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1.
Rev Med Interne ; 40(10): 684-692, 2019 Oct.
Article in French | MEDLINE | ID: mdl-31126662

ABSTRACT

Clonal hematopoiesis of undetermined significance or CHIP describes the identification, in individuals without hematologic disease, of one or more somatic mutations in hematopoietic cells. These mutations, detected by high-throughput genes sequencing (Next-Generation Sequencing or NGS), affect genes first identified in acute myeloid leukemia or myelodysplastic syndrome, such as DNMT3A, TET2 and ASXL1. CHIP is associated with an increased risk of malignant hemopathy, both myeloid and lymphoid, evaluated from 0.5 to 1% per year. CHIP is also associated with an increased risk of overall mortality and cardiovascular diseases. CHIP detection using NGS is currently limited to basic science field, but recent studies suggest that it may be of clinical interest.


Subject(s)
DNA (Cytosine-5-)-Methyltransferases/genetics , DNA-Binding Proteins/genetics , Hematologic Neoplasms/genetics , Hematopoiesis/genetics , Proto-Oncogene Proteins/genetics , Repressor Proteins/genetics , DNA Methyltransferase 3A , Dioxygenases , Genetic Predisposition to Disease , Hematologic Neoplasms/mortality , High-Throughput Nucleotide Sequencing , Humans , Leukemia, Myeloid, Acute/genetics , Mutation , Myelodysplastic Syndromes/genetics
2.
Aquat Toxicol ; 198: 118-128, 2018 May.
Article in English | MEDLINE | ID: mdl-29529467

ABSTRACT

This paper deals with species sensitivity distributions (SSDs) for the lipophilic insecticide lufenuron and benthic arthropods based on sediment-spiked laboratory toxicity tests. This compound that inhibits chitin synthesis and moulting of arthropods persists in sediment. Using field-collected sediment, toxicity tests were conducted with three macro-crustaceans and six insects. The Hazardous Concentration to 5% of the tested species, the HC5 (and 95% confidence limit), derived from an SSD constructed with 10d-LC50's was 2.2 (1.2-5.7) µg/g organic carbon (OC) in dry sediment. In addition, HC5 values derived from SSDs constructed with 28d-LC10 and 28-d LC50 values were 0.13 (0.02-1.50) µg/g OC and 2.0 (1.3-5.5) µg/g OC, respectively. In 28d toxicity tests with Chironomus riparius and Hyalella azteca, a higher sensitivity was observed when using lufenuron-spiked field-collected sediment than in lufenuron-spiked artificial sediment. Overall, the non-biting midge C. riparius appeared to be a representative and sensitive standard test species to assess effects of lufenuron exposure in sediment. The Tier-1 (based on standard test species), Tier-2 (based on standard and additional test species) and Tier-3 (model ecosystem approach) regulatory acceptable concentrations (RACs) for sediment-spiked lufenuron did not differ substantially. The Tier-2 RAC was the lowest. Since to our knowledge this study is the first in the open literature that evaluates the tiered approach in the sediment effect assessment procedure for pesticides, we advocate that similar evaluations should be conducted for pesticides that differ in toxic mode-of-action.


Subject(s)
Arthropods/drug effects , Benzamides/toxicity , Biological Assay/methods , Ecosystem , Geologic Sediments/chemistry , Toxicity Tests , Amphipoda/drug effects , Animals , Chironomidae/drug effects , Lethal Dose 50 , Species Specificity , Water Pollutants, Chemical/toxicity
5.
Eur J Histochem ; 57(1): e8, 2013 Feb 19.
Article in English | MEDLINE | ID: mdl-23549467

ABSTRACT

The aim of the present work was to evaluate the expression of 8-OHdG (8-hydroxydeoxyguanosine) in the benthic fish Zosterisessor ophiocephalus collected in two differently polluted sites of the Venetian lagoon (Porto Marghera and Caroman). We compared our data on 8-OHdG with those of CYP1A (Cytochrome P450, family 1, subfamily A, polypeptide 1), which is a well known biomarker for detoxification of contaminants. Immunohistochemistry with an antibody to 8-OHdG showed immunopositivity in nuclei of hepatocytes as well as in melanomacrophage centres of spleen and kidney, whereas an anti-CYP1A antibody exhibited positive immunostaining in the liver, kidney and ovary. The liver of males showed higher expression of both proteins than females. In animals from Porto Marghera site, the enzymatic assay for 8-OHdG exhibited higher levels in liver of males than in females. Western Blot analysis using the antibody anti-CYP1A recognized the presence of a band of about 60 kDa in the liver of males and females. Males exhibited a strong band, whereas in females the band showed a lower intensity. By using Real-Time PCR, the mRNA expression of CYP1A did not show any differences between males and females from each site, but it was at borderline significance level. Comparing the two sites, mRNA expression of CYP1A was significantly higher in the liver of both males and females from Porto Marghera than that of Caroman. The present data suggest that pollutants are bio-available as demonstrated by our biomarker analyses and may have a harmful effect on aquatic organisms such as Z. ophiocephalus. We report that the highest levels of hepatic 8-OHdG and CYP1A expression were detected in males, showing clear gender specificity.


