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1.
Healthcare (Basel) ; 11(16)2023 Aug 21.
Article in English | MEDLINE | ID: mdl-37628550

ABSTRACT

INTRODUCTION: This study was designed to evaluate whether the Workshop on Basic Principles for Clinical Gynaecological Exploration, offered to medical students, improves theoretical-practical knowledge, safety, confidence, global satisfaction and the achievement of the proposed objectives in the area of gynaecological clinical examinations. MATERIALS AND METHODS: This was a quasi-experimental pre-post-learning study carried out at the Gynaecology and Obstetrics department of Gregorio Marañón Hospital in Madrid (Spain). The volunteer participants were 4th-year students earning a degree in Medicine during the 2020-2021 and 2021-2022 academic years. The study period was divided into the following stages: pre-workshop, intra-workshop and 2 weeks post-workshop. In the pre-workshop stage, students completed a brief online course to prepare for the workshop. The effectiveness of the workshop was evaluated through multiple-choice tests and self-administered questionnaires to assess self-assurance, self-confidence, self-satisfaction and the achievement of the objectives. RESULTS: Of the 277 students invited in both academic years, 256 attended the workshop (92.4%), with a total participation in the different stages of the study greater than 70%. A total of 82.5% of the students in the 2020-2021 academic year and 80.6% of students in the 2021-2022 academic year did not have any type of experience performing gynaecological clinical examinations. Between the pre-workshop and 2 weeks post-workshop stages, there was significant improvement in theoretical-practical knowledge (improvement mean = 1.38 and 1.21 in 2020-2021 and 2021-2022 academic years, respectively). The security and confidence of the students prior to the workshop were low (average scores less than 5 points) in both academic years. However, post-workshop scores for satisfaction and the achievement of objectives were high in the two academic years; all the values approached or exceeded 8 points. CONCLUSIONS: Our students, after outstanding participation, evaluated the BPCGE, and improved their theoretical and practical knowledge, as well as their skills in a gynaecological clinical examination. Moreover, in their view, after the workshop, they felt very satisfied, far outreaching the proposed aims. In addition, excellent results were maintained over time, year after year.

2.
J Pediatr Gastroenterol Nutr ; 76(5): 610-615, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36821846

ABSTRACT

OBJECTIVES: Patients hospitalized with inflammatory bowel disease (IBD) have increased risk of venous thromboembolism (VTE). The aim of this study was to determine whether the adoption of a VTE protocol would change rates of medical VTE prophylaxis (low molecular weight heparin) in patients with IBD and a central venous catheter (CVC), while subsequently decreasing the incidence of VTE in this population. METHODS: A protocol for VTE prophylaxis in IBD was established in March of 2018. Every patient hospitalized with an IBD flare and central venous access from March 2013 to March 2020 was identified. Study data, including patient demographics, rates of Doppler ultrasound (US), and rates of VTE were collected using International Classification of Diseases (ICD)-10 codes, CPT codes, and chart review retrospectively. Determination of an IBD flare was based on physician global assessment. Groups were compared with independent-sample t tests and chi-squared tests. RESULTS: A total of 313 hospitalizations across 187 different patients were identified that met criteria including IBD and central venous access. VTE prophylaxis increased from 5.24% (n = 12) prior to the intervention to 63.10% (n = 53) after the intervention [chi-square (1, N = 313) = 125.0192, P < 0.001]. Rate of Doppler US increased from 9.17% (n = 21) prior to the intervention to 17.86% (n = 15) after the intervention [chi-square (1, N = 313) = 4.5562, P < 0.05]. Diagnosis of VTE increased from 0.87% (n = 2) prior to the intervention to 7.14% (n = 6) after the intervention [chi-square (1, N = 313) = 9.6992, P < 0.01]. There were no significant differences in the demographic characteristics pre- versus post-intervention. CONCLUSIONS: Rates of Doppler US and VTE prophylaxis use increased significantly after implementation of a VTE protocol. Rates of VTE diagnosis also increased, though we suspect this may be due to missed diagnoses prior to implementation of the protocol and increased risk awareness after the protocol was established.


