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Biomedical subjects

M Pujol

Publications and source records attributed to M Pujol.

At least 37 records · Page 2Linked to original sources

Outcome of unrelated bone marrow donor searches in 174 children resulting in 45 patients transplanted in the HLA-matched and -mismatched situation.

The aim of the study was to evaluate the outcome of unrelated bone marrow donor (UBMD) searches initiated for 174 children between 1986 and 1997. Seven patients were registered twice so that a total of 181 UBMD searches took place. At the time of registration, patients suffered from hematological malignancies (n = 121), non-malignant hemopathies (n = 26) and inborn errors (n = 34). Forty-five of the patients (26%) were given transplants from unrelated donors of whom 26 (58%) were HLA-mismatched transplants. Our strategy accepted HLA mismatches at the time of donor selection, using Thymoglobuline as part of the conditioning regimen. Of the 45 patients given unrelated donor transplants, overall survival was 60% at 3 years and concerned 27 patients of whom 14 were from HLA-mismatched donors. Disease-free survival for hematological malignancies was 65% in HLA-matched transplants and 50% in HLA-mismatched transplants. For some patients (16%) urgency led us to use alternative options: non-identical related donor (n = 14), autograft (n = 10), related cord blood transplant (n = 4). For others, UBMD searches were stopped because of favorable evolution (n = 29), death (n = 24), disease progression (n = 22) or other reasons (n = 21). By the end of the follow-up period, 88 patients had died (50%), 75 (43%) are currently alive with or without being transplanted of whom eight are still having active searches and 11 are no longer contactable. In conclusion, in severe disease in children, an immediate transplant from a partially matched donor might be preferable to a prolonged search for a full match. Consequently, this strategy increases the number of patients for whom a suitable donor can be found. We have chosen this option in order not to delay BMT; in so doing we have obtained encouraging results which include high overall survival, low incidence of acute GVHD grade III-IV and low percentage of relapse even in mismatched pairs.

Adolescent↗

Immune hemolytic anemia induced by 6-mercaptopurine.

BACKGROUND: Myelosuppression is the main hematotoxic effect of 6-mercaptopurine (6-MP), which is an antimetabolite chemotherapy drug. Immune hemolytic anemia associated with this drug has not been previously reported. CASE REPORT: A 67-year-old man with chronic myelomonocytic leukemia presented with anemia 2 weeks after 6-MP therapy had been initiated. Additional tests provided laboratory evidence of hemolysis. When treatment was stopped, the patient's condition and laboratory results showed a progressive improvement. RESULTS: The direct antiglobulin test was positive for IgG. The eluate and the serum were not reactive with panel red cells but reacted with 6-MP-treated red cells, while the normal serum pool was unreactive. The direct antiglobulin test was no longer positive by 20 days after the cessation of 6-MP therapy. CONCLUSION: This drug, 6-MP, should be added to the list of drugs that have been reported to cause immune hemolytic anemia by means of the so-called hapten mechanism.

Aged↗

Emergence and rapid spread of carbapenem resistance during a large and sustained hospital outbreak of multiresistant Acinetobacter baumannii.

Beginning in 1992, a sustained outbreak of multiresistant Acinetobacter baumannii infections was noted in our 1,000-bed hospital in Barcelona, Spain, resulting in considerable overuse of imipenem, to which the organisms were uniformly susceptible. In January 1997, carbapenem-resistant (CR) A. baumannii strains emerged and rapidly disseminated in the intensive care units (ICUs), prompting us to conduct a prospective investigation. It was an 18-month longitudinal intervention study aimed at the identification of the clinical and microbiological epidemiology of the outbreak and its response to a multicomponent infection control strategy. From January 1997 to June 1998, clinical samples from 153 (8%) of 1,836 consecutive ICU patients were found to contain CR A. baumannii. Isolates were verified to be A. baumannii by restriction analysis of the 16S-23S ribosomal genes and the intergenic spacer region. Molecular typing by repetitive extragenic palindromic sequence-based PCR and pulsed-field gel electrophoresis showed that the emergence of carbapenem resistance was not by the selection of resistant mutants but was by the introduction of two new epidemic clones that were different from those responsible for the endemic. Multivariate regression analysis selected those patients with previous carriage of CR A. baumannii (relative risk [RR], 35.3; 95% confidence interval [CI], 7.2 to 173.1), those patients who had previously received therapy with carbapenems (RR, 4.6; 95% CI, 1.3 to 15.6), or those who were admitted into a ward with a high density of patients infected with CR A. baumannii (RR, 1.7; 95% CI, 1.2 to 2.5) to be at a significantly greater risk for the development of clinical colonization or infection with CR A. baumannii strains. In accordance, a combined infection control strategy was designed and implemented, including the sequential closure of all ICUs for decontamination, strict compliance with cross-transmission prevention protocols, and a program that restricted the use of carbapenem. Subsequently, a sharp reduction in the incidence rates of infection or colonization with A. baumannii, whether resistant or susceptible to carbapenems, was shown, although an alarming dominance of the carbapenem-resistant clones was shown at the end of the study.

