bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic scaling of SJ‐8029, a novel anticancer agent possessing microtubule and topoisomerase inhibiting activities, by species‐invariant time methods
Authors: Shin Beom S. , Kim Dong H. , Cho Chang Y. , Park Si K. , Chung Sun G. , Cho Eui H. , Lee Sun H. , Joo Jeong H. , Kwon Ho S. , Lee Kang C. , Yoo Sun D.
Published: May 2003

This study examined the pharmacokinetic disposition of SJ‐8029, a novel anticancer agent possessing microtubule and topoisomerase inhibiting activities, in mice, rats, rabbits and dogs after i.v. administration. The serum concentration‐time curves of SJ‐8029 were best described by tri‐exponential equations in all these animal species. The mean Cl, Vss and t1/2 were 0.3 l/h, 0.1 l and 63.2 min in mice, 1.5 l/h, 1.6 l and 247.7 min in rats, 13.8 l/h, 39.6 l and 245.9 min in rabbits, and 29.2 l/h, 44.6 l and 117.4 min in dogs, respectively. Based on animal data, the pharmacokinetics of SJ‐8029 were predicted in humans using simple allometry and also by several species‐invariant time transformations using kallynochron, apolysichron and dienetichron times. The human pharmacokinetic parameters of Cl, Vss and t1/2 predicted by the simple allometry and various species‐invariant time methods were 50.4–145.0 l/h, 369.0–579.8 l and 242.0–1448.3 min, respectively. These preliminary parameter values may be useful in designing early pharmacokinetic studies of SJ‐8029 in humans. Copyright © 2003 John Wiley & Sons, Ltd.
Time dependent pharmacokinetics of albendazole in human
Authors: Mirfazaelian A. , Rouini M. R. , Dadashzadeh S.
Published: May 2003

The pharmacokinetics of the main metabolites of albendazole (albendazole sulphoxide (ABZ‐SO) and albendazole sulphone (ABZ‐SO2)) were studied in 12 healthy human volunteers in a double blind design on the first and last days of oral administration of 800 mg albendazole daily for 15 days.

No significant differences were observed in Cmax, Tmax and Vd/F of ABZ‐SO, whereas the AUC, AUMC and T1/2 of this metabolite were significantly reduced and Cl/F was significantly increased in multiple dosing. There were also no significant differences in the Cmax, Tmax, Vd/F and T1/2 of ABZ‐SO2, whereas the AUC and AUMC of this metabolite were significantly reduced and Cl/F was significantly increased in multiple dosing.

These observations suggest time dependent pharmacokinetics of albendazole (observed for ABZ‐SO and ABZ‐SO2), which was explained on the basis of the induction of enzymes involved in the metabolism of ABZ‐SO (albendazole sulphoxide) to metabolites other than albendazole sulphone in multiple dosing. Copyright © 2003 John Wiley & Sons, Ltd.
Lack of interaction between HEPP, a new antiepileptic agent, and carbamazepine in rabbits
Authors: García A. Luis , Medina R. Liz , Pérez M. Rodolfo , Jung C. Helgi
Published: May 2003

The effect of the combination of a new anticonvulsant drug HEPP and carbamazepine (CBZ) on the pharmacokinetics of HEPP and CBZ was investigated using rabbits as an animal model. The study was performed in 18 male New Zealand white rabbits which were randomly divided into three groups, according to a balanced incomplete block design of three treatments and two periods. Plasma concentrations for HEPP and CBZ were assayed using HPLC methods. The results showed that the pharmacokinetic parameters Cmax, AUC and t1/2 were not statistically different when HEPP was administered alone and with CBZ, (AUC0−α 82.86±19.40 vs 83.24±12.56 µg h ml−1; t 1 2 β 3.40±0.29 vs 3.36±0.45 h; Cmax 18.93±2.99 vs 19.79±2.68 micro;g ml−1 and Tmax 1.27±0.16 vs 1.22±0.11 h for HEPP alone and HEPP plus CBZ respectively. Evaluation of the pharmacokinetic parameters of CBZ showed, AUC0−inf 61.5±21.7 vs 67.4±23.8 µg h ml−1; t12 4.60±1.54 vs 4.41±1.35 h; Cmax 8.45±3.83 vs 8.70±2.59 micro;g ml−1 when the drug was administered alone and CBZ plus HEPP, respectively. Our data indicate that there is no effect on the pharmacokinetics of either HEPP or CBZ, when they are administered simultaneously. Copyright © 2003 John Wiley & Sons, Ltd.
Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects
Authors: Wójcicki Jerzy , Jaroszynska Maria , Droździk Marek , Pawlik Andrzej , Gawrońska‐Szklarz Barbara , Sterna Rozalia
Published: May 2003

The lipophilic beta‐adrenoreceptor antagonist propranolol and hydrophilic atenolol have been studied to define their pharmacokinetic and pharmacodynamic characteristics in obese patients. A total of 43 subjects were allocated into three study groups: (1) healthy, lean, normolipaemic volunteers, (2) obese normolipaemic subjects, and (3) obese patients with lipid disorders. A crossover method with an interval of 2 weeks was applied for oral 80 mg propranolol and oral 100 mg atenolol administration. Heart rate as well as systolic and diastolic blood pressure were recorded during 24 h. At each time‐point of measurement blood serum concentration of propranolol and atenolol were evaluated. Pharmacokinetic parameters of the drugs were calculated using a one‐compartment open model for extravascular administration. There were no statistically significant differences in blood serum concentrations of propranolol between the studied groups. The concentrations of atenolol were significantly lower in both normolipaemic and hyperlipidaemic obese subjects. A trend towards increase in Vd/F and Cl/F of propranolol in obese patients with hyperlipidaemia were noted. In the case of water‐soluble atenolol, the AUC, Cmax, Cl/(F×BW) were significantly lower in obese hyperlipidaemic and normolipaemic patients in comparison with lean subjects. The pharmacodynamic effects of propranolol and atenolol in obese and lean subjects were of similar magnitude. The observed differences between obese and non‐obese persons were clinically not relevant. Copyright © 2003 John Wiley & Sons, Ltd.
Effect of length of sampling schedule and washout interval on magnitude of drug carryover from period 1 to period 2 in two‐period, two‐treatment bioequivalence studies and its attendant effects on determination of bioequivalence
Authors: Dhariwal Kuldeep , Jackson Andre
Published: May 2003

