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[Ischemic or non-ischemic central artery occlusion. An explanation for the development or lack of development of neovascularization].

In a retrospective study we analyzed 29 central retinal artery occlusions (CRAO) with reference to the findings of ophthalmodynamometry (ODM) and fluorescein angiograms (FLA). We tried to find explanations for the relatively low rate of neovascularization in CRAO and predictive constellations for CRAO that will develop neovascularization. In 5 eyes the pathologic findings were classed as ischemic ophthalmopathy because of carotid or ophthalmic artery stenosis: 2 of these 5 eyes showed iris neovascularization (rubeosis iridis), while the other 3 "only" showed a CRAO with no clinical signs of ischemic ophthalmopathy. Of the remaining 24 eyes with CRAO there were 2 eyes with rubeosis iridis, which could be attributed to the CRAO itself (8.3%). FLA revealed ischemic perfusion of the retina in these 2 cases. ODM revealed reperfusion of the central artery (CRA) in 17 of 25 eyes with CRAO (71%) within the first 2 weeks. In 2 blind eyes that were re-examined 3 and 5 months after CRAO no iris or retinal neovascularization was found despite persisting malperfusion of CRA. In these 2 cases the minimal retinal perfusion needed because of complete retinal necrosis was sufficient explanation for the nonevolution of neovascularization. If ischemia is the essential condition for neovascularization, we can propose two explanations for non-development of neovascularization after CRAO: either there is adequate recanalization (majority of cases) or the need for perfusion is minimal or zero. Only in cases of persisting malperfusion and partially surviving retinal tissue (function!) will neovascularization perhaps develop. ODM is an adequate method of estimating the perfusion of CRA.

Blood Flow Velocity↗

Developing intervention/prevention strategies for individuals at high risk of developing hereditary ovarian cancer.

In 1994, an estimated 24,000 new cases of ovarian cancer will be diagnosed in the United States. Most of these patients will have disease spread beyond the ovary at the time of diagnosis; despite tumor debulking and aggressive platinum-based chemotherapy, their long-term prognosis is poor. In view of the advanced stage of disease at the time of diagnosis and the poor results of conventional therapy, advances in early detection and/or prevention are desperately needed. The recent recognition that a family history of the disease is perhaps the strongest risk factor for the development of ovarian cancer offers a unique opportunity to identify women at high risk for ovarian cancer and to develop effective screening methods and prevention/intervention strategies for these high-risk women. The results of the breakout session "Developing Strategies for Intervention/Prevention Trials for Individuals at Risk of Hereditary Ovarian Cancer" are summarized here. The majority of the discussion in this session focused on three major issues: 1) identification of moderate- and high-risk individuals who would potentially benefit from screening, prevention, and intervention efforts; 2) assessment of the effectiveness of current screening modalities and the usefulness of current intervention/prevention strategies; and 3) recommendations for clinical trial design.

Clinical Trials as Topic↗

Postnatal development and the differential expression of presynaptic terminal-associated proteins in the developing retina of the Brazilian opossum, Monodelphis domestica.

In the present study we have characterized the postnatal (PN) development of the retina in the Brazilian opossum, Monodelphis domestica. Monodelphis, a small, pouchless marsupial, undergoes a protracted period of postnatal development. Using bromodeoxyuridine immunohistochemistry, we have investigated postnatal neurogenesis of the retina. In addition, we have examined the differentiation of the retina by using antibodies directed against the presynaptic terminal-associated proteins synaptotagmin, Rab3A, synaptophysin and synaptosomal-associated protein-25 (SNAP-25), and have characterized their spatial and temporal distribution during postnatal development. This study is the first systematic comparison of the developmental expression of multiple presynaptic terminal-associated proteins in relation to retinal neurogenesis and differentiation. At birth (1PN), the Monodelphis retina was relatively undifferentiated morphologically and birthdating analysis revealed mitotically active cells throughout the retina. The 8PN retina was organized into two cellular layers: an outer region of mitotically active neuroepithelial cells and an inner region of postmitotic cells. The inner plexiform layer formed between 5PN and 10PN, and exhibited unique patterns of immunoreactivity with the antibodies used in this analysis. By 25PN the retina was well laminated, and synaptotagmin-, Rab3A-, synaptophysin- and SNAP-25-like immunoreactivities exhibited distinct and specific patterns within the plexiform layers, although they had not yet achieved their mature, adult patterns. These results indicate that each of these proteins exhibits developmentally regulated changes in its cellular localization, and therefore may play important roles during morphogenesis and synaptogenesis of the vertebrate retina.

