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PubMed1998

[Epidemiology of osteoporosis].

Epidemiological studies have identified osteoporosis as a disease of significant public health impact and have delineated numerous potential risk factors. Nevertheless, it has proven difficult to establish preventive strategies for several reasons. First, there has been no final agreement on the definition of osteoporosis, which has hampered efforts to characterize the magnitude of the problem as a whole. Secondly, as osteoporosis is a multifactorial chronic disorder, effective programs for risk assessment and intervention depend on the development of complex disease models. In summarizing the contributions of epidemiological studies to the current understanding of osteoporosis this review intends to outline the scientific background for the European Vertebral Osteoporosis Study (EVOS) and its successors.

Cross-Sectional Studies↗
PubMed2004

[RPE transplantation: the challenges and the future].

Transplantation of RPE cells represents a potential therapeutic intervention for various retinal degenerations including complex, multifactorial age-related macular degeneration (AMD). Prerequisite for a successful RPE transplantation is the isolation of suitable cells, which must establish themselves in the host eye to develop functionality similar to that of healthy RPE cells in vivo. Autologous cells can be harvested from the peripheral retina. Ex vivo gene manipulation offers the possibility that even a dysfunctional donor RPE cell can be restored to perform a required specific function in the retina which may in turn help prevent or slow down the degenerative process in the host eye. The problem of cultured RPE cells is that they lose many of their normal phenotypic characteristics, which also leads to a reduction of their functional capacity. Currently highly "stressed" RPE cells are transplanted, whether fresh or cultured, which may not establish their normal in vivo functions. The generation of a genetically engineered cell line with all the functions of a healthy RPE cell and the use of retinal stem cells represent alternative and promising approaches for the future.

Forecasting↗
PubMed1977

Feasibility of localizing ectopic testes by 131I-labeled luteinizing hormone scintigraphy.

A new method for localizing ectopic testes preoperatively was investigated in rats. Twenty hours after administration of iodine-131 luteinizing hormone the position of normal descended testes was easily identified by scintigraphy. Clinically, this technique may offer a noninvasive and practical means of locating testes undetected by palpation. The complexity and hazards of the surgical intervention to follow would thus be greatly reduced.

Animals↗
PubMed2005

Improvement of a questionnaire measuring activity limitations in rising and sitting down in patients with lower-extremity disorders living at home.

OBJECTIVE: To improve a self-administered questionnaire that includes 42 dichotomous items and measures activity limitations in rising and sitting down (R&S) in patients with lower-extremity disorders who live at home. DESIGN: Cross-sectional study. SETTING: Outpatient clinics of secondary and tertiary care centers. PARTICIPANTS: Patients (N=759; 47% men; mean age +/- standard deviation, 60.7+/-15.2y) living at home, with lower-extremity disorders resulting from stroke, poliomyelitis, osteoarthritis, amputation, and complex regional pain syndrome type I. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: (1) Unidimensionality, indicating that items assess only a single construct; (2) fit with the one-parameter logistic model (OPLM), yielding information about patient and item location parameters; (3) intratest reliability, indicating consistency of patients' item scores; and (4) content validity, indicating completeness with which the items cover the important aspects of the construct that they are attempting to represent. RESULTS: Thirty-nine of 42 items: (1) loaded on 1 component (variance explained, 59%; item component loadings, >or=.51), (2) showed good fit with the OPLM (P=.15), (3) had a good intratest reliability (Cronbach alpha=.96), and (4) had a good content validity (all important aspects represented). CONCLUSIONS: A unidimensional scale that fits with the OPLM has been developed for measuring activity limitations in R&S in patients with lower-extremity disorders who live at home.

Activities of Daily Living↗
PubMed2005

Developing and implementing emergency medicine programs globally.

International EM development requires a comprehensive assessment of the current system and careful planning to ensure that the most important needs are addressed. Modeling a country's EM system after an existing foreign system underestimates the complex needs for instituting appropriate system interventions. Planning must include all stakeholders. With appropriate planning, international interventions can contribute to health system advancement.

Emergency Medical Services↗
PubMed2004

Vaginal douching among adolescent and young women: more challenges than progress.

