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1.
Biodegradation ; 33(1): 33-43, 2022 02.
Article in English | MEDLINE | ID: mdl-34657229

ABSTRACT

The metallurgical industry is one of the main sources of heavy metal pollution, which represents a severe threat to life. Metals can be removed from aqueous solutions by using microbial biomasses. This paper analyses the heavy metal biosorption capacity of Serratia marcescens strain 16 in single and multimetallic systems. The results obtained show that Co(II), Ni(II) and Zn(II) biosorption in monometallic systems is two to three times higher than in the presence of bi-metallic and multimetallic solutions. Fourier transform infrared spectroscopy confirmed that carbonyl, carboxyl and hydroxyl were the main functional groups, as well as the amide bands I and II involved in metal uptake, which are present in external structures of the bacterial cell. The results obtained demonstrated the viability of S. marcescens strain 16 as a biosorbent for the design of eco-friendly technologies for the treatment of waste liquor.


Subject(s)
Metals, Heavy , Nickel , Adsorption , Biodegradation, Environmental , Cobalt/analysis , Copper , Hydrogen-Ion Concentration , Ions/analysis , Kinetics , Serratia marcescens , Zinc/analysis
2.
Environ Monit Assess ; 194(3): 167, 2022 Feb 10.
Article in English | MEDLINE | ID: mdl-35142917

ABSTRACT

The treatment of metal-polluted wastes is a challenging issue of environmental concern. Metals can be removed using microbial biomass, and this is an interesting approach towards the design of eco-friendly technologies for liquid waste treatment. The study reported here aimed to optimize nickel and cobalt biosorption from aqueous solutions using three native metal-resistant Serratia marcescens strains. Ni(II) and Co(II) biosorption by S. marcescens strains was found to fit better to Langmuir's model, with maximum uptake capacities of 13.5 mg g-1 for Ni(II) ions and 19.9 mg g-1 for Co(II) ions. Different experimental conditions of initial metal concentration, pH, initial biomass, and temperature were optimized using the Plackett-Burman method, and, finally, biomass and metal concentration were studied using the response surface methodology (RSM) to improve biosorption. The optimum uptake capacities for Co(II) ions by the three biosorbents used were obtained for initial metal concentrations of 35-40 mg L-1 and an initial biomass of 6 mg. For Ni(II) ions, the optimum uptake capacity was achieved with 1 mg of initial biomass for S. marcescens C-1 and C-19, and with 7 mg for S. marcescens C-16, with initial concentrations of 20-50 mg L-1. The results obtained demonstrate the viability of native S. marcescens strains as biosorbents for Ni(II) and Co(II) removal. This study also contributes to our understanding of the potential uses of serpentine microbial populations for the design of environmental cleanup technologies.


Subject(s)
Cobalt , Nickel , Adsorption , Biomass , Environmental Monitoring , Hydrogen-Ion Concentration , Kinetics , Serratia marcescens
3.
Environ Sci Technol ; 49(11): 6674-82, 2015 Jun 02.
Article in English | MEDLINE | ID: mdl-25923144

ABSTRACT

Biomining of sulfidic ores has been applied for almost five decades. However, the bioprocessing of oxide ores such as laterites lags commercially behind. Recently, the Ferredox process was proposed to treat limonitic laterite ores by means of anaerobic reductive dissolution (AnRD), which was found to be more effective than aerobic bioleaching by fungi and other bacteria. We show here that the ferric iron reduction mediated by Acidithiobacillus thiooxidans can be applied to an aerobic reductive dissolution (AeRD) of nickel laterite tailings. AeRD using a consortium of Acidithiobacillus thiooxidans and Acidithiobacillus ferrooxidans extracted similar amounts of nickel (53-57%) and cobalt (55-60%) in only 7 days as AnRD using Acidithiobacillus ferrooxidans. The economic and environmental advantages of AeRD for processing of laterite tailings comprise no requirement for an anoxic atmosphere, 1.8-fold less acid consumption than for AnRD, as well as nickel and cobalt recovered in a ferrous-based pregnant leach solution (PLS), facilitating the subsequent metal recovery. In addition, an aerobic acid regeneration stage is proposed. Therefore, AeRD process development can be considered as environmentally friendly for treating laterites with low operational costs and as an attractive alternative to AnRD.


