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Biomedical subjects

E Connor

Publications and source records attributed to E Connor.

At least 19 recordsLinked to original sources
PubMed2000

Pentosan polysulfate decreases proliferation and extracellular matrix deposition by vascular smooth muscle cells isolated from failed hemodialysis access grafts.

BACKGROUND: Vascular access failure is a major cause of morbidity, and increased costs in patients undergoing maintenance hemodialysis. Stenosis, the most common underlying cause of loss of patency in failed grafts, appears to be caused by an obstructing mass of tissue containing proliferating smooth muscle cells and their associated extracellular matrix. METHODS: To determine whether this process was amenable to pharmacologic intervention and/or prevention, we obtained samples of the material occluding vascular accesses from 7 patients undergoing revision surgery in order to characterize the cells contributing to the stenosis. In all 7 patients the outgrowth contained predominantly smooth muscle-like cells admixed with fibroblasts, which produced a large amount of type IV and type I collagen. RESULTS: Treatment with pentosan polysulfate inhibited cell proliferation and significantly reduced the accumulation of types I and type IV collagens. This was associated with increase in metalloproteinase-9 (MMP-9) and a shift of tissue inhibitor of metalloproteinase-3 (TIMP-3) from the cell layer into the medium. CONCLUSION: These data suggest that pentosan polysulfate (PPS) may have a favorable effect in patients with a polytetrafluoroethylene (PFTE) graft by decreasing cell proliferation and collagen deposition.

Blood Vessel Prosthesis↗
PubMed1999

Effect of human immunodeficiency virus infection on serum beta2-microglobulin levels in pregnant women.

OBJECTIVE: To assess serum beta2-microglobulin levels in human immunodeficiency virus (HIV)-infected and uninfected pregnant women, variations of serum beta2-microglobulin levels during pregnancy and postpartum, factors that might influence beta2-microglobulin levels in pregnant women, and the association between beta2-microglobulin and perinatal HIV-1 transmission. METHODS: We assayed 374 stored (-70C) serum samples from pregnant women enrolled in the Newark perinatal HIV-1-transmission study and 18 nonpregnant women for beta2-microglobulin using a microparticulate enzyme immunoassay. The Student t test, Wilcoxon rank test, binomial test, and Spearman correlation coefficient were used for statistical analysis, with P < .05 considered statistically significant. A linear regression model was used to assess the effect of independent variables on serum beta2-microglobulin levels. RESULTS: There were no significant differences (P = .16) in serum beta2-microglobulin levels between pregnant and nonpregnant HIV-negative women (1.07+/-0.35 versus 0.99+/-0.18 mg/L). Beta2-Microglobulin levels did not vary throughout pregnancy and postpartum, irrespective of HIV serostatus. Substance abuse did not alter beta2-microglobulin levels. Human immunodeficiency virus infection caused significant increases of this surrogate marker, but it could not discriminate among disease stages. Beta2-Microglobulin levels at delivery were lower among women who delivered HIV-infected infants. CONCLUSION: Human immunodeficiency virus infection was associated with increased serum beta2-microglobulin levels in pregnant women and was the most significant correlate of increases of that marker. Pregnancy and substance use during pregnancy did not influence levels of serum beta2-microglobulin significantly.

Adult↗
PubMed1999

Making sense of the electronic resource marketplace: trends in health-related electronic resources.

Changes in the practice of medicine and technological developments offer librarians unprecedented opportunities to select and organize electronic resources, use the Web to deliver content throughout the organization, and improve knowledge at the point of need. The confusing array of available products, access routes, and pricing plans makes it difficult to anticipate the needs of users, identify the top resources, budget effectively, make sound collection management decisions, and organize the resources effectively and seamlessly. The electronic resource marketplace requires much vigilance, considerable patience, and continuous evaluation. There are several strategies that librarians can employ to stay ahead of the electronic resource curve, including taking advantage of free trials from publishers; marketing free trials and involving users in evaluating new products; watching and testing products marketed to the clientele; agreeing to beta test new products and services; working with aggregators or republishers; joining vendor advisory boards; benchmarking institutional resources against five to eight competitors; and forming or joining a consortium for group negotiating and purchasing. This article provides a brief snapshot of leading biomedical resources; showcases several libraries that have excelled in identifying, acquiring, and organizing electronic resources; and discusses strategies and trends of potential interest to biomedical librarians, especially those working in hospital settings.

Computer Communication Networks↗
PubMed1998

Characterization of mutations in patients with autoimmune polyglandular syndrome type 1 (APS1).

