1984), S. 603-608 
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; pinacidil pyridine-N-oxide ; urinary excretion ; protein binding ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Preliminary investigation in 3 healthy volunteers suggested that intravenous pinacidil in a dose of 0.2 mg/kg had a potent but well-tolerated hypotensive action in the supine position. Facial flushing, uncomfortable chest sensation and distressing postural hypotension occurred at serum concentrations above 300 ng/ml. Pinacidil, 0.2 mg/kg, was given intravenously over 4 min to 15 healthy volunteers in the supine position. Maximum fall in mean arterial pressure (MAP) was 15.7±6.0 mmHg. Maximum rise in heart rate was 23.8±6.6 beats/min. Pinacidil serum distribution half-life ( $${\text{T}}_{{\raise0.7ex\hbox{${\text{1}}$} \!\mathord{\left/ {\vphantom {{\text{1}} {{\text{2}}\alpha }}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{${{\text{2}}\alpha }$}}}$$ ) was 13.4±8.5 min and elimination half-life ( $${\text{T}}_{{\raise0.7ex\hbox{${\text{1}}$} \!\mathord{\left/ {\vphantom {{\text{1}} {{\text{2}}\beta }}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{${{\text{2}}\beta }$}}}$$ ) was 2.13±0.49 h. The apparent volume of distribution (Vdβ) was 90.3±13.21 and total body clearance was 31.1±9.61/h. Pinacidil was approximately 40% bound to plasma protein over the concentration range 40–400 ng/ml. Urinary excretion of unchanged pinacidil accounted for 5.7 ± 1.3% of the administered dose over 24 hours and urinary excretion of the major metabolite, pinacidil pyridine-N-oxide, was 31.6±9.2% of the administered dose. It was concluded that intravenous pinacidil is a potent vasodilator hypotensive compound, with a duration of action between 1.5 and 2 h.
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  • 30
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    European journal of clinical pharmacology 26 (1984), S. 661-661 
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; elimination half-liefe ; compartment model
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  • 31
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    European journal of clinical pharmacology 27 (1984), S. 13-17 
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; blood pressure decrease ; drug combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The medication of patients receiving hydralazine, captopril and minoxidil was replaced by a new galenical form, long-acting nifedipine. An additional decrease in blood pressure was observed in most of the patients. Renal function was maintained in all of them. Adverse reactions may be reduced by the use of long-acting nifedipine, which would permit a reduction in the dosage of captopril and minoxidil.
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  • 32
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    European journal of clinical pharmacology 27 (1984), S. 23-27 
    ISSN: 1432-1041
    Keywords: hypertension ; alpha2-adrenoceptors ; blood pressure ; clonidine ; guanfacine ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time courses of the changes in plasma growth hormone and noradrenaline concentrations in response to 15 min infusions of clonidine 0.2 mgs and guanfacine 2 mgs, were studied in six normal volunteers, in a double-blind, randomised, crossover study. Plasma noradrenaline fell within 15 min of the commencement of drug administration, by 36±14% after clonidine (p〈0.05) and by 32±11% (p〈0.05) after guanfacine. Plasma growth hormone was not significantly elevated until the 30th minute to 12.0±4.7 lU/ml (p〈0.05) after clonidine and 14.7±11.5 lU/ml (p〈0.05) after guanfacine, having been undetectable prior to both drugs. The reduction in plasma noradrenaline by these α2-adrenergic agonists, prior to activation of central adrenoceptors as detected by changes in plasma growth hormone, is evidence for a peripheral component in their sympatholytic effect.
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  • 33
    ISSN: 1432-1041
    Keywords: beta-blockers ; hypertension ; ISA ; CS ; cold extremities
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Patients with essential hypertension were interviewed prior to entering therapeutic studies in general practice. Patients’ age, sex and details of antihypertensive therapy (if any) were noted, as were their spontaneously reported symptoms. Complaints of cold extremities were highest in those taking a beta-blocker (4.1%). Those untreated or taking other therapies complained less often. Those patients taking a beta-blocker with ISA complained less often (3.1%) of cold extremities than those taking a beta-blocker without ISA (5.2%).
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  • 34
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    European journal of clinical pharmacology 27 (1984), S. 287-289 
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; vasodilator ; patients ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A new vasodilator drug, pinacidil, N″-cyano-N-4-pyridyl-N′-1, 2,2-trimethylpropylguanidine, was studied in an open trial in 15 patients with moderate to severe hypertension. Four patients received pinacidil monotherapy, and in 11 patients it was used with a diuretic or a beta-blocker. In all but one patient normotension was achieved with a mean daily pinacidil dose of 46.7 mg b.i.d. (range 20–100 mg). Side effects were few and were action-related. There was no evidence of early toxicity. Pinacidil is a promising new antihypertensive vasodilator, which deserves further clinical evaluation.
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  • 35
    ISSN: 1573-8221
    Keywords: hypertension ; β-adrenoreceptors ; lymphocytes ; man
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    Topics: Biology , Medicine
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  • 36
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    Bulletin of experimental biology and medicine 98 (1984), S. 1283-1285 
    ISSN: 1573-8221
    Keywords: cerebral microcirculation ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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    Journal of Biomedical Materials Research 5 (1971), S. 135-148 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Hollow fibers have been produced and evaluated for use as membrane oxygenators in an artificial heart device. Gas permeable capillaries now commercially available are unsuitable for this use because of: (1) low percent open cross-sectional area, (2) large internal diameter, and (3) high cost. A number of polymers were initially selected for evaluation because of their reported high gas permeabilities. Those selected include a number of rubbers of various compositions, certain poly-α-olefins and an experimental thermoplastic silicone rubber copolymer. These materials were first evaluated as flat membranes (films) for their gas permeabilities and also for ease of preparation in hollow fiber form. Hollow fibers were prepared from the most promising of those studied, poly-4-methylpentene-1 and the thermoplastic polydimethylsiloxane copolymer. Fibers, ranging in the size from 30 to 300 μ ID, were spun with open cross-sectional areas of 40-65%. Oxygen and carbon dioxide permeabilities measured on these fibers were compared to that of SilasticDow Corning medical grade poly (dimethylsiloxane). rubber membranes. These permeabilities range from 1/20 that of Silastic rubber for unmodified poly-4-methylpentene-1 to 2/3 for the thermoplastic silicone copolymer. Modification of poly-4-methylpentene-1 has made it possible to increase it's permeability by tenfold, while still maintaining physical properties necessary to spin and fabricate this material.
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    Journal of Biomedical Materials Research 5 (1971), S. 41-47 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Advanced forms of elemental carbon were identified as potential implantable prosthetic materials and a study was conducted to determine specific applications. A survey of the carbon industry established material sources and specifications on available types of material. Specimen materials were supplied to several research organizations for in-vivo evaluation and produced acceptable results. Specific designs have been generated for a broad range of implantable prosthetics and prototypes have been provided for preliminary evaluation. The feasibilty of an organic mechanical attachment between cortical bone tissues and elemental carbon has been successfully demonstrated.