Animals↗

Developing curricula to promote preventive medicine skills. The Teaching Immunization for Medical Education (TIME) Project. TIME Development Committee.

CONTEXT: Vaccines are underused in the United States, resulting in needless morbidity. Many experts have concluded that clinician education is critical to increasing the nation's vaccination rates. OBJECTIVE: To develop and evaluate case-based curricular materials on immunizations that promote preventive medicine skills. DESIGN: Before-and-after trial of an educational intervention. SETTING AND PARTICIPANTS: Medical schools and primary care residency programs from 20 institutions across the United States participated in the Teaching Immunization for Medical Education (TIME) project. INTERVENTION: A multidisciplinary team developed learning objectives, abstracted clinical cases, and created case-based modules that use contextual learning and small-group interaction to solve clinical and public health problems. The case-based methods are multistation clinical teaching scenarios (MCTS) and problem-based learning (PBL). MAIN OUTCOME MEASURES: Knowledge gained by learners from pretest to posttest and the overall ratings of the sessions by learners and facilitators based on evaluation questionnaires. RESULTS: Pretest and posttest results were obtained on a total of 1122 learners for all modules combined. For the MCTS method, mean scores increased from the 10-item pretest to the posttest by 3.1 items for measles, 3.8 for influenza, 1.8 for hepatitis B, 3.9 for pertussis, 1.9 for adult vaccination, 1.9 for childhood vaccination, and 2.6 for Haemophilus influenzae type b (P<.01 for each). For the PBL method, mean scores increased by 3.4 items for measles, 3.3 for influenza, 2.6 for hepatitis B, and 2.5 for pertussis (P<.01 for each). Most learners (MCTS, 98%; PBL, 89%) and most facilitators (MCTS, 97%; PBL, 100%) rated the sessions overall as very good or good. CONCLUSIONS: Use of TIME modules increases knowledge about immunizations, an essential step to improving vaccination practices of future clinicians. Given the realities of decreased faculty time and budgets, educators face major challenges in developing case-based curricula that prepare learners for the 21st century. Nationally tested libraries of cases such as the TIME modules address this dilemma.

Adult↗

Evolutionarily conserved mechanisms regulating neural development: lessons from the development of Drosophila peripheral nervous systems.

Functions of genes regulating the development of Drosophila peripheral nervous systems are summarized herein. These genes can be classified into 6 groups: <1> prepattern genes, <2> proneural genes, <3> neurogenic genes, <4> neuronal precursor genes, <5> neuronal precursor type selector genes, and <6> cell-division and lineage genes. The mechanisms described herein provide excellent paradigms in the regulation of the development of other tissues in Drosophila, as well as in other organisms, including vertebrates. The roles of two different inhibitory mechanisms, i.e. Notch-signaling and Argos, in the development of Drosophila neural precursor cells are also discussed.

Animals↗

Distribution of TAG-1 and synaptophysin in the developing cerebellar cortex: relationship to Purkinje cell dendritic development.

