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PubMed2004

Minor neurological dysfunction, cognitive development, and somatic development at the age of 3 to 7 years after dexamethasone treatment in very-low birth-weight infants.

The objective of this study was to assess minor neurological dysfunction, cognitive development, and somatic development after dexamethasone therapy in very-low-birthweight infants. Thirty-three children after dexamethasone treatment were matched to 33 children without dexamethasone treatment. Data were assessed at the age of 3-7 years. Dexamethasone was started between the 7th and the 28th day of life over 7 days with a total dose of 2.35 mg/kg/day. Exclusion criteria were asphyxia, malformations, major surgical interventions, small for gestational age, intraventricular haemorrhage grades III and IV, periventricular leukomalacia, and severe psychomotor retardation. Each child was examined by a neuropediatrician for minor neurological dysfunctions and tested by a psychologist for cognitive development with a Kaufman Assessment Battery for Children and a Draw-a-Man Test. There were no differences in demographic data, growth, and socio-economic status between the two groups. Fine motor skills and gross motor function were significantly better in the control group (p<0.01). In the Draw-a-Man Test, the control group showed better results (p<0.001). There were no differences in development of speech, social development, and the Kaufman Assessment Battery for Children. After dexamethasone treatment, children showed a higher rate of minor neurological dysfunctions. Neurological development was affected even without neurological diagnosis. Further long-term follow-up studies will be necessary to fully evaluate the impact of dexamethasone on neurological and cognitive development.

Child↗

PubMed2004

Time course of development of posterior vitreous detachment in the fellow eye after development in the first eye.

PURPOSE: To determine when posterior vitreous detachment (PVD) develops in the fellow eye after development in the first eye. DESIGN: Prospective, observational case series. PARTICIPANTS: Fifty-one patients with acute unilateral PVD participated in the study. METHODS: All patients underwent a comprehensive ocular examination, including a dynamic vitreous examination using biomicroscopy with and without a preset lens and retinal examination with scleral depression, every 3 months at least until PVD developed in the fellow eye. RESULTS: Posterior vitreous detachment developed in 4 eyes (8%) within 6 months, 12 eyes (24%) within 1 year, 24 eyes (47%) within 18 months, 33 eyes (65%) within 2 years, 41 eyes (80%) within 30 months, and 46 eyes (90%) within 3 years. In 5 eyes (10%), PVD did not develop during the follow-up period of more than 3 years. CONCLUSIONS: Posterior vitreous detachment develops frequently in the fellow eye from 6 months to 2 years after development in the first. These findings are useful for the management of patients with unilateral PVD.

Aged↗

PubMed2005

[Occupational allergic contact dermatitis from color developers used in automatic developing].

The color developers CD2, CD3 and CD4 and the black-and-white developer TSS are well known contact allergens that affect those who work in photographic processing. The frequency of occupational allergic contact dermatitis from color developers has decreased in recent years because of the fact that most photo developing takes place automatically, reducing exposure to different chemicals used in developing. We present a case of occupational allergic contact dermatitis in a non-atopic male who had worked for the last 5 years in a photography shop equipped with an automatic developing machine. The clinical morphology of the lesions was eczematous, and the patch tests showed contact sensitization to CD2, CD3, CD4 and TSS. The clinical symptoms cleared up when direct contact with the developing product containing CD3 and CD4 was avoided.

Adult↗

PubMed1982

The development of clinical tuberculosis following infection with tubercle bacilli. 1. A theoretical model for the development of clinical tuberculosis following infection, linking from data on the risk of tuberculous infection and the incidence of clinical tuberculosis in the Netherlands.