Acinetobacter↗

Peritoneal response to a septic challenge. Comparison between open laparotomy, pneumoperitoneum laparoscopy, and wall lift laparoscopy.

BACKGROUND: Laparoscopic surgery has a lower incidence of surgical infection than open surgery. Differential factors that may modify the bacterial biology and explain this finding to some extent include CO(2) atmosphere, less desiccation of intraabdominal structures, fewer temperature changes, and a better preserved peritoneal and systemic immune response. Previous data suggest that the immune response and acute phase response are better preserved after laparoscopy. Therefore, we designed a study to evaluate the early peritoneal response to sepsis in an experimental peritonitis model comparing open surgery with CO(2) and abdominal wall lift laparoscopy. METHODS: The study subjects comprised 360 mice distributed into the following four groups: group 1, n = 72 (controls); group 2, n = 96 (open surgery), 2-3 cm laparotomy, with abdominal cavity exposed to the air for 30 min; group 3, n = 96, CO(2) laparoscopy (5 mmHg pneumoperitoneum) for 30 min; group 4, n = 96, wall lift laparoscopy for 30 min. Intraabdominal contamination in the four groups was induced with 1 ml of E. coli suspension (1 x 10(4) CFU/ml) 10 min before abdomen closure. Peritoneal fluid and blood samples were obtained 1.5, 3, 24, and 72 h after surgery, and TNF, IL-1, and IL-6 were measured (via ELISA), as well as quantitative culture. RESULTS: The number of CFU (colony-forming units) obtained in peritoneal fluid and positive blood culture rates were significantly lower in the laparoscopic groups than in the open group. IL-1 peritoneal levels were significantly lower after 24 h and 72 h in the laparoscopy groups. IL-6 levels decreased sharply in the laparoscopy groups at 24 h and 72 h. There were no differences between the two types of laparoscopy models (CO(2) and wall lift). CONCLUSIONS: Peritoneal response to sepsis is better preserved after laparoscopy than after open surgery. CO(2) does not seem to influence bacterial growth. According to these findings, laparoscopy entails less local trauma and better preserved intraabdominal conditions.

Animals↗

[Prevalence of xerostomia in the general population].

OBJECTIVE: Principally, to establish the prevalence of xerostomia in the general population and, second, to find the association of xerostomia with the consumption of tranquillizers and anti-depression, anti-allergy, anti-Hypertension and hypnotic drugs. DESIGN: A crossover study of prevalence. SETTING: The urban area of Sant Joan Despí, Barcelona. PARTICIPANTS: Random sample, stratified by age and gender (268 people). MEASUREMENTS AND MAIN RESULTS: A telephone survey on xerostomia and drugs intake was conducted. Prevalence in the population of xerostomia was 9.7%. There was a linear relationship between being older and greater prevalence of xerostomia. The differences found for gender was not significant. There was an association between xerostomia and intake of the aforesaid drugs. CONCLUSIONS: The high prevalence of xerostomia and its association with commonly used drugs should arouse doctors to seek adequate solutions.

Adolescent↗

Clinical and epidemiological findings in mechanically-ventilated patients with methicillin-resistant Staphylococcus aureus pneumonia.

