Modelling and simulation of flow and agglomeration in deep veins valves using discrete multi physics.

The hemodynamics in flexible deep veins valves is modelled by means of discrete multi-physics and an agglomeration algorithm is implemented to account for blood accrual in the flow. Computer simulations of a number of valves typologies are carried out. The results show that the rigidity and the length of the valve leaflets play a crucial role on both mechanical stress and stagnation in the flow. Rigid and short membranes may be inefficient in preventing blood reflux, but reduce the volume of stagnant blood potentially lowering the chances of thrombosis. Additionally, we also show that in venous valves, cell agglomeration is driven by stagnation rather than mechanical stress.

Ca2+ in the dense tubules: a model of platelet Ca2+ load.

In this work, we explored the relationship between the freely exchangeable Ca2+ (FECa2+) in the dense tubules (DT) and the sarco(endo)plasmic reticulum (SER) Ca2+-ATPase (SERCA) in circulating human platelets and examined the relationship between blood pressure (BP) and these platelet parameters. Studying platelets from 32 healthy men, we showed that the maximal reaction velocity (Vmax) of the SERCA significantly correlated with FECa2+ in the DT and with the protein expressions of SERCA 2 and 3. BP positively correlated with both the Vmax of the SERCA (r=.462, P=.010) and the FECa2+ sequestered in the DT (r=.492, P=.005). The relationships between these platelet Ca2+ parameters and BP were in part confounded by increased levels of serum triglycerides and diminished HDL cholesterol with a higher BP. No correlation was observed between the resting cytosolic Ca2+ and BP. Collectively, these findings indicate that (1) an increase in the cellular Ca2+ load in platelets is expressed by a higher activity of the SERCA and an increase in the expressions of SERCA 2 and 3 proteins, coupled with an increase in the FECa2+ in the DT, and (2) a higher BP is associated with an increase in platelet Ca2+ load in human beings, expressed by a rise in the FECa2+ in the DT and the upregulation of SERCA activity.

Differences between store-dependent Ca2+ fluxes in lymphocytes from African Americans and whites.

OBJECTIVE: To investigate differences between store-dependent Ca2+ in African American and white men. METHOD: Thapsigargin, a potent and specific inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase, was used as a probe to elicit store-dependent Ca2+ fluxes. Treatment with this agent caused a rise in the cytosolic free Ca2+ due to the egress of Ca2+ from thapsigargin-sensitive Ca2+ stores and the acceleration of external Ca2+ influx through store-dependent Ca2+ channels. DESIGN: Lymphocytes were obtained from 22 African Americans and 23 whites. These cells were subjected to thapsigargin treatment and changes in the cellular Ca2+ profiles were monitored. RESULTS: Both in Ca(2+)-free and in Ca(2+)-containing media the increases in cytosolic free Ca2+ concentrations after thapsigargin treatment were greater in lymphocytes from African Americans than they were in those from whites. The greater levels of cytosolic Ca2+ concentration were coupled with higher rates of Ca2+ extrusion in thapsigargin-treated lymphocytes from African Americans. CONCLUSIONS: These findings suggest that store-dependent Ca2+ fluxes are greater in lymphocytes from African Americans than they are in those from whites. This phenomenon increases the Ca2+ turnover rate and might augment the sensitivity to agonists acting through Ca2+ signaling systems, thereby predisposing African Americans to essential hypertension.

Increased calcium stores in platelets from African Americans.

Differences in cation transport have been observed between African Americans and whites. These differences may underlie the increased predisposition of African Americans to essential hypertension. To further explore these racial differences, we used platelets as a cellular model for calcium regulation. We measured 45Ca fluxes in platelets from 21 African American and 25 white men. Additionally, using fura 2, we measured cytosolic free calcium levels in resting platelets and platelets treated with ouabain and thrombin. Platelet 45Ca uptake was described by two exchangeable pools: a small, rapidly exchangeable pool and a larger, slowly exchangeable pool. Both pools were larger in platelets from African Americans than from whites (263 versus 185 pmol per 1 x 10(8) platelets for the rapidly exchangeable pool, P < .05; 744 versus 532 pmol per 1 x 10(8) platelets for the slowly exchangeable pool, P < .01). 45Ca washout was described by a rapidly exchangeable pool and a static pool. The former was also higher in platelets from African Americans than from whites (246 versus 202 pmol per 1 x 10(8) platelets, P < .01). The cytosolic free calcium concentrations in resting platelets were lower in African Americans than in whites. After treatment with ouabain and thrombin, the sustained posttransient levels of cytosolic free calcium increased to a greater extent in platelets from African Americans (46.7 nmol/L) than from whites (34.5 nmol/L, P = .033). Platelets from African Americans demonstrate higher intracellular calcium stores than platelets from whites. This racial difference could explain the sensitivity of African Americans to vasoactive agents acting through calcium mobilization from intracellular stores and cytosolic calcium.

