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31.
GK Rivera D Pinkel JV Simone ML Hancock WM Crist 《Canadian Metallurgical Quarterly》1993,329(18):1289-1295
BACKGROUND: Therapy for childhood lymphoblastic leukemia has evolved during the past three decades, but key questions about what are the least toxic, most effective forms of treatment remain unanswered because of the lack of comprehensive follow-up information. METHODS: To assess long-term outcome in the series of clinical trials conducted at St. Jude Hospital, we compared the results of treatment typical of four eras: exploratory combination chemotherapy (era 1, 1962 to 1966; 91 patients), regimens for the control of meningeal leukemia (era 2, 1967 to 1979; 825 patients), limited intensification of therapy (era 3, 1979 to 1983; 428 patients), and extended intensification of therapy (era 4, 1984 to 1988; 358 patients). ("Intensification" refers to strategies of systemic chemotherapy that are more aggressive than conventional ones.) The major end points were survival and event-free survival; we also calculated the relative risk of treatment failure and the rate of relapse or death after treatment ended (post-treatment failure rate). RESULTS: The probability of event-free survival improved significantly in each successive era (P < 0.001 by the log-rank test), reaching 71 percent in era 4. There was a decrease of approximately 50 percent in the risk of treatment failure from one era to the next in each subgroup of patients defined according to different combinations of the leukocyte count, race, age, and sex. Leukemia appeared to be eradicated in patients who remained in complete remission for three years or more after treatment in era 4. The incidence of death due to nonleukemic causes remained 4 to 6 percent despite the trend toward more intensive treatment. An estimated 765 patients (45 percent) are long-term survivors; most of them (80 percent) have no health problems related to leukemia or its treatment. CONCLUSIONS: The development and successful application of preventive therapy for meningeal leukemia, followed by the intensification of systemic chemotherapy, has progressively improved the rate of cure of childhood lymphoblastic leukemia, with relatively few adverse sequelae. 相似文献
32.
A precise calculation of the amount of intraalveolar fluid is the basis of a quantitative analysis of intraalveolar compounds. Different approaches have been made to cover this important problem. Here, we report a comparative study with five markers: 99mTc-DTPA, 51Cr-EDTA, inulin, urea, and methylene blue in animal experiments as well as in human experiments. The marker substances were added to the lavage fluid, and the "dilution" of the markers, i.e., the alveolar fluid, was calculated. The results showed that in animals with healthy lungs the tracer methods are able to calculate amounts of intraalveolar fluid that are comparable to morphologic findings. In animals as well as in humans, methylene blue and inulin were shown to be useless in determining alveolar fluid volume compared with the tracer methods. In humans, the calculations with the urea method and with Tc-DTPA were in the same magnitude, but there was no individual correlation. We conclude that, at present, the methods to quantitate alveolar fluid volume lack precision and add nothing to a deeper understanding of alveolar biology. 相似文献
33.
LM Goldenhar AM Ruder LM Ewers S Earnest WM Haag MR Petersen 《Canadian Metallurgical Quarterly》1999,35(2):112-123
BACKGROUND: Occupational scientists agree there are hazards associated with dry-cleaning, but do dry-cleaning owners and workers concur? Knowledge of owners' and workers' perceptions can help guide intervention efforts to reduce worker exposure. To better understand these issues, a qualitative study was conducted using focus group methodology and constant comparative analysis. METHODS: Two owner and four worker focus groups were held. RESULTS: Findings suggest that overall, health and safety issues were not of great concern. Owners were primarily concerned with the economic impact of regulations. Workers did express some anxiety about solvent exposure and burns, but most felt that these hazards were "just part of the job." Also, other than the installation of air-conditioning in the shops and the provision of health benefits, workers could not think of ways health and safety on the job could be improved. CONCLUSIONS: These findings will be used to develop comprehensive safety and health interventions (e.g., engineering plus education and training) in dry-cleaning shops. 相似文献
34.
