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The health transition in developing countries: a role for internists from the developed world.

Demographic and epidemiologic changes that have occurred in the past five decades in many developing countries provide new opportunities for internists from developed countries to contribute to improvements in international health. These changes, called the "health transition," are characterized by major growth in the number and proportion of middle-aged and elderly persons and in the frequency of the chronic diseases that occur in these age groups. The health transition is the result of concentrated national and international efforts to improve maternal and child health by emphasizing primary care and community-organized outreach services. In many developing countries, such efforts have been responsible for a decrease in the birth rate; reduced maternal mortality; improved preventive services; and a vigorous therapeutic approach to infantile diarrhea and respiratory infection, which, in turn, have resulted in the reduced infant mortality and the increased life expectancy that defines the health transition. These changes, often accompanied by increasing urbanization and industrialization, are creating health problems similar to those seen in the "developed" world but are occurring in countries that have far fewer resources. Internists interested in working in developing countries can therefore bring their skills, experience, and perspective to bear on these problems, primarily by working within well-structured programs, the aim of which is to strengthen the capacity of the organizations and institutions within these countries to cope with the rising tide of chronic adult diseases.

Delivery of Health Care↗

Systems development of child mental health services in developing countries.

This article reviews recent findings in the epidemiology of childhood psychiatric disorders in the developing world and the relationship of epidemiology to system development. Examples of systems developed in the Third World are discussed. The experience with attention-deficit/hyperactivity disorder and the development of a comprehensive system of care around it in Lebanon are described. Cultural factors that affect special populations in childhood mental health are examined. The article concludes with recommendations for systems development in Third World countries.

Adolescent↗

Effect of maternal undernutrition during pregnancy on early ovarian development and subsequent follicular development in sheep fetuses.

Gonad development in female sheep fetuses is thought to occur in a number of key stages. The aim of this study was to determine the effects of maternal undernutrition, applied at one or more of these critical stages, on fetal ovarian development. Groups of ewes (n = 11-19) were fed rations providing either 100% (high; H) or 50% (low; L) of energy requirements for live weight maintenance during selected 'windows' during gestation. Control ewes (HH and HHH) were fed the H ration from mating until they were killed at days 50, 65 (HH) or 110 (HHH) of gestation, whereas ewes of other groups were fed the L ration for the periods between day 0 and day 30 of gestation (LH and LHH), day 31 and day 50 or 65 of gestation (HL and HLH), day 65 and day 110 of gestation (HHL) or day 0 of gestation until the animals were killed (LL and LLL). At day 50 of gestation, there was no effect of nutritional treatment on mean fetal mass but compared with HH animals, mean fetal ovarian mass was significantly lower in HL (P < 0.05) and LL (P < 0.001) animals. At day 65 of gestation, there were significantly fewer germ cells (P < 0.05) at the resting, diplotene stage of initial meiosis in LL animals than there were in HH animals, indicating delayed germ cell maturation and onset of meiosis. Qualitative assessment of proliferative cell nuclear antigen immunostaining indicated that, at day 50 of gestation, staining was located predominantly in the germ cells, whereas by day 65 of gestation, staining was confined predominantly to somatic cells. Undernutrition in each one of these windows was associated with delayed ovarian follicular development (P < 0.05-0.001) as measured by development of the granulosa cell layer at day 110 of gestation. This study demonstrates that undernutrition before and during folliculogenesis can delay fetal follicular development.

Analysis of Variance↗

Sex dimorphism in development dynamics and in development progression of morphological features in human foetuses.