Subject(s)
Cell Nucleus/metabolism , Cytochrome P-450 CYP1A1/biosynthesis , Deoxyguanosine/analogs & derivatives , Fish Proteins/biosynthesis , Gene Expression Regulation, Enzymologic , Perciformes/metabolism , Water Pollutants/adverse effects , 8-Hydroxy-2'-Deoxyguanosine , Animals , Deoxyguanosine/biosynthesis , Female , Italy , Male , Organ Specificity , Sex Characteristics
6.
World J Gastroenterol ; 14(1): 46-52, 2008 Jan 07.
Article in English | MEDLINE | ID: mdl-18176960

ABSTRACT

AIM: To evaluate the factors involved in the impairment of health-related quality of life (HRQOL) in patients with celiac disease. METHODS: A multicenter, cross-sectional prospective study was performed in patients with celiac disease who completed two HRQOL questionnaires: the gastrointestinal quality of life index (GIQLI) and the EuroQol-5D (EQ). RESULTS: Three hundred and forty patients (163 controlled with a gluten-free diet, and 177 newly diagnosed with a normal diet) were included. The GIQLI score was significantly better in patients on a gluten-free diet (GFD) than in non-treated patients on their usual diet, both in terms of the overall score (3.3 vs 2.7, respectively; P < 0.001), as well as on the individual questionnaire dimensions. Both the preference value of the EQ as the visual analogue scale were significantly better in treated than in non-treated patients (0.93 vs 0.72 P < 0.001 and 80 vs 70 P < 0.001, respectively). Variables significantly associated with a worse HRQOL score were female gender, failure to adhere to a GFD, and symptomatic status. CONCLUSION: In untreated celiac disease, the most important factors that influence patient perception of health are the presence of symptoms and a normal diet. HRQOL improves to levels similar to those described in the general population in celiac disease patients well controlled with a GFD.


Subject(s)
Celiac Disease/physiopathology , Celiac Disease/psychology , Health Status , Quality of Life , Adult , Female , Humans , Male , Middle Aged , Surveys and Questionnaires
7.
Inflamm Bowel Dis ; 11(5): 488-96, 2005 May.
Article in English | MEDLINE | ID: mdl-15867589

ABSTRACT

BACKGROUND: Inflammatory bowel disease impairs patients' perception of health and has a negative impact on health-related quality of life (HRQOL). Most studies include patients from a single hospital. This may bias limit results through the use of small patient samples and/or samples within a restricted disease spectrum. METHODS: HRQOL was measured in patients with ulcerative colitis (UC) and Crohn's disease (CD) from 9 hospitals located in different geographical areas in Spain using 2 questionnaires: the Spanish version of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the EuroQol. Results are expressed as medians. RESULTS: The study included 1156 patients (528 patients with UC and 628 with CD; median age, 35 yr; slight predominance of women, 617 versus 539). HRQOL worsened in parallel with disease severity to a similar extent in both UC (IBDQ scores of 6.1, 4.7, and 4.0 for the 3 disease severity groups, respectively) and CD (IBDQ scores of 6.1, 5.0, and 4.1, respectively). A similar inverse relation between clinical activity and quality of life was observed when EuroQol preference values were used. All 5 dimensions of the IBDQ showed significantly lower scores in patients with active UC and CD than in patients in remission. The pattern of scores by IBDQ dimensions differed between patients in relapse (who scored worse on the digestive symptoms dimension) and patients in remission. Variables related with disease activity, time of evolution since diagnosis and female sex, were significantly associated with having a worse perception of HRQOL. The type of disease or geographical area of residence did not influence results on the IBDQ. CONCLUSIONS: UC and CD impair patients' HRQOL, and the degree of impairment depends on disease activity but is independent of the type of disease and place of residence.


