Association between the presence of the Panton-Valentine leukocidin-encoding gene and a lower rate of survival among hospitalized pulmonary patients with staphylococcal disease.
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Biomedical subjects
Publications and source records attributed to A Moreno.
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Hepatitis C recurrence after liver transplantation (LT) is universal, and frequently leads to cirrhosis and death. The aim of our study was to assess the efficacy and safety of 48-weeks of full-dose peg-interferon-alpha-2a (n = 4) or alpha-2b (n = 51) plus ribavirin (>11 mg/kg/day) in a multicentric cohort of 55 patients > or =12 months after LT. All subjects had histologically proven HCV recurrence, excluding severe cholestatic recurrence. Mean age was 54.3 +/- 9.7, 77% male, 90.9% genotype 1, 32.7% cirrhotics. All but 5 patients received monotherapy with tacrolimus (54.5%), cyclosporine (30.7%) or mycophenolate mofetil (5.5%). The rates of end-of-treatment response and sustained virological response (SVR) were 66.7% and 43.6%, respectively. Low baseline HCV-RNA (p = 0.005) and a length from LT to therapy between 2-4 years (p = 0.011) were predictors of SVR. The lack of achieving a viral load decrease > or =1-log10 at week 4 and/or 2-log10 at week 12 was 100% predictive of failure. The most frequent side effects were neutropenia (76,4%), anemia (60%) and infectious complications (30.9%). Toxicity led to peg-interferon withdrawal in 16 (29%) subjects. In 15 patients with post-treatment biopsy, the histological activity index was significantly improved (p = 0.006), whereas fibrosis did not change (p = 0.14). Three patients died (cholangitis, hepatic artery thrombosis and lung cancer). In conclusion, HCV therapy after LT was very effective, although it led to a significant rate of toxicity.
The aim of this study is to evaluate the efficacy of the eprinomectin pour-on in naturally Oestrus ovis-infested sheep. To carry out this trial, 14 naturally infected sheep from the same flock were used. The animals were randomly distributed in three groups: group 1 (non-treated sheep), group 2 treated with 0.5 mg/kg bodyweight and group 3 treated with 1 mg/kg bodyweight of eprinomectin. The sheep were slaughtered 15 days after treatment and their heads were sectioned to count and identify larvae instar. The following results were obtained: Group 1: the average was 34 live and 0.75 dead larvae per sheep. Group 2: the efficacy of the eprinomectin was 83.5% against O. ovis group 3: the efficacy of the eprinomectin pour-on was 100%. Drug analysis was made to determine plasma eprinomectin concentration 9 days after treatment and the average concentrations in groups 2 and 3 were 1.23 and 3.04 ng/ml, respectively. The statistical study showed a significant difference between the efficacy and the dose used, and there was correlation between the plasma concentration of eprinomectin and the dose. The efficacy and easy application allow us to take into account this endectocide as an alternative method in the integral control of parasites in sheep.
BACKGROUND: Since abnormalities in prostanoid metabolism occur in the lower airway of patients with cystic fibrosis (CF), it is likely that they could also be detected in the nose. METHODS: The degree of mRNA and protein expression of cyclo-oxygenase (COX) enzymes 1 (COX-1) and 2 (COX-2) was examined using quantitative reverse competitive polymerase chain reaction (RT-PCR) and Western blot analysis in the nasal polyps from 10 patients with CF, nasal polyps from 10 non-CF patients and 11 nasal mucosa specimens. The results are presented as 10(6) cDNA molecules/mug total RNA and the densitometric ratio between protein and beta-actin. RESULTS: COX-1 mRNA levels were significantly higher in CF nasal polyps (median 2.34, 25-75th percentiles 1.6-3.2) than in the nasal mucosa (0.78, 0.11-1.21), while there was no difference with non-CF nasal polyps (1.11, 0.80-3.15). COX-1 protein levels were significantly higher in CF nasal polyps (3.63, 2.71-4.27) than in nasal mucosa (1.55, 0.66-2.33) and non-CF nasal polyps (2.19, 1.72-3.68). COX-2 mRNA was significantly higher in CF nasal polyps (3.34, 2.42-7.05) than in nasal mucosa (1.69, 0.19-3.50). No differences were found in COX-2 mRNA expression between CF and non-CF polyps (1.38, 0.12-6.07). COX-2 protein levels were also significantly higher in CF nasal polyps (0.23, 0.04-0.34) than in non-CF nasal polyps (0.011, 0.009-0.016) or nasal mucosa (0.014, 0.014-0.016). CONCLUSIONS: Upregulation in the expression of COX-1 and COX-2 could explain the high production of prostanoids reported in CF. These findings raise questions regarding the potential use of selective or non-selective COX-2 non-steroidal anti-inflammatory treatment in CF.