Translation of clinical and neuropsychological instruments into French: the CERAD experience.

The increasing number of international and epidemiological studies of Alzheimer's disease points to the need for linguistically equivalent translations of measures for identifying the presence, types, and severity of dementia in cross-cultural populations. In translating the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuropsychological instruments into French, several linguistic issues have emerged such as semantic, phonetic, and word-frequency equivalences. In verbal memory tests, these problems, though minor in appearance, can be major pitfalls in studies comparing cognitive function in populations differing in language. Description of the translation procedure and examples of problems encountered are presented, with measures taken to resolve them.

Incipient and overt diabetic nephropathy in African Americans with NIDDM.

OBJECTIVE--To determine the prevalence of incipient and overt nephropathy in African-American subjects with non-insulin-dependent diabetes mellitus (NIDDM) attending a hospital clinic. Contributory factors, such as blood pressure (BP), duration and age at onset of diabetes, hyperglycemia, hyperlipidemia, and body mass index (BMI) also were evaluated. RESEARCH DESIGN AND METHODS--We recruited 116 African-American subjects with NIDDM for this cross-sectional, descriptive, and analytical study. BP, BMI, 24-h urine albumin excretion, creatinine clearance, serum creatinine, lipids, and GHb levels were measured. Albumin excretion rate (AER) was calculated, and subjects were divided into three groups: no nephropathy (AER < 20 micrograms/min), incipient nephropathy (AER 20-200 micrograms/min), and overt nephropathy (AER > 200 micrograms/min). Frequency of hypertension and nephropathy was analyzed by chi 2 testing, group means were compared using analysis of variance, and linear correlations were performed between AER and other variables. Multiple regression analysis was used to examine the association of these variables while controlling for the effects of other variables. RESULTS--Increased AER was present in 50% of our subjects; 31% had incipient and 19% had overt nephropathy. Hypertension was present in 72.4%; nephropathy, particularly overt nephropathy, was significantly more prevalent in the hypertensive group. Mean BP and diastolic blood pressure (dBP) were higher in the groups with incipient and overt nephropathy, and systolic blood pressure (sBP) was increased in overt nephropathy. Men with either form of nephropathy had higher sBP, dBP, and mean BP, whereas only women with overt nephropathy had increased sBP and mean BP. Subjects with incipient or overt nephropathy had a longer duration of diabetes, and those with overt nephropathy had a younger age at onset of diabetes. By multiple regression analysis, AER correlated with younger age at diabetes onset, but not with diabetes duration. No correlation with age, lipid levels, or GHb was noted. BMI correlated with AER. CONCLUSIONS--Incipient and overt nephropathy were observed frequently in these African-American subjects with NIDDM. Albuminuria correlated with BP, younger age at diabetes onset, and BMI. Association of albuminuria and increased cardiovascular mortality may place 50% of inner-city African-American patients with NIDDM at risk for developing cardiovascular complications.

Recruitment of black elderly for clinical research studies of dementia: the CERAD experience.

Nine Consortium to Establish a Registry for Alzheimer's Disease (CERAD) sites were surveyed to identify barriers to recruiting black subjects. Major cited obstacles were expenses, transportation difficulties, and especially lack of rapport with clinic staff. Major factors in overcoming these barriers are a good referral network involving the black community, community education about Alzheimer's disease (AD), and professional staff who are particularly sensitive to the needs of the black population. CERAD efforts to increase community awareness of Alzheimer's disease and staff sensitivity to minority needs have nearly doubled the proportion of black subjects enrolled.

The Duke University program for integrating ethics and human values into medical education.

In its second year of development, this program blends cognitive and affective approaches to integrating ethics and human values into medical education. The core of this effort is the establishment of direct and continuing relationships between the four advisory deans and their medical student advisees through small groups that continue throughout the four years of medical school. Clinical correlation seminars, lecture/discussions, the humanities, clinical clerkships, and electives are components of this integration process. Both basic science and clinical faculty members have observed positive changes in the degree and depth of participation, discussion, and interest, as well as in the general attitudes of the students.