"They're kept in a bubble": Healthcare professionals' views on transitioning young adults with congenital heart disease from paediatric to adult care.

BACKGROUND: Due to medical advances, growing numbers of adolescents with congenital heart disease (CHD) survive into adulthood and transferring from paediatric to adult healthcare. This transfer is significant step in a young person's life, and this study examines the views of Irish healthcare professionals' on how best to manage this transition. METHODS: Purposeful sampling was used to invite participation by healthcare professionals (HCPs) from a variety of disciplines whose caseloads include adolescents and young adults with CHD. Fourteen professionals participated in semistructured interviews regarding their experiences of the transition process and their recommendations. Data were collected during Spring 2016 and analysed using thematic analysis. RESULTS: Results indicated that the current approach to transition and transfer could be improved. Professionals identified barriers hindering the transition process such as cultural and attitudinal differences between HCPs dealing with child and adult patients, inadequate preparation and education of patients about their condition, parental reluctance to transfer, and concern about parents' role in on-going treatment. Measures such as better support and education for both the patients and their parents were recommended, in order to facilitate a smoother transition process for all parties involved. Additionally, HCPs identified the need for better collaboration and communication, both between paediatric and adult healthcare professionals and between hospitals, to ensure greater continuity of care for patients. CONCLUSIONS: Action is required in order to improve the current transition process. Measures need to be taken to address the barriers that currently prevent a smooth transition process for young adult CHD patients. Professionals recommended the implementation of a structured transition clinic to deal with the wide variety of needs of transitioning adolescent patients and their families. Recommendations for future research are also made.

Biological community structure on patch reefs in Biscayne National Park, FL, USA.

Coral reef ecosystem management benefits from continual quantitative assessment of the resources being managed, plus assessment of factors that affect distribution patterns of organisms in the ecosystem. In this study, we investigate the relationships among physical, benthic, and fish variables in an effort to help explain the distribution patterns of organisms on patch reefs within Biscayne National Park, FL, USA. We visited a total of 196 randomly selected sampling stations on 12 shallow (<10 m) patch reefs and measured physical variables (e.g., substratum rugosity, substratum type) and benthic and fish community variables. We also incorporated data on substratum rugosity collected remotely via airborne laser surveying (Experimental Advanced Airborne Research Lidar-EAARL). Across all stations, only weak relationships were found between physical, benthic cover, and fish assemblage variables. Much of the variance was attributable to a "reef effect," meaning that community structure and organism abundances were more variable at stations among reefs than within reefs. However, when the reef effect was accounted for and removed statistically, patterns were detected. Within reefs, juvenile scarids were most abundant at stations with high coverage of the fleshy macroalgae Dictyota spp., and the calcified alga Halimeda tuna was most abundant at stations with low EAARL rugosity. Explanations for the overwhelming importance of "reef" in explaining variance in our dataset could include the stochastic arrangement of organisms on patch reefs related to variable larval recruitment in space and time and/or strong historical effects due to patchy disturbances (e.g., hurricanes, fishing), as well as legacy effects of prior residents ("priority" effects).

Postnatal development of the human lateral geniculate nucleus: relationship to a critical period for the visual system.

The cross-sectional areas of 31,800 dorsal lateral geniculate nucleus cells were measured in 53 human brains ranging in age from newborn to 40 years. Geniculate cells increase in size rapidly during the first 6 to 12 months of postnatal life, with cells in the parvocellular layers developing faster than cells in the magnocellular layers. At least 2 years are required before all cells have reached their adult size.

Epigenetic modification of the X chromosome influences susceptibility to polycystic ovary syndrome.