Subject(s)
Central Venous Catheters , Inflammatory Bowel Diseases , Venous Thromboembolism , Humans , Child , Venous Thromboembolism/diagnostic imaging , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Retrospective Studies , Central Venous Catheters/adverse effects , Anticoagulants/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Hospitalization , Risk Factors
4.
Clin Ther ; 43(5): e86-e102, 2021 05.
Article in English | MEDLINE | ID: mdl-33812699

ABSTRACT

PURPOSE: We aimed to elucidate the influence on analgesic effect of genetic polymorphisms in enzymes responsible for biotransformation of tramadol and ibuprofen or other possible genes involved in their mechanism of action. METHODS: The study population comprised 118 patients from a multicenter, randomized, double-blind, placebo-controlled, Phase III clinical trial that assessed the analgesic efficacy and tolerability of a single dose of ibuprofen (arginine)/tramadol 400/37.5 mg compared with ibuprofen arginine 400 mg alone, tramadol 50 mg alone, and placebo in patients with moderate to severe pain after dental surgery. We analyzed 32 polymorphisms in the cytochrome P450 (CYP) enzymes COMT, ABCB1, SLC22A1, OPRM1, and SLC22A1. FINDINGS: We did not find any statistically significant difference among CYP2C9 phenotypes related to ibuprofen response, although CYP2C9 poor metabolizers had a longer effect (higher pain relief at 6 hours). Likewise, we did not find any statistically significant difference among PTGS2 genotypes, contradicting previously publications. IMPLICATIONS: There was not a clear effect of CYP2D6 phenotype on tramadol response, although CYP2D6 poor metabolizers had a slower analgesic effect. Concerning the transport of CYP2D6, we observed a better response in individuals carrying ABCB1 mutated alleles, which might correlate with higher tramadol plasma levels. Finally, we found a statistically significant better response in patients carrying the OPRM1 A118G G allele, which contradicts the previous reports. Measuring the active metabolite O-desmethyl-tramadol formation would be of great importance to better evaluate this association because O-desmethyl-tramadol has a higher µ-opioid receptor affinity compared with the parent drug. EudraCT.ema.europa.eu identifier: 2013-004637-33.


Subject(s)
Tramadol , Analgesics, Opioid , Double-Blind Method , Humans , Ibuprofen/therapeutic use , Pain , Pain, Postoperative/drug therapy , Pain, Postoperative/genetics , Polymorphism, Genetic/genetics
5.
Regen Med ; 15(9): 2053-2065, 2020 09.
Article in English | MEDLINE | ID: mdl-33245008

ABSTRACT

Venous leg ulcers (VLU) represent an uphill economic, health and social burden, aggravated in the elderly. Best-practice care interventions are often insufficient and alternative therapies need to be explored. Herein, we have treated for the first time a chronic VLU in an elderly patient by combining cell therapy and tissue engineering in the context of a compassionate use. The administration of allogeneic adipose-derived mesenchymal stromal cells (MSCs) embedded in a plasma-based bioengineered dermis covering the ulcer bed and also injected into the ulcer margins led to the complete closure of a 10-year recalcitrant VLU in an 85-year-old patient. Regenerative properties of MSCs might be boosted by the use of bioengineered matrices for their delivery.