During postnatal cerebellar development, differentiating Purkinje cell (PC) dendrites extend towards the pial surface and progressively contact immature granule cell parallel fiber (PF) axons in the deep external granule layer (EGL), thus forming a zone of synaptic contact called the molecular layer (ML). The neuronal cell adhesion molecule, TAG-1, is transiently expressed on PF axons in the deep EGL (Yamamoto et al. [1986] J. Neurosci. 12:3576-3594). To determine the spatiotemporal relationship between Purkinje cell dendritic differentiation and the cessation of TAG-1 expression, sagittal sections from developing rat cerebellum were double-labeled for TAG-1 and the Purkinje cell-specific marker, calbindin, by using indirect immunofluorescence. At postnatal day 2 (P2) and P5, confocal microscopy revealed that TAG-1 immunoreactivity began above the furthest superficial extent of the Purkinje cell apical dendritic cap. By P10, PC dendrites penetrated partially into the TAG-1-positive deep EGL, creating a narrow region of overlap in TAG-1/calbindin staining at the deep EGL/ML border. In contrast, at P15 and P20, TAG-1 staining began directly above the furthest superficial extent of the Purkinje cell dendrites, with little or no overlap in TAG-1/calbindin staining. Staining for the synaptic vesicle glycoprotein, synaptophysin, was dim throughout most of the TAG-1-positive deep EGL, although bright synaptophysin immunoreactivity was observed throughout the ML. Overlap in TAG-1/synaptophysin staining was observed primarily at the deep EGL/ML border, suggesting that robust expression of synaptophysin in granule cells does not begin until after contact with Purkinje cell dendrites has been initiated. Our results suggest that factors present in the developing ML may influence the cessation of TAG-1 expression and the initiation of synaptophysin expression at the border region between the ML and the deep EGL.

Animals↗

Leadership development: a collaborative approach to curriculum development and delivery.

The Leadership Programme in the National Health Service, Lanarkshire, Scotland began in 2002. The programme has been endorsed by the employer, accredited by a higher education institution and approved by the National Health Service Education Board in Scotland as a recognised continuing professional development programme. The success of the programme is due to the combined efforts of the teaching team from the Practice Development Centre, the different stakeholders within the health service in Lanarkshire and Queen Margaret University College, Edinburgh. The focus of this article is the nature of the collaboration between the partners from the initial ideas to the initiation, validation and ongoing delivery of the programme. The article will provide an account of the criteria for partners and key features of the collaboration as well as quality assurance aspects. It will also draw upon the outcomes of the programme in terms of student views and achievement as well as the benefits to the partners.

Adult↗

Chapter 28: Studies to assess the long-term efficacy and effectiveness of HPV vaccination in developed and developing countries.

We review studies of the implementation of human papillomavirus (HPV) vaccination programmes in developed and developing countries. The review spans the period from establishment of long-term vaccine efficacy follow-up studies, operational research on issues of vaccine preparedness, and relevant predictive modelling studies during the pre-licensure phase to plans of phase IV effectiveness trials, forms of epidemiological surveillance, and further operational research in the post-licensure phase. Much of the research is already ongoing. Depending on the results of the planned immuno bridging studies among HIV-negative and HIV-positive women, further phase III and/or phase IV trials may be warranted.

Developed Countries↗

Can a developed country's maternal mortality review be used as the 'gold standard' for a developing country?

BACKGROUND: Relative to other public health problems, maternal mortality ratio (MMR) differences between developed and developing countries are greater than expected. South Africa (SA) produced its first national report on maternal deaths in 1998. UK's last report covered the period 1994-1996. OBJECTIVE AND METHOD: Compare the two reports to document reasons for the MMR differences using the Safe Motherhood analytical model of maternal mortality as a template. RESULTS: The MMR for SA was estimated to be 12.3 times greater than the UK's. Under-reporting was bigger in SA. Substandard medical care was common, but other quality of care issues were not assessed. Disease pattern differences included AIDS, non-pregnancy-related infections and postpartum haemorrhage in SA compared to thromboembolism and medical disorders in the UK. Autopsies were problematic. Demographic differences centred around ethnic origins. Biological differences may involve the immune system. Socio-economic or behavioural factors were not documented. CONCLUSIONS: Awareness of the magnitude of the problem requires better data collection systems. Sepsis and HIV/AIDS are a major problem in SA. Beyond the mutually common problem of substandard medical care, other quality of care issues were inadequately assessed.

Behavior↗

Utility of the MacArthur-Bates communicative development inventory in identifying language abilities of late-talking and typically developing toddlers.

