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PubMed2001

Preferential transduction of neurons by canine adenovirus vectors and their efficient retrograde transport in vivo.

In the central nervous system (CNS), there are innate obstacles to the modification of neurons: their relative low abundance versus glia and oligodendrocytes, the inaccessibility of certain target populations, and the volume one can inject safely. Our aim in this study was to characterize the in vivo efficacy of a novel viral vector derived from a canine adenovirus (CAV-2). Here we show that CAV-2 preferentially transduced i) rat olfactory sensory neurons; ii) rodent CNS neurons in vitro and in vivo; and, more clinically relevant, iii) neurons in organotypic slices of human cortical brain. CAV-2 also showed a high disposition for retrograde axonal transport in vivo. We examined the molecular basis of neuronal targeting by CAV-2 and suggest that due to CAR (coxsackie adenovirus receptor) expression on neuronal cells-and not oligodendrocytes, glia, myofibers, and nasal epithelial cells-CAV-2 vectors transduced neurons preferentially in these diverse tissues.

Adenoviruses, Canine↗
PubMed1995

[Methods and intervention in populations with high-risk for cancer].

Prevention envisions either a reduction in the incidence of a disease through direct action against its causes, or a reduction of the consequences of that disease (especially mortality), by action against the process leading to clinical expression of the underlying pathology. As in therapeutic medicine, preventive measures must be thoroughly evaluated for efficacy and secondary effects before they become standard recommendations. Two levels of evaluation can be identified: evaluation of feasibility, acceptability, involving quality control of the proposed programme, evaluation of results according to previously defined and quantified objectives. In order to demonstrate that the risk-benefit ratio of a preventive strategy is favorable, results in the intervention group must be compared with those in the control group, just as is done in therapeutic trials. Further more, prevention applies generally to healthy subject ie those not needing medical care and for whom, in the majority of cases, there will be no direct benefit. As a consequence, careful ethical consideration must be given to such programme. In particular, calculating the risk-benefit ratio must take into account the mental and social well being of people whose lives will be "medicalized" as a result of such intervention. Measurement of the consequences of such preventive actions on the life style and mental health of the population subjected to them necessitates the development of specific tools adapted to such situations. Research in methodology in this area is essential. If a population with almost 100% risk for a disease can be identified (genetic risk for example), aggressive preventive intervention can be limited to only that group. It must be emphasized that identification of subjects at risk, no matter how reliable, is not an end in itself. It is only justified, on a medical point of view, if we can offer these individuals a preventive programme with demonstrated benefit. The primacy of collective benefit over individual interest mandates that preventive intervention be based on voluntary informed consent of the target population. An alternative to individual consent could be, in some occasion, a "collective" consent.

Anticarcinogenic Agents↗
PubMed1994

Serological screening of coeliac disease: choosing the optimal procedure according to various prevalence values.

The aim of this study was to select the best approach for screening coeliac disease patients among populations with different grades of disease prevalence. The diagnostic performance was assessed of class A and G antigliadin antibodies and class A antiendomysium antibodies in 93 consecutive outpatients with suspected malabsorption, 44 of whom (47%) had coeliac disease according to duodenal histological tests. Class G antigliadin antibodies provided the worst diagnostic values, whereas a high diagnostic validity was found for the other two tests. The positive predictive value corrected for the disease prevalence expected in coeliac disease relatives (5%) and the general population (0.2%) fell to 30% and < 2% respectively for class A antigliadin antibodies, whereas it remained 100% for antiendomysium antibodies in both situations, providing an optimal value for their use as a screening test and as a valid alternative to duodenal biopsy when this is not feasible. The high cost of anti-endomysium antibodies and the invasive nature of duodenal biopsy prevent them being used widely as screening procedures. A cost effective two step approach was simulated measuring class A antigliadin antibodies in all subjects of the target population (first step), and performing a confirmation test (antiendomysium antibodies or duodenal biopsy) only in subjects positive for antigliadin antibodies. The results show that such a procedure should be recommended only for subjects with an expected low disease prevalence--that is, 5% for coeliac disease relatives and 0.2% for the general population--as the positive predictive value was always 100% with an acceptable false negative rate (6% and 11% respectively), irrespective of which of the two confirmation tests was used. This approach avoids the use of the confirmation test in 63% and 89% of subjects respectively for the two levels of prevalence, resulting in a considerable reduction of the cost. Patients seen for suspected malabsorption with an expected high prevalence of coeliac disease should not have such a serological screening procedure. In conclusion, antigliadin antibodies are useful to screen for asymptomatic coeliac disease in non-hospital communities if antiendomysium anti-bodies are used as a confirmation test: the latter is reasonable valid alternative to duodenal biopsy.