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    Journal of Biomedical Materials Research 5 (1971), S. 69-89 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The success of material implants in the vascular system has been limited by the fact that the intial events of blood coagulation on foreign material surfaces are not understood. Many materials have been evaluated in the search for a suitable implant material in this system. Recent success of porous ceramic materials in bone-ceramic compatibility studies stimulated the feeling that these materials should be tested in other body tissues such as the blood.Ceramic disks of Al2O3 and TiO2 were evaluated using a contact angle measurement technique to determine the characteristics of these material surfaces before and after exposure to a blood environment. This technique involved measuring the contact angle of sessile drops of various liquids on these surfaces with a microscope fitted with a goniometer eyepiece. By plotting these contact angles according to the procedure of Zisman, the characteristics of the surfaces could be evaluated.The clean ceramic disks were found to be extremely wettable even after exposure to a physiological saline environment. On exposure of these disks to a blood environment, it was observed that some type of film was adsorbed from the blood onto the ceramic surface during the initial minutes of exposure. This film had wetting characteristics consistent with layers of fibrinogen.
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    Journal of Biomedical Materials Research 5 (1971), S. 143-159 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The skeletal attachment of a limb prosthesis approaches two specific and separate problems in tissue reaction to prosthetic materials: Skeletal fixation and trancutaneous interface.The skeletal fixation problem must be looked upon as a method to distribute the stress concentration of prosthetic material in such a manner so that living tissue is not embarrassed by prolonged excessive pressures. One must consider the functional mechanical stresses separate from the toxicological reaction of living tissues to prosthetic materials. Our current experience identifies the fact that vitreous carbon is extremely benign from the standpoint of living tissue reaction. Moreover, when placed in the configuration of irregular surfaces, it apparently encourages bone growth contiguous with the material. To this point, however, the reaction of living material to broad surfaces contiguous with vitreous carbon has not placed under concentration of functional stresses. Porous ceramic to this date has not supplied an appropriate answer to this problem.Transcutaneous perforation is available in the clinical sense only when a method can be presented which requires no specific hygiene and dressing. No drainage at all must be the rule at a transcutaneous perforation. Vitreous carbon in our experience so far has made contiguous epithealization feasible down the neck of a skin perforation. Four millimeters, from our experience, seems to be an appropriate location of epithelial downgrowth before transition into non epithealized connective tissue is available. The use of fixation skirts is felt to be necessary to provide stable, transcutaneous perforation.This paper presents evidence of the favorable tissue reaction both from a skeletal and cutaneous standpoint to vitreous carbon materials. A specific design for the successful skeletal fixation limb prosthesis is as yet not currently available and must await further clinical experience with human skin reaction to transcutaneous devices.
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    Journal of Biomedical Materials Research 5 (1971), S. 231-249 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A study has been made of the ceramic-epoxy composite “Cerosium.” Experiments were conducted to evaluate the tissue reaction to such material and the extent of bonding established between ceramic and the tissues in which it was implanted. It was found that this material was well tolerated by the body and obtained definite fixation within the tissues when implanted into both bone and tendon. This occurred, however, not by the active infiltration of tissue but by fibrous encapsulation and it is recommended that for more meaningful stabilization, material of larger pore size is required.When Cerosium was implanted into the knee joints of rabbits, it was found to be unsuitable for intra-articular use because of the abrasive effect on the opposing cartilage and bone surfaces and the susceptibility of the material itself to abrasive wear. Furthermore, a full mechanical evaluation of standard specimens of Cerosium showed it to be degraded within the body due to a breakdown of the impregnating polymer.Ceramic-epoxy composites require a strong matrix and a totally stable impregnating material. While mechanically suited to replacing weight bearing surfaces, a smooth surface glaze is essential to avoid abrasive effects upon the opposing bone surface. Further investigation is required before these materials can be fully accepted into the armamentarium of the implant surgeon.
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    Journal of Biomedical Materials Research 8 (1974), S. 115-126 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A standardized readily reproducible experimental model has been developed to assess the relative importance of the chemical and physical configuration of sutures as determinants of early infection in contaminated wounds. The chemical structure of the suture appeared to be the most important factor in the development of surgical infection. The incidence of infection in contaminated tissues containing either polypropylene sutures or nylon sutures was lower than the infection rate of tissues subjected to any other nonabsorbable suture. Among the absorbable sutures, polyglycolic acid (PGA) sutures evoked the least inflammatory response. The infection rate of contaminated tissues containing the PGA sutures was not significantly different from the incidence of infection of tissues subjected to the least reactive nonabsorbable sutures. The physical configuration of the suture played a relatively unimportant role in the development of early infection. The infection rate of contaminated tissues containing monofilament nonabsorbable sutures did not differ significantly from the incidence of infection of tissues subjected to multifilament sutures made from the same material. Coating the multifilament suture with either silicone, wax, or Teflon did not alter the incidence of early infection in the contaminated tissue. Finally, the presence of even the least reactive suture in contaminated subdermal tissue potentiated the development of infection.
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    Journal of Biomedical Materials Research 8 (1974), S. 163-173 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Experiments were conducted to further the understanding of tendon reconstructive surgery.A series of 20 dogs was used for replacement of the forepaw extensor carpi radialis tendon (a single tendon only is present in the dog) with active gliding tendon implants. The implants were attached distally and proximally so that new tendon prosthetic designs could be studied as well as new sheath development under gliding conditions.The results, recorded in this paper, show that a “gliding implant” can convert a nonspecific bed of connective tissue or scar into a specific living envelope comparable to a tendon sheath system. This system has been shown to be capable of lubricating and supporting a gliding artificial implant while augmenting normal tendon function. Degrees of active and passive gliding can take place for indefinite periods, providing the mechanical and dynamic capabilities of the new system are understood and controlled. The mature sheath will show a predictable physiologic response to unfavorable stimuli.Further evidence that the new gliding system functions as a physiologic sheath is borne out by the fact that the implant can be replaced in Stage II by a long free tendon graft. The graft is apparently supported in part by fluid nutrition and filmy adhesions between the distal and proximal anastomosis.
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    Journal of Biomedical Materials Research 8 (1974), S. 365-371 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The mandibular staple is an endosseous implant that will permit the attachment of a lower deture in cases of severe alveolar bone atrophy. It is placed through a submental incision and inserted into seven parallel holes drilled into the mandible. A curved bar containing seven pins is inserted in the holes and is place against the inferior border of the mandibular symphysis. The two lateral most pins project into the mouth and the five retentive pins remain completely buried in bone. Two fasteners are screwed down on the threading of the intraoral pins. Later a bridge containing Dalbo attachments is cemented to the fasteners which allow attachment to a lower denture. A series of 25 patients have been completed with 20 successful patients for survival rate of 80%. The longest case has been in for five years and the average case has been in for 3 years. Stainless steel, titanium and ceramic coated titanium has been with apparently equal success. Patient acceptance has been excellent.