CONTEXT: The cause of polycystic ovary syndrome (PCOS) is unknown, although genetic and environmental influences are clearly implicated. Some genetic studies have suggested the involvement of X-linked genes in PCOS, but the influence of X chromosome inactivation (XCI) on manifestation of this disorder has not previously been examined. OBJECTIVE: The objective of the study was to test the null hypothesis that XCI has no influence on clinical presentation of PCOS. DESIGN: We examined patterns of XCI between sister pairs with the same genotype at a polymorphic locus on the X chromosome in families with PCOS. SETTING: The study was conducted at a private practice. PARTICIPANTS: PCOS was defined as hyperandrogenemia with chronic anovulation. Forty families were studied in which DNA was obtained from at least one parent, the proband, and one sister that could be accurately diagnosed as being affected or unaffected. MAIN OUTCOME MEASURE(S): Relative expression of two X-linked alleles was determined, and the ratio of one to the other represented the pattern of XCI. RESULTS: The statistical odds on a different clinical presentation between sisters was approximately 29 times higher in sister pairs with different patterns of XCI, compared with sister pairs with the same pattern of XCI (odds ratio 28.9; 95% confidence interval 4.0-206; P = 0.0008). CONCLUSIONS: This study provides evidence to refute the null hypothesis and propose a closer inspection of X-linked genes in PCOS, one in which both genotype and epigenotype are considered. Environmental determinants of PCOS may alter clinical presentation via epigenetic modifications, which currently remain undetected in traditional genetic analyses.

Polyclonal lymphocytosis of T-cells associated with human T-cell leukemia virus I.

A patient with antibodies to human T-cell leukemia virus type I and the presence of integrated sequences of this virus in T-lymphocytes was investigated. In contrast to previous reports, the T-cell lymphocytosis was found to be polyclonal by analysis of human T-cell leukemia virus type I integration sites and T-cell antigen receptor rearrangements. Polyclonal T-cell infection by human T-cell leukemia virus type I may represent an infrequently observed stage of leukemogenesis.

Mutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independence.

Progression to androgen-independent growth of human prostate cancers may be mediated by alterations in the structure and/or expression of the androgen receptor (AR) gene. To date, mutations in the AR gene have largely been identified in hormone refractory tumors. In this study, single-strand conformational polymorphism analysis and DNA sequencing of the entire AR gene coding region was performed on 25 primary prostate tumors sampled prior to initiation of hormonal (i.e. , androgen ablation) therapy. Base changes leading to amino acid substitutions in the AR were identified in 11 (44%) tumors. The presence of AR amino acid substitutions was associated with decreased immunohistochemical staining for AR in tumor cells and the rapid failure of subsequent hormonal therapies. Single-strand conformational polymorphism analysis of exons 2, 3, and 8 of the X-linked hypoxanthine guanine phosphoribosyl transferase (HPRT) gene in the same samples revealed no bandshifts, suggesting that the high frequency of AR gene mutations detected was not a consequence of generalized genetic instability. These data indicate that AR gene mutations occur commonly in advanced prostate cancers prior to endocrine treatment of disease and may contribute to altered androgen responsiveness of the tumors.

Effect of adults' self-regulation of diabetes on quality-of-life outcomes.

OBJECTIVE: To examine the relationships among cognitive representations of diabetes, diabetes-specific health behaviors, and quality of life using Leventhal and Diefenbach's self-regulation model of illness (Leventhal H, Diefenbach M: The active side of illness cognition. In Mental Representation in Health and Illness. SkeltonJA, Croyle RT, Eds. New York, Springer-Verlag, 1991, p. 247-272). RESEARCH DESIGN AND METHODS: This research involved secondary analysis of a mailed survey completed by 296 adults (ages 20-90 years). Structural equation modeling was conducted to investigate relationships among cognitive representations, diabetes-specific health behaviors, and quality of life. Model differences by diabetes type were also investigated. RESULTS: Findings indicated that certain cognitive representation constructs were related to increased diabetes-specific health behaviors, decreased sense of burden, and positive quality-of-life outcomes. Individuals levels of understanding of diabetes and their perceptions of control over diabetes were the most significant predictors of outcomes. However, diabetes-specific health behaviors were related to an increased sense of burden that was negatively associated with quality of life. Multigroup analyses indicated that this self-regulatory model provided a good fit for individuals with type 1 diabetes, those with type 2 diabetes who take insulin, and those with type 2 diabetes who do not take insulin. CONCLUSIONS: These findings advance what is known about cognitive representations of illness and the self-regulation of diabetes as well as the relationships between cognitive representations of illness, quality of life, and behavioral factors. In particular, results from this study suggest the need for further study to address ways of reducing the burden of diabetes associated with health behaviors and decreased quality of life.

Multiple responses to administration of liposome-encapsulated hemoglobin (LEH): Effects on hematopoiesis and serum IL-6 levels.