Subject(s)
Leg Ulcer , Mesenchymal Stem Cells , Varicose Ulcer , Adipose Tissue , Aged , Aged, 80 and over , Humans , Leg Ulcer/therapy , Tissue Engineering
7.
J Hand Surg Am ; 45(12): 1134-1140, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32718787

ABSTRACT

PURPOSE: Although fifth metacarpal neck fractures are typically treated nonsurgically, most often with closed reduction and orthosis immobilization, cast immobilization may not improve outcomes compared with buddy taping without reduction. The aim of this study was to compare functional outcomes of buddy taping versus reduction and cast immobilization in patients with fifth metacarpal neck fractures. METHODS: Adult patients with acute fifth metacarpal neck fractures with less than 70º volar angulation and without rotational deformity were randomly assigned to be treated either with buddy taping or a cast after closed reduction. The primary outcome was the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire score at 9 weeks. Secondary outcomes included the DASH score at 3 weeks and 1 year, range of motion of the metacarpophalangeal joint, pain, grip strength, return to work, radiographic angulation, and complication rate. RESULTS: We recruited 72 patients between August 2016 and January 2018. After 3 weeks, the DASH score was significantly lower for patients treated with buddy taping (19.7 ± 19.7) compared with cast immobilization (44.6 ± 15.0). At 9 weeks, clinical outcomes in the buddy taping group were better in terms of range of motion and DASH score, with a mean difference of 6.3 points, which did not exceed the minimally clinically important difference. There were more complications in the cast immobilization group. Fracture angulation after reduction was followed by a loss of reduction at 3 weeks' follow-up and equivalent residual radiographic volar angulation was observed at 3 and 9 weeks after injury in both groups. Duration of time off from work was 28 days shorter with buddy taping compared with cast treatment. CONCLUSIONS: There is no benefit to reduction and orthosis immobilization of fifth metacarpal neck fractures with an initial angulation less than 70°. Use of buddy taping and early mobilization had good clinical results as well as significant improvement in time lost from work. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.


Subject(s)
Fractures, Bone , Hand Injuries , Metacarpal Bones , Adult , Casts, Surgical , Fractures, Bone/diagnostic imaging , Fractures, Bone/therapy , Humans , Metacarpal Bones/diagnostic imaging , Metacarpal Bones/injuries , Prospective Studies , Range of Motion, Articular , Treatment Outcome
8.
J Glob Antimicrob Resist ; 19: 241-251, 2019 12.
Article in English | MEDLINE | ID: mdl-31176754

ABSTRACT

OBJECTIVES: Bacterial viability and enrichment of resistance resulting from three different amikacin administration schedules with respect to haemodialysis (HD) were assessed against three OXA-48-producing Klebsiella pneumoniae isolated during an outbreak in a Spanish hospital. METHODS: A previously described two-compartment dynamic system was used. Three possible amikacin administration schedules were simulated: (i) haemodialysis immediately after amikacin infusion (pre-HD); (ii) infusion immediately after haemodialysis (post-HD); and (iii) infusion at 50% interdialytic period. Amikacin standard dose (SD) and double dose (DD) were simulated for each schedule. Values of Cmax/MIC, Cmax/MPC (mutant prevention concentration), AUC0-48h/MIC, AUC0-48h/MPC and %TMSW (percentage of time that the concentration was inside the mutant selection window) were determined with experimental data and were correlated with the area under the bacterial killing curve of the total population and the resistant subpopulation. RESULTS: Both with SD and DD, the pre-HD schedule resulted in increases at 48h in bacterial counts of the total population at the expense of enrichment of pre-existing resistant subpopulations from 12h onwards for all strains. The estimated %TMSW that prevented enrichment of resistant mutants was <61.5%. The AUC0-48h/MPC (with values of ≈40 being associated with countering of increases in resistant subpopulations) was better than the %TMSW as a predictive parameter. CONCLUSION: This study showed that the longest times concentrations were above the MPC (i.e. highest AUC0-48h/MPC, lowest %TMSW), the lowest enrichment of resistant subpopulations. This implies use of the highest possible amikacin dose (limited by toxicity) and post-HD as the best administration schedule.


