ISSN:1075-2765    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:1075-2765    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Occlusion of lower extremity vascular bypass grafts results in acute limb-threatening ischemia. The underlying cause of graft failure generally is distal anastomosis stenosis, and relief of culprit stenosis is a required to maintain long-term patency. Of the three thrombolytic agents used for prolonged infusion to accomplish fibrinolysis, streptokinase was the first to be used and is limited owing to the antigenicity that precludes repeated use. Urokinase had been the mainstay of thrombolytic therapy until it was withdrawn by the U.S. Food and Drug Administration in 1999 because of the potential of transmission of infectious agents during its manufacturing process. Recombinant tissue plasminogen activator (rt-PA) has not been studied adequately to assess safety and efficacy, and there are no standardized dosing guidelines. We report our experience with six patients presenting with acute limb-threatening ischemia attributable to thrombosis of synthetic lower extremity bypass grafts. After thrombolysis using rt-PA (mean bolus dose, 12.2 ± 3.6 mg; range, 6–15 mg administered over 5 minutes followed by infusion at 2 mg/h for 15.6 ± 6.4 hours; total dose, 51 ± 16 mg), successful thrombolysis was achieved in 84% of the patients. The primary patency rate was 75% and the secondary patency rate 100% at 16 weeks. One patient underwent amputation owing to unsuccessful thrombolysis. No major bleeding or vascular complications occurred. We conclude that intra-arterial thrombolysis using rt-PA is a safe and effective therapy for patients with thrombotic occlusion of synthetic lower extremity bypass grafts presenting with acute limb-threatening ischemia and allows a high rate of secondary patency, avoiding amputation.

ISSN:1075-2765    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The objective of this study was to assess the degree of QT dispersion and effect of thrombolytic therapy on QT dispersion in elderly (age ≥65 years) versus younger (age <65 years) patients with acute myocardial infarction. The QT dispersion was measured manually in 10 ± 2 leads of 12-lead electrocardiograms on admission, at completion of thrombolytic therapy, and at day 2 after thrombolytic therapy in 36 elderly (73 ± 5.7 years) and 36 younger (59.9 ± 7.7 years) patients with acute myocardial infarction. Before initiation of thrombolytic therapy, elderly patients had higher absolute and corrected QT dispersion than younger patients (absolute QT dispersion: 76.3 ± 7.3 versus 69.6 ± 7.5 milliseconds, respectively,P< 0.0001; corrected QT dispersion: 77.9 ± 7.6 versus 70.8 ± 7.4 milliseconds, respectively,P< 0.001). The difference in QT dispersion between elderly and younger patients persisted at the completion of thrombolytic therapy (absolute QT dispersion: 75.1 ± 7.2 versus 69.1 ± 8.4 milliseconds, respectively,P= 0.001; corrected QT dispersion: 77.2 ± 7.2 versus 70.7 ± 8.0 milliseconds, respectively,P= 0.001) and at day 2 after thrombolytic therapy (absolute QT dispersion: 74.1 ± 8.2 versus 69 ± 9.1 milliseconds, respectively,P= 0.01; corrected QT dispersion: 76.0 ± 7.9 versus 70.5 ± 8.8 milliseconds, respectively,P= 0.006). Compared with the prethrombolytic values, there was no significant change in absolute and corrected QT dispersion at the completion of thrombolytic therapy or at day 2 after thrombolytic therapy in elderly or younger patients. Elderly patients with acute myocardial infarction have higher QT dispersion than younger patients with acute myocardial infarction, and QT dispersion does not change early after thrombolytic therapy in elderly or younger patients.

ISSN:1075-2765    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The aim of this study was to evaluate the utility of the American Pain Society (APS) questionnaire in the assessment of osteoarthritis (OA) pain and to determine the onset of action of celecoxib in the treatment of acute flare pain in patients with OA of the knee or hip. Pooled data from three pivotal, randomized, double-blind, placebo-controlled, 12-week trials of patients with OA who exhibited a flare of disease activity after withdrawal of nonsteroidal anti-inflammatory drug or analgesic therapy were evaluated. Patients completed the APS Pain Measure Questionnaire, which evaluates pain intensity and quality of life, at baseline and daily for the first 7 days of therapy. In addition, patients underwent a range of standard OA assessments to evaluate the analgesic efficacy of celecoxib up to 12 weeks. Three thousand two hundred fifty-eight patients were enrolled in the three studies, of whom 2041 completed the APS questionnaire (1010 received celecoxib, 513 received naproxen, and 518 received placebo). Within the first 24 hours, celecoxib at a dose of 200 or 400 mg/d significantly reduced the amount of acute pain experienced compared with placebo for four of the five measures, and statistical significance for the remaining parameter, “pain in the last 24 hours,” was achieved on day 2. Celecoxib at a dose of 200 to 400 mg/d provided similar efficacy to naproxen at a dose of 1000 mg/d. The pain relief observed with celecoxib was maintained for the APS evaluation period. Long-term efficacy assessments showed the efficacy of 200 mg/d of celecoxib to be continuous and maintained for at least the 12 weeks of the study and that it was equivalent to 400 mg/d of celecoxib and 1000 mg/d of naproxen. This study demonstrates that the APS questionnaire is a useful measure of pain and therapeutic response in OA. Celecoxib furthermore seems to be an effective acute and chronic analgesic in OA.