Subject(s)
Acidithiobacillus/metabolism , Cobalt/isolation & purification , Mining/methods , Nickel/isolation & purification , Acidithiobacillus thiooxidans/metabolism , Aerobiosis , Cobalt/metabolism , Iron/metabolism , Microbial Consortia , Nickel/metabolism , Solubility
4.
Neurologia ; 29(5): 271-9, 2014 Jun.
Article in English, Spanish | MEDLINE | ID: mdl-24139388

ABSTRACT

OBJECTIVE: Patients with acute stroke are more likely to survive and achieve independence if they are treated in a stroke unit. Available information in our setting is scarce. We analyse the outcomes of our patients on the basis of cumulative experience in a stroke unit. PATIENTS AND METHODS: A retrospective cohort study of patients admitted to a stroke unit. We differentiate between two groups according to the year of admission: group A (July 2007-December 2009) and group B (January 2010-December 2011), analysing early outcome based on the score on the National Institute of Health stroke scale and mortality at discharge, and medium-term outcome in terms of mortality and functional status according to the modified Rankin scale at three months. RESULTS: A total 1070 patients were included. There were no differences between groups with respect to favourable outcome (68.3% vs 63.9), hospital mortality (5.1% vs 6.6%), or 90-day mortality (12.8% vs 13.1%). The percentage of patients who were independent at 90 days was greater in group B (56.3% vs 65.5%, P=.03). In the multivariate analysis adjusted for stroke subtype and fibrinolytic therapy, the association between patient independence and admission period remained present. CONCLUSIONS: The probability of functional independence in our patients increased alongside accumulated experience in our stroke unit with no differences in mortality.


Subject(s)
Stroke , Aged , Female , Hospital Mortality , Hospital Units/organization & administration , Humans , Male , Multivariate Analysis , Neurology/organization & administration , Retrospective Studies , Stroke/classification , Stroke/mortality , Stroke/therapy , Thrombolytic Therapy/methods , Treatment Outcome
5.
Neurologia ; 28(6): 361-5, 2013.
Article in English, Spanish | MEDLINE | ID: mdl-23246213

ABSTRACT

INTRODUCTION: Type 1 neurofibromatosis is the most common neurocutaneous syndrome. Most published case series study the paediatric population. MATERIAL AND METHODS: Cross-sectional study of cases of type 1 neurofibromatosis from neurology departments that were recorded in a database. We analysed the different clinical variables providing the diagnosis as well as demographic and neuroradiological variables. RESULTS: We found a total of 31 patients with type 1 neurofibromatosis. The mean age was 28.9 years and 58.4% were women. Subjects with unidentified bright objects (UBOs) were younger than those without them (22.45±8.22 years vs. 32.5±10.64; P=.011). In contrast, subjects with neurofibromas were older than those without them (30.56±10.68 years vs. 18.25±4.34; P=.032). No sex differences were found in the presentation of clinical or radiological variables. Seven patients (22.6%) had tumours; 3 were optic pathway gliomas (1 bilateral), 3 were plexiform neurofibromas, and 1 was a pilocytic astrocytoma in the brainstem. CONCLUSIONS: Patients with type 1 neurofibromatosis presented both peripheral neurofibromas and tumorous lesions of the central nervous system. Subjects with neurofibromas were older than those who did not present them, while subjects with UBOs were younger than those without such lesions.


Subject(s)
Neurofibromatosis 1/diagnosis , Adult , Cross-Sectional Studies , Female , Humans , Male , Neurofibromatosis 1/diagnostic imaging , Neuroradiography , Young Adult
6.
Br J Dermatol ; 166(3): 616-23, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21999437

