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  • 11
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'adénocarcinome pancréatique est caractérisé par un taux de résecabilité bas et une survie réduite. Entre Septembre 1974 et Décembre 1992, 149 (59%) des 253 patients ayant un adénocarcinome du pancréas ont eu unc résection. Une duodénopancréatectomie céphalique a été faite chez 105 patients, une pancréatectomie totale chez 36 et une pancréatectomie distale chez 8. L'extirpation de la tumeur a été associée à une lymphadénectomie et à l'exérèse du plexus nerveux rétropancréatique. Soixant dixneuf patients (53%) des 149 patients ont une résection du trone porte. Seize des 79 patients ont également eu une résection des artères adjacentes. Trois patients sont décédés dans les 30 jours postopératoires immédiats alors que 17 sont décédés entre 2 et 7 mois après. La mortalité des patients ayant une résection combinée du pancréas et du tronc porte a été de 9.5% similaire à celle des patients ayant eu une résection du pancréas seule (10%). La résection à but curatif est nécessaire pour envisager une survie à long terme. La survie à 5 ans chez 61 patients ayant eu une résection à visée curatrice a été de 15%. Dix patients ont survécu plus de cinq ans. Les patients ayant des métastases lymphatiques et un envahissement de la veine porte ont survécu plus long temps. Dans le but d'améliorer cette survie, mais sans succès, 35 patients ont eu une irradiation peropératoire. La chimiothérapie par 5-fluorouracile dans la veine porte semble avoir diminué le nombre de métastases chez 25 patients. Si nous avons amélioré quelque peu le pronostic, nous sommes encore loin du but et il faut continuer les essais.
    Abstract: Resumen El cáncer de los canales pancreáticos se caracteriza por baja tasa de resecabilidad y muy corta tasa de sobrevida a largo plazo. Entre septiembre de 1974 y diciembre de 1992 fueron sometidos a resección 149 (59%) de 235 pacientes con este tipo de cáncer en nuestra institución. Los procedimientos quirúrgicos realizados fueron la pancreatoduodenectomía en 105 casos, la pancreatectomía total en 36 y la pancreatectomía distal en 8. El tumor fue extirpado junto con una extensa disección de los ganglios linfáticos y la resección del plejo nervioso retroperitoneal. En 79 (53%) de los 149 pacientes se realizó la resección combinada del páncreas y de la vena porta y en 79 también se paracticó resección de las arterias adyacentes. Tres pacientes murieron en los primeros 30 días luego de la cirugía y otros 17 sucumbieron entre 2 y 7 meses. La mortalidad en los pacientes sometidos a pancreatectomía y resección de la vena porta (9.5%) fue similar a la de los pacientes sometidos a pancreatectomía solamente (10%). La resección curativa aparece necesaria para lograr sobrevida a largo plazo. La tasa de sobrevida a cinco años en 61 pacientes con resección curativa fue 15%; 10 pacientes sobrevivieron más de 5 años. Pacientes con metástasis ganglionares y con invasión cancerosa de la vena porta pudieron sobrevivir por largo tiempo. Con el objeto de mejorar la tasa de sobrevida, se practicó irradiación intraoperatoria en 35 pacientes, sin éxito. La quimioterapia con 5 fluoruracilo en infusión por vía de la vena porta fue ensayada en 25 pacientes, lo cual resultó en disminución de las metástasis hepáticas. Aunque hemos logrado progreso inicial en nuestro propósito de mejorar el tratemiento, todavía estamos lejos de las metas y aparece necesario continuar con ensayos clínicos adicionales.
