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Biomedical subjects

E Livingston

Publications and source records attributed to E Livingston.

At least 19 recordsLinked to original sources
PubMed2006

Systemic sensitivity to corticosteroids in smokers with asthma.

Cigarette smokers with asthma are insensitive to the therapeutic effects of corticosteroids. It is not known whether this insensitivity to corticosteroids in smokers affects tissue sites beyond the airways. A total of 75 asthmatic subjects (39 smokers) and 78 healthy controls (30 smokers) were recruited to an observational study. The cutaneous and peripheral blood lymphocyte responses to corticosteroids were measured. The cutaneous vasoconstrictor response to topical beclometasone was measured by applying different concentrations of beclometasone solutions to the skin in a random double-blind manner. The degree of blanching at each concentration was graded after 18 h. The sensitivity of peripheral blood lymphocytes to corticosteroids was assessed by measuring the suppressive effect of dexamethasone on lymphocyte proliferation stimulated by phytohaemagglutinin (PHA). Total mean+/-sd cutaneous vasoconstrictor response score to beclometasone was reduced in smokers with asthma to 5.39+/-3.58 versus 7.26+/-3.05 in never-smokers with asthma; and in all smokers to 6.47+/-3.33 versus 7.86+/-2.81 in all never-smokers. The sensitivity to corticosteroids of lymphocytes stimulated by PHA was similar between groups. In conclusion, smokers with asthma have an impaired cutaneous vasoconstrictor response to topical corticosteroids compared with never-smokers with asthma. This finding suggests that the insensitivity to corticosteroids in smokers with asthma affects tissue sites other than the airways.

Adult↗
PubMed2005

Serum and sputum neurotrophin levels in chronic persistent cough.

BACKGROUND: Neurotrophins (NTs) are a family of growth factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin3 (NT-3) that are involved in inflammation. Serum and induced sputum NT levels are increased in asthma and in cough because of idiopathic pulmonary fibrosis, respectively. Neurogenic inflammation is implicated in the pathogenesis of chronic cough in individuals with normal chest radiography, but the role of NTs in this condition is unknown. OBJECTIVE: To assess if NT levels are elevated in the serum and airways in subjects with chronic persistent cough. METHODS: Eighty-one subjects with chronic cough persistent for over 1 year; with normal chest radiography and spirometry were included. Thirty healthy subjects were controls. Serum NGF, BDNF and NT-3 were measured by enzyme immunoassay. In a subset, NGF was measured in induced sputum. Sputum cell counts and allergen-specific serum IgE were measured and all patients received specific sequential treatment trials to achieve a final diagnosis for the cough. RESULTS: There was no significant difference either in the levels of serum or sputum NTs in chronic cough subjects compared with controls or between the most common causes of cough: post-nasal drip syndrome, gastro-oesophageal reflux disease, asthma and bronchiectasis. The median (inter-quartile range) for sputum NGF (pg/mL) was 516 (296-772) in healthy controls and 580 (312-880) in subjects with chronic cough (P=0.284). There was no correlation between NT levels and sputum cell counts. Sputum NGF levels correlated with duration of cough (r=0.34, P=0.002). CONCLUSION: NTs are not elevated in induced sputum or serum of subjects with chronic persistent cough. This implies that NTs do not have a central role in perpetuating airway inflammation in chronic persistent cough.

Adult↗
PubMed2004

Asthma and cigarette smoking.

In most developed countries approximately 25% of adults with asthma are current cigarette smokers. Asthma and active cigarette smoking interact to cause more severe symptoms, accelerated decline in lung function, and impaired short-term therapeutic response to corticosteroids. Cigarette smoking may modify inflammation that is associated with asthma, although there is limited published data on airway pathology in smokers with asthma. To date, the evidence points towards a combination of both heightened and suppressed inflammatory responses in smokers compared with nonsmokers with asthma. The mechanisms of corticosteroid resistance in asthmatic smokers are unexplained, but could be as a result of alterations in airway inflammatory cell phenotypes (e.g. increased neutrophils or reduced eosinophils), changes in the glucocorticoid receptor-alpha to -beta ratio (e.g. overexpression of glucocorticoid receptor beta), and increased activation of pro-inflammatory transcription factors (e.g. nuclear factor-kappaB) or reduced histone deacetylase activity. In conclusion, every effort should be made to encourage asthmatics who smoke to stop, although the effects of smoking cessation upon reversing the adverse effects of tobacco smoke on asthma control, therapeutic response to corticosteroids and airway pathology have yet to be fully elucidated. Alternative or additional therapies to inhaled corticosteroids are needed for asthmatic patients who are unable to quit smoking.

Adrenal Cortex Hormones↗
PubMed2001

Human endomucin is an endothelial marker.