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    Journal of Biomedical Materials Research 8 (1974), S. 391-399 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A study sponsored by the National Institute of Dental Research has as its major goal the development of easily fabricated and implantable dental anchors for replacement of missing or extracted teeth. Tissue ingrowth fixes the anchors in the mandibular or maxillary bone where they can serve as a base for future attachment of prefabricated dental caps, bridges, or other dental prostheses. More immediate objectives are to determine the suitability of specific porous titanium and ceramic materials for anchor applications, to develop satisfactory designs and fabrication procedures for producing these devices, and to define material/bone interface bonding characteristics through in vivo studies. The value of the Hanford Miniature Swine as a human analog for dental research is being assessed concurrently.
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    Journal of Biomedical Materials Research 8 (1974), S. 49-64 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A series of nonporous glasses and glass materials designed with controlled surface ion activities to allow chemical bonding to bone are described. Surface reactivities of these materials in vitro are correlated with biological activities in vivo and in tissue culture. Direct chemical bonding of the materials to bone is demonstrated. The mechanism for development of this bond is through the production of an amorphous ion surface gel on the bioglass. This gel induces osteogenesis by a chemotactic response of osteoblasts.
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    Journal of Biomedical Materials Research 8 (1974), S. 99-113 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: One method of providing an artificial limb for an amputee might be to attach the external prosthesis directly to the skeleton but a major problem is the behavior of the tissues at the point where the prosthesis penetrates the skin surface. Preliminary experiments have been carried out using small flexible implants in porcine skin to study the principles involved. It is confirmed that the epidermis grows down into the dermis around the nonporous materials and the implant-skin junction is unstable and readily becomes infected. It was found that polytetrafluorethylene with pores of 10 μm diameter and hydron sponge with pores of 40 μm diameter became invaded by fibrous tissue and this appeared to prevent the migration of epidermis alongside the implants and a stable ring of epidermal tissue was formed near the skin surface. A review of other situations where epidermal migration is taking place suggests that epidermis is able to migrate through damaged collagenous tissue, possibly with the help of leucocytic enzymes, but that epidermal cell movement is halted when the epidermal sheet is confronted by heathly collagen bundles.
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    Journal of Biomedical Materials Research 8 (1974), S. 145-153 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Polymeric materials are becoming increasingly popular as prosthetic materials in orthopedic surgery. One of these materials, polyethylene, is capable of being fabricated in a porous form suitable for tissue ingrowth. Porous polyethylene appears to be well suited for prosthesis attachment when bonded to its solid form of other prosthetic materials. Extensive bone growth into porous cylindrical specimens implanted in the canine femur has occurred as early as four weeks. Ingrown tissues appear normal and there is minimal inflammatory response. Mechanical strength of the porous material, though not as great as that of the solid material, does appear to be sufficient for certain orthopedic applications. Current research is directed toward determining interfacial strengths and the mechanical properties of the porous polyethylene-bone composite.
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    Journal of Biomedical Materials Research 8 (1974), S. 185-196 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: An investigation was conducted to determine the general physical characteristics of self-curing acrylic resin systems in terms of their potential utilization in total hip arthroplasty.Exothermic temperature, working and setting times were monitored with thermocouples placed in acrylic masses insulated via a Teflon mold. Mechanical strengths were run in an Instron testing machine. The same trends were noted in all systems studied.As thickness or mass increased, the maximum temperature and the setting time increased. As the powder to liquid ratio increased (thereby relatively less liquid), the maximum temperature, set times and dough times decreased, while the working time was essentially unaffected. As the ambient temperature decreased, the maximum temperature decreased while the dough, working and setting times increased.The mechanical strengths of the systems cured at one atmosphere are low compared to high temperature and pressure curing. Flowability of the materials decreases quickly as final set time is approached.Although trends are similar in many self-curing acylic systems minors shifts in complex proprietary compositions can produce a wide span or working and setting times. Because the surgical team controls such parameters as the mass employed, the amount of liquid introduced, and the ambient temperature it is important that they continuously re-evaluate their handling procedures particularly if new acrylic cements would be introduced.
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    Journal of Biomedical Materials Research 8 (1974), S. v 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Journal of Biomedical Materials Research 8 (1974), S. 271-283 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Through a survey of hip replacement arthroplasty the paper establishes the case for objective evaluation of these joints in the patient. It then outlines a simple, non-invasive technique, based on Paul's (1967) locomotion studies, to assess pre- and postoperative functional capability. Preliminary results which establish viability of the procedure are presented.
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    Journal of Biomedical Materials Research 8 (1974), S. 319-328 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A porous titanium alloy called void metal composite (VMC) was investigated for use in knee prosthesis fixation. The interfacial ingrowth fixation of VMC intrameduallary, subchondral, and variable density implants in goat femora was evaluated biomechanically and histologically at six weeks and five months. Biomechanical tests were done under static shear and dynamic, cyclic (fatigue) loading conditions. Readily identifiable bone, strong fixation, and excellent biocompatibility were typical. Some subarticular implants appeared to induce normal hyaline cartilage overgrowth.
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    Journal of Biomedical Materials Research 8 (1974), S. 87-90 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Journal of Biomedical Materials Research 8 (1974), S. 97-117 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A significant variation occurred in the inflammatory response to polyethylene and polyurethane when embedded subcutaneously in experimental animals. This variation apparently is related to the composition of the plastic and adsorption of proteins. The attraction of polymorphonuclear leucocytes by plastics apparently is related to the electrostatic and/or electrokinetic imbalance that occurs at or near the site of implantation.Polyurethane and polyethylene were selected for this study since preliminary observations had shown a variation in inflammatory response when they were embedded subcutaneously in the mouse. From this study it is evident that: (1) variations occurred in the inflammatory reaction in the subcutaneous tissue of mice and rabbits following the embedding of polyethylene and polyurethane; (2) polymorphonuclear leucocytes began to emigrate within hours after these two plastics were implanted, reaching their maximum number within 24 to 48 hr; (3) polymorphonuclear leucocytes usually were absent after the 6th experimental day in mice with polyurethane, but were present for 232 days in mice with polyethylene; (4) polymorphonuclear leucocytes were present in the rabbit for only a few days following subcutaneous implantation of polyethylene and polyurethane; and (5) leucocytes around the implanted polyurethane in the rabbit began to degenerate within 48 hr. The mechanism for this degeneration is not known.