    Notes: Abstract Pancreatic duct cell cancer is characterized by a low resectability rate and a low long-term survival rate. Between September 1974 and December 1992 in our institution, 149 (59%) of the 253 patients with this cancer underwent resection. The operative procedures were pancreatoduodenectomy in 105 patients, total pancreatectomy in 36, and distal pancreatectomy in 8. The tumor was extirpated with extensive dissection of the lymph nodes and excision of the nerve plexus in the retroperitoneum. Of the 149 patients, 79 (53%) underwent combined resection of the pancreas and the portal vein; 16 of the 79 patients also underwent resection of the adjacent arteries. Three patients died within 30 days after surgery, and 17 other patients succumbed within 2 to 7 months. The mortality among patients undergoing pancreatectomy and resection of the portal vein (9.5%) was similar to that of patients with pancreatectomy alone (10%). Curative resection was necessary for long-term survival. The 5-year survival rate in 61 patients with the curative resection was 15%. Ten patients lived more than 5 years. Even patients with lymph node metastases and cancer invasion of the portal vein had a prolonged survival. Intraoperative irradiation was carried out in 35 patients to improve the survival rate, but without success. Infusion chemotherapy with 5-fluorouracil via the portal vein was tried in 25 patients, resulting in a decrease in liver metastasis. We have made some progress in the first step toward improving treatment, although we are far from the goal and it is necessary to conduct additional trials.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Biomedical microdevices 2 (1999), S. 151-157 
    ISSN: 1572-8781
    Keywords: tensile test ; collagen fiber ; mechanical property ; patellar tendon ; biomechanics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Tensile properties of collagen fibers of approximately 1 μm in diameter were determined using a newly developed micro tensile test system for cells and fine fibrous biological tissues. The test system consists of a thermostatic test chamber, an inverted microscope, micromanipulators, a direct drive linear actuator, a cantilever-type load cell, and a video dimension analyzer (VDA). The fibers were isolated with a mechanical method from collagen fascicles (approximately 300 μm in diameter) cut out from the rabbit patellar tendon. The ends of each fiber were attached to the tips of a pair of glass microtubes (15 to 20 μm in outer diameter) using a cyanoacrylate adhesive. One of the microtubes was attached to the load cell; the other one was connected to the linear actuator which was utilized to stretch the fiber. Load applied to the fiber was measured with the load cell, while its elongation was determined with the VDA using the images of the edges of the adhesive as markers. Tangent modulus, tensile strength, and strain at failure of the tested fibers were 54.3± 25.1 MPa, 8.5± 2.6 MPa, and 21.6± 3.0%, respectively. These values were much different from those of collagen fascicles (300 μm in diameter) cut out from the rabbit patellar tendon and also from those of the bulk patellar tendon (Trans. ASME, J. Biomech. Eng. 121, 124–294, 1999); for example, tensile strength and strain at failure of the fibers were approximately 50 and 200% of those of the fascicles, respectively. These results suggest that the mechanical interactions between fibers and between fibers and ground substances contribute much to the mechanical properties of collagen fascicles and bulk tendons.
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  • 13
    ISSN: 1437-7780
    Keywords: HGF ; cancer chemotherapy ; pneumonia ; silicosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study, we report plasma hepatocyte growth factor (HGF) levels during cancer chemotherapy and the relationship between plasma HGF and pneumonia onset in 19 patients with primary lung cancer. These measurements are compared with patients plasma HGF levels prior to cancer chemotherapy, as well as with plasma HGF levels in 23 control patients with silicosis. Plasma HGF, as well as peripheral white blood cells and C-reactive protein, were measured every three days during cancer chemotherapy. In the eight patients who did not develop pneumonia, plasma HGF remained within normal limits. In the 11 patients who did develop pneumonia, however, HGF exceeded normal limits three days after the onset of infection. Further-more, the maximum HGF concentration was significantly higher in the 11 patients with pneumonia (0.62±0.12 ng/mL) than in the eight without complications (0.24±0.02,P〈0.01), in the entire lung cancer group prior to chemotherapy (0.17±0.01,P〈0.01), or in the 23 control patients with silicosis (0.22±0.01,P〈0.01). This suggests that HGF may play a role in repairing lung damage due to pneumonia.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 38 (1996), S. S74 
    ISSN: 1432-0843