Subject(s)
Colitis, Ulcerative/physiopathology , Colitis, Ulcerative/psychology , Crohn Disease/physiopathology , Crohn Disease/psychology , Health Status , Quality of Life , Adult , Emotions , Female , Humans , Interpersonal Relations , Male , Middle Aged , Self Concept , Severity of Illness Index , Spain
8.
J Investig Allergol Clin Immunol ; 14(2): 159-61, 2004.
Article in English | MEDLINE | ID: mdl-15301307

ABSTRACT

A case of a child with Crohn's disease who developed an eosinophilic gastroenteritis is reported. Although symptoms of eosinophilic gastroenteritis at age 8 could mimic those of Crohn's disease, laboratory, radiographic and histologically studies are clearly different. Peripheral blood eosinophilia (7,476 cells per mm3), high serum IgE level (1,050 kU/l) and normal C-reactive protein and erythrocyte sedimentation rate are common in eosinophilic gastroenteritis and uncommon in Crohn's disease. Eosinophilic gastroenteritis was due to bovine serum albumin (BSA) hypersensitivity, confirmed with skin tests, serum levels to specific IgE and a SDS-PAGE IgE-immunoblotting. A strict meat-free diet was started, with progressive relief of symptoms and decrease of eosinophil count twelve months later; the patient became fully symptom-free and eosinophil count was normal.


Subject(s)
Crohn Disease/complications , Food Hypersensitivity/complications , Gastroenteritis/complications , Animals , Cattle , Child , Crohn Disease/immunology , Eosinophilia/complications , Eosinophilia/immunology , Food Hypersensitivity/immunology , Gastroenteritis/immunology , Humans , Immunoglobulin E/blood , Male , Meat , Serum Albumin, Bovine/immunology , Skin Tests
9.
Allergol Immunopathol (Madr) ; 30(5): 255-8, 2002.
Article in English | MEDLINE | ID: mdl-12396958

ABSTRACT

Helicobacter pylori has been involved in the pathogenesis of chronic idiopathic urticaria (CIU) in patients suffering both CIU and H. pylori infection. We selected 49 patients with 13C urea breath test positive, long-lasting CIU and H. pylori infection; 20 remained symptomatic, had positive urease test or H. pylori histologic identification in gastric biopsy material and accepted to participate in a pacebo-controlled treatment trial. They were randomized for a 7-day, double-blind, placebo-controlled H. pylori eradication treatment with amoxicillin, clarithromycin and omeprazol or placebo. H. pylori eradication was assessed by a second 13C urea breath test six weeks after the end of treatment. We observed a significant improvement of more than 70 % of CIU; baseline clinical score was seen in 4 of the 9 (44 %) patients who eradicated H. pylori after active treatment and in 1 of the 7 (12,3 %) of those who did not (p = 0.19). No clinical differences in CIU characteristics were found between patients with and without improvement. No serious adverse effects were observed in either treatment group. We conclude that the eradication of H. pylori may be useful for patients suffering long-lasting CIU and H. pylori infection, although theses results did not reach statistical significance probably owing to the strict conditions of the recruitment.


Subject(s)
Gastritis/drug therapy , Helicobacter Infections/drug therapy , Helicobacter pylori , Urticaria/etiology , Adult , Amoxicillin/therapeutic use , Angioedema/etiology , Anti-Ulcer Agents/therapeutic use , Bacterial Proteins/analysis , Biopsy , Breath Tests , Chronic Disease , Clarithromycin/therapeutic use , Double-Blind Method , Drug Therapy, Combination/therapeutic use , Female , Gastric Mucosa/chemistry , Gastric Mucosa/microbiology , Gastritis/complications , Gastritis/diagnosis , Gastritis/microbiology , Gastroscopy , Helicobacter Infections/complications , Helicobacter Infections/diagnosis , Helicobacter pylori/enzymology , Helicobacter pylori/isolation & purification , Humans , Male , Middle Aged , Omeprazole/therapeutic use , Prospective Studies , Treatment Outcome , Urease/analysis
10.
Allergol. immunopatol ; 30(5): 255-258, sept. 2002.
Article in En | IBECS | ID: ibc-17160

