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Biomedical subjects

V Edwards

Publications and source records attributed to V Edwards.

At least 19 recordsLinked to original sources
PubMed2001

Raffinose improves 24-hour lung preservation in low potassium dextran glucose solution: a histologic and ultrastructural analysis.

BACKGROUND: We have previously shown that the addition of raffinose to low potassium dextran (LPD) preservation solution improves transplanted rat lung function after 24 hours of storage. The mechanisms by which raffinose acts are unclear. The aim of this study was to examine the histologic and ultrastructural correlates of this enhanced pulmonary function after preservation with raffinose. METHODS: In a randomized, blinded study, rat lungs were flushed with LPD, or LPD containing 30 mmol/L of raffinose, and stored for 24 hours at 4 degrees C. Control lungs were flushed with LPD but not stored (n = 5 each group). Changes in postpreservation edema were determined. In addition, lungs were flushed with a trypan blue solution to quantify cell death, and examined using both light and electron microscopy. RESULTS: The LPD lungs gained significantly more weight (25.5%+/-5.5%) compared with raffinose-LPD lungs (5.2%+/-5.3%; p < 0.0001). There were higher percentages of dead cells in the LPD lungs (29%+/-0.3% of total cells) compared with raffinose-LPD lungs (14%+/-1.4%; p < 0.001) and control lungs (0.2%+/-5%; p < 0.001). Control lungs maintained normal ultrastructure, whereas LPD lungs showed a decreased number of intact type II pneumocytes and significant cellular necrosis. Interstitial and alveolar edema with interstitial macrophage infiltration was also observed. Alveolar capillaries were collapsed. In contrast, raffinose-LPD lungs showed only mild alterations such as minimal interstitial edematous expansion, fewer damaged cells, and minimal capillary injury. CONCLUSIONS: Raffinose exerts a cytoprotective effect on pulmonary grafts during preservation, which explains the previously documented improved function. This simple modification of LPD with raffinose may provide clinical benefit in extended pulmonary preservation.

Animals↗
PubMed2001

Factors associated with prevalent hepatitis C: differences among young adult injection drug users in lower and upper Manhattan, New York City.

OBJECTIVES: This study examined correlates of prevalent hepatitis C virus (HCV) infection among young adult injection drug users in 2 neighborhoods in New York City. METHODS: Injection drug users aged 18 to 29 years were street recruited from the Lower East Side and Harlem. Participants were interviewed about drug use and sex practices; venipuncture was performed for hepatitis B virus (HBV), HCV, and HIV serologies. RESULTS: In both sites, testing positive for HCV antibody (anti-HCV) was associated with having injected for more than 3 years. Additionally, HCV infection was positively associated with injecting with someone known to have had hepatitis (but the association was significant only in the Lower East Side) and with sharing cotton (but the association was statistically significant only in Harlem). Being in drug treatment and older than 24 years were associated with HCV in the Lower East Side but not in Harlem. Receiving money for sex was associated with anti-HCV positivity in Harlem but not in the Lower East Side. CONCLUSIONS: Several differences in factors associated with prevalent HCV infection existed among 2 populations of young injection drug users from the same city. Indirect transmission of HCV may occur.

Adolescent↗
PubMed2000

Development of a questionnaire (OPQ) to assess patient's knowledge about osteoporosis.

OBJECTIVE: to develop a self-administered questionnaire (OPQ) to assess the patient's knowledge about osteoporosis. METHODS: An initial item pool of 71 questions was developed with input from clinicians involved in the management of patients with osteoporosis. It was piloted in ten patients for face validity and comprehension. The questionnaire was then administered to 50 first-time attendees at a specialist osteoporosis unit. After item analysis using index of difficulty and index of discrimination, 20 items were selected for the final questionnaire (OPQ). These were in the areas of general information (5), risk factors (7), consequences and treatment (four each). RESULTS: the average index of difficulty and index of discrimination (D) of the 20 items was 0.56 (>0.75 is suggestive of a poor discriminator) and 54.8% (D value of 50% is associated with highest level of item discrimination) respectively. This means that all the items actively discriminated between high and low scorers. The Flesch readability index was 74.3 (a score between 70 and 100 means a document is easily understood) and the reliability coefficient was 0.84 (acceptable range 0.8-0.9). Criterion validity (verification that the scale measures what it claims to measure) was confirmed by the method of contrasted groups where members of an osteoporosis awareness charity had a significantly higher score than the first time attendees (13.6 +/- 4.3 vs. 8.5 +/- 5.4; P=0.003). CONCLUSIONS: we have developed a self-report, 20-item questionnaire (OPQ) to assess the patient's knowledge about osteoporosis. Psychometric analysis has shown that the items have a satisfactory index of difficulty and discrimination. The OPQ is internally reliable, valid and easily understandable. It can be used to identify individuals in need of educational interventions as well as assess the effectiveness of education efforts as a part of management of osteoporosis.