We describe the first two unrelated Spanish patients with creatine transporter deficiency initially identified by brain proton magnetic resonance spectroscopy (MRS). The clinical phenotype was characterized by severe mental retardation, epilepsy, autism, severe speech delay and absence of brain creatine by MRS. Urine creatine/creatinine ratio was increased and creatine uptake in fibroblasts was impaired in both patients. On DNA sequence analysis of the SLC6A8/creatine transporter gene, one hemizygous mutation was found in each patient: one mutation was novel and consisted of a deletion of two nucleotides c.878-879delTC in exon 5, resulting in a frameshift (p.Lys293fsX3), and in the other patient a known deletion of three nucleotides 1222-1224delTTC in exon 8 resulting in p.Phe408del. Creatine treatment for one year failed to improve the neurological symptoms and was associated with a striking increase in body weight in both patients (13 and 16 kg, respectively).
In order to transport and cryopreserve human tissues, it is essential to have an easy-to-use recipient where tissues can be kept in sterile conditions. Here we show the results obtained by using Macopharma's tissue freezing bags, an aluminium-polyethylene multilayer bag, in our tissue bank of the Centro Comunitario de Sangre y Tejidos de Asturias. Five hundred and twenty-seven cancellous bone homografts were obtained from hospitals located 120 km around our Bank. The homografts were submitted to bacteriological controls and sent to our bank in these bags. They were stored at -70 degrees C and sent in dry ice to about 50 hospitals, where the tissue was bacteriologically controlled and grafted. Furthermore, the behaviour of these bags at -140 degrees C (vapour nitrogen) or -196 degrees C (liquid nitrogen) was tested. Our results indicate that Macopharma aluminium-polyethylene bags are suitable for the transporting and cryopreserving of cancellous bone homografts. These bags could also be used for keeping tissues in nitrogen containers.
INTRODUCTION: The use of Celsior solution for organ preservation has not been thoroughly studied in pancreas transplantation. The aim of this study was to compare University of Wisconsin and Celsior solutions for preservation of pancreas grafts. PATIENTS AND METHODS: From March 1995 to December 2005, 72 patients with type 1 diabetes underwent pancreas transplantation. There were 42 men and 30 women, with a mean age at transplantation of 38.1 +/- 7.5 years (range: 27 to 55 years), and a mean duration of diabetes of 22.5 +/- 6.6 years. Recipients were classified into two groups according to the preservation solution: (A) Celsior (n = 28, 38.9%) and (B) Wisconsin (n = 44, 61.1%). RESULTS: The donor and recipient characteristics were similar in both groups. There were five cases of venous thrombosis in the Wisconsin group and two in the Celsior group (P = NS). The venous drainage technique in the former group was portocaval in 19 patients and portoiliac in 25; in the Celsior group, portocaval in 23 patients and portoiliac in five (P = .001). Enteric drainage was used in 19 patients from the Celsior group and 17 patients from the Wisconsin group (P = .01). Actuarial 2-year graft survival was 74.6% in the Wisconsin group and 77.4% in the Celsior group (P = NS). CONCLUSIONS: No differences were observed in venous thrombosis between the two groups. The lower rate of venous thrombosis with the portocaval technique was related to the type of venous drainage rather than the type of preservation solution. Celsior solution may be considered as good as Wisconsin solution for pancreas transplantation.