Liposome-encapsulated hemoglobin (LEH) has been tested in animals as an oxygen-carrying red cell substitute and has been shown to be beneficial in the treatment of hemorrhagic shock. The effects of LEH on immune responses have not been studied thoroughly in any well-controlled model. Using a murine model, we evaluated nephrotoxicity and hepatotoxicity as well as immune function parameters following LEH administration. Following intravenous administration of LEH, 1) a serum spike of interleukin-6 (IL-6) occurred in mice at 4-8 hours, with no elevation of IL-1, tumor necrosis factor (TNF), or interferon-gamma (IFN-gamma); 2) the serum liver function enzymes SGOT (AST, aspartate aminotransferase) and SGPT (ALT, alanine aminotransferase) were elevated at 48 hours; 3) only a slight increase in serum antibody to bovine hemoglobin was observed; and 4) increased hematopoietic activity was observed in the spleen and bone marrow. The finding that only IL-6 but not the associated TNF, IL-1, or IFN-gamma is secreted in vivo following LEH administration is novel and may have significance in defining the mechanisms underlying specific adverse responses observed with LEH administration in animals.

The androgen receptor CAG repeat polymorphism and X-chromosome inactivation in Australian Caucasian women with infertility related to polycystic ovary syndrome.

The human androgen receptor (AR) gene contains a polymorphic trinucleotide (CAG) repeat sequence in exon 1. The number of CAG repeats may confer differential receptor activity, and specific ranges of variants have been correlated with androgen-sensitive disease processes. Polycystic ovary syndrome (PCOS) is a female condition characterized by androgen excess and infertility, many features of which are effected through the AR. We compared frequency distributions of CAG repeat alleles and their pattern of expression via X-inactivation analysis among 83 fertile women and 122 infertile women with PCOS, all of Australian Caucasian ethnicity. A population comparison with 831 predominantly fertile Australian women was also used. PCR-based assays were used to genotype each woman and assess allele inactivation patterns after digestion of DNA with methylation-sensitive HpaII. Infertile women with PCOS exhibited a greater frequency of CAG alleles or biallelic means greater than 22 repeats compared with both the fertile control group (P < 0.05) and the general population (P < 0.01). Preferential expression of longer CAG repeat alleles was also observed in PCOS and correlated with increased serum T. We conclude that the AR (CAG)n gene locus and/or its differential methylation patterns influence the disease process leading to PCOS.

Development of the dorsal lateral geniculate nucleus in normal and visually deprived cats.

Although much is known about the cell size changes that take place in the cat dorsal lateral geniculate nucleus as a result of visual deprivation, very little is known about the time course of either of these changes or the changes that occur during normal development. In addition, all previous studies of lateral geniculate nucleus cell size have been confined to the dorsal laminae A and A1 since the more ventral "C" laminae are impossible to identify in normal Nissl stained material. However, it is possible to extend the cell measurement data to laminae C, C1, and C2 by using autoradiographic techniques. Cross-sectional area measurements of dorsal lateral geniculate nucleus cells were made in 47 normally reared kittens and 45 monocularly deprived kittens. All of the normal kittens and 39 of the 45 deprived kittens were studied during the first 70 days of postnatal life. Six deprived cats used to study the deprivation induced changes in cell size in the "C" laminae were allowed to survive for longer periods. In normal kittens, lateral geniculate nucleus cells grow rapidly during the first four weeks of life. Cells in the deprived layers also grow rapidly during this time, however, at the end of the first month their growth stops and a slow shrinkage takes place over the next several weeks. In the "C" laminae of deprived cats significant changes in cell size are confined to layer C. Although many of the deprived cats show greater deprivation induced changes in cell size in the binocular segment of the lateral geniculate nucleus than in the monocular segment, other cats show approximately equal changes in cell size in the two regions. In addition, some cats exhibit little, if any, deprivation induced change in lamina A cell size but do show quite severe cell shrinkage in lamina A1.

Translaminar growth of axons in the kitten dorsal lateral geniculate nucleus following removal of one eye.