The study material comprised 3889 foetuses of both sexes, aged 20-42 weeks. t-Student test has been applied to evaluate the existence of potential sex-dependent differentiation of developmental trends as assessed by weekly measurements of selected somatic features and by the weight of internal organs. The regression coefficients of the analysed variables have been compared against the opposite sex. The rate of development of the analysed features in consecutive weeks has been found to be sex-related. Highest sex-related differences have been observed for the total body weight and for the weight of internal organs, with the exception of the adrenals, and the differences have been significant enough to justify the existence of contrasting, sex-dependent patterns of development of the analysed variables. The development of the analysed morphological features has been depicted by curvilinear regression. When described by various degree polynomials the development course of the analysed features displays sex-related differences. Only the change in the weight of the adrenals is similar for both sexes. The evaluation of the developmental advancement of the analysed features has revealed that they are usually at a more advanced development level in female foetuses.

Body Height↗

Development shows some backbone. HFSP Workshop on Genetic Control of Vertebrate Development cosponsored by the Human Frontier Science Program, European Science Foundation, and European Molecular Biology Organization, Les Diablerets, Switzerland, May 26-30, 1991.

This meeting aptly illustrated the power of a combined analysis of development in a range of vertebrate systems. Each system has its own inherent strengths: the mouse has gene transfer technology and targeted mutagenesis, the frog and chick have experimental embryology, and the zebrafish has genetics. It is the synergistic effect of considering all of these systems in combination that is without measure. In the past, the study of vertebrate development has been relegated to a largely descriptive phase. Initially, this was through analysis of morphological changes taking place during development. More recently, this has taken the form of cataloging the expression patterns of genes transcribed in development. It is clear that we are now entering an era when a functional analysis of development can get underway.

Animals↗

A comparison between the disease status of hospitalized dogs from developed and those from developing communities.

The health status of canine populations within developed and those within developing communities was studied in a retrospective survey and compared. There were significant differences in the prevalence of disease amongst the hospitalised dogs from the 2 communities. Dogs from developing communities were mainly young cross-bred dogs which suffered from infectious diseases (44%), trauma (22%) and parasitic diseases (11%). There was a high mortality rate (30%) and 82% of these patients suffered from diseases that could have been prevented. The dogs from developed communities were mainly adult or old pure-bred dogs that suffered mainly from organ diseases (57%). There was a low mortality rate (10%) while only 31% suffered from diseases that could have been prevented. Based on the epidemiological findings, it was evident that owners of dogs in the developing communities required education in primary and secondary prevention of disease.

Animals↗

Social competence as a positive youth development construct: conceptual bases and implications for curriculum development.

Two major aspects of social competence were studied in this section: positive human relationships and clear self-identity. The concepts of human relationships and identity development are delineated. The importance of the development of a national identity for Hong Kong adolescents is also explained. The social competence program units focus on issues relating to national and racial identity, and human relationships (especially the resolution of interpersonal conflicts in the family and between good friends). The general goal is to foster the development of a clear national and racial identity, and positive human relationships. This paper is part of the development of the positive youth development program in Hong Kong.

Adolescent↗

Prenatal development of the adrenal in pig Sus scrofa dom. Part II. Adrenal cortex development in the second part of pregnancy.

The development of the adrenal cortex in pig fetuses between the 50 and 112 day of pregnancy were investigated with histological and histochemical methods and in electron microscope. Three consecutive generations of the cortical cells were observed. They had features of steroidogenic cells and differed with mature of mitochondria and in amount of SER and in enzyme activity. The earliest differentiated fetal cortical cells demonstrated alkaline phosphatase activity and giant mitochondria. They were translocated from the periphery to the center of the adrenal, where they degenerated and disappeared in the late pregnancy. The second generation--transitional cortical cells appeared about 70 day of development. They have pleomorphic mitochondria and abundant SER and low alkaline phosphatase activity. The last generation--the definitive cortical cells differentiated from 100 day of development and their number increased till the parturition. They had active 3-beta-hydroxysteroid dehydrogenase, spherical mitochondria and characteristic concentric whorls of SER. A probable role of the three generations of cortical cells is was discussed. In the subcapsular region of fetal adrenal undifferentiated and differentiating cells were observed, forming glomerularlike groups. Their role in the formation of cortical blastema and future zona glomerulosa was discussed. In the first part of the studies the formation of the mesenchymal primordium of the adrenal cortex was examined in early fetuses of domestic pig, and then differentiation of mesenchymal cells into steroidogenic cortical cells. The changes encountered then at the ultrastructural level consisted of an increased area of SER and greater number of mitochondria. At the same time, the shape of mitochondria altered and the cristae from lamellar became tubular. In the period around 50 day of development fetal adrenal was already a separate organ, with a capsule, composed of cords of fetal cortical cells divided by the blood vessels and strands of chromaffinoblasts penetrating the adrenal. Fetal cortical cells were characterized by alkaline phosphatase activity. The following study presents farther development of the adrenal cortex till the time of birth.

