Numerical modeling of drug delivery in a dynamic solid tumor microvasculature.

The complicated capillary network induced by angiogenesis is one of the main reasons of unsuccessful cancer therapy. A multi-scale mathematical method which simulates drug transport to a solid tumor is used in this study to investigate how capillary network structure affects drug delivery. The mathematical method involves processes such as blood flow through vessels, solute and fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. The effect of heterogeneous dynamic network on interstitial fluid flow and drug delivery is investigated by this multi-scale method. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network and fluid flow in normal and tumor tissues. Finally, convection-diffusion equation is used to simulate drug delivery. Three approaches are used to simulate drug transport based on the developed mathematical method: without a vascular network, using a static vascular network, and a dynamic vascular network. The avascular approach predicts more uniform and higher drug concentration than vascular approaches since the simplified assumptions are implemented in this method. The dynamic network which uses more realistic assumptions predicts more irregular blood vessels, high interstitial pressure, and more heterogeneity in drug distribution than other two approaches.

Association between Migraine and Quality of Life, Mental Health, Sleeping Disorders, and Health Care Utilization Among Older African American Adults.

PURPOSE: This study examines the associations between migraine headaches, well-being, and health care use among a sample of underserved older African American adults. Controlling for relevant variables, the association between migraine headaches and (1) health care utilization, (2) health-related quality of life (HRQoL), and (3) physical and mental health outcomes was examined. METHODS: Our sample included 760 older African American adults from South Los Angeles recruited through convenience and snowball sampling. In addition to demographic variables, our survey included validated instruments, such as the SF-12 QoL, Short-Form McGill Pain Questionnaire, and the Geriatric Depression Scale. Data analysis included 12 independent multivariate models using multiple linear regression, log transferred linear regression, binary and multinomial logistic regression, and generalized linear regression with Poisson distribution. RESULTS: Having migraine was associated with three categories of outcomes: (1) higher level of health care utilization measured by (i) emergency department admissions and (ii) number of medication use; (2) lower level of HRQoL and health status measured by (i) lower self-rated health (ii) physical QoL, and (iii) mental QoL; and (3) worse physical and mental health outcomes measured by (i) higher number of depressive symptoms, (ii) higher level of pain, (iii) sleep disorder, and (iv) being disabled. CONCLUSIONS: Migraine headache significantly was associated with quality of life, health care utilization, and many health outcomes of underserved African American middle-aged and older adults. Diagnoses and treatments of migraine among underserved older African American adults require multi-faceted and culturally sensitive interventional studies.

Boom boom pow: Shock-facilitated aqueous alteration and evidence for two shock events in the Martian nakhlite meteorites.

Nakhlite meteorites are ~1.4 to 1.3 Ga old igneous rocks, aqueously altered on Mars ~630 Ma ago. We test the theory that water-rock interaction was impact driven. Electron backscatter diffraction demonstrates that the meteorites Miller Range 03346 and Lafayette were heterogeneously deformed, leading to localized regions of brecciation, plastic deformation, and mechanical twinning of augite. Numerical modeling shows that the pattern of deformation is consistent with shock-generated compressive and tensile stresses. Mesostasis within shocked areas was aqueously altered to phyllosilicates, carbonates, and oxides, suggesting a genetic link between the two processes. We propose that an impact ~630 Ma ago simultaneously deformed the nakhlite parent rocks and generated liquid water by melting of permafrost. Ensuing water-rock interaction focused on shocked mesostasis with a high density of reactive sites. The nakhlite source location must have two spatially correlated craters, one ~630 Ma old and another, ejecting the meteorites, ~11 Ma ago.

Importance of timing of magnesium administration in the isolated ischemic-reperfused rat heart: role of K(ATP) channels.

