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P Zapater

Publications and source records attributed to P Zapater.

At least 19 recordsLinked to original sources
PubMed2006

Functional status of beta-2-adrenoceptor in isolated membranes of mature erythrocytes from patients with cirrhosis and oesophageal varices.

Propranolol is a widely used drug for prophylaxis of variceal bleeding in patients with cirrhosis, but not all patients show an adequate clinical response. This variability may be in relation to beta adrenoceptor activity, but no information is available in this setting. Thirty-nine patients with advanced cirrhosis and presence of oesophageal varices were sequentially included. We studied the function of beta-2-adrenoceptor in isolated membranes of mature erythrocytes obtained from patients by measuring cyclic AMP (cAMP) production before and after isoproterenol. Blood samples obtained from 11 healthy volunteers were used as control. Patients showed a six-fold increase in the mean basal cAMP production as compared to healthy volunteers. Isoproterenol produced a small, non-significantly and highly variable increase in the AC activity in patients compared with controls. cAMP values remain stable after three months of continuous treatment with oral beta-blockers in both groups. Patients without antecedent of variceal bleeding or with an active alcohol intake showed a significantly higher isoproterenol effect. In conclusion, beta-receptor function in human erythrocytes membranes is altered in patients with cirrhosis and oesophageal varices.

Adenylyl Cyclases↗
PubMed2006

A comparison of two different dosages of somatostatin combined with sclerotherapy for the treatment of acute esophageal variceal bleeding: a prospective randomized trial.

BACKGROUND: the association of somatostatin (SMT) with endoscopic therapy in patients with cirrhosis and variceal bleeding significantly improves the control of the bleeding episode, and hemodynamic data have shown that a dosage of 500 mg/h allows a more marked reduction of portal pressure versus the usual dosage of 250 mg/h. AIM: to assess if the 500 mg/h dosage is associated with an improved outcome. METHODS: sixty-two patients with variceal bleeding were included in the study. Patients were randomized to receive the usual dosage of SMT (group I: 250 mg/h), or a double dosage (group II: 500 mg/h), together with emergency endoscopic sclerotherapy. RESULTS: the control of the bleeding episode was similar in both groups of patients. Early rebleeding was less frequent in patients receiving double vs. single dosage of SMT (p = 0.06). When considering patients with advanced liver disease (Child-Pugh B or C) early rebleeding was significantly less frequent in patients receiving the 500 mg/h dose of SMT (39 vs. 13%, p = 0.03). CONCLUSIONS: the perfusion of higher doses of SMT (500 mg/h) in association with emergency sclerotherapy in patients with cirrhosis and esophageal hemorrhage significantly decreases the rate of early rebleeding in patients with more advanced stages of liver disease.

Acute Disease↗
PubMed2006

Cross-reactivity among amide-type local anesthetics in a case of allergy to mepivacaine.

Among the various adverse reactions to local anesthetics, IgE-mediated reactions, particularly to the more commonly used amide group, are extremely rare. We report the case of a 39-year-old man who suffered itching and generalized urticaria with facial angioedema 15 minutes after administration of mepivacaine. Skin tests revealed a strong positive reaction to mepivacaine, lidocaine, and ropivacaine, but negative reactions to bupivacaine and levobupivacaine. Furthermore, double-blind placebo-controlled subcutaneous challenge with bupivacaine and levobupivacaine was well tolerated. We conclude that an extensive allergologic study must be carried out in rare cases of true allergic reaction to amide-type local anesthetics in order to rule out cross reactivity.

Adult↗
PubMed2005

Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer.

