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71.
72.
Background
Haemorrhage after Cardio Pulmonary Bypass (CPB) Surgery is a well recognised complication that leads to significant morbidity and mortality. The incidence varies between 5-25% depending upon the clinical situation. Several factors are implicated as causative but none have been precisely proved.Methods
Our study was an attempt to evaluate the haemostatic defect with particular reference to platelet function abnormalities during cardio pulmonary bypass surgery, in order to reduce the morbidity and mortality associated with post CPB haemorrhage. Flow cytometric evaluation of different platelet glycoproteins like GPIb/IX, GPIIb/IIIa and GMP-140 was done.Results
The marker expression showed deregulation during surgery which returned to base after bypass was terminated. In contrast, the cases with bleeding showed significant variation. P-Selectin (GMP 140) expression decreased progressively till 3rd post-operative day showing lack of activation of platelets in cases of severe bleeding.Conclusion
Longer duration of CPB initiates plasmin generation through heparin, which raises the PAI-1-tPA complex and thereby down regulating the functions of platelets. This suggests a link between duration of CPB, bleeding, platelet dysfunction and fibrinolysis. Hence serial estimations of the levels of GMP-140 and tPA can predict severe bleeding.Key Words: CardioPulmonary Bypass, Platelet dysfunction, flowcytometry, platelet glycoproteins, haemorrhage 相似文献73.
74.
Neff GW O'Brien CB Shire NJ DeManno A Kahn S Rideman E Safdar K Madariaga J Rudich SR 《Transplantation proceedings》2004,36(10):3071-3074
INTRODUCTION: Liver transplant recipients with allograft failure due to recurrent hepatitis C virus (HCV) infection often develop marked muscle wasting and ascites prior to death and are denied repeat liver transplantation. We sought to determine whether topical testosterone therapy is associated with improved muscle mass and survival in patients with chronic allograft failure post-liver transplant. METHODS: We performed a retrospective review of liver transplant recipients with chronic allograft failure. Group 1 patients were treated for >6 months with testosterone gel 1%; group 2 patients were untreated. RESULTS: Fourteen patients were identified with stage 3 or 4 fibrosis, muscle wasting, and allograft failure due to recurrent HCV. Group 1 (n=9) patients had statistically significant improvement in albumin, testosterone, muscle strength, well-being, and MELD/CTP scores, while there was no improvement seen for any of these parameters in group 2 (n=5). There were no deaths in group 1, while four of five patients in group 2 died on average 84 days posttransplant. Adverse effects of testosterone treatment included lower extremity edema (which resolved upon dose adjustment), hypertension, and pruritus. CONCLUSIONS: Topical testosterone gel appears to increase muscle strength, stimulate albumin synthesis, and improve survival in patients with allograft failure post-liver transplant. 相似文献
75.
76.
Shire N 《The journal of gender-specific medicine : JGSM : the official journal of the Partnership for Women's Health at Columbia》2002,5(2):48-54
Societies globally have a long road ahead in eliminating health risks and discrepancies due to race and ethnicity, gender, culture, and illiteracy. In terms of race, for example, females and African-Americans are less likely to be referred for cardiac catheterization, and Caucasians are more likely than minorities to receive pain management in the emergency room. Regarding gender, physiologic differences certainly account for some divergent health outcomes, but they do not explain how women and men have different prevalences of diseases that are not obviously gender-specific. Cultural beliefs play a vital role in determining health choices, and health care professionals need a deeper understanding of these beliefs prior to promoting certain health interventions. Illiteracy may also prevent a person from following health instructions, and the strong association between illiteracy and poverty may exert powerful, negative influences on health outcomes. Employing the characteristics of social marketing (synchronous messages, reinforcement, and actionability) may help society to overcome some of the obstacles. 相似文献
77.
Harris RJ Kabakoff B Macchi FD Shen FJ Kwong M Andya JD Shire SJ Bjork N Totpal K Chen AB 《Journal of chromatography. B, Biomedical sciences and applications》2001,752(2):233-245
Seven forms of a therapeutic recombinant antibody that binds to the her2/neu gene product were resolved by cation-exchange chromatography. Structural differences were assigned by peptide mapping and HIC after papain digestion. Deamidation of light chain asparagine 30 to aspartate in one or both light chains is responsible for two acidic forms. A low potency form is due to isomerization of heavy chain aspartate 102; the Asp102 succinimide is also present in a basic peak fraction. Forms with both Asn30 deamidation and Asp102 isomerization modifications were isolated. Deamidation of heavy chain Asn55 to isoaspartate was also detected. Isoelectric focusing in a polyacrylamide gel was used to verify the assignments. All modifications were found in complementarity determining regions. 相似文献
78.