ABSTRACT

Helicobacter pylori has been involved in the pathogenesis of chronic idiopathic urticaria (CIU) in patients suffering both CIU and H. pylori infection. We selected 49 patients with 13C urea breath test positive, long-lasting CIU and H. pylori infection; 20 remained symptomatic, had positive urease test or H. pylori histologic identification in gastric biopsy material and accepted to participate in a pacebo-controlled treatment trial. They were randomized for a 7-day, double-blind, placebo-controlled H. pylori eradication treatment with amoxicillin, clarithromycin and omeprazol or placebo. H. pylori eradication was assessed by a second 13C urea breath test six weeks after the end of treatment. We observed a significant improvement of more than 70 % of CIU; baseline clinical score was seen in 4 of the 9 (44 %) patients who eradicated H. pylori after active treatment and in 1 of the 7 (12,3 %) of those who did not (p = 0.19). No clinical differences in CIU characteristics were found between patients with and without improvement. No serious adverse effects were observed in either treatment group. We conclude that the eradication of H. pylori may be useful for patients suffering long-lasting CIU and H. pylori infection, although theses results did not reach statistical significance probably owing to the strict conditions of the recruitment (AU)


La infección por Helicobacter pylori ha sido implicada en la patogénesis de la urticaria crónica idiopática (UCI), sin embargo los resultados de los diversos estudios publicados son contradictorios. Seleccionamos 49 pacientes con UCI de larga evolución y con una prueba del aliento con urea 13C positiva. De ellos 20 que estaban con síntomas activos y que presentaron una prueba de la ureasa positiva o identificación histológica de H. pylori en el material de la biopsia gástrica aceptaron participar en un estudio ciego con tratamiento activo controlado con placebo. Para ello se aleatorizaron para tratamiento erradicador de H. pylori con amoxicilina, claritromicina y omeprazol durante 7 días o para placebo. La erradicación de la infección por H. pylori fue valorada por una segunda prueba del aliento con urea 13C, 6 semanas después de acabado el tratamiento. Los resultados mostraron una mejoría superior al 70 per cent del baremo clínico basal en 4 de los 9 pacientes (44 per cent) que erradicaron la infección después de realizar el tratamiento activo y en uno de los 7 (12,3 per cent) que no lo hicieron (p=0,19). No encontramos características clínicas diferentes entre los pacientes que mejoraron y los que no. No se registraron reacciones adversas destacables en ninguno de los grupos de tratamiento. Concluimos que la erradicación de la infección por H. pylori puede ser útil en algunos pacientes afectados de UCI de larga evolución con infección por H. pylori, aunque los resultados no llegaron a ser estadísticamente significativos debido a las estrictas condiciones del reclutamiento (AU)


Subject(s)
Middle Aged , Adult , Male , Female , Humans , Helicobacter pylori , Urease , Urticaria , Helicobacter Infections , Clarithromycin , Treatment Outcome , Omeprazole , Prospective Studies , Biopsy , Angioedema , Anti-Ulcer Agents , Bacterial Proteins , Chronic Disease , Drug Therapy, Combination , Double-Blind Method , Amoxicillin , Gastric Mucosa , Gastritis , Gastroscopy , Helicobacter Infections , Drug Therapy, Combination , Breath Tests
11.
Gut ; 51(2): 164-8, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12117873

ABSTRACT

BACKGROUND: Dietary fat has been suggested to determine the therapeutic effect of enteral diets in Crohn's disease. AIM: To assess the efficacy of two whole protein based diets with different fat compositions (n6 polyunsaturated fatty acids v monounsaturated fatty acids) in inducing clinical remission in active Crohn's disease compared with steroids. METHODS: Sixty two patients with active Crohn's disease were randomised to receive, for not more than 4 weeks: (a) a polymeric enteral diet containing 35 g of lipids per 1000 kcal, high in oleate (79%) and low in linoleate (6.5%) (PEN1), (b) an identical enteral diet except for the type of fat which was high in linoleate (45%) and low in oleate (28%) (PEN2), or (c) oral prednisone (1 mg/kg/day). Diets were double blindly administered. The steroid group received a conventional ward diet. Treatment failure was considered when remission was not achieved at week 4. Clinical activity and biological and nutritional parameters were monitored. Independent predictors of remission were identified by stepwise logistic regression analysis. RESULTS: Overall remission rates (by intention to treat) were 20% (4/20) for PEN1, 52% (12/23) for PEN2, and 79% (15/19) for steroids (overall p=0.001; p<0.0005 steroids v PEN1, and p=0.056 PEN2 v PEN1). After excluding those patients who were non-compliant during the first week (per protocol analysis), remission rates were 27%, 63%, and 79%, respectively (p=0.008, steroids and PEN2 v PEN1). After adjusting for confounding variables, PEN1 remained significantly associated with a poor response. CONCLUSION: The type of dietary fat may be of importance for the primary therapeutic effect of enteral nutrition in active Crohn's disease.