AIM: Some retrospective studies have shown a lack of benefit of 5-fluorouracil (5-FU) adjuvant chemotherapy in patients with mismatch repair (MMR) deficient colorectal cancer. Our aim was to assess if this molecular marker can predict benefit from 5-FU adjuvant chemotherapy. A second objective was to determine if MMR status influences short term survival. METHODS: We included 754 patients with a median follow up of 728.5 days (range 1-1097). A total of 260 patients with stage II or III tumours received 5-FU adjuvant chemotherapy, according to standard clinical criteria and irrespective of their MMR status. A tumour was considered MMR deficient when either BAT-26 showed instability or there was loss of MLH1 or MSH2 protein expression. RESULTS: At the end of the follow up period, 206 patients died and 120 presented with tumour recurrence. Sixty six (8.8%) patients had MMR deficient tumours. There were no significant differences in overall survival (MMR competent 72.1%; MMR deficient 78.8%; p = 0.3) or disease free survival (MMR competent 61.3%; MMR deficient 72.3%; p = 0.08). In patients with stage II and III tumours, benefit from 5-FU adjuvant chemotherapy was restricted to patients with MMR competent tumours (overall survival: chemotherapy 87.1%; non-chemotherapy 73.5%; log rank, p = 0.00001). Patients with MMR deficient tumours did not benefit from adjuvant chemotherapy (overall survival: chemotherapy 89.5%; non-chemotherapy 82.4%; log rank, p = 0.4). CONCLUSIONS: Benefit from 5-FU adjuvant chemotherapy depends on the MMR status of tumours in patients with colorectal cancer. 5-FU adjuvant chemotherapy improves survival in patients with MMR competent tumours but this benefit from chemotherapy cannot be extended to patients with MMR deficient tumours.

Aged↗
PubMed2005

Norfloxacin decreases bacterial adherence of quinolone-resistant strains of Escherichia coli isolated from patients with cirrhosis.

BACKGROUND: Long-term administration of norfloxacin is recommended for secondary prophylaxis of spontaneous bacterial peritonitis in cirrhosis, but it may be associated with the development of quinolone-resistant bacteria in stools. However, these bacteria rarely cause infections. AIM: To assess bacterial adherence of either quinolone-sensitive or -resistant Escherichia coli obtained from stools of cirrhotic patients, as one of the main virulence factors, and its variations when sub-minimum inhibitory concentration of norfloxacin were added to the medium. METHODS: E. coli strains were co-cultured with oral epithelial cells obtained from patients in presence/absence of norfloxacin. Bacterial adherence was measured as percentage of cells exhibiting positive adherence and the number of bacteria attached to epithelial cells. RESULTS: 37 sensitive and 22 resistant E. coli strains were studied. Bacterial adherence was similar in both series (78% vs. 81%, P = N.S.), and these percentages were similarly and significantly reduced when subminimum inhibitory concentration of norfloxacin was added to the culture medium (P < 0.001). CONCLUSIONS: Bacterial adherence of E. coli obtained from patients with cirrhosis is unrelated to the sensitivity/resistance to quinolones, and is similarly reduced in both cases when subminimum inhibitory concentration of norfloxacin is added to the medium.

Anti-Infective Agents↗
PubMed2005

Teratogenicity with angiotensin II receptor antagonists in pregnancy.

Angiotensin converting enzyme (ACE) inhibitors and angiotensin II (AT-II)-receptor-antagonists have been demonstrated to cause fetotoxicity when administered to women during the second and third trimester of pregnancy. Although use of ACE inhibitors during the first trimester of pregnancy seems to be safe, with no associated teratogenicity, there is not sufficient information regarding the safety of first-trimester exposure to AT-II-receptor-antagonists. We report a case of exencephaly and unilateral renal agenesia in a fetus of a diabetic woman who became pregnant while taking irbesartan.

Abnormalities, Drug-Induced↗
PubMed2005

Treatment with pegylated interferon alpha-2b and ribavirin in patients unresponsive to previous treatments with standard interferon as monotherapy or combined with ribavirin.

BACKGROUND: Little information is available on the effect of pegylated interferon (PEG) and ribavirin (RBV) in patients with chronic hepatitis due to virus C (CHC) who were non-responders to previous treatment. OBJECTIVES: To evaluate response to treatment in patients who were non-responders to previous treatment. METHODS: One hundred and twenty-four patients who were non-responders to previous treatment were included. All patients were treated with PEG alpha 2b interferon (dose: 1.5 mg/kg body weight) and RBV (weight-dependent dosage). A qualitative PCR of virus C after six months was evaluated. In those in whom this was positive, treatment was discontinued; in those who were negative treatment was continued to the end of the year. RESULTS: Response following treatment (RFT) was 35.4% (44 patients), and sustained viral response (SVR) 29.8% (37 patients). No relation was observed between RFT, SVR and any previous treatment. RFT was dependent on low initial viremia and SVR was significantly and independently related to low serum hepatitis C RNA and a non-1 genotype. In general, treatment was well tolerated. Medication was discontinued in 5 patients, and doses reduced in 18. CONCLUSION: On retreatment with PEG and RBV a SVR of 29.8% was achieved in patients who had not responded to previous treatment, so its use in this group of patients is indicated.