The practice of vaginal douching dates back centuries. Numerous studies have shown that douching is quite prevalent and often begins during adolescence. Motivation for the initiation and maintenance of this practice appears complex, and presents challenges to the intervention efforts. The practice of douching remains controversial. Douching has been implicated in numerous adverse reproductive health outcomes such as increased risk for pelvic inflammatory disease, ectopic pregnancy, reduced fertility, and bacterial vaginosis. However, recent studies in developing countries have suggested that in certain circumstances, douching may actually be beneficial. We summarize key findings from the review of published literature and ongoing research, as well as highlight research challenges to our understanding of the role of vaginal douching in reproductive health.

Female↗
PubMed2005

Primary care, social inequalities and all-cause, heart disease and cancer mortality in US counties: a comparison between urban and non-urban areas.

OBJECTIVE: The objective of this study was to test whether the association between primary care and income inequality on all-cause, heart disease and cancer mortality at county level differs in urban (Metropolitan Statistical Area-MSA) compared with non-urban (non-MSA) areas. STUDY DESIGN: The study consisted of a cross-sectional analysis of county-level data stratified by MSA and non-MSA areas in 1990. Dependent variables included age and sex-standardized (per 100,000) all-cause, heart disease and cancer mortality. Independent variables included primary care resources, income inequality, education levels, unemployment, racial/ethnic composition and income levels. METHODS: One-way analysis of variance and multivariate ordinary least squares regression were employed for each health outcome. RESULTS: Among non-MSA counties, those in the highest income inequality category experienced 11% higher all-cause mortality, 9% higher heart disease mortality, and 9% higher cancer mortality than counties in the lowest income inequality quartile, while controlling for other health determinants. Non-MSA counties with higher primary care experienced 2% lower all-cause mortality, 4% lower heart disease mortality, and 3% lower cancer mortality than non-MSA counties with lower primary care. MSA counties with median levels of income inequality experienced approximately 6% higher all-cause mortality, 7% higher heart disease mortality, and 7% higher cancer mortality than counties in the lowest income inequality quartile. MSA counties with low primary care (less than 75th percentile) had significantly lower levels of all-cause, heart disease and cancer mortality than those counties with high primary care. CONCLUSIONS: In non-MSA counties, increasing primary physician supply could be one way to address the health needs of rural populations. In MSA counties, the association between primary care and health outcomes appears to be more complex and is likely to require intervention that focuses on multiple fronts.

Analysis of Variance↗
PubMed2001

Using the nursing minimum data set for the Netherlands (NMDSN) to illustrate differences in patient populations and variations in nursing activities.

RATIONALE: A nursing minimum data set (NMDS) provides data that are useful to legitimate nurses' contribution to healthcare. In Belgium and the US, such NMDS are operational, other countries are developing it, among which is the Netherlands. OBJECTIVE: To evaluate whether the nursing minimum data set for the Netherlands (NMDSN) is suitable to describe the diversity of patient populations and the variability of nursing care. METHODOLOGY: Using the NMDSN data collection forms, patient data were collected from 15 different hospital wards. During one week, nurses manually completed the NMDSN list for every patient. The data analysis methodology from the Belgian MVG was used, including ridit analysis and graphs. RESULTS: The NMDSN includes items related to hospital, patient demographics, medical condition, nursing process, nursing phenomena, nursing interventions, outcomes of nursing care, and complexity of care. There were 686 individual patients in the study, while for the data analysis their 2090 patient days in the hospital were used. Frequencies of nursing phenomena, nursing activities and results of care were calculated, transformed into ridit scores, and presented graphically as 'fingerprints'. CONCLUSION: The set of NMDSN items allows illustrating the diversity of patient populations, and variation in nursing care by means of 'fingerprints'.

Activities of Daily Living↗
PubMed1992

Psychological modulation of the delayed type hypersensitivity skin test.

Considerable data have demonstrated that psychological states can influence the immune system in animals. Whether human immune function can be intentionally modulated by the central nervous system is unknown. This article presents data from two studies that sought to demonstrate intentional modulation of the immune system by psychological interventions. It also discusses the methodological complexities involved with this type of research in humans.

Adult↗
PubMed1999

Adding medications in the emergency department: effect on knowledge of medications in older adults.