Over the 5-year period from 1990 to 1994, a prospective cohort study was conducted to define the clinical and epidemiological characteristics of ventilator-associated methicillin-resistant Staphylococcus aureus (MRSA) pneumonia acquired during a large-scale outbreak of MRSA infection. Of 2411 mechanically ventilated patients, 347 (14.4%) acquired MRSA, 220 (63.4%) had MRSA positive respiratory tract samples and 41 (18.6%) developed ventilator-associated MRSA pneumonia. The overall attack rate for ventilator-associated MRSA pneumonia was 1.56 episodes/1000 ventilator days, but annual attack rates varied according to the trend of the outbreak (range 4.9-0.2). In comparison with methicillin-sensitive Staphylococcus aureus (MSSA), which was implicated in 98 episodes of ventilator-associated pneumonia, MRSA caused exclusively late-onset ventilator-associated pneumonia, while MSSA caused both early-onset [55 of 98 (56.1%) episodes] and late-onset [43 of 98 (43.8%) episodes] ventilator-associated pneumonia. Logistic regression analysis of all patients with Staphylococcus aureus pneumonia revealed intubation for more than 3 days (odds ratio (OR),1.11; confidence interval (CI):1.03-1.18) and prior bronchoscopy (OR,5.8; CI,1.85-18.19) to be independent variables associated with MRSA pneumonia. The results indicate that MRSA ventilator-associated pneumonia is a frequent complication in intensive care patients, manifesting itself as late-onset pneumonia in patients who have been intubated for prolonged periods and/or have often undergoing previous bronchoscopy.

Adult↗

pH-induced destabilization of lipid bilayers by a peptide from the VP3 protein of the capsid of hepatitis A virus.

The membrane destabilizing and fusogenic properties of the synthetic peptide VP3(110-121), corresponding to an immunogenic sequence of the hepatitis A virus (HAV) VP3 capsid protein, were studied. By tryptophan fluorescence and acryalmide quenching it was demonstrated that the peptide binds liposomes of POPC-SM-DPPE (47 + 39 + 14) and POPC-SM-DPPE-DOTAP (40 + 33 + 12 + 15) and penetrates the membrane, at both neutral and acidic pH (POPC = 1-palmitoyl-2-oleoylglycero-sn-3-phosphocholine; SM = sphingomyelin; DPPE = 1,2-dipalmitoylphosphatidylethanolamine; DOTAP = 1,2-dioleoyl-3-trimethylammoniumpropane). VP3(110-121) did not have membrane-destabilizing properties at neutral pH. Acid-induced destabilization of the vesicles was demonstrated by fluorescence techniques and dynamic light scattering. VP3(110-121) induced aggregation of POPC-SM-DPPE-DOTAP (40 + 33 + 12 + 15) vesicles, lipid mixing and leakage of vesicle contents, all consistent with fusion of vesicles. In POPC-SM-DPPE (47 + 39 + 14) vesicles, at acidic pH, VP3(110-121) induced membrane destabilization with leakage of contents but without aggregation of vesicles or lipid mixing. The peptide only showed fusogenic properties when bound to the vesicles at neutral pH before acidification to pH below 6.0, and no effect was seen if the peptide was added to vesicles already set at acidic pH. These results may have physiological significance in the mechanism of infection of host hepatic cells by HAV.

Capsid↗

Essential monoclonal gammopathy with an IgM paraprotein that is a cryoglobulin with cold agglutinin and EDTA-dependent platelet antibody properties.

A patient with apparent anaemia and thrombocytopenia caused by a monoclonal paraprotein is described. The patient's serum contained a monoclonal IgM kappa, a cryoglobulin and a cold agglutinin. The cryoglobulin, similar to the serum paraprotein, was a monoclonal IgM kappa. Serum was studied to determine the relationship of the cryoglobulin with the cold agglutinin. The cryoglobulin and cold agglutinin were found to be the same paraprotein. Moreover, with absorption and elution techniques the reactivity of the autoantibody with both erythrocytes and platelets was demonstrated. Reports of cryoprecipitable cold agglutinins are rare and therefore this case is exceptional given that the IgM kappa paraprotein was found to be a cold agglutinin which was also reactive with platelets.