ISSN:1075-2765    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

This study was designed to validate oxygen saturation measurements from the NOVA CO-Oximeter (NOVA Biomedical Corporation, Waltham, MA), the i-STAT System (Sensor Devices, Waukesha, WI), and the Corning 170 blood gas analyzer (Bayer Corporation, East Walpole, MA) under conditions similar to the clinical application of a hemoglobin-based oxygen carrier (HBOC, hemoglobin glutamer–200 [bovine]; Oxyglobin, Biopure Corporation, Cambridge, MA).A canine model was used for both in vitro and in vivo experiments. In vivo experiments were conducted in a canine laboratory, and in vitro experiments were conducted in a tonometry laboratory. Study subjects were six mixed-breed dogs, each weighing approximately 30 kg. In the first set of experiments, the target blood po2levels were reached by tonometry. In the second set of experiments, quantitative measurements of total oxygen content with the LEXO2CON-K (HOSPEX Fiberoptics, Chestnut Hill, MA) were performed, immediately followed by measurements with the NOVA CO-Oximeter and the i-STAT system. HBOC was added in concentrations of 16.2, 32.5, 65, and 97.5 g/L. To analyze the clinical significance of the differences in the results obtained with the each investigated instrument, blood samples from dogs treated with HBOC after acute hemorrhagic shock were used. Oxygen saturation, oxygen content, and po2were measured. There was a strong correlation between the oxygen saturation values measured with the investigated instruments in samples after tonometry and known po2. The total calculated oxygen content varied by 5% based on results generated by calculations using the investigated instruments. The results did not change with different oxygenation of the sample. The differences among methods were not significant when the HBOC concentration was 16.2 g/L. Higher concentrations of HBOC increased the difference between calculated and measured oxygen content; the i-STAT system demonstrated a greater deviation compared with the results of the other two instruments. Systemic oxygen uptake using the investigated instruments showed a high correlation with values based on LEXO2CON-K measurements (R= 0.97 for CO-Oximeter,R= 0.96 for Corning 170 blood gas analyzer, andR= 0.79 for i-STAT system). Systemic oxygen uptake values based on CO-Oximeter and Corning 170 blood gas analyzer data showed 75% accuracy; i-STAT system accuracy was 63% for control samples and 50% for samples after HBOC infusion.

ISSN:1075-2765    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Amlodipine is a dihydropyridine calcium antagonist and is widely used for the treatment of cardiovascular diseases. Amlodipine has two stereoisomers [R(+), S(−)], and only the S(−) isomer exerts vasodilating action. In this preliminary study, amlodipine (5 mg) was given to three elderly hypertensive patients once daily for 10 days. Blood samples were obtained, and serum concentrations of R(+)- and S(−)-amlodipine were measured by a gas chromatographic method. The R(+)/S(−) ratio of plasma amlodipine in these elderly subjects was greater than that reported in young subjects. These results suggest that the influence of aging on the pharmacokinetic profiles might differ between the R(+)- and S(−)-isomers of amlodipine.

