Numerical Simulation and Experimental Validation of Blood Flow in Arteries with Structured-Tree Outflow Conditions

Blood flow in the large systemic arteries is modeled using one-dimensional equations derived from the axisymmetric Navier–Stokes equations for flow in compliant and tapering vessels. The arterial tree is truncated after the first few generations of large arteries with the remaining small arteries and arterioles providing outflow boundary conditions for the large arteries. By modeling the small arteries and arterioles as a structured tree, a semi-analytical approach based on a linearized version of the governing equations can be used to derive an expression for the root impedance of the structured tree in the frequency domain. In the time domain, this provides the proper outflow boundary condition. The structured tree is a binary asymmetric tree in which the radii of the daughter vessels are scaled linearly with the radius of the parent vessel. Blood flow and pressure in the large vessels are computed as functions of time and axial distance within each of the arteries. Comparison between the simulations and magnetic resonance measurements in the ascending aorta and nine peripheral locations in one individual shows excellent agreement between the two. © 2000 Biomedical Engineering Society. PAC00: 8719Uv     

Pseudodicentric chromosome 18 diagnosed by chromosome painting and primed in situ labelling (PRINS).

We report on a newborn white male infant with marked dysmorphic features and various congenital malformations. The initial clinical evaluation showed Crouzon-like features as well as some features of trisomy 18 syndrome and trisomy 13 syndrome. The results from conventional cytogenetic analysis showed a structurally abnormal chromosome replacing one normal chromosome 18, but only by applying molecular cytogenetic methods could the architecture of this abnormal chromosome be characterised clearly. The primed in situ labelling (PRINS) technique, using a newly synthesised alpha 18 oligonucleotide, showed the dicentric pattern and direct chromosome painting established the origin to be from chromosome 18. The combination of conventional cytogenetics and molecular cytogenetics showed the karyotype in the proband to be 45,XY,-14,-18,-21,+t(14;21),+psu dic(18) (qter-->cen-->p11.3: :p11.3-->psu cen-->qter). This was supported by molecular analysis using chromosome 18 specific DNA markers, which showed the paternal origin of the abnormal chromosome.     

Thrombocytopenia in a retrovirally-induced murine erythroleukemia.

A variant strain of Rauscher leukemia virus (RLV-A) obtained from a transplantable murine monomyelocytic leukemia causes a disease characterized by frank anemia, wasting, hepatosplenomegaly and erythroblastosis. The involvement of platelets in this disease are reported here. The RLV-A induced a severe thrombocytopenia (25 percent of control level) at the terminal stage of disease. This thrombocytopenia was not associated with disseminated intravascular coagulopathy since the prothrombin times were always within normal limits. The partial thromboplastin time was elevated in the terminal stages of disease and was found to be associated with factor deficiencies, possibly owing to the presence of anti-factor antibodies, in the intrinsic coagulation pathway, especially factor VIII. Further, splenectomy did not abolish the thrombocytopenia, since splenectomized, virally infected animals also developed severe thrombocytopenia (29 percent of control levels). The ensuing splenomegaly during progression of disease was not the cause of the thrombocytopenia. A physiological response to the severe thrombocytopenia was the production of larger size platelets. At terminal stages of the disease, platelet volume increased to 4.2 mu 3 (normal is 3.0 mu 3). An increase in platelet volume was also observed in splenectomized, virally infected animals. Electron microscopy indicated that these circulating platelets contained c-type viral particles. Viral infection was associated with decreased life span of circulating platelets, as measured by 75Se-methionine at mid and terminal stages of the disease. Our results suggest that direct viral infection of platelets and/or megakaryocytes with subsequent cell lysis is a possible cause of the observed thrombocytopenia observed in RLVA-induced disease and may also occur in other retrovirally-induced diseases.     

X-linked resistance of mice to high doses of herpes simplex virus type 2 correlates with early interferon production.

