Showing papers by "Case Western Reserve University published in 1999"
TL;DR: In this article, the authors investigate how the interorganizational networks of young companies affect their ability to acquire the resources necessary for survival and growth and propose that third parties rely on the prominence of the affiliates of those companies to make judgments about their quality and that young companies "endorsed by prominent exchange partners will perform better than otherwise comparable ventures that lack prominent associates.
Abstract: This paper investigates how the interorganizational networks of young companies affect their ability to acquire the resources necessary for survival and growth. We propose that, faced with great uncertainty about the quality of young companies, third parties rely on the prominence of the affiliates of those companies to make judgments about their quality and that young companies “endorsed” by prominent exchange partners will perform better than otherwise comparable ventures that lack prominent associates. Results of an empirical examination of the rate of initial public offering (IPO) and the market capitalization at IPO of the members of a large sample of venture-capital-backed biotechnology firms show that privately held biotech firms with prominent strategic alliance partners and organizational equity investors go to IPO faster and earn greater valuations at IPO than firms that lack such connections. We also empirically demonstrate that much of the benefit of having prominent affiliates stems from the ...
2,620 citations
TL;DR: The Berlin Questionnaire was evaluated for the usefulness of this instrument in identifying patients with sleep apnea in primary care settings and was shown to be useful in sleep clinic and community surveys.
Abstract: Although sleep apnea is common, it often goes undiagnosed in primary care encounters. The Berlin Questionnaire was found to be a means of identifying patients who are likely to have sleep apnea.
2,478 citations
Book•
15 Jun 1999TL;DR: In this article, the authors present a review of the properties of a single Nucleus to a magnetic field and its properties in the context of MR imaging, which includes the following: Magnetic Field Inhomogeneity effects and T-2 Dephasing.
Abstract: Magnetic Resonance Imaging: A Preview. Classical of a Single Nucleus to a Magnetic Field. Rotating Reference Frames and Resonance. Magnetization, Relaxation and the Bloch Equation. The Quantum Mechanical Basis of Precession and Excitation. The Quantum Mechanical Basis of Thermal Equilibrium and Longitudinal Relaxation. Signal Detection Concepts. Introductory Signal Acquisition Methods: Free Induction Decay, Spin Echoes, Inversion Recovery and Spectroscopy. One-Dimensional Fourier Imaging, k-Space and Gradient Echoes. Multi-Dimensional Fourier Imaging and Slice Excitation. The Continuous and Discrete Fourier Transforms. Sampling and Aliasing in Image Reconstruction. Filtering and Resolution in Fourier Transform Image Reconstruction. Projection Reconstruction of Images. Signal, Contrast and Noise. A Closer Look at Radiofrequency Pulses. Water/Fat Separation Techniques. Fast Imaging in the Steady State. Segmented k-Space and Echo Planar Imaging. Magnetic Field Inhomogeneity Effects and T-2 Dephasing. Random Walks, Relaxation and Diffusion. Spin Density, T-1 and T-2 Quantification Methods in MR Imaging. Motion Artifacts and Flow Compensation. MR Angiography and Flow Quantification. Magnetic Properties of Tissues: Theory and Measurement. Sequence Design, Artifacts and Nomenclature. Introduction to MRI Coils and Magnets. Appendices. Index.
2,140 citations
TL;DR: A tissue engineering approach was developed to produce arbitrary lengths of vascular graft material from smooth muscle and endothelial cells that were derived from a biopsy of vascular tissue, with patency documented up to 24 days by digital angiography.
Abstract: A tissue engineering approach was developed to produce arbitrary lengths of vascular graft material from smooth muscle and endothelial cells that were derived from a biopsy of vascular tissue. Bovine vessels cultured under pulsatile conditions had rupture strengths greater than 2000 millimeters of mercury, suture retention strengths of up to 90 grams, and collagen contents of up to 50 percent. Cultured vessels also showed contractile responses to pharmacological agents and contained smooth muscle cells that displayed markers of differentiation such as calponin and myosin heavy chains. Tissue-engineered arteries were implanted in miniature swine, with patency documented up to 24 days by digital angiography.
1,801 citations
TL;DR: The findings suggest that symptomatic adjacent-segment disease is the result of progressive spondylosis and patients should be informed of the substantial possibility that new disease will develop at an adjacent level over the long term.