The present study investigated the validity of the MacArthur-Bates Communicative Development Inventory (CDI) for a group of toddlers 30 months of age. Study 1 examined the concurrent validity of the CDI for a group of 38 late talkers. Significant correlations were found between the CDI and direct measures of language abilities. Study 2 used likelihood ratio analysis to determine how well the CDI sorted 100 toddlers (38 late talkers and 62 children with a history of normal language development) according to language status based on direct assessment measures. The analyses showed that the CDI was effective in identifying children with low language skills up to the 11th percentile and in identifying children with normal language skills above the 49th percentile.

Case-Control Studies↗

Screening for cervical cancer: different problems in the developing and the developed world.

Cervical cancer incidence and mortality has been reduced by effective screening programmes particularly in British Columbia and the Nordic countries. There remains two outstanding problems. The first is overtreatment of dysplasia in the developed world. However, in the developing world cervical cancer is the most important female cancer. In these countries the Western model of cytology based screening is impractical and inappropriate. New strategies of better health education and novel methods of screening such as visual inspection are the most cost-effective means of reducing mortality from this cancer.

Developed Countries↗

The development of complex sentence interpretation in typically developing children compared with children with specific language impairments or early unilateral focal lesions.

This study compared sentence comprehension skills in typically developing children 5-17 years of age, children with language impairment (LI) and children with focal brain injuries (FL) acquired in the pre/perinatal period. Participants were asked to process sentences 'on-line', choosing the agent in sentences that varied in syntactic complexity (actives, passives, subject clefts and object clefts), and in the presence or absence of a subject-verb agreement contrast. Results revealed that accuracy and processing speeds vary with syntactic complexity in all groups, reflecting the frequency and regularity of sentence types. Developmental changes continued throughout childhood, as children became faster and more accurate at processing more complex sentence structures. Children with LI and children with FL were quite profoundly delayed, displaying profiles similar to, or more impaired than those of younger children, but there was no evidence in the FL group for a disadvantage in left- vs. right-hemisphere-damaged children. Children with LI showed one unique pattern: higher than normal costs (reflected in reaction times) in using converging information from subject-verb agreement, in line with studies suggesting special vulnerabilities in grammatical morphology in this group. Results are discussed in terms of the Competition Model, a theory of language processing designed to account for the statistical changes in performance that are observed during development, and the probabilistic deficits in children with language impairments.

Adolescent↗

VD education in developing countries. A comparison with developed countries.

No new method of control of the sexually transmitted diseases is imminent. Reliance has to be placed on existing methods including health education. Health education has a double role, being a primary method in its own right, and--of equal or greater importance--being involved in the enforcement of all of the other tried methods. A comparison is made of the situation in countries with a developed or an underdeveloped venereal disease control service, in respect of organization, statistical reporting, the various agencies treating venereal disease, clinic and diagnostic facilities, personnel concerned in venereal disease management, and other aspects. The vicious circle inherent in developing countries is outlined. A lack of awareness of the extent of the problem and the presence of other serious competing diseases lead to a low budget, thence to poor diagnostic and treatment facilities, and to few cases being seen in the official clinics and hospitals. Thus relatively small numbers of cases are reported and there is consequently a continuing lack of awareness of the problem. A method of cutting through such a circle is suggested, and the importance of health education activities during this period is emphasized.

Developing Countries↗

PAX8, TITF1, and FOXE1 gene expression patterns during human development: new insights into human thyroid development and thyroid dysgenesis-associated malformations.

Thyroid dysgenesis (TD) is responsible for most cases of congenital hypothyroidism, a condition that affects about one in 4000 newborns. Mutations in PAX8, TITF1, or FOXE1 may account for congenital hypothyroidism in patients with either isolated TD or TD with associated malformations involving kidney, lung, forebrain, and palate. Pax8, titf1, and foxe1 are expressed in the mouse thyroid bud as soon as it differentiates on the pharyngeal floor. Because the spatio-temporal expression of these genes is unknown in humans, we decided to study them at different stages of human embryonic and fetal development. PAX8 and TITF1 were first expressed in the median thyroid primordium. Interestingly, PAX8 was also expressed in the thyroglossal duct and the ultimobranchial bodies. Human FOXE1 expression was detected later than in the mouse. PAX8 was also expressed in the developing central nervous system and kidney, including the ureteric bud and the main collecting ducts. TITF1 was expressed in the ventral forebrain and lung. FOXE1 expression was detected in the oropharyngeal epithelium and thymus. In conclusion, the expression patterns described here show some differences from those reported in the mouse. They explain the malformations associated with TD in patients carrying PAX8, TITF1, and FOXE1 gene mutations.