Adrenal Cortex↗

Modern approaches to vaccine development with special reference to the needs of developing countries.

Vaccination has proved to be one of the most effective public health measures to control infectious diseases. The eradication of smallpox by world-wide vaccination represents one of mankind's greatest achievements. Despite the availability of vaccines to control many diseases, they are generally under-used in many developing and some developed countries. However, there are many diseases for which current vaccines are inadequate or vaccines cannot be prepared using conventional approaches. This article describes the new approaches which are now available and are being used extensively to develop new vaccines against viral, bacterial and parasitic diseases. Success has already been achieved in a few cases and the prospect for others is encouraging. In addition, progress is being made to develop vaccines to control human fertility as this development is seen to complement the control of infectious diseases.

Developing Countries↗

Language development: a sensory development and signal processing perspective.

The relationship between the development of sensory mechanisms and the maturation of language behavior is poorly understood. From the outset it is important to distinguish between what is necessary for the development of any language system versus what is involved in the development of the verbal language system in the unimpaired child. The presence of highly sophisticated language systems among persons who communicate manually reminds us that no single source of sensory information is absolutely required for the development of at least some form of language system. Nevertheless, there persists a general belief that the availability of an accurate representation of the acoustic environment will facilitate at least the normal process of language acquisition. A more tenable question is whether the completeness or accuracy of the sensory representation places limitations on the emergence of language comprehension and production. I think this is unlikely, unless the relatively untested area of the maturation of "nonlinear processing mechanisms" provides information different than that obtained from more traditional linear systems analysis approaches. The relative integrity of the language systems of the hearing impaired, despite very dramatic differences in auditory sensitivity and frequency-resolving power, argues strongly that whatever mechanisms account for language organization are relatively immune to significant alterations in sensory input. Caution must be exercised here, however, since these comments generally refer to the outcome of studies performed on persons with acquired hearing loss. Naturalistic or descriptive studies of patients with congenital hearing loss are always susceptible to the criticism that whatever agent or agents produced the sensory impairment may also have produced concomitant impairment of nonsensory mechanisms. Nevertheless, comparisons of young infants and hearing-impaired adults, with respect to behavioral studies, suggest that there is a sufficiently rich sensory representation of the acoustic environment to permit the development of language skills much earlier than they naturally emerge. Electrophysiologic comparisons of human newborns and adults also suggest that the diminished auditory sensitivity and alterations in the frequency contour of sensitivity are insufficient to explain age differences in language comprehension and production performance. It may well be that the brain mechanisms responsible for the establishment of language behavior are sufficiently flexible to accommodate even a greatly impoverished sensory representation.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain↗

Motor development and the mind: the potential role of motor abilities as a determinant of aspects of perceptual development.

Recent advances in the science of human movement have enabled developmental psychologists to discover unique patterns of organization and control in infant motor behavior and development, provoking a resurgence of interest in this topic. In this article, we emphasize the role that motor development may play in determining developmental sequences or "timetables" in other domains. Specifically, we argue that particular motor achievements may be integral to developments in the domains of haptic perception and depth perception. In both cases, there is a high degree of fit between the developmental sequence in which certain perceptual sensitivities unfold and the ages at which the corresponding motor abilities onset. The discussions may provide new contexts in which to consider the developments of haptic perception and depth perception. The general purpose, however, is to highlight the wide-ranging influence of motor development during infancy.