Adolescent↗
PubMed1994

Synergistic actions of stem cell factor and other burst-promoting activities on proliferation of CD34+ highly purified blood progenitors expressing HLA-DR or different levels of c-kit protein.

We studied the synergistic effects of stem cell factor (SCF) and other burst-promoting activities (BPAs) such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or IL-9 on proliferation of human peripheral blood-derived highly purified progenitors. SCF, IL-3, GM-CSF, and IL-9 showed significant BPA when CD34+HLA-DR+ cells were used as the target population. IL-3 exerted the most potent BPA, and GM-CSF supported approximately 40% to 70% of the erythroid burst-forming units that are responsive to IL-3. SCF and IL-9 showed much weaker BPA than that of IL-3 or GM-CSF. Combinations of IL-3 with other BPAs did not show synergistic actions supporting erythroid-burst formation. However, GM-CSF showed a significant additive effect with IL-9 or SCF. When CD34+c-kithigh cells were used as the target, SCF showed a much stronger BPA. Also, a distinct additive effect between SCF and IL-3 or GM-CSF on erythrocyte-containing mixed colony formation was observed. On the other hand, when CD34+c-kitlow cells were used as the target, SCF, IL-3, and GM-CSF could express BPA. In contrast, IL-9 alone failed to support erythroid-burst formation. Because CD34+c-kithigh cells weakly expressed CD34 antigen, these cells appeared to be more mature progenitors than CD34+c-kitlow cells. These results suggest that IL-9 acts on more mature progenitors than those of SCF, IL-3, or GM-CSF and that the primary target of SCF is multipotential progenitors at the very early stage of development.

Animals↗
PubMedDate not supplied

[Prevalence of arterial hypertension and related factors in a marginated rural population].

OBJECTIVE: To determine the prevalence and risk factors related to systemic arterial hypertension (SAH) in the rural marginated population of Durango, Mexico. MATERIAL AND METHODS: A comparative cross-sectional study was performed in 627 rural communities, approximately 90% of which have 250 inhabitants or less. The arterial pressure and sociodemographic variables were determined. RESULTS: A total of 5,802 subjects were studied, 4,452 women (76.7%) and 1,350 men (23.3%). SAH was found in 1,271 individuals (21.9%; CI 95% 20.8-23.0) of which 1,011 were women (22.71%; CI 95% 21.5-23.9) and 260 were men (19.26%; CI 95% 17.2-21.4). Of the target population, 3,018 individuals (52.0%) live in communities of less than 250 inhabitants, 2,080 (60.9%) women and 938 (31.1%) men. In this group, SAH was identified in 445 cases (14.74%; CI 95% 13.5-16.0) of which 326 are women (15.7%; CI 95% 14.1-17.3) and 119, men (12.7%; CI 95% 10.6-14.9). The main risk factors related to SAH were obesity, type 2 diabetes, alcohol and tobacco consumption. CONCLUSIONS: The prevalence of SAH in the rural marginated population is apparently related to the degree of development of the communities.

Adult↗
PubMed1998

Factors affecting participation in a mammography screening program among members of an urban Detroit health maintenance organization.

