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PubMed2004

Role of virus-induced myocardial affections in sudden infant death syndrome: a prospective postmortem study.

The cause of sudden infant death syndrome (SIDS) is an unresolved problem of high relevance. Previous studies indicate a role of infections. In our prospective study, we investigated the frequency of virus-induced myocardial affections in SIDS. Postmortem samples from SIDS victims and control subjects were investigated prospectively. Pediatric cases of unnatural death served as controls. Samples were studied for enteroviruses, adenoviruses, parvovirus B19, and Epstein-Barr virus applying PCR. Immunohistochemical investigations for inflammatory cells, the necrosis marker C5b-9((m)) complement complex, and the enteroviral capsid protein VP1 were performed. Overall, 62 SIDS victims were studied. As controls, 11 infants were enrolled. Enteroviruses were detected in 14 (22.5%), adenoviruses in 2 (3.2%), Epstein-Barr viruses in 3 (4.8%), and parvovirus B19 in 7 (11.2%) cases of SIDS. Control group samples were completely virus negative. Compared with controls, immunohistochemical investigations partially revealed a significant increase in the number of T lymphocytes in SIDS myocardial samples (p < 0.05). Furthermore, cases with elevated numbers of leukocytes and macrophages, microfocal C5b-9((m))(+) necroses, and enteroviral VP1 capsid protein within the myocardium were detected. Applying a comprehensive combination of molecular and immunohistochemical techniques, our results demonstrate a clearly higher prevalence of viral myocardial affections in SIDS. Our results emphasize the importance of PCR-based diagnosis of viral myocardial affections. We suggest preliminary criteria for cellular immunohistochemical diagnosis of viral myocardial affections derived from our findings. For future investigations in SIDS, we suggest a comprehensive approach that includes PCR and immunohistochemistry. Our results offer novel strategies for diagnosis of pediatric myocardial viral affections.

Adenoviruses, Human↗
PubMed1999

Affective verbal memory in patients with temporal lobe epilepsy.

Eighteen epileptic patients with unilateral temporal lobe epilepsy (9 left, 9 right) were evaluated with a verbal memory task involving recall of 2 stories, 1 with affective content and 1 that was neutral. A trend for better performance by the group with intact left hemispheres was found for a quantitative score of number of story units recalled. For a qualitative score of number of symbolic distortions, a main effect of affective load was found, such that more distortions were made for the story with affective than neutral content. This effect remained significant when the left temporal lobe epilepsy patients were analyzed separately and was not found for the right temporal lobe epilepsy patients alone. Additional analyses for the subset of 5 patients with left and 6 patients with right temporal lobectomies involving removal of the hippocampus and amygdala were in the same direction as the analyses for all 18 participants. These findings are consistent with other reports of material-specific memory deficits, such that verbal memory deficits are associated with left temporal lobe epilepsy. The differences between performance on the affective and neutral stories for the left and right temporal lobe epilepsy patients are discussed and related to the role of the amygdala in affective processing.

Adult↗
PubMed2000

Formulation variables affecting drug release from xanthan gum matrices at laboratory scale and pilot scale.

The purpose of this research was to study processing variables at the laboratory and pilot scales that can affect hydration rates of xanthan gum matrices containing diclofenac sodium and the rate of drug release. Tablets from the laboratory scale and pilot scale proceedings were made by wet granulation. Swelling indices of xanthan gum formulations prepared with different amounts of water were measured in water under a magnifying lens. Granules were thermally treated in an oven at 60 degrees C, 70 degrees C, and 80 degrees C to study the effects of elevated temperatures on drug release from xanthan gum matrices. Granules from the pilot scale formulations were bulkier compared to their laboratory scale counterparts, resulting in more porous, softer tablets. Drug release was linear from xanthan gum matrices prepared at the laboratory scale and pilot scales; however, release was faster from the pilot scales. Thermal treatment of the granules did not affect the swelling index and rate of drug release from tablets in both the pilot and laboratory scale proceedings. On the other hand, the release from both proceedings was affected by the amount of water used for granulation and the speed of the impeller during granulation. The data suggest that processing variables that affect the degree of wetness during granulation, such as increase in impeller speed and increase in amount of water used for granulation, also may affect the swelling index of xanthan gum matrices and therefore the rate of drug release.