Autoimmune polyglandular syndrome type 1 (APS1), also known as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), is an autosomal recessive disorder characterized by the failure of several endocrine glands as well as nonendocrine organs. The autoimmune regulator (AIRE) gene responsible for APS1 on chromosome 21q22.3 has recently been identified. Here, we have characterized mutations in the AIRE gene by direct DNA sequencing in 16 unrelated APS1 families ascertained mainly from the USA. Our analyses identified four different mutations (a 13-bp deletion, a 2-bp insertion, one nonsense mutation, and one potential splice/donor site mutation) that are likely to be pathogenic. Fifty-six percent (9/16) of the patients contained at least one copy of a 13-bp deletion (1094-1106del) in exon 8 (seven homozygotes and two compound heterozygotes). A nonsense mutation (R257X) in exon 6 was also found in 31.3% (5/16) of the USA patients. These data are important for genetic diagnosis and counseling for families with autoimmune endocrine syndromes.

Female↗
PubMed1998

Safety, tolerance and pharmacokinetics of a humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. MEDI-493 Study Group.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants. MEDI-493 (palivizumab) is a humanized monoclonal antibody to the fusion protein of RSV and is active in animal models for prevention of pulmonary RSV replication. OBJECTIVE: To describe the safety, tolerance, immunogenicity and pharmacokinetics of repeat intravenous doses of MEDI-493 in premature infants or infants with bronchopulmonary dysplasia. DESIGN: Phase I/II multicenter, randomized, double blind, placebo-controlled, dose escalation trial. PATIENT POPULATION: Infants born prematurely (< or = 35 weeks of gestation) who were < or = 6 months of age and infants with bronchopulmonary dysplasia who were < or = 24 months of age were eligible for study participation. STUDY AGENTS: Participants received 3, 10 or 15 mg/kg MEDI-493 or 0.9% saline intravenously every 30 days for up to five doses. RESULTS: MEDI-493 was safe and well-tolerated and did not induce a specific anti-MEDI-493 response. The mean half-life of 20 days was comparable with that of other immunoglobulin G preparations. Mean trough serum concentrations 30 days after Infusion 1 were 6.8, 36.1 and 60.6 microg/ml for the 3-, 10- and 15-mg/kg dose groups, respectively. After Infusion 2 the trough concentrations were 11.9, 45.2 and 70.7 microg/ml. After subsequent doses the mean trough values ranged from 14 to 18 microg/ml in those given 3 mg/kg and were > 40 microg/ml for patients who received 10 or 15 mg/kg MEDI-493 (46 to 72 microg/ml and 88 to 96 microg/ml, respectively). CONCLUSIONS: MEDI-493 was safe and well-tolerated in this high risk pediatric population. Mean serum concentrations of MEDI-493 that have been shown to produce a 2-log reduction in pulmonary RSV titer in cotton rats were maintained when 10 or 15 mg/kg MEDI-493 was given every 30 days to pediatric patients at high risk for serious RSV disease. Monthly doses of 15 mg/kg maintained concentrations of > 40 microg/ml for the majority of patients.

Antibodies, Monoclonal↗
PubMed1998

Safety and pharmacokinetics of an intramuscular humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. The MEDI-493 Study Group.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory disease in infants and children. MEDI-493 (palivizumab, Synagis) is a humanized monoclonal IgG1 antibody to the fusion protein of RSV, and it is highly active in vitro against RSV A and B strains. OBJECTIVE: To describe the safety, tolerance, immunogenicity and pharmacokinetics of monthly intramuscular injections of MEDI-493 among premature infants and children with bronchopulmonary dysplasia and to compare these data with information previously obtained with intravenous dosing. DESIGN: A Phase I/II multicenter, open label, escalating dose clinical trial. PATIENT POPULATION AND DOSING REGIMEN: Children (n=65) born prematurely at < or =35 weeks of gestation who were < or =6 months of age (n=41) and children with bronchopulmonary dysplasia who were < or =24 months of age (n=24) were enrolled. From 1 to 5 monthly injections were given at doses of 5 mg/kg (n=11), 10 mg/kg (n=6) and 15 mg/kg (n=48). Serum was collected before administration of each dose, 30 days after the last dose, and 2, 7 and 14 days after the first and second doses for measurement of MEDI-493 concentrations by enzyme-linked immunosorbent assay. RESULTS: The pharmacokinetics of MEDI-493 were similar to those of other human IgG1 antibodies. Mean serum MEDI-493 concentrations were 91.1 microg/ml (range, 52.3 to 174.0) 2 days after the initial dose of 15 mg/kg and 49.2 microg/ml (range, 13.5 to 132.0) at 30 days. Monthly dosing of 15 mg/kg maintained mean trough concentrations of approximately 70 microg/ml. These concentrations were similar to previously published trough concentrations after i.v. administration. MEDI-493 injections were well-tolerated. Only three children had adverse events judged to be possibly related to MEDI-493. Ten children had transient, low titer anti-MEDI-493 binding titers (1:10 to 1:40) which were not associated with a pattern of specific adverse events or alterations of MEDI-493 concentrations. Two patients in the 5-mg/kg dose group were hospitalized for RSV; no RSV hospitalizations were found in the higher dose groups. CONCLUSIONS: MEDI-493 was safe and well-tolerated. Monthly intramuscular doses of 15 mg/kg maintained mean trough serum concentrations that were above 40 microg/ml (the value associated with 99% reduction of pulmonary RSV in the cotton rat model). These concentrations were similar to those previously reported with i.v. administration of MEDI-493.