Abstract: Background: We studied the incidence, prevalence, and radiographic progression of symptomatic adjacent-segment disease, which we defined as the development of new radiculopathy or myelopathy referable to a motion segment adjacent to the site of a previous anterior arthrodesis of the cervical spine. Methods: A consecutive series of 374 patients who had a total of 409 anterior cervical arthrodeses for the treatment of cervical spondylosis with radiculopathy or myelopathy, or both, were followed for a maximum of twenty-one years after the operation. The annual incidence of symptomatic adjacent-segment disease was defined as the percentage of patients who had been disease-free at the start of a given year of follow-up in whom new disease developed during that year. The prevalence was defined as the percentage of all patients in whom symptomatic adjacent-segment disease developed within a given period of follow-up. The natural history of the disease was predicted with use of a Kaplan-Meier survivorship analysis. The hypothesis that new disease at an adjacent level is more likely to develop following a multilevel arthrodesis than it is following a single-level arthrodesis was tested with logistic regression. Results: Symptomatic adjacent-segment disease occurred at a relatively constant incidence of 2.9 percent per year (range, 0.0 to 4.8 percent per year) during the ten years after the operation. Survivorship analysis predicted that 25.6 percent of the patients (95 percent confidence interval, 20 to 32 percent) who had an anterior cervical arthrodesis would have new disease at an adjacent level within ten years after the operation. There were highly significant differences among the motion segments with regard to the likelihood of symptomatic adjacent-segment disease (p < 0.0001); the greatest risk was at the interspaces between the fifth and sixth and between the sixth and seventh cervical vertebrae. Contrary to our hypothesis, we found that the risk of new disease at an adjacent level was significantly lower following a multilevel arthrodesis than it was following a single-level arthrodesis (p < 0.001). More than two-thirds of all patients in whom the new disease developed had failure of nonoperative management and needed additional operative procedures. Conclusions: Symptomatic adjacent-segment disease may affect more than one-fourth of all patients within ten years after an anterior cervical arthrodesis. A single-level arthrodesis involving the fifth or sixth cervical vertebra and preexisting radiographic evidence of degeneration at adjacent levels appear to be the greatest risk factors for new disease. Therefore, we believe that all degenerated segments causing radiculopathy or myelopathy should be included in an anterior cervical arthrodesis. Although our findings suggest that symptomatic adjacent-segment disease is the result of progressive spondylosis, patients should be informed of the substantial possibility that new disease will develop at an adjacent level over the long term.
1,514 citations
TL;DR: The mode of action of antifungals and their mechanisms of resistance are discussed, and an attempt is made to discuss the correlation between fungal and bacterial resistance.
Abstract: The increased use of antibacterial and antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the study of antimicrobial resistance from different angles. Areas addressed include mechanisms underlying this resistance, improved methods to detect resistance when it occurs, alternate options for the treatment of infections caused by resistant organisms, and strategies to prevent and control the emergence and spread of resistance. In this review, the mode of action of antifungals and their mechanisms of resistance are discussed. Additionally, an attempt is made to discuss the correlation between fungal and bacterial resistance. Antifungals can be grouped into three classes based on their site of action: azoles, which inhibit the synthesis of ergosterol (the main fungal sterol); polyenes, which interact with fungal membrane sterols physicochemically; and 5-fluorocytosine, which inhibits macromolecular synthesis. Many different types of mechanisms contribute to the development of resistance to antifungals. These mechanisms include alteration in drug target, alteration in sterol biosynthesis, reduction in the intercellular concentration of target enzyme, and overexpression of the antifungal drug target. Although the comparison between the mechanisms of resistance to antifungals and antibacterials is necessarily limited by several factors defined in the review, a correlation between the two exists. For example, modification of enzymes which serve as targets for antimicrobial action and the involvement of membrane pumps in the extrusion of drugs are well characterized in both the eukaryotic and prokaryotic cells.
1,489 citations
TL;DR: The development of an abbreviated version of the Test of Functional Health Literacy in Adults (TOFHLA) to measure patients' ability to read and understand health-related materials that can be used by health educators to identify individuals who require special assistance to achieve learning goals is described.
1,457 citations
TL;DR: In this article, computer assisted cell counting was used to reveal abnormal cytoarchitecture in left rostral and caudal orbitofrontal and dorsolateral prefrontal cortical regions in subjects with major depression as compared to psychiatrically normal controls.
1,412 citations
TL;DR: The present data demonstrate the existence of six phenotypic variants of sCJD, and the physicochemical properties of PrPSc in conjunction with the PRNP codon 129 genotype largely determine this phenotypesic variability, and allow a molecular classification of the disease variants.