Chemistry, Pharmaceutical↗
PubMed2005

A new dominant distal myopathy affecting posterior leg and anterior upper limb muscles.

OBJECTIVE: To report a dominant, slowly progressive early onset distal myopathy with sparing of the tibialis anterior. METHODS: Twelve affected and two possibly affected members from an Australian kindred were examined and investigated by EMG, imaging studies, histopathology, and genetic analysis. RESULTS: Affected patients had a slowly progressive condition with symmetric, distal weakness and wasting of the anterior upper and posterior lower limbs, with sparing of tibialis anterior, even in advanced disease. All patients remained ambulant and there was no evidence of cardiac or respiratory muscle involvement. Serum creatine kinase levels were either normal or mildly elevated. Imaging studies showed widespread involvement of the posterior and lateral leg compartments. Proximal muscles were radiologically abnormal only in advanced disease. Muscles that were mildly affected clinically appeared normal on imaging. EMG in nine patients showed widespread myopathic changes. Muscle histopathology in four patients showed either end stage muscle or nonspecific myopathic findings without inflammation or vacuoles. Microsatellite markers for distal myopathy loci were analyzed and all known distal myopathy phenotype genes and linkage regions were formally excluded by multipoint analysis. CONCLUSIONS: The affected patients in this kindred display a clinically distinct myopathy, with selective involvement of posterior lower and anterior upper limb muscles. The genetic analysis suggests the existence of one more distal myopathy locus.

Adolescent↗
PubMed1996

Mutations affecting the development of the embryonic zebrafish brain.

In a large scale mutagenesis screen for embryonic mutants in zebrafish, we have identified 63 mutations in 24 loci affecting the morphogenesis of the zebrafish brain. The expression of marker genes and the integrity of the axonal scaffold have been studied to investigate abnormalities in regionalization, neurogenesis and axonogenesis in the brain. Mutants can be broadly classified into two groups, one affecting regionalization along the anterior-posterior or dorsal-ventral axis, and the other affecting general features of brain morphology. The first group includes one locus that is required to generate the anlage of the midbrain-hindbrain boundary region at the beginning of somitogenesis. Four loci were identified that affect dorsal-ventral patterning of the brain, including the previously described cyclops locus. Mutant embryos of this class show a reduction of ventral neuroectodermal structures and variable fusion of the eyes. The second group includes a large class of mutations affecting the formation of brain ventricles. Analysis of this class reveals the requirement of a functional cardiovascular system for ventricle enlargement during embryogenesis. Mutations in one locus lead to the formation of supernumerary primary neurons, a phenotype reminiscent of neurogenic mutants in Drosophila. Other mutant phenotypes described here range from abnormalities in the fasciculation and outgrowth of axons to defects in the diameter of the neural tube. The identified loci establish the genetic foundation for a further analysis of the development of the zebrafish embryonic brain.

Animals↗
PubMed1996

Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo.

As part of a large-scale mutagenesis screen of the zebrafish genome, we have identified 58 mutations that affect the formation and function of the cardiovascular system. The cardiovascular system is particularly amenable for screening in the transparent zebrafish embryo because the heart and blood vessels are prominent and their function easily examined. We have classified the mutations affecting the heart into those that affect primarily either morphogenesis or function. Nine mutations clearly disrupt the formation of the heart. cloche deletes the endocardium. In cloche mutants, the myocardial layer forms in the absence of the endocardium but is dysmorphic and exhibits a weak contractility. Two loci, miles apart and bonnie and clyde, play a critical role in the fusion of the bilateral tubular primordia. Three mutations lead to an abnormally large heart and one to the formation of a diminutive, dysmorphic heart. We have found no mutation that deletes the myocardial cells altogether, but one, pandora, appears to eliminate the ventricle selectively. Seven mutations interfere with vascular integrity, as indicated by hemorrhage at particular sites. In terms of cardiac function, one large group exhibits a weak beat. In this group, five loci affect both chambers and seven a specific chamber (the atrium or ventricle). For example, the weak atrium mutation exhibits an atrium that becomes silent but has a normally beating ventricle. Seven mutations affect the rhythm of the heart causing, for example, a slow rate, a fibrillating pattern or an apparent block to conduction. In several other mutants, regurgitation of blood flow from ventricle to atrium is the most prominent abnormality, due either to the absence of valves or to poor coordination between the chambers with regard to the timing of contraction. The mutations identified in this screen point to discrete and critical steps in the formation and function of the heart and vasculature.