Antibodies, Monoclonal↗
PubMed1996

Autoantibodies to the extracellular domain of the calcium sensing receptor in patients with acquired hypoparathyroidism.

Acquired hypoparathyroidism (AH) has been considered to result from an autoimmune process but the self-antigens have not been identified. We studied 25 patients with AH, of which 17 had type I autoimmune polyglandular syndrome and 8 had AH associated with autoimmune hypothyroidism. Five of 25 (20%) AH sera reacted to a membrane-associated antigen of 120-140 kD in human parathyroid gland extracts using immunoblot analysis. This is the exact size of the calcium sensing receptor (Ca-SR). The AH sera were then tested by immunoblot using a membrane fraction of HEK-293 cells transfected with Ca-SR cDNA. Eight of 25 (32%) AH sera reacted to a 120-140-kD protein, which closely matched that recognized by the anti-Ca-SR IgG raised in rabbits. The Ca-SR cDNA was translated in vitro into two parts in order to identify the antigenic epitopes. By using this technique, 14 of 25 (56%) AH sera were positive to the extracellular domain of the Ca-SR, whereas none of the AH patients sera reacted to the intracellular domain. The reactivity of the positive sera was completely removed after pre-absorption with the Ca-SR containing membranes. Sera from 50 patients with various other autoimmune diseases as well as 22 normal controls were also tested, and none of them was positive. In conclusion, the Ca-SR has been identified as an autoantigen in AH.

Autoantibodies↗
PubMed1996

Although DR3-DQB1*0201 may be associated with multiple component diseases of the autoimmune polyglandular syndromes, the human leukocyte antigen DR4-DQB1*0302 haplotype is implicated only in beta-cell autoimmunity.

Human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles were analyzed using a PCR-based sequence-specific priming technique in 16 patients with autoimmune polyglandular syndrome type I (APS-I), 31 patients with APS-II, and 110 patients with component diseases of APS-II, including 9 patients with isolated Addison's disease, 43 patients with Hashimoto's thyroiditis, 22 patients with Graves' disease, and 36 patients with vitiligo. No significant associations was observed between HLA and APS-I patients in our data set, nor was sharing of HLA haplotypes by sibling pairs affected by APS I significantly different from the random expectation. Thus, HLA-DRB1 and -DQB1 genes are probably not involved in APS-I. To delineate the associations between HLA-DRB1, DQB1, and APS-II, we analyzed APS-II patients with or without beta-cell autoimmunity [i.e. insulin-dependent diabetes (IDD) and/or islet cell or glutamic acid decarboxylase autoantibodies]. Our results suggest that the association between DR4-DQB1*0302 and APS-II was entirely due to the presence of pancreatic beta-cell autoimmunity, since this haplotype was otherwise not significantly associated with APS-II or with any other of its component diseases. In contrast, the DR3-DQB1*0201 haplotype was associated not only with IDD, but also with APS-II in the absence of pancreatic beta-cell autoimmunity, as were several its component diseases, including isolated Addison's disease, Graves' disease, and Hashimoto's thyroiditis. Interestingly, the frequency of DQB1*0602, a dominantly protective allele against IDD, was not significantly decreased in the APS-II patients with IDD or beta-cell autoimmunity, albeit the patient numbers were small. This phenomenon may suggest that the development of autoimmunity to nonpancreatic endocrine glands may predispose autoimmunity to the pancreatic beta-cells and involve genes other than those of the MHC.

Adolescent↗
PubMed1996

Cell cycle-specific behavior of erythropoietin.