The distribution of retinal afferents to the dorsal lateral geniculate nucleus of the cat following the early removal of one eye has been studied using autoradiographic as well as degeneration techniques. The degeneration techniques have confirmed earlier observations that axons from the remaining, normal eye grow across laminar borders into the deafferented lamina A. Autoradiographic techniques, however, have shown further examples of translaminar growth between lamina A nadlamina A1 as well as between lamina A1 and lamina C. Although the possibility exists that such growth also occurs between the other C laminae (C1, C2 and C3) such growth is harder to demonstrate since no well defined interlaminar regions exist in this part of the nucleus. In the monocular segment of the nucleus degeneration techniques have shown some translaminar invasion of the deafferented lamina A. Autoradiographic techniques have demonstrated similar growth as well as an abnormal invasion of the most lateral parts of the monocular segment. This latter growth originates in the optic tract as it curves around the nucleus on the way to the superior colliculus.

Prenatal development of the human lateral geniculate nucleus.

The development of the human lateral geniculate nucleus has been studied on Nissl- and silver-stained sections from 61 fetal human brains collected during normal autopsy procedure. The age of the fetuses, which ranged from 16 to 40 (newborn) weeks was determined by comparing crown-to-rump lengths and body weights to the values published by Streeter ('20). The development of the human lateral geniculate nucleus is remarkably similar to that described for the rhesus monkey (Rakic, '77). As a result of the late growth of the pulvinar, the human lateral geniculate nucleus is displaced and rotated such that, at around week 24, the nucleus had come to lie along the ventrolateral border of the thalamus. The cellular laminae that characterize the adult nucleus are formed over a 3-week period of time beginning around the 22nd week of gestation. More caudal parts of the nucleus laminate first. During this same period of time, the optic disc representation in laminae 4 and 6 is also formed. Throughout most of the development of the human lateral geniculate nucleus, individual rows of cells can be seen extending across the nucleus. Although such rows of cells are best seen before the nucleus laminates, in older laminated nuclei the rows of cells are oriented either perpendicular or oblique, but never parallel, to the plane of the laminae. Previous findings in both the monkey (Rakic, '77) and human (Hickey and Guillery, '79) suggest it is possible that these rows of cells can be used to define the lines of projection through the nucleus. Incoming optic tract fibers run along, rather than perpendicular to, these rows of cells.

Variability of laminar patterns in the human lateral geniculate nucleus.

The structure of the human lateral geniculate nucleus has been studied on serial Nissl stained sections from 57 human brains. Most of the brains were from neurologically normal individuals and were obtained during routine autopsy procedures. The laminar arrangement within the human nucleus is surprisingly variable. It is always possible to recognize a small segment with two layers (the monocular segment), one with four layers and one with six layers. Often an 8-layered segment can also be seen. The posterior half of the nucleus, within which central vision is represented, is made up mainly of six layers, and is the least variable part of the nucleus. Here the layers lie roughly parallel to each other. In the anterior half of the nucleus the laminar arrangement is more variable, and the layers often form complex and irregular interdigitations with each other. The 8-layered segment varies greatly in size and may be absent. It generally lies at the edge of the 4-layered segment not, as might have been expected, within the borders of the 6-layered segment. In many parts of the nucleus nerve cells are organized in short rows that run perpendicular to the layers; also, individual nerve cells are elongated in this direction. This neuronal orientation follows the lines of projection that are defined by the borders of a zone of retrograde degeneration, and also corresponds to the orientation of a cellular discontinuity that probably is the geniculate representation of the blind spot. Thus, we conclude that the neuronal orientation indicates the lines of projection within the nucleus.

A study of Golgi preparations from the human lateral geniculate nucleus.