WM Pardridge 《Canadian Metallurgical Quarterly》1998,23(5):635-644
We have examined the effects of the macrocyclic lactone protein kinase C (PKC) activator bryostatin 1 on taxol-induced apoptosis and inhibition of clonogenicity in the human monocytic leukemia cell line U937. Exposure of cells to bryostatin 1 (10 nM; 15 hr) after (but not before) a 6-hr incubation with 0.5 microM taxol significantly increased apoptosis and resulted in an approximately 3 log reduction in clonogenicity. Cell cycle analysis revealed that the increase in apoptotic cells following bryostatin 1 treatment occurred primarily in the population undergoing taxol-mediated G2M arrest. The actions of bryostatin 1 were not attributable to potentiation of taxol-induced tubulin stabilization or to a reduction in the intracellular retention of taxol. Following exposure of cells to taxol, the Bcl-2 protein displayed an alteration in mobility that was not modified appreciably by bryostatin 1 treatment. The mobility shift in Bcl-2 protein from cells exposed to taxol followed by bryostatin 1 was eliminated by treatment of lysates with the protein phosphatase 2A (PP2A); the latter effect was blocked by okadaic acid. Treatment of cells with taxol followed by bryostatin 1 did not increase the amount of total Bax (compared with treatment with taxol alone), but did increase the amount of free Bax in the supernatant fraction. Finally, the ability of bryostatin 1 to potentiate taxol-induced apoptosis in U937 cells was mimicked closely by 2'-amino-3'-methoxyflavone (PD98059), a specific inhibitor of the mitogen-activated protein kinase (MAPK) kinase (MEK). Collectively, these findings indicate that bryostatin 1 increases the susceptibility of U937 cells to taxol-induced apoptosis and inhibition of clonogenicity. They also raise the possibility that this phenomenon may involve functional alterations in Bcl-2 and/or other proteins involved in regulation of the cell death pathway. 相似文献
35.
OBJECTIVES: After fluid percussion brain injury (FPI) in the newborn pig, pial arteries constrict and responses to dilator stimuli, including opioids, are blunted. This study was designed to determine if altered release of prostaglandins contributes to blunted opioid dilation of cerebral arteries in newborn piglets following brain injury. DESIGN: Prospective, in vivo, cerebral hemodynamic animal study. SETTING: University research laboratory. SUBJECTS: Newborn (1- to 5-days old) piglets of either gender. INTERVENTIONS: In anesthetized, newborn, 1- to 5-day-old pigs, a closed cranial window was used to measure pial artery diameter and to collect cortical periarachnoid cerebrospinal fluid (CSF) for determination of 6-keto-PGF1alpha, the stable metabolite of prostaglandin I2 (PGI2) and thromboxane B2 (TXB2), the stable metabolite of TXA2, via radioimmunoassay. FPI of moderate severity (1.9 to 2.3 atmospheres) was produced by using a pendulum to strike a piston on a saline-filled cylinder that was fluid coupled to the brain via a hollow screw inserted through the cranium. MEASUREMENTS AND MAIN RESULTS: Methionine enkephalin (Met) vasodilation was blunted after FPI but was partially restored with indomethacin pretreatment (5 mg/kg i.v.) (8 +/- 1 [SEM] %, 13 +/- 1%, and 20 +/- 1% vs. 1 +/- 1%, 3 +/- 1%, and 5 +/- 1% vs. 7 +/- 1%, 10 +/- 1%, and 15 +/- 1%, respectively, for 10(-10), 10(-8), and 10(-6) M Met during control conditions, after FPI, and after FPI pretreated with indomethacin, n = 6). Similarly, restoration of Met dilation after FPI was observed with SQ 29,548, a TXA2 antagonist. Met-induced 6-keto-PGF1alpha release was blunted following FPI (889 +/- 20, 1130 +/- 33, and 1886 +/- 59 vs. 2630 +/- 36, 2775 +/- 30, and 2825 +/- 36 pg/mL for control, 10(-10), and 10(-6) M Met before and after FPI, respectively, n = 6). In contrast, Met-induced TXB2 release was enhanced after FPI (340 +/- 20, 423 +/- 25, and 473 +/- 30 pg/mL vs. 518 +/- 30, 726 +/- 90, and 901 +/- 35 pg/mL for control, 10(-10), and 10(-6) M Met before and after FPI, respectively, n = 6). Leucine enkephalin- and dynorphin-induced dilation and associated prostaglandin release were similarly altered following FPI. Beta endorphin-induced constriction was enhanced following FPI, and these potentiated responses were blunted after indomethacin or SQ 29,548 pretreatment. CONCLUSIONS: These data show that FPI increases CSF 6-keto-PGF1alpha and TXB2 concentrations. These data suggest that altered release of prostaglandins by opioids contribute to impaired cerebral hemodynamics following FPI in piglets. 相似文献
36.
Men develop perioperative ulnar neuropathies more frequently than women. To determine the role of anatomical gender differences in the development of these neuropathies, we performed several studies of the anatomy of the ulnar nerve, cubital tunnel, and elbow region. These studies included detailed dissection of male and female embalmed and unembalmed cadavers, ultrasound measurements of the tissue layers at the elbow, and measurement of various dimensions of the coronoid process of the ulna in multiple skeletal sets. No gross anatomical differences were found between genders regarding the course of the ulnar nerve through the upper limb. However, there was a strikingly larger (2-19 times greater) fat content on the medial aspect of the elbow in women compared to men, and the tubercle of the coronoid process was approximately 1.5 times larger in men (P < or = .002, rank sum test). Our finding suggest that the tubercle of the coronoid process is a likely area for external compression-induced ischemia of the ulnar nerve because the nerve and its arterial supply (the posterior ulnar recurrent artery) are covered at the tubercle only by skin, subcutaneous fat, and a very thin aponeurosis of the flexor carpi ulnaris. Importantly, this tubercle is larger and the nerve and blood vessels passing by it are less protected by subcutaneous fat in men than in women. These two anatomical differences between men and women may contribute to the increased frequency of perioperative ulnar neuropathy induced by external pressure at the medial aspect of the elbow in men. 相似文献
37.