The relationships between post‐dosing blood sampling schedules and length of washout interval on the percent of drug carryover into period 2, in a two‐treatment, two‐period, crossover bioequivalence study was investigated. Observed simulations were done using a two‐compartment model with a beta half‐life of 100 h, sampling to 200 and 300 h, followed by 1 to 4 washout half‐lives. These data were compared with simulations with sampling for 200 and 300 h and no carryover between periods (i.e. true data) and used to establish the per cent carryover. Pseudo‐observed concentration period 2 data were also generated for an experimental amiodarone bioequivalence study by adding either 5%, 10% or 50% of the period 2 Cmax value to the observed concentrations of selected subjects (i.e. those with longest half‐lives) to give a pseudo‐plasma concentration profile. Further investigation via simulation was done by including or excluding subjects with time 0 concentrations of 1%–10% of period 2 Cmax. The simulated data indicated that up to a 3% carryover of AUC into the second period of a bioequivalence study had no effect on the power of the 90% CI for AUC and Cmax. For amiodarone, second period pre‐dose drug concentrations equal to as much as 50% of the observed period 2 Cmax value had less effect on the 90% CI (i.e. compared with the true data) for AUC and Cmax than did subject deletion. Copyright © 2003 John Wiley & Sons, Ltd.
Revisiting the role of retinoid signaling in skeletal development
Authors: Weston Andrea D. , Hoffman Lisa M. , Underhill T. Michael
Published: May 2003

Several years ago, it was discovered that an imbalance of vitamin A during embryonic development has dramatic teratogenic effects. These effects have since been attributed to vitamin A's most active metabolite, retinoic acid (RA), which itself profoundly influences the development of multiple organs including the skeleton. After decades of study, researchers are still uncovering the molecular basis whereby retinoids regulate skeletal development. Retinoid signaling involves several components, from the enzymes that control the synthesis and degradation of RA, to the cytoplasmic RA‐binding proteins, and the nuclear receptors that modulate gene transcription. As new functions for each component continue to be discovered, their developmental roles appear increasingly complex. Interestingly, each component has been implicated in skeletal development. Moreover, retinoid signaling comes into play at distinct stages throughout the developmental sequence of skeletogenesis, highlighting a fundamental role for this pathway in forming the adult skeleton. Consistent with these roles, manipulation of the retinoid signaling pathway significantly affects the expression of the skeletogenic master regulatory factors, Sox9 and Cbfa1. In addition to the fact that we now have a greater understanding of the retinoid signaling pathway on a molecular level, much more information is now available to begin placing retinoid signaling within the context of other factors that regulate skeletogenesis. Here we review these recent advances and describe our current understanding of how retinoid signaling functions to coordinate skeletal development. We also discuss future directions and clinical implications in this field. Birth Defects Research (Part C) 69:156–173, 2003. © 2003 Wiley‐Liss, Inc.
Morphogenesis and dysmorphogenesis of the appendicular skeleton
Authors: Shum Lillian , Coleman Cynthia M. , Hatakeyama Yuji , Tuan Rocky S.
Published: May 2003

Cartilage patterning and differentiation are prerequisites for skeletal development through endochondral ossification (EO). Multipotential mesenchymal cells undergo a complex process of cell fate determination to become chondroprogenitors and eventually differentiate into chondrocytes. These developmental processes require the orchestration of cell–cell and cell–matrix interactions. In this review, we present limb bud development as a model for cartilage patterning and differentiation. We summarize the molecular and cellular events and signaling pathways for axis patterning, cell condensation, cell fate determination, digit formation, interdigital apoptosis, EO, and joint formation. The interconnected nature of these pathways underscores the effects of genetic and teratogenic perturbations that result in skeletal birth defects. The topics reviewed also include limb dysmorphogenesis as a result of genetic disorders and environmental factors, including FGFR, GLI3, GDF5/CDMP1, Sox9, and Cbfa1 mutations, as well as thalidomide‐ and alcohol‐induced malformations. Understanding the complex interactions involved in cartilage development and EO provides insight into mechanisms underlying the biology of normal cartilage, congenital disorders, and pathologic adult cartilage. Birth Defects Research (Part C) 69:102–122, 2003. Published 2003 Wiley‐Liss, Inc.
Hyaluronan and CD44: Strategic players for cell–matrix interactions during chondrogenesis and matrix assembly
Authors: Knudson Cheryl B.
Published: May 2003

Embryonic induction, soluble and insoluble factors, receptors, and signal transduction are orchestrated for the morphogenesis of the cartilage elements. The interaction of cells with the extracellular matrix (ECM) may lead to altered cellular response to morphogens based on the formation of new adhesive contacts, or the uncoupling of cell–matrix interactions. Hyaluronan's influence on cell behavior, and its intimate association with cells are accomplished by a wide variety of specific binding proteins for hyaluronan. The temporal expression of the hyaluronan receptor CD44 (which is expressed as several alternatively spliced variants) may be strategic to many of these cell–matrix interactions during chondrogenesis. CD44 expression is temporally coincident with the reduction of intercellular spaces at the regions of future cartilage deposition. The spatial organization of CD44 at the cell surface may function to establish or regulate the structure of the pericellular matrix dependent on a hyaluronan scaffold. As the ECM is modified during embryogenesis, the cellular response to inductive signals may be altered. An uncoupling of chondrocyte–hyaluronan interaction leads to chondrocytic chondrolysis. Thus, consideration of cell–matrix interactions during chondrogenesis, in the light of our current understanding of the temporal and spatial expression of signaling morphogens, should become a promising focus of future research endeavors. Birth Defects Research (Part C) 69: 174–196, 2003. © 2003 Wiley‐Liss, Inc.
Development of synovial joints
Authors: Archer Charles W. , Dowthwaite Gary P. , Francis‐West Philippa
Published: May 2003