The murine erythropoietin-dependent erythroleukemia cell line, HCD-57, was employed to study the cell cycle-specific behavior of erythropoietin. Cell cycle duration for HCD-57 cells was approximately 12 hours and was uninfluenced by erythropoietin. Populations of HCD-57 cells synchronized in G1 by centrifugal elutriation were able to pass through one complete cell cycle in the absence of erythropoietin but, thereafter, arrested in G1 as identified by propidium iodide staining and flow cytometry. Analysis of cell cycle behavior using the metachromic dye acridine orange, however, revealed that HCD-57 cells pass through a G0 cell cycle phase and, like serum-deprived 3T3 cells, actually arrest in G0 when deprived of erythropoietin. Expression of the cell cycle regulatory protein p34cdc2 was invariant throughout the cell cycle in HCD-57 cells. p34cdc2 was constitutively phosphorylated in G0 cells, and this effect was not modified by erythropoietin. Erythropoietin receptor distribution was log normal in HCD-57 cells in each phase of the cell cycle. The affinity of these surface receptors for erythropoietin was essentially invariant throughout the cell cycle, but receptor expression was upregulated in G2M cells as compared with cells in G1 or S phase. Taken together, these data indicate that erythropoietin has an important role in the G0-G1 to S phase transition but, based on receptor expression, is involved in other phases of the cell cycle as well.

Animals↗
PubMed1994

The role of tyrosinase in autoimmune vitiligo.

Vitiligo is a common depigmenting skin disease, associated with certain autoimmune endocrinopathies, and autoantibodies to several antigens can be found in melanoma cells. We set out to identify the antigens. We examined 26 patients with vitiligo and associated endocrine disease. Of these, 18 patients (77%) and 8 immediate family members had autoantibodies specific for a 69 kDa protein in HTB-70 human melanoma cells that was not seen in control cells. The autoantibody-positive patient sera reacted with recombinant human tyrosinase expressed in Escherichia coli seen by western blots, as did antibodies raised in rabbits against hamster tyrosinase, but not to recombinant tyrosinase-related protein. Not one of 31 normal controls or 8 patients with alopecia or systemic lupus erythematosus had tyrosinase autoantibodies but a small proportion (12%) of 42 patients with autoimmune endocrine disease without a history of vitiligo had them. The results show that tyrosinase, an enzyme important in melanin formation, is a principal autoantigen of autoimmune vitiligo.

Animals↗
PubMed1994

Treatment of HIV infection in infancy.

Treatment for HIV infection and preventive methods for HIV-associated infections are now routinely available and recommended for the management of HIV-infected children. These strategies have been associated with improvement in the quality and duration of life for HIV-infected adults and children. The institution of these interventions is dependent on recognition of infants at risk for infection (born to mothers with HIV infection), early diagnosis of HIV infection in infants and young children, and careful clinical and immunologic monitoring. As with other chronic illnesses, management of HIV-infected children should be comprehensive and should involve the active participation of both the primary pediatrician and the HIV specialist. Optimization of interventional strategies is dependent on ongoing and planned clinical trials.

AIDS Vaccines↗
PubMed1994

Erythropoietin stimulates serine kinase activity in erythropoietin-dependent cells.

Protein phosphorylation is an early event that follows the interaction of erythropoietin (Epo) with its receptor, even though this receptor lacks a kinase domain. To further define the role of protein kinases in Epo-mediated signal transduction, the effect of Epo on serine-threonine kinase activity was examined in the Epo-dependent cell line, HCD-57, using a kinase renaturation assay. In HCD-57 cells synchronized in G0 phase by centrifugal elutriation, multiple serine-threonine kinases were constitutively active, and exposure to Epo was associated with an increase in the activity of kinases with apparent molecular masses of 170, 120, and 90-95 kD. Phosphoamino acid analysis established the covalent incorporation of 32P into serine and threonine for constitutively active kinases and into serine alone for the 90-95 kD kinase. Reelectrophoresis experiments established that 32P incorporation represented kinase autophosphorylation as opposed to protein substrate phosphorylation. Epo-associated serine kinase autophosphorylation was both hormone concentration and time dependent as well as restricted to the G0, G1, and S phases of the cell cycle. Cell fractionation studies localized the activity of the 90-95 kD serine kinase to the plasma membrane.

Animals↗
PubMed1993

Lack of detectable human immunodeficiency virus infection in antibody-negative children born to human immunodeficiency virus-infected mothers.