Subject(s)
Amikacin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Klebsiella Infections/prevention & control , Klebsiella pneumoniae/drug effects , Microbial Viability/drug effects , Renal Dialysis , Amikacin/pharmacokinetics , Amikacin/therapeutic use , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/therapeutic use , Computer Simulation , Cross Infection/drug therapy , Cross Infection/microbiology , Cross Infection/prevention & control , Drug Administration Schedule , Humans , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/enzymology , Microbial Sensitivity Tests , Spain , Time Factors , beta-Lactamases
9.
Front Immunol ; 10: 1151, 2019.
Article in English | MEDLINE | ID: mdl-31231366

ABSTRACT

Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI.

10.
Clin Nutr ; 38(4): 1588-1593, 2019 08.
Article in English | MEDLINE | ID: mdl-30097364

ABSTRACT

BACKGROUND: The term "Immunonutrition" (IMN) describes the enteral administration of certain substrates with a theoretical immunomodulating function. From all the elements conforming these IMN formulas, Omega-3 fatty acids (O3FA) are hypothesized to be the most important component for immunomodulation, with increased anti-inflammatory and antioxidant effect. PATIENTS AND METHODS: A prospective randomized clinical trial of all the patients undergoing laparoscopic Roux-en-Y gastric bypass was performed. Patients were randomly assigned into 2 groups: those patients receiving a preoperative balanced energy high-protein formula (Control Group) and those ones who received the same preoperative nutritional formula enriched with O3FA (Experimental Group). In both groups, there was a restriction to 900 Kcal/day. Nutritional intervention started 10 days before surgery and was maintained up to 8 h before the surgical act. Preoperative weight loss, postoperative pain, complications and acute phase reactants were investigated. RESULTS: 40 patients were included in the study, 20 in each group. Preoperative excess weight loss (EWL) with the prescribed treatment was 10.6 ± 7.7% in Control Group and 14.1 ± 5.8% in the Experimental Group (p = 0.024). Mean postoperative pain was 25 ± 9.2 mm in Control group and 10,9 ± 4,4 mm in Experimental Group (p = 0.015). CRP determined 24 h after surgery was significantly lower in the Experimental Group than in the Control Group. There were not significant differences in complications, mortality or readmission rates between groups. CONCLUSIONS: The use of a nutritional supplement enriched with O3FA is associated with a greater preoperative weight loss, reduced postoperative pain and decreased postoperative levels of C reactive protein.


Subject(s)
Fatty Acids, Omega-3 , Gastric Bypass/adverse effects , Pain, Postoperative , Adult , C-Reactive Protein/analysis , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-3/therapeutic use , Female , Humans , Male , Middle Aged , Pain, Postoperative/blood , Pain, Postoperative/drug therapy , Pain, Postoperative/epidemiology , Pain, Postoperative/prevention & control , Preoperative Care , Weight Loss/physiology
11.
Basic Clin Pharmacol Toxicol ; 116(3): 257-63, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25154757

ABSTRACT

Use of non-steroidal anti-inflammatory drugs in cirrhosis has been associated with impairment of renal function based on its ability to inhibit the renal production of prostaglandins. Renal effects of dipyrone in patients with cirrhosis have not been evaluated. We aimed to assess the renal effect of therapeutic doses of dipyrone used for short periods of time in patients with cirrhosis. Twenty-nine patients with cirrhosis were included in an observer-blind clinical trial. Patients were randomized to receive three times a day oral acetaminophen (500 mg; N = 15) or dipyrone (575 mg; N = 14) for 72 hr. Serum and urine samples were obtained at baseline, 48 and 72 hr, and cystatin C, creatinine, aldosterone, 6-keto-Prostaglandin-F1 alpha and prostaglandin E2 were measured. Cystatin C and creatinine levels remained comparable in patients treated with acetaminophen and dipyrone. Urine and serum prostaglandins concentrations were significantly decreased at 72 hr in patients treated with dipyrone regardless of the status of ascites. One patient with ascites treated with dipyrone required a paracentesis and developed renal insufficiency. We conclude that dipyrone and acetaminophen did not reduce renal function when used for short periods of time (up to 72 hr) in patients with cirrhosis. However, considering that dipyrone lowered renal vasodilator prostaglandins synthesis, acetaminophen appears as the safest choice with respect to kidney function in cirrhosis.