Brain↗

Brevican in the developing hippocampal fimbria: differential expression in myelinating oligodendrocytes and adult astrocytes suggests a dual role for brevican in central nervous system fiber tract development.

Brevican is one of the most abundant extracellular matrix proteoglycans in the mammalian brain. We have previously shown that brevican produced by gray matter astrocytes constitutes a major component of perineuronal extracellular matrix in the adult brain. In this paper, we investigate the expression of brevican in the postnatal hippocampal fimbria to explore the role of the proteoglycan in central nervous system fiber tract development. We demonstrate that brevican is expressed by both oligodendrocytes and white matter astrocytes in the fimbria, but the expression of brevican in these two glial cell types is differently regulated during development. At P14, brevican immunoreactivity was observed throughout the fimbria, with particularly strong immunoreactivity in the developing interfascicular glial rows. In situ hybridization showed that oligodendrocytes in the glial rows strongly express brevican during the second and third postnatal weeks. Expression in oligodendrocytes was then down-regulated after P21. In the adult fimbria, no brevican expression was observed in oligodendrocytes. The time window of brevican expression coincides with the phase in which immature oligodendrocytes actively extend membrane processes and enwrap axon fibers. In contrast, the expression in astrocytes started around P21 as oligodendrocytes began to down-regulate the expression. In the adult fimbria, brevican expression was restricted to astrocytes. In situ hybridization with isoform-specific probes and RNase protection assays showed that the authentic, secreted form of brevican, not the glycosylphosphatidylinositol-anchored variant, is the predominant species expressed in the developing fimbria. Our results suggest that brevican plays a dual role in developing and adult fiber tracts.

Aging↗

Quantitative analyses of neuronal development in the lateral motor column of mouse spinal cord. II. Development of motor neuronal organelles.

The development of organelles within presumptive alpha motor neuronal somata was studied by electron microscopic morphometric analysis. Cells with large nuclei were selected for sampling from the lateral motor column of the brachial spinal cord of mouse embryos ranging in age from embryonic day 11 (E11) through E16. The first objective was to compare the cytodifferentiation of alpha motor neuronal somata among three genetically different strains of mice that differ in the development of forelimb reflex behavior and associated pathway synaptogenesis (Vaughn et al., '75). On the basis of multiple linear regression analyses, no significant differences were found among strains for either the initial levels or rates of cytodifferentiation. As a result, the data were combined for all three strains to analyze organelle changes during early neuronal development. The average areas of perikaryal cytoplasm and nuclei increased significantly. In addition, the relative areas of nucleoli, mitochondria, Golgi complexes, and rough endoplasmic reticulum increased, while the relative areas of heterochromatin and "free" ribosomes decreased. There were significant increases in the number of mitochondria and Golgi complexes per unit area of perikaryal cytoplasm. The average size of mitochondria appeared to increase during development, but was significantly smaller in adult alpha motor neurons than in embryonic specimens. In contrast, the average size of individual Golgi complexes was relatively constant throughout embryonic development, as well as in the adult. In general, the cytodifferentiation of alpha motor neurons appeared to progress in a relatively constant, linear fashion between E11 and E16.

Animals↗

Selective localization of polyribosomes beneath developing synapses: a quantitative analysis of the relationships between polyribosomes and developing synapses in the hippocampus and dentate gyrus.