Female↗
PubMed2000

Selection of viable cardiomyocytes for cell transplantation using three-dimensional tissue culture.

BACKGROUND: We developed a three-dimensional cardiac tissue culture system to select viable and contractile cells for the purpose of cardiomyocyte transplantation. In this study we will show that reaggregation of cardiomyocytes in culture is an active process indicative of cardiomyocyte viability and functionality. METHODS: Myocardial tissue from newborn mice has been enzymatically digested, incubated in culture inserts, and studied by phase contrast microscopy, conventional histology, immunohistochemistry, electron microscopy, and TUNEL assay. RESULTS: Cells that are plated on nonadhesive surfaces, reaggregate to spontaneously contracting cell aggregates. The capacity to reaggregate was significantly dependent from the age of the tissue donor (P<0.0001) and on the method of enzymatic dissociation (P<0.0001). The majority of cells within the aggregates consisted of cardiomyocytes. After 24 hr incubation, significant amounts of laminin and fibronectin had been deposited between the cells. Ultrastructural analysis revealed viable cardiomyocytes attached to each other by tight junctions. The apoptotic rate within the aggregates was 11.4+/-4.6 vs. 44.5+/-10.5% immediately after dissociation (P<0.05). CONCLUSIONS: The capacity to form spontaneously contracting aggregates is an inherent characteristic of viable cardiomyocytes in 3-dimensional cultures, which could be successfully exploited for cellular cardiomyocyte transplantation.

Animals↗
PubMed2000

The effect of polyethylene particle chemistry on human monocyte-macrophage function in vitro.

Osteolysis remains the most important problem in orthopedic implant failure. Wear debris from the implant contains polyethylene (PE) particulate which has been shown to activate monocyte-derived macrophages (MDM). Although the response of MDM has been shown to be influenced by the size, shape, and chemical type of PE, the effect of chemically altered PE on MDM has not been studied. In this study, human MDM were seeded onto glass coverslips coated with virgin high density (HD)PE and chemically modified HDPE (impregnated with ppm levels of CoCl(2) and oxidized by heat) mixed with type I collagen and cultured for 96 h. Light microscopic evaluation demonstrated consistent phagocytosis of the HDPE particulate that was confirmed by scanning electron and transmission electron microscopy with little evidence of cytotoxicity. Evaluation of pro-inflammatory mediator secretion by MDMs in response to the virgin and chemically modified HDPE revealed significant differences in interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and IL-6 secretion. A significant elevation of IL-1 secretion was observed after initial exposure to virgin HDPE particles compared with controls (p = 0.001). IL-1 secretion was also elevated in the low oxidized particle groups (p = 0.001), whereas the highly oxidized particles were not different than controls. Secretion of both IL-6 (p = 0.03) and TNF-alpha (p = 0.007) were significantly elevated by the low oxidized HDPE particles whereas the virgin and highly oxidized groups showed no difference. The different effects on MDM activation when HDPE surface chemistry was altered, highlight the importance of defining the particle properties when studying the role of MDM activation in in vitro systems and extrapolating these observations to the in vivo situation.

Biocompatible Materials↗
PubMed2000

Cell death in human lung transplantation: apoptosis induction in human lungs during ischemia and after transplantation.