Synovial joints arise through two main processes. In long bone elements, cartilaginous differentiation occurs across the locations of the prospective joints that then segment secondarily. This process occurs through the development of a noncartilaginous region known as the interzone. The interzone becomes an important signaling center to the opposing elements, which can regulate growth through such factors as GDF‐5. The interzone also expresses bone morphogenetic proteins (BMPs) and their antagonists, such as noggin. Overexpression of BMPs, or the loss of noggin leads to joint fusions. The interzone also expresses Wnt‐14, which appears to be specific for this region in the developing anlagen, and regulates its nonchondrogenic nature. Cavitation of the joint follows, driven by selective high‐level synthesis of hyaluronan by interzone cells and presumptive synovial cells. In addition, as the interzone disperses during cavity enlargement, data are now accruing that suggest that both the synovium and articular cartilage develop from this population. Finally, the development of articular cartilage progresses through appositional growth driven by a progenitor/stem cell subpopulation that resides in the articular surface. The individual elements of the skeleton are connected together at regions termed joints or articulations. Classically, there are three broad categories of joints: immovable joints (syntharthroses); mixed articulations, in which the range of movement is limited (amphiarthroses); and the movable, or synovial, joints (diarthroses). This review concentrates on the development of the synovial joints. Birth Defects Research (Part C) 69:144–155, 2003. © 2003 Wiley‐Liss, Inc.
Comparison of qualitative and quantitative analyses of age‐related changes in clivus bone marrow on MR imaging
Authors: Bayramoǧlu Alp , Aydingöz Üstün , Hayran Mutlu , Öztürk Hakan , Cumhur Meserret
Published: June 2003

Magnetic resonance (MR) imaging is capable of detecting a wide spectrum of diseases involving clivus bone marrow. To evaluate any pathology in this region, the normal MR signal intensity patterns according to age should be known. Assessment of clivus bone marrow is usually and more efficiently made visually (qualitatively) on routine MR imaging. To compare the qualitative and quantitative analyses of age‐related changes in clivus bone marrow on MR imaging, midsagittal T1‐weighted MR images of the clivus bone marrow were prospectively evaluated in 201 subjects. MR signal intensity patterns of clivus bone marrow were qualitatively graded from I to III according to the proportions of low and high signal intensity areas within the clivus (Grade I: predominantly hypointense, Grade III: predominantly hyperintense). Signal intensity measurements were also made from the clivus, pons, and the cerebrospinal fluid within the fourth ventricle. Grade I pattern was observed in 92% of the subjects in the first decade, whereas Grade III pattern was not seen in this decade; Grade I pattern was absent in all but one of the subjects over the age of 50. Mean values of clivus/pons and clivus/CSF signal intensity measurements gradually increased with age in both males and females. Comparison of these ratios in each gender showed statistically significant higher values for males (P < 0.05). Comparison of the qualitative and quantitative results showed that calculated mean values of intensity ratios for each grade were different from each other; however, there was an overlap of the ranges of signal intensity ratios for Grades II and III. Visual evaluation of the clivus bone marrow MR signal is validated with the quantitative assessment results. Statistically significant higher intensity ratios in males may reflect a difference between gender in the bone mineral content under the influence of sex hormones. Clin. Anat. 16:304–308, 2003. © 2003 Wiley‐Liss, Inc.
Bilateral asymmetric deficiency of the pectoralis major muscle
Authors: Mosconi Tony , Kamath Sylvia
Published: June 2003

We observed a rare, bilateral congenital deficiency of the pectoralis major muscle in a 72‐year‐old female cadaver in our gross anatomy dissection laboratory. The outward appearance of the anterior thoracic wall, which included well‐developed breasts, revealed no obvious abnormalities. Upon dissection, the following features were observed: 1) on the left side, the sternal portion of the sternocostal head of the pectoralis major muscle was absent, the costal portion of the sternocostal head and the clavicular head were both well developed, a normal pectoralis minor was present, and the deltoid and subclavius muscles were not hypertrophied as is often the case when the pectoralis major muscle is deficient; 2) on the right side, the entire pectoralis major muscle was absent and the pectoralis minor, deltoid, and coracobrachialis muscles were infiltrated with connective tissue and fat; and 3) on both sides, the lateral pectoral nerves were absent and the medial pectoral nerves were present. The absence of the lateral pectoral nerves suggests that the deficiencies in the pectoralis major muscles are congenital malformations resulting from a developmental failure of the embryonic muscles rather than a sequel to polio or Poland's syndrome. Clin. Anat. 16:346–349, 2003. © 2003 Wiley‐Liss, Inc.
Median nerve penetration by a muscular branch of the brachial artery
Authors: Roy T. S.
Published: June 2003

Arterial variations in the distal half of the arm are common (Anagnostopoulou and Venieratos 1999, J. Anat. 195:471–476). We observed a rare variant of a muscular branch of the brachial artery that penetrated the median nerve in the lower part of the arm. After its origin from the posteromedial surface of the brachial artery, the muscular branch passed through a nervous loop in the median nerve to enter and supply the brachialis muscle. At the site of arterial penetration, the nerve displayed perineurial thickening and increased fasciculation and interfascicular connective tissue. Three small branches of the artery supplied the nerve fascicles. We did not observe nerve compression or muscular changes, but the possibility of altered clinical symptoms produced by irritation from arterial pulsation cannot be ruled out. This variation may be clinically important because symptoms of median nerve compression arising from similar variations are often confused with more common causes, such as radiculopathy and carpal tunnel syndrome. Clin. Anat. 16:335–339, 2003. © 2003 Wiley‐Liss, Inc.
Duplicated inferior vena cava and crossed renal ectopia with abdominal aortic aneurysm: Preoperative anatomic studies facilitate surgery
Authors: Shaw M. B. K. , Cutress M. , Papavassiliou V. , White S. , Thompson M. , Sayers R.
Published: June 2003