Adult↗
PubMed2004

Pharmacokinetic variations of acetaminophen according to liver dysfunction and portal hypertension status.

AIM: To study the pharmacokinetic and metabolism profiles of a single dose of acetaminophen in patients with cirrhosis. METHODS: Oral acetaminophen (1000 mg) was administered to seven healthy subjects and 14 patients with cirrhosis (nine Child-Pugh A or B and five Child-Pugh C grade), being five without and nine with oesophageal varices. Plasma levels of acetaminophen and its metabolites were determined by HPLC. RESULTS: Patients showed a higher mean area under the curve concentration-time (67.4 +/- 22.4 mg h/L vs. 38.8 +/- 4.3 mg h/L; P = 0.01), a lower clearance (166.7 +/- 85.0 mL/min vs. 367.8 +/- 62.5 mL/min; P = 0.01) and higher elimination half-life (3.8 +/- 1.1 h vs. 2.0 +/- 0.4 h; P = 0.01) of acetaminophen than healthy volunteers. The appearance in blood and the urinary excretion of metabolites in patients did not differ from healthy subjects. Absorption profile was faster in patients. Patients with lower mean and systolic arterial pressure had lower AUC of acetaminophen, independently of liver dysfunction stage. CONCLUSIONS: Patients with cirrhosis had a higher AUC and lower clearance of acetaminophen. Acetaminophen attained earlier therapeutic concentrations in patients with oesophageal varices. Mean and systolic arterial pressures were significantly associated with AUC suggesting the importance of the haemodynamic function on the pharmacokinetics of acetaminophen in patients with cirrhosis.

Acetaminophen↗
PubMed2004

Bacterial DNA activates cell mediated immune response and nitric oxide overproduction in peritoneal macrophages from patients with cirrhosis and ascites.

BACKGROUND AND AIMS: Translocation of intestinal bacteria to ascitic fluid is probably the first step in the development of episodes of spontaneous bacterial peritonitis in patients with cirrhosis. We have recently reported the detection of bacterial DNA in blood and ascitic fluid from patients with advanced cirrhosis, what we consider as molecular evidence of bacterial translocation. Several studies have shown the immunogenic role of bacterial DNA in vitro, and we hypothesised that the presence of bacterial DNA could activate the type I immune response in peritoneal macrophages from these patients, leading to greater cytokine synthesis (interleukin (IL)-2 and IL-12, tumour necrosis factor alpha, and interferon gamma) and effector molecules such as nitric oxide. METHODS: Peritoneal macrophages obtained from patients with cirrhosis and culture negative non-neutrocytic ascitic fluid were collected and characterised by flow cytometry. Inducible nitric oxide synthase, nitric oxide levels, and cytokine production were measured by immunoenzymometric assays in basal and harvested conditions according to the presence/absence of bacterial DNA. RESULTS: The ability of peritoneal macrophages to synthesise nitric oxide and levels of all cytokines were significantly increased in patients with bacterial DNA. There was a positive correlation between inducible nitric oxide synthase and nitric oxide levels. CONCLUSIONS: The presence of bacterial DNA in patients with decompensated cirrhosis is associated with marked activation of peritoneal macrophages, as evidenced by nitric oxide synthesising ability, together with enhanced cytokine production.

Aged↗
PubMed2002

[Toxic hepatitis associated with tamoxifen use. A case report and literature review].

Tamoxifen is an antiestrogenic drug that acts by binding to the estrogen receptor. The drug is used as a co-adjuvant treatment in advanced breast cancer expressing the oestrogen-receptor protein. Clinical trials of tamoxifen have shown its efficacy in reducing mortality and recurrence rates over a five-year treatment. Cases of tamoxifen-associated hepatotoxicity have been described, including cholestasis with or without cytolysis and steatohepatitis. We report the case of a female patient who developed hepatic alterations while undergoing continuous tamoxifen treatment. We also present an overview of similar cases published to date and comment on the advisability of continuing or suppressing this treatment in patients with hepatotoxicity or after a five-year treatment period.