Subject(s)
Crohn Disease/diet therapy , Dietary Fats/administration & dosage , Enteral Nutrition , Food, Formulated , Acute Disease , Adolescent , Adult , Crohn Disease/drug therapy , Double-Blind Method , Europe , Female , Glucocorticoids/therapeutic use , Humans , Linoleic Acid/administration & dosage , Male , Middle Aged , Oleic Acid/administration & dosage , Regression Analysis
12.
Gastroenterology ; 121(5): 1073-9, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11677198

ABSTRACT

BACKGROUND & AIMS: The efficacy of hormonal therapy for recurrent bleeding from gastrointestinal angiodysplasia remains uncertain. We investigated the efficacy of long-term estrogen-progestagen therapy in the prevention of rebleeding from gastrointestinal angiodysplasia. METHODS: Seventy-two noncirrhotic patients bleeding from gastrointestinal angiodysplasia confirmed by endoscopy or angiography were randomized to receive in double-blind conditions treatment with ethinylestradiol (0.01 mg) plus norethisterone (2 mg) (1 tablet/d), or placebo (1 tablet/d) for a minimum period of 1 year (range: 1-2 years). RESULTS: Four patients could not be assessed because they did not attend the first follow-up visit. Failure of treatment occurred in 13 of 33 (39%) patients in the treatment group and in 16 of 35 (46%) patients in the placebo group (P = NS). No significant differences between groups were found according to number of bleeding episodes (0.7 +/- 1.0 vs. 0.9 +/- 1.5) and transfusional requirements (0.9 +/- 1.9 vs. 0.7 +/- 1.5 units). Treatment received was not an independent predictor for rebleeding prevention in the multivariate regression analysis. Severe adverse events (2 vs. 1) and mortality (0 vs. 1 patient, respectively) were similar between the treatment and placebo groups. CONCLUSIONS: Continuous estrogen-progestagen treatment is not useful in the prevention of rebleeding from gastrointestinal angiodysplasia.


Subject(s)
Angiodysplasia/drug therapy , Ethinyl Estradiol/administration & dosage , Gastrointestinal Hemorrhage/prevention & control , Norethindrone/administration & dosage , Adult , Aged , Angiodysplasia/complications , Double-Blind Method , Ethinyl Estradiol/adverse effects , Female , Humans , Male , Middle Aged , Norethindrone/adverse effects , Recurrence
13.
Hepatology ; 32(1): 36-42, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10869286

ABSTRACT

Steroids are recommended in severe alcohol-induced hepatitis, but some data suggest that artificial nutrition could also be effective. We conducted a randomized trial comparing the short- and long-term effects of total enteral nutrition or steroids in these patients. A total of 71 patients (80% cirrhotic) were randomized to receive 40 mg/d prednisolone (n = 36) or enteral tube feeding (2,000 kcal/d) for 28 days (n = 35), and were followed for 1 year or until death. Side effects of treatment occurred in 5 patients on steroids and 10 on enteral nutrition (not significant). Eight enterally fed patients were prematurely withdrawn from the trial. Mortality during treatment was similar in both groups (9 of 36 vs. 11 of 35, intention-to-treat) but occurred earlier with enteral feeding (median 7 vs. 23 days; P =.025). Mortality during follow-up was higher with steroids (10 of 27 vs. 2 of 24 intention-to-treat; P =. 04). Seven steroid patients died within the first 1.5 months of follow-up. In contrast to total enteral nutrition (TEN), infections accounted for 9 of 10 follow-up deaths in the steroid group. In conclusion, enteral feeding does not seem to be worse than steroids in the short-term treatment of severe alcohol-induced hepatitis, although death occurs earlier with enteral nutrition. However, steroid therapy is associated with a higher mortality rate in the immediate weeks after treatment, mainly because of infections. A possible synergistic effect of both treatments should be investigated.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Enteral Nutrition , Hepatitis, Alcoholic/therapy , Adult , Aged , Female , Follow-Up Studies , Hepatitis, Alcoholic/mortality , Hospitalization , Humans , Male , Middle Aged , Nutritional Status , Prospective Studies
14.
Eur J Gastroenterol Hepatol ; 11(4): 413-20, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10321759