Abdominal aortic aneurysm in association with duplication of the inferior vena cava and crossed renal ectopia is described for the first time. Preoperative imaging with computer‐aided tomography provided good visualization of the local anatomy, allowing the surgical approach to be adapted for the best access to the surgical site. A retroperitoneal approach was successfully used for repair of the abdominal aortic aneurysm. Clin. Anat. 16:355–357, 2003. © 2003 Wiley‐Liss, Inc.
Dual sensory innervation of the dorsum of the thumb
Authors: Madhavi C. , Holla S. J.
Published: June 2003

The value of the thumb has been described as being almost equal to the rest of the fingers combined (Decker and du Plessis, eds. 1986, Lee McGregor's synopsis of surgical anatomy. 12th ed. p 496). Normal hand function is dependent upon the integrity of both the sensory and motor innervation of the thumb. A thorough knowledge of normal and anomalous sensory innervation of the digits has clinical application because of the increased use of local anesthesia and developments in plastic surgery involving the skin of the digits. Herein is reported an unusual variation in the sensory innervation of the thumb in an adult cadaver. The normal innervation of the dorsum of the thumb is reviewed, and the clinical importance of this variation is discussed. Clin. Anat. 16:344–345, 2003. © 2003 Wiley‐Liss, Inc.
Anomalous flexor digiti minimi brevis in Guyon's canal
Authors: Madhavi C. , Holla S. J.
Published: June 2003

In an adult male cadaver, the flexor digiti minimi brevis, a muscle of the hypothenar eminence, was found to arise from the superficial transverse septum (between the superficially placed flexor carpi ulnaris, palmaris longus, and flexor carpi radialis muscles, and the deeply placed flexor digitorum superficialis muscle) in the distal fourth of the flexor aspect of the left forearm. The muscle exhibited two strata of muscle fibers at its origin. The superficial stratum was a thin layer of transversely running fibers confined to the forearm, which has not been previously reported. The deep stratum, a thick layer of longitudinally running fibers, formed the bulk of the muscle. It traversed Guyon's canal superficial to the ulnar nerve and vessels to reach the hypothenar eminence. Its course through Guyon's canal could be a cause for ulnar tunnel syndrome. The ulnar nerve trunk innervated not only the anomalous flexor digiti minimi brevis muscle, but also abductor digiti minimi and palmaris brevis. This may be due to the common phylogeny of these three muscles from the same muscle mass. Clin. Anat. 16:340–343, 2003. © 2003 Wiley‐Liss, Inc.
Lateral femoral cutaneous neuralgia: An anatomical insight
Authors: Dias Filho L.C. , Valença M.M. , Guimarães Filho F.A.V. , Medeiros R.C. , Silva R.A.M. , Morais M.G.V. , Valente F.P. , França S.M.L.
Published: June 2003

A detailed anatomic study was carried out on the lateral femoral cutaneous nerve to better understand the etiology and treatment of lateral femoral cutaneous neuralgia. As it passed from the pelvis into the thigh, the lateral femoral cutaneous nerve ran through an “aponeuroticofascial tunnel,” beginning at the iliopubic tract and ending at the inguinal ligament; as it passed through the tunnel, an enlargement in its side‐to‐side diameter was observed, suggesting that the fascial structures proximal to the inguinal ligament may be implicated in the genesis of lateral femoral cutaneous neuralgia. The finding of pseudoneuromas at this location, distant from the inguinal ligament, supports this hypothesis. The anterior superior iliac spine is located approximately 0.7 cm from the lateral femoral cutaneous nerve and serves as the bony landmark for nerve localization. Within the first 3 cm of leaving the pelvis, the lateral femoral cutaneous nerve was observed deep to the fascia lata; therefore, surgical dissection within the subcutaneous fascia may be conducted with relative impunity near the anterior superior iliac spine just inferior to the inguinal ligament. In 36% of cases there was no posterior branch of the nerve, which is correlated to lateral femoral cutaneous neuralgia symptoms often being limited to the anterior branch region. An accessory nerve was found in 30% of cases. Clin. Anat. 16:309–316, 2003. © 2003 Wiley‐Liss, Inc.
Left atrial isomerism: Clinicopathologic findings in a 14‐year‐old boy
Authors: Chatrath Ritu , O'Leary Patrick W. , Edwards William D.
Published: June 2003

Visceral heterotaxy syndromes have been associated with complex congenital heart disease and several attempts have been made to classify these lesions. One area of controversy that remains is the existence of atrial isomerism. In this case report we provide definite anatomic evidence of the existence of left atrial isomerism, wherein both the atria have smooth walls, finger‐like appendages, and absence of the pectinate muscles and sinus node. Clin. Anat. 16:331–334, 2003. © 2003 Wiley‐Liss, Inc.
Zur Produktgestaltung kohäsiver Pulver – Mechanische Eigenschaften, Kompressions‐ und Fließverhalten
Authors: Tomas J.
Published: June 2003

Mit der Modellvorstellung „steife Partikel mit weichen Kontakten“ werden die drei Fließbedingungen eines Pulverkontinuums (beginnendes und stationäres Fließen, Verfestigung) auf partikelmechanischer Grundlage formuliert. Damit ist der unmittelbare Einfluss des Kontaktverhaltens auf das Fließverhalten analytisch darstellbar. Mit Hilfe eines Kompressibilitätsindex lässt sich das Verdichtungsverhalten einschätzen. Zusätzlich werden die Kompressionsrate und die spezifische Kompressionsarbeit eingeführt. Damit können die Zusammenhänge zwischen Kontaktnachgiebigkeit, Haftkraftverstärkung und Pulverfließfähigkeit auf physikalischer Grundlage beurteilt werden. Mit diesen Modellen können die Antwortfunktionen auf extreme Beanspruchungs‐ und Fließzustände bei verfahrenstechnischen Prozessen, Lager‐ und Fördervorgängen hinreichend beschrieben werden. Selbstverständlich lassen sich damit auch zweckmäßige Schlussfolgerungen für die marktgerechte Produktgestaltung in der stoffwandelnden Industrie ziehen.
Stabilität von Dispersionen
Authors: Bellmann C.
Published: June 2003