Information on the risk of tuberculous infection in the Netherlands has been linked with information on the incidence of tuberculosis, in an attempt to estimate the risks of developing the disease following infection or reinfection. It was postulated that: (a) those with a recent primary infection had a characteristic risk of developing progressive primary tuberculosis; (b) those with a distant (i.e. not recent) primary infection and a recent reinfection had a characteristic risk of developing exogenous tuberculosis; and (c) those with a distant primary infection but no recent reinfection had a characteristic risk of developing endogenous tuberculosis. The information on the risk of tuberculous infection was used to estimate the size of the population in each of these infection classes for different age-groups and calendar years in the Netherlands. Using multiple regression to link these population figures with the information on tuberculosis incidence in the same age group and calendar year, it was possible to estimate the above risks of developing tuberculosis. For Netherlands males aged 15-69 years during the period 1951-70 the three risks of developing pulmonary tuberculosis were estimated to be: (a) 5.06 per cent annually (for 5 years) following primary infection; (b) 1.91 per cent annually (for 5 years) following reinfection; (c) 0.0253 per cent annually, after the first 5 years following primary infection, in the absence of reinfection. The corresponding (and significantly different) estimated annual risks of development of pulmonary tuberculosis for females were 5.85, 1.10 and 0.0020 per cent respectively. From these risks, it may be estimated that the degree of protection conferred by a distant primary infection, against pulmonary tuberculosis arising from a recent reinfection, was 63 per cent for males and 81 per cent for females. The estimated relative proportions of cases of progressive primary, exogenous and endogenous tuberculosis varied considerably with age and calendar year. Progressive primary tuberculosis was dominant at the younger ages, exogenous and endogenous tuberculosis at older ages. At these older ages, the great majority of cases in the Netherlands in the early 1950s appeared to be exogenous in origin, but by 1970, with the decrease in the risk of infection, the exogenous contribution had dwindled substantially, especially among males.

Adolescent↗

PubMed2004

Development of overweight associated with childbearing depends on smoking habit: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

OBJECTIVE: To prospectively evaluate whether childbearing leads to development of overweight in women and to evaluate the role of other known risk factors. RESEARCH METHODS AND PROCEDURES: A prospective, multicenter observational study, the Coronary Artery Risk Development in Young Adults (CARDIA) Study from 1986 to 1996, examined subjects at baseline and in follow-up years 2, 5, 7, and 10. Included were 998 (328 black and 670 white) nulliparous women, age 18-30 years, who were not overweight at baseline. Relative odds for incident overweight (BMI > or = 25 kg/m2) associated with parity change (0, 1, or 2+) and risk factors were estimated using discrete-time survival models adjusted for baseline and time-dependent covariates. RESULTS: Parity change-association with development of overweight depended on smoking habit (interaction, p < 0.001). In multivariate adjusted models, 1 and 2+ births vs. 0, respectively, were associated with increased risk for development of overweight among never smokers [odds ratio (OR) = 2.66; 95% confidence interval (CI): 1.80, 3.93, and 2.10, 95% CI: 1.24, 3.56] and decreased risk among current smokers (OR = 0.41; 95% CI: 0.17, 0.96, and 0.36, 95% CI: 0.08, 1.65). Risk was increased for black vs. white race (OR = 3.49; 95% CI: 2.59, 4.69), frequent weight cycling (OR = 1.45; 95% CI: 1.03, 2.04), and high school education or less (OR = 2.21; 95% CI: 1.50, 3.26) and was decreased for highest physical activity quartile (OR = 0.62; 95% CI: 0.43, 0.90). DISCUSSION: Childbearing contributes to development of overweight in nonsmokers but not in smokers, where development of overweight is less likely in women who bear children. Race, education, and behaviors are important factors in development of overweight in young women.

Adolescent↗

PubMed2001

Selective development of a strong Th2 cytokine profile in high-risk children who develop atopy: risk factors and regulatory role of IFN-gamma, IL-4 and IL-10.

BACKGROUND: The immunological processes in early life and their relation to allergic sensitization leading to a Th2 cytokine profile are still not well understood. OBJECTIVE: To analyse the environmental and genetic risk factors and immunological responses at birth in relation to the development of atopic disease at 12 months of age in a longitudinal study of high-risk children. METHODS: High-risk children were followed from birth till 12 months of age. Mononuclear cells obtained at birth and 6 and 12 months thereafter were analysed for their proliferative and cytokine responses after polyclonal and allergen-specific stimulation. RESULTS: At 12 months of age 25% children had developed an atopic disease. Two atopic parents, parental smoking and atopic dermatitis of at least one of the parents were significant risk factors. In cord blood of newborns who developed atopy, an increased percentage of CD4+CD45RO+ cells and an increased polyclonal-stimulated proliferation were observed. Furthermore, an impaired allergen-induced, but not polyclonal-stimulated IFN-gamma production was found, suggesting a regulatory defect. At 6 and 12 months of age, a strong Th2 profile (characterized by increased levels of IL-4, IL-5, and IL-13) after both polyclonal and, to a lesser extent, allergen-specific stimulation was found in the children developing atopy. Allergen-induced IL-10 production at 12 months of age was only observed in the non-atopic children. CONCLUSION: Our data indicate that the first 6 months of life represent a critical time window for the initiation of immunological changes resulting in the development of atopy. The selective development of a Th2 cytokine profile in high-risk children who develop atopy is due to increased production of Th2 cytokines, possibly caused by impaired allergen-induced IFN-gamma production in the neonatal period. Furthermore, the decreased allergen-induced IL-10 levels observed in the atopic children at 12 months of age may result in a lack of down-regulation of the inflammatory process.