Abstract: Phenotypic heterogeneity in sporadic Creutzfeldt-Jakob disease (sCJD) is well documented, but there is not yet a systematic classification of the disease variants. In a previous study, we showed that the polymorphic codon 129 of the prion protein gene (PRNP), and two types of protease-resistant prion protein (PrP(Sc)) with distinct physicochemical properties, are major determinants of these variants. To define the full spectrum of variants, we have examined a series of 300 sCJD patients. Clinical features, PRNP genotype, and PrP(Sc) properties were determined in all subjects. In 187, we also studied neuropathological features and immunohistochemical pattern of PrP(Sc) deposition. Seventy percent of subjects showed the classic CJD phenotype, PrP(Sc) type 1, and at least one methionine allele at codon 129; 25% of cases displayed the ataxic and kuru-plaque variants, associated to PrP(Sc) type 2, and valine homozygosity or heterozygosity at codon 129, respectively. Two additional variants, which included a thalamic form of CJD and a phenotype characterized by prominent dementia and cortical pathology, were linked to PrP(Sc) type 2 and methionine homozygosity. Finally, a rare phenotype characterized by progressive dementia was linked to PrP(Sc) type 1 and valine homozygosity. The present data demonstrate the existence of six phenotypic variants of sCJD. The physicochemical properties of PrP(Sc) in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability, and allow a molecular classification of the disease variants.
1,324 citations
TL;DR: In this paper, the relationship between stocks and flows of organizational knowledge and firm performance in the biotechnology industry was investigated, and it was shown that location is a significant predictor of firm performance as are products in the pipeline and firm citations.
Abstract: The knowledge-based view of the firm is a recent approach to understanding the relationship between firm capabilities and firm performance. Specifically, this approach suggests that knowledge generation, accumulation and application may be the source of superior performance. Other research has conceptualized organizational knowledge in terms of stocks of accumulated knowledge in the firm and flows of knowledge into the firm. This paper tests the relationship between stocks and flows of organizational knowledge and firm performance in the biotechnology industry. We suggest that a firm’s geographic location, alliances with other institutions and organizations and R&D expenditures are representative of knowledge flows, while products in the pipeline, firm citations and patents are indicative of knowledge stocks. Through factor analysis, we develop an aggregated measure of location from several variables. A regression model suggests that location is a significant predictor of firm performance as are products in the pipeline and firm citations. A major contribution of this investigation is the operationalization of geographic location and its statistically significant link to firm performance. Copyright © 1999 John Wiley & Sons, Ltd.
1,231 citations
TL;DR: The importance of upper and lower respiratory problems and obesity as risk factors for sleep-disordered breathing in children and adolescents is suggested, and increased risk in African Americans appears to be independent of the effects of obesity or respiratory problems.
Abstract: This study examined risk factors for sleep-disordered breathing (SDB) in children and adolescents; specifically, quantifying risk associated with obesity, race, and upper and lower respiratory problems. Subjects were participants in a genetic-epidemiologic study of SDB and included 399 children and adolescents 2 to 18 yr of age, recruited as members of families with a member (a proband) with known sleep apnea (31 index families) or as members of neighborhood control families (30 families). SDB was assessed with home overnight multichannel monitoring and SDB was defined based on an apneahypopnea index >/= 10 (moderately affected) or < 5 (unaffected). SDB of moderate level was significantly associated with obesity (odds ratio, 4.59; 95% confidence interval [CI], 1.58 to 13.33) and African-American race (odds ratio, 3.49; 95% CI, 1.56 to 8.32) but not with sex or age. After adjusting for obesity, proband sampling, race and familial clustering, sinus problems and persistent wheeze each independently (of the other) predicted SDB. These data suggest the importance of upper and lower respiratory problems and obesity as risk factors for SDB in children and adolescents. Increased risk in African Americans appears to be independent of the effects of obesity or respiratory problems.
TL;DR: The degree of nucleotide polymorphism across these human genes, and orthologous great ape sequences, is highly variable and is correlated with the effects of functional conservation on gene sequences.
Abstract: Sequence variation in human genes is largely confined to single-nucleotide polymorphisms (SNPs) and is valuable in tests of association with common diseases and pharmacogenetic traits. We performed a systematic and comprehensive survey of molecular variation to assess the nature, pattern and frequency of SNPs in 75 candidate human genes for blood-pressure homeostasis and hypertension. We assayed 28 Mb (190 kb in 148 alleles) of genomic sequence, comprising the 5´ and 3´ untranslated regions (UTRs), introns and coding sequence of these genes, for sequence differences in individuals of African and Northern European descent using high-density variant detection arrays (VDAs). We identified 874 candidate human SNPs, of which 22% were confirmed by DNA sequencing to reveal a discordancy rate of 21% for VDA detection. The SNPs detected have an average minor allele frequency of 11%, and 387 are within the coding sequence (cSNPs). Of all cSNPs, 54% lead to a predicted change in the protein sequence, implying a high level of human protein diversity. These protein-altering SNPs are 38% of the total number of such SNPs expected, are more likely to be population-specific and are rarer in the human population, directly demonstrating the effects of natural selection on human genes. Overall, the degree of nucleotide polymorphism across these human genes, and orthologous great ape sequences, is highly variable and is correlated with the effects of functional conservation on gene sequences.