The identification of novel endothelial markers is important in the study of angiogenesis, and may have potential uses in cancer diagnosis and treatment. We have isolated potential markers of tumor angiogenesis by screening human umbilical vein endothelial cells (HUVECs) treated with tumor conditioned media. Using suppression subtractive hybridization (SSH), we found endomucin, a potential cell surface marker upregulated in this system. Human endomucin is predicted to encode a 261-aa, 27.5-kDa protein with a transmembrane sequence and multiple glycosylation sites. Northern and in situ hybridization studies show that human endomucin expression is largely, if not uniquely, endothelial cell-specific. Human endomucin is present abundantly in highly vascular tissues such as heart, kidney, and lung. It is seen in human aortic endothelial cells (HAECs) as well as in human microvascular endothelial cells (HMVECs). Furthermore, its expression is increased when endothelial cells are proliferating or are stimulated by tumor-conditioned media or specific angiogenic factors such as bFGF (basic fibroblast growth factor) and TNFalpha (tumor necrosis factor), suggesting that endomucin may have a role in tumor angiogenesis.

Amino Acid Sequence↗
PubMed2001

Ultrasonographic evaluation of the cervix: transperineal versus endovaginal imaging.

OBJECTIVE: This study compares transperineal and endovaginal ultrasonography of the gravid cervix to evaluate image quality and assess for a systematic difference in cervical lengths measured by the 2 techniques. METHODS: Transperineal and endovaginal ultrasonography of the cervix was performed on 64 pregnant women. Two physicians reviewed the images and rated the relative diagnostic value of the techniques for assessing the cervix and for evaluating for placenta previa. Cervical length was measured prospectively in both techniques. Data were analyzed to determine if there is a systematic difference in length using the 2 approaches and if length differences are dependent on gestational age. RESULTS: There was a strong reviewer preference for endovaginal ultrasonographic images over transperineal images for both assessing the cervix (P< .001) and evaluating for placenta previa (P< .001). Despite this, transperineal and endovaginal ultrasonographic images were frequently rated as similar in diagnostic quality by both reviewers for depicting the cervix (35.9% of patients) and evaluating for placenta previa (57.8% of patients). The mean length of the cervix was slightly shorter at transperineal ultrasonography (28.4 mm) than at endovaginal ultrasonography (30.1 mm). When cervical lengths were subdivided by gestational age, however, a significant length discrepancy was found only in the 14- to 20-week gestational age range. In this age range, mean cervical length at transperineal ultrasonography (28.6 mm) averaged 5.5 mm less than at endovaginal ultrasonography (34.1 mm). CONCLUSIONS: Both transperineal and endovaginal ultrasonography can provide satisfactory images of the cervix, but endovaginal images are frequently superior to transperineal images. Endovaginal ultrasonography should be considered the optimal method for imaging the cervix in most situations. Transabdominal or transperineal ultrasonography can also be used, but if the cervix is not adequately depicted from these perspectives, endovaginal ultrasonography is indicated. Transperineal measurements of cervical length can be significantly shorter than endovaginal measurements, particularly before 20 weeks; therefore, short cervical lengths documented at transperineal ultrasonography before 20 weeks should be confirmed by endovaginal ultrasonography.

Cervix Uteri↗
PubMed2000

Activation of pancreatic acinar cells on isolation from tissue: cytokine upregulation via p38 MAP kinase.

Cytokines produced by pancreatic acinar cells may mediate cell death and recruitment of inflammatory cells into pancreas in pancreatitis and other disorders. Here, we demonstrate mRNA expression for a number of cytokines in acini isolated from rat pancreas. Using RNA from microscopically selected individual cells, we confirmed the acinar cell as a source for cytokine expression. Competitive RT-PCR, Western blot analysis, and immunocytochemistry showed large amounts of monocyte chemotactic protein-1 and interleukin-6 compared with other cytokines. Cytokine expression was inhibited by either inhibitors of p38 mitogen-activated protein kinase (MAPK), SB-202190 and SB-203580, or (less strongly) by the transcription factor nuclear factor (NF)-kappaB inhibitor MG-132. A combination of SB-203580 and MG-132 inhibited mRNA expression of all cytokines by >90%. The results suggest a major role for p38 MAPK and involvement of NF-kappaB in cytokine expression in pancreatic acinar cells. In contrast to isolated acini, we detected no or very low cytokine expression in normal rat pancreas. Our results indicate that activation of p38 MAPK, transcription factors, and cytokines occurs during removal of the pancreas from the animal and isolation of acini.

Animals↗
PubMed1999

Pharmacokinetics of didanosine in antepartum and postpartum human immunodeficiency virus--infected pregnant women and their neonates: an AIDS clinical trials group study.