The Golgi method was used to study nerve cells and their processes in the human lateral geniculate nucleus. Only a few axons were successfully impregnated. These enter the nucleus from the optic radiations and were tentatively identified as corticogeniculate axons. In one brain from a 2-week-old infant these axons showed unusually dense terminal arbors, suggesting that significant developmental changes occur in this fiber system postnatally. Neurons in the magnocellular layers show a great variety of dendritic patterns, and are not readily grouped into well-defined morphological classes. At one extreme are cells with a restricted dendritic arbor, having dendrites that run a sinuous course close to the perikaryon. At the other extreme, cells have a more extended dendritic arbor; their dendrites are long, relatively straight in some cells, markedly tortuous in others. There is a continuous range of intermediate cell types between the "restricted" and the "extended" cells. Many magnocellular dendrites cross freely into adjacent layers; whereas the short dendrites of restricted cells rarely cross from one layer to another, the dendrites of extended cells may either be confined to a single layer (intralaminar) or may have a translaminar distribution across two or even three layers. Small cells, with dendrites entirely confined to an interlaminar region, have been seen in the magnocellular division of the nucleus on either side of layers 2. Parvocellular elements also show a wide range of dendritic patterns, but the extreme forms of restricted and extended cells are not seen. Parvocellular dendrites commonly are oriented perpendicular to the layers and generally show an intralaminar distribution; translaminar dendrites are extremely rare. A minority of parvocellular neurons have most of their dendrites confined to an interlaminar zone. These "interlaminar" cells have large perikarya close to or in the interlaminar zones, and show a predominant dendritic orientation parallel to the layers. A few parvocellular elements with complex axoniform dendrites were seen, and these dendrites, too, tend to run parallel rather than perpendicular to the layers.

Morphology of C-laminae neurons in the dorsal lateral geniculate nucleus of the cat: a Golgi impregnation study.

On the basis of their dendritic morphology, neurons in the C-laminae of the cat's dorsal lateral geniculate nucleus (dLGN) have been divided into five groups. These groupings are based on previous descriptions of the neuronal types present in the dLGN of the cat (Guillery, '66; Famiglietti, '70; Updyke, '79). Class 1, 2, 3, and 5 neurons in the C-laminae are essentially identical to their counterparts in the A-laminae, with one exception. The dendritic orientation of class 2, 3, and 5 neurons found in the C-laminae is, for the most part, parallel to the laminar borders. In the A-laminae, class 2 and 5 neurons show no preference in their dendritic orientation and class 3 neuron dendritic orientation is predominantly perpendicular to the laminar borders. Class 4 neurons are found in all C-laminae and make up the bulk of the impregnated neurons. They are morphologically distinct from A-laminae neurons but exhibit a broad range of structural characteristics.

The distribution of retino-collicular axon terminals in rhesus monkey.

The retino-collicular projections in rhesus monkeys were studied using standard autoradiographic and degeneration techniques. A computer based technique was developed which provided a flattened visual display of the retinal projection onto the entire superior colliculus, quantified the area covered by such projections for different segments of the colliculus and showed how this morphological pattern varied with depth beneath the collicular surface. In the anterolateral third of the colliculus (i.e., the foveal representation) the retinal projection was light, confined to a narrow region of the superficial gray and contributed primarily by the contralateral eye. In the remaining binocular segment of the superior colliculus the retinal projections showed a marked degree of local patterning, that in many instances appeared as bands of label. By combining eye removal and eye injection procedures in a single animal and comparing adjacent sections processed for autoradiography and stained for degeneration, it was possible to assess the amount of overlap between retino-collicular projections from the two eyes. These experiments showed that total segregation of retinal afferents does occur in the monkey superior colliculus, but what occurs more often is a situation where the density of inputs from the two eyes varies reciprocally as one moves across the part of the colliculus that represents the binocular visual field.

Genesis of neurons in the dorsal lateral geniculate nucleus of the cat.

Neurons that will ultimately form the dorsal and ventral lateral geniculate nuclei, the medial interlaminar nucleus, the perigeniculate nucleus, and the nucleus reticularis of the cat undergo their final cell division beginning on, or slightly before, embryonic day 22 (E22) and ending on, or before, E32. Early in this period, neurogenesis proceeds for all of these geniculate nuclei, whereas only in the dorsal lateral geniculate nucleus does cell birth continue until E32. Distinct spatiotemporal gradients of cell birth are not obvious within any of the individual geniculate nuclei. For the dorsal lateral geniculate nucleus in particular, and for the other geniculate nuclei in general, neurons born early in this period exhibit a full range of adult soma sizes, including large and small neurons. Neurons born late in this period exhibit only small adult somas. The location and size of a neuron within the dorsal lateral geniculate nucleus provide clues to that cell's functional properties. On the basis of presently available information regarding the relationship between structure and function of neurons in the cat's dorsal lateral geniculate nucleus, the findings described here suggest that all functional classes of neurons in the dorsal lateral geniculate nucleus are born at the same time throughout most of this period.