Aged↗

Delayed haemolytic transfusion reaction due to anti-M antibody.

A female patient with delayed haemolytic transfusion reaction due to anti-M antibody is described. Diagnosis was based on laboratory evidence of haemolysis and on characteristic serological findings. Anti-M was detected in the recipient's serum 7 d after the last transfusion episode. This alloantibody had not been present in the pretransfusion serum. In addition, the direct antiglobulin test was positive on post-transfusion testing and the implicated antibody was eluted from post-transfused red cells. Delayed haemolytic transfusion reactions have long been recognized as a potential hazard of transfusion therapy, but such cases due to anti-M are extremely rare.

Adenocarcinoma↗

Efficacy of sulbactam alone and in combination with ampicillin in nosocomial infections caused by multiresistant Acinetobacter baumannii.

From March 1995 to March 1997, sulbactam was prospectively evaluated in patients with non-life-threatening multiresistant Acinetobacter baumannii infections. During this period, 47 patients were treated with sulbactam; of them, five were excluded because they had received < or =48 h of sulbactam therapy. A total of 42 patients, 27 males and 15 females with a mean age of 60+/-15 years, were finally evaluated. Infections were as follows: surgical wound, 19; tracheobronchitis, 12; urinary tract, 7; catheter-related bacteraemia, 2; and pneumonia, 2. Eighteen patients received intravenous sulbactam alone (1 g every 8 h) and 24 patients received intravenous sulbactam/ampicillin (1 g:2 g every 8 h) with no major adverse effects. Of the 42 patients, 39 improved or were cured and showed A. baumannii eradication and one patient had persistence of wound infection after 8 days of sulbactam/ampicillin requiring surgical debridement. Two patients died after 3 days of therapy (one of the deaths was attributable to A. baumannii infection). The in-vitro activity of the sulbactam/ampicillin combination was by virtue of the antimicrobial activity exhibited by sulbactam. Killing curves showed that sulbactam was bacteriostatic; no synergy was observed between ampicillin and sulbactam. Our results indicate that sulbactam may prove effective for non-life-threatening A. baumannii infections. Its role in the treatment of severe infections is unknown. However, the current formulation of sulbactam alone may allow its use at higher doses and provide new potential synergic combinations, particularly for those infections by A. baumannii resistant to imipenem.

Acinetobacter↗

Epidemiology and successful control of a large outbreak due to Klebsiella pneumoniae producing extended-spectrum beta-lactamases.

An outbreak due to extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) was detected from May 1993 to June 1995. A total of 145 patients, particularly patients in intensive care units (ICUs) (107 patients [72%]), were colonized or infected. Infection developed in 92 (63%) patients, and primary bacteremia caused by ESBL-KP was the most frequent infection (40 of 92 patients [43%]). A single clone of ESBL-KP was identified by pulsed-field gel electrophoresis analysis throughout the whole period, and no molecular epidemiological relationship could be found between the epidemic strain and non-ESBL-KP isolates. To determine risk factors for ESBL-KP infection weekly rectal swabs were obtained in three serial incidence surveys (470 patients); the probabilities of carriage of ESBL-KP in the digestive tract were 33% (October and November 1993), 40% (May and June 1994), and 0% (October and November 1995) at 10 days of ICU admission. A logistic regression model identified prior carriage of ESBL-KP in the digestive tract (odds ratio, 3.4; 95% confidence interval 1.1 to 10.4) as an independent variable associated with ESBL-KP infection. A statistically significant correlation was observed between the restricted use of oxyimino-beta-lactams (189 defined daily doses [DDD]/ 1,000 patient-days to 24 DDD/1,000 patient-days) and the trends of ESBL-KP infection (r = 0.7; P = 0.03).

Anti-Bacterial Agents↗

Prophylactic platelet transfusion threshold during therapy for adult acute myeloid leukemia: 10,000/microL versus 20,000/microL.