Breast cancer mortality rates remain disproportionately high among black women despite recent improvements in mammography screening utilization. We conducted a telephone survey among a sample of women (N = 202) participating in a randomized controlled trial investigating the effectiveness of a mammography reminder letter that was one component of a breast cancer control intervention strategy. The objectives of the survey were to ascertain the extent to which the letter reminder was received and acted upon, and to determine attitudes and breast cancer control practices in the target population. The study was conducted among members of a large health maintenance organization serving predominantly black women in Detroit, Michigan. Forty-eight percent of the participants completed a mammogram during the year after the letter was sent. While 72% of the women remembered receiving the letter reminder, only 5% responded to the recommendations in the letter. Important predictors of mammography completion included past mammogram utilization (OR: 2.49; 95% CI: 1.05-5.93), a prior physician recommendation for a mammogram (OR: 1.99; 95% CI: 1.00-3.95) and subject's knowledge of her primary physician's name (OR: 2.05; 95% CI: 0.91-4.60). Letter reminders promoting primary care visits were relatively ineffective since few women reported being prompted by the letter recommendation. Strategies which target physician mammography referral behavior may have an important impact on mammography utilization among inner-city women.

Adult↗
PubMed1992

Taming demons: the reduction of harm resulting from use of illicit drugs.

Restricting availability is the major response to illicit drugs in most Western countries including Australia. Prohibition may reduce harm when the drug in question is in low demand, controls are difficult to subvert, and when similar drugs are less toxic or unavailable. However, the health, social and economic costs of supply reduction are substantial and increasing for both injecting drug users and the general community. Population adjusted mortality of heroin users has doubled in Australia in the last decade. The possible impact of supply reduction policy on the spread of HIV infection among IDUs is an important but largely neglected consideration. The effectiveness of supply restriction policy in decreasing the availability of drugs or in reducing drug-related harm is unlikely to be increased significantly by more vigorous implementation of supply reduction or adoption of new technology. Conversely, on the basis of existing data, greater availability of HIV prevention measures attractive to the target population (including especially drug treatment such as methadone maintenance) is likely to be effective and cost-effective. The costs and benefits of innovative methods of providing currently illicit drugs to those who are determined to use them requires careful evaluation and comparison with existing policies. Policy on illicit drugs in most countries including Australia is still dominated by concern about drug use rather than focused on the need to reduce drug-related problems which is the agreed aim of national drug policy.

Australia↗
PubMedDate not supplied

Health care delivery to farmworkers in the Southwest: an innovative nursing clinic.

The migrant and seasonal farmworkers of the United States constitute a medically underserved population with many health care needs. Barriers to health care among farmworker families include financial constraints, cultural factors, restrictive labor practices, and absence of accessible clinics in rural areas. The Migrant Health Outreach Program is a federally funded mobile nursing clinic created to deliver health care to farmworkers where they live and work. The Migrant Health Outreach Team, composed of family nurse practitioners, registered nurses, and health care workers, offers primary care including health care maintenance and treatment of acute and chronic illness. The mobile nursing clinic serves the target population of farmworkers as a successful alternative to a traditional medical clinic.

Adolescent↗
PubMed2006

The development of a multidisciplinary fall risk evaluation tool for demented nursing home patients in the Netherlands.

BACKGROUND: Demented nursing home patients are at high risk for falls. Falls and associated injuries can have a considerable influence on the autonomy and quality of life of patients. The prevention of falls among demented patients is therefore an important issue. In order to intervene in an efficient way in this group of patients, it is important to systematically evaluate the fall risk profile of each individual patient so that for each patient tailor-made preventive measures can be taken. Therefore, the objective of the present study is to develop a feasible and evidence based multidisciplinary fall risk evaluation tool to be used for tailoring preventive interventions to the needs of individual demented patients. METHODS: To develop this multidisciplinary fall risk evaluation tool we have chosen to combine scientific evidence on the one hand and experts' opinions on the other hand. Firstly, relevant risk factors for falling in elderly persons were gathered from the literature. Secondly, a group of Dutch experts in the field of falls and fall prevention in the elderly were consulted to judge the suitability of these risk factors for use in a multidisciplinary fall risk evaluation tool for demented nursing home patients. Thirdly, in order to generate a compact list of the most relevant risk factors for falling in demented elderly, all risk factors had to fulfill a set of criteria indicating their relevance for this specific target population. Lastly the final list of risk factors resulting from the above mentioned procedure was presented to the expert group. The members were also asked to give their opinion about the practical use of the tool. RESULTS: The multidisciplinary fall risk evaluation tool we developed includes the following items: previous falls, use of medication, locomotor functions, and (correct) choice and use of assistive and protective devices. The tool is developed for the multidisciplinary teams of the nursing homes. CONCLUSION: This evidence and practice based multidisciplinary fall risk evaluation tool targets the preventive interventions aimed to prevent falls and their negative consequences in demented nursing home patients.

