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Patterns of hepatitis B virus DNA integration in liver tissue of children with chronic infections.

Although an integration of hepatitis B virus (HBV) DNA in children with chronic HBV infection has been documented at early phases of the disease, the incidence of this process is not known. Therefore we examined nine liver DNA specimens from chronic HBV carriers ages 5-14 years and one sample from a neonate delivered of a carrier mother, in order to determine the HBV DNA patterns of these patients at different ages and phases of chronic infection. The integrated HBV DNA was detected by Southern blot hybridization and analyzed by molecular cloning. Southern blot showed a smear pattern of HBV DNA integration in four of six chronic hepatitis patients (ages 5-14), as well as in one asymptomatic carrier (age 12). Multiple and random integrations occurred during chronic infections in childhood. The neonate did not, however, show signs of any integrations, suggesting that integration starts after HBV multiplication. A band pattern that suggested clonal growth of integrated liver cells was found in a chronic active hepatitis patient (age 9) and in one of two hepatocellular carcinoma patients (age 11). Molecular cloning in two cases with chronic active hepatitis showed that the HBV genome structure was preserved in five of six HBV DNA inserts. Our findings confirm that HBV DNA integration can occur at early stages of chronic HBV infection. In Japanese children, the process of integration seems to be common regardless of HBeAg/anti-HBe status.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Leading with integrity: a qualitative research study.

This research paper gives an account of a study into the relationship between leadership and integrity. There is a critical analysis of the current literature for effective, successful and ethical leadership particularly, integrity. The purpose and aim of this paper is to build on the current notions of leadership within the literature, debate contemporary approaches, focussing specifically on practices within the UK National Health Service in the early 21st century. This leads to a discussion of the literature on ethical leadership theory, which includes public service values, ethical relationships and leading with integrity. A small study was undertaken consisting of 18 interviews with leaders and managers within a District General HospitaL Using the Repertory Grid technique and analysis 15 themes emerged from the constructs elicited, which were compared to the literature for leadership and integrity and other studies. As well as finding areas of overlap, a number of additional constructs were elicited which suggested that effective leadership correlates with integrity and the presence of integrity will improve organisational effectiveness. The study identified that perceptions of leadership character and behaviour are used to judge the effectiveness and integrity of a leader. However, the ethical implications and consequences of leaders' scope of power and influence such as policy and strategy are somewhat neglected and lacking in debate. The findings suggest that leaders are not judged according to the ethical nature of decision making, and leading and managing complex change but that the importance of integrity and ethical leadership correlated with higher levels of hierarchical status and that it is assumed by virtue of status and success that leaders lead with integrity. Finally, the findings of this study seem to suggest that nurse leadership capability is developing as a consequence of recent national investment.

Delivery of Health Care↗

Education needs for integrated care: a literature review.

AIM: This paper reports a systematic review to identify the education needs of the workforce within primary care to promote the effective delivery of integrated health and social care services. BACKGROUND: The need for different professionals to work more closely dominates global health policy. The drive to develop a workforce prepared for the future is crucial to the success of integrated services. However, some have argued that nurses are ill-equipped to meet the challenges of integrated service provision. The ability to work interprofessionally is an important skill which needs to be developed to support integrated working. METHODS: Structured searches were undertaken on organizational websites and the Caredata, CINAHL, Cochrane Library, MEDLINE, Sociofile databases between December 2002 and April 2004 to identify policy documents and primary research studies. The robustness of identified research studies were appraised using recognized appraisal tools. FINDINGS: Six themes were identified which indicate essential elements needed for integrated care. The need for effective communication between professional groups within teams and an emphasis on role awareness are central to the success of integrated services. In addition, education about the importance of partnership working and the need for professionals to develop skills in relation to practice development and leadership through professional and personal development is needed to support integrated working. CONCLUSION: Education which embeds essential attributes to integrated working is needed to advance nursing practice for interprofessional working. Further research exploring this and its impact on integrated provision is essential to ensure that evidence-based services are provided. The reinforcement of partnerships between higher education institutions and health and social care organizations should ensure that the workforce is educated to manage continuous change in service delivery. Innovative ways of teaching and learning which promote inter-professional working need to be explored.