Subject(s)
Dipyrone/adverse effects , Kidney/drug effects , Liver Cirrhosis/drug therapy , Prostaglandins/metabolism , Acetaminophen/administration & dosage , Acetaminophen/adverse effects , Acetaminophen/therapeutic use , Adult , Aged , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/adverse effects , Analgesics, Non-Narcotic/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Ascites/drug therapy , Dipyrone/administration & dosage , Dipyrone/therapeutic use , Female , Humans , Kidney Function Tests , Male , Middle Aged , Single-Blind Method , Time Factors
12.
Emerg Med J ; 31(9): 706-13, 2014 Sep.
Article in English | MEDLINE | ID: mdl-23793945

ABSTRACT

BACKGROUND: The mainstay of treatment for acutely decompensated heart failure (ADHF) is intravenous diuretic therapy either as a bolus or via continuous infusion. OBJECTIVES: We evaluated the clinical effects and safety of three strategies of intravenous furosemide administration used in emergency departments (EDs) for ADHF. METHODS: We performed a multicentre, randomised, parallel-group study. Patients with ADHF were randomised within 2 h of ED arrival to receive furosemide by continuous infusion (10 mg/h, group 1) or boluses (20 mg/6 h, group 2; or 20 mg/8 h, group 3). The primary end point was total diuresis, and secondary end points were dyspnoea, orthopnoea, extension of rales and peripheral oedema, blood pressure, respiratory and heart rates, and pulse oximetry, which were measured at arrival and 3, 6, 12 and 24 h after treatment onset. We also measured serum creatinine, sodium and potassium levels at arrival and after 24 h. RESULTS: Group 1 patients (n=36) showed greater 24 h diuresis (3705 mL) than those in groups 2 (n=37) and 3 (n=36) (3093 and 2670 mL, respectively; p<0.01), and this greater diuretic effect was observed earlier. However, no differences were observed among groups in the nine secondary clinical end points evaluated. Creatinine deterioration developed in 15.6% of patients, hyponatraemia in 9.2%, and hypokalaemia in 19.3%, with the only difference among groups observed in hypokalaemia (group 1, 36.3%; group 2, 13.5%; group 3, 8.3%; p<0.01). CONCLUSIONS: In patients with ADHF attending the ED, boluses of furosemide have a smaller diuretic effect but provide similar clinical relief, similar preservation of renal function, and a lower incidence of hypokalaemia than continuous infusion. TRIAL REGISTRATION NUMBER: This randomised trial was registered in the European Clinical Trial Database (EudraCT) with the reference number 2008-004488-20.


Subject(s)
Diuretics/administration & dosage , Furosemide/administration & dosage , Heart Failure/drug therapy , Renal Insufficiency/drug therapy , Acute Disease , Aged , Aged, 80 and over , Biomarkers/blood , Creatinine/blood , Diuretics/adverse effects , Female , Furosemide/adverse effects , Humans , Hypokalemia/etiology , Hyponatremia/etiology , Infusions, Intravenous , Male , Qualitative Research , Renal Insufficiency/blood , Surveys and Questionnaires
13.
Eur J Clin Invest ; 41(1): 8-15, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20731703