ABSTRACT

BACKGROUND: Although there is strong evidence implicating genetic predisposition in the pathogenesis of the chronic inflammatory bowel diseases, the number and identity of susceptibility genes remain uncertain. Cytokine genes are tentative candidate loci, but data regarding association studies in different populations are conflicting. AIMS: To determine potential associations of interleukin-1 receptor antagonist (IL-1ra), tumour necrosis factor alpha (TNF alpha), and tumour necrosis factor beta (TNF beta) gene polymorphisms with ulcerative colitis or subsets of ulcerative colitis in a Spanish population. METHODS: Genotyping for IL-1ra, TNF alpha and TNF beta gene polymorphisms was performed by the polymerase chain reaction in 95 patients with ulcerative colitis and 74 healthy controls. A variable number of tandem repeats (VNTR) in the IL-1ra gene, and a single base pair polymorphism in the TNF alpha gene promoter region (-308) and in the first intron of the TNF beta gene were analysed. Anti-neutrophil cytoplasmic antibodies (ANCA) were detected using an indirect immunofluorescence assay. RESULTS: There were no significant differences between ulcerative colitis patients and controls in either polymorphism analysed, nor between ulcerative colitis subgroups as a function of the clinical disease pattern. However, when stratified by their ANCA status, perinuclear ANCA (p-ANCA) ulcerative colitis showed an increased frequency of the genotype 1,2 of the IL-1ra gene compared with ANCA-negative ulcerative colitis (52% versus 28%; P = 0.02, Pcorr = 0.1). Furthermore, p-ANCA ulcerative colitis had a statistically significant increase of this genotype compared with cytoplasmic ANCA (c-ANCA)/ANCA-negative ulcerative colitis (52% versus 26.5%; P = 0.01, Pcorr = 0.05). CONCLUSIONS: In the Spanish population studied, the polymorphisms analysed in the IL-1ra, TNF alpha and TNF beta genes are unlikely to be important in the overall susceptibility to ulcerative colitis. However, the combination of a subclinical (p-ANCA) and a genetic (IL-1ra gene) marker identified a distinct ulcerative colitis subgroup (p-ANCA; IL-1ra genotype 1,2). These findings provide further evidence of genetic heterogeneity within ulcerative colitis, and support the concept that ANCA may represent a subclinical marker of genetic heterogeneity.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/analysis , Colitis, Ulcerative/genetics , Genetic Heterogeneity , Polymorphism, Genetic , Receptors, Interleukin-1/antagonists & inhibitors , Receptors, Interleukin-1/genetics , Adolescent , Adult , Aged , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/immunology , Female , Genotype , Humans , Lymphotoxin-alpha/genetics , Male , Middle Aged , Minisatellite Repeats , Spain , Tumor Necrosis Factor-alpha/genetics
15.
J Crit Care ; 14(1): 20-8, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10102720

ABSTRACT

PURPOSE: Liquid perfluorochemicals reduce the production of reaction oxygen species by alveolar macrophages. We sought to determine whether the use of liquid perfluorochemicals in vivo during liquid ventilation would attenuate oxidative damage to the lung. MATERIALS AND METHODS: Healthy infant piglets (n = 16) were instrumented for mechanical ventilation and received intravenous oleic acid to create an acute lung injury. The animals were assigned to a nontreatment group receiving conventional mechanical ventilation or a treatment group receiving partial liquid ventilation with a liquid perfluorochemical. Following sacrifice, the bronchoalveolar lavage and lung parenchyma were analyzed for evidence of oxidative damage to lipids and proteins by determination of TBARS and carbonylated protein residues, respectively. RESULTS: Mortality in the control group was 50% at the completion of the study compared with no deaths in the partial liquid ventilation group (P = .025). The alveolar-arterial oxygen difference was more favorable following injury in the partial liquid ventilation group. The liquid ventilation group demonstrated a 32% reduction in TBARS (P = .043) and a 14% reduction in carbonylated protein residues (P = .061). CONCLUSION: These data suggest that partial liquid ventilation supports gas exchange and reduces mortality in association with a reduction in the production of reactive oxygen species and the concomitant attenuation of tissue damage during the early phase of acute lung injury.


