Activation of factor XI in plasma is dependent on factor XII [see comments]

The activation of factor XI initiates the intrinsic coagulation pathway. Until recently it was believed that the main activator of factor XI is factor XIIa in conjunction with the cofactor high molecular weight kininogen on a negatively charged surface. Two recent reports have presented evidence that in a purified system factor XI is activatable by thrombin together with the soluble polyanion dextran sulfate. To assess the physiological relevance of these findings we studied the activation of factor XI in normal and factor XII-deficient plasma. We used either kaolin/cephalin or dextran sulfate as a surface for the intrinsic coagulation pathway, tissue factor to generate thrombin via the extrinsic pathway, or the addition of alpha-thrombin directly. 125I-factor XI, added to factor XI-deficient plasma at physiologic concentrations (35 nmol/L), is rapidly cleaved on incubation with kaolin. The kinetics appear to be exponential with half the maximum cleavage at 5 minutes. Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided. Tissue factor (1:500) added to plasma did not induce cleavage of factor XI during a 90-minute incubation, although fibrin formation within 30 seconds indicated that thrombin was generated via the extrinsic pathway. Adding 1 mumol/L alpha-thrombin (equivalent to 50% prothrombin activation) directly to factor XII deficient or normal plasma (with or without kaolin/cephalin/Ca2+ or dextran sulfate) led to instantaneous fibrinogen cleavage, but again no cleavage of factor XI was observable. We conclude that in plasma surroundings factor XI is not activated by thrombin, and that proposals of thrombin initiation of the intrinsic coagulation cascade are not supportable.     

Patient preferences for coronary artery bypass graft surgery or percutaneous intervention in multivessel coronary artery disease

Objectives: Determine if patients prefer multivessel percutaneous coronary intervention (mv‐PCI) over coronary artery bypass graft surgery (CABG) for treatment of symptomatic multivessel coronary artery disease (mv‐CAD) despite high 1‐year risk. Background: Patient risk perception and preference for CABG or mv‐PCI to treat medically refractory mv‐CAD are poorly understood. We hypothesize that patients prefer mv‐PCI instead of CABG even when quoted high mv‐PCI risk. Methods: 585 patients and 31 physicians were presented standardized questionnaires with a hypothetical scenario describing chest pain and medically refractory mv‐CAD. CABG or mv‐PCI was presented as treatment options. Risk scenarios included variable 1‐year risks of death, stroke, and repeat procedures for mv‐PCI and fixed risks for CABG. Participants indicated their preference of revascularization method based on the presented risks. We calculated the odds that patients or physicians would favor mv‐PCI over CABG across a range of quoted risks of death, stroke, and repeat procedures. Results: For nearly all quoted risks, patients preferred mv‐PCI over CABG, even when the risk of death was double the risk with CABG or the risk of repeat procedures was more than three times that for CABG (P < 0.0001). Compared to patients, physicians chose mv‐PCI less often than CABG as the risk of death and repeat procedures increased (P < 0.001 and P = 0.004, respectively). Conclusion: Patients favor mv‐PCI over CABG to treat mv‐CAD, even if 1‐year risks of death and repeat procedures far exceed risk with CABG. Physicians are more influenced by actual risk and prefer mv‐PCI less than patients despite similarly quoted 1‐year risks. © 2013 Wiley Periodicals, Inc.     

Serological status: a predictor of response to intensive therapy in rheumatoid arthritis

BackgroundRheumatoid arthritis is the most common chronic inflammatory disease in the UK. Serological status such as rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) positivity predict poor outcomes. Early intensive treatment regimens targeting remission reduce disease activity, structural damage, and long-term disability. However, we do not know whether all patients with active disease should have such intensive treatment regimens. Can serological status be used to predict the need for intensive therapy?MethodsWe analysed samples from a published randomised controlled trial which compared four treatment regimens in patients with early active rheumatoid arthritis (disease duration <2 years): methotrexate monotherapy, double therapy (methotrexate plus either ciclosporin or prednisolone), and triple therapy (methotrexate plus ciclosporin plus prednisolone). The trial randomised 467 patients (68% female, median age 54 years [IQR 46–63]). Disease activity was assessed with the disease activity score of 28 joints (DAS28). Remission was defined as DAS28 less than 2·6 at 24 months. RF isotypes (IgM and IgA) and ACPA levels were measured with commercial ELISA kits. Statistical analysis used Pearson's chi-squared test.Findings402 (86%) patients were positive for IgM RF, 346 (74%) for IgA RF, and 346 (74%) for ACPA. 98 (21%) patients achieved remission at 24 months. In RF IgM negative cases (n=65) the proportion of patients achieving remission at 24 months was similar in all treatment groups (25%, 22%, and 30% for monotherapy, double therapy, and triple therapy, respectively). In RF IgM positive cases, significantly fewer patients achieved remission with monotherapy (13/65, 17%) and double therapy (24/157, 15%) than with triple therapy (27/80, 34%) (p=0·001). There were similar, consistent findings with IgA RF and ACPA, with significantly more seropositive patients achieving remission with triple therapy than with monotherapy.InterpretationContemporary treatment of rheumatoid arthritis emphasises the use of intensive therapy to achieve remission. However, we have shown that not all patients require such an aggressive approach to therapy. Given the heterogeneity of the diease, treatment should be personalised to the individual, which would minimise costs of treatment as well as potentially toxic side-effects. Our study shows that only seropositive patients with rheumatoid arthritis should be given more intensive therapies.FundingNational Institute for Health Research.     