Allergens↗

PubMed2001

Ward sisters' objectives in developing nursing and problems with development.

AIM: The study aimed at ascertaining the objectives, development strategies and problems of ward sisters in developing nursing. BACKGROUND: More knowledge is needed of first-line management in order to be able to develop organizations and ward sisters' professional training. METHODS: Data collection was by a questionnaire completed by 37 ward sisters in two Finnish hospitals. Thirty-six ward sisters responded to the open-ended questions and their answers were analysed using content analysis. FINDINGS: As for their objectives, ward sisters emphasized a functioning working community and good care. Good care was based on a variety of theoretical ideas, on the quality and economy of care. The means by which these objectives could be achieved were process thinking, reflection on action, leadership and the development of the working community. The leadership strategies mentioned were profit management and participatory leadership. In developing the working community, ward sisters relied on collaboration, good climate and training. Ward sisters' problems with developing nursing care were related to resources, work organization and the working community. CONCLUSIONS: Besides expertise in nursing, ward sisters are required to have skills in leading and developing the working community, collaboration and especially the ward's climate.

Adult↗

PubMedDate not supplied

Development and use of biomarkers in oncology drug development.

Successful development and use of biomarkers will improve the productivity of oncology drug development. Recognition of the importance of biomarkers for speeding drug development is reflected in the precise definitions and concepts proposed by an NIH Working Group to standardize terminology and promote a more coherent and systematic approach to the development and use of biomarkers. Potential clinical biomarkers of drug efficacy are often identified through pre-clinical studies or basic research. Identification of potential biomarkers for use in oncology is moving rapidly forward through continuing advances in clinical imaging technologies, especially molecular and functional imaging. Other rapid advances are a product of the growing availability of new scientific reagents for established technologies and of high-throughput genomic and proteomic technologies that can generate hundreds of potential biomarkers for further evaluation. In certain cases, conventional clinical diagnostic techniques or assays can be adapted for use in pre-clinical models to evaluate their ability to serve as biomarkers for predicting clinical responses to new drug candidates. Evaluation (pre-clinical and clinical) of a potential biomarker is often the longest stage of biomarker development, and standards for evaluation or validation depend on the intended use and stage of clinical development. Biomarkers verified for use in preclinical studies can be used to help select appropriate animal models and lead compounds. Biomarkers verified for use in clinical trials can confirm a drug's pharmacological or biological mechanism of action, guide protocol design, aid patient and dose selection, and help to minimize safety risks. Oncology drug development can be optimized by using a tiered set of clinical biomarkers that predict compound efficacy and safety with increasing confidence at each rise in tier thereby aiding corporate decision-making about advancing compounds. In oncology, a special class of extensively evaluated biomarkers of efficacy (surrogate endpoints) that generally correlate with desired clinical outcomes can be used as a basis for corporate decisions as well as for gaining accelerated provisional regulatory approval of a drug.

Animals↗

PubMed1998

A novel mammalian wnt gene, WNT8B, shows brain-restricted expression in early development, with sharply delimited expression boundaries in the developing forebrain.