ABSTRACT

BACKGROUND: Bacterial infections are common complications arising in patients with cirrhosis and ascites. Translocation of bacterial DNA is a dynamic process that is associated with an increased inflammatory response and a poor prognosis in this setting. The aim of this study was to study whether peritoneal macrophages remain in a chronic primed status to allow a rapid response to subsequent events of bacterial translocation. PATIENTS AND METHODS: Peritoneal monocyte-derived macrophages were isolated from 25 patients with cirrhosis and non-infected ascites and compared with donor's blood monocytes. Activation cell-surface markers were screened using flow-cytometry, and the phosphorylation state of ERK 1/2, p38 MAP Kinase, PKB/Akt and transcription factors c-Jun and p65 NFκB were evaluated using Western blot. Synthesis of tumour necrosis factor alpha, interleukin 6 (IL-6) and interleukin-10 (IL-10) at baseline and in response to bacterial stimuli was evaluated using ELISA. RESULTS: A high expression of CD54, CD86 and HLA-DR at baseline was displayed by peritoneal macrophages. Increased phosphorylated levels of ERK1/2, protein kinase B (PKB) and c-Jun, together with IL-6 production, were observed in peritoneal macrophages at baseline compared with donors' blood monocytes. A positive correlation was established between basal IL-6 levels and extracellular signal-regulated kinase (ERK) phosphorylation in peritoneal macrophages from patients with cirrhosis (r=0·9; P=0·005). Addition of lipopolysaccharide induced higher phosphorylation levels of all studied signalling intermediates than synthetic-oligodeoxydinucleotides, but similar end-stage p65 NFκB. CONCLUSIONS: A sustained immune response is present in ascitic fluid of cirrhotic patients, even in the temporal absence of bacterial antigens. This would facilitate a fast response, probably controlled by IL-6, against repeated bacterial-DNA translocation or in liver chronic inflammation.


Subject(s)
Ascitic Fluid/immunology , Bacterial Translocation/immunology , Liver Cirrhosis/immunology , Macrophages, Peritoneal/immunology , Mitogen-Activated Protein Kinases/immunology , Adult , Aged , Cytokines/immunology , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Humans , Interleukin-6/metabolism , Male , Middle Aged , Monocytes/immunology , Phosphorylation , Prospective Studies
14.
J Mol Med (Berl) ; 88(5): 487-95, 2010 May.
Article in English | MEDLINE | ID: mdl-20087563

ABSTRACT

Bacterial translocation in patients with cirrhosis induces a marked proinflammatory activity that may be different against viable bacteria or bacterial products. The aim of this study is to identify new markers of bacterial translocation by investigating bacterial-driven peptides and correlate their presence with the inflammatory response. Patients with cirrhosis and ascites were included. An analysis by two-dimensional polyacrylamide gel electrophoresis of ascitic fluid total protein from patients (n = 47) and from frequently detected bacterial strains was performed. Two-dimensional maps were digitally compared. The identification of possible markers was performed by mass spectrometry. TNF-alpha, IFN-gamma, IL-12, nitric oxide, and proteins of the complement and lipopolysaccharide-binding protein levels were measured in ascitic fluid samples of patients by enzyme-linked immunosorbent assay. Patients were distributed according to the presence (group I, n = 16) and absence (group II, n = 31) of serum and ascitic fluid bacterial DNA. Among clinical and analytical differences between groups, only mean arterial pressure was significantly higher in patients from group II. Identified bacterial peptides were associated with bacterial protection against immune defenses and included glyceraldehyde-3-phosphate dehydrogenase A, Porin OmpC, and HSP60. Eight patients from group I also showed bacterial peptides, whereas none from group II did. All studied mediators of immune activation were significantly higher in patients with bacterial DNA than in patients without bacterial DNA. TNF-alpha, IFN-gamma, and proteins of the complement were significantly increased in patients with bacterial peptides versus those without bacterial peptides. Bacterial peptide translocation is present in the ascitic fluid of a subgroup of patients with advanced cirrhosis and is associated with an increased immune response.


