The Impact of Orthopaedic Surgery on The Quality of Life of Haemophilia Patients With or Without Inhibitors: A Systematic Review of The Literature

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Polymorphisms at the F12 and KLKB1 loci have significant trait association with activation of the renin-angiotensin system

BACKGROUND: Plasma coagulation Factor XIIa (Hageman factor; encoded by F12) and kallikrein (KAL or Fletcher factor; encoded by KLKB1) are proteases of the kallikerin-kinin system involved in converting the inactive circulating prorenin to renin. Renin is a key enzyme in the formation of angiotensin II, which regulates blood pressure, fluid and electrolyte balance and is a biomarker for cardiovascular, metabolic and renal function. The renin-angiotensin system is implicated in extinction learning in posttraumatic stress disorder. METHODS & RESULTS: Active plasma renin was measured from two independent cohorts- civilian twins and siblings, as well as U.S. Marines, for a total of 1,180 subjects. Genotyping these subjects revealed that the carriers of the minor alleles at the two loci- F12 and KLKB1 had a significant association with reduced levels of active plasma renin. Meta-analyses confirmed the association across cohorts. In vitro studies verified digestion of human recombinant pro-renin by kallikrein (KAL) to generate active renin. Subsequently, the active renin was able to digest the synthetic substrate angiotensinogen to angiotensin-I. Examination of mouse juxtaglomerular cell line and mouse kidney sections showed co-localization of KAL with renin. Expression of either REN or KLKB1 was regulated in cell line and rodent models of hypertension in response to oxidative stress, interleukin or arterial blood pressure changes. CONCLUSIONS: The functional variants of KLKB1 (rs3733402) and F12 (rs1801020) disrupted the cascade of enzymatic events, resulting in diminished formation of active renin. Using genetic, cellular and molecular approaches we found that conversion of zymogen prorenin to renin was influenced by these polymorphisms. The study suggests that the variant version of protease factor XIIa due to the amino acid substitution had reduced ability to activate prekallikrein to KAL. As a result KAL has reduced efficacy in converting prorenin to renin and this step of the pathway leading to activation of renin affords a potential therapeutic target

Pancreas allograft thrombosis.

Thrombosis of the transplanted pancreas is a common and often catastrophic event. Predisposing factors include the hypercoagulable state of many patients with diabetic renal failure, preservation-related graft endothelial injury, and low-velocity venous flow. Clinical management includes optimization of modifiable risk factors, controlled anticoagulation, graft monitoring, and early therapeutic intervention

Importance of age at infection with HIV-1 for survival and development of AIDS in UK haemophilia population. UK Haemophilia Centre Directors' Organisation.

BACKGROUND: Greater age at infection with HIV-1 is known to be associated with shorter time to development of AIDS, but the size of the differences between people infected in infancy and those infected in old age has not been examined in a single large population of patients with death as an endpoint. We, therefore, investigated the role of age at seroconversion in the entire UK population of haemophiliacs. METHODS: We studied 1216 HIV-1-infected haemophilia patients in the UK who were registered with the National Haemophilia Register and were alive on Jan 1, 1985. Their estimated ages at HIV-1 seroconversion ranged from 8 months to 79 years. FINDINGS: 10 years after seroconversion 67% (95% Cl 64-69) of the population were still alive. Survival was strongly related to age at seroconversion (86% [82-90], 72% [68-76], 45% [39-51], and 12% [5-21] at 10 years among those patients who seroconverted at ages < 15, 15-34, 35-54, and > or = 55). This steep age-gradient in survival was not explained by deaths expected in the absence of HIV infection or by confounding with other factors such as haemophilia type or severity. The age-gradient was steeper for survival (ie, time from HIV-1 infection to death) than for time to diagnosis of AIDS, partly because survival after an AIDS diagnosis was poorer in older patients, and there was also a substantial increase in mortality among HIV-infected patients who did not satisfy the formal AIDS definition and this increase was greater in older patients. INTERPRETATION: Age at infection with HIV-1 is a more important determinant of survival than has previously been appreciated. Age should, therefore, be considered in future studies of disease progression, and studies that compare people infected at different ages should provide insight into the biology of the immune response to HIV-1

Mortality before and after HIV infection in the complete UK population of haemophiliacs. UK Haemophilia Centre Directors' Organisation.

During 1977-91, 6,278 males diagnosed with haemophilia were living in the UK. During 1979-86, 1,227 were infected with the human immunodeficiency virus (HIV-1) as a result of transfusion therapy (median estimated seroconversion date, October 1982). Among 2,448 with severe haemophilia, the annual death rate was stable at 8 per 1,000 during 1977-84; during 1985-92 death rates remained at 8 per 1,000 among HIV-seronegative patients but rose steeply in seropositive patients, reaching 81 per 1,000 in 1991-92. Among 3,830 with mild or moderate haemophilia, the pattern was similar, with an initial death rate of 4 per 1,000 in 1977-84, rising to 85 per 1,000 in 1991-92 in seropositive patients. During 1985-92, there were 403 deaths in HIV seropositive patients, whereas 60 would have been predicted from rates in seronegatives, suggesting that 85% of the deaths in seropositive patients were due to HIV infection. Most of the excess deaths were certified as due to AIDS or to conditions recognized as being associated with AIDS

Relationship between microbial activity and microbial community structure in six full-scale anaerobic digesters

High activity levels and balanced anaerobic microbial communities are necessary to attain proper anaerobic digestion performance. Therefore, this work was focused on the kinetic performance and the microbial community structure of six full-scale anaerobic digesters and one lab-scale co-digester. Hydrolytic (0.6-3.5 g COD g(-1) VSS d(-1)) and methanogenic (0.01-0.84 g COD g(-1) VSS d(-1)) activities depended on the type of biomass, whereas no significant differences were observed among the acidogenic activities (1.5-2.2 g COD g(-1) VSS d(-1)). In most cases, the higher the hydrolytic and the methanogenic activity, the higher the Bacteroidetes and Archaea percentages, respectively, in the biomasses. Hydrogenotrophic methanogenic activity was always higher than acetoclastic methanogenic activity, and the highest values were achieved in those biomasses with lower percentages of Methanosaeta. in sum, the combination of molecular tools with activity tests seems to be essential for a better characterization of anaerobic biomasses

Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV.

Since the 1970s, mortality in the hemophilia population has been dominated by human immunodeficiency virus (HIV) and few reports have described mortality in uninfected individuals. This study presents mortality in 6018 people with hemophilia A or B in the United Kingdom during 1977 to 1998 who were not infected with HIV, with follow-up until January 1, 2000. Given disease severity and factor inhibitor status, all-cause mortality did not differ significantly between hemophilia A and hemophilia B. In severe hemophilia, all-cause mortality did not change significantly during 1977 to 1999. During this period, it exceeded mortality in the general population by a factor of 2.69 (95% confidence interval [CI]: 2.37-3.05), and median life expectancy in severe hemophilia was 63 years. In moderate/mild hemophilia, all-cause mortality did not change significantly during 1985 to 1999, and median life expectancy was 75 years. Compared with mortality in the general population, mortality from bleeding and its consequences, and from liver diseases and Hodgkin disease, was increased, but for ischemic heart disease it was lower, at only 62% (95% CI: 51%-76%) of general population rates, and for 14 other specific causes it did not differ significantly from general population rates. There was no evidence of any death from variant Creutzfeldt-Jakob disease or from conditions that could be confused with it