TL;DR: It is demonstrated that patients with concurrent DVT/PE and malignancy have a more than threefold higher risk of recurrent thromboembolic disease and death (from and cause) than patients with DVt/PE without malignancies.
TL;DR: Repolarization alternans at the level of the single cell accounts for T- wave alternans on the surface ECG and establishes a mechanism linking T-wave alternans of the ECG to the pathogenesis of sudden cardiac death.
Abstract: Background—Although T-wave alternans has been closely associated with vulnerability to ventricular arrhythmias, the cellular processes underlying T-wave alternans and their role, if any, in the mechanism of reentry remain unclear. Methods and Results—T-wave alternans on the surface ECG was elicited in 8 Langendorff-perfused guinea pig hearts during fixed-rate pacing while action potentials were recorded simultaneously from 128 epicardial sites with voltage-sensitive dyes. Alternans of the repolarization phase of the action potential was observed above a critical threshold heart rate (HR) (209±46 bpm) that was significantly lower (by 57±36 bpm) than the HR threshold for alternation of action potential depolarization. The magnitude (range, 2.7 to 47.0 mV) and HR threshold (range, 171 to 272 bpm) of repolarization alternans varied substantially between cells across the epicardial surface. T-wave alternans on the surface ECG was explained primarily by beat-to-beat alternation in the time course of cellular re...
Yale University1, George Washington University2, Indiana University – Purdue University Indianapolis3, Case Western Reserve University4, University of Cincinnati5, National Institutes of Health6, University of Texas Southwestern Medical Center7, Wayne State University8, University of Miami9, University of Tennessee Health Science Center10, Emory University11, Stanford University12, University of New Mexico13
TL;DR: Appropriate-for-gestational age infants who survived to hospital discharge without developing chronic lung disease, severe intraventricular hemorrhage, necrotizing enterocolitis, or late onset-sepsis gained weight faster than comparable infants with those morbidities.
Abstract: Background. The interpretation of growth rates for very low birth weight infants is obscured by limited data, recent changes in perinatal care, and the uncertain effects of multiple therapies. Objectives. To develop contemporary postnatal growth curves for very low birth weight preterm infants and to relate growth velocity to birth weight, nutritional practices, fetal growth status (small- or appropriate-for-gestational-age), and major neonatal morbidities (chronic lung disease, nosocomial infection or late-onset infection, severe intraventricular hemorrhage, and necrotizing enterocolitis). Design. Large, multicenter, prospective cohort study. Methods. Growth was prospectively assessed for 1660 infants with birth weights between 501 to 1500 g admitted by 24 hours of age to 1 of the 12 National Institute of Child Health and Human Development Neonatal Research Network centers between August 31, 1994 and August 9, 1995. Infants were included if they survived >7 days (168 hours) and were free of major congenital anomalies. Anthropometric measures (body weight, length, head circumference, and midarm circumference) were performed from birth until discharge, transfer, death, age 120 days, or a body weight of 2000 g. To obtain representative data, nutritional practices were not altered by the study protocol. Results. Postnatal growth curves suitable for clinical and research use were constructed for body weight, length, head circumference, and midarm circumference. Once birth weight was regained, weight gain (14.4–16.1 g/kg/d) approximated intrauterine rates. However, at hospital discharge, most infants born between 24 and 29 weeks of gestation had not achieved the median birth weight of the reference fetus at the same postmenstrual age. Gestational age, race, and gender had no effect on growth within 100-g birth weight strata. Appropriate-for-gestational age infants who survived to hospital discharge without developing chronic lung disease, severe intraventricular hemorrhage, necrotizing enterocolitis, or late onset-sepsis gained weight faster than comparable infants with those morbidities. More rapid weight gain was also associated with a shorter duration of parenteral nutrition providing at least 75% of the total daily fluid volume, an earlier age at the initiation of enteral feedings, and an earlier age at achievement of full enteral feedings. Conclusions. These growth curves may be used to better understand postnatal growth, to help identify infants developing illnesses affecting growth, and to aid in the design of future research. They should not be taken as optimal. Randomized clinical trials should be performed to evaluate whether different nutritional management practices will permit birth weight to be regained earlier and result in more rapid growth, more appropriate body composition, and improved short- and long-term outcomes.