Previous studies have revealed that polyribosomes are selectively localized beneath post-synaptic sites on central nervous system (CNS) neurons, and are particularly prominent during periods of synapse growth. The present study evaluates whether polyribosomes are most prominent at a consistent time in the developmental history of the synapse, or instead at a consistent time in the life of the organism regardless of the state of synaptic maturation (suggesting a globally acting factor). We compare the time course of synaptogenesis and the association between polyribosomes and developing synapses in three regions that develop at different rates: the external and internal blades of the dentate gyrus, and the CA1 region of the hippocampus proper. Each region was examined electron microscopically at 1, 4, 7, 10, 15, 20, 28 and over 120 days of age, evaluating: (1) synapse density (the number of synaptic profiles/area of neuropil), (2) the width of the neuropil layers, (3) the proportion of synapses with underlying polyribosomes, and (4) the number of polyribosome-containing synapses/area of neuropil. As anticipated on the basis of the differences in cytogenesis, the time course of synaptogenesis was different in the three regions. In the external blade of the dentate gyrus, synapse density increased in a nearly linear fashion between birth and 15 days of age, and then continued to increase at a somewhat slower rate until 28 days of age. Synapse development in the internal blade was delayed by several days in comparison to the external blade. In CA1, synapse density increased slowly between 1 and 7 days, and then at a rapid rate between 7 and 28 days of age. In all three regions, the proportion of synapses with underlying polyribosomes was highest between 1 and 7 days of age, and then decreased as synapse density increased. However, the peak in the number of polyribosome-containing synapses/unit area of neuropil occurred at different times in the three regions (4-7 days of age in the external blade of the dentate gyrus and in CA1, and 20 days of age in the internal blade). In addition to further defining the relationship between polyribosomes and developing synapses, the present study provides a data base on the time course of synapse development in the hippocampus and dentate gyrus, which will be useful for comparisons with other measures.

Aging↗

Embryonic development of the cornea in the eye of the clearnose skate, Raja eglanteria: I. Stromal development in the absence of an endothelium.

Embryos of the clearnose skate, Raja eglanteria, develop in sea water at 20-22 degrees C, hatching after 82 +/- 4 days (Luer and Gilbert, Environ. Biol. Fishes, 13:161-171, 1985). Eyes develop as steadily enlarging spheres whose corneas have the same radius of curvature as the sclera. The cornea begins development as a 2-cell thick epithelium beneath which by Day 12 there is only a basal lamina and a wispy matrix separating it from the underlying lens. This matrix, modified by Day 16, is displaced on Day 22 by a few orthogonal plies of fibrillar primary stroma. Ply number increases to at least 13 by Day 30, reaching the final number of 20 +/- 2 by Day 42. Stromal fibroblasts (keratocytes) appear at the corneal periphery by Day 22, and in increased numbers by Day 30, a time at which no keratocytes are seen in the central stroma. However, by Day 40, many fibroblasts are present at the corneal periphery, invading the primary stroma between plies, occasionally reaching even the central cornea. By Day 53, keratocytes are present between all plies, from corneal periphery to center. Thickness of each ply in this secondary stroma increases, but the number of plies remains the same as in the primary stroma. Bowman's layer, non-invaded matrix beneath the epithelial basal lamina, is not evident until Day 53. Sutural fibers, first seen on Day 22, originate in the corneal epithelial basal lamina, traversing perpendicularly the plies of the primary stroma. Sutural fibers persist throughout development of the secondary stroma and into adulthood. In contrast to chicks, skate corneas remain transparent throughout development, and never form an endothelium.

Animals↗

Anterior pituitary and adrenal cortical hormones accelerate or inhibit tadpole hindlimb growth and development depending on stage of spontaneous development or thyroxine concentration in induced metamorphosis.