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    Journal of Biomedical Materials Research 8 (1974), S. 185-188 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Journal of Biomedical Materials Research 8 (1974), S. v 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: Two types of dense Al2O3 ceramics (99.6% purity, 96% purity) were tested in the following fields of interest.1Wear resistibility using a pin and disk method under distilled water and human synovial fluid. Both types showed minimal initial corpuscular wear.2Biocompatibility of ceramic wear particles in mice and rats after injection by different ways. The crystal material is permanently deposited in macrophages, after transport via lymphpatic and blood vessels also in the RES without chronic inflammatory and progressive fibrotic response.3Under moderate stress conditions ceramic plates are fixed firmly by new bone formation within 2-3 months according to tetracycline label studies of bone growth in rats.4A new ceramic total hip prosthesis with two different socket designs for cement free fixation in bone is proposed and used in sheep experiments. The results of a 4 month experiment is presented showing firm fixation of the prosthesis under full stress conditions.
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    Journal of Biomedical Materials Research 8 (1974), S. 85-97 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A study of the tissue compatibility of aluminum oxide implants under different stress conditions in rabbits was performed over four- and eight-week implantation periods. The specific objectives were to examine endosteal bone ingrowth into aluminum oxide coneshaped plugs in amputated tibiae, while additional pellet-shaped implants in the tibiae and femora of rabbits with amputated and nonamputated limbs were studied to determine: (1) if the degree of loading placed on the amputated limb was sufficient to promote bone activity, (2) the degree of inertness and/or toxicity of the aluminum oxide implants, and (3) a possible cause of bone spurs.The results of the radiographic, histologic and microradiographic analyses of the in vivo implants demonstrated that there was little mineralized bone ingrowth into the coneshaped aluminum oxide implants in the amputated tibiae. The study also showed that the aluminum oxide pellet implants in the tibiae and femora of the nonamputated limbs demonstrated excellent mineralized bone ingrowth into surface and internal pores. By comparing these results with the incomplete ingrowth into corresponding pellet implants in the tibiae and femora of amputated limbs, it was determined that a lack of weight bearing and damage to the musculature and vascularity following amputation were interfering with the normal bone activity and therefore bone ingrowth.Angiographs and radiographs of the amputated tibiae demonstrated that bone spurs were present and that they originated at the site of the periosteal damage. Their cause was believed to be associated with an increase in the vascularity of the adjacent tissues.
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    Journal of Biomedical Materials Research 8 (1974), S. 137-144 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Ceramic materials for permanent implantation in osseous tissue, called osteoceramics, were based on an equimolar mixture of Ca3(PO4)2 and MgAl2O4. Tooth roots with dense regions and with regions of controlled porosity for tissue ingrowth were made from the material. They were implanted submucosally in the mandible and maxilla of dogs. Tissue response was aceptable and strong attachment occurred. Thin sections are presented showing the interface of the alveolar bone and the prosthesis.
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    Journal of Biomedical Materials Research 8 (1974), S. 155-162 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Clinical studies will permit only small sections of tendon sheaths to be removed for biopsy at restricted levels as the sheaths were to be used for tendon grafting. In active gliding programs, biopsy has been limited to small sheath sections in immediate relation to the distal or proximal anastomosis where gliding motion may be induced or minimal. In the passive gliding programs, biopsy has been limited to the most proximal segments where considerable folding of the sheath occurs or cul-de-sac buckling of the implant may produce irritation.As these were the only practical clinical sources of sheath sections for biopsy and study, the authors felt that a comparison study of sheath development in animals would broaden our understanding in humans. With this objective in mind, three canine laboratory studies were carried out where, for pure purposes of investigation, entire sheath sections were removed at designated time intervals for study.The flexible implants were well accepted, affording the opportunity to observe development of early sheaths in a controlled connective tissue environment, free from the stress of joint motion.The semi-rigid implants showed equal acceptance in side-by-side tissue level of the same dog as the flexible implant. This influenced changes in artificial tendon development from extrusion to the more exacting mold fabrication. It seemed evident that the degree of increase in stiffness of the new artificial tendons to gain a superior surface for gliding and increased strength would not change tissue acceptance providing flexibility was maintained.The cellular response in this study did not seem to represent a foreign body phenomena but an orderly acceptance of the soft tissue environment to the smooth surface of the inert implant.It is concluded that this study confirmed in animals the clinical findings of Mayer, Bunnell, Milgram, and Carroll.The consistent orderly development of the new sheaths formed in response to the static implants is impressive. The authors believe the appearance of these histologic sections are likely correlations with the development of new sheaths around the Hunter Tendon Prosthesis during the three-four week postoperative period when the hand is resting in a functional dressing.
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    Journal of Biomedical Materials Research 8 (1974), S. 197-207 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Poly-α-amino acids have been investigated for possible use in a wide variety of biomedical applications. These range from dialysis membranes to artificial skin substitutes to degradable sutures. The large number of available α-amino acids potentially provides an extremely large number of poly-α-amino acids. The majority of materials investigated to date are copolymers composed of two components, one of which usually provides the desired property for the given application.This paper deals with the further examination of a series of γ-benzyl-L-glutamate-L-leucine copolymers. Evidence is provided on the effect of these copolymers on the biological environment as determined by implantation in rats up to 200 days. In vitro tests were also performed and the effect of these tests on the stress-strain properties of one of the copolymers is presented.Preliminary evidence on biodegradable copolymer films is also included. These materials have free γ-carboxyl groups on the glutamate components.
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    Journal of Biomedical Materials Research 8 (1974), S. 427-434 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Following the classification of tissues according to their “dominant” and “interactive” components the paper surveys their load-deformation behavior, highlighting in particular the significance of time dependence. This leads to a discussion of the implant/tissue interaction in which the complexity that could be created by varying load and deformation time rates at the interface is explored.
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    Notes: The compatibility of implanted ceramic materials with autogenous bone, and the subsequently noted influence of the ceramic on the rate of new bone formation, were investigated to evaluate such materials for use in orthopedic implants. Three ceramic materials, aluminium oxide (Al2O3), zirconium oxide (ZrO2), and calcium aluminate (yCaO · xAl2O3) were tested. These were placed in the femurs of rhesus monkeys for periods of 50, 100, and 350 days. Definite compatability between the autogenous bone and the materials was exhibited for the implant time periods evaluated. No toxicogenic activity was noted in any of the biochemical, biomedical, and ceramographic evolutions. An added benefit resulted from the calcium aluminate composition, which was fabricated as a two-phase oxide material to make it slightly soluble in the body fluids. In the 50- and 100- day implants, the bone penetrated the ceramic for distances up to 100 μ while the ceramic dissolved and the pores enlarged. In addition, the mineralization in the area of the calcium aluminate was greater than that found around the other ceramics. Radiographs over the entire 350-day implant period confirmed the increased callus formation around all of the materials with no signs of rejection evident in the surrounding osseous or soft tissues. After 350 days the entire pore area of the calcium aluminate ceramic was infiltrated with a columnar substance which on the basis of scanning electron microscope procedures was considered to be mineralized osteoid.