INTRODUCTION: Older adults constitute 20% of the ED population. Of older patients discharged from the emergency department, 40% receive at least one new medication to add to their already complex medication regimen. The purpose of this study was to determine the effect of increasing medication complexity on knowledge of newly prescribed medications for older adults discharged from the emergency department. METHODS: The complexity of self-administered medications after ED treatment was measured with the Medication Complexity Index to determine its potential influence on the patient's knowledge of medication. The Knowledge of Medication Subtest, a measure of the effectiveness of medication teaching, was administered by telephone interview 48 to 72 hours after ED discharge. RESULTS: Sixty rural ED patients ranging in age from 60 to 98 years completed the study. Higher medication complexity after the addition of medications in the emergency department was associated with less knowledge of their medications (r = 0.37, P =. 004). DISCUSSION: The increase in medication complexity that results from ED therapeutic intervention may decrease knowledge of medications. A heightened emphasis should be placed on effective medication teaching, counseling, and follow-up for older adult ED patients.

Age Factors↗
PubMed1984

Defining electromechanical dissociation.

Electromechanical dissociation (EMD) implies organized electrical depolarization of the heart without synchronous myocardial fiber shortening and, therefore, without cardiac output. Experimentally EMD can be produced by inducing ventricular fibrillation, not performing cardiopulmonary resuscitation, and applying a defibrillating shock after a few minutes. The result is frequently the restoration of electrical activity of the heart; however, because of diffuse myocardial ischemia, there is no mechanical contraction. The simultaneous electrocardiogram and arterial pressure tracings can reveal a variety of organized ECG rhythms (sinus rhythm, all degrees of heart block, idioventricular rhythm, etc), all without an arterial pressure. Attempts to correct these rhythms with pharmacologic therapy or with pacemakers are of no avail. Therapy must be directed toward the restoration of myocardial perfusion. In contrast, the patient with heart block or other severe bradydysrhythmias in which there is a palpable pulse generated with the QRS complex usually respond well to pharmacologic intervention or pacing. The prognosis of patients with EMD is poor, but rational therapy implies the application of techniques that increase coronary perfusion and thereby decrease the diffuse myocardial ischemia.

Animals↗
PubMed1997

Immunity aging. I. The chronic perduration of the thymus acute involution at puberty? Or the participation of the lymphoid organs and cells in fatal physiologic decline?

The author has focused the subject on the perduration of puberty thymus involution as a cause of immunity aging, a term in which he does not include senescence. The decrease between immune reactions against HIV1 at 25 years of age and those at 35 is considerable; the decrease is also indirectly revealed by spontaneous tumor exponentially growing incidence after 40 years in man and its equivalent, 16 months in mice: the immunity parameters indicate a regression correlated with this incidence growth. He regrets the neglect of suppressor cell and anti-idiotype problems by the basic immunologic research. Given the role of cofactors non specifically related to the antigen, such as that CD28 and its ligands, he suggests the interest to approach immunology via the science of chaos and fractals, which would be more appropriate than classical methodology to study highly complex phenomena on which apparently minimal interventions may induce considerable effects.

Adult↗
PubMed1998

Platelet Inhibition in Cardiovascular Disease Management: Aspirin and Beyond.

Intracoronary thrombosis is the central event in the pathophysiology of the acute coronary syndromes and of the complications of percutaneous coronary intervention. Hemostasis and thrombosis involve a complex series of interactions of both platelets and the coagulation system. Standard antithrombotic therapy for cardiovascular disease typically combines use of antiplatelet therapy with aspirin and antithrombin therapy with heparin. Ticlopidine appears to be a reasonable alternative as an antiplatelet agent in the patient who is intolerant of aspirin. The combination of ticlopidine and aspirin may be especially effective in preventing coronary events in the post-coronary stenting patient. Clopidogrel may offer incremental benefit beyond aspirin in a broad array of vascular diseases, but the cost effectiveness of such a strategy remains to be determined. Finally, potent antiplatelet therapy with platelet glycoprotein IIb/IIIa receptor inhibition clearly improves angioplasty outcomes and may have a role in the treatment of patients with acute coronary syndromes.

Journal Article↗
PubMed1997

Mitochondrial implication in accidental and programmed cell death: apoptosis and necrosis.