ABSTRACT

BACKGROUND: Although thalidomide has been shown to be effective in patients with refractory cutaneous lupus erythematosus (CLE), its use is still hampered by its potential severe side-effects and the current restricted availability. OBJECTIVES: To evaluate prospectively the clinical efficacy and safety of low-dose thalidomide in an observational study and to establish prognostic factors of clinical outcome. METHODS: Sixty consecutive patients with refractory CLE were treated with thalidomide (100 mg daily). Clinical response was assessed by the CLE Disease Area and Severity Index (CLASI). Clinical and immunological parameters were evaluated during treatment. RESULTS: Patients were followed for up to 8 years (range 2-18). One patient discontinued treatment because of side-effects. Of the 59 remaining patients, 58 (98%) achieved clinical response, already noticeable at 2 weeks following treatment. Complete response occurred in 50 patients (85%). Clinical relapse was frequent (70%) and usually occurred 5 months after withdrawal or reduction of thalidomide. Subacute CLE (SCLE) was the predicting factor of long-term remission after therapy discontinuation [odds ratio (OR) 30, 95% confidence interval (CI) 5·82-154·63], whereas discoid lupus erythematosus (DLE) was predictive of relapse (OR 5·71, 95% CI 1·36-24·06). Eleven patients (18%) reported paraesthesia; in five of the 11, nerve conduction studies confirmed a sensory polyneuropathy. Neurological symptoms resolved in 12 months (range 6-18) after thalidomide withdrawal. Two patients, heavy smokers and without antiphospholipid antibodies, had a cerebral ischaemic event. CONCLUSIONS: Low-dose thalidomide is an effective treatment for refractory CLE, but its benefits need to be balanced against the potential adverse effects. Whereas DLE forms tended to relapse and required a long-term maintenance dose of thalidomide, SCLE forms showed a sustained remission after withdrawal.


Subject(s)
Dermatologic Agents/administration & dosage , Lupus Erythematosus, Cutaneous/drug therapy , Thalidomide/administration & dosage , Adult , Chronic Disease , Dermatologic Agents/adverse effects , Female , Humans , Long-Term Care , Male , Middle Aged , Prospective Studies , Recurrence , Remission Induction , Thalidomide/adverse effects , Treatment Outcome , Young Adult
7.
Rheumatol Int ; 32(4): 927-32, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21240499

ABSTRACT

The significance of beta2-glycoprotein I (ß2GPI) polymorphisms in the production of anti-ß2GPI and other antiphospholipid autoantibodies (aPL) and in the pathogenesis of primary antiphospholipid syndrome (PAPS) is not well understood. We performed a study comparing the distribution of polymorphisms at codons 247 (Val247Leu) and 316 (Trp316Ser) of the ß2GPI gene in a Caucasian Spanish population of PAPS patients and healthy controls, and then making correlations with the development of anti-ß2GPI antibodies and other aPL and associated clinical manifestations. A total of 57 PAPS patients and 100 control subjects were included. In the analysis of Val247Leu polymorphism, alleles (V and L) and genotypes (V/V, V/L, L/L) were similarly distributed in PAPS patients and controls (P = 0.66 and P = 0.22, respectively). Regarding Trp316Ser polymorphism, we found a higher percentage of patients with respect to controls expressing S allele (11.4 vs. 5%, P = 0.02) and T/S genotype (22.8 vs. 10%, P = 0.02). However, when we compared T/T and T/S genotypes in PAPS patients, we found no differences regarding generation of anti-ß2GPI, other aPL and clinical manifestations favoring any genotype. Our findings suggest that among Spanish Caucasians, polymorphisms at codon 247 (Val247Leu) do not seem to influence PAPS pathogenesis. On the contrary, polymorphisms at codon 316 (Trp316Ser), by means of an increased S allele and T/S genotype presence in Spanish Caucasian patients, might play a role in the pathogenic development of PAPS, although mechanism would not involve an increased production of anti-ß2GPI and other aPL.


Subject(s)
Antiphospholipid Syndrome/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , beta 2-Glycoprotein I/genetics , Adult , Alleles , Antibodies, Antiphospholipid/genetics , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/immunology , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Spain , White People/genetics
8.
Int J Clin Pract ; 66(7): 675-83, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22698419