More than one-half of the children born to women with human immunodeficiency virus (HIV) infection are not infected with HIV. Most of these children, although born antibody-positive, lose maternal antibody and remain asymptomatic. However, it has been unclear how many antibody-negative children of HIV-infected women may truly be infected despite the loss of passively acquired maternal antibody. One hundred nine children who lost maternal antibody after birth to HIV-infected women recruited in four United States maternal HIV transmission studies were examined for HIV infection. Polymerase chain reaction (PCR) was used to determine whether children had HIV proviral DNA in peripheral blood mononuclear cells. A total of 268 samples from 109 children were tested. Clinical status and other laboratory findings were also evaluated. The median age at last follow-up was 25 months (range, 12 to 48 months). One hundred seven (98%) children were negative by PCR on all samples tested. None (95% confidence interval, 0.0 to 1.9%) of 109 children had a repeatedly positive PCR. Two children had single positive PCR results that could not be confirmed on subsequent testing. No other laboratory or clinical findings supported HIV infection in either of these children. The loss of HIV antibody in an asymptomatic child born to an HIV-infected woman strongly suggests that the child is not infected with HIV. Single positive PCR results, particularly in the absence of other clinical or laboratory evidence of HIV infection, should not be used alone to diagnose HIV infection.

AIDS Serodiagnosis↗
PubMed1993

Safety, tolerance, and pharmacokinetics of systemic ribavirin in children with human immunodeficiency virus infection.

Eleven pediatric patients, aged 1 to 10 years and with symptomatic human immunodeficiency virus infection, were treated with 6 or 10 mg of oral ribavirin per kg of body weight daily for 60 days. Safety and pharmacokinetic parameters were monitored; five children had comprehensive pharmacokinetic evaluations. The children tolerated the drug well, and treatment was not associated with any clinically significant adverse effects. Peak concentrations in plasma of 2.5 and 3.0 microM were reached at 90 min after single oral doses of 6 and 10 mg/kg, respectively. The mean systemic availability of oral ribavirin was 42.3%. After 60 days of ribavirin administration, mean trough concentrations in plasma of 2.6 and 4.1 microM were obtained. Ribavirin penetrated well into the cerebrospinal fluid, achieving 70% of the concentration in plasma at steady state.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Enzyme immunoassay for detection of human immunodeficiency virus-specific immunoglobulin A antibodies.

Early diagnosis of human immunodeficiency virus (HIV) infection may be difficult in adults with acute or recent HIV infection and in infants with perinatally acquired HIV. Detection of HIV-specific immunoglobulin A (IgA) antibodies in infant serum by Western blot (immunoblot) has been suggested as a reliable method to identify HIV-infected infants, especially those over the age of 6 months, and as an adjunct to diagnosis of acute HIV infection in adults. We developed a simple enzyme immunoassay for detection of HIV-specific IgA, using standard commercially available reagents. Enzyme immunoassay was comparable to Western blot for detection of HIV-specific IgA in sera from adults (n = 216), older children (n = 49), and infants born to HIV-infected mothers (n = 65). Specificity was 100% and sensitivity ranged from 80 to 92%. IgA-enzyme immunoassay is a simple, highly sensitive method for detection of HIV-specific IgA antibodies and is easily adapted to the standard clinical laboratory.

Adolescent↗
PubMed1993

Current epidemiology of tuberculosis.

After years of decline, tuberculosis has become an increasing cause of morbidity and mortality in the United States. Chronic problems of poverty, homelessness, substandard housing, and poor access to health care have combined to help maintain a reservoir of infected persons. The addition of HIV-associated immunodeficiency has allowed many of these infected individuals, whose infections ordinarily would have remained dormant, to develop tuberculosis at younger ages. In addition, increasing numbers of cases of tuberculosis are being identified among young foreign-born adults from countries of high tuberculosis prevalence. Transmission from these young adults has occurred in increasing numbers to children. These children form an enlarging pool of infected persons that will continue the cycle of tuberculous infection and disease for future generations. Renewed emphasis and resources need to be placed on tuberculosis, particularly in the public health sector. Only in this manner will early detection and treatment of those with infection and disease occur and the cycle of tuberculosis be broken.

AIDS-Related Opportunistic Infections↗
PubMed1993

Advocacy, guardianship and the GP.

Australians have come to realise that they have a right to access high quality health care through their general practitioner. It is essential that people with cognitive impairments through intellectual disability, psychiatric disorders, senility or brain damage are not denied equity of access through their inability to seek medical attention. Those who cannot make reasonable decisions or who cannot understand and give legal consent to operative procedures may need to have a guardian appointed to protect their rights. In other situations an advocate may be appointed if the person's rights are in jeopardy. The general practitioner is often the first person to become aware of the needs of disabled people and is well placed to intervene to ensure the protection of their rights. This includes the right to good health care.

Australia↗