Herstellung und Einsatz disperser Systeme gewinnen in der Industrie immer größere Bedeutung. Auch im täglichen Leben begegnen wir häufig solchen Systemen (z. B. Nahrungsmittel, Pharmazeutika usw.). Die Erforschung der Gesetzmäßigkeiten der Kolloidchemie ermöglicht, neue Stoffe zu entwickeln oder vorhandene zu verbessern. Ein zentraler Ansatzpunkt hierbei ist die Stabilität solcher kolloidalen Systeme. Eines der physikalischen Modelle zur Kolloidstabiltät liefert die DLVO‐Theorie. Entsprechend den physikalischen Bedingungen einer solchen Stabilisierungsform kann diese in vielfältiger Weise beeinflusst werden. Die hier vorzustellenden Arbeiten befassen sich mit dem Einsatz elektrokinetischer Messmethoden zur Untersuchung der Wechselwirkungskräfte in dispersen Systemen. An Beispielen soll der Einfluss von pH‐Wert, Elektrolytkonzentration und ‐wertigkeit auf die Kolloidstabilität gezeigt werden. Nicht immer erfüllen die untersuchten Dispersionen die Bedingungen des DLVO‐Modells. Ursachen für dieses Verhalten sollen diskutiert werden.
Mikrohohlkugeln
Authors: Bertling J. , Blömer J. , Kümmel R.
Published: June 2003

Mikrohohlkugeln sind mindestens zweiphasige, sphärisch symmetrische Feststoffteilchen, für die eine große Zahl potenzieller Nutzungen bekannt ist und deren Marktvolumen kontinuierlich ansteigt. Während der wesentliche Teil des Bedarfs an Mikrohohlkugeln noch durch anorganische Nebenprodukte thermischer Prozesse gedeckt wird, gewinnen zur Herstellung maßgeschneiderter Strukturen zunehmend Sprüh‐ und Vertropfungsprozesse, Emulsions‐ und Suspensionstechniken sowie Wirbelschichtverfahren technisches Interesse. Grenzflächeneffekte dominieren sowohl die Bildung als auch die Eigenschaften von Mikrohohlkugeln. Unter Nutzung von Templattechniken können bisher nicht zugängliche Strukturen erzeugt werden. Die Modellierung der Wandbildungsprozesse ermöglicht es, die Bildungsmecha‐nismen besser zu verstehen und das Scale‐up zu vereinfachen.
Partikelherstellung unter Einsatz überkritischer Fluide
Authors: Kröber H. , Teipel U.
Published: June 2003

No abstracts.
Beschichtung von Partikeln in mit überkritischen Fluiden betriebenen Wirbelschichten
Authors: Vogt C. , Schreiber R. , Werther J. , Brunner G.
Published: June 2003

No abstracts.
Praxisgerechte Präsentation von Partikelgrößen‐Verteilungen
Authors: Hess W.F.
Published: June 2003

No abstracts.
Experiment und mathematische Modellierung zur Feststoffbildung bei der Sprühtrocknung
Authors: Seydel P. , Sengespeick A. , Blömer J. , Bertling J.
Published: June 2003

No abstracts.
Coating of Pastilles by Crystallization
Authors: Kim J.‐W. , Ulrich J.
Published: June 2003

No abstracts.
Verbesserung eines Modells für die Kristallhabitusvorhersage mit Hilfe von PBC‐Vektoren
Authors: Schmiech P. , Ulrich J.
Published: June 2003

No abstracts.
Transluzente Polycarbonatwerkstoffe
Authors: Proft B.
Published: June 2003

No abstracts.
Totaloxidation von Methan und chlorierten Kohlenwasserstoffen an A1–xSrxMnO3/ZrO2‐Trägerkatalysatoren
Authors: Stephan K. , Kießling D. , Hackenberger M. , Wendt G.
Published: June 2003

No abstracts.
Haftkraftmessungen an modifizierten Oberflächen – Eine AFM‐Anwendung
Authors: Hoffmann B. , Kubier B. , Husemann K.
Published: June 2003

No abstracts.
Nichtlineare Schätzung von Gemischzusammensetzungen aus Nah‐Infrarot‐Spektren
Authors: Dadhe K.
Published: June 2003

No abstracts.
Einfluss von Luftfeuchtigkeit und Oberflächenbeschaffenheit auf das Fließverhalten
Authors: Thümmler S. , Höhne D. , Husemann K.
Published: June 2003

No abstracts.
Stoffverlustminimierte Prozesstechnik – Wann lohnen sich Regeneratoren und Konzentratoren?
Authors: Fischwasser K. , Schwarz R. , Süß M.
Published: June 2003

Ein Hauptgebiet des Umweltschutzes sind chemische und elektrochemische Oberflächenbehandlungsprozesse wie das Galvanisieren, Beizen, Ätzen, Anodisieren u. a. Derartige Oberflächenbehandlungen verursachen häufig einen hohen Chemikalienverbrauch sowie große Mengen Abwasser und schwermetallhaltige Abfälle. Eine stoffverlustminimierte Prozesstechnik ist das Resultat einer Systemoptimierung zwischen interner Stoffkreislaufschließung und externer Abfallverwertung. Kostensenkungen, Prozesssicherheit, Qualitätssicherung und Umweltverträglichkeit sind Ziele der komplexen Systemoptimierung. Prozesseinheiten, bestehend aus Prozessstufe für die Oberflächenbehandlung (Prozesslösung), Spültechnik, Konzentrator und Regenerator stehen im Mittelpunkt der Systemoptimierung. In diesem Beitrag wird der Zusammenhang verschiedener Prozesskriterien diskutiert. Der optimale interne Rückführgrad für Spülwasserkonzentrate, die Prozesschemikalien von der Oberflächenbehandlung enthalten, ist ein Schlüsselkriterium bei der Systemoptimierung.
Herstellung von normgerechtem Biodiesel aus Rapsöl und Altfetten – Verfahrenskonzept
Authors: Haupt J. , Dimmig T. , Dittmar T. , Ondruschka B. , Heyn B. , Lauterbach M.
Published: June 2003

