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61.
Trimetrexate for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome 总被引:12,自引:0,他引:12
C J Allegra B A Chabner C U Tuazon D Ogata-Arakaki B Baird J C Drake J T Simmons E E Lack J H Shelhamer F Balis 《The New England journal of medicine》1987,317(16):978-985
Preclinical studies have demonstrated that trimetrexate is a potent inhibitor of dihydrofolate reductase from Pneumocystis carinii. On the basis of this evidence, this lipid-soluble antifolate was used as an antipneumocystis agent in 49 patients with the acquired immunodeficiency syndrome (AIDS) and pneumocystis pneumonia. Simultaneous treatment with the reduced folate leucovorin was used as a specific antidote to protect host tissues from the toxic effects of the antifolate without affecting the antipneumocystis action of trimetrexate. Patients were assigned to three groups and treated for 21 days: in Group I, trimetrexate with leucovorin was used as salvage therapy in patients in whom standard treatments (both pentamidine isethionate and trimethoprim-sulfamethoxazole) could not be tolerated or had failed (16 patients); in Group II, trimetrexate with leucovorin was used as initial therapy in patients with a history of sulfonamide inefficacy or intolerance (16 patients); and in Group III, trimetrexate with leucovorin plus sulfadiazine was used as initial therapy (17 patients). The response and survival rates were, respectively, 69 percent and 69 percent in Group I; 63 percent and 88 percent in Group II; and 71 percent and 77 percent in Group III. Trimetrexate therapy had minimal toxicity; transient neutropenia or thrombocytopenia occurred in 12 patients and mild elevation of serum aminotransferases in 4. We conclude that the combination of trimetrexate and leucovorin is safe and effective for the initial treatment of pneumocystis pneumonia in patients with AIDS and for the treatment of patients with intolerance or lack of response to standard therapies. 相似文献
62.
Patrik Pipkorn Candy Costantini Curt Reynolds Michael Wall Margaret Drake Alvin Sanico David Proud Alkis Togias 《Annals of allergy, asthma & immunology》2008,101(1):82-89
BACKGROUND: Olopatadine, an antihistamine used in allergic conjunctivitis, is under development as a nasal preparation for the treatment of allergic rhinitis. OBJECTIVES: To evaluate the efficacy of olopatadine in suppressing symptoms and biomarkers of the immediate reaction induced by nasal allergen provocation and to compare olopatadine with azelastine in the same model. METHODS: The study was approved by the Johns Hopkins University institutional review board, and all subjects gave written consent. We studied 20 asymptomatic subjects with seasonal allergic rhinitis. The study had 2 randomized, double-blind, placebo-controlled, crossover phases that evaluated 2 concentrations of olopatadine, 0.1% and 0.2%. In a third exploratory phase, olopatadine, 0.1%, was compared with topical azelastine, 0.1%, in a patient-masked design. Efficacy variables were the allergen-induced sneezes, other clinical symptoms, and the levels of histamine, tryptase, albumin, lysozyme, and cysteinyl-leukotrienes (third study only) in nasal lavage fluids. RESULTS: Both concentrations of olopatadine produced significant inhibition of all nasal symptoms, compared with placebo. Olopatadine, 0.1%, inhibited lysozyme levels, but olopatadine, 0.2%, inhibited histamine, albumin, and lysozyme. The effects of olopatadine, 0.1%, were comparable to those of azelastine, 0.1%. CONCLUSIONS: Olopatadine, at 0.1% and 0.2% concentrations, was effective in suppressing allergen-induced nasal symptoms. At 0.2%, olopatadine provided evidence suggestive of inhibition of mast cell degranulation. 相似文献
63.
64.
Anatomic bases for liver transplantation 总被引:1,自引:0,他引:1
Summary This study gathers the anatomic implications for a good liver transplantation. During hepatic removal a left hepatic a.exists in 20% of cases; a right hepatic artery originating from the superior mesenteric a. (SMA) can be the only arterial supply in 9% of cases; the whole lesser omentum has to be removed and the SMA from 6 cm to its origin. The SMA must be freed from the celiac ganglia and its ostium removed with the celiac trunk in an aortic patch cut on the anterior side in order to avoid the renal ostia. During total hepatectomy, dissection of the portal triad is often difficult because of portal hypertension dilating accessory portal veins (parabiliary arcade) and pedicular lymphatics. Nerve plexuses are thick in front of the hepatic artery or behind the portal triad. Transection of triangular ligaments leads to the retrohepatic inferior vena cava (IVC) that must be freed from its posterior tributaries (right suprarenal vein and inferior phrenic veins flowing either into the IVC or into the hepatic veins). One big problem during hepatic replacement is the biliary anastomosis which must be well irrigated. In the recipient, dissection up to the hilum preserves hepatic and pancreatico-duodenal pedicles. The biliary tract of the graft must be cut low, behind the pancreas, and several centimeters of the gastroduodenal artery must be preserved to save hepatic and gastroduodenal pedicles.
