A three-dimensional multidimensional gas-kinetic scheme for the Navier-Stokes equations under gravitational fields

This paper extends the gas-kinetic scheme for one-dimensional inviscid shallow water equations (J. Comput. Phys. 178 (2002), pp. 533-562) to multidimensional gas dynamic equations under gravitational fields. Four important issues in the construction of a well-balanced scheme for gas dynamic equations are addressed. First, the inclusion of the gravitational source term into the flux function is necessary. Second, to achieve second-order accuracy of a well-balanced scheme, the Chapman-Enskog expansion of the Boltzmann equation with the inclusion of the external force term is used. Third, to avoid artificial heating in an isolated system under a gravitational field, the source term treatment inside each cell has to be evaluated consistently with the flux evaluation at the cell interface. Fourth, the multidimensional approach with the inclusion of tangential gradients in two-dimensional and three-dimensional cases becomes important in order to maintain the accuracy of the scheme. Many numerical examples are used to validate the above issues, which include the comparison between the solutions from the current scheme and the Strang splitting method. The methodology developed in this paper can also be applied to other systems, such as semi-conductor device simulations under electric fields.Comment: The name of first author was misspelled as C.T.Tian in the published paper. 35 pages,9 figure

The deficiency of C1 inhibitor and its treatment

In this article, we review the traditional therapies of hereditary angioedema (HAE) that have been used for several years. Some of these therapies were proposed before the definition of the underlying defect and the understanding of the pathogenesis of the disease. We also describe new compounds under investigation at present as potential therapies for HAE. Two of these new therapies (a plasma-kallikrein inhibitor and a bradykinin B(2)-receptor antagonist) have been developed based on the understanding that the pathogenesis of symptoms was mainly due to kallikrein activation and bradykinin release. (c) 2007 Elsevier GmbH. All rights reserved

C1 inhibitor gene expression in patients with hereditary angioedema : quantitative evaluation by means of real-time RT-PCR

Background: Hereditary angioedema (HAE) is caused by heterozygous defects in the Cl inhibitor (Cl-INH) gene (SERPINGI/CINH). In patients' plasma Cl-INH levels range between 5% and 30% of normal levels (ie, far from the 50% expected for an autosomal dominant defect). Most patients have antigenic and functional deficiency (type I HAE), and 15% have reduced Cl-INH function but normal to increased antigen because of the presence of a dysfunctional protein (type II HAE). Objective: We sought to contribute to the understanding of the pattern of C1-INH gene expression in patients with HAE. Methods: We used real-time quantitative RT-PCR to measure C1-INH mRNA levels in PBMCs of 57 patients with HAE typed for mutations in the SERPINGI/CINH gene. Results: Thirty-six different mutations were identified in genomic DNA. Compared with healthy control subjects, Cl-INH mRNA was significantly and similarly reduced in patients with type I and type II HAE (40% and 47%, respectively; P <.0001). By means of direct sequencing of cDNAs, we found that 74% of patients with type I HAE carrying small mutations presented significant amounts of mutated transcripts at the mRNA level, suggesting that both allelic mRNA products were reduced to approximately 50%. In 4 patients carrying large deletions expected to fully inactivate expression from the mutant allele, Cl-INH mRNA was 23% on average compared with that seen in control subjects, confirming that normal mRNA was strongly underexpressed. Conclusions: These new findings, combined with previous evidence of increased Cl-INH consumption, might explain the plasma levels of normal Cl-INH that are markedly less than the expected 50%

Increased expression of C1-inhibitor mRNA in patients with hereditary angioedema treated with Danazol

The attenuated androgen Danazol can partially reverse the biochemical defect and prevent angioedema in patients with inherited C1-inhibitor (C1-INH) deficiency (hereditary angioedema, HAE). Though its clinical effectiveness is independent from significant increase of C1-INH plasma levels, its mechanism of action remains unknown. Since angioedema is a local phenomenon, it could be controlled by restoring tissue levels of C1-INH. We measured the expression of C1-INH mRNA in peripheral blood mononuclear cells (PBMCs) of 13 patients with HAE type 1 (seven untreated and asymptomatic, and six on Danazol at the minimal effective dose) and of eight normal controls. mRNA levels were quantitated by computerized optical densitometry of reverse transcriptase-PCR products, normalized for the amount of glyceraldehyde-3-phosphate-dehydrogenase and expressed as percent of normal pooled RNAs. Each determination represented the mean of three separate experiments. Measurement of C1-INH mRNA in two patients before and after 1 month of Danazol 400 mg per day demonstrated a post-treatment increase of 15 and 21%, respectively. When HAE patients and controls were analyzed as groups, C1-INH mRNA levels of patients untreated and asymptomatic (median 73%, range 65-78) were significantly lower (P=0.001) compared to controls (median 101%, range 87-121) and to patients on Danazol (median 91%, range 82-96); the difference among the last two groups was not statistically significant. Our data demonstrate that minimal effective doses of Danazol increase the expression of C1-INH mRNA in PBMC of HAE patients even in the absence of a significant increase of C1-INH plasma levels