Attitude of Health Personnel↗

Complexity and integration in sexual ornamentation: an example with carotenoid and melanin plumage pigmentation.

Sexual ornaments often consist of several components produced by distinct developmental processes. The complexity of sexual ornaments might be favoured by mate choice of individual components in different environments which ultimately results in weak interrelationships (integration) among the developmental processes that produce these components. At the same time, sexual selection for greater exaggeration of individual components favours their stronger co-dependence on organismal resources. This should ultimately produce stronger condition-mediated integration among ornaments' components in individuals with the most exaggerated ornamentation. Here we distinguish between these two sources of integration by examining the relationship between integration and elaboration of sexual ornamentation in three bird species: two with carotenoid-based sexual ornamentation (the house finch, Carpodacus mexicanus and common redpoll, Carduelis flammea) and a species with melanin-based sexual ornamentation (house sparrow, Passer domesticus). We found that integration of components varied with elaboration of carotenoid-based ornamentation but not of melanin ornamentation. In the house finches, integration was the highest in individuals with small ornaments and decreased with ornament elaboration whereas the pattern was the opposite in common redpolls. These results suggest that in these species integration and complexity of carotenoid-based ornamental components are due to shared condition-dependence of distinct developmental pathways, whereas integration and complexity of the melanin ornamentation is due to organismal integration of developmental pathways and is largely condition- and environment-invariant. Thus, functionally, ornamentation of the house sparrows can be considered a single trait, whereas complexity of the house finch and redpoll ornamentation varies with ornament elaboration and individual condition.

Animals↗

Cre-mediated site-specific gene integration for consistent transgene expression in rice.

To minimize expression variability amongst transgenic lines, we have utilized the strategy of Cre/lox-mediated site-specific gene integration. This method allows the precise integration of a transgene in a lox site previously placed in the genome. Using the biolistic method for DNA delivery, we have generated several site-specific integrant lines, derived from three different target lines. About 80% of the selected lines contain precise integration of the gusA reporter gene and fall into two categories: single-copy (SC) lines that contain site-specific integration without additional random integrations, and multicopy (MC) lines that contain random integrations in addition to the site-specific integration. The expression of the gusA gene was studied in callus cells and regenerated plants. The isogenic SC lines displayed significantly lower expression variation, whereas much higher expression variation was observed in MC lines. Furthermore, stable inheritance of the gusA gene was observed in T1 plants derived from a subset of SC lines. This demonstrates that consistent gene expression can be obtained in rice by Cre-mediated site-specific integration.

Journal Article↗

Evolutionary integration and morphological diversification in complex morphological structures: mandible shape divergence in spiny rats (Rodentia, Echimyidae).

The rodent mandible has become a paradigm for studies on the development and evolution of complex morphological structures. We use a combination of geometric and multivariate morphometric methods in order to assess the correspondence between integration patterns and a priori biological models in the context of evolutionary shape divergence in the mandible of rodents of the family Echimyidae. The correlation of shape distances among operational taxonomic units (individuals, species, genera) in separate morphogenetic components allowed the construction of integration matrices among mandible components for data sets corresponding to varying levels of genetic divergence (intergeneric, interspecific, and intrapopulational). The integration matrices were associated with a priori biological (developmental, genetical, modular) models, and the maximum integration axes (singular warps) were compared with realized axes of maximum interspecific variation (relative warps). The integration pattern and intensity were not stable in data sets with different levels of genetic divergence, and the varying functional demands during the ecological radiation in the family were probably responsible for the differences in observed integration patterns. Developmental and genetic models were significantly associated with the interspecific integration patterns observed, suggesting a role for neutral evolution during the evolutionary divergence of mandible shape. However, directional and stabilizing selection were not discarded as processes responsible for the generation of interspecific integration. The choreography of the morphogenetic components in the mandible is highly flexible and the integrated groups of components can be reorganized depending on functional demands during evolutionary shape changes.

Animals↗

Integrated acidity and the pathophysiology of gastroesophageal reflux disease.