There is a growing interest for the beneficial effect of magnesium (Mg) in cardiovascular disorders. A number of cardiovascular disorders including myocardial infarction, arrhythmias and congestive heart failure have been associated with low extra- cellular or intracellular concentrations of Mg. The efficiency of the preconditioning effect of Mg on cardiac function and infarct size in the globally ischemic-reperfused isolated rat heart was studied together with the role of ATP-sensitive potassium (K(ATP)) channels in protection induced by Mg. Rat hearts were Langendorff perfused, subjected to 30 min of global ischemia and 90 min of reperfusion, including treatment groups which focused on different times of Mg (8 mmol/l) use. Infarct size was measured by triphenyltetrazolium chloride (TTC) method. The left ventricular function was assessed by left ventricular developed pressure (LVDP), heart rate (HR) and coronary flow (CF). The administration of Mg before ischemia had an anti-infarct effect in rat hearts and improved cardiac function. The protective effects of magnesium was abolished by the blocking of K(ATP) channels and suggests that K-ATP channel has an important role in the heart protection effect of Mg as a preconditioning agent.

A novel approach for early evaluation of orthodontic process by a numerical thermomechanical analysis.

The main objective of this paper is to propose a novel method that provides an opportunity to evaluate an orthodontic process at early phase of the treatment. This was accomplished by finding out a correlation between the applied orthodontic force and thermal variations in the tooth structure. To this end, geometry of the human tooth surrounded by the connective soft tissue called the periodontal ligament and the bone was constructed by employing dental CT scan images of a specific case. The periodontal ligament was modeled by finite strain viscoelastic model through a nonlinear stress-strain relation (hyperelasticity) and nonlinear stress-time relation (viscoelasticity). The tooth structure was loaded by a lateral force with 15 different quantities applied to 20 different locations, along the midedge of the tooth crown. The resultant compressive stress in the periodontal ligament was considered as the cause of elevated cell activity that was modeled by a transient heat flux in the thermal analysis. The heat flux value was estimated by conducting an experiment on a pair of rats. The numerical results showed that by applying an orthodontic force to the tooth structure, a significant temperature rise was observed. By measuring the temperature rise, the orthodontic process can be evaluated.

Clinical evaluation of desferrioxamine (DFO) for removal of thallium ions in rat.

An investigation was conducted to evaluate the ability of DFO following the administration of thallium salt in male Wistar rats. Thallium was introduced to several groups of weanling male Wistar rats via different means, through drink, food and intraperitoneal injection. A control group was fed on a diet containing a normal level of iron. After a period of 30 days, all the rats administered thallium were severely anemic and showed toxicity symptoms through loss of hair, an increase in thallium and a decrease in iron levels in the blood. Chelation therapy was carried out to remove the toxic element from the body. The ability of desferrioxamine (DFO) in removing thallium was investigated by injection of this chelator for one week to the remaining rats of similar groups. The results showed that the thallium level present in the blood was significantly reduced and, at the same time, the iron concentration returned to the normal level. It was concluded that DFO chelator is able to remove thallium from the body and could be used for the treatment of complications and eradication of symptoms of thallium intoxication.

Correlates of recency of eye examination among elderly African-Americans.

This study uses a theoretical model of health services utilization to assess the effects of predisposing, enabling, and need-for-care characteristics on recency of eye examinations among a sample of 998 elderly African-American persons. More than 64% of participants reported that they had had eye examinations within the last 12 months. Multiple logistics regression analysis explains 13.3% of the variance of eye examinations. This data indicates that recency of eye examination is related to health locus of control, private insurance, Medicare, insulin-dependent diabetes, and presence of eye disease. No significant relationship between recency of eye examination and self-rated health status, social support, vision impairment, and non-insulin-dependent diabetes were detected. The lack of association between non-insulin-dependent diabetes and the recency of eye examination suggests that the amount of preventive care in place may not be adequate. This data shows that the unique contributions of need characteristics account for a major variance of recency of eye examination. However, enabling characteristics play a significant role in sending the participants of this study to eye-specialists, even after need-for-care factors are held constant.

Prevalence and causes of low vision and blindness in the Extreme North Province of Cameroon, West Africa.

