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91.
Results of eight multicenter, randomized, placebo-controlled, double-blind, parallel-group studies were pooled to assess the efficacy of the angiotensin II-receptor blocker irbesartan over the dose range of 1 to 900 mg. A total of 2955 adults with a seated diastolic blood pressure of 95 to 110 mm Hg were randomized to treatment with oral irbesartan once daily or placebo for 6 to 8 weeks. Office blood pressure was measured at trough (24+/-3 hours after the last dose) and peak (3+/-1 hours after the last dose) by mercury sphygmomanometry. Demographic characteristics (mean blood pressure; 151/101 mm Hg; mean age, 54 years; 63% male; and 82% white) were similar across all dose groups. After the groups were pooled, antihypertensive efficacy was assessed by therapeutic response (trough seated diastolic blood pressure <90 mm Hg or a reduction from baseline of > or = 10 mm Hg) and by modeling of the maximum reductions in trough and peak seated diastolic and systolic blood pressure. Antihypertensive effects increased with increasing doses and reached a plateau at > or = 300 mg. Irbesartan 150 mg provided placebo-subtracted reductions in trough seated systolic and diastolic blood pressure of approximately 8 and approximately 5 mm Hg, respectively, with 56% of patients displaying a favorable response. In conclusion, irbesartan provides clinically significant blood pressure lowering, with a clear relationship between (log) dose and antihypertensive effect.  相似文献   
92.
Several compounds, structurally related to the insect growth regulator Fenoxycarb, exhibited interesting inhibition action to control proliferation of Trypanosoma cruzi, the parasite responsible for Chagas' disease. Some of these drugs were shown to be potent growth inhibitors of this parasite. All of these drugs had previously presented juvenoid activity on several non-related bug species such as Tenebrio molitor, Galleria mellonella, Dysdercus cingulatos, and Pyrrhocoris apterus.  相似文献   
93.
Vascular nephropathies are a steadily increasing cause of end-stage renal failure. Arterionephrosclerosis and arteriolonephrosclerosis are common features in the hypertensive patient. This is especially true for blacks of African descent, in whom hypertension and nephrovasculopathies are a major cause of renal insufficiency. That primary hypertension leads to renal vascular lesions, glomerular obsolescence and interstitial fibrosis has long been established. It should not, however, obscure the fact that renal vascular lesions can be observed in animal models as well as in some humans, especially young blacks, in the absence of, or anticipating the onset of hypertension. This leads to considering the hypothesis that nephroangiosclerosis might stem from a genetic defect in the renal vascular bed and that this defect is strongly associated with the hypertensive trait. Atherosclerotic renal disease is a major, potentially treatable cause of chronic renal disease is a major, potentially treatable cause of chronic renal failure, especially in whites. It leads to renal atrophy, but the ischemic kidney retains a vigorous potential for tubular cell regeneration, which pleads for early recognition and treatment. Recent data suggest that renal ischemia, be it due to renal artery stenosis or to cholesterol crystal embolism, ranks among the multiple causes of secondary focal segmental glomerulosclerosis. Irrespective of its initial mechanism, ischemia induces renal fibrosis, the pathophysiology of which is centered on increased generation of angiotensin II. Finally, renal vascular lesions are commonly observed in the course of various nephropathies, even in the absence of hypertension, and the relationship between these lesions and the unfavorable prognosis of glomerulopathies, especially primary focal-segmental glomerulosclerosis, membranous glomerulopathy and IgA glomerulonephritis, remains to be elucidated. Expanding knowledge of the spectrum of nephrovasculopathies opens perspectives for investigating, understanding and treating a major mechanism of progressive renal insufficiency.  相似文献   
94.