Animals↗
PubMed1996

Mutations affecting craniofacial development in zebrafish.

In a large-scale screen for mutations affecting embryogenesis in zebrafish, we identified 48 mutations in 34 genetic loci specifically affecting craniofacial development. Mutants were analyzed for abnormalities in the cartilaginous head skeleton. Further, the expression of marker genes was studied to investigate potential abnormalities in mutant rhombencephalon, neural crest, and pharyngeal endoderm. The results suggest that the identified mutations affect three distinct aspects of craniofacial development. In one group, mutations affect the overall pattern of the craniofacial skeleton, suggesting that the genes are involved in the specification of these elements. Another large group of mutations affects differentiation and morphogenesis of cartilage, and may provide insight into the genetic control of chondrogenesis. The last group of mutations leads to the abnormal arrangement of skeletal elements and may uncover important tissue-tissue interactions underlying jaw development.

Animals↗
PubMed1996

Mutations affecting cell fates and cellular rearrangements during gastrulation in zebrafish.

One of the major challenges of developmental biology is understanding the inductive and morphogenetic processes that shape the vertebrate embryo. In a large-scale genetic screen for zygotic effect, embryonic lethal mutations in zebrafish we have identified 25 mutations that affect specification of cell fates and/or cellular rearrangements during gastrulation. These mutations define at least 14 complementation groups, four of which correspond to previously identified genes. Phenotypic analysis of the ten novel loci revealed three groups of mutations causing distinct effects on cell fates in the gastrula. One group comprises mutations that lead to deficiencies in dorsal mesodermal fates and affect central nervous system patterning. Mutations from the second group affect formation of ventroposterior embryonic structures. We suggest that mutations in these two groups identify genes necessary for the formation, maintenance or function of the dorsal organizer and the ventral signaling pathway, respectively. Mutations in the third group affect primarily cellular rearrangements during gastrulation and have complex effects on cell fates in the embryo. This group, and to some extent mutations from the first two groups, affect the major morphogenetic processes, epiboly, convergence and extension, and tail morphogenesis. These mutations provide an approach to understanding the genetic control of gastrulation in vertebrates.

Animals↗
PubMed1999

[Research on the influences that affect the physician's perception of discharge summaries. A survey of outpatient department physicians].

The object of this study was to improve the completion of discharge summaries. The purpose of this article is: 1. to describe the perceptions of outpatient department physicians as to whether incomplete discharge summaries affect outpatient medical care or not, and 2. to elucidate the factors contributing to their perceptions. The physicians were randomly selected from among "the National Certified Training Hospitals" and "Japan Society for Quality in Health Care", and the size of the hospitals, the medical record management system and the format of the discharge summary were chosen for analysis of the factors that affect physicians' perceptions. Of the 2,304 questionnaires sent, 935 (40.6%) were returned. The results showed that 832 (89.0%) of the physicians thought that outpatient medical care would be affected if discharge summaries were not completed. Based on the analysis of the factors affecting the perceptions of the physicians, there was a trend showing that the influence was lower in small hospitals (p < 0.05), that the centralized management system for medical records had a higher influence (p < 0.05), and that the format of the discharge summary also affects physician's perceptions (p < 0.05).