TL;DR: In this article, the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression was conducted, where outpatients with bipolar I disorder experiencing a major depressive episode (DSM-IV) or placebo as monotherapy for 7 weeks.
Abstract: Background More treatment options for bipolar depression are needed. Currently available antidepressants may increase the risk of mania and rapid cycling, and mood stabilizers appear to be less effective in treating depression than mania. Preliminary data suggest that lamotrigine, an established antiepileptic drug, may be effective for both the depression and mania associated with bipolar disorder. This is the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression. Methods Outpatients with bipolar I disorder experiencing a major depressive episode (DSM-IV, N = 195) received lamotrigine (50 or 200 mg/day) or placebo as monotherapy for 7 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale, and the Clinical Global Impressions scale for Severity (CGI-S) and Improvement (CGI-I) were completed at each weekly visit. Results Lamotrigine 200 mg/day demonstrated significant antidepressant efficacy on the 17-item HAM-D, HAM-D Item 1, MADRS, CGI-S, and CGI-I compared with placebo. Improvements were seen as early as week 3. Lamotrigine 50 mg/day also demonstrated efficacy compared with placebo on several measures. The proportions of patients exhibiting a response on CGI-I were 51%, 41%, and 26% for lamotrigine 200 mg/day, lamotrigine 50 mg/day, and placebo groups, respectively. Adverse events and other safety results were similar across treatment groups, except for a higher rate of headache in the lamotrigine groups. Conclusion Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression.
TL;DR: Experiments testing the self-serving bias (SSB; taking credit for personal success but blaming external factors for personal failure) have used a multitude of moderators (i.e., role, task importanc... as discussed by the authors ).
Abstract: Experiments testing the self-serving bias (SSB; taking credit for personal success but blaming external factors for personal failure) have used a multitude of moderators (i.e., role, task importanc...
TL;DR: It is shown that functional Gfp-MinD accumulates alternately in either one of the cell halves in what appears to be a rapidly oscillating membrane association-dissociation cycle imposed by MinE.
Abstract: Accurate placement of the division septum at the midpoint of Escherichia coli cells requires the combined action of a general division inhibitor (MinC), a site-specific suppressor of division inhibition (MinE), and an ATPase (MinD) that is required for proper functioning of both MinC and MinE. We previously showed that a functional MinE-Gfp fusion accumulates in a ring structure at/near the middle of cells. Here we show that functional Gfp-MinD accumulates alternately in either one of the cell halves in what appears to be a rapidly oscillating membrane association-dissociation cycle imposed by MinE. The results indicate that MinD represents a novel type of dynamic cellular element in bacteria, with multiple roles in directing the division apparatus to the middle of the cell.
TL;DR: It is concluded that, with current methods of care, the limits of viability have been reached and the continuing toll of major neonatal morbidity and neurodevelopmental handicap are of serious concern.
TL;DR: Surprisingly, the oxidized nucleoside was associated predominantly with RNA because immunoreaction was diminished greatly by preincubation in RNase but only slightly by DNase, the first evidence of increased RNA oxidation restricted to vulnerable neurons in AD.
Abstract: In this study we used an in situ approach to identify the oxidized nucleosides 8-hydroxydeoxyguanosine (8OHdG) and 8-hydroxyguanosine (8OHG), markers of oxidative damage to DNA and RNA, respectively, in cases of Alzheimer’s disease (AD). The goal was to determine whether nuclear and mitochondrial DNA as well as RNA is damaged in AD. Immunoreactivity with monoclonal antibodies 1F7 or 15A3 recognizing both 8OHdG and 8OHG was prominent in the cytoplasm and to a lesser extent in the nucleolus and nuclear envelope in neurons within the hippocampus, subiculum, and entorhinal cortex as well as frontal, temporal, and occipital neocortex in cases of AD, whereas similar structures were immunolabeled only faintly in controls. Relative density measurement showed that there was a significant increase ( p < 0.0001) in 8OHdG and 8OHG immunoreactivity with 1F7 in cases of AD ( n = 22) as compared with senile ( n = 13), presenile ( n = 10), or young controls ( n = 4). Surprisingly, the oxidized nucleoside was associated predominantly with RNA because immunoreaction was diminished greatly by preincubation in RNase but only slightly by DNase. This is the first evidence of increased RNA oxidation restricted to vulnerable neurons in AD. The subcellular localization of damaged RNA showing cytoplasmic predominance is consistent with the hypothesis that mitochondria may be a major source of reactive oxygen species that cause oxidative damage in AD.