Didanosine (ddI) pharmacokinetics in antepartum and postpartum human immunodeficiency virus (HIV)-infected women and their neonates were studied. HIV-infected pregnant women received an intravenous (iv) ddI infusion (1.6 mg/kg/h) or an oral dose (200 mg bid or 125 mg bid) at 31 weeks antepartum and 6 weeks postpartum. Blood samples were obtained regularly up to 6 or 8 h after drug administration. The same oral dose of ddI (bid) was administered until labor began. Then, ddI was infused iv until delivery. An oral pharmacokinetic study (60 mg/m2) was conducted in infants at day 1 and at week 6 after birth. Plasma concentrations of ddI were measured by radioimmunoassay. After iv ddI administration, only the maternal plasma clearance was found to be significantly increased antepartum (1028+/-231 mL/min) versus postpartum (707+/-213 mL/min). No pharmacokinetic parameters after oral administration were significantly affected by pregnancy. The pharmacokinetics of ddI in the neonates were highly variable. We conclude that the oral ddI dose need not be adjusted during pregnancy.

Anti-HIV Agents↗
PubMed1999

Species and genotypic diversities and similarities of pathogenic yeasts colonizing women.

We examined the patterns of strain relatedness among pathogenic yeasts from within and among groups of women to determine whether there were significant associations between genotype and host condition or body site. A total of 80 yeast strains were isolated, identified, and genotyped from 49 female volunteers, who were placed in three groups: (i) 19 women with AIDS, (ii) 11 pregnant women without human immunodeficiency virus (HIV) infection, and (iii) 19 women who were neither pregnant nor infected with HIV. Seven yeast species were recovered, including 59 isolates of Candida albicans, 9 isolates of Candida parapsilosis, 5 isolates of Candida krusei, 3 isolates of Candida glabrata, 2 isolates of Saccharomyces cerevisiae, and 1 isolate each of Candida tropicalis and Candida lusitaniae. Seventy unique genotypes were identified by PCR fingerprinting with the M13 core sequence and by random amplified polymorphic DNA analysis. Of the nine shared genotypes, isolates from three different hosts were of one genotype and pairs of strains from different body sites of the same host shared each of the other eight genotypes. Genetic similarities among groups of strains were calculated and compared. We found no significant difference in the patterns of relatedness of strains from the three body sites (oral cavity, vagina, and rectum), regardless of host conditions. The yeast microflora of all three host groups had similar species and genotypic diversities. Furthermore, a single host can be colonized with multiple species or multiple genotypes of the same species at the same or different body sites, indicating dynamic processes of yeast colonization on women.

AIDS-Related Opportunistic Infections↗
PubMed1998

Familial supernumerary marker chromosome evolution through three generations.

A mosaic chromosome complement, 46,XY/47,XY,+r(15), was detected at prenatal diagnosis. Family studies showed the mother and one of her two children to have a bisatellited supernumerary marker chromosome (SMC) in all lymphocytes examined. The maternal grandfather also showed a bisatellited SMC, but in only 2 per cent of his lymphocytes. NOR, DA/DAPI, and chromosome 15 centromere and short arm-specific probes confirmed the identify of the bisatellited SMC and of ring SMC as derived from chromosome 15. An apparently normal male was born at full term. At age 1 year, the baby continues to have normal growth and development. The bisatellited 15 likely originated by somatic mutation in the grandfather (2 per cent cells), was transmitted unchanged to the daughter and grandson (germline transmission, no mosaicism), and then evolved by excising the satellites and forming a ring SMC in the index case. Progressive changes in the frequency and subsequent changes in the structure of this SMC illustrate the unusual characteristics of chromosome 15.

Adult↗
PubMed1998

Initial multicenter experience with double nucleoside therapy for human immunodeficiency virus infection during pregnancy.

OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications. METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV infection status. RESULTS: For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 +/- 8.2 weeks, with a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6 weeks. Duration of therapy with two agents was 20.6 +/- 10.4 weeks overall, with no women stopping medications because of side effects or toxicity. No significant changes in maternal laboratory values were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of newborns, with no children needing transfusion; mild elevations of liver function tests, primarily aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1-13.2%). CONCLUSION: Combination antiretroviral therapy during pregnancy with two nucleoside analogs was well-tolerated by mothers and newborns, with no significant short-term toxicities or side effects noted. Surveillance of exposed newborns' hematologic and liver function appears warranted.

Adult↗
PubMed1998

AIDS-related malignancies.

