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Mechanisms of Fibril Formation and Cellular Response
Published in Martha Skinner, John L. Berk, Lawreen H. Connors, David C. Seldin, XIth International Symposium on Amyloidosis, 2007
Martha Skinner, John L. Berk, Lawreen H. Connors, David C. Seldin
To confirm the absence of wt TTR, an IEF mixing study was performed. Equal volumes of serum from a normal control and ATTR #B0626 were combined and mixed sample was analyzed by IEF. Three bands were observed on the gel corresponding to the wt protein, TTR-Ile 122, and an unknown band (Figure 2). The results indicate that no wt TTR was present in the serum of the patient.
Antimicrobial Cycling Programs
Published in Robert C. Owens, Lautenbach Ebbing, Antimicrobial Resistance, 2007
Bernard C. Camins, Victoria J. Fraser
The two latest published studies on antimicrobial cycling have much-improved study designs. Both studies included an evaluation of an antimicrobial mixing intervention. During the mixing intervention, each patient who met the inclusion criteria for antimicrobial treatment was assigned to receive a different antimicrobial regimen as opposed to receiving the same antimicrobial regimen during the antimicrobial cycling intervention. In the first study, empiric treatment for suspected Pseudomonas infections was either accomplished through a typical antimicrobial cycling or a mixing program in two ICUs. The antimicrobial cycling program included four cycling regimens that were cycled over four one-month periods while the mixing program used the same order of antimicrobial classes as the cycling regimens but these were prescribed consecutively for each patient who met the entry criteria. Surveillance cultures were obtained from the patients’ oropharynx, respiratory tract, and the rectum three times a week. Even though compliance rates for empiric coverage for suspected Pseudomonas infections were never higher than 45%, this study produced some interesting results. There was a trend towards a higher proportion of patients acquiring Pseudomonas isolates resistant to ceftazidime, imipenem, and meropenem during the mixing protocol compared to the cycling periods. There was even a significantly higher proportion of patients who acquired a Pseudomonas isolate resistant to cefepime during the mixing period compared to the cycling period (9% vs. 3%). No differences in the development of resistant Gram-negative bacterial infections and overall mortality between the two periods were noted, since this study was not powered to look at differences in these outcomes (17). This study suggests that antimicrobial cycling may be more effective in preventing the acquisition of resistant Pseudomonas than the mixing strategy. This finding contradicts what has been predicted by mathematical models (20). Unfortunately, there are several limitations to this study. Compliance with the preferred regimens was low, which could explain the inferiority of the mixing regimen. The duration of each cycling regimen (1 month) was also shorter than what is recommended by most experts (3–4 months). This last limitation would have biased the study in favor of the mixing study so this limitation does not explain the study findings.
Acquired hemophilia A
Published in Baylor University Medical Center Proceedings, 2020
Yadav Pandey, Dinesh Atwal, Manojna Konda, Arya Roy, Appalanaidu Sasapu
The most common initial clinical presentation is bleeding, which can occur spontaneously or after surgery.6 Bleeding is often severe and life threatening with a high mortality rate.7 AHA should be suspected in any bleeding patient with elevated aPTT and a normal prothrombin time. The first step in a suspected case after excluding the use or presence of heparin is to perform a mixing study8(Figure 1). Failure to correct the aPTT is suggestive of the presence of coagulation inhibitor and warrants checking for FVIII activity along with FVIII inhibitor titer (Bethesda assay), which is performed by serial dilution of the patient’s plasma incubated with pooled plasma to calculate the BU. A higher BU signifies stronger inhibition of anticoagulation. Patients should be evaluated for underlying autoimmune disease and malignancy as a cause of AHA as indicated.
Donor-to-recipient transmission of factor XII deficiency by orthotopic liver transplantation
Published in Baylor University Medical Center Proceedings, 2019
Hussien Elsiesy, Mohamed Shawakat, Waleed Alhamoudi, Mohamed Alsebayel, John Renz, Hany Elbeshbeshy, Mohamed Abdelfattah, Faisal Abaalkhail
The differential diagnosis of an isolated increase in aPTT (normal prothrombin time/INR and platelet count) and its clinical significance if acquired through transplantation is shown in Table 3. Etiological diagnosis of a prolonged aPTT requires a detailed interview for a personal and family history of bleeding, examination for evidence of recurrent or inappropriate bleeding, and additional testing. Failure of the aPTT to correct with a mixing study suggests a lupus anticoagulant or acquired factor VIII or factor IX deficiency due to antibodies. The specific defect can be diagnosed by testing of factor levels. The transmission of other coagulation factor deficiencies causing a prolonged aPTT does not result in clinically significant problems in the recipient (Table 2). Consultation with a hematologist will help ensure that a potentially serious condition is not transmitted through transplantation, even in the limited time available for donor evaluation.
A case of acquired hemophilia A in an elderly female
Published in Journal of Community Hospital Internal Medicine Perspectives, 2018
Kiranveer Kaur, Abhishek Kalla
Isolated prolongation of aPTT with normal prothrombin time (PT), thrombin time (TT), and platelet count is indicative of either a factor deficiency in intrinsic pathway or a factor inhibitor. Other common causes are heparin therapy or lupus anticoagulant [9,10]. The next step is to perform a mixing study, in which the patient’s plasma is combined with normal plasma in a 1:1 ratio and incubated at 37 °C for at least an hour. If the patient’s sample has a factor deficiency, the mixed sample should correct the aPTT. If an inhibitor is present in the patient’s plasma, the aPTT will continue to be prolonged. Sensitivity of detection of mild inhibitors is increased if ratio of patient to control plasma is increased to 4:1 and incubated for 2 h [11]. To avoid misinterpretation as lupus inhibitor, a confirmatory step is advised to measure Factor VIII activity, which will be low in these cases. After confirming the presence of the inhibitor, the Bethesda assay is used to evaluate inhibitor titer levels. Neither factor VIII activity nor inhibitor titer correlates well with the disease activity or severity of bleeding [10].