TL;DR: Compared with a no-exercise control group, the participants who performed the self-control exercises showed significant improvement in self-regulatory capacity as measured by quitting faster on a hand-grip exercise task following a thought-suppression exercise.
Abstract: This study examined the results of repeated exercises of self-control in relation to self-regulatory strength over time. A sample of 69 U.S. college students spent 2 weeks doing 1 of 3 self-control exercises: monitoring and improving posture, regulating mood, or monitoring and recording eating. Compared with a no-exercise control group, the participants who performed the self-control exercises showed significant improvement in self-regulatory capacity as measured by quitting faster on a hand-grip exercise task following a thought-suppression exercise.
TL;DR: The impact of VLBW birth varies with child medical risk status, age, and developmental outcome, and follow-up programs should incorporate psychological screening and support services for mothers of V LBW infants in the immediate postnatal period.
Abstract: ContextFew studies document how parents adapt to the
experience of a very low-birth-weight (VLBW; <1500 g) birth despite
societal concerns about the ethics and justification of intensive care
for these infants.ObjectiveTo determine the degree and type of stress experienced
over time by mothers whose infants vary in degree of prematurity and
medical and developmental risk.DesignLongitudinal prospective follow-up study of a cohort of
mothers of high- and low-risk VLBW and term infants from birth to 3
years.SettingAll level III neonatal intensive care units from a large
midwestern metropolitan region.ParticipantsMothers and infants prospectively and
consecutively enrolled in a longitudinal study between 1989 and 1991.
High-risk VLBW infants were diagnosed as having bronchopulmonary
dysplasia, and comparison groups were low-risk VLBW infants without
bronchopulmonary dysplasia and term infants (>36 weeks, >2500 g).Main Outcome MeasuresStandardized, normative self-report measures
of maternal psychological distress, parenting stress, family impact,
and life stressors.ResultsMothers of VLBW infants (high risk, n=122; low
risk, n=84) had more psychological distress than mothers of term
infants (n=123) at 1 month (13% vs 1%; P=.003). At 2
years, mothers of low-risk VLBW infants did not differ from term
mothers, while mothers of high-risk infants continued to report
psychological distress. By 3 years, mothers of high-risk VLBW children
did not differ from mothers of term children in distress symptoms,
while parenting stress remained greater. Severity of maternal
depression was related to lower child developmental outcomes in both
VLBW groups.ConclusionsThe impact of VLBW birth varies with child medical
risk status, age, and developmental outcome. Follow-up programs should
incorporate psychological screening and support services for mothers of
VLBW infants in the immediate postnatal period, with monitoring of
mothers of high-risk VLBW infants.
TL;DR: The complete human genome nucleotide sequence and technologies for assessing sequence variation on a genome–scale will prompt comprehensive studies of comparative genomic diversity in human populations across the globe.
Abstract: The complete human genome nucleotide sequence and technologies for assessing sequence variation on a genome-scale will prompt comprehensive studies of comparative genomic diversity in human populations across the globe. These studies, besides rejuvenating population genetics and our interest in how genetic variation is created and maintained, will provide the intellectual basis for understanding the genetic basis for complex diseases and traits.
TL;DR: Results suggest that oxidative damage to cytoplasmic nucleic acid is selectively increased in midbrain, especially the SN, of PD patients and much less so in MSA-P and DLB patients.
Abstract: Oxidative damage, including modification of nucleic acids, may contribute to dopaminergic neurodegeneration in the substantia nigra (SN) of patients with Parkinson's disease (PD). To investigate the extent and distribution of nucleic acid oxidative damage in these vulnerable dopaminergic neurons, we immunohistochemically characterized a common product of nucleic acid oxidation, 8-hydroxyguanosine (8OHG). In PD patients, cytoplasmic 8OHG immunoreactivity was intense in neurons of the SN, and present to a lesser extent in neurons of the nucleus raphe dorsalis and oculomotor nucleus, and occasionally in glia. The proportion of 8OHG immunoreactive SN neurons was significantly greater in PD patients compared to age-matched controls. Midbrain sections from patients with multiple system atrophy-Parkinsonian type (MSA-P) and dementia with Lewy bodies (DLB) also were examined. These showed increased cytoplasmic 8OHG immunoreactivity in SN neurons in both MSA-P and DLB compared to controls; however, the proportion of positive neurons was significantly less than in PD patients. The regional distribution of 8OHG immunoreactive neurons within the SN corresponded to the distribution of neurodegeneration for these three diseases. Nuclear 8OHG immunoreactivity was not observed in any individual. The type of cytoplasmic nucleic acid responsible for 8OHG immunoreactivity was analyzed by preincubating midbrain sections from PD patients with RNase, DNase, or both enzymes. 8OHG immunoreactivity was substantially diminished by either RNase or DNase, and completely ablated by both enzymes. These results suggest that oxidative damage to cytoplasmic nucleic acid is selectively increased in midbrain, especially the SN, of PD patients and much less so in MSA-P and DLB patients. Moreover, oxidative damage to nucleic acid is largely restricted to cytoplasm with both RNA and mitochondrial DNA as targets.