Our current knowledge of mammalian forebrain development is meagre. The comparatively few relevant anatomical landmarks are, however, being supplemented by gene expression studies which are able to identify subsets of anatomical structures. We previously described cloning, subchromosomal localization and preliminary structural characterization of the human WNT8B gene, the first mammalian Wnt8b gene to be reported. Wnt genes encode intercellular signalling molecules which play a variety of critical roles in early development, including, in several cases, a presumed role in brain development. In the current report we present the full-length cDNA sequence and genomic organization of the human Wnt8b gene and report studies of expression of the Wnt8b gene in human and mouse embryos. The human and mouse expression patterns appeared identical and were restricted to the developing brain, with the great majority of expression being found in the developing forebrain. In the latter case expression was confined to the germinative neuroepithelium of three sharply delimited regions: the dorsomedial wall of the telencephalic ventricles (which includes the developing hippocampus), a discrete region of the dorsal thalamus and the mammillary and retromammillary regions of the posterior hypothalamus. Expression in the developing hippocampus may suggest a role for WNT8B in patterning of this region and subchromosomal localization of the human gene to 10q24 may suggest it as a candidate gene for partial epilepsy in families where the disease has been linked to markers in this region.

Amino Acid Sequence↗

PubMed1998

HLA-A locus mismatches and development of antibodies to HLA after lung transplantation correlate with the development of bronchiolitis obliterans syndrome.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the most common cause of morbidity and mortality after lung transplantation (LT). A retrospective analysis of clinical and immunologic variables were done to identify those that might predict the development of BOS. METHODS: Of 112 LT performed over a 42-month interval, 94 survived at least 3 months and form the basis of this analysis. There was a minimum of 21 months follow-up. BOS was defined on the basis of declining spirometry (FEV1 <80% of baseline) and/or the presence of histologic obliterative bronchiolitis. All variables analyzed were subjected first to a univariate analysis; those variables appearing to carry significance were then subjected to a multivariate logistic regression analysis. RESULTS: Univariate analysis revealed the following to be predictors of the development of BOS: age (the probability of developing BOS declined with advancing age); donor/recipient HLA-A locus mismatch, with actuarial freedom from BOS being significantly greater with no A-locus mismatches versus cases with one or two mismatches (P=0.031); and development of anti-HLA antibodies after transplantation (P=0.006 vs. recipients without detectable antibodies). In multivariate analysis, only HLA locus mismatch and development of anti-HLA antibodies were significant independent predictors of the development of BOS. The remaining clinical variables (gender, type of LT, indication for LT, graft ischemic time, use of cardiopulmonary bypass, cytomegalovirus) and immunologic variables (crossmatch, frequent early acute rejection) did not correlate with the development of BOS. CONCLUSIONS: These data suggest that BOS is the result of an immune process, that differences at the HLA-A locus may play an important role in this process, and antibody-mediated injury may play a role in BOS.

Adult↗

PubMedDate not supplied

Benzodiazepine receptor development in cultures of fetal mouse cerebral cortex mimics its development in vivo.

Using a recently developed assay method which maintains cell integrity, we have performed a developmental study of the benzodiazepine (BDZ) receptor on cells of fetal mouse cortex in cultures which were either 'neuron-poor' or 'neuron-rich'. The developmental profile of the BDZ receptor in culture, when assayed on the intact cell, closely mimicked its development in vivo, reaching maximum values at 35-42 days after conception. Further, the time course of development paralleled that reported for GABA neurons both in vivo and in vitro. We have also shown that the relative delay in development of the clonazepam-displaceable portion of BDZ binding approximated a similar delay in the reported development of glutamic acid decarboxylase activity, both parameters presumably reflecting specific neuronal development. Thus, the ontogenesis of specific BDZ receptor binding in culture bears marked similarity to the time course of development of the GABAergic system.

Animals↗

PubMed2003

Morpholino antisense oligonucleotide-mediated gene knockdown during thymocyte development reveals role for Runx3 transcription factor in CD4 silencing during development of CD4-/CD8+ thymocytes.