ABSTRACT

AIMS: Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON), a global, non-interventional, surveillance study, aims to evaluate the safety of sorafenib in all patients with unresectable hepatocellular carcinoma (uHCC) under real-life practice conditions, particularly Child-Pugh B patients, who were not well represented in clinical trials. METHODS: Treatment decisions are determined by each physician according to local prescribing guidelines and clinical practice. Patients with uHCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Demographic data and medical and disease history are recorded at entry. Sorafenib dosing and adverse events (AEs) are collected throughout the study. RESULTS: From January 2009 to April 2011, >3000 patients from 39 countries were enrolled. The prespecified first interim analysis was conducted when the initial approximately 500 treated patients had been followed up for ≥4 months; 479 were valid for safety evaluation. Preplanned subgroup analyses indicate differences in patient characteristics, disease aetiology and previous treatments by region. Variation in sorafenib dosing by specialty are also observed; Child-Pugh status did not appear to influence the starting dose of sorafenib. The type and incidence of AEs was consistent with findings from previous clinical studies. AE profiles were comparable between Child-Pugh subgroups. DISCUSSION: The GIDEON study is generating a large, robust database from a broad population of patients with uHCC. First interim analyses have shown global and regional differences in patient characteristics, disease aetiology and practice patterns. Subsequent planned analyses will allow further evaluation of early trends.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzenesulfonates/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Decision Making , Liver Neoplasms/drug therapy , Professional Practice , Pyridines/therapeutic use , Female , Humans , Male , Multicenter Studies as Topic , Niacinamide/analogs & derivatives , Phenylurea Compounds , Randomized Controlled Trials as Topic , Residence Characteristics , Sorafenib , Specialization/statistics & numerical data
9.
Nat Med ; 6(9): 1048-51, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10973327

ABSTRACT

Galanin is widely distributed in enteric nerve terminals lining the gastrointestinal tract. We previously showed that pathogenic Escherichia coli, but not normal commensal organisms, increase galanin-1 receptor expression by epithelial cells lining the colon (i.e., colonocytes). When present, galanin-1 receptor activation by ligand causes colonocyte Cl- secretion. We herein demonstrate that disparate pathogens including Salmonella typhimurium and Shigella flexerii also increase colonocyte galanin-1 receptor expression, whose activation is responsible for a principal component of the increased colonic fluid secretion observed. Although eliminating the GAL1R gene by homologous recombination does not alter basal colonic fluid secretion, removal of one or both alleles completely attenuates the increase in fluid secretion due to infection with enteric pathogens. Galanin-1 receptor up-regulation therefore represents a novel mechanism accounting for the increased colonic fluid secretion observed in infectious diarrhea due to several different pathogens.


Subject(s)
Body Fluids/metabolism , Colon/metabolism , Enterobacteriaceae Infections/metabolism , Enterobacteriaceae/pathogenicity , Intestinal Secretions/metabolism , Receptors, Neuropeptide/biosynthesis , Animals , Mice , Mice, Mutant Strains , Receptors, Galanin , Salmonella typhimurium/pathogenicity , Shigella flexneri/pathogenicity , Up-Regulation
10.
Int J Immunogenet ; 38(6): 529-31, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21923648

ABSTRACT

In this work, we proposed to determine the association of the PTPN22*R620W SNP with primary antiphospholipid syndrome (PAPS) in a case-control association study of Spanish Caucasian individuals. A total of 81 PAPS patients were compared with 81 blood-donor healthy control subjects. PTPN22 SNP (R620W) genotyping was performed by using a polymerase chain reaction-restricted fragment length polymorphism assay. No statistically significant differences were found between control subjects and PAPS patients for the PTPN22*R620W genotypes (P = 0.214). No statistically significant differences were found according to either the presence or absence of antiphospholipid antibodies or the clinical manifestations associated to PAPS. Our results indicate that this functional PTPN22*R620W polymorphism is not associated to PAPS; it seems not to be a risk factor in our Spanish population. The effect of the PTPN22 SNP on clinical manifestations and presence of antiphospholipid antibodies in APS warrants further investigations.


Subject(s)
Amino Acid Substitution/genetics , Antiphospholipid Syndrome/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/immunology , Case-Control Studies , Female , Gene Frequency/genetics , Genetics, Population , Humans , Male , Middle Aged , Spain
11.
Int J Clin Pract ; 64(8): 1034-41, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20642705