TL;DR: In this article, the effectiveness of trivalent influenza vaccine in reducing infection, illness, and absence from work in young, healthy health care professionals was evaluated over three consecutive years, from 1992-1993 to 1994-1995.
Abstract: ContextData are limited and conflicting regarding the
effectiveness of influenza vaccine in health care professionals.ObjectiveTo determine the effectiveness of trivalent influenza
vaccine in reducing infection, illness, and absence from work in young,
healthy health care professionals.DesignRandomized, prospective, double-blind, controlled trial
over 3 consecutive years, from 1992-1993 to 1994-1995.SettingTwo large teaching hospitals in Baltimore, Md.ParticipantsTwo hundred sixty-four hospital-based health care
professionals without chronic medical problems were recruited; 49
participated for 2 seasons; 24 participated for 3 seasons. The mean age
was 28.4 years, 75% were resident physicians, and 57% were women.InterventionParticipants were randomly assigned to receive either
an influenza vaccine or a control (meningococcal vaccine, pneumococcal
vaccine, or placebo). Serum samples for antibody assays were collected
at the time of vaccination, 1 month after vaccination, and at the end
of the influenza season. Active weekly surveillance for illness was
conducted during each influenza epidemic period.Main Outcome MeasuresSerologically defined influenza infection
(4-fold increase in hemagglutination-inhibiting antibodies), days of
febrile respiratory illness, and days absent from work.ResultsWe conducted 359 person-winters of serologic
surveillance (99.4% follow-up) and 4746 person-weeks of illness
surveillance (100% follow-up). Twenty-four (13.4%) of 179 control
subjects and 3 (1.7%) of 180 influenza vaccine recipients had
serologic evidence of influenza type A or B infection during the study
period. Vaccine efficacy against serologically defined infection was
88% for influenza A (95% confidence interval [CI], 47%-97%;
P=.001) and 89% for influenza B (95% CI,
14%-99%; P=.03). Among influenza vaccinees,
cumulative days of reported febrile respiratory illness were 28.7 per
100 subjects compared with 40.6 per 100 subjects in controls
(P=.57) and days of absence were 9.9 per 100
subjects vs 21.1 per 100 subjects in controls
(P=.41).ConclusionsInfluenza vaccine is effective in preventing infection
by influenza A and B in health care professionals and may reduce
reported days of work absence and febrile respiratory illness. These
data support a policy of annual influenza vaccination of health care
professionals.
TL;DR: It is demonstrated in vivo that inflammatory processes alone initiate a cascade of secondary tissue damage, progressive cavitation, and glial scarring in the CNS and that anti-inflammatory agents modulating transcription via the nuclear hormone receptor peroxisome proliferator–activated receptor-γ may be therapeutic in preventinggressive cavitation by limiting inflammation and subsequent secondary damage after CNS injury.
Abstract: Post-traumatic cystic cavitation, in which the size and severity of a CNS injury progress from a small area of direct trauma to a greatly enlarged secondary injury surrounded by glial scar tissue, is a poorly understood complication of damage to the brain and spinal cord. Using minimally invasive techniques to avoid primary physical injury, this study demonstrates in vivo that inflammatory processes alone initiate a cascade of secondary tissue damage, progressive cavitation, and glial scarring in the CNS. An in vitro model allowed us to test the hypothesis that specific molecules that stimulate macrophage inflammatory activation are an important step in initiating secondary neuropathology. Time-lapse video analyses of inflammation-induced cavitation in our in vitro model revealed that this process occurs primarily via a previously undescribed cellular mechanism involving dramatic astrocyte morphological changes and rapid migration. The physical process of cavitation leads to astrocyte abandonment of neuronal processes, neurite stretching, and secondary injury. The macrophage mannose receptor and the complement receptor type 3 beta2-integrin are implicated in the cascade that induces cavity and scar formation. We also demonstrate that anti-inflammatory agents modulating transcription via the nuclear hormone receptor peroxisome proliferator-activated receptor-gamma may be therapeutic in preventing progressive cavitation by limiting inflammation and subsequent secondary damage after CNS injury.
TL;DR: These results offer compelling evidence that the major environmental impediment to regeneration in the adult CNS is the molecular barrier that forms directly at the lesion site, and that degenerating white matter beyond the glial scar has a far greater intrinsic ability to support axon regeneration than previously thought possible.