No abstracts.
Herstellung organischer Nanopartikel und deren Stabilisierung in wässrigen Lösungen (RESSAS)
Authors: Türk M.
Published: June 2003

No abstracts.
Has the investment in public cancer education delivered observable changes in knowledge over the past 10 years?
Authors: Paul Christine , Tzelepis Flora , Walsh Raoul A. , Girgis Afaf , King Lesley , McKenzie Jeanie
Published: May 2003

BACKGROUND

During the 1990s, Western countries, such as Australia, directed substantial funds toward public cancer education. An important indicator of whether this investment has been worthwhile is a shift over time in the proportion of the population who have accurate knowledge regarding cancer.

METHODS

In the year 2000, a cross‐sectional telephone survey was administered to 685 residents selected from the New South Wales (Australia) Electronic White Pages telephone directory. This study replicated in part a survey conducted in 1989.

RESULTS

In the 2000 survey, smoking (96.0%) and sun exposure (80.4%) were well‐known as risk factors for lung cancer and melanoma, respectively. However, community knowledge of risk factors for colorectal, breast, cervical, and prostate cancer was poor. Most respondents were able to nominate mammograms (82.2%) and Pap tests (86.8%) as screening tests for breast and cervical cancer, respectively. Approximately two‐thirds of the sample were able to nominate foods that reduce the risk of developing cancer. Compared with the 1989 data, there appeared to have been improvements in community knowledge of mammograms as a screening test for breast cancer. For the other cancers, knowledge gains appeared smaller or marginal. With regard to the lifetime risk of developing these cancers, community understanding remains poor. Predictors of greater knowledge include a higher level of education.

CONCLUSIONS

Where ongoing investments have been made, like in the case of breast cancer education, there have been improvements in community knowledge. However, major challenges remain. Potential targets for future public education campaigns are discussed. Cancer 2003;97:2931–9. © 2003 American Cancer Society.

DOI 10.1002/cncr.11393
A Phase I/II study of strontium‐89 combined with gemcitabine in the treatment of patients with androgen independent prostate carcinoma and bone metastases
Authors: Pagliaro Lance C. , Delpassand Ebrahim S. , Williams Dallas , Millikan Randall E. , Tu Shi‐Ming , Logothetis Christopher J.
Published: May 2003

BACKGROUND

The objectives of the current study were to determine the maximum tolerated dose and to evaluate the efficacy of gemcitabine given in combination with strontium‐89 to patients with androgen independent prostate carcinoma.

METHODS

Patients with androgen‐independent prostate carcinoma and painful osteoblastic bone metastases were eligible. On a 12‐week course, patients received gemcitabine (600 mg/m2 or 800 mg/m2) on Days 1, 8, 15, 43, 50, and 57. A single dose of strontium‐89 (55 μCi/kg) was administered on Day 8.

RESULTS

Fifteen patients were registered, and all were assessable for response and toxicity. Four patients were treated at Dose Level 1 (gemcitabine 600 mg/m2) without dose‐limiting toxicity. Eleven patients received a total of 13 courses at Dose Level 2 (gemcitabine 800 mg/m2). Platelet nadirs of 25,000–50,000 platelets per μL were common at Dose Level 2, and 1 patient had Grade 4 thrombocytopenia that was dose‐limiting. Granulocyte nadirs up to < 500 granulocytes per μL occurred in 4 patients at Dose Level 2 and were reversible. There were no responses, as measured by prostate specific antigen concentration, although 6 patients (40%) had stable disease.

CONCLUSIONS

The authors concluded that 800 mg/m2 gemcitabine was the maximum tolerated dose for the combination. The study was terminated on the basis that an overall response rate > than 10% was unlikely. Further study at this dose level and schedule is not warranted. Cancer 2003;97:2988–94. © 2003 American Cancer Society.

DOI 10.1002/cncr.11412
Laparoscopic sentinel lymph node procedure using a combination of patent blue and radioisotope in women with cervical carcinoma
Authors: Barranger Emmanuel , Grahek Dany , Cortez Annie , Talbot Jean Noel , Uzan Serge , Darai Emile
Published: May 2003

BACKGROUND

The authors evaluated the feasibility of a laparoscopic sentinel lymph node (SN) procedure with combined radioisotopic and patent blue labeling in patients with cervical carcinoma.

METHODS

Thirteen women (median age, 52.5 years) with cervical carcinoma (Stage Ia2 in 1 patient, Stage Ib1 in 10 patients, Stage Ib2 in 1 patient, and Stage IIa in 1 patient) underwent a laparoscopic SN procedure using an endoscopic γ probe after both radioactive isotope and patent blue injections. After the procedure, all patients underwent complete laparoscopic pelvic lymphadenectomy and either laparoscopic radical hysterectomy (eight patients) or the Schauta–Amreich operation (five patients).

RESULTS

SNs (mean, 1.7 SNs per patient; range, 1–3 SNs per patient) were identified in 12 of 13 patients. A median of 10.5 pelvic lymph nodes per patient (range, 4–17 pelvic lymph nodes per patient) were removed. No lymph node involvement was detected in SNs with hematoxylin and eosin staining. Immunohistochemical studies identified four metastatic SNs in two patients, with micrometastases in two SNs from the first patient and isolated tumor cells in two SNs from the second patient. No false‐negative SN results were obtained.

CONCLUSIONS

The results of this study suggest that SN detection with a combination of radiocolloid and patent blue is feasible in patients with cervical carcinoma. The combination of laparoscopy and the SN procedure permitted minimally invasive management of early‐stage disease. Cancer 2003;97:3003–9. © 2003 American Cancer Society.