Ambulatory Care↗
PubMed2004

A consistent abnormality in the average local smoothness of fetal heart rate in growth-restricted fetuses affected by severe pre-eclampsia.

An abnormality in cardiovascular regulation during the prenatal period has been suggested to be the pathophysiological link between fetal growth restriction and adult hypertension. The purpose of this study was to determine how consistently abnormal the local smoothness of the very-short-term heart rate is in growth-restricted fetuses associated with severe pre-eclamptic pregnancy. Multifractal Hurst analysis on the structure function of heart rate was performed in control fetuses (n =150), in fetuses affected by severe pre-eclampsia and not showing growth restriction (n =66) and in fetuses affected by severe pre-eclampsia and showing growth restriction (n =58). The very-short-term (< or =15 heart beats) generalized Hurst exponents of the order of -5 to 5 in three groups were compared. Each exponent quantifies an average local heart rate smoothness at 15-successive-heart rate sites, which were specified by the magnitude of the heart rate variation within the sites determined by and positively correlated with the order of the exponent. This means that the fetal heart rates within the sites of q > or =2 have a large fetal heart rate (FHR) variation, and those within the sites of q < or =-2 have a small FHR variation. In the fetuses affected by severe pre-eclampsia and not showing growth restriction, only values of the exponents of the order > or =2 were abnormally lower. In the fetuses affected by severe pre-eclampsia and showing growth restriction, the values of the exponents of all orders were abnormally lower. In conclusion, the local smoothness of heart rate is consistently abnormal regardless of the magnitude of heart rate variation within a very-short-term period in growth-restricted fetuses affected by severe pre-eclampsia.

Adult↗
PubMed2004

Using the blink reflex as measured by electromyogram to assess cranial nerve involvement in people affected by leprosy.

Damage to the peripheral nervous system is particularly frequent in leprosy patients. Trigeminal and facial nerves are among the most commonly affected. The aim of our study was to evaluate the efficacy of the blink reflex as a method for diagnosis of cranial nerve involvement in people affected by leprosy. We studied 37 affected people (mean age: 38 yrs, 20 female and 17 male) and 35 age-matched healthy subjects (mean age: 34 yrs, 20 female and 15 male). Blink reflexes were obtained after unilateral electrical stimulation of the supraorbital nerve for quantitative analysis of 3 responses, early ipsilateral phasic component (R1), late ipsilateral tonic component (R2i), and late contralateral tonic component (R2c). Nerve conduction parameters were studied in all subjects. The latencies of both the ipsilateral early phasic component (R1) and bilateral late tonic components (R2i and R2c) in people affected by leprosy were significantly prolonged compared with the controls. Out of 37 people affected by leprosy, 22 (59%) showed abnormalities R1 latency, 28 (75%) R2i latency and 31 (83%) R2c latency. No correlation was observed between prolonged latencies and duration of the disease. We conclude that blink reflex testing, which can be easily and rapidly performed in an EMG laboratory using standard equipment, can provide useful and objective information for the diagnosis of cranial nerve lesions and for the determination of the degree thereof.

Adult↗
PubMed2003

Factors affecting intestinal absorption of highly lipophilic food microconstituents (fat-soluble vitamins, carotenoids and phytosterols).

Highly lipophilic food microconstituents (HLFMs) with octanol-water partition coefficients log10 P(c) > 8 include the fat-soluble vitamins (A, E, D and K) and phytochemicals with potential health benefits, the carotenoids and phytosterols. It has been assumed that these compounds have the same metabolism in the human upper gastrointestinal tract and that they follow the same fate as lipids. However, a literature review shows that the metabolism of HLFMs in the upper gastrointestinal tract depends on each HLFM species. For example, some HLFM esters are hydrolyzed mainly by pancreatic lipase, others by bile salt-stimulated lipase; some HLFMs are apparently absorbed by passive diffusion, others by a transporter. Also, although some factors (HLFM molecular species, fat, food matrix) affect absorption efficiency of most HLFMs, other factors (fibers, microconstituents) apparently affect absorption only of some HLFMs. The mnemonic acronym SLAMENGHI, previously proposed to list the factors affecting the bioavailability of carotenoids, was used here to review current knowledge of the factors suspected to affect the intestinal absorption of HLFMs. The available data reveal numerous gaps in the knowledge of the metabolism of HLFMs and the factors that affect their absorption. These gaps need to be filled to be able to formulate HLFMs so as to promote greater absorption efficiency.