Subject(s)
Ascites/microbiology , Bacterial Proteins/analysis , Bacterial Translocation , Liver Cirrhosis/complications , Liver Cirrhosis/microbiology , Peritonitis/diagnosis , Proteomics/methods , Adult , Aged , Amino Acid Sequence , Ascites/immunology , Ascitic Fluid/immunology , Ascitic Fluid/microbiology , Bacterial Proteins/isolation & purification , Cytokines/immunology , Escherichia coli/physiology , Female , Humans , Klebsiella pneumoniae/physiology , Liver Cirrhosis/immunology , Male , Middle Aged , Molecular Sequence Data , Peptides/analysis , Peptides/isolation & purification , Peritonitis/etiology , Peritonitis/microbiology
15.
Gastroenterology ; 137(5): 1669-79.e1, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19660462

ABSTRACT

BACKGROUND & AIMS: Patients with cirrhosis undergoing selective intestinal decontamination with norfloxacin show a reduction in serum cytokine levels, probably because of a combined effect of norfloxacin on bowel flora and neutrophils. METHODS: Thirty-one patients with cirrhosis receiving norfloxacin (400 mg/day) were included. Blood samples were collected at 0.5-4 hours (peak samples group, n = 47) and at 22-24 hours (trough samples group, n = 84) after dose. Fifty-nine ascitic fluid samples were obtained. Single doses of norfloxacin and trimethoprim/sulfamethoxazole were administered to 13 and 5 patients, respectively, (temporal profile group) and samples were collected at 0, 0.5, 1, 1.5, 2, 4, and 24 hours. Norfloxacin, trimethoprim/sulfamethoxazole, cytokines, nitric oxide, expression levels of nuclear factor (NF)-kappaB and inhibitor of NF-kappaB (IkB-alpha), neutrophil oxidative burst, and rate of apoptotic events were determined. RESULTS: All samples were bacterial DNA negative and had no significant levels of lipopolysaccharide. Serum and ascitic levels of tumor necrosis factor-alpha, interferon-gamma, interleukin-12, and nitric oxide were significantly lower in peak than in trough samples. A correlation was present between serum norfloxacins concentrations and tumor necrosis factor-alpha (r = -0.68; P < .001), interferon-gamma (r = -0.66; P < .001), interleukin-12 (r = -0.66; P < .001), and nitric oxide (r = -0.68; P < .001). Serum norfloxacin's highest concentrations (1 +/- 0.5 microg/mL) were achieved at 1-2 hours and concurred in time with the lower levels of cytokines and nitric oxide. Intracellular norfloxacin's highest levels (2 +/- 1 microg/mL/10(7) cells) were observed at 2 hours and concurred with a lower NF-kappaB expression, a reduced anion superoxide generation, and apoptotic rate in response to phorbol myristate acetate. Trimethoprim/sulfamethoxazole did not significantly modulate cytokine expression. CONCLUSIONS: Norfloxacin but not trimethoprim/sulfamethoxazole modulates inflammatory response and directly affects neutrophils in patients with cirrhosis.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cytokines/metabolism , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Norfloxacin/pharmacology , Respiratory Burst/drug effects , Aged , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/etiology , Bacterial Infections/prevention & control , Cohort Studies , Cross-Over Studies , Female , Humans , Liver Cirrhosis/therapy , Male , Middle Aged , NF-kappa B/metabolism , Neutrophil Activation/drug effects , Norfloxacin/therapeutic use , Peritonitis/etiology , Peritonitis/prevention & control
16.
Pharmacoepidemiol Drug Saf ; 18(4): 291-300, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19165760