Abstract: We have recently reported that minimally disturbed adult CNS white matter can support regeneration of adult axons by using a novel microtransplantation technique to inject minute volumes of dissociated adult rat dorsal root ganglion neurons directly into adult rat CNS pathways (Davies et al., 1997). This atraumatic injection procedure minimized scarring and allowed considerable numbers of regenerating adult axons immediate access to the adult CNS glial terrain where they rapidly extended for long distances. A critical question remained as to whether degenerating white matter at acute and chronic stages (up to 3 months) after injury could still support regeneration. To investigate this, we have microtransplanted adult sensory neurons into degenerating white matter of the adult rat spinal cord several millimeters rostral to a severe lesion of the dorsal columns. Regeneration of donor sensory axons in both directions away from the site of transplantation was robust even within white matter undergoing fulminant Wallerian degeneration despite intimate contact with myelin. Along their route, the regrowing axons extended large numbers of collaterals into the adjacent dorsal horn. However, after entering the lesion, the rapidly extending growth cones stopped and became dystrophic within high concentrations of reactive glial matrix. Our results offer compelling evidence that the major environmental impediment to regeneration in the adult CNS is the molecular barrier that forms directly at the lesion site, and that degenerating white matter beyond the glial scar has a far greater intrinsic ability to support axon regeneration than previously thought possible.
TL;DR: Combining in vitro manipulated mesenchymal stem cells with porous ceramics can be expected to effect sufficient new bone-forming capability, which can thereby provide tissue engineering approaches to patients with skeletal defects in order to regenerate skeletal tissues.
Abstract: Mesenchymal stem cells reside in bone marrow and, when these cells are incorporated into porous ceramics, the composites exhibit osteo-chondrogenic phenotypic expression in ectopic (subcutaneous and intramuscular) or orthotopic sites. The expressional cascade is dependent upon the material properties of the delivery vehicle. Bioactive ceramics provide a suitable substrate for the attachment of the cells. This is followed by osteogenic differentiation directly on the surface of the ceramic, which results in bone bonding. Nonbioactive materials show neither surface-dependent cell differentiation nor bone bonding. The number of mesenchymal stem cells in fresh adult bone marrow is small, about one per one-hundred-thousand nucleated cells, and decreases with donor age. In vitro cell culture technology can be used to mitotically expand these cells without the loss of their developmental potency regardless of donor age. The implanted composite of porous ceramic and culture-expanded mesenchymal stem cells exhibits in vivo osteo-chondrogenic differentiation. In certain culture conditions, these stem cells differentiate into osteoblasts, which make bone matrix on the ceramic surface. Such in vitro prefabricated bone within the ceramic provides immediate new bone-forming capability after in vivo implantation. Prior to loading of the cultured, marrow-derived mesenchymal stem cells into the porous ceramics, exogenous genes can be introduced into these cells in culture. Combining in vitro manipulated mesenchymal stem cells with porous ceramics can be expected to effect sufficient new bone-forming capability, which can thereby provide tissue engineering approaches to patients with skeletal defects in order to regenerate skeletal tissues.
TL;DR: In this article, the longitudinal changes in insulin sensitivity, insulin response, and endogenous (primarily hepatic) glucose production and suppression during insulin infusion in women with normal glucose tolerance (control) and gestational diabetes mellitus before and during a planned pregnancy were evaluated.
TL;DR: Flow cytometric and cytogenetic analysis showed that this cell line represents one hyper DNA-diploid stem line with two clonal, evolved cytogenetics sublines, and like the parental C WR22 and CWR22R xenografts, thiscell line expresses prostate specific antigen.
Abstract: A cell line has been derived from a human prostatic carcinoma xenograft, CWR22R. This represents one of very few available cell lines representative of this disease. The cell line is derived from a xenograft that was serially propagated in mice after castration-induced regression and relapse of the parental, androgen-dependent CWR22 xenograft. Flow cytometric and cytogenetic analysis showed that this cell line represents one hyper DNA-diploid stem line with two clonal, evolved cytogenetic sublines. The basic karyotype is close to that of the grandparent xenograft, CWR22, and is relatively simple with 50 chromosomes. In nude mice, the line forms tumors with morphology similar to that of the xenografts, and like the parental CWR22 and CWR22R xenografts, this cell line expresses prostate specific antigen. Growth is weakly stimulated by dihydroxytestosterone and lysates are immunoreactive with androgen receptor antibody by Western blot analysis. Growth is stimulated by epidermal growth factor but is not inhibited by transforming growth factor-beta1.