    Keywords: Key words Thrombopoietin ; CFU-MK ; Megakaryocyte ; Platelet ; Thrombocytopenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recently, four groups reported the cloning of thrombopoietin (TPO), also called c-Mpl ligand, from various species. In this study, we examined the in vitro and in vivo biological activity of TPO and its therapeutic efficacy in experimental animal models. Recombinant human TPO (rhTPO) supported the formation of only megakaryocyte (MK) colonies from rat marrow MK progenitor cells [colony-forming units-megakaryocyte (CFU-MK)] and predominantly acted on GpIIb/IIIa+ CFU-MK at the late stage of differentiation. MKs generated from rat GpIIb/IIIa+ CFU-MK after 3 days of liquid culture in the presence of rhTPO had mature characteristics. rhTPO stimulated an increase in the size of TPO-induced cultured rat MKs and in the number of elongated cytoplasmic processes, also called proplatelets, from these MKs in a dose-dependent manner. Administration of rhTPO to normal BALB/c mice daily for 5 days caused dose-dependent thrombocytosis. Treatment with rhTPO induced an increase in the size and number of marrow MKs and an expansion of the marrow CFU-MK pool. We further examined the effects of rhTPO on chemotherapy-induced thrombocytopenia in animal models. Following treatment with mitomycin C, mice received daily injections of various doses of rhTPO. Administration of rhTPO reduced the severity of thrombocytopenia and accelerated the recovery of platelets in a dose-dependent fashion: there was a significant reduction in the decrease in numbers of marrow MKs and CFU-MK with rhTPO treatment. Treatment with rhTPO also significantly improved neutropenia in mitomycin C-treated mice. Similar therapeutic efficacy was observed in cynomolgus monkeys with thrombocytopenia induced by nimustine. In addition, there was no significant change in several serum-chemistry parameters, in C-reactive protein, an acute phase protein, or in some variables involved in the blood-coagulation system. Furthermore, platelets from mice made thrombocytotic by repeated administration of rhTPO showed normal aggregation function. These results strongly suggest the clinical usefulness of rhTPO for the treatment of thrombocytopenia.
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  • 15
    ISSN: 1573-0778
    Keywords: differentiation ; proliferation ; thrombopoietin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract We have isolated and characterized a thrombopoietin (TPO)-dependent BF-TE22 cell line endogenously expressing murine Mpl, which is a subclone of murine pro-B Ba/F3 cells. TPO stimulated the proliferation of BF-TE22 cells in a dose-dependent manner, and also induced the expression of megakaryocyte lineage-specific AP-51 and CD61 cell surface antigens. The results indicate that the murine Mpl on BF-TE22 cells can transmit both proliferation and megakaryocyte lineage-specific differentiation signals to cells. Furthermore, it was shown that IL-3 inhibits the TPO-induced differentiation signals of BF-TE22 cells. These results suggest that the signals mediated by IL-3 predominate over those of TPO in BF-TE22 cells. Thus, BF-TE22 cells will be useful for the biological and biochemical studies of the TPO-Mpl signal transduction mechanism.
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  • 16
    ISSN: 1573-7241
    Keywords: flecainide acetate ; electrophysiological effects ; guinea-pig left atrial muscle ; stretch
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The electrophysiological effects of flecainide acetate (3×10−6 M) on stretched atrial tissue were investigated using guinea-pig left atrial muscle fibers. Before stretching, the resting membrane potential was not affected by flecainide at 1 Hz, although the overshoot potential (Eov) and the action potential duration at 50% repolarization (APD50) were slightly but significantly decreased by 2±1 mV and 2±1 msec, respectively. The effective refractory period (ERP) was increased by 3±1 msec. The reduction of $$\dot V$$ max was 20.6±1.2%. The half-maximum potential (Vh) of the relationship between $$\dot V$$ max and the resting potential was shifted to become more negative by flecainide (from −60.6±2.1 mV to −63.2±1.7 mV). After 90–120 min of washout with drug-free Tyrode's solution, the tissue was mechanically stretched to 150% of its slack length. Stretching significantly decreased the $$\dot V$$ max by 16.9±3.1%, along with a slight but significant increase in ERP (3±1 msec) and shifted Vh to become more negative (from −60.6±2.1 to −63.1±1.8 mV). In the presence of flecainide, $$\dot V$$ max further decreased by 20.2±2.6%, and Vh shifted from −63.1±1.8 to −65.0±1.5 mV. Comparison with the control unstretched fibers showed that flecainide significantly decreased $$\dot V$$ max by 34.0±2.7%, reduced the resting membrane potential by 3±1 mV, decreased Eov by 4±1 mV, and shifted Vh from −60.6±2.1 to −65.0±1.5 mV, while the APD50 and ERP did not change. In conclusion, the reduction of $$\dot V$$ max in the presence of flecainide was much greater in the stretched atrial muscle fibers than in the unstretched fibers, because the $$\dot V$$ max-resting potential relationship was shifted towards more negative potentials by both flecainide and stretching. These results suggest that flecainide exerts a stronger antiarrhythmic action on stretched atrial muscle fibers than on normal fibers.