OBJECTIVE: To examine the presence and extent of apoptosis as well as the affected cell types in human lung tissue before, during, and after transplantation. SUMMARY BACKGROUND DATA: Apoptosis has been described in various human and animal models of ischemia-reperfusion injury, including heart, liver, and kidney, but not in lungs. Therefore, the presence of apoptosis and its role in human lungs after transplantation is not clear. METHODS: Lung tissue biopsies were obtained from 20 consecutive human lungs for transplantation after cold ischemic preservation (1-5 hours), after warm ischemia time (during implantation), and 30, 60, and 120 minutes after graft reperfusion. To detect and quantify apoptosis, fluorescent in situ end labeling of DNA fragments (TUNEL assay) was used. Electron microscopy was performed to verify the morphologic changes consistent with apoptosis and to identify the cell types, which were lost by apoptosis. RESULTS: Almost no evidence of apoptosis was found in specimens after immediate cold and warm ischemic periods. Significant increases in the numbers of cells undergoing apoptosis were observed after graft reperfusion in a time-dependent manner. The mean fraction of apoptotic cells at 30, 60, and 120 minutes after graft reperfusion were 16.6%, 22.1%, and 34.9% of total cells, respectively. Most of the apoptotic cells appeared to be alveolar type II pneumocytes, as confirmed by electron microscopy. CONCLUSIONS: Programmed cell death (apoptosis) appears to be a significant type of cell loss in human lungs after transplantation, and this may contribute to ischemia-reperfusion injury during the early phase of graft reperfusion. This cell loss might be responsible for severe organ dysfunction, which is seen in 20% of patients after lung transplantation. Therefore, this work is of importance to surgeons for the future development of interventions to prevent cell death in transplantation.

Adolescent↗
PubMed1999

A comparison of cell phenotypes in hemimegalencephaly and tuberous sclerosis.

Hemimegalencephaly, an uncommon sporadic nonfamilial congenital dysplastic abnormality of the central nervous system, constitutes a pathological spectrum of neuronal migration disorders, but consistently includes abnormal large neurons similar to those in the cortical tubers of tuberous sclerosis. Microscopically, there are also cells with homogeneous and weakly eosinophilic cytoplasm with a single eccentric nucleus, sometimes called balloon cells (likewise prominent in tuberous sclerosis). We looked for immunohistochemical and ultrastructural differences in the large neurons and balloon cells between hemimegalencephaly and tuberous sclerosis. Microtubule-associated protein 1B and 2, phosphorylated and non-phosphorylated neurofilament and synaptophysin identify the large neurons and distinguish them from balloon cells in both entities. Balloon cells in hemimegalencephaly showed no immunoreactivity for TSC2 gene product, tuberin, and vimentin, but similar cells in tuber tissue showed consistent immunoreactivity. Balloon cells in hemimegalencephaly showed no immunoreactivity for glial fibrillary acidic protein, but some cells in tubers showed such immunoreactivity. Ultrastructurally, balloon cells in hemimegalencephaly contained very few lysosomes, microfilaments, and microtubules, but abundant lipofuscin granules. Similar cells in tubers had prominent lysosomes, more microfilaments and microtubules, and very few lipofuscin granules. The resemblance between abnormal cells in hemimegalencephaly and tuberous sclerosis is superficial; their immunohistochemistry and electron microscopic profiles show distinct differences.

Adolescent↗
PubMed1999

Use of fluorescent amplified fragment length polymorphism (fAELP) to characterise methicillin-resistant Staphylococcus aureus.

The new PCR-based genotyping technique, fluorescent amplified fragment length polymorphism (fAFLP), was compared for discriminatory power and reproducibility with standard phenotypic methods, a coagulase gene (coa) restriction fragment length polymorphism (RFLP) method and pulsed-field gel electrophoresis (PFGE), in typing 34 isolates and four reference strains of methicillin-resistant Staphylococcus aureus (MRSA). The fAFLP showed from 40 to 75 fragments, 50 to 450 base pairs (bp) in size. Based on replicate studies, the isolates were judged indistinguishable when their fAFLP pattern was >93.7% similar. Only two of the isolates were indistinguishable by this criterion. Thirty-one MRSA fell into four major fAFLP groups (1, 2, 3 and 4) at the level of >79.9% similarity. Three other isolates and an EMRSA-16 strain fell outside these major groups. Within both fAFLP groups 1 and 2, two subgroups, A and B, could be identified at approximately 82.0% similarity. While most isolates within group 1 could also be separated by their phenotypic and coagulase gene (coa) RFLP pattern, all the isolates within fAFLP groups 2A and 2B were identical on the basis of these characters. The MRSA within fAFLP groups 3 and 4 were heterogeneous by their phenotypic characteristics and coa gene RFLP patterns. fAFLP was reproducible and distinguished between MRSA isolates that appeared identical by other methods. It is likely to contribute to the epidemiological analysis of outbreaks of MRSA infection.