DOI 10.1002/cncr.11423
Treatment of Philadelphia chromosome–positive chronic myelogenous leukemia with weekly polyethylene glycol formulation of interferon‐alpha‐2b and low‐dose cytosine arabinoside
Authors: Garcia‐Manero Guillermo , Talpaz Moshe , Giles Francis J. , Cortes Jorge , Faderl Stefan , O'Brien Susan , Thomas Deborah , Verstovsek Srdan , Beth Rios Mary , Shan Jianquin , Ferrajoli Alessandra , Wierda William , Kantarjian Hagop M.
Published: May 2003

BACKGROUND

To evaluate the activity and toxicity of weekly Schering 54301, a polyethylene glycol formulation of interferon‐ α‐2b (PEG‐IFN‐α‐2b), with cytosine arabinoside (ara‐C) in patients with chronic myelogenous leukemia (CML).

METHODS

Seventy‐six patients with Philadelphia chromosome (Ph)‐positive early chronic‐phase CML were treated with the combination of PEG‐IFN‐α‐2b and ara‐C (10 mg daily subcutaneously [s.c.]). The starting dose of PEG‐IFN‐α‐2b was 6 μg/kg s.c. weekly in the first 24 patients but was reduced to 4.5 μg/kg in the next 52 patients.

RESULTS

Overall, 73% of patients had a complete hematologic response, 35% of patients had a major cytogenetic response (Ph < 35%), and 21% of patients had a complete cytogenetic response (Ph = 0%). With a median follow‐up of 19 months, the estimated 2‐year survival rate was 89%. Therapy was discontinued in 24% of patients due to Grade III–IV toxicity. Frequent severe side effects that required dose reductions included neutropenia (49%), fatigue (43%), and neurologic toxicity (17%). The median PEG‐IFN‐α‐2b and ara‐C doses delivered were 3 μg/kg weekly and 7.5 mg daily, respectively, at 12 months of therapy. The activity and toxicity profiles of this combination was similar to those observed in historical patients treated with IFN‐α and cytarabine.

CONCLUSIONS

The combination of PEG‐IFN‐α‐2b and ara‐C is active but has significant toxicity in patients with chronic‐phase CML at the dose schedule used. The recommended dose of PEG‐IFN‐α‐2b in future combination studies is 3 μg/kg or less. Cancer 2003;97:3010–6. © 2003 American Cancer Society.

DOI 10.1002/cncr.11424
Involvement of the p38 mitogen‐activated protein kinase cascade in hepatocellular carcinoma
Authors: Iyoda Kenya , Sasaki Yutaka , Horimoto Masayoshi , Toyama Takashi , Yakushijin Takayuki , Sakakibara Mitsuru , Takehara Tetsuo , Fujimoto Jiro , Hori Masatsugu , Wands Jack R. , Hayashi Norio
Published: May 2003

BACKGROUND

The mitogen‐activated protein kinase (MAPK) cascade is activated in response to various extracellular stimuli. The authors investigated the involvement of the p38 MAPK, a member of the MAPK superfamily, cascade in hepatoma cell lines and in human hepatocellular carcinoma (HCC) tissue specimens.

METHODS

Constitutively active mutant of MAPK kinase 6 (MKK6), which is upstream of p38 MAPK, was transfected into the HepG2 and HuH7 human hepatoma cell lines. The constitutive active mutant was constructed by replacing Ser‐189 and Thr‐193 with Glu. The growth and death of mutant MKK6‐transfected hepatoma cells were analyzed by the WST‐1 and sub‐G1 assays. The surgically resected livers of 20 HCC patients were divided histologically into tumorous (T) and nontumorous (NT) lesions. p38 MAPK activity was analyzed using in vitro kinase assay and MKK6 activity was measured using Western blot analysis.

RESULTS

Mutant MKK6 transfection increased p38 MAPK activity, cytochrome c release from the mitochondria to the cytosol, and caspase‐3 activity, accompanied by apoptosis. In contrast, SB203580, a p38 MAPK‐specific inhibitor, prevented MKK6‐induced apoptosis in hepatoma cell lines. In the T lesions of 20 HCC parients, p38 MAPK and MKK6 activities were significantly lower compared with NT lesions (P < 0.05). There was a significant positive correlation between p38 MAPK and MKK6 activity (r = 0.507, P < 0.05). Larger tumors (> 20 mm) exhibited lower levels of p38 MAPK and MKK6 activity than did smaller tumors (P < 0.05).

CONCLUSIONS

These findings suggested that reduction of the p38 MAPK cascade may account, in part, for the resistance to apoptosis, leading to the unrestricted cell growth of human HCC. Cancer 2003;97:3017–26. © 2003 American Cancer Society.

DOI 10.1002/cncr.11425
Hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C virus infection
Authors: Ohata Kazuyuki , Hamasaki Keisuke , Toriyama Kan , Matsumoto Kojiro , Saeki Akira , Yanagi Kenji , Abiru Seigou , Nakagawa Yuichi , Shigeno Masaya , Miyazoe Seiji , Ichikawa Tatsuki , Ishikawa Hiroki , Nakao Kazuhiko , Eguchi Katsumi
Published: May 2003

BACKGROUND

Hepatic steatosis is one of the histopathologic features of chronic hepatitis C. It was reported recently that the expression of hepatitis C virus (HCV) core protein in transgenic mice induced hepatocellular carcinoma (HCC) in association with steatosis. The objective of this study was to determine the relation between hepatic steatosis and hepatocarcinogenesis in patients with chronic HCV infection.

METHODS

The authors studied 161 patients with chronic HCV infection who were diagnosed at Nagasaki University Hospital, Nagasaki, Japan, between January 1980 and December 1999. Age, gender, body mass index (BMI), habitual drinking, diabetes mellitus, serum alanine aminotransferase (ALT) level, HCV serotype, serum level of HCV core protein, interferon (IFN) treatment, hepatic fibrosis inflammation, and hepatic steatosis were studied with regard to their significance in the development of HCC using univariate and multivariate analyses.