Antineoplastic Agents, Hormonal↗
PubMed2002

A prospective study of the clarithromycin-digoxin interaction in elderly patients.

The study was a prospective observational trial carried out to assess the clarithromycin-digoxin interaction in elderly patients chronically taking digoxin. Digoxin concentrations were determined before and after concomitant treatment with clarithromycin. A Bayesian approach was used to calculate digoxin pharmacokinetics. In the seven patients who were studied there was a significant increase in digoxin concentration after 4-7 days of clarithromycin treatment; digoxin clearance and elimination rate constant were 56-60% lower and elimination half-life was 82% longer. The pharmacokinetic clarithromycin-digoxin interaction in the elderly may be much more frequent than has been assumed up to now.

Aged↗
PubMed2001

Tumor necrosis factor-alpha, interleukin-6, and nitric oxide in sterile ascitic fluid and serum from patients with cirrhosis who subsequently develop ascitic fluid infection.

Ascitic fluid infection probably results from repeated episodes of bacteremia and seeding of ascitic fluid. The outcome of these episodes of colonization is probably a function of serum and ascitic fluid defense mechanisms and the virulence of the organism. Patients who develop spontaneous bacterial peritonitis may have serum and ascitic fluid characteristics that are different from those who do not develop infection. We prospectively collected serum and ascitic fluid specimens at the time of admission from patients with sterile cirrhotic ascites, and tested these specimens for interleukin-6, tumor necrosis factor-alpha, and nitric oxide and compared these results as well as other characteristics of patients who did not develop infection to those who did. An elevated baseline serum tumor necrosis factor-alpha as well as an increased proportion of polymorphonuclear leukocytes in sterile ascitic fluid from patients who subsequently developed infection probably represent a subclinical activation of defense mechanisms from prior silent colonizations with bacteria.

Adult↗
PubMed2000

Absence of an interaction between ibuprofen and zaleplon.

The potential interaction between zaleplon and ibuprofen was studied. Healthy adult volunteers were given a dose of zaleplon 10 mg alone, a dose of ibuprofen 600 mg alone, or a dose of zaleplon 10 mg and a dose of ibuprofen 600 mg concomitantly in an open-label, randomized, three-period crossover study. There was a seven-day washout period between treatments. Venous blood samples were collected for pharmacokinetic analysis at various intervals up to 14 hours after drug administration. A total of 17 subjects (11 men and 6 women) completed the study. There were no significant differences between zaleplon monotherapy and combination therapy in mean +/- SD, of zaleplon clearance (CL) (2.80 +/- 0.72 versus 2.72 +/- 0.89 L/hr/kg, respectively), maximum plasma concentration (Cmax) (37.1 +/- 17.9 versus 39.8 +/- 20.0 ng/mL), or area under the concentration-versus-time curve (AUC) (56.7 +/- 22.8 versus 59.2 +/- 22.0 ng.hr/mL). There were no significant differences between ibuprofen monotherapy and combination therapy in ibuprofen CL (71.6 +/- 17.0 versus 71.7 +/- 14.9 L/hr/kg), Cmax (40.8 +/- 10.2 versus 40.4 +/- 10.0 micrograms/mL), or AUC (127.6 +/- 29.6 versus 126.4 +/- 29.7 micrograms.hr/mL). Three subjects had one or more adverse effects with zaleplon alone, one subject had one or more with ibuprofen alone, and one subject had one or more with combination therapy. The adverse effects were mild and resolved without intervention. There was no evidence of a significant interaction between zaleplon and ibuprofen.

Acetamides↗
PubMed2000

A beta-2-adrenergic receptor activates adenylate cyclase in human erythrocyte membranes at physiological calcium plasma concentrations.