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  • 17
    ISSN: 1573-2568
    Keywords: hepatolithiasis ; cholesterol ; bile acid ; gallstone ; bile ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A detailed comparison was made of the bile acid composition in gallstones (brown pigment stones) and paired bile and liver from both affected and unaffected lobes by gallstones, which were taken at operation from 16 patients with hepatolithiasis, with the aim of elucidating whether stone formation is derived from possible local disturbances limited to intrahepatic bile ducts. Brown pigment stones in the intrahepatic bile ducts, most of which were accompanied by bile with high cholesterol saturation, had significantly more cholesterol, and less calcium bilirubinate and bile acid than those found in the extrahepatic bile ducts. Intrahepatic gallstones had significantly lower amounts of secondary and unconjugated bile acids, the bile acids modified by bacterial intervention, than extrahepatic stones. Bile specimens from both affected and unaffected lobes showed significantly increased molar percentages of cholesterol and decreased percentages of bile acids than bile from controls. In contrast, liver specimens from both lobes showed significantly higher concentrations of total bile acids. Secondary bile acids were present in a much lower proportion in bile and liver from both lobes than in bile and liver from controls. On the other hand, unconjugated bile acids were present in a much higher proportion in bile and liver from patients and only in negligible amounts in bile from controls. Furthermore, the plasma levels of mevalonate and those of 7α-hydroxy-4-cholestene-3-one were found to be significantly higher and lower in patients than in controls, respectively, indicating that in hepatolithiasis cholesterol synthesis might increase and bile acid synthesis might decrease in the liver. These findings suggested that alterations of bile acid composition in gallstones, bile, and liver of patients with hepatolithiasis may be attributed to not only secondary changes resulting from local disturbances limited to intrahepatic bile ducts but also possible primary alterations of hepatocyte metabolism, such as bile acid conjugation and primary defects in cholesterol and bile acid synthesis.
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  • 18
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The metabolism of 5-(4′-chloro-n-butyl)picolinic acid, which inhibits dopamine β-hydroxylase and exhibits an antihypertensive effect, has been studied by gas chromatography mass spectrometry, utilising characteristic reaction products after derivatization. In rat urine five metabolites were identified by mass spectral analysis. It is found that four were elongated by a C2 unit in the carboxyl group at the 2-position on the pyridine ring and accounted for approximately 50% of the radioactivity in the 24 hour urine. The facts show that the metabolic pathway corresponding to the chain elongation of fatty acids is the major route of metabolism for this drug in the rat. Furthermore, this pathway would be confirmed in man, rabbit, guinea pig and mouse.
    Additional Material: 11 Ill.
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  • 19
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A specific and sensitive method for the simultaneous determination of bestatin and its major metabolite, p-hydroxybestatin in human serum has been developed by selected ion monitoring using the corresponding deuterated internal standards. The N-trifluoroacetamide-O-trimethylsilyl ether derivatives of the trideuteromethyl esters of bestatin and p-hydroxybestatin were suitable for quantitation by selected ion monitoring. The determination limit of these compounds by the present method is 1 ng ml-1 in human serum.
    Additional Material: 7 Ill.
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  • 20
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The mass spectral characterization of nine kinds of estrogen glucuronides was investigated. The glucuronides were analysed after conversion to n-propyl ester-O-TMS ether derivatives by gas chromatography mass spectrometry. The fragmentation of these derivatives is discussed using deuterium labels and TMS-d9 imidazole. A clear-cut difference was found between aliphatic and aromatic glucuronic acid conjugates. In particular the [M - 362]+· fragment ion was characteristic in the mass spectra of estrogen 3-glucuronides. On the other hand, four isomers of estriol and 16-epiestriol glucuronides containing an aliphatic acetal linkage were also characterized by the fragment ions of mle value 204, 345, 415 and 431 and their relative intensities. Thus, all nine estrogen glucuronides were discriminated mass spectrometrically.
    Additional Material: 7 Ill.
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