Coagulase↗
PubMed1999

PCR-RFLP analysis of the coagulase gene of Staphylococcus aureus: application to the differentiation of epidemic and sporadic methicillin-resistant strains.

Preventing cross-infection with epidemic strains of methicillin-resistant Staphylococcus aureus (MRSA) requires effective control measures. These call for simple, rapid, discriminatory and reproducible methods for typing this pathogen. In this study 140 isolates/strains from 105 hospitals in England and Wales, representing 72 diverse phage types, were analysed by bacteriophage typing and PCR coagulase (coa) gene restriction fragment length polymorphism (RFLP). Isolates gave a coa gene PCR product that was either 660 base pairs (bp), 603 bp or 547 pb in size. The PCR products were digested with Alu I and Cfo I, and the fragments separated by gel electrophoresis. Eight coa gene RFLP patterns, numbered 1 to 8, were observed. Pattern 3 was most common (N = 25 isolates), followed by patterns 2 and 5 (18 isolates each), pattern 1 (14 isolates), pattern 4 (11 isolates), pattern 7 (10 isolates), pattern 8 (eight isolates) and pattern 6 (six isolates). Isolates of the same phage type often gave different coa gene RFLP patterns, and the patterns within the epidemic types EMRSA-03, EMRSA-15 and EMRSA-16 were heterogeneous. Thus, representatives of EMRSA-03 were subtyped to coa RFLP patterns 1 and 2, those of EMRSA-05 to coa RFLP patterns 1, 2, 7 and 8, and those for EMRSA-16 to coa RFLP patterns 2, 3, 4, 5 and 6. The range of patterns within single phage types of S. aureus could help to discriminate between isolates/strains, and in a hierarchical approach coa gene RFLP could occupy an intermediate position between phage typing and pulsed-field gel electrophoresis (PFGE).

Bacteriophage Typing↗
PubMed1999

Analysis of chromosome 22q as an aid to the diagnosis of rhabdoid tumor: a case report.

Malignant rhabdoid tumor is a highly aggressive tumor of childhood that may present as a soft-tissue primary tumor. We report a soft-tissue neoplasm that was polyphenotypic by immunohistochemical expression of epithelial, mesenchymal, and neural markers and did not meet the criteria for any of the usual pediatric small round-cell tumors. The findings raised the diagnosis of rhabdoid tumor, leading to testing for WT1 mRNA and protein expression, which were positive, as has been reported for renal rhabdoid tumor. This tumor had the typical clinical behavior of rhabdoid tumor with therapy resistance and early tumor-related death. Multicolor spectral karyotyping of this neoplasm showed a balanced translocation between chromosomes 1 and 22 with breakpoints at 1p36 and 22q11-12. The latter region is commonly involved in rhabdoid tumor. This change was also identified by fluorescence in situ hybridization. This case suggests that studies of chromosome 22 may be required to distinguish rhabdoid tumor from other soft-tissue tumors.

Chromosomes, Human, Pair 22↗
PubMed1999

Central neurocytoma: morphological, flow cytometric, polymerase chain reaction, fluorescence in situ hybridization, and karyotypic analyses. Case report.