The effect of prolactin, growth hormone, and various adrenal corticoids on hindlimb growth, development, and differentiation was studied in Rana pipiens larvae. Experiments were performed at different stages of spontaneous development and during metamorphosis induced in premetamorphic tadpoles by various concentrations of exogenous T4. Prolactin at 10 micrograms/day inhibited the limb at spontaneous premetamorphosis, had no effect at prometamorphosis or when administered with 3.8 nM T4, and synergized with T4 at 63 nM T4 and above. Growth hormone (10 or 20 micrograms/day) promoted limb growth and development during premetamorphosis but had no effect on spontaneous or induced metamorphosis thereafter, nor did it stimulate limb epidermal differentiation. The adrenal corticoids inhibited limb growth and epidermal cell proliferation during pre- and prometamorphosis but had no effect on limb morphogenesis or differentiation. The depressive effect of corticoids during spontaneous metamorphosis is at least partly through thyroid inhibition since hydrocortisone significantly reduced follicle cell height, lumen diameter, and cell proliferation in the thyroid. During induced metamorphosis, steroids (0.29 microM), especially corticosterone and aldosterone, antagonized the effect of 0.38 to 1.2 nM T4 on the limb. All steroids except deoxycorticosterone synergized with 3.8 nM T4, and at 31 nM T4, approximating the climax level with permeability factors taken into account, all corticoids synergized with T4 to promote limb growth and development. Aldosterone antagonized T4 at a higher T4 level than the other corticoids. The effect of all steroids except corticosterone was also corticoid dose-dependent. The results show the importance of the T4 concentrations in interactions of T4 with other hormones and suggest a scheme for hormonal control of limb growth and morphogenesis during metamorphosis. During premetamorphosis growth hormone synergizes with low endogenous T4 to promote initial limb growth and development while prolactin opposes this action. During prometamorphosis, as growth hormone and prolactin become ineffective corticosteroids begin to synergize with the rising level of endogenous T4. At climax, prolactin also augments the action of T4 to bring about rapid hindlimb growth.

Adrenal Cortex Hormones↗

Mechanistic basis of life history evolution in anuran amphibians: thyroid gland development in the direct-developing frog, Eleutherodactylus coqui.

Direct development is a widespread, alternative life history in Recent amphibians. There is no free-living, aquatic larva; adult features form in the embryo and are present at hatching. The mechanistic bases of direct development remain relatively unexplored. The current study describes the embryonic ontogeny of the thyroid gland in the direct-developing frog Eleutherodactylus coqui (Leptodactylidae) and quantifies histological changes that occur in the gland after its initial appearance. The thyroid gland of E. coqui is first apparent at Townsend-Stewart stage 10, approximately two-thirds of the way through embryogenesis. Soon after this the thyroid begins to accumulate follicular colloid. Quantitative analyses of thyroid histology reveal embryonic peaks in two measures, follicle number and follicle volume, which are followed by declines in these measures prior to hatching. These peaks in thyroid activity in E. coqui are correlated with morphological changes that are directly comparable to metamorphic changes in frogs that retain the ancestral, biphasic life history. In metamorphic taxa, a histologically identifiable thyroid gland does not form until the larval period, well after hatching. Nevertheless, measures of thyroid histology observed in E. coqui follow the pattern reported for metamorphosing amphibians. The present results support the hypothesis that the evolution of direct development in anurans is associated with precocious development and activity of the thyroid axis.

Animals↗

Development of the interferon system. I. In chicken cells development in ovo continues on time in vitro.

When confluent monolayers of cells derived from chicken embryos of different gestational age were cultured for several days without a medium change, a condition termed in vitro aging, the cells' developed an increased capacity to express the interferon (IFN) system. The capacity to both produce IFN and to respond to its antiviral action were enhanced up to 1000- and 100-fold, respectively. Remarkably, the programmed development of the IFN system in these cells seemed to continue virtually uninterrupted after monodispersion of the cells and seeding at high cell density. Cells prepared from young embryos required more time to develop the IFN system than cells from older embryos with the yield of IFN, and sensitivity to its action, related directly to the total in ovo and in vitro age of the cells in culture. For example, essentially the same yields of IFN were obtained from cell cultures made from 5-d-old embryos "aged" for 10 d in vitro, as were obtained from 10-d-old embryos whose cells were aged in vitro for 5 d. In contrast, inducibility of 2'-5' oligoadenylate synthetase by IFN and the induction of heat shock genes by elevated temperature are not enhanced with in vitro aging. The programmed development of the IFN system that starts in ovo seems to continue on schedule in vitro, making the development of the IFN system in chick embryo cells appear as a time-dependent process.

2',5'-Oligoadenylate Synthetase↗