Age Factors↗
PubMed2006

Children in genocide: extreme traumatization and the 'affect propeller'.

The author bases this paper on extensive research concerning children in genocide with a starting point in the Holocaust and in the genocide in Rwanda 1994. She demonstrates indicators for psychological phenomena concerning the child survivors' affect regulating that appeared in life histories presented in videotaped in-depth interviews. The psychological phenomena concern experiences of persecution and ways of coming to terms with recurring memory images and affects. The interviews that have been analysed in detail form a basis for an emerging conceptual model about trauma- and generational-linking processes within each individual--the 'affect propeller'. An overall conclusion from this study is that past traumatic experiences are recovered not as memories in the usual sense of the word, but as affects invading the present. Accordingly, affects seem to tell the story of the past traumatic experiences.

Adoption↗
PubMed2003

Affective, behavioral, and cognitive functioning in adolescents with multiple suicide attempts.

The purpose of this study was to examine affective, behavioral, and cognitive functioning in adolescents with multiple suicide attempts. Forty-seven adolescents with a history of multiple suicide attempts (MA) were compared to 74 single suicide attempters (SA) on psychiatric diagnosis, depressive symptoms, affect regulation, self-mutilation, alcohol use, and hopelessness. Results revealed that the MA group was more likely to be diagnosed with a mood disorder, and reported more severe depressive symptoms and anger, in comparison to the SA group. Behaviorally, the MA group had higher rates of disruptive behavior disorders and higher levels of affect dysregulation and serious self-mutilation than the SA group. Further, greater levels of hopelessness were reported by the MA than the SA group. After controlling for a mood disorder diagnosis, only differences in anger, affect dysregulation, and serious self-mutilation remained significant. Overall, results suggest that treatment with adolescent suicide attempters might specifically target anger and affect dysregulation to reduce risk for future suicidal behavior.

Adolescent↗
PubMed2006

Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults.

Among younger adults, the ability to willfully regulate negative affect, enabling effective responses to stressful experiences, engages regions of prefrontal cortex (PFC) and the amygdala. Because regions of PFC and the amygdala are known to influence the hypothalamic-pituitary-adrenal axis, here we test whether PFC and amygdala responses during emotion regulation predict the diurnal pattern of salivary cortisol secretion. We also test whether PFC and amygdala regions are engaged during emotion regulation in older (62- to 64-year-old) rather than younger individuals. We measured brain activity using functional magnetic resonance imaging as participants regulated (increased or decreased) their affective responses or attended to negative picture stimuli. We also collected saliva samples for 1 week at home for cortisol assay. Consistent with previous work in younger samples, increasing negative affect resulted in ventral lateral, dorsolateral, and dorsomedial regions of PFC and amygdala activation. In contrast to previous work, decreasing negative affect did not produce the predicted robust pattern of higher PFC and lower amygdala activation. Individuals demonstrating the predicted effect (decrease < attend in the amygdala), however, exhibited higher signal in ventromedial prefrontal cortex (VMPFC) for the same contrast. Furthermore, participants displaying higher VMPFC and lower amygdala signal when decreasing compared with the attention control condition evidenced steeper, more normative declines in cortisol over the course of the day. Individual differences yielded the predicted link between brain function while reducing negative affect in the laboratory and diurnal regulation of endocrine activity in the home environment.

Age Factors↗
PubMed2006

High-resolution mapping of quantitative trait loci affecting increased life span in Drosophila melanogaster.