Breen E. D. Curley J. G. Overcashier D. E. Hsu C. C. Shire S. J. 《Pharmaceutical research》2001,18(9):1345-1353
Purpose. To determine the effect of moisture and the role of the glass transition temperature (Tg) on the stability of a high concentration, lyophilized, monoclonal antibody.
Methods. A humanized monoclonal antibody was lyophilized in a sucrose/histidine/polysorbate 20 formulation. Residual moistures were from 1 to 8%. Tg values were measured by modulated DSC. Vials were stored at temperatures from 5 to 50°C for 6 or 12 months. Aggregation was monitored by size exclusion chromatography and Asp isomerization by hydrophobic interaction chromatography. Changes in secondary structure were monitored by Fourier transform infrared (FTIR).
Results. Tg values varied from 80°C at 1% moisture to 25°C at 8% moisture. There was no cake collapse and were no differences in the secondary structure by FTIR. All formulations were stable at 5°C. High moisture cakes had higher aggregation rates than drier samples if stored above their Tg values. Intermediate moisture vials were more stable to aggregation than dry vials. High moisture samples had increased rates of Asp isomerization at elevated temperatures both above and below their Tg values. Chemical and physical degradation pathways followed Arrhenius kinetics during storage in the glassy state. Only Asp isomerization followed the Arrhenius model above the Tg value. Both chemical and physical stability at T Tg were fitted to Williams-Landel-Ferry (WLF) kinetics. The WLF constants were dependent on the nature of the degradation system and were not characteristic of the solid system.
Conclusion. High moisture levels decreased chemical stability of the formulation regardless of whether the protein was in a glassy or rubbery state. In contrast, physical stability was not compromised, and may even be enhanced, by increasing residual moisture if storage is below the Tg value. 相似文献
79.
葛根素对高血压患者血浆内皮素和一氧化氮的影响 总被引:29,自引:0,他引:29
目的:检测正常人与高血压病(EH)患者血浆内皮素、一气体氮的变化及葛根素对其的干预效应。方法:EH对照组口服苯磺酸氨氯地平5mg/d,或合和盐酸苯那普利10mg/d,每日一次,15d为一疗程。EH伍用治疗组同时合用5%GNS250ml+葛根素注射液400mg静滴,两组治疗前后检测血浆ET、NO水平变化。结果:EH各组血浆ET较正常人组均显著增高(P〈0.01),血浆NO水平及NO/ET比值除轻度E 相似文献
80.
Andya JD Maa YF Costantino HR Nguyen PA Dasovich N Sweeney TD Hsu CC Shire SJ 《Pharmaceutical research》1999,16(3):350-358
Purpose. To study the effect of trehalose, lactose, and mannitol on the biochemical stability and aerosol performance of spray-dried powders of an anti-IgE humanized monoclonal antibody.
Methods. Protein aggregation of spray-dried powders stored at various temperature and relative humidity conditions was assayed by size exclusion chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein glycation was determined by isoelectric focusing and affinity chromatography. Crystallization was examined by X-ray powder diffraction. Aerosol performance was assessed as the fine particle fraction (FPF) of the powders blended with coarse carrier lactose, and was determined using a multiple stage liquid impinger.
Results. Soluble protein aggregation consisting of non-covalent and disulfide-linked covalent dimers and trimers occurred during storage. Aggregate was minimized by formulation with trehalose at or above a molar ratio in the range of 300:1 to 500:1 (excipient:protein). However, the powders were excessively cohesive and unsuitable for aerosol administration. Lactose had a similar stabilizing effect, and the powders exhibited acceptable aerosol performance, but protein glycation was observed during storage. The addition of mannitol also reduced aggregation, while maintaining the FPF, but only up to a molar ratio of 200:1. Further increased mannitol resulted in crystallization, which had a detrimental effect on protein stability and aerosol performance.
Conclusions. Protein stability was improved by formulation with carbohydrate. However, a balance must be achieved between the addition of enough stabilizer to improve protein biochemical stability without compromising blended powder aerosol performance. 相似文献