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    Journal of Biomedical Materials Research 5 (1971), S. 53-62 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A series of DL-methionine/L-leucine copolymers was prepared from the coresponding N-carboxy-anhydrides. The copolymers formed clear flexible films having low water vapor transmission rates. Peroxide oxidation of the pendant methyl-theioethyl groups to methyl-sulfinoethyl groups enhanced the hydrophilic properties of the membranes, and the water vapor transmission rates rapidly increased with an increase in the number of pendant methyl-sulfinoethyl groups. Increasing the leucine content of the membranes produced a 13-fold increase in the carbon dioxide permeability and a 6-fold increase in oxygen permeability, whereas, an increase in the methionine content doubled the carbon dioxide-oxygen separation factor.Synthetic poly (α-amino acids) are very similar to naturally occurring proteins with respect to composition and conformation. Because of these similarities, they are being considered in aerosol spray bandages, synthetic skin applications and as coatings for plastic prostheses. The unusual permeability characteristics of the DL-methionine/L-leucine copolymers make them interesting membranes for possible use in artificial kidney machines and blood oxygenators.
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    Journal of Biomedical Materials Research 5 (1971), S. 63-79 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The flexural tests on 37 whole equine metacarpus bones are described and the results are given in terms of fundamental material properties as a function of age. The moduli of elasticity, rupture, and failure increase then decrease with increasing age. The rupture and failure deformations decrease with age. The stiffness and fragility indices increase with age. Averaging the data for all ages, the modulus of rupture was 35 ksi, the deflection at rupture was 0.22 inches, and the modulus of elasticity was 1.7 × 10 psi. The flexural rupture strength is about twice the uniaxial compression strength and about five times greater than the torsional strength for whole bone tests. The moduli of elasticity are about the same for flexure and uniaxial compression, and about five times greater than the torsional modulus of rigidity for whole equine bone.
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    Journal of Biomedical Materials Research 5 (1971) 
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    Keywords: Chemistry ; Polymer and Materials Science
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  • 67
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    Notes: A porous ceramic, in the form of small discs, has been implanted into the upper tibiae of adult mongrel dogs in survival experiments. A similar sized disc of a metal (vitallium, titanium, or stainless steel) was also implanted, for comparison, into each tibia. The tissue specimens were studied by microangiography and correlated histology. At the 4-month, and longer, intervals, the specimens were sectioned with the ceramic disc in situ. Injected capillaries were then observed to have penetrated the ceramic.The metals became surrounded by a shell of new-bone, lined by a fibrous membrane of varying thickness. The ceramic implants, on the other hand, appeared to have remained inert within the cancellous area of the tibiae, not surrounded by either a membrane or an osseous shell.Implications of these findings were discussed and further experiments, some of which are in progress, were proposed.
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    Notes: The management of severe flexor tendon injuries of the hand has been dramatically improved by tendon sheath reconstruction with an artificial tendon, followed by conventional tendon grafting. The purpose of this study was to investigate the nature of neosheath formation.In 25 chickens, the flexor tendons and sheaths in a toe were excised and replaced with a United States Army artificial tendon. An artificial tendon was also placed in the back, and four weeks later, tendons and surrounding tissue as well as normal tendon sheaths were excised and submitted for light, transmission electron microscopy and scanning electron microscopy.In all instances, neosheaths formed around the silastic coated artificial tendon. The neosheaths formed in the foot and back were similar to normal sheath, having the same cellular and fibrous composition. Reconstruction of the normal anatomy with an artificial tendon explains why this surgical technique gives superior results to other less physiologic procedures in patients with severe hand injuries.
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  • 69
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    Journal of Biomedical Materials Research 8 (1974), S. 219-226 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The biomaterials engineer of today has an extremely limited choice of approved metallic implant alloys with which to conduct his studies. There is essentially no incentive for larger companies to initiate basic research in the biomaterials field. New alloys which would have the best chance of developing as biomaterials would be “spin-off” alloys from somewhat related industries and currently in production. MP35N is just such a spin-off alloy with a background of years of in-vitro testing and use in corrosive environments. When compared to the desired implant material requirements, the material properties required of MP35N for present applications readily indicate its potential use as a biomaterial.It is a castable alloy which exhibits good as-cast ductility. In the wrought condition, yield strength levels from 60,000 to over 310,000 psi are possible with accompanying good ductility characteristics. Excellent stress corrosion cracking resistance and improved fatigue strength over present cast implant material are also characteristic of MP35N. Results, to date, from in-vivo tests indicate tissue compatibility of MP35N at least comparable to HS-21 (Vitallium).Possible medical applications for MP35N would include hip and knee joints, bone plates, heart pacer electrodes, suture wire and clips, and Endosseous blade implants.
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    Journal of Biomedical Materials Research 8 (1974), S. 285-288 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The bone-implant interface and the accompanying difficulties with fixation continue to be a major area of research activity. Biological fixation would appear to be the ideal method of fixation. Press-fit metal implants may be part of a larger answer that may include sintering, coatings, or both.
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    Journal of Biomedical Materials Research 18 (1984) 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Journal of Biomedical Materials Research 18 (1984), S. v 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Journal of Biomedical Materials Research 18 (1984), S. 413-425 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A complete study of the static and dynamic strength of complete maxillary dentures was undertaken. First, the denture base material was investigated in its various forms from the point of view of tension, creep, relaxation, fatigue, and the effect of a corrosive environment. Complete dentures were tested under static compression, and the distribution of stresses along the midline of the upper dentures was determined by means of strain rosettes and by reciprocating compression, the determination of their fatigue strength. The results were found to conform with experience as far as lifetime of complete dentures is concerned.
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    Journal of Biomedical Materials Research 18 (1984), S. 435-462 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: Many authors have examined the mechanical properties of bone cement and the various factors that affect its mechanical behavior. This article presents a comprehensive survey on the reported mechanical properties of bone cement. Variables that influence the mechanical properties, such as handling characteristics, strain rate, loading modes, additives, porosity, blood inclusion, in vivo environment, temperature, etc. have also been reviewed. The importance of specifying these variables in reporting test results on the mechanical properties of bone cement is pointed out. Previous attempts to improve the mechanical properties of bone cement are also summarized. Future research areas important for fully characterizing the physical properties of PMMA are also suggested.
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    Journal of Biomedical Materials Research 18 (1984), S. 137-146 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: Randomly cross-linked copolymers of 2-hydroxyethyl-methacrylate (HEMA) and methyl-methacrylate (MMA) have been prepared and studied in the dry and swollen state. Tensile and indentation tests indicate that by changing the composition of copolymers, it is possible to obtain materials with a wide range of mechanical properties and corresponding glass transition temperatures. Water diffusion coefficients in sorption and desorption experiments have been calculated and compared.