Both physiological cell death (apoptosis) and at least some cases of accidental cell death (necrosis) involve a two-step-process. At first level, numerous physiological or pathological stimuli can trigger mitochondrial permeability transition which constitutes a rate-limiting event and initiates the common phase of the death process. Mitochondrial permeability transition (PT) involves the formation of proteaceous, regulated pores, probably by apposition of inner and outer mitochondrial membrane proteins which cooperate to form the mitochondrial PT pore complex. Inhibition of PT by pharmacological intervention on mitochondrial structures or mitochondrial expression of the apoptosis-inhibitory oncoprotein Bcl-2 thus can prevent cell death. At a second level, the consequences of mitochondrial dysfunction (collapse of the mitochondrial transmembrane potential, uncoupling of the respiratory chain, hyperproduction of superoxide anions, disruption of mitochondrial biogenesis, outflow of matrix calcium and glutathione, and release of soluble intermembrane proteins) can entail a biogenetic catastrophe culminating in the disruption of plasma membrane integrity (necrosis) and/or the activation and action of apoptogenic proteases with secondary endonuclease activation and consequent oligonucleosomal DNA fragmentation (apoptosis). The acquisition of the biochemical and ultrastructural features of apoptosis critically relies on the liberation of apoptogenic proteases or protease activators from the mitochondrial intermembrane space. This scenario applies to very different models of cell death. The notion that mitochondrial events control cell death has major implications for the development of death-inhibitory drugs.

Animals↗
PubMed1994

Apoptosis and its role in human disease.

In a landmark paper published over two decades ago, Kerr et al. proposed the term apoptosis "for a hitherto little recognized mechanism of controlled cell deletion, which appears to play a complementary but opposite role to mitosis in the regulation of animal cell populations". In the ensuing years, this natural cell death process was studied at the basic science level, primarily with a view to understanding its roles in cancer and in the development and maintenance of the immune system. More recently, however, evidence has suggested a role for the failure of normal apoptosis control in many of the major diseases of the industrialized world. Though complex, apoptosis appears amenable to therapeutic intervention. The range of modern pharmaceutical strategies available to treat such disregulated gene-directed processes offers promise for advances in the control of cancer, immune system and neurodegenerative disorders, heart disease, and perhaps even the aging process itself.

Aging↗
PubMed2002

MAPPIT: a cytokine receptor-based two-hybrid method in mammalian cells.

Identifying novel targets for therapy in allergic disease: protein interactions inside the cell Therapy of allergic disease currently relies on pharmacological manipulation of mediators or immunotherapy. Drugs have been developed to target specific mediators and their receptors: for example antihistamines blocking the H1 receptor have been refined to maximize antagonism and reduce central side-effects or adverse effects of activity on other receptors such as muscarinic cholinergic receptors. Traditional pharmacological approaches identify new surface receptors against which chemists will then design or screen compounds for activity: examples are H3 or H4 histamine receptors. With the advent of the sequenced human genome we are faced with a vast array of genes and proteins that interact to define normal physiology or indeed pathology. A major challenge to biotechnology is to evolve novel techniques to understand the function and interaction of these myriad proteins. One particular area of current interest is the signalling cascades downstream of surface receptors. For many years pathways have appeared overlapping and to offer little chance of specific intervention. However, greater understanding of the complexity and integration of signalling, together with the possibility of directing drugs to specific cells has aroused considerable interest in this area for novel therapeutics. Indeed, targeting events within the cell has been done for many years with steroids. Here, Jan Tavernier and colleagues describe some signalling pathways relevant to allergic disease and potential methods for understanding protein interactions that allow mapping of the cascades. In particular they describe an elegant new system of analysis of protein-protein interactions in a mammalian system, which they have developed, termed MAPPIT. The basis of the system is an engineered receptor with JAK kinase but which lacks STAT activation sites. To the cytoplasmic end of the receptor is added a bait protein of interest, and the cell line can then be transduced with plasmid containing 'prey' cDNA from a library of interest linked to an active STAT binding site. If this cDNA encodes a protein which, upon expression, is activated and recruited to the membrane complex, it will bind to the receptor via the bait, then STAT activation will occur and activate a reporter gene system such as luciferase or puromycin resistance. This novel system allows study of known protein-protein interactions by targeted mutagenesis, or screening for novel interactions. It has the advantage over existing systems such as yeast 2 hybrid that it uses mammalian cells and thus can reproduce the physiological conditions for protein processing or activation. As new genes and proteins are linked to the atopic phenotypes, systems such as this hold promise of rapidly defining their function and interacting proteins and may be important in linking genomics and proteomics with function and pharmacology in the future.

Animals↗