Reduced effects of monocular deprivation on a population of A-laminae neurons in the cat's dorsal lateral geniculate nucleus.

The generation of nerve cells for the cat's dorsal lateral geniculate nucleus takes place between embryonic day (E) 22 and E32. Neurons generated before E28 exhibit a full range of soma sizes and morphological features, whereas neurons generated after E28 have only smaller somata and a more limited array of morphological features. We measured the effects of monocular deprivation on neurons in the cat's dorsal lateral geniculate nucleus that were generated at different times, with birthdates defined by injections of 3H-thymidine. Whereas populations of nerve cells generated before E28 exhibit changes in cell size that are, on average, typical of those seen in monocularly deprived cats, populations of nerve cells generated after E28 are, on average, less affected by visual deprivation.

An analysis of the time of origin of neurons in the entorhinal and subicular cortices of the cat.

The [3H]thymidine autoradiographic method was used to determine the birth dates of neurons in the cat parahippocampal gyrus. Cat fetuses were exposed to a single pulse of the radioactive marker between the 20th and 55th embryonic days. All animals were delivered normally and allowed to survive for 2-6 months postnatal. The resulting autoradiographs demonstrate three spatiotemporal gradients of cell birth in the entorhinal and subicular cortices. First, an inside-out gradient is apparent; i.e., neurons in the deeper layers are born earlier than those in the more superficial layers. Second, a rhino to dentate gradient exists. Accordingly, cells closer to the lateral entorhinal region tend to be generated earlier than those further away. Third, a temporal to septal gradient is present. Neurons close to the anterior pole of the temporal lobe are born earlier than those more caudally located. Whereas the first two gradients have been observed in other species, the latter gradient has not been reported consistently. Three exceptions to these overall gradients exist. First, neurons near the layer I/II border are born earlier than the majority of the layer II neurons. Second, neurons near the transition zone between two adjacent regions are born earlier than neurons located in the middle of each region. Third, the prosubiculum and subiculum do not exhibit a clear inside-out or temporal to septal gradient.

Quantitative studies of cell size in the cat's dorsal lateral geniculate nucleus following visual deprivation.

The effects of visual deprivation upon dorsal lateral geniculate (DLG) cell size were compared for seven kittens reared with monocular lid-suture (MD), seven with binocular lid-suture (BD), and six with one eye lid-sutured and the other eye enucleated soon after birth (MD-E). Six additional kittens were reared normally for comparison. For each kitten the cross-sectional areas of 300 cells were measured in one or both nuclei. Measurements were taken from the binocular segment of laminae A and A1 and the monocular segment of lamina A. In agreement with previous studies, cells in the binocular segment of the deprived laminae of MD cats were smaller (33-34%) than those in the non-deprived laminae. Comparisons with normal animals indicated that this difference was due to an increase (10-15%) in size of cells in the non-deprived laminae as well as a decrease (23-25%) in size of cells in the deprived laminae. Cells in the monocular segment also were affected by deprivation in MD cats, and this effect increased with the age (and duration of the deprivation) of the animal. However, it was always smaller than the decrease in cell size in the binocular portion of the DLG. In BD kittens, DLG cells were smaller (7-12%) than normal in all portions of the nucleus, including both the binocular and monocular segments. Direct comparisons between the deprived laminae of MD and BD kittens indicated that the decrease in cell size was greater for MD kittens in the binocular segment, but tended to be greater for BD kittens in the monocular segment. In MD-E kittens, DLG cells in the deprived laminae were smaller (11-17%) than normal in all portions of the nucleus, including both the binocular and monocular segments. Thus, the effects of deprivation were similar to those in BD kittens, even though inputs from the deprived eye had been placed at a competitive advantage in MD-E kittens. These results indicate that two factors may affect cell size in the DLG of visually deprived cats: deprivation per se and abnormal binocular competition. Finally, separate analyses for the ten largest and the ten smallest cells in each lamina of each cat were carried out in an attempt to determine if the changes in cell size were limited to the largest cells. In every case, differences observed for the total sample of cells were paralleled by differences from normal of both the largest cells present and the smallest cells present in the deprived laminae. Since at least two alternative interpretations can account for this finding, the question of whether the large cells are selectively affected by visual deprivation remains unanswered in the cat.