Limited life span and senescence are near-universal characteristics of eukaryotic organisms, controlled by many interacting quantitative trait loci (QTL) with individually small effects, whose expression is sensitive to the environment. Analyses of mutations in model organisms have shown that genes affecting stress resistance and metabolism affect life span across diverse taxa. However, there is considerable segregating variation for life span in nature, and relatively little is known about the genetic basis of this variation. Replicated lines of Drosophila that have evolved increased longevity as a correlated response to selection for postponed senescence are valuable resources for identifying QTL affecting naturally occurring variation in life span. Here, we used deficiency complementation mapping to identify at least 11 QTL on chromosome 3 that affect variation in life span between five old (O) lines selected for postponed senescence and their five base (B) population control lines. Most QTL were sex specific, and all but one affected multiple O lines. The latter observation is consistent with alleles at intermediate frequency in the base population contributing to the response to selection for postponed senescence. The QTL were mapped with high resolution and contained from 12 to 170 positional candidate genes.

Animals↗
PubMedDate not supplied

Tissue Doppler imaging for detection of radial and longitudinal myocardial dysfunction in a family of cats affected by dystrophin-deficient hypertrophic muscular dystrophy.

Diagnosis of feline hypertrophic cardiomyopathy currently is based on the presence of myocardial hypertrophy detected using conventional echocardiography. The accuracy of tissue Doppler imaging (TDI) for earlier detection of the disease has never been described. The objective of this sudy was to quantify left ventricular free wall (LVFW) velocities in cats with hypertrophic muscular dystrophy (HFMD) during preclinical cardiomyopathy using TDI. The study animals included 22 healthy controls and 7 cats belonging to a family of cats with HFMD (2 affected adult males, 2 heterozygous adult females, one 2.5-month-old affected male kitten, and 2 phenotypically normal female kittens from the same litter). All cats were examined via conventional echocardiography and 2-dimensional color TDI. No LVFW hypertrophy was detected in the 2 carriers or in the affected kitten when using conventional echocardiography and histologic examination, respectively. The LVFW also was normal for 1 affected male and at the upper limit of normal for the 2nd male. Conversely, LVFW dysfunction was detected in all affected and carrier cats with HFMD when using TDI. TDI consistently detects LVFW dysfunction in cats with HFMD despite the absence of myocardial hypertrophy. Therefore, TDI appears more sensitive than conventional echocardiography in detecting regional myocardial abnormalities.

Animals↗
PubMed2002

Total knee arthroplasty in limbs affected by poliomyelitis.

BACKGROUND: Little information is available regarding the results and complications of total knee arthroplasty in limbs affected by poliomyelitis with severe knee degeneration. METHODS: We performed a retrospective chart and radiograph review of patients with a history of poliomyelitis involving a limb that subsequently underwent primary total knee arthroplasty between 1970 and 2000. Sixteen total knee arthroplasties were performed in limbs affected by poliomyelitis in fifteen patients. Eleven patients were followed for a minimum of two years, one (two knees) died before the minimum two-year follow-up could be completed, and three were followed for less than two years. No patient was lost to follow-up. RESULTS: There were two periprosthetic fractures, one peroneal nerve palsy, one avulsion of the patellar tendon, and four cases of recurrent instability. These complications were related to the poor bone quality, valgus deformity, patella baja, poor musculature, and attenuated soft tissues commonly found in knees affected by poliomyelitis. Knee Society pain and knee scores were improved postoperatively for all nine knees with a two-year follow-up that had had at least antigravity quadriceps strength prior to surgery. However, Knee Society function scores remained at 0 or worsened for six of the eleven knees followed for at least two years, including those with less than antigravity strength, and four of the nine knees with at least antigravity strength. None of the prostheses loosened. CONCLUSIONS: Pain and knee scores improved following total knee arthroplasty in patients with a history of poliomyelitis and antigravity quadriceps strength, but there was less pain relief in patients with less than antigravity quadriceps strength. Recurrence of instability and progressive functional deterioration is possible in all knees affected by poliomyelitis that have undergone total knee replacement, but they appear to occur more commonly in more severely affected knees.

Aged↗