Subject(s)
Emulsions/pharmacology , Fluorocarbons/pharmacology , Lung/pathology , Positive-Pressure Respiration , Pulmonary Gas Exchange/drug effects , Thiobarbituric Acid Reactive Substances/metabolism , Animals , Animals, Newborn , Hemodynamics , Hydrocarbons, Brominated , Lung/drug effects , Lung/metabolism , Positive-Pressure Respiration/methods , Survival Analysis , Swine
16.
Crit Care Med ; 27(12): 2716-23, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10628616

ABSTRACT

OBJECTIVE: To determine the spatial distribution of pulmonary blood flow in three groups of piglets: partial liquid ventilation in normal piglets, partial liquid ventilation during acute lung injury, and conventional gas ventilation during acute lung injury. DESIGN: Prospective randomized study. SETTING: A university medical school laboratory approved for animal research. SUBJECTS: Neonatal piglets. INTERVENTIONS: Regional pulmonary blood flow was studied in 21 piglets in the supine position randomized to three different groups: a normal group that received partial liquid ventilation (Normal-PLV) and two acute lung injury groups that received an oleic acid-induced lung injury: partial liquid ventilation during acute lung injury (OA-PLV) and conventional gas ventilation during acute lung injury (OA-Control). Acute lung injury was induced by infusing oleic acid (0.15 mL/kg iv) over 30 mins. Partial liquid ventilation was instituted with perflubron (LiquiVent, 30 mL/kg) after 30 mins in the Normal-PLV and OA-PLV groups. MEASUREMENTS AND MAIN RESULTS: Arterial and venous blood gases, hemodynamics, and pulmonary mechanics were measured every 15 mins throughout the hour-long study. Pulmonary blood flow was assessed by fluorescent microsphere technique at baseline and after 30, 45, and 60 mins. In the Normal-PLV piglets, pulmonary blood flow decreased from baseline (before injury or partial liquid ventilation) in the most dependent areas of the lung (F ratio = 3.227; p < .001). In the OA-PLV piglets, pulmonary blood flow was preserved over time throughout the lung (F ratio = 1.079; p = .38). In the OA-Control piglets, pulmonary blood flow decreased in the most dependent areas of the lung and increased from baseline in less dependent slices over time (F ratio = 2.48; p = .003). CONCLUSIONS: The spatial distribution of regional pulmonary blood flow is preserved during partial liquid ventilation compared with gas ventilation in oleic acid-induced lung injury.


Subject(s)
Lung Diseases/physiopathology , Pulmonary Circulation , Pulmonary Gas Exchange , Respiration, Artificial/methods , Animals , Animals, Newborn , Hemodynamics , Lung Diseases/chemically induced , Lung Diseases/therapy , Microspheres , Oleic Acid , Swine
17.
Crit Care Med ; 26(9): 1593-5, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9751599

ABSTRACT

OBJECTIVE: To assess the clinical use of the Dynamic Objective Risk Assessment (DORA) severity of illness score in a site remote from its development. DESIGN: Prospective chart review. SETTING: Tertiary referral pediatric intensive care unit (PICU). PATIENTS: One hundred sixty consecutive admissions involving 621 patient days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pediatric Risk of Mortality (PRISM) scores were collected daily for all PICU patient days. Collection of data was performed by a physician not directly involved in the ordering of vital signs or laboratory data. The daily DORA score was calculated from the previous day's PRISM score and the admission PRISM score according to a previously described formula. The DORA score determines the patient's risk of mortality for the next 24 hrs. Also documented were the tests not ordered for each patient day. The sensitivity and specificity of the DORA score in our patient population were very similar to that previously reported using the previously described 1% cutoff for predicted mortality. We also noted that the tests ordered were related to the physician's perception of the patient's degree of sickness, and were themselves predictive of outcome. CONCLUSION: An outcome scoring system created in one group of PICUs can be applied to patients in another PICU remote from where the scoring system was developed with similar ability to predict outcome.


Subject(s)
Critical Illness/classification , Intensive Care Units, Pediatric/statistics & numerical data , Risk Assessment , Severity of Illness Index , Adolescent , Child , Child, Preschool , Female , Forecasting , Hospitals, Pediatric , Humans , Infant , Infant, Newborn , Male , New York , Outcome Assessment, Health Care , Probability , Prospective Studies , Sensitivity and Specificity , Survival Analysis
18.
Inflamm Bowel Dis ; 4(1): 1-5, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9552221

ABSTRACT

The inflammatory activity of colonic mucosal lesions may be stimulated by intraluminal bacteria. Our aim was to investigate whether administration of broad-spectrum antibiotics decreases inflammatory activity in ulcerative colitis. To this end, we performed a randomized, 5-day study with either oral enterically coated amoxicillin-clavulanic acid (1 g + 250 mg, t.i.d.); i.v. methylprednisolone (40 mg/day) and oral placebo (t.i.d.); or both i.v. methylprednisolone and oral amoxicillin-clavulanic acid as above, in 30 patients with clinically active ulcerative colitis. Before and after 5 days of treatment, intestinal inflammation was assessed by the quantification of mucosal release of eicosanoids and interleukin-8 by rectal dialysis in each patient. Breath H2 excretion after oral lactulose was determined as an index of metabolic activity of colonic flora. The total release of (IL-8) interleukin-8 and eicosanoids significantly decreased in patients treated with antibiotic or steroids and antibiotic. Antibiotic treatment, but not steroids, markedly inhibited breath H2 excretion. In conclusion, short-term treatment with enteric-coated amoxicillin-clavulanic acid decreases the intraluminal release of IL-8 and other inflammatory mediators.