Bases anatomiques de la transplantation hépatique
Résumé Ce travail rassemble les notions anatomiques nécessaires au bon déroulement d'une transplantation hépatique. Le prélèvement du greffon doit enlever tout le petit omentum contenant une éventuelle a. hépatique gauche née de l'a. gastrique gauche (20%) et emporter l'a. mésentérique supérieure jusqu'à 6 cm de son origine pour ne pas oublier une a. hépatique droite née de cette dernière: son ostium est pris avec le tronc clique dans un patch aortique découpé sur la face antérieure. Lors de l'hépatectomie totale, la dissection du pédicule hépatique est rendue délicate par l'hypertension portale qui dilate les veines portes diets accessoires (arcade parabiliaire) et les lymphatiques pédiculaires. Les plexus nerveux sont riches devant l'artère hépatique et derrière le pédicule. La section des ligaments triangulaires droit et gauche amène à la veine cave inférieure (VCI) rétro-hépatique qu'il faut libérer de ses afférences postérieures (en particulier la veine surrénale principale droite toujours haut située et les veines phréniques inférieures qui s'abouchent soit dans la VCI soit dans les veines hépatiques du carrefour). Lors du remplacement, l'anastomose biliaire doit être vascularisée. Chez le receveur la dissection jusqu'au hile permet de conserver les pédicules. La voie biliaire du greffon doit être coupée bas derrière le pancréas et les premiers centimètres de l'artère gastro-duodénale conservés pour préserver les pédicules hépatique et pancréaticoduodénal.相似文献
65.
Thrombin enhancement of interleukin-1 and tumor necrosis factor-alpha induced polymorphonuclear leukocyte migration. 总被引:3,自引:0,他引:3
W T Drake N N Lopes J W Fenton A C Issekutz 《Laboratory investigation; a journal of technical methods and pathology》1992,67(5):617-627
BACKGROUND: Cytokines such as IL-1 alpha and tumor necrosis factor-alpha (TNF-alpha) activate vascular endothelium to express leukocyte adhesion molecules that promote polymorphonuclear leukocyte (PMNL) migration and to synthesize tissue factor, thus making the endothelium a procoagulant surface. alpha-Thrombin, generated during coagulation, also activates endothelial cells. Since all these processes are likely involved in inflammation, the effect of alpha-thrombin on PMNL interaction with cytokine activated endothelium was investigated. EXPERIMENTAL DESIGN: Human umbilical vein endothelium was grown on polycarbonate filters to investigate the effects interleukin-1 alpha (IL-1 alpha), TNF-alpha, and alpha-thrombin on PMNL transendothelial migration quantitated with 51Cr-labeled PMNL, and on endothelial monolayer permeability, quantitated with 125I-labeled albumin (HSA). To evaluate the expression of endothelial-leukocyte adhesion molecules, enzyme-linked immunosorbent assay was performed on human umbilical vein endothelium monolayers. The effect of thrombin on PMNL accumulation and plasma exudation in inflammation was studied in a rabbit dermal model, using 51Cr-labeled blood leukocytes and [125I]HSA respectively. RESULTS: On resting human umbilical vein endothelium, alpha-thrombin induced a transient increase (2.5- to 4-fold) in monolayer permeability lasting 30 minutes. Slight but significant transendothelial migration of 51Cr-labeled PMNL was induced by alpha-thrombin (7.4 +/- 0.6% of cells added, unstimulated = 1.9 +/- 0.4%), although this response was less than that induced by f-norLeu-Leu-Phe (17%), IL-1 alpha (29%) or TNF-alpha (21%). alpha-Thrombin enhanced the initial rate of IL-1, TNF-alpha and f-norLeu-Leu-Phe induced PMNL transendothelial migration in an additive or supradditive manner (e.g., with IL-1 alpha+alpha-thrombin, migration was 58% greater than additive at 15 to 30 minutes, p < 0.001). Catalytically inactivated alpha-thrombin, D-phenylalanyl-L-propyl-L-arginine chloromethyl ketone and diisopropyl-fluorophosphate alpha-thrombin, did not enhance migration or permeability. In dermal inflammation in rabbits, alpha-thrombin (10 units/site) induced an increase in plasma protein exudation, with only a mild infiltration of PMNL. However, alpha-thrombin synergistically enhanced the PMNL infiltration induced by IL-1 alpha, TNF-alpha, but not that induced by zymosan activated plasma (C5a) or IL-8 (neutrophil-activating peptide-1). These measurements were confirmed histologically. Investigations into the mechanisms of the enhancement of PMNL migration indicated that individually vascular permeability changes, prostaglandins, platelet activating factor, and P-selectin expression did not account for the observation effects. CONCLUSIONS: Alpha-thrombin may have a role in synergistically enhancing PMNL infiltration at sites of inflammation, in part via enzymatic action on the cytokine activated endothelium. The mechanisms involved in this effect are likely a complex interaction. 相似文献
66.