More information is needed about the subtype of the beta-adrenergic receptor coupled to the G-protein-adenylate cyclase (AC) system in human erythrocytes and about the optimal experimental conditions to study this system. In this study we describe the characteristics of spontaneous and beta-agonist-activated AC in human erythrocytes. Human erythrocyte membranes were isolated and AC activity was utilized to assess the quantity of cAMP. Our data show that the subtype beta-2 is the functional beta-adrenergic receptor involved in such activation; this modifies the beta-adrenergic-stimulated activity of AC in human erythrocytes. Isoproterenol in a medium with calcium (1-10 mM, range that includes physiological plasma concentrations) enhances the activation of AC; this effect was blocked by propranolol, but not by atenolol. We conclude that in human erythrocytes subtype beta-2 is the functional beta-adrenergic receptor and that such a response depends to a large extent on Ca(2+) concentrations.

Adenylyl Cyclases↗
PubMed2000

Comparative pharmacoeconomic study of vancomycin and teicoplanin in intensive care patients.

Randomized clinical trials and meta-analyses have not demonstrated any statistically significant differences between teicoplanin and vancomycin with regard to efficacy. A cost-minimization analysis was conducted to compare the economical impact of the treatment with vancomycin and teicoplanin in intensive care patients. Information on resource utilization was retrospectively collected from 100 consecutive clinical histories of patients hospitalized in a Spanish Intensive Care Unit, who had been given a glycopeptide antibiotic (50 teicoplanin and 50 vancomycin) for the treatment of a suspected or proven infection. Although personnel, material, and monitoring costs were higher in the vancomycin group, the acquisition costs and the total costs were much lower in this group, so the resulting total costs per day were 5508 ptas (33 euros) for vancomycin-treated patients and 9893 ptas (59.5 euros) for teicoplanin-treated patients. The savings with vancomycin for a 10-day course of treatment would be approximately 40697 ptas (244.5 euros) per patient. Results were consistent for a variety of conditions that were included in the sensitivity analysis.

Adolescent↗
PubMed1999

Effects of dotarizine and flunarizine on chromaffin cell viability and cytosolic Ca2+.

Dotarizine (a novel piperazine derivative with antimigraine properties) and flunarizine (a Ca2+ channel antagonist) were compared concerning: first, their ability to cause chromaffin cell damage in vitro; second, the possible correlation of their octanol/water partition coefficients and those of another 28 compounds (i.e., Ca2+ channel antagonists, blockers of histamine H1 receptors, antimycotics, beta-adrenoceptor antagonists, neuroleptics), with their ability to cause cell damage; third, their capacity to protect the cells against the damaging effects of veratridine; and fourth, their capabilities to enhance the basal cytosolic Ca2+ concentration in fura-2-loaded single chromaffin cells, or to modify the pattern of [Ca2+]i oscillations elicited by veratridine. After 24-h exposure to 1-30 microM dotarizine, the viability of bovine adrenal chromaffin cells (measured under phase contrast or as lactate dehydrogenase, released into the medium) was similar to that of control, untreated cells; at 100 microM, 80% lactate dehydrogenase release was produced. At 1-3 microM flunarizine caused no cell damage; however 10 microM caused 20% lactate dehydrogenase release and 30 and 100 microM over 90% lactate dehydrogenase release. The time course of cell damage was considerably faster for flunarizine, in comparison to dotarizine. Out of 30 molecules tested (at 10 microM), having different octanol/water partition coefficients (log P), dotarizine was among the molecules causing no cell damage; flunarizine caused 20% cell loss, lidoflazine and verapamil over 50% cell loss, and penfluridol, draflazine, astemizole or nifedipine over 80% cell loss. No correlation was found between log P and cytotoxicity. Both dotarizine (10-30 microM) and flunarizine (3-10 microM) provided protection against veratridine-induced cell death; however, at 30 microM dotarizine afforded a pronounced protection while flunarizine enhanced the cytotoxic effects of veratridine. Dotarizine (30 microM) (but not flunarizine) caused a prompt transient elevation of the basal [Ca2+]i. Both compounds abolished the K+-induced increases of [Ca2+]i as well as the oscillations of [Ca2+]i induced by veratridine. The blocking effects of dotarizine were readily reversed after washout, while those of flunarizine were long-lasting. These differences might be relevant to the clinical use of dotarizine as an antimigraine drug.

Animals↗