The introduction of mycophenolate mofetil (MMF) was an important advance in immunosuppressive therapy, although its use is limited by adverse gastrointestinal events. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) has been developed to avoid these side effects. Recent clinical trials have demonstrated that EC-MPS is a safe drug in both de novo and maintenance renal transplant patients. In this prospective study, therapeutically equivalent doses of EC-MPS were administered to 39 stable kidney transplant patients receiving MMF. After 3 months of treatment with EC-MPS the incidence of adverse gastrointestinal events was lower (15.8% of the patients). There were higher levels of mycophenolic acid after conversion to EC-MPS, probably due to better absorption. These factors allowed decreased doses and levels of calcineurin inhibitors without increasing the risk of graft rejection. At 3 months postconversion, serum creatinine improved from the mean baseline value of 1.83 +/- 0.12 mg/dL to 1.70 +/- 0.10 mg/dL. In conclusion, EC-MPS was well tolerated in maintenance renal transplant patients with adverse gastrointestinal events secondary to MMF.
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OBJECTIVE: To validate a monitor for transcutaneous measurement of oxygen saturation (SpO2) and partial pressure of carbon dioxide (TcPCO2). PATIENTS AND METHODS: This observational study included 140 Caucasian nonsmokers without jaundice. Patients underwent forced spirometry, measurement of SpO2 and TcPCO2 with the SenTec monitor, and arterial blood gas analysis (readings with 2 devices) during the stabilization phase of the monitor. In the statistical analysis, values from the 2 devices for measuring arterial blood gases were compared by mean differences for PaCO2 and oxygen saturation (SaO2). The arithmetic mean of the 2 blood gas measurements was calculated and relations between them and the SpO2 and TcPCO2 were assessed by the Pearson correlation coefficient (r) and the intraclass correlation coefficient (ICC) as a measure of agreement. Bland-Altman analysis was used to test data dispersion. RESULTS: Ten patients were excluded due to a systematic error in the gas calibrator. The mean (SD) time to stabilization of the monitor before reading was 13.9 (2.4) minutes. The forced expiratory volume in the first second was greater than 80% in 40 patients, between 60% and 79% in 23, between 40% and 59% in 30, and less than 40% in 37. The mean (SD) differences between arterial blood gas measurements were 0.28 (1.0) mm Hg for PaCO2, -0.06% (0.86%) for SaO2, and -0.9 (2.7) mm Hg for PaO2. In the tests for correlation and agreement, r was 0.74 and ICC was 0.73 for SaO2 and SpO2; r was 0.92 and ICC was 0.92 for PaCO2 and TcPCO2. The subgroup analyses did not show any noteworthy differences. The Bland Altman analysis showed no significant dispersion. It was observed that the SenTec monitor underestimated oxygen saturation values by around 1% with respect to SaO2 and overestimated carbon dioxide pressure by 1 mm Hg with respect to PaCO2 values. CONCLUSIONS: The stabilization time recommended for the SenTec monitor before taking a reading is 20 minutes. The overestimates and underestimates by the monitor are not clinically relevant. Finally, the values for SpO2 and TcPCO2 measured by the validated monitor are reliable.