ABSTRACT

BACKGROUND/AIM: The number of patients receiving amiodarone will increase in future years. As clinically significant hepatotoxicity associated with oral amiodarone is infrequent and difficult to predict, a new Bayesian-developed model is proposed to help in the causality assessment of amiodarone-induced liver injury. METHODS: Incidence of abnormal liver enzymes in patients receiving amiodarone was obtained from placebo controlled clinical trials. Published case reports of amiodarone-induced hepatotoxicity were identified through a literature search. Maximum number of expected hepatotoxicity cases in amiodarone and placebo-treated patients was calculated using Poisson distribution. The calculated odds ratio was used as a Prior Odds (PrO) to subsequent quantification, using a Bayesian-approach, of individual amiodarone-induced hepatotoxicity likelihood. RESULTS: PrO of amiodarone-induced hepatotoxicity was 0.48. Thirty nine amiodarone-associated hepatotoxicity case reports were retrieved. Half of published case reports developed an irreversible damage. The amiodarone Bayesian model combining information about latency period and period of remission, together with analytical parameters properly defines the toxicity profile shown in published case reports. The analytical pattern defined by this model is different from the one expected if liver injury in published cases was caused by other etiologies. CONCLUSIONS: A method based on a Bayesian-approach, which links information from clinical trials with clinical hepatotoxicity profile from published case reports can be a useful tool for amiodarone-induced liver injury causality assessment. At present, this method is limited due to scarcity and quality of available data. Further efforts are needed to improve model ability in order to identify amiodarone-induced liver injury.


Subject(s)
Amiodarone/adverse effects , Anti-Arrhythmia Agents/adverse effects , Bayes Theorem , Chemical and Drug Induced Liver Injury , Models, Biological , Administration, Oral , Adult , Aged , Aged, 80 and over , Amiodarone/administration & dosage , Anti-Arrhythmia Agents/administration & dosage , Clinical Enzyme Tests , Drug Administration Schedule , Female , Humans , Liver Diseases/diagnosis , Male , Middle Aged , Odds Ratio , Poisson Distribution , Reproducibility of Results , Risk Assessment , Risk Factors
18.
Hepatology ; 48(6): 1924-31, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19003911

ABSTRACT

UNLABELLED: We tested the hypothesis that the presence of bacterial DNA (bactDNA) in ascitic fluid and serum is associated with decreased survival in patients with cirrhosis. In a prospective, multicenter study, we analyzed the clinical evolution of 156 patients with cirrhosis and ascites (first or recurrence) with lower than 250 polymorphonuclear cells (PMN)/muL, negative ascites bacteriological culture, and absence of other bacterial infections being admitted for evaluation of large-volume paracentesis, according to the presence of bactDNA at admission. Survival, causes of death, and successive hospital admissions were determined during a 12-month follow-up period. BactDNA was detected in 48 patients. The most prevalent identified bactDNA corresponded to Escherichia coli (n = 32/48 patients, 66.6%). Patients were followed for 12 months after inclusion and in this period 34 patients died: 16 of 108 (15%) bactDNA negative versus 18 of 48 (38%) bactDNA positive (P = 0.003). The most frequent cause of death was acute-on-chronic liver failure in both groups (7/16 and 9/18 in patients without or with bactDNA, respectively), although more prevalent in the first month of follow-up in patients with presence of bactDNA (0 versus 4/7). When considering patients with model for end-stage liver disease (MELD) score less than 15, mortality was significantly higher in those with presence of bactDNA. Spontaneous bacterial peritonitis developed similarly in patients with or without bactDNA at admission. CONCLUSION: The presence of bactDNA in a patient with cirrhosis during an ascitic episode is an indicator of poor prognosis. This fact may be related to the development of acute-on-chronic liver failure at short term and does not predict the development of spontaneous bacterial peritonitis.


Subject(s)
Ascitic Fluid/microbiology , DNA, Bacterial/blood , Liver Cirrhosis/microbiology , Adult , Aged , Aged, 80 and over , Ascites/epidemiology , Ascites/microbiology , Escherichia coli/genetics , Female , Follow-Up Studies , Humans , Incidence , Kaplan-Meier Estimate , Liver Cirrhosis/metabolism , Liver Cirrhosis/mortality , Liver Failure/epidemiology , Liver Failure/microbiology , Male , Middle Aged , Multivariate Analysis , Neutrophils/microbiology , Peritonitis/epidemiology , Peritonitis/microbiology , Prognosis , Prospective Studies , Risk Factors
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