A survey to determine the prevalence and causes of blindness and visual impairment in the Extreme North Province of Cameroon was conducted in the Spring of 1992. A total of 10,647 people age 6 years and older was selected from a multi-stage, clustered sample stratified by ecological zone. The subjects were examined by ophthalmologist-led teams for visual acuity and ocular diseases. Approximately 1.2% of the sample was bilaterally blind by the World Health Organization classification (Category 3) of vision less than the ability to count fingers at 3 meters. Similarly to results found in other developing countries, senile cataract was the most common diagnosis encountered and the most frequent principal cause of low vision and blindness.

Computer-aided, case-based diagnosis of mammographic regions of interest containing microcalcifications.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the effectiveness of a mapped-database diagnostic system in reducing the incidence of benign biopsies and misdiagnosed cancers among mammographic regions of interest (ROIs). MATERIALS AND METHODS: A novel neural network was devised (a) to respond to a query ROI by recommending to biopsy or not to biopsy and (b) to map each ROI in the database as a dot on a computer screen. The network was designed so that clusters in the array of dots help the radiologist to find proved ROIs visually similar to the query ROI. This mapped-database diagnostic system was restricted to ROIs with visible microcalcifications. The neural network was trained with a stored database of 80 biopsy-proved ROIs. RESULTS: Four radiologists acting independently on 100 ROIs recommended biopsies for 18, 15, 28, and 18 benign ROIs and misdiagnosed cancers in 11, 12, 7, and eight ROIs, respectively. Interaction with the mapped-database system reduced the numbers of benign biopsies to 11, eight, 18, and 10 cases and of misdiagnosed cancers to eight, seven, four, and three cases, respectively. Statistical analysis indicated that three radiologists achieved significant improvements at P < or = .02 and the fourth achieved a substantial improvement at P < or = .07. CONCLUSION: By using a mapped database of proved mammographic ROIs containing microcalcifications, radiologists may statistically significantly reduce the numbers of benign biopsies and misdiagnosed cancers.

Paranoid ideation among elderly African American persons.

PURPOSE: The prevalence and correlates of paranoid ideation were investigated. DESIGN AND METHODS: On the basis of a sample of 998 independently living elderly African American persons in a cross-sectional study, the study used the Brief Symptom Inventory to measure paranoid ideation and 14 independent variables, including demographic characteristics, cognitive deficit, depression, self-reported memory functioning, emotional and instrumental support, stressful life events, limitation of daily activities, self-rated health status, and self-rated hearing and vision. RESULTS AND IMPLICATIONS: Paranoid ideation (symptoms of paranoia) was found in 10% of this sample. A multiple regression analysis of the data revealed that of the 14 independent variables used in this study, 6 (income, instrumental support, hearing, stressful life events, self-reported memory deficit, and depression) showed a significant relationship with paranoid ideation.

Voting behavior among low-income black elderly: a multielection perspective.

We examined voting behavior among 370 low-income older African-American citizens who reside in New Orleans by assessing the impact of various predictors on electoral participation in a series of seven elections. Elders who were active in their community, with a strong sense of citizen duty, who identified themselves as strong Democrats, and with higher levels of education were more likely to vote.

Emergency department utilization, hospital admissions, and physician visits among elderly African American persons.

This study uses a theoretical model of health services utilization to examine (a) emergency department utilization, (b) hospital admissions, and (c) office-based physician visits among a sample of 998 low-income elderly African American persons. Poisson Regression analysis was used to estimate the parameters specified in the Andersen behavioral model. Some of the more interesting results include the following: (a) a greater frequency of emergency room visits among respondents with a lower level of accessibility to physician services, (b) a lack of a significant relationship between some chronic illnesses such as diabetes and heart problems and the frequency of office-based physician visits, (c) a greater number of hospital admissions among insured persons, and (d) a significant impact of the health locus of control indexes on all three types of health care utilization. The results of this study challenge the assumption that hospital and emergency use are the results of nondiscretionary behavior.

The relationship between chronic illness and depression in a community of urban black elderly persons.