OBJECTIVES: The aim of this study was to demonstrate that integrated esophageal and gastric acidity values, calculated from 24-h pH recordings, can provide more precise quantitative temporal data than the conventional pH parameters historically associated with gastroesophageal reflux disease (GERD) investigations. METHODS: Esophagogastroduodenoscopy results and pH tracings from 20 GERD subjects with > or =10% esophageal acid contact time were studied. Integrated gastric and esophageal acidity were calculated from time-weighted average hydrogen ion concentrations at each second of the 24-h recording period. RESULTS: Integrated esophageal acidity correlated with grade of esophagitis. Two quite distinct GERD subtypes were identified, with either a monophasic or biphasic pattern of integrated esophageal acidity. "Biphasic" subjects differed from "monophasic" subjects in terms of magnitude and pattern of integrated esophageal acidity. Although both groups had significant integrated nocturnal gastric acidity, only the biphasic GERD subjects had concomitant increases in nocturnal integrated esophageal acidity. Esophagitis grade was correlated with magnitude rather than pattern of integrated esophageal acidity, and it was possible to calculate a reflux coefficient that seems to provide an estimate of the quantitative motor disturbance present in GERD. CONCLUSIONS: Integrated esophageal and gastric acidity provide quantitative measures of GERD pathophysiology and, compared to conventional pH parameters, should enhance evaluation of therapeutic interventions.

Acids↗

Disabling of the oculomotor neural integrator by kainic acid injections in the prepositus-vestibular complex of the cat.

1. This study was intended to test the candidature of the prepositus-vestibular nuclear complex for being the location of the oculomotor neural integrator (Robinson's integrator). 2. Microinjections of kainic acid (2 micrograms dissolved in 1 microliter) were made in awake cats. Injection sites were located either in the prepositus hypoglossi nucleus (p.h.), the medial vestibular nucleus (m.v.n.), the medial longitudinal fasciculus (m.l.f.) or in the magnocellular tegmental field of the reticular formation. 3. Theory predicts that a complete disabling of the neural integrator will cause (a) an exponential post-saccadic drift whose time constant will be 0.16 s in the dark (b) a phase lead of +93 deg as the vestibulo-ocular reflex is tested at 0.10 Hz in the dark and (c) a nearly complete abolition of the optokinetic nystagmus (o.k.n.). 4. About 1 h after a unilateral kainic acid injection in the p.h., we observed (a) a large bilateral post-saccadic drift (time constant sometimes as low as 0.2 s) (b) a large phase lead at 0.10 Hz (range: from +69 to +98 deg) (c) an abolition of the o.k.n. control injection of phosphate buffer in the p.h. did not produce any deficit. 5. A unilateral kainic acid injection in the m.v.n. induced a nystagmus followed by signs of bilateral failure of the neural integrator similar to those observed after kainic acid injection in the p.h. 6. Injection near the mid-line, between the two p.h. nuclei, induced a defect of the neural integrator less than that observed after kainic acid injection in either the p.h. or the m.v.n. Injection of kainic acid in the magnocellular tegmental field of the reticular formation did not produce any sign of failure of the neural integrator. No post-saccadic drift was observed. 7. We have concluded that (a) the p.h. nucleus is involved in the integration processing, and that (b) the m.v.n. is involved either in the integration processing or in the relaying of the output of the neural integrator to the oculomotoneurones.

Animals↗

Study of noise propagation and the effects of insufficient numbers of projection angles and detector samplings for iterative reconstruction using planar-integral data.