To evaluate, among 70 hepatitis C virus (HCV)-monoinfected and 36 human immunodeficiency virus (HIV)-coinfected naïve patients with genotypes 1/4 receiving weight-adjusted pegylated interferon-alpha-2b/ribavirin, viral kinetics and the feasibility to predict treatment failure measuring early HCV-RNA decreases. HCV-RNA was assessed at baseline, weeks 4, 12 and 24. Receiver operating characteristic (ROC) curves were calculated to determine the most sensitive cut-off values of viral decrease at week 4 predicting treatment failure. Baseline predictors of failure were evaluated by univariate and multivariate analyses. Despite similar baseline HCV-RNA (5.75 vs 5.72 log(10)IU/ml, P = 0.6), HCV monoinfection led to significantly lower HCV-RNA values at weeks 4 (3.7 vs 4.3 log(10)IU/ml, P = 0.01), 12 (2.3 vs 3.5 log(10)IU/ml, P = 0.01) and 24 (1.4 vs 3.3 log(10)IU/ml, P = 0.001) and a higher rates of viral clearance at weeks 24 (60%vs 36%, P = 0.02), 48 (46%vs 25%, P = 0.03) and 72 (37%vs 17%). The lack of achieving an HCV-RNA decrease of at least 1 log(10) at week 4 was highly predictive of treatment failure for HCV-monoinfected patients (Se 100%, Sp 50%, positive predictive value (PPV) 57%, negative predictive value (NPV) 100%, ROC curve area, 0.86 [95% confidence interval (CI) 0.77-0.95], but not for HCV/HIV-coinfected patients (cut-off, 0 log(10), Se 100%, Sp 27%, PPV 21%, NPV 100%, ROC curve area, 0.71 (95% CI 0.49-0.93). HIV coinfection was independently associated with failure (odds ratio 2.95, 95% CI 1.08-8.04, P = 0.01). Thus the magnitude of HCV-RNA decreases at week 4 correlated with treatment response. Significant differences in viral kinetics and cut-off values predicting nonresponse suggest a slower HCV clearance rate in HIV coinfection, which was independently associated with treatment failure.
Calciphylaxis is an uncommon disease characterized by calcification of dermal vessels that determines skin necrosis. Calciphylaxis has been almost exclusively reported in association with renal failure and altered phosphor-calcium metabolism. Only a few cases have been described in hyperparathyroidism, malignancies, and, recently, cirrhosis. We report a patient that developed calciphylaxis related to end-stage alcoholic cirrhosis, without any alteration in the phosphocalcic and parathyroid hormone metabolisms. Possible contributing factors were repeated albumin infusions and low levels of protein C and S.
The effects of omeprazole and lansoprazole (CYP3A4 inhibitors) on the pharmacokinetics of a single dose of ivabradine (metabolized via CYP3A4) and its active metabolite (S18982) were assessed. Pharmacodynamics and safety were secondary objectives. An open-label, randomized, crossover, phase I, pharmacokinetic interaction design was used. Volunteers received a single oral dose of ivabradine (10 mg), were randomized to receive either omeprazole (40 mg) or lansoprazole (60 mg) for 5 days, and were administered an ivabradine dose on the sixth day. Crossover was performed after washout. Pharmacokinetic parameters for ivabradine did not vary significantly after omeprazole (C(max): 45.0 +/- 36.6 vs 42.7 +/- 27.6 ng/mL, P = .98; AUC: 128 +/- 87 vs 126 +/- 63 ng/mL, P = .82) or lansoprazole administration (C(max): 45.0 +/- 36.6 vs 41.3 +/- 29.4 ng/mL, P = .70; AUC: 128 +/- 87 vs 123 +/- 50, P = .73). Analyses of S18982 pharmacokinetic parameters showed similar results. Coadministration of either omeprazole or lansoprazole did not significantly affect the pharmacokinetics of a single dose of ivabradine. No pharmacodynamic interaction or safety concerns were evidenced.
BACKGROUND: short-bowel transplantation has experienced a substantial growth worldwide following improved results from the late 1990's on, and its coverage by Medicare. According to the International Registry (1985-2005), a total of 1,292 intestinal transplants for 1,210 patients in 65 hospitals across 20 countries have been carried out thus far. OBJECTIVE: to know short-term (6 months) results regarding patient and graft survival from the first Spanish series of intestinal transplants in adult recipients. MATERIAL AND METHODS: we present our experience in the assessment of 20 potential candidates to short-bowel transplantation between June 2004 and October 2005. Of these, 10 patients were rejected and 4 were transplanted, which makes up the sample of our study. RESULTS: to this date 5 transplants have been carried out in 4 patients (2 retransplants, 2 desmoid tumors, 1 short bowel syndrome after excision as a result of mesenteric ischemia). Upon study completion and after a mean follow-up of 180 days (range 90-190 days) all recipients are alive, and all grafts but one (75%) are fully operational, with complete digestive autonomy. All patients received induction with alemtuzumab except one, who received thymoglobulin; in all induction was initiated with no steroids. CONCLUSIONS: intestinal transplantation represents a therapeutic option that is applicable in our setting and valid for recipients with an indication who have no other feasible alternative to keep their intestinal failure under control.