The relationship between depression and chronic illness among the elderly population has often been investigated. However, the impact of individual chronic illnesses while controlling for the impact of various psychosocial factors is still not well understood. This is particularly true among Black elderly persons. In a cross-sectional study, the impact of selected chronic illnesses and psychosocial variables on depression was investigated among 1,022 Black urban elderly persons who reside in New Orleans, Louisiana. Depression was greatest among those with more financial difficulties, more stressful life events, lower self-perceptions, less support from friends, and less instrumental support. Multiple regression analysis determined that depression was greatest among elderly persons who reported kidney, vision, and/or circulation problems. These findings suggest that elderly persons may perceive these three illnesses as more debilitating than other chronic illnesses.

Sensory impairments and subjective well-being among aged African American persons.

The limited number of studies concerning the prevalence of hearing loss and vision impairment and their causes, and the lack of strategies to prevent or treat the deleterious effects of hearing loss and vision impairment, point to a significant gap in the knowledge base concerning aged minority populations. This cross-sectional study evaluated the relationship between vision and hearing impairment and psychological well-being among a sample of 988 elderly African American persons. Fair or poor vision or hearing was reported for 36.5% and 26% of our sample, respectively. Reported prevalence rates for these impairments are considerably higher than rates previously documented in comparable studies of elderly people conducted in general (i.e., predominantly White) populations. Eighty-four percent of our study participants attempted to improve their vision through the use of eyeglasses. By contrast, only 4.3% of individuals in the study who described their hearing as poor reported using hearing aids. Using multivariate analysis and other related variables that have previously been identified as common predictors of psychological well-being, the findings of this study suggest that poor vision is independently associated with a lower level of psychological well-being among aged African Americans even after adjusting for sociodemographic characteristics, functional limitations, perceived health status, and cognition. Poor hearing was also found to be associated with a lower level of psychological well-being; however, this relationship was not independent but was mediated by the effect of hearing on functional status. These data indicate considerable potential for improved psychological well-being for African American elderly people through visual and audiological rehabilitation.

Failure to have prescriptions filled among Black elderly.

Despite extensive research on drug consumption and compliance with drug regimens within the geriatric population, little attention has been given to the failure to have prescriptions filled among elderly in general and Black elderly in particular. The prevalence and correlates of patients' failure to have prescriptions filled were investigated for a sample of 571 Black elderly. In terms of prevalence, 12.8% of this sample asserted that they had received a prescription from a physician and not had it filled during the 6 months period prior to interview. Multivariate logistic regression was employed to detect the significant predictors of this type of noncompliance. According to our data, failure to have prescriptions filled was significantly greater among Black elderly with higher levels of anxiety, those with lower levels of internal health locus of control, those who did not have prescription medication coverage through Medicaid, those who were currently using prescription medications, those who consumed greater numbers of over-the-counter medications, and those who reported more financial problems. Implications of these findings are discussed.

The reading habits of family practice residents.

BACKGROUND AND OBJECTIVES: Little is known about the reading habits of family practice residents. This study describes the reading practices of family practice residents, including how much time they spend reading and what information sources they use, identifies factors that may be used by educators to stimulate resident reading, and identifies factors that may inhibit or discourage reading. METHODS: A questionnaire about reading habits was mailed to 613 randomly selected resident members of the American Academy of Family Physicians in March 1994. RESULTS: Of 613 questionnaires sent, 314 (51%) were completed and returned. Participants reported reading an average of 3.7 hours per week and were most often motivated to read to obtain information related to clinical cases or to prepare for an upcoming presentation. Pocket manuals were the most frequently read and original scientific research the least frequently read sources of medical information. Fatigue and family responsibilities were the factors most important in preventing reading. Year in residency, moonlighting hours, age, gender, or household size were not associated with reported reading time. CONCLUSIONS: Clinical cases and upcoming presentations may be the best motivators of resident reading. Training programs need to continue to develop strategies to minimize resident fatigue, which may lead to increased reading among trainees. The importance of original scientific research articles during residency training is unclear.

Correlates of HIV risk-taking behaviors among African-American college students: the effect of HIV knowledge, motivation, and behavioral skills.