A rotating slat collimator can be used to acquire planar-integral data. It achieves higher geometric efficiency than a parallel-hole collimator by accepting more photons, but the planar-integral data contain less tomographic information that may result in larger noise amplification in the reconstruction. Lodge evaluated the rotating slat system and the parallel-hole system based on noise behavior for an FBP reconstruction. Here, we evaluate the noise propagation properties of the two collimation systems for iterative reconstruction. We extend Huesman's noise propagation analysis of the line-integral system to the planar-integral case, and show that approximately 2.0(D/dp) SPECT angles, 2.5(D/dp) self-spinning angles at each detector position, and a 0.5dp detector sampling interval are required in order for the planar-integral data to be efficiently utilized. Here, D is the diameter of the object and dp is the linear dimension of the voxels that subdivide the object. The noise propagation behaviors of the two systems are then compared based on a least-square reconstruction using the ratio of the SNR in the image reconstructed using a planar-integral system to that reconstructed using a line-integral system. The ratio is found to be proportional to the square root of F/D, where F is a geometric efficiency factor. This result has been verified by computer simulations. It confirms that for an iterative reconstruction, the noise tradeoff of the two systems is not only dependent on the increase of the geometric efficiency afforded by the planar projection method, but also dependent on the size of the object. The planar-integral system works better for small objects, while the line-integral system performs better for large ones. This result is consistent with Lodge's results based on the FBP method.

Artifacts↗

Spectral integration in bands of modulated or unmodulated noise.

Spectral integration was measured for pure-tone signals masked by unmodulated or modulated noise bands centered at the signal frequencies. The bands were typically 100 Hz wide, and when modulated, they were sinusoidally amplitude modulated at a rate of 8 Hz and a depth of 100%. In experiment 1, thresholds were first measured for each individual pure tone of a triplet in the presence of its respective masker band, and then for those three tones added together at their respective threshold levels, masked by their respective masker bands. Four sets of triplets were used: 250, 1000, 4000 Hz; 354, 1000, 2828 Hz; 500, 1000, 2000 Hz; and 800, 1000, 1200 Hz. When the masker bands were unmodulated, the amount of spectral integration was about 2.4 dB for all triplets, consistent with the integration expected based on the multiband energy detector model. When the bands were modulated, the amount of integration depended upon the spacing between masker bands; for the two widest spacings, the integration was between about 0 and 3 dB, whereas for the two closest spacings, the integration was approximately 5 dB. Experiments 2 and 3 addressed the cause of this greater spectral integration in the presence of the modulated masker bands with closer spacing. The second experiment demonstrated that sensitivity (d') was proportional to signal power regardless of whether the background noise was modulated or not, and thus the greater integration in dB in the presence of the modulated noise bands could not be accounted for by shallower psychometric functions in those conditions. Instead, the third experiment showed that the greater integration was likely due to the fact that the masker bands were comodulated. In other words, it was probably due to cues related to comodulation masking release when all three bands (and signals) were present.

Adult↗

H-NS regulation of virulence gene expression in enteroinvasive Escherichia coli harboring the virulence plasmid integrated into the host chromosome.

We have previously shown that integration of the virulence plasmid pINV into the chromosome of enteroinvasive Escherichia coli and of Shigella flexneri makes these strains noninvasive (C. Zagaglia, M. Casalino, B. Colonna, C. Conti, A. Calconi, and M. Nicoletti, Infect. Immun. 59:792-799, 1991). In this work, we have studied the transcription of the virulence regulatory genes virB, virF, and hns (virR) in wild-type enteroinvasive E. coli HN280 and in its pINV-integrated derivative HN280/32. While transcription of virF and of hns is not affected by pINV integration, transcription of virB is severely reduced even if integration does not occur within the virB locus. This indicates that VirF cannot activate virB transcription when pINV is integrated, and this lack of expression accounts for the noninvasive phenotype of HN280/32. Virulence gene expression in strains HN280 and HN280/32, as well as in derivatives harboring a mxiC::lacZ operon fusion either on the autonomously replicating pINV or on the integrated pINV, was studied. The effect of the introduction of plasmids carrying virB (pBNI) or virF (pHW745 and pMYSH6504), and of a delta hns deletion, in the different strains was evaluated by measuring beta-galactosidase activity, virB transcription, and virB-regulated virulence phenotypes like synthesis of Ipa proteins, contact-mediated hemolysis, and capacity to invade HeLa cells. The introduction of pBN1 or of the delta hns deletion in pINV-integrated strains induces temperature-regulated expression or temperature-independent expression, respectively, of beta-galactosidase activity and of all virulence phenotypes, while an increase in virF gene dosage does not, in spite of a high-level induction of virB transcription. Moreover, a wild-type hns gene placed in trans fully reversed the induction of beta-galactosidase activity due to the delta hns deletion. These results indicate that virB transcription is negatively regulated by H-NS both at 30 and at 37 degrees C in pINV-integrated strains and that there is also a dose-dependent effect of VirF on virB transcription. The negative effect of H-NS on virB transcription at the permissive temperature of 37 degrees C could be due to changes in the DNA topology occurring upon pINV integration that favor more stable binding of H-NS to the virB promoter DNA region. At 30 degrees C, the introduction of the high-copy-number plasmid pMYSH6504 (but not of the low-copy-number pHW745) or of the deltahns deletion induces, in strains harboring an autonomously replicating pINV, beta-galactosidase activity, virB transcription, and expression of the virulence phenotypes, indicating that, as for HN280/32, the increase in virF gene dosage overcomes the negative regulatory effect of H-NS on virB transcription. Moreover, we have found that virF transcription is finely modulated by temperature and, with E. coli K-12 strains containing a virF-lacZ gene fusion, by H-NS. This leads us to speculate that, in enteroinvasive bacteria, the level of Virf inside the cell controls the temperature-regulated expression of invasion genes.