The results of cytogenetic and molecular genetic analysis of a central neurocytoma are presented. Central neurocytomas are intriguing neoplasms that exhibit primarily neuronal, but also glial characteristics, which indicate an origin from a pluripotential neuroglial precursor. The authors describe an intraventricular neurocytoma in an 11-year-old boy that showed anaplastic features with widespread necrosis and mitoses, as well as extensive calcification and foci that exhibited marked neuronal differentiation with clusters of ganglion cells. Immunohistochemical examination showed prominent synaptophysin and neurofilament positivity and focal glial fibrillary acidic protein positivity. Electron microscopy revealed abundant neuritic processes with microtubules and dense core granules as well as mature ganglion cells. Flow cytometry studies revealed increased S (7.8%) and G2M (9.7%) phase components. Molecular and cytogenetic studies were undertaken to assess whether there were similarities to two other tumor types that exhibit neuronal differentiation, the neuroblastoma and medulloblastoma. Polymerase chain reaction and fluorescence in situ hybridization (FISH) analysis revealed no evidence of amplification of the MYCN oncogene or chromosome 1p deletion, which are common in neuroblastomas. Chromosomal analysis by G banding revealed a complex karyotype, with counts in the near-diploidy range (45-48). Two chromosomes 1 appeared normal on G banding and FISH analysis, with p58 signals present on the distal p arm of both chromosomes 1; however, three additional copies of distal 1q were present in rearrangements with 4 and 7. Although the histological findings indicate a kinship to the neuroblastoma and medulloblastoma, the central neurocytoma appears to have a different karyotypic profile, although more cases need to be assessed using molecular genetic analysis.

Brain Neoplasms↗
PubMed1998

Synthetic peptide-based DNA complexes for nonviral gene delivery.

A major advantage of synthetic peptide-based DNA delivery systems is its flexibility. By design, the composition of the final complex can be easily modified in response to experimental results in vitro and in vivo to take advantage of specific peptide sequences to overcome extra- and intracellular barriers to gene delivery. The extreme heterogeneity which greatly complicates both the kinetics of DNA-poly(L-lysine) interaction and the thermodynamic stability of the final DNA complexes is avoided. Other unique features include the absence of biohazards related to the viral genome as well as the production of the viral vector and the absence of limitations on the size of the therapeutic genes that can be inserted in the recombinant viral vector. In principle, if the gene can be cloned into an expression plasmid, it can be delivered as a synthetic DNA complex. Since these synthetic delivery systems are composed of small peptides which may be poorly antigenic, they hold the promise of repeated gene administration, a highly desirable feature which will be important for gene targeting in vivo to endothelial cells, monocytes, hepatocytes and tumor cells.

Journal Article↗
PubMed1998

An ultrastructural study of the intimal hyperplasia in healing microarterial anastomoses.

The purpose of the study was to investigate the ultrastructure of intimal hyperplastic cells. End-to-end microarterial anastomoses were studied in a rabbit free-tissue-transfer model. There were five experimental groups, with 1, 3, 7, 14, or 28 days follow-up. At sacrifice the anastomoses were tested for patency and then examined by light and electron microscopy. At days 1 and 3 the repaired intima was covered with macrophages and extravasated erythrocytes. At day 7 spindle-shaped fibroblasts with copious rough endoplasmic reticulum were seen. Some of these cells also contained pinocytotic vesicles, filaments with focal densities, and subplasmalemmal attachment sites, the features of smooth muscle cells. At day 14, more cells contained smooth muscle features and these features were also more pronounced. These young myofibroblasts were plumper than adjacent fibroblasts. At day 28 mature myofibroblasts with a full complement of organelles were present. The results, therefore, supported the hypothesis that myofibroblasts are present in the intimal hyperplasia of healing microarterial anastomoses.

Anastomosis, Surgical↗
PubMed1998

Rapid reperfusion causes stress failure in ischemic rat lungs.