Mice inoculated intraperitoneally with herpes simplex virus type 2 develop focal necrotizing hepatitis and eventually die from ascending myelitis and encephalitis. The genetics of resistance to the infection were analyzed in crosses between resistant C57BL/10 mice and susceptible BALB/c mice. It was shown that the resistance of C57BL/10 mice to hepatitis induction was influenced by an X-linked dominant gene as previously shown for the GR mouse strain. The course of infection in the liver pointed to early, natural defense mechanisms as being responsible for the difference between the mouse strains, whereas the clearance of virus from the liver, probably mediated by specific immunity, was exerted at the same time and with equal efficiency for all groups of mice. In mortality experiments, resistance was shown to be an autointerference phenomenon in that a considerable number of C57BL/10 mice survived an intraperitoneal injection of 10(6) PFU, whereas all mice were killed by 10(5) PFU. This resistance of C57BL/10 mice to high doses of HSV-2 was retrieved in all groups of F1 mice in crosses between C57BL/10 and BALB/c mice except the (BALB/c female X C57 male) male group, in which the mice receive the X chromosome from the susceptible BALB/c female. Thus, the autointerference phenomenon also seems to be influenced by loci on the X chromosome. A similar pattern of inheritance was observed when early interferon induction (4 to 5 h after infection) in response to HSV-2 was measured. The possible relevance of this early interferon response in conjunction with other potential natural defense mechanisms is discussed.     

Experimental transmission of Bartonella henselae by the cat flea.

Bartonella henselae is an emerging bacterial pathogen, causing cat scratch disease and bacillary angiomatosis. Cats bacteremic with B. henselae constitute a large reservoir from which humans become infected. Prevention of human infection depends on elucidation of the natural history and means of feline infection. We studied 47 cattery cats in a private home for 12 months to determine the longitudinal prevalence of B. henselae bacteremia, the prevalence of B. henselae in the fleas infesting these cats, and whether B. henselae is transmitted experimentally to cats via fleas. Vector-mediated transmission of B.henselae isolates was evaluated by removing fleas from the naturally bacteremic, flea-infested cattery cats and transferring these fleas to specific-pathogen-free (SPF) kittens housed in a controlled, arthropod-free University Animal Facility. B. henselae bacteremia was detected in 89% of the 47 naturally infected cattery cats. A total of 132 fleas were removed from cats whose blood was simultaneously cultured during different seasons and were tested individually for the presence of B. henselae DNA by PCR. B. henselae DNA was detected in 34% of 132 fleas, with seasonal variation, but without an association between the presence or the level of bacteremia in the corresponding cat. Cat fleas removed from bacteremic cattery cats transmitted B. henselae to five SPF kittens in two separate experiments; however, control SPF kittens housed with highly bacteremic kittens in the absence of fleas did not become infected. These data demonstrate that the cat flea readily transmits B. henselae to cats. Control of feline infestation with this arthropod vector may provide an important strategy for the prevention of infection of both humans and cats.     

Serum antibodies to Pseudomonas aeruginosa outer-membrane proteins and iron-regulated membrane proteins at different stages of chronic cystic fibrosis lung infection

Serum samples collected over periods up to 15 years from nine patients with cystic fibrosis (CF) were investigated by immunoblotting and crossed immuno-electrophoresis (CIE) for antibodies to Pseudomonas aeruginosa outer-membrane proteins (OMPs). The earliest antibody response to OMPs was directed against proteins G, H1 and I. Detection by immunoblotting sometimes preceded the CIE response; the appearance of antibodies to the other major OMPs was co-incident with an increase in CIE precipitins. Isolation of the mucoid form of P. aeruginosa was associated with a rapid increase in both precipitin numbers and antibodies detected by immunoblotting. Antibodies to iron-regulated OMPs could be detected in all the serum samples that showed eight or more CIE precipitins but their presence became pronounced only in the advanced stages of disease. The clinical strain used in this study and other isolates from CF patients showed several atypical OMPs, perhaps as a consequence of antibiotic therapy or related to the serum sensitivity of mucoid P. aeruginosa. Their expression in vivo was confirmed by detecting antibodies to them in patients' serum.     