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a complicated condition influenced by multiple confounding factors, making optimum patient management extremely challenging. Ethnicity, stage at diagnosis, comorbidities and tumour morphology affect outcomes and vary from region to region, and there is no common language to assess patient prognosis and make treatment recommendations. Despite recent efforts to reduce the incidence of HCC, most patients present with unresectable disease. Non-surgical treatments include ablation, transarterial chemoembolisation and the multikinase inhibitor, sorafenib, but their effects in all patient subgroups are not known and further information is needed to optimise the use of these treatments. AIMS: The Global Investigation of Therapeutic DEcisions in Hepatocellular Carcinoma and Of its Treatment with SorafeNib (GIDEON) study (ClinicalTrials.gov identifier NCT00812175; http://clinicaltrials.gov/) is an ongoing global, prospective, non-interventional study of patients with unresectable HCC who are eligible for systemic therapy and for whom the decision has been taken to treat with sorafenib under real-life practice conditions. The aim of this study is to evaluate the safety and efficacy of sorafenib in different subgroups, especially Child-Pugh B where data are limited. DISCUSSION: This study will recruit 3000 patients from > 40 countries and follow them for approximately 5 years to compile a large and robust database of information that will be used to analyse local, regional and global differences in baseline characteristics, disease aetiology, treatment practice patterns and treatment outcomes, with a view to improve the knowledge base used to guide physician treatment decisions and to improve patient outcomes.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzenesulfonates/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Clinical Trials as Topic/methods , Liver Neoplasms/drug therapy , Pyridines/therapeutic use , Clinical Trials, Phase IV as Topic/methods , Humans , Niacinamide/analogs & derivatives , Patient Selection , Phenylurea Compounds , Prospective Studies , Research Design , Sorafenib , Treatment Outcome
12.
Vaccine ; 38(6): 1486-1493, 2020 02 05.
Article in English | MEDLINE | ID: mdl-31822427

ABSTRACT

Infectious bronchitis (IB) is a highly contagious respiratory disease of poultry, caused by the avian coronavirus infectious bronchitis virus (IBV). Currently, one of the most relevant genotypes circulating worldwide is IBV-QX (GI-19), for which vaccines have been developed by passaging virulent QX strains in embryonated chicken eggs. Here we explored the attenuated phenotype of a commercially available QX live vaccine, IB Primo QX, in specific pathogens free broilers. At hatch, birds were inoculated with QX vaccine or its virulent progenitor IBV-D388, and postmortem swabs and tissues were collected each day up to eight days post infection to assess viral replication and morphological changes. In the trachea, viral RNA replication and protein expression were comparable in both groups. Both viruses induced morphologically comparable lesions in the trachea, albeit with a short delay in the vaccinated birds. In contrast, in the kidney, QX vaccine viral RNA was nearly absent, which coincided with the lack of any morphological changes in this organ. This was in contrast to high viral RNA titers and abundant lesions in the kidney after IBV D388 infection. Furthermore, QX vaccine showed reduced ability to reach and replicate in conjunctivae and intestines including cloaca, resulting in significantly lower titers and delayed protein expression, respectively. Nephropathogenic IBVs might reach the kidney also via an ascending route from the cloaca, based on our observation that viral RNA was detected in the cloaca one day before detection in the kidney. In the kidney distal tubular segments, collecting ducts and ureter were positive for viral antigen. Taken together, the attenuated phenotype of QX vaccine seems to rely on slower dissemination and lower replication in target tissues other than the site of inoculation.


Subject(s)
Infectious bronchitis virus , Viral Vaccines/pharmacokinetics , Animals , Chickens , Cloaca/virology , Coronavirus Infections/prevention & control , Female , Infectious bronchitis virus/immunology , Infectious bronchitis virus/pathogenicity , Infectious bronchitis virus/physiology , Kidney/pathology , Kidney/virology , Male , Tissue Distribution , Trachea/pathology , Trachea/virology , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/pharmacokinetics , Viral Vaccines/administration & dosage , Virus Replication
13.
Am J Transplant ; 9(9): 2113-8, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19624565

ABSTRACT

The aims of this study were to determine whether disparities in waiting list outcomes exist for Hispanics and African Americans during the post-MELD era, and to investigate interactions between disparities and geography. Scientific Registry of Transplant Recipients data were used to compare Hispanics and African Americans to Caucasians listed between 2003 and 2008. Endpoints included (i) receipt of a liver transplant and (ii) death or removal from the waiting list for being too sick or medically unsuitable. Adjustment for possible confounders was performed using multivariate Cox regression, with adjustment for geographic variation using a fixed-effects multilevel model. In multivariate analysis, African Americans have similar hazard of transplantation and death/removal as Caucasians during the post-MELD era. However, Hispanics are less likely to receive a transplant than Caucasians despite adjustment for potential confounders (HR 0.80, 95% CI 0.77-0.83), while having a similar hazard of death/removal. This effect disappeared after adjusting for unequal regional distribution of Hispanics, who represent 8% of patients in donation service areas (DSAs) having median waiting times of < or = 155 days versus 19% in DSAs with median waiting times of >155 days. In conclusion, disparities in liver transplantation exist for Hispanics during the post-MELD era, caused by geographic variation in organ availability.