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BACKGROUND: To facilitate the design of strategies for prevention of invasive aspergillosis in solid-organ transplant recipients, this study investigates whether the development of early-onset and late-onset aspergillosis are related to different risk factors, thereby distinguishing 2 risk populations for this serious complication. METHODS: A retrospective case-control study was performed, including 156 cases of proven or probable invasive aspergillosis in patients recruited from 11 Spanish centers since the start of the centers' transplantation programs. RESULTS: Among all patients, 57% had early-onset IA (i.e., occurred during the first 3 months after transplantation). Risk factor analysis in this group identified as significantly associated risk factors a more complicated postoperative period, repeated bacterial infections or cytomegalovirus disease, and renal failure or the need for dialysis. Among patients with late-onset infections (i.e., occurred > 3 months after transplantation), who comprised 43% of cases, the patients at risk were older, were in an overimmunosuppressed state because of chronic transplant rejection or allograft dysfunction, and had posttransplantation renal failure. CONCLUSIONS: Risk factors in patients with early-onset cases and patients with late-onset cases of posttransplantation invasive aspergillosis are not the same, a fact that could have implications for the preventive approaches used for this infection.
Although macromolecular purity is thought to be essential for the growth of flawless protein crystals, only a few studies have investigated how contaminants alter the crystallization process and crystal quality. Likewise, the outcome of a crystallization process may vary with the crystallization method. Here, it is reported how these two variables affect the crystallogenesis of aspartyl-tRNA synthetase from the eubacterium Thermus thermophilus. This homodimeric enzyme (Mr=130,000) possesses a multi-domain architecture and crystallizes either in a monoclinic or an orthorhombic habit. Minute amounts of protein impurities alter to a different extent the growth of each crystal form. The best synthetase crystals are only obtained when the crystallizing solution is either enclosed in capillaries or immobilized in agarose gel. In these two environments convection is reduced with regard to that existing in an unconstrained solution.
BACKGROUND: Bacteremia and septic shock remain important causes of morbidity and mortality after solid-organ transplantation. The aim of this study was to assess the characteristics and risk factors for mortality among patients with bloodstream infections and shock. METHODS: From January 1991 to December 2000, all episodes of bloodstream infection were prospectively examined, considering bacteremia or fungemia as significant according to the CDC criteria. Septic shock was diagnosed in a patient with systemic inflammatory response syndrome and persistent dysfunction of at least one organ caused by hypoperfusion despite hemodynamic support. RESULTS: There were 466 episodes of bacteremia in 382 patients, with 66 of them developing septic shock. Risk factors for developing shock were age >50 (P = .006), liver transplant (P = .029), nosocomial infection (P = .034), pulmonary focus (P = .0001), P. aeruginosa infection (P = .001), and polymicrobial etiology (P = .039). On multivariate analysis, only age, nosocomial infection, and pulmonary source were significant. Among 66 shock patients, bacteremia was due to gram-negative bacteria in 53%, gram-positive bacteria in 24%, fungal in 7.5%, and polymicrobial in 12% of patients. The most frequent source was the lung (26%). Empiric antimicrobial therapy was correctly chosen in 79%; however, 36 patients died (54%), including 27 despite correct therapy. Urinary tract infections had less mortality than other foci. CONCLUSIONS: Risk factors for developing septic shock in bacteremia were age more than 50 years, nosocomial acquisition, and pulmonary focus. Despite adequate empiric antibiotic therapy, the mortality remained high.