Anti-diabetogenic effect of fusidic acid in diabetes prone BB rats.

Fusidic acid and its sodium salt (fusidin) are anti-staphylococcal drugs. In vitro studies have shown that they prevent the lymphocyte co-stimulatory activities of the cytokines IL-1 and IL-6 in a manner similar to that of cyclosporin A, and prevent the inhibitory effect of IL-1 on glucose-induced insulin production. As IL-1 and IL-6 are thought to play a role in the pathogenesis of Type 1 diabetes, the aim of this study was to investigate whether fusidin could influence the disease incidence of the spontaneously diabetic BB rat model. Accordingly, a group of 50 BB rats receiving fusidin dissolved in their drinking water were compared to a control group of 55 rats over a period of 200 days. The incidence of diabetes was found to be 52% in the experimental group and 71% in the control group (P < 0.05). The degree of insulitis and the number of islets at histological examination were similar among the non-diabetic animals whereas the diabetic fusidin-treated animals showed a higher degree of islet preservation than the diabetic control rats. The results are highly indicative of an anti-diabetogenic effect of fusidin.     

Lp(a) lipoprotein level predicts survival and major coronary events in the Scandinavian Simvastatin Survival Study

The Scandinavian Simvastatin Survival Study (4S) was a double-blind. randomized placebo-controlled multi-centre clinical trial of long-term Simvastatin therapy in patients with coronary heart disease who had total cholesterol levels between 5.5 and 8.0 mmol/1, comprising 4444 patients, equally distributed to a Simvastatin and a placebo group. Patients achieved a significant 30% relative reduction in overall mortality with Simvastatin therapy through a 42% relative reduction in coronary heart disease mortality. Lp(a) lipoprotein levels in Scandinavian coronary heart disease patients were strikingly higher than in healthy controls. Numbers of deaths in the Simvastatin group differed significantly between quartiles of Lp(a) lipoprotein levels, the reduction in deaths being most pronounced in the second (next to lowest) quartile. Subjects with major coronary events had significantly higher Lp(a) lipoprotein levels than subjects without such events, in all groups. The relationship between Lp(a) lipoprotein level and total mortality as well as between Lp(a) lipoprotein level and major coronary events was significantly different from zero, in logistic regression analyses. The findings show that Lp(a) lipoprotein predicts major coronary events as well as death in secondary prevention with Simvastatin. This prospective study provides independent confirmation that a high Lp(a) lipoprotein level is a significant coronary heart disease risk factor.     

Proliferation and telomere length in acutely mobilized blood mononuclear cells in HIV infected patients

The aim of the study was to investigate the mobilization of T cells in response to a stressful challenge (adrenalin stimulation), and to access T cells resided in the peripheral lymphoid organs in HIV infected patients. Seventeen patients and eight HIV seronegative controls received an adrenalin infusion for 1 h. Blood was sampled before, during and 1 h after adrenalin infusion. Proliferation and mean telomere restriction fragment length (telomeres) of blood mononuclear cells (BMNC) and purified CD8+ and CD4+ cells were investigated at all time points. In patients, the proliferation to pokeweed mitogens (PWM) was lower and decreased more during adrenalin infusion. After adrenalin infusion the proliferation to PWM was restored only in the controls. In all subjects telomeres in CD4+ cells declined during adrenalin infusion. Additionally, the patients had shortened telomeres in their CD8+ cells, and particularly HAART treated patients had shortened telomeres in all cell-subtypes. The finding that patients mobilized cells with an impaired proliferation to PWM during and after adrenalin infusion has possible clinical relevance for HIV infected patients during pathological stressful conditions, such as sepsis, surgery and burns. However, this study did not find a correlation between impaired proliferation and telomeres. It is concluded that physiological stress further aggravates the HIV-induced immune deficiency.