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    Notes: Although dogs have been used widely to study the healing of large caliber synthetic grafts, hypercoagulability probably makes the dog a poor model for studies of small caliber vascular prostheses. The baboon's coagulation system is similar to man's, but large caliber baboon grafts were reported to endothelialize rapidly. In this study the healing pattern of 4mm internal diameter Dacron carotid interpositon grafts in baboons was determined using specimens harvested at time points between 2 weeks and 18 months post-implantation and examined with light and scanning electron microscopy. The luminal surface of baboon grafts in the acute healing phase (〈1 month) was comparable to that reported in the literature for dogs. Baboon grafts did not completely endothelialize until 10-12 weeks post-implantation. For work with small caliber vascular protheses, the dog appears to have no advantage over the baboon as an animal model on the basis of graft healing.
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    Journal of Biomedical Materials Research 18 (1984) 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Journal of Biomedical Materials Research 18 (1984), S. 395-401 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The macrophage plays a pivotal role in both wound healing and cellular response to implants, including percutaneous devices. Within twenty-four hours macrophages were found in close contact with the implant surface. Eventually fibroplasts and connective tissue proliferate, and finally the implant will be encapsulated. The presence of macrophages is essential for the activation of collagen synthesis by fibroplasts. Implant shape and surface can profoundly affect macrophage behavior. At rough implant surfaces macrophages with giant cells are present for many months with the possibility of chronic granulomatous reactions. Superior tissue compatibility should be associated with smooth, well contoured implants with no acute angles.
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    Journal of Biomedical Materials Research 18 (1984), S. 427-434 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: A Ni-45 wt % Ti (Ni-50 at % Ti) alloy was cast into molds of magnesia and silica investments by use of a dental argon-arc pressure casting machine with a copper crucible. The castings exhibited shape memory properties. The shape recovery process was sharper in the specimens cast in magnesia investment molds than in those cast in silica (phosphate-bonded) investment molds. The latter casting had a hard region of the periphery, suggesting that shape recovery process may be affected by reaction of molten metal with silica. Furthermore, the alloy possessed the adequate mechanical properties for consideration as crown-and-bridge prostheses.
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    Notes: The release of corrosion products by implants has become a matter of concern. Using a microsphere model, the release of chromium, cobalt, and nickel, secondary to implantation of various surface area exposures of F-75, a cast cobalt-chromium alloy, was studied over a 30 day period in the rat. Dose related elevations were observed in the serum concentration of chromium and cobalt but not of nickel, with the maxima being achieved at 3 days after metal implantation followed by declines in concentration. The chromium elevation, approximately twelvefold for a surface area to body weight (SA/BW) ratio of 300 x is similar to that previously reported in patients receiving total hip replacement arthoplasties. However, the cobalt elevation, twentyfold for a SA/BW ratio of 300 x, has not been previously observed. These serum concentration changes are as yet unexplained, but are probably not due to fibrous capsule maturation or alloy repassivation.
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    Journal of Biomedical Materials Research 18 (1984), S. 547-559 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: An in situ immunoradiometric assay was devised to quantitate human fibrinogen deposited on hemodialysis membrane, Cuprophane, from in vitro exposure to fibrinogen solution and from ex vivo extracorporally clinical use. The method requires a monospecific 125I-labeled antifibrinogen-IgG purified by DEAE chromatography and immunoadsorption. The labeled antifibrinogen IgG was shown to react specifically with fibrinogen adsorbed and immobilized (by glutaraldehyde) on Cuprophane. Other plasma proteins such as human albumin, IgG, or α-thrombin, adsorbed singly or coadsorbed with fibrinogen on the surface did not seem to affect the fibrinogen-antifibrinogen reaction. The presence of blood cells such as platelets and granulocytes with fibrinogen on Cuprophane reduced only slightly the uptake of 125I-antifibrinogen-IgG. The examination of fibrinogen-fibrin deposition on clinically used Cuprophane by this technique and by autoradiography of the same material following 125I-antifibrinogen-IgG conjugation indicated that the deposition of fibrinogen was heavy and heterogeneous. We concluded that this in situ method may be useful to monitor fibrinogen-fibrin deposition and adsorption of other plasma proteins that occur under in vitro, ex vivo, and in vivo conditions.
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    Journal of Biomedical Materials Research 18 (1984), S. 601-607 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: This study was undertaken to examine the effectiveness of a commercially available n-butyl-2-cyanoacrylate (Histoacryl blueTri-Hawk International, 1570 Barré, Montréal, H4L 4M6 Quebec.) as a local treatment for cutaneous ulcers. Two ulcers, approximately 0.5 cm2 each, were made on the backs of 30 hamsters. The right side was covered with a thin film of tissue adhesive, while the left side was left untreated as a control. Animals were sacrificed at various times post-operatively, the tissue excised, processed, and examined with the light microscope. Results showed that cyanoacrylate decreased the inflammatory exudate early in the experiment, and epithelial migration occurred slightly earlier in experimental tissue. Scab formation was absent in experimental sites until the layer of adhesive was lost. After 2 days, healing was comparable in both experimental and control, and the sites were indistinguishable histologically at day 5.
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    Journal of Biomedical Materials Research 18 (1984) 
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    Keywords: Chemistry ; Polymer and Materials Science
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    Journal of Biomedical Materials Research 18 (1984), S. 895-909 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: An alternative to the usual technique of preclotting porous textile vascular prostheses prior to surgical implantation is to render them impermeable to blood by impregnation with a cross-linked albumin filler matrix. This material subsequently becomes the foundation for cellular development. The compatibility of such impregnated fabrics with newly formed endothelial cells has been evaluated by an in vitro organotypic culture method. This technique enables the characterization and numeration of cells that develop on blood contact surfaces and enables determination of their rate of development. Woven, knitted, and velour fabrics were evaluated folllowing coating with albumin and either storage in Tyrode solution or 40% ethanol or desiccation by critical point drying. Preclotted cardiovascular repair fabrics prepared according to conventional surgical protocol served as controls. The identification of the newly formed cells was confirmed histologically. The most extensive and rapid cellular development was observed on the woven fabric and is believed may have resulted from the smoother surface topography of this substrate. Good cellular development was noted particularly on fabrics which had been stored in Tyrode solution. Ethanol had a deleterious effect on the apparent compatibility.