During thymic T cell development, immature CD4(+)/CD8(+) thymocytes develop into either CD4(+)/CD8(-) helper or CD4(-)/CD8(+) CTLs. The molecular mechanisms governing the complex selection and differentiation steps during thymic T cell development are not well understood. Here we developed a novel approach to investigate gene function during thymocyte development. We transfected ex vivo isolated immature thymocytes with gene-specific morpholino antisense oligonucleotides and induced differentiation in cell or organ cultures. A morpholino oligonucleotide specific for CD8alpha strongly reduces CD8 expression. To our knowledge, this is the first demonstrated gene knockdown by morpholino oligonucleotides in primary lymphocytes. Using this approach, we show here that the transcription factor Runx3 is involved in silencing of CD4 expression during CD8 T cell differentiation. Runx3 protein expression appears late in thymocyte differentiation and is confined to mature CD8 single-positive thymocytes, whereas Runx3 mRNA is transcribed in mature CD4 and CD8 thymocytes. Therefore, Runx3 protein expression is regulated at a post-transcriptional level. The knockdown of Runx3 protein expression through morpholino oligonucleotides inhibited the development of CD4(-)/CD8(+) T cells. Instead, mature cells with a CD4(+)/CD8(+) phenotype accumulated. Potential Runx binding sites were identified in the CD4 gene silencer element, which are bound by Runx protein in EMSAs. Mutagenesis of potential Runx binding sites in the CD4 gene silencer abolished silencing activity in a reporter gene assay, indicating that Runx3 is involved in CD4 gene silencing. The experimental approach developed here should be valuable for the functional analysis of other candidate genes in T cell differentiation.

Amino Acid Sequence↗

PubMed1985

Dynamics of the control of body pattern in the development of Xenopus laevis. II. Timing and pattern in the development of single blastomeres (presumptive lateral halves) isolated at the 2-cell stage.

Xenopus embryos have been selected in which the first cleavage plane is tending strongly to correspond with that of bilateral symmetry for the future larval pattern. The two blastomeres produced by this cleavage have been separated and allowed to develop as reciprocal pairs of presumptive lateral-half isolates. The early development and the time course of the gastrulation movements, and the qualitative and quantitative aspects of larval mesodermal patterns, have been studied in relation to synchronously fertilized controls. The result is restoration of bilateral symmetry for developmental potential, and production of a pair of small gastrulae and larvae with qualitatively complete body plans but 50% of control cell numbers each (see Kageura & Yamana, 1983). Most commonly, however, the resulting small patterns deviate from the normal range in their proportions in at least one of two ways. The notochord territory is rarely, if ever, under-represented (i.e. notochords contain at least 50% control cell numbers) but it is frequently over-represented, in some cases approximating that of control whole embryos. Reciprocal pairs of isolates thus tend, on average, to produce more notochordal tissue than they would have if developing normally. Secondly, the balance of cell population sizes assigned to somites up and down the axis is altered so that relatively anterior members of the series are less scaled down than those in trunk and tail regions. The mesodermal plan developed by a lateral-half isolate is thus characteristically intermediate between that of a small, harmonious larva (the proportional presumptive fates of the materials, apart from loss of bilaterality), and that of the mosaically developing presumptive dorsoanterior cell pair from the 4-cell stage, discussed in the previous paper. A minority of the lateral isolates does develop a harmonious and thus well-regulated body plan, however, and the normality or otherwise of the schedules of gastrulation timing in isolates seems a good predictor of their morphogenetic performance in this respect. The results are discussed as informing us about the dynamics of the interactions, prior to gastrular stages, that underlie the normal mesoderm development.

Animals↗

PubMed1998

CD16 cross-linking blocks rearrangement of the TCR beta locus and development of alpha beta T cells and induces development of NK cells from thymic progenitors.

Mouse thymocytes normally develop into T lymphocytes, but the embryonic thymus also contains precursor cells capable of developing into NK cells. Here, we describe conditions that induce pro-T cells to develop into NK cells. CD16 is expressed on thymic pro-T cells. We observed that CD16 cross-linking during culture of embryonic thymic organs suppressed rearrangement of the TCR beta locus (but did not inhibit TCR gamma locus rearrangement). Rearrangement of the TCR beta locus is normally required for development to the CD4+CD8+, and this development was also suppressed by CD16 cross-linking. The ability of CD16 cross-linking to block alpha beta T cell development was not attributable to toxic effects, but rather was accompanied by promotion of development into NK cells, identified based on molecular and functional criteria. These results suggest that common lymphoid precursors can respond to environmental signals to commit to the alpha beta T vs NK developmental pathways.