Drugs in these categories may have effects on several organs in addition to the liver. For example, amiodarone may produce thyroid and corneal injury apart from or in addition to the phospholipidosis seen in the liver. Oral contraceptive steroids remain a rare but important concern for developing hepatic adenomas and possibly hepatocellular carcinoma, as well as a risk factor for developing Budd-Chiari syndrome in long-term users. Among the antihyperlipidemic agents, nicotinic acid, especially the sustained release formulations, may produce severe of even fatal hepatic injury. Increasing numbers of reports of hepatotoxicity from newer beta blockers and angiotensin-converting enzyme inhibitors require ongoing vigilance in patients receiving these medications. 相似文献
38.
CC Hermsen E Mommers T van de Wiel RW Sauerwein WM Eling 《Canadian Metallurgical Quarterly》1998,178(4):1225-1227
Experimental cerebral malaria (ECM) can be induced in C57B1 mice by infection with Plasmodium berghei K173 parasites. Behavioral changes shortly before they die of ECM may reflect disturbance of the integrity of the blood-brain barrier (BBB). Folic acid elicits strong convulsive activity if the permeability of the BBB is increased. Administration of folic acid to mice during development of ECM induced convulsions. Interventions known to prevent fatal outcome from ECM, such as splenectomy or treatment with anti-CD4 or anti-CD8 monoclonal antibodies, also prevented sensitivity to folic acid-induced convulsions. In addition, infected mice with ECM and sensitive to folic acid-induced convulsions, recovered from this sensitivity after treatment with anti-T cell antibodies within 4 h. These data suggest that disturbance of the permeability of the BBB can be reversed and depends on the involvement of T cells. 相似文献
39.
RA Memon WM Holleran AH Moser T Seki Y Uchida J Fuller JK Shigenaga C Grunfeld KR Feingold 《Canadian Metallurgical Quarterly》1998,18(8):1257-1265
Alterations in triglyceride and cholesterol metabolism often accompany inflammatory diseases and infections. We studied the effects of endotoxin (lipopolysaccharide [LPS]) and cytokines on hepatic sphingolipid synthesis, activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid synthesis, and lipoprotein sphingolipid content in Syrian hamsters. Administration of LPS induced a 2-fold increase in hepatic SPT activity. The increase in activity first occurred at 16 hours, peaked at 24 hours, and was sustained for at least 48 hours. Low doses of LPS produced maximal increases in SPT activity, with half-maximal effect seen at approximately 0.3 microg LPS/100 g body weight. LPS increased hepatic SPT mRNA levels 2-fold, suggesting that the increase in SPT activity was due to an increase in SPT mRNA. LPS treatment also produced 75% and 2.5-fold increases in hepatic sphingomyelin and ceramide synthesis, respectively. Many of the metabolic effects of LPS are mediated by cytokines. Interleukin 1 (IL-1), but not tumor necrosis factor, increased both SPT activity and mRNA levels in the liver of intact animals, whereas both IL-1 and tumor necrosis factor increased SPT mRNA levels in HepG2 cells. IL- produced a 3-fold increase in SPT mRNA in HepG2 cells, and the half-maximal dose was 2 ng/mL. IL-1 also increased the secretion of sphingolipids into the medium. Analysis of serum lipoprotein fractions demonstrated that very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein isolated from animals treated with LPS contained significantly higher amounts of ceramide, glucosylceramide, and sphingomyelin. Taken together, these results indicate that LPS and cytokines stimulate hepatic sphingolipid synthesis, which results in an altered structure of circulating lipoproteins and may promote atherogenesis. 相似文献
40.
RW Samsel TH Lewis WM Sanders LD Wood PT Schumacker 《Canadian Metallurgical Quarterly》1994,9(1):25-33
An in vivo antitumor screening of extracts of Gomphrena martiana indicated positive activity in the petroleum ether extract, and its further bioactivity-directed fractionation resulted in a lipophilic flavonoid fraction. Upon inoculation of various doses of 5,6,7-trisubstituted flavones on two murine tumor lines, Sarcoma 180 and Ehrlich's carcinoma, a decrease of tumor growth was observed. An in vitro KB cultured cell screen indicated cytotoxicity. 相似文献