Subject(s)
Healthcare Disparities , Liver Diseases/ethnology , Liver Diseases/therapy , Liver Transplantation/methods , Tissue and Organ Procurement , Aged , Female , Geography , Hispanic or Latino , Humans , Male , Middle Aged , Proportional Hazards Models , Regression Analysis , Time Factors , Treatment Outcome , Waiting Lists , White People
15.
Am J Transplant ; 8(4): 839-46, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18318783

ABSTRACT

No empirical studies have defined the posttransplant survival that would justify expansion of the Milan criteria for liver transplantation of hepatocellular carcinoma. We created a Markov model comparing the survival benefit of transplantation for a patient with >Milan HCC, versus the harm caused to other patients on the waiting list. In the base-case analysis, the strategy of transplanting the patient with >Milan HCC resulted in a 44% increased risk of death and a utility loss of 3 quality-adjusted years of life across the pre- and posttransplant periods for a nationally representative cohort of patients on the waiting list. This harm outweighed the benefit of transplantation for a patient with >Milan HCC having a 5-year posttransplant survival of less than 61%. This survival threshold was most sensitive to geographic variations in organ shortage, with the threshold varying from 25% (Region 3) to >72% (Regions 1, 5, 7 and 9). In conclusion, expansion of the Milan criteria will require demonstrating high survival rates for the newly eligible patients-approximately 61% at 5 years after transplantation. In regions with less severe organ shortage, a more aggressive approach to transplanting these patients may be justified.


Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Liver Transplantation/physiology , Neoplasm Transplantation/adverse effects , Tissue Donors , Graft Survival , Humans , Liver Transplantation/mortality , Living Donors , Markov Chains , Patient Selection , Retrospective Studies , Survival Analysis , Treatment Outcome , Waiting Lists
16.
J Clin Invest ; 104(3): 253-62, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10430606

ABSTRACT

Galanin is widely distributed in enteric nerve terminals lining the human gastrointestinal (GI) tract. We have shown previously that galanin-1 receptors (Gal1-R) are expressed by epithelial cells lining the human GI tract, and upon activation cause Cl- secretion. Because expression of this receptor is transcriptionally regulated by nuclear factor-kappa B (NF-kappa B), which is activated by enteric pathogens as a part of the host epithelial response to infection, we investigated whether such bacterial pathogens could directly increase Gal1-R expression in the T84-cell model system. Pathogenic Escherichia coli, but not nonpathogenic E. coli, activate a p50/p65 NF-kappa B complex that binds to oligonucleotides corresponding to a recognition site located within the 5' flanking region of the human GAL1R gene. Pathogenic E. coli, but not normal commensal organisms, increase Gal1-R mRNA synthesis and [(125)I]galanin binding sites. Whereas galanin increases short-circuit current (Isc) approximately 5-fold in uninfected T84 cells, exposure to pathogenic, but not nonpathogenic, E. coli results in galanin increasing Isc approximately 20-fold. To confirm the validity of these in vitro observations, we also studied C57BL/6J mice infected with enterohemorrhagic E. coli (EHEC) by gavage. Infection caused a progressive increase in both NF-kappa B activation and Gal1-R expression, with maximal levels of both observed 3 days after gavage. Ussing chamber studies revealed that colons infected with EHEC, but not those exposed to normal colonic flora, markedly increased Isc in response to galanin. These data indicate that pathogen-induced increases in Gal1-R expression by epithelial cells lining the colon may represent a novel unifying pathway responsible for at least a portion of the excessive fluid secretion observed during infectious diarrhea.