A qualitative investigation of fathers' experiences of looking after a child with a life-limiting illness, in process and in retrospect

Child life-limiting illnesses are those from which there is no reasonable hope of cure and from which children will die. Only recently have these illnesses been recognized as a discrete category and thus relatively little research has focused specifically upon this group of children and their families. This study utilized qualitative methods to investigate the experience of fathers, a group who are often under-represented in child illness research. The research aim was to gain an understanding of fathers' experiences of having a child with a life-limiting illness, its impact upon them, and their perceptions of service provision. The data from eight interviews was analysed using Interpretative Phenomenological Analysis. Four main themes emerged highlighting the fathers' feeling that their world had been turned upside down, how they lived with the knowledge their child would die, how men perceive themselves as different from women, and the fathers' wish to contribute to changing and improving how other fathers might cope with a child with a life-limiting illness. The results are discussed particularly in relation to gender issues. Various implications for clinical practice and service provision are considered. Suggestions are also made for future research.     

Mycobacterial Infections After Renal Transplantation

Mycobacterial infections occurred in 11 of 633 (1.7 per cent)recipients of successful renal transplants. There were no casesof tuberculosis in patients receiving chemoprophylaxis, butamongst those who did not receive prophylaxis disease occurredin six of the 27 (22 per cent) high-risk patients. The majorcause of morbidity during treatment was renal allograft rejection,largely due to reduction in immunosuppressive drug therapy.     

Surgical bacterial infections and antimicrobial susceptibility patterns at Lilongwe Central Hospital

A cross sectional study was done between October 1999 and February 2000 to determine antimicrobial susceptibility patterns of consecutive bacterial isolates of 102 clinical samples among surgical in-patients at Lilongwe Central Hospital (LCH), Malawi. Antimicrobial susceptibility was determined using comparative disc diffusion techniques. 83 (81.4%) samples were culture positive for bacterial growth while 19 (18.6%) grew nothing. Of the 93 culture positive specimens, Staphylococcus aureus was the predominant organism 43(51.8%) followed by Proteus species 8(9.6%) and E. coli 7(8.4%). Overall, 98.6% of all isolates tested against ciprofloxacin were susceptible, and against gentamicin and flucloxacin were 84.8% and 66.7% respectively. 59.3% of isolates tested against chloramphenicol were resistant. We recommend a review on the use of chloramphenicol as first-line antimicrobial therapy among surgical in-patients at Lilongwe Central Hospital. We also recommend restricted use of antimicrobials so as to minimise development of drug resistance. Periodic susceptibility studies are necessary to guide judicious use of antibiotics.     

Perforation of the colon due to endometriosis

Endometriosis is a common disease which affects the bowel in 12 to 35% of cases. Despite extensive serosal and intramural involvement, the intestinal mucosa usually remains intact and bowel perforation rarely occurs. We describe a patient with perforation of the sigmoid colon due to endometriosis. To our knowledge, this is the first such case to be reported in the radiologic literature.     

Perforation of the colon due to endometriosis

Endometriosis is a common disease which affects the bowel in 12 to 35% of cases. Despite extensive serosal and intramural involvement, the intestinal mucosa usually remains intact and bowel perforation rarely occurs. We describe a patient with perforation of the sigmoid colon due to endometriosis. To our knowledge, this is the first such case to be reported in the radiologic literature.     

Graves′病患者经~(131)碘治疗后循环活性T细胞亚群的动态观察

本文应用直接、间接双色免疫荧光染色,流体细胞测定仪技术,观察了经~(131)碘治疗的23例Graves′病患者的循环活性T细胞亚群的动态变化。~(131)碘治疗后的第一个月至第三个月,HLA-DR、Ta_1和UCHL_1活性T细胞亚群数目明显增加,以Vicia-villosa为标志的抗抑制细胞亚群较治疗前明显增加。实验结果提示:Graves′病患者经~(131)碘治疗后的抗甲状腺自身抗体浓度增加可能是由于T细胞的激活和抗抑制细胞亚群增加的共同结果。     

Predicting length of hospitalization of sick neonates from their initial status.

It has been suggested that the estimated date of confinement (EDC) may be used to predict the length of hospital stay for sick newborns. We have found this method unreliable and designed the following study to develop a mathematical model to predict length of stay (LOS). We reviewed the records of 393 neonates. Statistical analysis was performed using multiple linear regression. The factors that reached statistical significance were birth weight (BW), gestational age (GA), and a combined respiratory score (RES). The RES was developed to quantify the degree of initial respiratory illness. Through this model we developed the following formula: log(e) (LOS) = 4.395-0.023 (GA) -0.00054(BW) + 0.0274 (RES). The R value is 0.78. The model predicts an LOS +/- 10 days in 73% of cases. Overall, this model yields a 29% improvement in predictability of LOS compared with a model which used EDC only. This formula may provide useful information for parents and caregivers of hospitalized neonates.