BACKGROUND AND OBJECTIVE: Drug resistance has become a major cause of treatment failure in patients with acute leukemia. P-glycoprotein (Pgp), which is associated with the multidrug resistance (MDR) phenotype, has been reported to be an important predictor of treatment outcome. The aim of this study was to analyze the value of Pgp expression in bone marrow or peripheral blood as a predictor of the response to remission induction chemotherapy as well as the duration of remission in patients with de novo acute myeloid leukemia (AML). DESIGN AND METHODS: We examined the expression of Pgp in 82 patients with de novo AML using an immunocytochemical assay with the C219 monoclonal antibody. RESULTS: Twenty-seven of the 82 patients (33%) were C219-positive in from 1% to 100% of their cells. Thirteen cases (16%) showed a positive reaction in more than 50% of the leukemic cells. Only hyperleukocytosis was significantly associated with higher expression of Pgp. Although 8 of the 13 cases (62%) with more than 50% of cells having Pgp expression were CD34-positive, this association was not statistically significant. A univariate analysis of resistance to induction therapy showed a significantly higher resistance rate in patients with increased Pgp expression (P = 0.01) as well as in those patients with decreased reactivity to myeloperoxidase. The multivariate analysis revealed the independent prognostic value of Pgp expression. C219 reactivity did not have an influence on remission duration. INTERPRETATION AND CONCLUSIONS: Our data indicate that P-glycoprotein expression is a reliable marker of resistance to induction treatment in patients with de novo AML.  相似文献   
95.
OBJECTIVE: We examined the effects of aprotinin on graft patency, prevalence of myocardial infarction, and blood loss in patients undergoing primary coronary surgery with cardiopulmonary bypass. METHODS: Patients from 13 international sites were randomized to receive intraoperative aprotinin (n = 436) or placebo (n = 434). Graft angiography was obtained a mean of 10.8 days after the operation. Electrocardiograms, cardiac enzymes, and blood loss and replacement were evaluated. RESULTS: In 796 assessable patients, aprotinin reduced thoracic drainage volume by 43% (P < .0001) and requirement for red blood cell administration by 49% (P < .0001). Among 703 patients with assessable saphenous vein grafts, occlusions occurred in 15.4% of aprotinin-treated patients and 10.9% of patients receiving placebo (P = .03). After we had adjusted for risk factors associated with vein graft occlusion, the aprotinin versus placebo risk ratio decreased from 1.7 to 1.05 (90% confidence interval, 0.6 to 1.8). These factors included female gender, lack of prior aspirin therapy, small and poor distal vessel quality, and possibly use of aprotinin-treated blood as excised vein perfusate. At United States sites, patients had characteristics more favorable for graft patency, and occlusions occurred in 9.4% of the aprotinin group and 9.5% of the placebo group (P = .72). At Danish and Israeli sites, where patients had more adverse characteristics, occlusions occurred in 23.0% of aprotinin- and 12.4% of placebo-treated patients (P = .01). Aprotinin did not affect the occurrence of myocardial infarction (aprotinin: 2.9%; placebo: 3.8%) or mortality (aprotinin: 1.4%; placebo: 1.6%). CONCLUSIONS: In this study, the probability of early vein graft occlusion was increased by aprotinin, but this outcome was promoted by multiple risk factors for graft occlusion.  相似文献   
96.
As part of a total mixed ration, two rumen-fistulated dairy cows were fed meat and bone meal that had been artificially contaminated with Salmonella spp. Samples from the rumen, feces, and milk were taken 3 d/wk and cultured for salmonella. Rectal temperatures and rumen pH were also measured at the time of sample collection. Over the 2-mo study, salmonella were intermittently recovered from rumen contents, from feces, and from necropsy specimens of rumen contents, cecal contents, and mesenteric lymph nodes. No excretion of salmonella in milk was detected. An elevated rumen pH was associated with increased isolation of salmonella. No clinical illness was observed for either cow. Meat and bone meal that has been contaminated with low concentrations of salmonella is unlikely to result in clinical illness in healthy adult lactating cows. However, dairy producers should continue to be concerned about feed biosecurity and water contamination of animal by-products to prevent and control contamination by salmonella.  相似文献   
97.