Subject(s)
Amoxicillin-Potassium Clavulanate Combination/administration & dosage , Colitis, Ulcerative/drug therapy , Drug Therapy, Combination/administration & dosage , Adolescent , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Colitis, Ulcerative/immunology , Eicosanoids/metabolism , Female , Humans , Interleukin-8/metabolism , Male , Methylprednisolone/therapeutic use , Middle Aged , Tablets, Enteric-Coated
19.
Med Clin (Barc) ; 110(1): 11-5, 1998 Jan 17.
Article in Spanish | MEDLINE | ID: mdl-9527980

ABSTRACT

BACKGROUND: The aim of the present study was to determine the prevalence and diagnostic usefulness of antineutrophil cytoplasmic antibodies (ANCA) in a Spanish population of patients with inflammatory bowel disease from the province of Tarragona. PATIENTS AND METHODS: One hundred and fifty-six sera obtained from 116 patients with inflammatory bowel disease (75 ulcerative colitis and 41 Crohn's disease) and 40 healthy controls were tested using an indirect immunofluorescence assay. RESULTS: ANCA were detected in 65% of patients with ulcerative colitis but in only 12% of patients with Crohn's disease (p < 0.01), and 2.5% of control subjects (p < 0.01). The overall sensitivity of the test for the diagnosis of ulcerative colitis was 65% with a specificity of 88% and a positive predictive value of 91%. Among patients with ulcerative colitis there was no relationship between the presence or titre of ANCA and the duration, the clinical course, the extent, the disease activity or the need for medical treatment. CONCLUSIONS: In the population studied, ANCA occur more commonly in ulcerative colitis than in Crohn's disease, as reported in other populations. Their determination in patients with inflammatory bowel disease may be useful to differentiate ulcerative colitis from Crohn's disease.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/blood , Inflammatory Bowel Diseases/blood , Adult , Colitis, Ulcerative/blood , Crohn Disease/blood , Female , Fluorescent Antibody Technique, Indirect , Humans , Male , Sensitivity and Specificity , Spain
20.
J Appl Physiol (1985) ; 84(1): 327-34, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9451653

ABSTRACT

Partial liquid ventilation using conventional ventilatory schemes improves lung function in animal models of respiratory failure. We examined the feasibility of high-frequency partial liquid ventilation in the preterm lamb with respiratory distress syndrome and evaluated its effect on pulmonary and systemic hemodynamics. Seventeen lambs were studied in three groups: high-frequency gas ventilation (Gas group), high-frequency partial liquid ventilation (Liquid group), and high-frequency partial liquid ventilation with hypoxia-hypercarbia (Liquid-Hypoxia group). High-frequency partial liquid ventilation increased oxygenation compared with high-frequency gas ventilation over 5 h (arterial oxygen tension 253 +/- 21.3 vs. 17 +/- 1.8 Torr; P < 0.001). Pulmonary vascular resistance decreased 78% (P < 0.001), pulmonary blood flow increased fivefold (P < 0.001), and aortic pressure was maintained (P < 0.01) in the Liquid group, in contrast to progressive hypoxemia, hypercarbia, and shock in the Gas group. Central venous pressure did not change. The Liquid-Hypoxia group was similar to the Gas group. We conclude that high-frequency partial liquid ventilation improves gas exchange and stabilizes pulmonary and systemic hemodynamics compared with high-frequency gas ventilation. The stabilization appears to be due in large part to improvement in gas exchange.


Subject(s)
Hemodynamics/physiology , High-Frequency Ventilation , Pulmonary Gas Exchange/physiology , Respiratory Distress Syndrome, Newborn/physiopathology , Animals , Animals, Newborn , Gestational Age , High-Frequency Jet Ventilation , Humans , Infant, Newborn , Lung/pathology , Lung/physiopathology , Oxygen/blood , Pulmonary Circulation/physiology , Respiratory Distress Syndrome, Newborn/pathology , Sheep , Vascular Resistance/physiology
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