In the US over one million persons are currently infected with the HIV, over half a million have had AIDS, and over 300,000 have died from AIDS. Worldwide, it is estimated that more than 17 million people are currently infected with HIV, and over 1,200,000 cases of AIDS have been reported to the World Health Organization. By some estimates, up to 40% of patients with AIDS will ultimately develop some form of cancer. Non-Hodgkin's lymphoma, Kaposi's sarcoma and invasive cervical cancer have a higher incidence in persons with HIV infection and all three are AIDS-defining illnesses. In addition, several reports suggest that a number of other malignancies may occur at an increased incidence in persons with HIV infection, including squamous-cell carcinoma of the head, neck and anus, plasmacytoma, melanoma, small-cell lung cancer, basal-cell cancer, and germ-cell tumours. Clinicians should become familiar with HIV-related malignancies as their incidence is expected to further increase as more effective therapies for HIV and associated opportunistic infections allow patients to live longer in an advanced state of immunodeficiency. In the current article, we will review the clinical and therapeutic aspects of the most common AIDS-related malignancies including non-Hodgkin's and Hodgkin's lymphomas, Kaposi's sarcoma and anogenital epithelial neoplasias.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Expression of adhesion molecules in malignant plasma cells in multiple myeloma: comparison with normal plasma cells and functional significance.

Malignant plasma cells in multiple myeloma are predominantly confined to the bone marrow, where they stimulate cytokine production by stromal cells and bone cells leading to osteoclast activation and formation of the characteristic lytic lesions in the skeleton. Adhesion molecules are critically involved in the cellular interactions between myeloma cells and stromal elements and may represent novel therapeutic targets to reduce osteolytic bone disease in multiple myeloma. Here, we review the literature on the adhesion molecule repertoire expressed by malignant plasma cells and discuss the evidence that adhesive interactions between myeloma cells and stromal cells stimulate production of bone-resorbing cytokines.

Bone Marrow↗
PubMed1996

Glucose-induced islet hyperemia is mediated by nitric oxide.

PURPOSE: To determine whether hyperglycemia affects pancreatic islet microcirculation in vivo and whether nitric oxide is a mediator. METHODS: Islet blood flow was measured before and after infusion of glucose during in vivo microscopy of mouse pancreatic islet. The pancreas of male BALB/c mice was exteriorized and viewed under the microscope utilizing monochromatic transmitted light. The carotid artery and tail vein were cannulated and systemic blood pressure was monitored continuously. Under fluorescent light, a 0.02 mL bolus of 2% fluorescein isothyocyanate (FITC-albumin) was injected intra-arterially and the first pulse of FITC-albumin through an islet capillary was videorecorded. Following equilibration, either glucose or normal saline 300 mg/g of body weight was given intravenously. Five minutes later, a second bolus was given and the second pulse was videorecorded. The study was repeated in the presence of N omega-nitro-L-arginine methyl ester (L-NAME). The FITC-albumin bolus mean transit time (TT) and observed cross time (OCT) through the islet were calculated using slow-motion video analysis of the recorded images. RESULTS: Infusion of glucose resulted in a significant increase in islet blood flow with no change in systemic blood pressure: baseline TT was 20 +/- 1.3 pixel/0.03 sec and baseline OCT was 0.6 +/- 0.04 seconds; during hyperglycemia, TT was 16.1 +/- 1 pixel/0.03 sec, and OCT was 0.48 +/- 0.03 seconds (n = 11, P < 0.05 versus basal via paired t-test). Continuous infusion of L-NAME negated the effect of hyperglycemia on islet blood flow: baseline TT was 20 +/- 1.8 pixel/0.03 sec and OCT was and 0.6 +/- 0.05 seconds; during hyperglycemia, TT was 20 +/- 1.1 pixel/0.03 sec and OCT was 0.6 +/- 0.33 seconds (n = 10; P < 0.05 versus glucose via unpaired t-test).

Animals↗
PubMed1996

Nonvisualization of the fetal gallbladder: frequency and prognostic importance.

PURPOSE: To assess the frequency of fetal gallbladder visualization through gestation and to determine the prognostic importance of nonvisualization. MATERIALS AND METHODS: Demonstration of the gallbladder was prospectively attempted in 578 consecutive second- and third-trimester obstetric ultrasound examinations. Data regarding gallbladder visualization were stratified into subgroups on the basis of estimated gestational age. Postnatal follow-up was performed in 80 fetuses with nonvisualization of the gallbladder. RESULTS: The gallbladder was seen on 477 of 578 (82.5%) fetal sonograms. The likelihood of gallbladder visualization increased with advancing gestational age, reaching a plateau of approximately 95% between 24 and 32 weeks. After 32 weeks, the frequency of visualization declined. Seventy-five of the 80 fetuses with nonvisualized gallbladders who underwent follow-up had normal outcomes. Except for one fetus with trisomy 21, all fetuses with abnormalities had relatively minor, non-life threatening problems that did not involve the gallbladder or biliary tract. CONCLUSION: Most fetuses with nonvisualization of the gallbladder have normal outcomes. The rate of nonvisualization of the fetal gallbladder is sufficiently high to undermine the utility of gallbladder visualization as a screen for fetal abnormality.

Female↗