B Deslaugiers Ph Vaysse JM Combes J Guitard J Moscovici M Visentin D Vardon J Bécue 《Surgical and radiologic anatomy : SRA》1994,16(2):173-177
Summary The dissection of 100 external jugular veins in 50 cadavers was the object of this anatomic study. A certain number of notions concerning the afferent veins, the mode of termination and the valvular system of this vessel were defined. 1)Afferent veins. Along its pathway toward the deep venous system, the external jugular vein successively received: the transverse cervical vein in 88 cases (88%), usually opposite the intersection of the external jugular vein with the dorsal border of the sterno- cleidomastoid muscle; the suprascapular vein in 47 cases (47%); the anterior jugular vein in 46 cases (46%); the cervical vein or anastomosis with the latter in 13 cases (13%). 2)Mode of termination. Forty-three subjects presented a symmetric mechanism. 100 anastomoses can be classed into three types: in 60 cases (60%), the external jugular vein flowed into the jugulo-subclavian venous confluence; in 36 cases (36%), in to the subclavian vein at a distance from its junction with the internal jugular vein; in 4 cases (4%) in to the trunk of the internal jugular vein. 3)Study of the valves. There were studied in 25 subjects (50 external jugular veins). The valves were found in the ostial and paraostial position in 49 out of 50 veins.
Contribution à l'étude des afférences et de la terminaison de la veine jugulaire externe
Résumé Cette étude anatomique repose sur la dissection de 100 vv. jugulaires externes chez 50 cadavres. Elle a permis de préciser un certain nombre de notions concernant les veines afférentes, le mode de terminaison et le système valvulaire de ce vaisseau. 1)Veines afférentes. Le long de son trajet vers le sytème veineux profond, la v. jugulaire externe reçoit successivement: la v. cervicale transverse dans 88 cas (88 %), habituellement en regard du croisement de la v. jugulaire externe avec le bord dorsal du m. sterno-cléido-mastoïdien ; la v. supra-scapulaire dans 47 cas (47 %); la v. jugulaire antérieure dans 46 cas (46 %) ; la v. céphalique ou une anastomose avec celle-ci dans 13 cas (13 %). 2)Mode de terminaison. Quarante trois sujets présentent un dispositif symétrique. Les 100 abouchements peuvent être classés en trois types : dans 60 cas (60 %) la v. jugulaire externe se déverse dans le confluent veineux jugulo-subclavier ; dans 36 cas (36 %), dans la v. subclavière à distance de sa réunion avec la v. jugulaire interne ; dans 4 cas (4 %) dans le tronc de la v. jugulaire interne. 3)Etude des valvules. Recherchées chez 25 sujets (50 vv. jugulaires externes), les valvules ont été retrouvées dans 49 cas sur 50 en position ostiale ou paraostiale.相似文献
67.
The ileoanal J pouch: radiographic evaluation 总被引:1,自引:0,他引:1
Endorectal ileoanal pull-through offers an attractive alternative to proctocolectomy and ileostomy for patients with ulcerative colitis, Gardner syndrome, and familial polyposis. To our knowledge, a careful radiographic analysis of the ileum, ileal pouch, and ileoanal anastomosis after ileoanal pull-through has not been reported. Thirty-two patients with ulcerative colitis, Gardner syndrome, and familial polyposis underwent colectomy, mucosal proctectomy, and endorectal ileoanal pull-through of a 15-cm ileal "J" pouch and loop ileostomy. Twenty-five (78%) of 32 of all the pouches radiographically demonstrated spiral folds extending from the middle of the pouch to the pectinate line. Other radiographic features included a mesenteric mass effect, pseudopolyps, and a central lucency that indicated intrapouch sutures. Radiographs provide useful information in the postoperative management of the ileal pull-through. 相似文献
68.
C J Allegra B A Chabner P W Sholar C Bagley J C Drake M E Lippman 《NCI monographs : a publication of the National Cancer Institute》1987,(5):199-202
The active metabolite of FUra, 5-fluorodeoxyuridine monophosphate (5-FdUMP), requires the presence of reduced folates to form a covalent ternary complex with the target enzyme thymidylate synthase (TS). In vitro and in vivo studies have demonstrated a potentiation of the cytotoxic effects of FUra when combined with the reduced folate, leucovorin. We have applied this concept to the treatment of metastatic breast cancer in a phase II trial, as recent clinical studies on patients with colorectal carcinoma have suggested an enhanced efficacy for the combination of FUra plus leucovorin. Patients entered on the present study are undergoing treatment with a 5-day daily regimen of leucovorin (500 mg/m2, iv) followed by FUra (375 mg/m2, iv). Toxicity and response data are currently being collected on patients who have failed "standard" combination regimens that included FUra. In patients with accessible tumor, serial biopsies are being obtained during treatment with the combination of FUra and leucovorin and during therapy with FUra alone to assess the degree of 5-FdUMP binding to the target enzyme, TS, in the presence and absence of exogenously administered leucovorin. Preliminary results from the biochemical studies suggest an enhanced saturation of TS by the fluorinated pyrimidine when administered with leucovorin. 相似文献
69.