Animals↗

Plasmid integration in a wide range of bacteria mediated by the integrase of Lactobacillus delbrueckii bacteriophage mv4.

Bacteriophage mv4 is a temperate phage infecting Lactobacillus delbrueckii subsp. bulgaricus. During lysogenization, the phage integrates its genome into the host chromosome at the 3' end of a tRNA(Ser) gene through a site-specific recombination process (L. Dupont et al., J. Bacteriol., 177:586-595, 1995). A nonreplicative vector (pMC1) based on the mv4 integrative elements (attP site and integrase-coding int gene) is able to integrate into the chromosome of a wide range of bacterial hosts, including Lactobacillus plantarum, Lactobacillus casei (two strains), Lactococcus lactis subsp. cremoris, Enterococcus faecalis, and Streptococcus pneumoniae. Integrative recombination of pMC1 into the chromosomes of all of these species is dependent on the int gene product and occurs specifically at the pMC1 attP site. The isolation and sequencing of pMC1 integration sites from these bacteria showed that in lactobacilli, pMC1 integrated into the conserved tRNA(Ser) gene. In the other bacterial species where this tRNA gene is less or not conserved; secondary integration sites either in potential protein-coding regions or in intergenic DNA were used. A consensus sequence was deduced from the analysis of the different integration sites. The comparison of these sequences demonstrated the flexibility of the integrase for the bacterial integration site and suggested the importance of the trinucleotide CCT at the 5' end of the core in the strand exchange reaction.

Bacteriophages↗

Integration of proviral DNA in chicken cells infected with Schmidt-Ruppin Rous sarcoma virus is not enhanced by DNA repair.

The effect DNA repair might have on the integration of exogenous proviral DNA into host cell DNA was investigated by comparing the efficiency of proviral DNA integration in normal chicken embryonic fibroblasts and in chicken embryonic fibroblasts treated with UV or 4-nitroquinoline-1-oxide. The cells were treated with UV or 4-nitroquinoline-1-oxide at various time intervals ranging from 6 h before to 24 h after infection with Schmidt-Ruppin strain A of Rous sarcoma virus. The chicken embryonic fibroblasts were subsequently cultured for 18 to 21 days to ensure maximal integration and elimination of nonintegrated exogenous proviral DNA before DNA was extracted. Integration of proviral DNA into the cellular genome was quantitated by hybridization of denatured cellular DNA on filters with an excess of (3)H-labeled 35S viral RNA. The copy number of the integrated proviruses in normal cells and in infected cells was also determined from the kinetics of liquid RNA-DNA hybridization in DNA excess. Both RNA excess and DNA excess methods of hybridization indicate that two to three copies of the endogenous provirus appear to be present per haploid normal chicken cell genome and that two to three copies of the provirus of Schmidt-Ruppin strain A of Rous sarcoma virus become integrated per haploid cell genome after infection. The copy number of viral genome equivalents integrated per cell treated with UV or 4-nitroquinoline-1-oxide at different time intervals before or after infection did not differ from the copy number in untreated but infected cells. This finding supports our previous report that the integration of oncornavirus proviral DNA is restricted to specific sites in the host cell DNA and suggests a specific mechanism for integration.