This study identifies theoretically based predictors of condom use in a sample of 253 sexually active African-American college students recruited from two historically African-American colleges. The Information-Motivation-Behavioral (IMB) skills model of AIDS-preventive behavior was employed to delineate the roles of HIV/AIDS knowledge, experiences with and attitudes toward condom use, peer influences, perceived vulnerability, monogamy, and behavioral skills. A predictive structural equation model revealed significant predictors of more condom use including: male gender, more sexual HIV knowledge, positive experiences and attitudes about condom use, nonmonogamy, and greater behavioral skills. Results imply that attention to behavioral skills for negotiating safer sex and training in the proper use of condoms are key elements in reducing high risk behaviors. Increasing the specific knowledge level of college students regarding the subtleties of sexual transmission of HIV is important and should be addressed. Heightening students' awareness of the limited protection of serial monogamy, and the need to address gender-specific training regarding required behavior change to reduce transmission of HIV should be an additional goal of college health professionals.

The frequency and predictors of helmet use among Iranian motorcyclists: A quantitative and qualitative study.

OBJECTIVE: This study examines the rate of helmet use and identifies barriers and facilitators of wearing helmets among Iranian motorcyclists. A mixed-method approach was used, including a structured seasonal survey with specific observations of a random sample of 6010 riders and qualitative methods that included 29 in-depth interviews and seven focus groups (n=31). RESULTS: Only 10% of motorcyclists wear a standard helmet while riding. However, another 23% of motorcyclists used non-standard or partial helmets that covered only part of the head and do not prevent head trauma injuries effectively. We observed only 2 of 264 child passengers and 22 of 1951 adult passengers wearing helmets. Almost no one used protective pants or clothing made to be more visible in traffic. Themes emerged from qualitative interviews and were grouped into three main categories: (1) helmet characteristics; (2) social and cultural factors; and (3) personal and psychological factors. CONCLUSION: Overall, the motorcyclists in our study believed that wearing a safety helmet protects them against serious injuries or death during a crash; however, only a small percentage of the motorcyclists used safety helmets. National intervention programs addressing motorcycle safety should aim to overcome barriers to and promote facilitators of helmet use, including providing inexpensive standard helmets, banning manufacturing/using unsafe partial or dummy helmets, as well as enforcing helmet use on a consistent basis.

Galanin receptor 3--a potential target for acute pancreatitis therapy.

BACKGROUND: Galanin participates in the pathogenesis of acute pancreatitis (AP). The galanin receptor (GALR) sub-types involved, however, are unclear. We aimed to determine GALRs messenger RNA (mRNA) expression in mouse pancreas, describe their localization, and ascertain if GALR2 and GALR3 are involved in AP. METHODS: Galanin receptor expression in murine whole pancreas, acinar, and islet cells was quantified by polymerase chain reaction amplification of reverse-transcribed RNA for mRNA, Western blot analysis for protein and in situ hybridization for GALR localization. Isolated acinar cells were used to determine galanin's effect on amylase secretion. Acute pancreatitis was induced in mice by caerulein injections. Mice, with and without AP, were treated with the highly selective GALR2 antagonist M871, or the specific GALR3 antagonist SNAP-37889. Indices of AP were measured at 12 h. KEY RESULTS: Murine pancreas expresses mRNA for GALRs. In islets the expression of all GALR are comparable, whereas in acinar cells GALR3 is predominantly expressed. Western blot analysis confirmed that the GALR proteins are expressed by acinar cells. In situ hybridization analysis confirmed that GALR3 mRNA is present in islet and acinar cells, while mRNA for GALR1 and 2 is confined to islets. Galanin did not influence basal and caerulein-stimulated amylase release from acinar cells. M871 treatment reduced some, whereas SNAP-37889 treatment reduced all indices of AP (by 40-80%). CONCLUSIONS & INFERENCES: Galanin receptor mRNA and protein are expressed in mouse pancreas, with GALR3 mRNA predominating. GALR3 antagonism reduced the severity of AP whereas GALR2 antagonism was less effective. GALR3 is a potential target for treatment of AP.