ISSN:1075-2765    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

We examined the effect ofSalmonella typhi(wild-type Ty2 and mutant strain TYT1231)-infected U937 cells on natural killer cell (NKC) cytotoxicity of peripheral blood mononuclear cells (PBMCs) and highly purified NKC (HPNKCs; CD16+/CD56+> 95%; the rest corresponding to CD3+T cells). We also analyzed the possible role of various protein kinases involved in natural cytotoxicity on these processes. PBMC cytotoxicity againstS typhi-infectedU937 cells was significantly higher (paired Studentttest;P< 0.05) than its lytic effect against noninfected cells (control) at the various effector-to-target cell ratios used (30:1 [24.4 ± 9.7, 25.1 ± 11.8, and 17.5 ± 8.6]; 50:1 [26.6 ± 9.7, 26.7 ± 12.8, and 21.2 ± 7.5] and 70:1 [32.4 ± 14.4, 30.1 ± 12.4, and 23.1 ± 7.2], respectively). PBMC NKC activity seemed to be dependent on such ratios and was similar against bothSalmonellastrains studied. Approximately half of the individual samples tested (n = 12; 8 male and 4 female subjects of comparable age) showed at least a 20% specific lysis increase against their own control; essentially no changes or smaller increases in NKC activity were observed in all other samples. Similar results were obtained using HPNKCs as effector cells (5:1 ratio [38.9 ± 12.3, 43.3 ± 11.2, and 27.5 ± 4.9] and 10:1 ratio [51.3 ± 9.1, 46.1 ± 9.8, and 37.7 ± 15.5, respectively]). In general, specimens significantly lysed after incubation with PBMCs responded in a similar manner to a challenge with HPNKCs. PBMC and HPNKC cytotoxicity againstS typhiwild-type-infected U937 cells was significantly decreased in a dose-dependent manner by the addition of genistein (50–200 &mgr;mol) or GFX (0.5–2.0 &mgr;mol) to the cytotoxicity assay mixture. NKC activity was almost completely inhibited at the highest genistein and GFX concentrations. In similar experiments, wortmannin (100–500 nmol) failed to inhibit PBMC cytotoxicity and significantly decreased HPNKC activity only at the highest concentration tested. These results show that in the process of NKC recognition and lysis ofS typhi-infected U937 cells, there is not a requisite for full bacterial intracellular survival capacity and thatS typhi-infected U937 cells are a significantly better target than noninfected U937 cells. NKC signaling pathways activated during theS typhi-infected U937 cell recognition and lysis process are mainly protein tyrosine kinase and protein kinase-C, and they can be blocked by the same protein kinase inhibitors known to inhibit natural cytotoxicity.

ISSN:1075-2765    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

When injected subcutaneously, extracts from the white berry mistletoe (Viscum album L) lead to a dose-dependent local inflammatory reaction at the injection site. From in vitro investigations withV albumextracts, the release of proinflammatory cytokines from peripheral blood mononuclear cells and from a human skin model (Skin2model; Advanced Tissue Sciences, La Jolla, CA) is known. This shows dose dependence for mistletoe lectin-I in the range of 0.02 ng/mL to 10.0 ng/mL. In this study, an investigation was conducted of which cytokines are released in the skin by the mistletoe lectin–standardized mistletoe extractsViscum albumQuFrF (VaQuFrF) and Iscador Qu Spzial (IQuS) (Institute Hiscia, Arlesheim, Switzerland) and whether dose dependency exists. The model used for this study is the multilayered skin model EpiDerm (MatTek Corporation, Ashland, MA), which consists of multilayered keratinocytes. The viability of the cell culture was measured after incubation with 0.01, 0.1, 0.2, 0.3, 0.5, and 15.0 ng/mL VaQuFrF or 0.01, 0.1, 0.2, 0.3, 0.5, 5.0, and 15.0 ng/mL IQuS. The release of interleukin (IL)-1&agr;, IL-2, IL-6, IL-8, IL-10, IL-12p40+70, IL-12p70, tumor necrosis factor-&agr; (TNF&agr;), interferon (IFN)-&agr;, IFN&ggr;, granulocyte macrophage–colony stimulating factor, and RANTES was determined after incubation with 0.5 ng/mL of IQuS ng/mL and VaQuFrF. The dose dependency of the release of IL-1&agr; and IL-6 after incubation with 0.5 and 15.0 ng/mL VaQuFrF or 0.5 ng/mL, 5.0 ng/mL, and 15.0 ng/mL IQuS and that of the release of IL-1&agr;, IL-2, IL-6, IL-10, and TNF&agr; after incubation with 0.01 ng/mL, 0.1 ng/mL, 0.2 ng/mL, 0.3 ng/mL, and 0.5 ng/mL VaQuFrF or IQuS were determined. A dose-dependent decrease of cellular viability and an increase of IL-1&agr;, IL-6, and TNF&agr; as well as the release of IL-8 could be demonstrated. These results are compatible with the hypothesis that the subcutaneous injection of VaQuFrF and IQuS leads to a release of proinflammatory cytokines at the injection site.

ISSN:1075-2765    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:1075-2765    

出版商:OVID    

年代:2003

数据来源: OVID