4-Nitroquinoline-1-oxide↗

Free and integrated forms of hepatitis B virus DNA in human hepatocellular carcinoma cells (PLC/342) propagated in nude mice.

Primary hepatocellular carcinoma cells (PLC/342) propagated in nude mice produce hepatitis B surface antigen of subtype adr, as well as core particles containing viral DNA and DNA polymerase. Free and integrated forms of hepatitis B virus (HBV) DNA in the tumor were isolated by molecular cloning, and their nucleotide sequences were determined. Both of the two representative clones of free HBV DNA had the same genomic length (3,158 base pairs) and had two stop codons as well as two deletions in the envelope gene. None of the seven distinct clones of integrated HBV DNA possessed the entire viral genome. The integrated clone sequences had deletions and rearrangements, and only two clones possessed the envelope gene including the promoter and enhancer sequences. The C gene, which codes for core protein, was preserved in the two free clones and one of the integrated clones. The P gene, which codes for DNA polymerase, had deletions at two positions of 21 and 36 base pairs in both free clones, but was carried in toto by one of the integrated clones. The nucleotide sequences of the S genes of two free and four integrated clones, as well as their two inverted repeats, were compared. All of the eight sequences of the S gene possessed two nucleotide substitutions in common that were not displayed by any of the reported HBV genomes. The sequences differed from one another by only 1.2%. They differed, however, from 11 reported HBV genomes of subtype adr by 2.4%, from an ayr genome by 1.9%, from 2 adw genomes by 6.9%, and from 2 ayw genomes by 5.9%. These results indicate that all free and integrated HBV DNA species in the PLC/342 tumor cell evolved from a common progenitor. The free HBV DNA underwent nucleotide substitutions during several integration events, resulting in integrated HBV DNA copies that were similar in sequence but distinct from the reported HBV genomes.

Animals↗

Integration of foveal orientation signals: distinct local and long-range spatial domains.

Human observers can discriminate the orientation of a stimulus configuration composed of a pair of collinear visual patterns much better than that of a single component pattern alone. Previous investigations of this type of orientation signal integration and of other similar visual integrative functions have shown that, for closely spaced elements, there is integration only for stimuli with the same contrast polarity (i.e., both lighter or both darker than the background) but, at greater separations, integration is independent of contrast polarity. Is this effect specific to differences in contrast polarity, which is known to be an important parameter in the organization of the visual system, or might there be a cluster of other stimulus dimensions that show similar effects, indicating a more widespread distinction between the processes limiting integration at local and long-range spatial scales? Here, we report a similar distance dependence for orientation signal integration across stimulus differences in binocular disparity, direction of motion, and direction of figure-ground assignment. We also demonstrate that the selectivity found at short separations cannot be explained only by "end-cuts," the small borders created at the junction of abutting contrasting patterns. These findings imply the existence of two distinct spatial domains for the integration of foveal orientation information: a local zone in which integration is highly selective for a number of salient stimulus parameters and a long-range domain in which integration is relatively unselective and only requires that patterns be roughly collinear.

Contrast Sensitivity↗

Linear regression of eye velocity on eye position and head velocity suggests a common oculomotor neural integrator.

The oculomotor system produces eye-position signals during fixations and head movements by integrating velocity-coded saccadic and vestibular inputs. A previous analysis of nucleus prepositus hypoglossi (nph) lesions in monkeys found that the integration time constant for maintaining fixations decreased, while that for the vestibulo-ocular reflex (VOR) did not. On this basis, it was concluded that saccadic inputs are integrated by the nph, but that the vestibular inputs are integrated elsewhere. We re-analyze the data from which this conclusion was drawn by performing a linear regression of eye velocity on eye position and head velocity to derive the time constant and velocity bias of an imperfect oculomotor neural integrator. The velocity-position regression procedure reveals that the integration time constants for both VOR and saccades decrease in tandem with consecutive nph lesions, consistent with the hypothesis of a single common integrator. The previous evaluation of the integrator time constant relied upon fitting methods that are prone to error in the presence of velocity bias and saccades. The algorithm used to evaluate imperfect fixations in the dark did not account for the nonzero null position of the eyes associated with velocity bias. The phase-shift analysis used in evaluating the response to sinusoidal vestibular input neglects the effect of saccadic resets of eye position on intersaccadic eye velocity, resulting in gross underestimates of the imperfections in integration during VOR. The linear regression method presented here is valid for both fixation and low head velocity VOR data and is easy to implement.