Animals↗

The effect of ethanol upon early development in mice and rats. XXII. The effect of chronic consumption of nonalcoholic beer upon preimplantation development in rats.

The effect upon preimplantation development of chronic consumption of nonalcoholic beer was investigated in rats (controlled on day 5 of pregnancy) by using the following criteria: mean number of embryos/animal, oviductal-uterine migration of embryos, developmental rate and number of pathologically modified embryos. It resulted that this beverage had a noxious effect (less marked than normal beer) upon preimplantation development, manifested by the decrease of the mean number of embryos/animal and the presence of abnormal embryos. These results suggest a possible action of various congeners present in this beverage, which potentiate the noxious effect of ethanol in the case of normal beer.

Animals↗

Gap-Junctional communication between developing Drosophila muscles is essential for their normal development.

Recent experiments have demonstrated that a family of proteins, known as the innexins, are structural components of invertebrate gap junctions. The shaking-B (shak-B) locus of Drosophila encodes two members of this emerging family, Shak-B(lethal) and Shak-B(neural). This study focuses on the role of Shak-B gap junctions in the development of embryonic and larval muscle. During embryogenesis, shak-B transcripts are expressed in a subset of the somatic muscles; expression is strong in ventral oblique muscles (VO4-6) but only weak in ventral longitudinals (VL3 and 4). Carboxyfluorescein injected into VO4 of wild-type early stage 16 embryos spreads, via gap junctions, to label adjacent muscles, including VL3 and 4. In shak-B2 embryos (in which the shak-B(neural) function is disrupted), dye injected into VO4 fails to spread into other muscles. In the first instar larva, when dye coupling between muscles is no longer present, another effect of the shak-B2 mutation is revealed by whole-cell voltage clamp. In a calcium-free saline, only two voltage-activated potassium currents are present in wild-type muscles; a fast IA and a slow IK current. In shak-B2 larvae, these two currents are significantly reduced in magnitude in VO4 and 5, but remain normal in VL3. Expression of shak-B(neural) in a shak-B2 background fully rescues both dye coupling in embryonic muscle and whole-cell currents in first instar VO4 and 5. Our observations show that Shak-B(neural) is one of a set of embryonic gap-junction proteins, and that it is required for the normal temporal development of potassium currents in some larval muscles.

Animals↗

Histologic, morphometric, and immunocytochemical analysis of myometrial development in rats and mice: I. Normal development.

Myometrial development from the prenatal to adult period was examined in rats and mice 1) by histologic and immunocytochemical methods with anti-actin, -vimentin, and -laminin to assess cytodifferentiation of smooth muscle and fibroblastic cells; and 2) by morphometric procedures to assess quantitatively the expression of cellular orientation in the emerging inner circular myometrial layer. Uterine mesenchymal cells initially were uniformly vimentin-positive, undifferentiated, and randomly oriented during the late fetal period. By the early neonatal period, three mesenchymal layers became recognizable histologically, the middle one of which (prospective circular myometrium) developed distinct circular orientation and differentiated into a layer composed of actin-positive smooth muscle cells. The cells of the inner mesenchymal layer initially exhibited radial orientation. By 10 days postpartum, the outer longitudinal mesenchymal layer differentiated into bundles of smooth muscle cells representing the longitudinal myometrium. The inner mesenchymal layer remained vimentin-positive and differentiated into the randomly ordered endometrial stroma. The cells of the middle and outer mesenchymal layers that were destined to form myometrium initially expressed vimentin throughout and then coexpressed vimentin and actin, but with time vimentin staining disappeared in the maturing smooth muscle cells as they expressed actin.

Actins↗