Angioedema associated with angiotensin-converting enzyme inhibitor use : outcome after switching to a different treatment

Background: Angiotensin-converting enzyme (ACE) inhibitors are associated with angioederna episodes that are potentially life-threatening. Few data are available on the outcome of patients reporting this adverse effect when they are switched to another drug. Scattered reports of angioedema associated with angiotensin 11 receptor blocker (ARB) use question the safety of using these drugs in patients with ACE inhibitor-related angioedema. We describe 64 consecutive patients with ACE inhibitor-related angioedema, the outcome after discontinuing this treatment, and the safety of using ARBs. Methods: Retrospective analysis of 64 consecutive patients (January 1993 to June 2002) presenting with angioedema onset while receiving treatment with an ACE inhibitor. Results: Patients were recommended to stop ACE inhibitor use, substituting it upon advice of the physician. Fifty-four patients were available for follow-up (median follow-up, 11 months; range, 1-80 months): 26 had switched to an ARB, 14 to a calcium antagonist, and 14 to other antihypertensive drugs. Angioedema disappeared or drastically reduced upon withdrawal of the ACE inhibitor in 46 patients (85%). For the remaining 8 patients, angioedema was due to a cause other than ACE inhibitor use in 2; angioedema persisted independent of the treatment and without apparent cause (idiopathic angioedema) in 4; angioedema persisted after switching to an ARB and disappeared upon its withdrawal in 2. Conclusions: Stopping ACE inhibitor use without further assessments is a successful measure in the large majority of patients developing angioedema while taking this drug. Only a small percentage of patients with ACE inhibitor-related angioedema continue with this symptom when switched to an ARB

Acquired deficiency of the inhibitor of the first complement component : presentation, diagnosis, course, and conventional management

Acquired deficiency of the inhibitor of the first complement component (C1-INH) is a rare, potentially life-threatening disease whose cause, course, and management are not completely defined. This article analyzes the etiopathogenetic mechanism, the clinical presentation, and the relationship between acquired C1-INH deficiency and lymphoproliferative disorders. Moreover, the authors give an overview of the outcome of the disease and the different therapies proposed to cure it

C1-inhibitor deficiency and angioedema

C1-inhibitor deficiency can be inherited or acquired; both conditions lead to recurrent angioedema that can be life threatening when the larynx is involved (hereditary angioedema, HAE; acquired angioedema, AAE). The genetic defect is due to the heterozygous deficiency of C1-Inh that is transmitted as an autosomal dominant trait. Mutations causing HAE have been found distributed over all exons and splice sites of C1-Inh structural gene: only a few of them have been found more than once. Depending on DNA defect, C1-Inh is not transcribed, or not translated or not secreted. Finally, in 15% of HAE patients, an antigenically normal, but non-functional C1-Inh is present in serum (HAE type II). C1-Inh deficiency can be acquired, due to an accelerated consumption. Such an accelerated consumption can depend on circulating autoantibodies that bind C1-Inh causing its inactivation and catabolism; or to associated diseases, usually lymphoproliferative diseases, that consume C1-Inh with different mechanisms. Effective therapies can prevent or revert angioedema symptoms in C1-Inh deficiency, the main problem of this condition remaining misdiagnosis. The common knowledge that angioedema is an allergic symptom frequently prevents a correct diagnostic approach: C1-Inh deficiency goes unrecognized and the disease can still be lethal. Correct prophylactic treatment is based on attenuated androgens in HAE and on antifibrinolytic agents in AAE. Life threatening laryngeal attacks and severe abdominal attacks are effectively reverted, in both conditions, with C1-Inh plasma concentrate. A special remark to this treatment should be made for autoantibody-mediated AAE where very high doses can be needed depending on the rate of C1-Inh consumption