Subject(s)
Chlorides/metabolism , Escherichia coli/pathogenicity , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Receptors, Neuropeptide/biosynthesis , Up-Regulation , Animals , Antibodies/chemistry , Binding Sites , Cell Line , Epithelial Cells/chemistry , Epithelial Cells/metabolism , Epithelial Cells/microbiology , Escherichia coli O157/pathogenicity , Humans , Intestinal Mucosa/cytology , Kinetics , Male , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , RNA, Messenger/biosynthesis , Receptors, Galanin , Receptors, Neuropeptide/genetics , Receptors, Neuropeptide/immunology , Receptors, Neuropeptide/physiology
17.
Aliment Pharmacol Ther ; 45(1): 169-177, 2017 01.
Article in English | MEDLINE | ID: mdl-27862091

ABSTRACT

BACKGROUND: Abdominal ultrasound fails to detect over one-fourth of hepatocellular carcinoma (HCC) at an early stage in patients with cirrhosis. Identifying patients in whom ultrasound is of inadequate quality can inform interventions to improve surveillance effectiveness. AIM: To evaluate and identify predictors of ultrasound quality in patients with cirrhosis. METHODS: We performed a retrospective cohort study among patients who underwent ultrasound examination for a cirrhosis-related indication between April 2015 and October 2015. Three fellowship-trained abdominal radiologists collectively reviewed all ultrasound exams and categorised exam quality as definitely adequate, likely adequate, likely inadequate and definitely inadequate to exclude liver lesions. We performed multivariable logistic regression to determine characteristics associated with inadequate ultrasound quality. RESULTS: Among 941 patients, 191 (20.3%) ultrasounds were inadequate for excluding HCC- 134 definitely inadequate and 57 likely inadequate. In multivariable analysis, inadequate quality was associated with male gender (OR 1.68, 95% CI 1.14-2.48), body mass index category (OR 1.67, 95% CI 1.45-1.93), Child-Pugh B or C cirrhosis (OR 1.93, 95% CI 1.32-2.81), alcohol-related cirrhosis (OR 2.11, 95% CI 1.33-3.37), NASH cirrhosis (OR 2.87, 95% CI 1.71-4.80), and in-patient status (OR 1.55, 95% CI 1.01-2.37). Ultrasounds were inadequate in over one-third of patients with Child-Pugh C cirrhosis, BMI >35, or NASH cirrhosis. CONCLUSIONS: One in five ultrasounds in patients with cirrhosis are inadequate for exclusion of HCC, which can contribute to surveillance failure. Alternative surveillance modalities are needed in subgroups prone to inadequate ultrasounds including obese patients, those with Child Pugh B or C cirrhosis, and those with alcohol- or NASH-related cirrhosis.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Population Surveillance , Ultrasonography/standards , Adult , Aged , Carcinoma, Hepatocellular/epidemiology , Cohort Studies , Female , Humans , Liver Cirrhosis/epidemiology , Liver Neoplasms/epidemiology , Male , Middle Aged , Population Surveillance/methods , Predictive Value of Tests , Retrospective Studies
18.
J Am Coll Cardiol ; 21(2): 298-307, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8425990

ABSTRACT

OBJECTIVES: This study was conducted to assess the relations among intracoronary ultrasound, angiographic and histologic data obtained from patients with coronary artery disease successfully treated by directional coronary atherectomy. In addition, it was designed to elucidate whether some aspects of intravascular ultrasound or pathologic findings could predict a propensity to restenosis. BACKGROUND: Intracoronary ultrasound is a useful technique in guiding and assessing atherectomy. However, there is little information about the characterization of the different types of coronary plaques and the changes observed in them after resection. Furthermore, the follow-up ultrasound appearance of previously treated lesions remains undepicted. METHODS: Fifty-two patients (54 +/- 10 years old) were studied. All were successfully treated by atherectomy with the aid of intracoronary ultrasound guidance. Qualitative and quantitative ultrasound and angiographic variables were derived before and after resection. Quantitative histologic morphometric information was also obtained from the specimens. In 22 patients, a follow-up echoangiographic reevaluation was performed 6 +/- 4 months later. RESULTS: Echogenic plaques had a higher collagen and calcium content, whereas echolucent plaques had an increased level of fibrin, nuclei and lipids. Ultrasound plaque reduction after atherectomy was greater in echolucent (76 +/- 21%) than in echogenic plaques (60 +/- 18%; p < 0.05). That reduction correlated with the weight of the resected material (r = 0.62; p < 0.01). At follow-up study, 13 of 22 patients had angiographic and ultrasound evidence of restenosis. Most recurrent lesions had a stenotic three-layer appearance. The incidence of restenosis of primary lesions treated with atherectomy was higher in echolucent (100%) than in echogenic (33%) plaques. Similarly, a higher proportion of nuclear content in the resected material was observed in patients who developed restenosis (2.1 +/- 0.7%) than in patients who had late success after atherectomy (1.2 +/- 0.6%). CONCLUSIONS: Our findings suggest that echolucent plaques are easier to resect than are echogenic plaques but frequently develop restenosis. In contrast, the resection of echogenic plaques, although often incomplete, is associated with better long-term results.