RESULTS

The cumulative incidence rates of HCC were 24%, 51%, and 63% at 5 years, 10 years, and 15 years, respectively. Multivariate analysis identified hepatic steatosis, together with aging, cirrhosis, and no IFN treatment, as independent and significant risk factors for HCC (P = 0.0135, P = 0.0390, P = 0.0068, and P = 0.0142, respectively). In addition, hepatic steatosis was correlated with BMI, serum ALT levels, and triglyceride levels.

CONCLUSIONS

The findings of the current study indicate that hepatic steatosis is a risk factor for HCC in patients with chronic HCV infection. Patients with chronic HCV and hepatic steatosis should be monitored carefully for HCC. Cancer 2003;97:3036–43. © 2003 American Cancer Society.

DOI 10.1002/cncr.11427
Predictive factors for suicidal ideation in patients with unresectable lung carcinoma
Authors: Fishbain David A.
Published: May 2003

DOI 10.1002/cncr.11429
Relationship between changes in hemoglobin level and quality of life during chemotherapy in anemic cancer patients receiving epoetin alfa therapy
Authors: Österborg Anders , Brandberg Yvonne
Published: May 2003

DOI 10.1002/cncr.11430
Coping and caring
Authors: Hanson Mary L. R.
Published: May 2003

For more than 50 years, Cancer has explored every facet of malignant disease, including morphology, therapy, epidemiology, biology, historical perspective, and basic science. However, the Editors of Cancer believe that the human beings who bear the burden of this illness have much to teach us, and we now solicit essays from patients and family members about their experience.

Barrie R. Cassileth, Ph.D. Integrative Medicine Service, Memorial Sloan‐Kettering Cancer Center, New York, New York.

A. Bernard Ackerman, M.D. Ackerman Academy of Dermatopathology, New York, New York. Cancer 2003;97:2940. © 2003 American Cancer Society.

DOI 10.1002/cncr.11431
Plasma levels of D‐dimer in lung carcinoma
Authors: Buccheri Gianfranco , Torchio Pierfederico , Ferrigno Domenico
Published: May 2003

BACKGROUND

The activation of the clotting‐fibrinolytic system in cancer patients is common and represents an unfavorable clinical sign. D‐dimer (DD) is a sensitive marker of fibrinolysis.

METHODS

The current study comprised 826 new lung carcinoma patients seen consecutively in a single institution over a 10‐year period (1992–2001). For each patient, 31 variables, including DD and survival duration, were available for analysis.

RESULTS

Only weak relationships between DD and the other variables were found. The DD variable correlated best with the level of lactate dehydrogenase, performance status, tissue polypeptide antigen, stage of disease, and the number of metastases (rho = 0.33, −0.25, 0.18, 0.18, and 0.15, respectively). The D‐dimer distinguished patients with different prognoses. The median survival periods were 154 days (95% confidence interval [CI], 122–189 days) and 308 days (95% CI, 227–409 days; log rank statistic, 26.56;P< 0.01), respectively, for abnormally elevated and normal values. The difference was greater in patients with adenocarcinoma and in patients presenting with a less advanced disease, especially in patients with pathologic Stage Ia disease. The best multivariate survival model selected 10 significant covariates, including DD.

CONCLUSIONS

The authors recommend measuring the plasma level of DD in all new lung carcinoma patients. This measurement may help to formulate individual prognoses and can be used to indicate adjuvant treatment for surgical patients. Cancer 2003;97:3044–52. © 2003 American Cancer Society.

DOI 10.1002/cncr.11432
Central nervous system metastases in women who receive trastuzumab‐based therapy for metastatic breast carcinoma
Authors: Bendell Johanna C. , Domchek Susan M. , Burstein Harold J. , Harris Lyndsay , Younger Jerry , Kuter Irene , Bunnell Craig , Rue Montse , Gelman Rebecca , Winer Eric
Published: May 2003

BACKGROUND

Women with HER‐2 overexpressing metastatic breast carcinoma benefit from trastuzumab‐based therapy, but trastuzumab does not cross the blood‐brain barrier. The authors characterized central nervous system (CNS) disease in these women.

METHODS

Using pharmacy records, the authors retrospectively identified 153 women treated with trastuzumab alone or with chemotherapy for HER‐2–positive metastatic breast carcinoma at Dana‐Farber Partners Cancer Care from June 1998 to December 2000. A study cohort of 122 patients was identified after excluding patients without adequate clinical follow‐up or who had CNS disease before trastuzumab treatment. Central nervous system disease was defined as one or more brain metastases or as leptomeningeal carcinomatosis. The median follow‐up of this cohort was 23 months.

RESULTS

Central nervous system metastases were identified in 34% of patients (95% confidence interval, 26–44%) at a median of 16 months after diagnosis of metastatic breast carcinoma and 6 months from the beginning of trastuzumab therapy. Ninety‐three percent of patients with CNS disease presented with clinical symptoms. Five percent of patients with CNS disease had leptomeningeal involvement alone, although 14% had leptomeningeal involvement and parenchymal brain metastases. Fifty percent of patients were responding or had stable disease while receiving trastuzumab at other disease sites at the time of diagnosis of CNS metastasis. The median survival period after CNS metastases was 13 months. Fifty percent of patients died of progressive CNS disease. Patients receiving trastuzumab as first‐line therapy for metastatic disease frequently developed brain metastases while responding to or stable on trastuzumab at other disease sites.

CONCLUSIONS

Metastatic breast carcinoma to the CNS is common among patients receiving trastuzumab‐based therapy, including patients responding to therapy outside the CNS. This may be due either to predilection for the CNS by HER‐2–positive tumor cells and/or poor penetration of the CNS by trastuzumab or to improved visceral disease control leading to a longer life and onset of late tumor spread to the CNS. Efforts to characterize other risk factors for development of CNS disease, optimal screening algorithms, and new treatment strategies may be warranted. Cancer 2003;97:2972–7. © 2003 American Cancer Society.

DOI 10.1002/cncr.11436