Accidental Falls↗
PubMed1996

[Demographic profile and health conditions of the elderly in a community in an urban area of southeastern Brazil].

Some specific characteristics of the aging of the Brazilian population in different areas, states and communities all over the country, have shown significant variations. Historical series of demographic and health indicators for the population in their sixties and over in Brazil, state of S. Paulo and in the municipal district of Araraquara are listed as follows: level of education and urban population growth rate, income distribution, mortality rates and main causes of death. In 1991 the aged constituted were 7.8% of the Brazilian population and 9.7% in Araraquara community. The elderly population (of 70 years of aged and above) as a proportion of the whole, has increased and already stands for 40%. The same trend holds good for both the proportion of aged within the urban population and their level of education which increased to 90% in 1991. The main causes of death are chronic degenerative diseases which have replaced the infectious illness: first, the diseases of the circulatory system (which account for more than 40% of all deaths) and the neoplasms (which let to 15% of the deaths). On the basis of these health and demographic data relating to people of 60 years of age and over, this study suggests some procedures for the improvement of the quality of the assistance given to the target population: a) the assistance give to the aged should be improved by providing gerontological training for general physicians and nurses, both of public and private clinics; b) the already existing educational activities for the aged, for health workers and for teachers of secondary education should be further developed; c) the number of day-hospitals should be increased for the purpose of avoiding unnecessary confinement so as maintain the low rate of institutionalization in homes for the elderly (0.7% in Araraquara). It is reported that at least 35% of the aged population in this area is entitled to private health assistance, which brings out the importance of including such services in the local health programs for this group.

Aged↗
PubMed1978

The Russian flu. Its history and implications for this year's influenza season.

From November 1977 through mid-January 1978 the population younger than 25 years in the Union of Soviet Socialist Republics experienced a widespread epidemic of mild influenza (Russian flu) caused by an H1N1 virus similar to the virus that circulated worldwide during the early 1950s. Outbreaks of Russian flu occurred in school populations and military recruits in the United States starting in mid-January. Many other countries reported outbreaks of H1N1 virus in the winter of 1978. Predictions of influenza activity are always hazardous, but most experts believe that the Russian flu may occur again in the fall and winter of 1978. Other type A and B strains may also circulate; therefore, a trivalent vaccine containing A/USSR, A/Texas, and B/Hong Kong virus strains will be available. It is recommended that the chronically ill and those 65 years and older be the target populations for annual vaccination.

Adolescent↗
PubMed1993

IL-2 expands and maintains IgM plasmablasts from a CD5+ subset contained within the germinal centre cell-enriched (surface IgD-/CD39- buoyant) fraction of human tonsil.

IL-2 was found to promote the rapid growth of a minority population contained within the germinal centre (GC) cell-enriched (CD39- and/or IgD- buoyant) fraction of human tonsillar B lymphocytes. The cells emerging in response to IL-2 had a high mitotic index and morphologically resembled plasmablasts. Cultures could be maintained in the absence of feeder cells for up to 3 weeks in IL-2 and were characterized by large amounts of IgM in their supernatants: approximately 40% of the cells contained readily detectable cytoplasmic IgM by day 10 of culture. Negligible quantities of IgG and IgA were found. The target population for IL-2-driven expansion and IgM secretion was smIg+/CD38+ and was subject to suppression by anti-IgM antibody. While only 8% of cells within the GC cell-enriched fraction were CD5+ (compared with 15% of high density resting B cells), their removal led to an 83% reduction in the amount of IgM produced in response to IL-2, IL2 selectively expanded this minor CD5+ subset such that by day 6 of culture they comprised 57% of all viable cells. Cultures established with IL-2 showed increasing expression of cytoplasmic Bcl-2 and withdrawal of growth factor resulted in cell death via apoptosis. We discuss these results in relation to CD5+ B cells and their potential role in antibody responses to TD antigens.