Subject(s)
Atherectomy, Coronary , Coronary Artery Disease/surgery , Coronary Vessels/diagnostic imaging , Coronary Angiography , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Coronary Vessels/pathology , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Recurrence , Time Factors , Ultrasonography
19.
Aliment Pharmacol Ther ; 22(3): 267-71, 2005 Aug 01.
Article in English | MEDLINE | ID: mdl-16091065

ABSTRACT

BACKGROUND: Obesity is a risk factor for adenocarcinomas of the oesophagus and gastric cardia. Diabetes mellitus might mediate that association. AIM: To estimate the risk of diabetes mellitus on the development of adenocarcinoma of distal oesophagus and gastric cardia beyond that of gastro-oesophageal reflux disease. METHODS: A case-control study was performed using a national administrative database of the Veterans Administration. RESULTS: A total of 311 cases of cancer and 10,154 controls were identified. Gender, age, and race were risks for cancer. Diabetes was diagnosed in 36% of cases, and 32% of controls (P = 0.15). Diabetic complications were diagnosed in 14% of cases and 13% of controls (P = 0.60). Multiple logistic regression confirmed the absence of an association between cancer and diabetes (odds ratio 1.1, 95% confidence interval 0.8-1.5) or diabetic complications (odds ratio 0.8, 95% confidence interval 0.6-1.3), adjusting for age, gender, and race. CONCLUSIONS: Within the limitations of this case-control study, there is no evidence of an association between diabetes and adenocarcinoma of the oesophagus or gastric cardia among US veterans with gastro-oesophageal reflux disease.


Subject(s)
Adenocarcinoma/etiology , Cardia , Diabetes Mellitus , Esophageal Neoplasms/etiology , Stomach Neoplasms/etiology , Adenocarcinoma/epidemiology , Aged , Case-Control Studies , Diabetes Complications/complications , Diabetes Complications/epidemiology , Diabetes Mellitus/epidemiology , Esophageal Neoplasms/epidemiology , Female , Gastroesophageal Reflux/complications , Humans , Male , Middle Aged , Risk Factors , Stomach Neoplasms/epidemiology , United States/epidemiology , Veterans/statistics & numerical data
20.
Vision Res ; 35(23-24): 3439-50, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8560810

ABSTRACT

An adaptive mechanism controls the strength of innervation to the two eyes independently. However, under some circumstances an adjustment in strength of innervation to one eye is generalized to the other. The coupling and uncoupling of the two eyes during saccadic motor learning was studied using the technique of intrasaccadic target displacements to provide a precise visual-motor error proportional to the commanded movement. Early adaptive changes (saccade plus fast vergence) were measured within the saccadic interval and late adaptive changes (vergence error) were measured after the saccadic interval. When one viewing eye was retrained using intrasaccadic displacements, saccadic amplitude changes generalized to the other nonviewing eye. Thus, rapid adaptive changes trained monocularly were transferred to the nonviewing eye. But when two eyes were viewing and an adaptive stimulus was provided to only one eye (binocular viewing-monocular training), adaptive changes also occurred in both eyes. Experiments described here suggest that the recalibration of the saccade occurs quickly as a conjugate adjustment of gain which is used to balance innervation to the two eyes. Thereafter, disconjugate mechanisms provide a further recalibration to each eye independently.


Subject(s)
Adaptation, Physiological , Saccades/physiology , Vision, Binocular/physiology , Adolescent , Adult , Female , Humans , Learning , Middle Aged , Time Factors , Vision, Monocular/physiology
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