Animals↗

PubMed1991

The WHO Collaborative Study of Neoplasia and Steroid Contraceptives: the influence of combined oral contraceptives on risk of neoplasms in developing and developed countries.

A hospital-based case-control study was conducted in eight developing and three developed countries to determine whether use of combined oral contraceptives alters risks of various cancers. An observed trend of increasing risk of invasive cervical cancer with duration of use may not represent a causal relationship and is the subject of further study. Decreased risks of ovarian and endometrial carcinomas in users likely indicate a protective effect of oral contraceptives, the degree of which was similar in developing and developed countries. A small increase in risk of breast cancer in recent and current users was found to be somewhat greater in developing than developed countries. Both causal and non-causal interpretations of this finding have been offered. No associations were found between oral contraceptives and in situ cervical, hepatocellular, cholangio, or gallbladder carcinomas, or uterine sarcomas; but the power of this study to detect alterations in risks of these neoplasms in long-term users was low.

Breast Neoplasms↗

PubMed2004

The opportunities and obstacles to collaboration between the developing and developed countries in the field of occupational health.

The 2.4 billion working people in the developing countries often have to endure employment conditions, which do not meet even basic occupational safety and health (OSH) standards. The lack of work safety, excessive work loads, and occupational physical, chemical and biological exposures result in occupational diseases, injuries and as many as 1.2 million fatalities each year. Furthermore, as little as 15% of workers in the developing countries have access to occupational health and safety services. Some collaboration between the industrialized and developing countries in the field of OSH has been practiced for 30 years but its volume has been modest compared to other sectors of development assistance. The lessons learned from 30 years of experience are that the most important OSH improving factors in developing countries include legal and policy instruments, national OSH programs, infrastructure for OSH implementation, and OSH services. The establishment of OSH expert human resources, centers serving as engines for research, training, as well as information and registration systems can also be considered as key factors in any such collaboration. A convincing government OSH policy, and close cooperation between social partners and the government are also critical factors that guarantee sustainable OSH programs in a developing country over a long-term basis.

Accidents, Occupational↗

PubMed1999

The burden of pneumococcal disease among adults in developed and developing countries: what is and is not known.

The burden of pneumococcal disease among adults in developed countries is neither widely known nor appreciated. The incidence of pneumococcal pneumonia is uncertain because a precise diagnosis cannot be obtained for most patients. Population-based data on invasive pneumococcal disease (e.g., bacteraemia and meningitis) suggest an annual incidence in all developed countries of > or =15-20 cases per 100,000 persons of all ages and > or =50 cases per 100,000 elderly adults (> or =65 years). In developing countries there are no population-based data on the burden of pneumococcal disease among adults. Studies of high risk groups, hospital-based studies, vaccine efficacy trials, extrapolations from surveillance of "native populations" in developed countries, and demographic studies in developing regions all suggest a high burden of disease. The broad variation in these estimates, however, indicates that better studies are needed. Increased use of pneumococcal vaccines among adults in all countries will depend on better scientific and public understanding of the burden of pneumococcal disease. In developing countries, intensive community-based studies of the impact of pneumococcal disease, or, alternatively, a "vaccine probe" approach, in which a population is vaccinated and the reduction in pneumonia is compared with that in a control population, could give more accurate estimates of the burden of disease and of the potential effectiveness of pneumococcal vaccination among adults.

Adult↗

PubMed2001

A review of the literature from developed and developing countries relating to the effects of hospitalization on children and parents.

There is a literature base about the care of children in hospital in developed nations, but little from, or about, developing countries. The aim of this review was to critically examine publications relating to the effect of hospitalization on children and their parents. 'Parents', in this context, were considered as the child's natural or adoptive parents, step-parents or any other context of parent-child relationship, in other words, the primary care-giver to the child. Most of the work reviewed from developed countries was sourced from the nursing literature, while in developing countries, the available literature was largely from medicine. Conclusions from developed countries indicated that parents should be allowed to stay in hospital with their child, and that care must be developmental-stage appropriate. Furthermore, staff need to be educated about special needs of children, children should be prepared for hospital admission (if possible) and parents' needs met. In developing countries, the meagre literature available suggested that recognition of the important role parents play in a child's hospitalization is starting to become recognized.

Adaptation, Psychological↗