Adenosine Triphosphatases↗
PubMed2003

Immunocontraception is induced in BALB/c mice inoculated with murine cytomegalovirus expressing mouse zona pellucida 3.

Immunocontraception, the prevention of oocyte fertilization through immunological means, could potentially be used to control plaguing mouse populations in Australia. This paper describes the construction of a mouse-specific betaherpesvirus, murine cytomegalovirus, which has been engineered to express the murine zona pellucida 3 (ZP3) gene. A single inoculation of this recombinant virus resulted in almost complete infertility, persistent anti-ZP3 antibody production, and profound changes to ovarian morphology in BALB/c mice in the absence of significant virus replication during the acute phase of infection. Murine cytomegalovirus may prove to be useful as a vector for the delivery of a mouse-specific immunocontraceptive agent to target populations of wild mice in the field.

Animals↗
PubMed2003

Results from a cardiovascular prevention campaign in persons aged 45-64 years.

The aim of this study was to screen a target population for modifiable cardiovascular risk factors and to find out how treatment goals were achieved in the treated population. All inhabitants aged between 45 and 64 years in the town of Lede in Belgium were invited by the local authorities for a free health check-up. In total, 629 subjects were screened. Total cholesterol > or = 250 mg/dl or triglycerides > or = 200 mg/dl was found in 38%, increased fasting glucose (> or = 110 mg/dl) in 8.6%, diabetes in 2.8%, increased systolic blood pressure (SBP) (> or = 140 mmHg) in 22% and increased diastolic blood pressure (DBP) (> or = 90 mmHg) in 8%. The low-density lipoprotein cholesterol (LDL-C) target level of 115 mg/dl was attained in 13% of treated women and 34% of treated men. Target levels for SBP and DBP were attained in 40% and 75% respectively of those treated. Fasting glucose < 120 mg/dl was found in 33% of the diabetic participants.

Belgium↗
PubMed1995

Present and future challenges of immunizations on the health of our patients.

A recent analysis demonstrated a change in incidence approaching 100% for diseases against which we routinely immunize in the United States. At present, measles, mumps, rubella, invasive Haemophilus disease, poliomyelitis, diphtheria and tetanus are well-controlled but not eliminated. Diseases that now pose special problems include pertussis, hepatitis A and B and varicella. The incidence of pertussis surged in 1994, possibly in part because of waning immunity in the immunized population. Acellular pertussis vaccines are available for booster doses in children but are not now recommended for adults. Licensure of acellular pertussis vaccines for primary immunization of infants is eagerly awaited. Recombinant hepatitis B vaccine has been licensed for more than 10 years but there has been little change in disease incidence in the United States. Routine immunization of infants is now recommended but concerns exist about cost and persistence of immunity into adolescence. Inactivated hepatitis A vaccines appear to be highly effective in preventing clinical hepatitis and controlling epidemics. Potential target populations include military personnel, day-care attendees and travelers. Hepatitis A vaccine may be recommended for all children after approval by the United States Food and Drug Administration and if a combination vaccine becomes available. A live, attenuated varicella vaccine developed in 1974 and unlicensed in the United States is safe and highly effective in preventing varicella in healthy and immunocompromised populations. It also appears to reduce subsequent development of herpes zoster. Vaccines against pneumococci (conjugate vaccine), respiratory syncytial virus, rotavirus, tuberculosis and human immunodeficiency virus are needed. Research and technology to develop these vaccines must be developed, and efficient delivery mechanisms must be created and implemented.

Child↗
PubMed2005

Identification of novel resident pulmonary stem cells: form and function of the lung side population.