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    Journal of Biomedical Materials Research 18 (1984), S. 695-705 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Human prothrombin in Tyrode's solution, in mock plasma (albumin, fibrinogen, and IgG mixture), and in citrated plasma adsorbs to Cuprophane, polyvinylchloride, and polyacrylonitrile surfaces. The adsorption of prothrombin is maximal in Tyrode's solution and minimal in plasma. The surface concentrations of prothrombin are highest on polyacrylonitrile, second on polyvinylchloride, and lowest on Cuprophane at all prothrombin concentrations tested in the bulk solution. Qualitative tests show that prothrombin adsorbed to polyvinylchloride can be activated by Taipan snake venom to generate thrombin that clots fibrinogen. However, more quantitative tests indicate that only part of the adsorbed prothrombin on all three materials can be activated to form thrombin exhibiting amidolytic activity. The partial reactivity of adsorbed prothrombin is further confirmed by release of 125I-peptide from surface bound 125I-prothrombin after treatment with Australian Taipan snake venom. Prothrombin bound to Cuprophane seems to promote granulocyte adhesion, but has no effect on platelet adhesion.
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    Journal of Biomedical Materials Research 18 (1984), S. 727-736 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Bovine pericardial tissue and tissue-derived bioprosthesis fixed in glutaraldehyde and stored in either glutaraldehyde or formaldehyde can induce cytotoxic reactions even after prolonged washing due to the slow leaching of the chemicals used for crosslinking and sterilizing. Sequential rinsing for up to 60 min was still not sufficient to eliminate cytotoxic effects. On the other hand, satisfactory results were obtained when cardiac valves made from glutaraldehyde fixed pericardium were stored in a solution containing 0.02% of propyl-hydroxy-benzoate and 0.18% methyl-hydroxy-benzoate. The valves stored in this solution and rinsed three times for 1 min in normal saline showed few signs of residual cytotoxicity. Rinsing in a solution containing glycine was partially effective in neutralizing the cytotoxic effect, and this or similar approaches offer good possibilities. The use of Chang cells grown in culture provides an excellent quantitative assay for the assessment of residual cytotoxicity and for evaluating the host response to different methods of fixation, storage, and rinsing of tissue derived bioprosthesis.
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    Journal of Biomedical Materials Research 18 (1984), S. 771-779 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Few in vitro systems for testing dental restorative materials have taken into account the protection afforded by the residual dentine in vivo. In turn opinions differ as to whether an increase in residual dentine thickness increases this protection. In this study an increase in the depth of dentine powder beneath zinc oxide eugenol (ZOE) reduced its toxicity, while this was not the case with the glass ionomer cement. Compaction of the powder had no effect, suggesting that protection was due to binding of the toxicant to the dentine rather than it acting as a physical barrier. Protein was shown to be very important in moderating the cytotoxicity of ZOE. These results suggest that in vivo the irritancy of some materials may be related to the depth of residual dentine but not others. The effect of exposure period and volume of these materials on their cytotoxicity was also investigated. Increasing the volume of ZOE while retaining the same surface area increased the toxicity of ZOE, while with the glass ionomer it had no effect.
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    Journal of Biomedical Materials Research 18 (1984), S. 881-894 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The macromolecular properties of 17 virgin commercial arterial prostheses and a series of explanted prostheses, both manufactured from poly(ethylene terephthalate) (PET) yarns, have been studied by gel permeation chromatography (GPC) and by differential scanning calorimetry (DSC). Only small differences were found between the average molecular weights and the degree of crystallinity of the unused reference grafts. A broadening of the DSC curves was observed for the prostheses containing texturized yarns compared with those made solely from flat, untexturized yarns. This broadening may be due to greater heterogeneity of the crystal sizes caused by the texturizing process and to the use of two or more different yarns with dissimilar thermal histories in the same prosthesis. Average molecular weights of the explant series were significantly lower than those of the corresponding reference grafts but almost time independent. The polydispersity index and the degree of crystallinity of the explants remained constant as a function of time. These results are discussed in regard to others available in the literature.
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    Notes: A cage implant system was utilized to quantitatively and qualitatively characterize in vivo leukocyte interactions with cast Biomer. Scanning electron microscopy (SEM) in conjunction with cytochemical staining procedures were used to investigate the cellular events at the leukocyte/Biomer interface as well as in the inflammatory exudate over a 21-day implantation period. SEM was used to characterize leukocyte morphology on the Biomer surface and the cytochemical stains were used to differentially count leukocytes and to demonstrate intracellular alkaline and acid phosphatase activity. The results showed that the population density of leukocytes on the Biomer surface diminished with implantation time. The population density of multinucleated foreign body giant cells remained constant with time, while the numbers of nuclei per giant cell increased. The differential analysis revealed that macrophages preferentially adhered to the Biomer surface compared to other leukocytes in the exudate. The phagocytic capability of all adherent leukocytes, including giant cells, decreased with time and this corresponded to changes in leukocyte morphology observed with SEM.
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    Journal of Biomedical Materials Research 18 (1984), S. 1017-1030 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Bioreactive-glass-coated hip prostheses were implanted in dogs for periods of time ranging from 3 to 17 months. The prostheses were tailor-made for each animal through the use of standard radiographs. However, such a procedure does not necessarily yield a close apposition between the glass layer and bone. As a result, the initial stability of the component can be lost before bone bonding is established. Secondary to this phenomenon, the micromotion can lead to a continuous disruption of the top film on the glass despite the evidence of various reaction layers on the glass surface.
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    Journal of Biomedical Materials Research 18 (1984), S. 961-968 
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Polyurethanes are finding increasing utilization in biomedical applications. Recently, the reported finding of methylene dianiline (4,4′-diaminodiphenylmethane, MDA) in the aqueous extracts of autoclaved 4,4′-diphenylmethane diisocyanatebased polyurethanes promoted our investigation of the origin and extent of extractable methylene dianiline in polyurethanes. A high-pressure liquid chromatography procedure using precolumn derivatization is utilized to selectively monitor the appearance of this diamine in the aqueous extracts of polyurethanes subjected to water immersion, heat aging, and various sterilization techniques. No MDA was found in the aqueous extracts of the treated polyurethane except for the case of prolonged steam autoclaving. The appearance of 3-5 ppb MDA in the extract under these conditions is attributed to hydrolysis of the polymer. The stability of the polyurethanes under most conditions renders these materials useful in biomedical applications.
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    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The binding of metal ions from salts and from corrosion products of 316 LVM stainless steel and MP-35 to blood cells and serum proteins was studied in vitro. In the first series of experiments, metal salts were added to whole blood and then the blood separated into red cells, white cells, and serum. Nickel from nickel chloride or corrosion products of stainless steel bound in very small quantities to blood cells. Cobalt from cobalt chloride bound to both red cells and white cells. Chromium from chromic chloride (Cr3+) bound to cells in very small quantities whereas chromium from potassium dichromate (Cr6+) and corrosion products showed very high to binding to red cells and some binding to white cells. In a second series of experiments the blood was separated into its components and then the metal salts were added and the binding pattern was identical. In a third series of experiments serum which had interacted with the metal salts or corrosion products was separated into its components by isolectric focusing on polyacrylamide gels. Almost all of the metal, whatever the source, was detected in the albumin region of the gels indicating strong binding to albumin. These studies on the cell and protein binding of the metals help to explain the dissemination of corrosion products from the site of the implant and subsequent systemic responses by some individuals.