Animals↗

Body-surface QRST integral mapping. Arrhythmogenic righ ventricular dysplasia versus idiopathic right ventricular tachycardia.

BACKGROUND: Ventricular tachycardia originating in the right ventricle may arise in the presence or absence of structural heart disease. The two main causes of right ventricular tachycardia are arrhythmogenic right ventricular dysplasia (ARVD) and idiopathic right ventricular tachycardia (IRVT) originating from the outflow tract. This study was carried out to determine whether body-surface QRST integral mapping can differentiate patients with ARVD from patients with IRVT. METHODS AND RESULTS: Body-surface QRST integral maps were obtained during sinus rhythm in 8 patients with ARVD, 8 patients with IRVT, and 27 healthy control subjects. QRST integral maps were analyzed both visually and mathematically. All control subjects had a normal dipolar QRST integral map. In all patients with ARVD, a specific dipolar QRST integral map with an abnormally large negative area covering the entire inferior and right anterior thorax was recorded. In 6 of 8 patients with IRVT, a normal map pattern was found, whereas the remaining 2 patients showed an abnormally large negative area on the right anterior thorax. CONCLUSIONS: Patients with ARVD display a specific abnormal QRST integral map that may be related to delayed repolarization in the structurally abnormal right ventricle. The majority of patients with IRVT demonstrate a normal QRST integral map. A slightly abnormal QRST integral map was noted in 2 of 8 patients with IRVT, which may be related to minor structural abnormalities, undetectable by the present routine diagnostic techniques. These preliminary results indicate that body-surface QRST integral mapping may become an important diagnostic tool to differentiate patients with ARVD from those with IRVT.

Adult↗

Adhesion structures of amniotic membranes integrated into human corneas.

PURPOSE: The aim of this study was to investigate the structural relationship between integrated amniotic membrane (AM) and corneal tissues in various integration patterns, focusing on adhesion structures along the interface. METHODS: Fourteen eyes of 14 patients (age, 65.8 +/- 13.5 years) underwent penetrating keratoplasty (PKP) 19.3 +/- 20.7 weeks after cryopreserved human AM transplantation (AMT). The corneal buttons (after PKP) and the corresponding original AM (before AMT) were examined with the use of transmission electron microscopy (TEM) and immunohistochemistry for integrin beta4, type VII collagen, and laminin. Main outcome measures included thickness of the corneal epithelium and AM, density of the epithelial desmosomes and hemidesmosomes, continuity, and thickness of the epithelial basement membrane. RESULTS: Integrated AM was found by slit lamp in only 2 of 14 patients, but histology and TEM revealed AM integration in 11 of 14 patients up to 77 weeks after AMT. No amniotic epithelial cell was detected in any cornea with integrated AM stroma. Three basic patterns of integration could be described: subepithelial, intraepithelial, and intrastromal. Hemidesmosomes anchored the corneal epithelial cells to the AM at a density up to 165.3 +/- 22.9 per 100 microm cell membrane length. Discontinuous basement membrane segments 17.2 +/- 4.9 nm thick could be detected. Desmosomes among recovered corneal epithelial cells were found at a density of 21.2 +/- 5.3 per 10 microm cell membrane length. CONCLUSIONS: The AM stroma can integrate into the host corneal tissue. Integration is associated with the formation of adhesion structures such as hemidesmosomes and desmosomes, which provide anchoring and stability of the regenerating corneal epithelium. The presence of integrated AM and adhesion structures with host corneal tissue supports the clinical experience obtained with AMT in ocular surface disease.

Aged↗