We have estimated the turnover and relative pool sizes of nascent-VLDL-TG and VLDL-remnants-TG in anesthetized rats. [1-14C]Palmitoyl- and [2-3H]glyceryl-labeled “VLDL”-TG (including nascent VLDL-TG and VLDL-remnants-TG) were prepared by injecting labeled palmitate and glycerol into donor rats. Labeled serum from these rats was then injected intravenously into nembutalized male rats and serial blood samples taken for 30 min. Special care was taken to define any early components in the labeled “VLDL”-TG disappearance curves. In other experiments, the donors were rendered functionally hepatectomized 30 min after injection of3H-glycerol and the endogenous labeled VLDL-TG was allowed to circulate 30–60 min before collection of the TG-labeled VLDL-remnants-containing serum. The latter was injected into 4 recipient nembutalized rats and the remnant-TG-turnover measured by serial sampling as above. In two cases,14C-“VLDL” and3H-VLDL-remnants were injected as a single bolus into ether-anesthetized rats. Despite its complex composition, “VLDL”-TG in most cases disappeared in a single exponential fashion for 30 min with an average half-life of 5.9 min in nembutalized and 2.8 in ether-anesthetized rats. VLDL-remnants-TG showed a more complex behavior, but contained a major rapid component with a mean t1/2 of ca. 1.5 min in both groups. The data, analyzed by multicompartmental analysis, were fitted to a simple model in which turnover of a larger nascent VLDL-TG pool with formation of a more rapidly turning over smaller pool of VLDL-remnant-TG is the rate-limiting step in overall TG removal from the d<1.006 fraction of rat serum. The data are consistent with our theoretical prediction that under these conditions the kinetics of the VLDL-remnants cannot be resolved from analysis of the total composite “VLDL” (nascent plus remnant) pool.  相似文献   
98.
This paper documents the first essential dynamics analysis of ras protein ligands and of the protein itself, showing important features of their dynamic properties. Essential dynamics analysis of 300 ps of full solvent molecular dynamics simulations revealed differences in structure and dynamics between GDP- and GTP-bound forms of H-ras-p21. Regions in the protein which exhibited a structural shift correspond to the switch regions described previously. Differences in dynamics between H-ras-p21 GDP and H-ras-p21 GTP may be related to interactions of ras with GAP and its receptor and effector. Molecular dynamics of free GDP (in the absence of protein) were performed in water for 2 ns and analysed using essential dynamics. The conformations of GDP and GTP when bound to the protein were compared with free GDP, revealing that the ligands bind to the protein in an energetically unfavourable conformation. GDP and GTP molecules from various other protein crystal structures were also analysed. These ligands adopt similar conformations to those seen in H-ras-p21.   相似文献   
99.
Characterisation of n-type GaAs, etched in a 5:1:1 mixture of H2SO4:H2O2:H2O, was performed using X-ray photoelectron spectroscopy (XPS) and electrochemical AC impedance. Quantitative XPS analysis of GaAs indicated that the as-received wafers had a gallium-rich native oxide which was not affected by solvent degreasing treatments. Subsequent, oxidative etching formed a thinner arsenic-rich oxide. It is suggested that etching causes initial thinning of the native oxide; subsequently, transport of Ga and As ions occurs through the film by high-field ionic conduction. Arsenic enrichment in the resultant oxide film arises from the greater mobility of Ga3+ ions compared with As3+ ions as well as the relative solubility of Ga2O3 compared with As2O3. The as-received oxide film thickness, determined from the ratio of the oxide to substrate XPS peaks, was approximately 1.1 nm. After etching this was reduced to about 0.7 nm. This thickness is consistent with the driving voltage for oxide formation being provided by the electrochemical potential difference between hydrogen peroxide and the GaAs wafer (i.e. between 0.4 V, for As, and 1.2 V, for Ga, at a nm V−1 ratio of 2). Capacitance measurements, derived from electrochemical impedance data, combined with film thickness data, gave a value of about 5 for the dielectric constant of As2O3.  相似文献   
100.
After all medical and audiological treatments have failed, tinnitus patients often get the advise to "learn to live with it". The aim of psycho-social treatment is assisting patients in the identification of tinnitus aggravating factors and teaching them various coping skills. Treating these problems is primarily recommended for patients suffering from other disorders, even related to tinnitus. Motivation for psycho-social treatment depends on the ability of patients to accept tinnitus as a fundamental fact in their existence.  相似文献   
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