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  • 93
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In an attempt to find an alternative procedure to the preclotting of porous textile vascular prostheses, the feasibility of an albumin coating and ethanol preservation technique has been evaluated by implanting albuminated polyester prostheses as substitutes in the thoracic aorta of dogs. Nine different grafts representing woven, knitted, and velour constructions were implanted for periods ranging from 4 h to 6 months. At the sacrifice, the grafts were excized for measurement of the thrombogenicity of the flow surface, for pathological examination by light microscopy and SEM, and for quantifying the changes in the textile structure during implantation. Also the kidneys were removed and examined for infarcts caused by trapped circulating emboli. The healing characteristics of the nine different grafts proved similar and followed the same sequence of events as preclotted control grafts. The albumin coating and ethanol preservation resulted in a somewhat slower rate of healing. Yet, given sufficient time, a more completely healed graft was achieved as evidenced by the presence of endothelial-like cells throughout the length of the graft. In addition, the albumin is believed to reinforce the textile structure by reducing the tendency to stretch and dilate in vivo.
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  • 94
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 18 (1984), S. 1115-1124 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: For intravascular implantation, a biofunctional surface seems to retard surface thrombosis upon synthetic materials. Prostaglandins, like PGI2, PGE1, and PGD2, etc., are believed to stimulate membrane-bound adenyl cyclase and thereby raise intracellular levels of c-AMP within platelets, which inhibit platelet adhesion and aggregation. A new procedure is suggested for the immobilization of prostaglandin E1 on an albuminated polymer matrix, through glutaraldehyde coupling. Materials thus prepared show dramatic antiplatelet effects, with regard to platelet adhesion, when compared with albumin-immobilized surfaces. The affinity of various modified surfaces toward platelet adhesion is studied, using washed platelets suspended in Tyrode's solution. Octane contact angle studies are used to develop an understanding of the varied nature of bound substrates at equilibrium on polymer surfaces. These are studied at the solid/liquid interface, which is closest to in vivo conditions. The plasma recalcification time demonstrates the anticoagulant properties of various surfaces. A possible role of PGE1 in reducing platelet activity in the presence and absence of vitamin C is discussed. This technique may be used in the development of nonthrombogenic surfaces on existing biomedical polymers. Simultaneous pharmaceutical modification of the blood with vitamin C may enhance the blood compatibility of the surface.
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  • 95
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 5 (1971), S. 59-74 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Excellent in vivo thromboresistance has been obtained for FEP Teflon and for a polyether urethane prepared with electronegative surfaces using the electret effect. In vitro tissue culture studies have shown a marked improvement in tissue compatibility for negatively electrified Teflon. Studies on other materials, including Hypalon rubber, sulfonate cross-linked Hypalon and Kel F have shown a moderate improvement in blood compatibility. These in vitro and in vivo experiments will be described. Surface physical properties of these electrified materials, including water contact angle and charge, have been measured. Correlations between surface physical measurements and blood compatibility data will be presented.
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  • 96
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 5 (1971), S. 105-127 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Flexible and rigid epoxy and urethane polymers containing heparin chemically and uniformly incorporated throughout and/or ionically complexed to quaternized amine grops were prepared and shown to have excellent thromboresistance in vitro and in vivo. These heparin-modified polymers were implanted into the vena cava of dogs and successfully passed multiple acute (2 hr) and chronic (2 week) exposure periods. It was also demonstrated that the chemically coupled heparinized epoxies had no measurable adverse effects on blood cells, platelets, or plasma proteins, and that the heparin was not extractable. Significantly, epoxies containing polyoxypropylene/polyoxyethylene glycol (an additive which had no thrombus-inhibiting properties of its own) also exhibited excellent thromboresistance when characterized in vivo in dogs. The applicability of these various materials for the fabrication of circulatory assist device components was demonstrated. The effect of polymer polarity, surface charge, and conductivity were investigated with indeterminate results and unmodified commercial polymers uniformly exhibited poor clotting characteristics. In vitro clot-inhibiting characteristics were shown to be a sufficient, but not necessary, condition for indicating in vivo thromboresistant activity in polymer systems.
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  • 97
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: These studies have furthered the development of a flexible impermeable encapsulant for implantable electronic devices. Medical grade silicone rubber, a widely used implantable material, is well known to be permeable to water vapor. We have demonstrated that silicone rubber is apparently permeated by electrolytes. This permeability to electrolytes can be blocked by impregnation of the silicone rubber with certain naturally occurring waxes during vulcanization. Implantation into living tissue has shown this material to be well tolerated. Of the natural waxes studied thus far, spermaceti has revealed the best overall properties as an impregnant for silicone rubber.
    Additional Material: 6 Ill.
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  • 98
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Expanding artificial implants are made of crosslinked hydorphilic polymers which imbibe body fluids and swell to a predetermined volume. The material is implanted in a dehydrated state; it then swells to fill a body cavity (i.e., vitreous cavity in the eye), or to give a form to the surrounding tissues (i.e., in plastic surgery). Such implants can be introduced in organs or tissues through a smaller incision than regular plastic and rubber implants, and have the advantage over injectable polymers in that they do not separate into globules and do not migrate from the area of implantation. The swelling equilibrium of slightly crosslinked poly (glyceryl methacrylate) [PGMA] hydrogels in salt solutions, urea, serum, and in the homogenized vitreous of the eye is given. Also, the swelling rate of PGMA in physiologic saline solution and in serum, as well as the swelling pressure-volume relationship of PGMA gels in water, is reported. The application of PGMA as an expanding implant inside the eye, and against its outer wall in retina surgery, is discussed.
    Additional Material: 7 Ill.
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  • 99
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    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 5 (1971), S. 459-488 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The true diffusive permeabilities of commercial, modified commercial, and laboratory cast regenerated cellulose membranes were measured with a batch dialyzer using 15 solutes (sodium chloride, nine radioactively labelled organic solutes, and five low molecular weight proteins) ranging in molecular weight from 58 to 68,000. Additional measurements included membrane thickness, water content, and strength properties, as well as equilibrium solute partition coefficients and solute diffusion coefficients in free solution. All commercial cellophanes were similar in sodium chloride permeability on a unit thickness basis and were significantly less permeable than hydrophilic wet gel membranes. This difference was attributed to the irreversible collapse of membrane structure upon drying. As the solute characteristic size increased, permeability decreased more sharply with commercial cellophane than with wet gel cellulose, the ratio between the two becoming an order of magnitude for large solutes. The ratio between the solute diffusion coefficient in the membrane and in free solution decreased exponentially with increasing solute size. The results suggest further work for higher permeability cellulosic hemodialysis membranes.
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  • 100
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    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 5 (1971), S. 529-529 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Type of Medium: Electronic Resource
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