Resident lung stem cells function to replace all lineages of pulmonary tissue, including mesenchyme, epithelium, and vasculature. The phenotype of the lung side population (SP) cells is currently under investigation; their function is currently unknown. Recent data suggest lung SP cells are an enriched tissue-specific source of organ-specific pulmonary precursors and, therefore, a source of adult stem cells. The adult lung SP cell population has been isolated and characterized for expression of markers indicative of stem cell, epithelial, and mesenchymal lineages. These studies determined that the adult mouse lung SP has epithelial and mesenchymal potential that resides within a CD45- mesenchymal subpopulation, as well as limited hematopoietic ability, which resides in the bone marrow-derived CD45+ subpopulation. The ability to identify these adult lung precursor cells allows us to further study the potential of these cells and their role in the regulation of tissue homeostasis and response to injury. The identification of this target population will potentially allow earlier treatment and, long term, a functional restoration of injured pulmonary tissue and lung health.

Animals↗
PubMed2006

Multilevel community-based intervention to increase access to sterile syringes among injection drug users through pharmacy sales in New York City.

OBJECTIVES: Research has indicated that there is minimal use of pharmacies among injection drug users (IDUs) in specific neighborhoods and among Black and Hispanic IDUs. We developed a community-based participatory research partnership to determine whether a multilevel intervention would increase sterile syringe access through a new policy allowing nonprescription syringe sales in pharmacies. METHODS: We targeted Harlem, NY (using the South Bronx for comparison), and disseminated informational material at community forums, pharmacist training programs, and counseling or outreach programs for IDUs. We compared cross-sectional samples in 3 target populations (pre- and postintervention): community members (attitudes and opinions), pharmacists (opinions and practices), and IDUs (risk behaviors). RESULTS: Among community members (N = 1496) and pharmacists (N = 131), negative opinions of IDU syringe sales decreased in Harlem whereas there was either no change or an increase in negative opinions in the comparison community. Although pharmacy use by IDUs (N=728) increased in both communities, pharmacy use increased significantly among Black IDUs in Harlem, but not in the comparison community; syringe reuse significantly decreased in Harlem, but not in the comparison community. CONCLUSIONS: Targeting the individual and the social environment through a multilevel community-based intervention reduced high-risk behavior, particularly among Black IDUs.

Adolescent↗
PubMedDate not supplied

[Competition for the promotion of essential generic drugs in Africa].

STATEMENT OF THE PROBLEM: in most sub-Saharan countries, an extensive economic crisis coupled with a low level of existing resources has put most pharmaceuticals beyond the reach of the general public. This situation was worsened by the devaluation of the Franc CFA in 1994. The supply of lowprice drugs and the improvement of rational drug use is now a priority. Unfortunately, essential generic drugs are little known and used in Africa. OBJECTIVE: 1. To improve the knowledge of and confidence in essential and generic drugs among providers, prescribers and consumers, through the participation of the general public in an incentive-based, creative competition; 2. To collect locally-adapted promotional material, to be used in the future promotion of essential and generic drugs in Africa. Design, setting and method: a competition was announced in June 1995, via various networks, in French-speaking Africa: the population was invited to create one or several items promoting essential generic drugs. These items included slogans, posters, songs and short plays. Over 550 entries were received before the deadline (15 October 1995), from 22 countries (mostly Sub-Saharan and French-speaking). The entries included 387 slogans, 94 posters, 22 plays, and various (photos, comic strips, songs, poems). RESULTS: 1. Greater awareness of essential generic drugs in Western Africa, through the publicity given to the competition; 2. Selection of a pool of approximately 200 promotional items, produced by the target populations, to be published in a catalog and distributed in African countries; 3. Insights into popular practices and representations of Western medications, and local re-interpretation of the concept. CONCLUSION: this public competition was effective at achieving three important goals: 1. Dynamic promotion (the competition was the opportunity for school projects, radio talkshows, etc. on generic drugs); 2. Re appropriation of a policy, thanks to a participative approach; 3. Analysis of the population's general comprehension of pharmaceuticals, through analysis of competition entries.

Advertising↗