OBJECTIVE: Rapid reperfusion may be injurious to the ischemic lung. Our aim was to confirm that slow reperfusion improves postischemic pulmonary function and to elucidate the ultrastructural changes associated with slow versus rapid reperfusion. METHODS. We used an ex vivo perfused rat lung transplant model to study the effect of slow versus rapid reperfusion on subsequent lung function and morphologic conditional. Functional assessment was performed in (1) fresh lung, slowly reperfused; (2) fresh lung, rapidly reperfused; (3) ischemic lung (4 hours at 22 degrees C), slowly reperfused; and (4) ischemic lung, rapidly reperfused. RESULTS: In group 4, the shunt fraction (P=.001), airway pressure (P=.001), and wet/dry ratio (P=.01) were significantly higher than in groups 1 through 3. Light and electron microscopy of slowly reperfused ischemic lungs (n=4) appeared normal. Rapidly reperfused ischemic lungs (n=4) demonstrated massive alveolar edema hemorrhage, and epithelial "blebbing" by light microscopy. Electron microscopy identified the blebbing as separation of the epithelial layer from an intact basement membrane by edema fluid. The epithelial layer was disrupted in numerous locations. Complete disruption of all layers of the blood-gas barrier was occasionally present. CONCLUSION: Rapid reperfusion of the ischemic lung is an important contributing factor to reperfusion lung injury resulting in mechanical stress failure of the alveolar/capillary barrier. Gradual reintroduction of blood flow to the ischemic lung improves oxygenation.

Animals↗
PubMed1998

Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study.

BACKGROUND: The relationship of health risk behavior and disease in adulthood to the breadth of exposure to childhood emotional, physical, or sexual abuse, and household dysfunction during childhood has not previously been described. METHODS: A questionnaire about adverse childhood experiences was mailed to 13,494 adults who had completed a standardized medical evaluation at a large HMO; 9,508 (70.5%) responded. Seven categories of adverse childhood experiences were studied: psychological, physical, or sexual abuse; violence against mother; or living with household members who were substance abusers, mentally ill or suicidal, or ever imprisoned. The number of categories of these adverse childhood experiences was then compared to measures of adult risk behavior, health status, and disease. Logistic regression was used to adjust for effects of demographic factors on the association between the cumulative number of categories of childhood exposures (range: 0-7) and risk factors for the leading causes of death in adult life. RESULTS: More than half of respondents reported at least one, and one-fourth reported > or = 2 categories of childhood exposures. We found a graded relationship between the number of categories of childhood exposure and each of the adult health risk behaviors and diseases that were studied (P < .001). Persons who had experienced four or more categories of childhood exposure, compared to those who had experienced none, had 4- to 12-fold increased health risks for alcoholism, drug abuse, depression, and suicide attempt; a 2- to 4-fold increase in smoking, poor self-rated health, > or = 50 sexual intercourse partners, and sexually transmitted disease; and 1.4- to 1.6-fold increase in physical inactivity and severe obesity. The number of categories of adverse childhood exposures showed a graded relationship to the presence of adult diseases including ischemic heart disease, cancer, chronic lung disease, skeletal fractures, and liver disease. The seven categories of adverse childhood experiences were strongly interrelated and persons with multiple categories of childhood exposure were likely to have multiple health risk factors later in life. CONCLUSIONS: We found a strong graded relationship between the breadth of exposure to abuse or household dysfunction during childhood and multiple risk factors for several of the leading causes of death in adults.

Adult↗
PubMed1997

Evaluation of the role of routine serial cranial computed tomography in the management of children with human immunodeficiency virus infection.

OBJECTIVE: To review the impact of routine follow-up cranial computed tomography (CT) scans on the management of children with human immunodeficiency virus (HIV) infection. DESIGN: Longitudinal data collected from 58 HIV-infected children followed in one center for mean of 3.8 +/- 1.8 years. SETTING: HIV/AIDS pediatric program following over 90% of the identified HIV-infected children in one region in Canada. RESULTS: The baseline CT scans showed intracranial abnormalities in 35 of 58 children (60%). In five children with basal ganglia calcifications (BGC) without cerebral atrophy, there has not been progressive encephalopathy. For the 43 children who had serial CT scans for routine follow-up, 34 (79%) had changes in the scans that were concordant with the clinical assessment. In all but five children with progressive ventricular and sulcal dilatation on CT scan, there was simultaneous clinical evidence of encephalopathy. Those five children were already on antiretroviral therapy, and therapy was not changed in response to the CT scan findings. CONCLUSION: Baseline CT scans provide useful diagnostic and prognostic information. Further research is needed to evaluate the role of cranial CT imaging in the management of pediatric HIV encephalopathy.

AIDS Dementia Complex↗