BACKGROUND AND OBJECTIVE: The threshold for prophylactic platelet transfusions has been classically established at 20,000/microL. In 48 patients with de novo acute myeloblastic leukemia (AML) we analyzed the effect of reducing the threshold for prophylactic platelet transfusion from 20,000/microL (group A) to 10,000/microL (group B) after induction and consolidation chemotherapy. DESIGN AND METHODS: Forty-eight adult patients with de novo AML diagnosed in a single institution in a nine year period were enrolled in the study. Between January 1989 and December 1993 the patients received prophylactic platelet transfusions when their platelet count was below 20,000/microL (group A), and from January 1994 to March 1998 prophylactic platelet transfusions were indicated below 10,000/microL or between 10,000/microL and 20,000/microL if there was any consumption factor. RESULTS: The mean number (SD) of platelet transfusions during induction was 8.4 (5.3) in group A and 8.5 (5.5) in group B; and during consolidation 4.7 (3.4) in group A and 4.6 (3.8) in group B (p = n.s.). Excluding the cases with consumption factors from the analysis, group B patients required 34% fewer transfusions during induction and 15.5% fewer during consolidation (p = 0.04). There were no differences between groups regarding major bleeding episodes. INTERPRETATION AND CONCLUSIONS: Our data show that the threshold for prophylactic platelet transfusion can be safely set at 10,000 microL during induction and consolidation chemotherapy for adult patients with de novo AML.

Acute Disease↗

Staphylococcus aureus nasal carriage as a marker for subsequent staphylococcal infections in intensive care unit patients.

From January to December 1994, 752 consecutive patients admitted to intensive care units (ICU) for more than two days were studied prospectively for Staphylococcus aureus colonization and infection. Nasal swabs were obtained at admission and weekly during the ICU stay. At ICU admission 166 patients (22.1%) were Staphylococcus aureus nasal carriers, while 586 were free of nasal colonization. Of the 166 nasal carriers, 163 harbored methicillin-sensitive Staphylococcus aureus (MSSA) and three methicillin-resistant Staphylococcus aureus (MRSA). During the ICU stay 24 of the 586 noncolonized patients became nasal carriers (11 MSSA and 13 MRSA), and one nasal carrier initially colonized by MSSA was reconlonized by MRSA. Staphylococcal infections were documented in 51 (6.8%) of the total 752 patients. After 14 days of ICU stay, the probability of developing staphylococcal infections was significantly higher for those patients who were nasal carriers at ICU admission than for those found to be initially negative (relative risk 59.6, 95% CI 20.37-184.32; p < 0.0001). In patients with ICU-acquired nasal colonization, most infections were documented prior to or at the time of the detection of the nasal colonization; thus, in this group of patients nasal carriage showed a lower predictive value for subsequent Staphylococcus aureus infections that that described classically. Paired isolates of nasal colonizing and clinical strains were studied by pulsed-field gel electrophoresis (PFGE) and mecA polymorphism analysis in 30 patients; identity was demonstrated in all but two patients. The results suggest that, outside the setting of an outbreak of MRSA, the detection of Staphylococcus aureus nasal carriers on admission may be particularly useful in identifying those patients who are at high risk for developing staphylococcal infections during their ICU stay.

Biomarkers↗

Risk factors for faecal carriage of Klebsiella pneumoniae producing extended spectrum beta-lactamase (ESBL-KP) in the intensive care unit.

In the course of an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) in an intensive care unit (ICU), we conducted active surveillance to determine the risk factors for ESBL-KP faecal colonization of patients. We used weekly rectal samples during a four-month period. ESBL-KP was found in the faeces of 72 of 188 (38%) patients, and 42 (58%) of them were colonized within the first week of admission to the ICU. The probability of remaining free of faecal colonization was less than 20% at 30 days of ICU admission. The risk factors associated with ESBL-KP faecal colonization were clinical severity score at admission (P = 0.004), arterial catheterization (P = 0.002), total parenteral nutrition (P = 0.04), urinary catheterization (P = 0.01), mechanical ventilation (P < 0.001), and previous antibiotic therapy (P = 0.04). A logistic regression analysis identified duration of urinary catheterization (OR:3.5; 95% CI 1.2-10.3) and mechanical ventilation (OR:4.6; 95% CI 1.1-19.3) as independent risk factors for ESBL-KP faecal colonization. Our results suggest that in an ESBL-KP prevalent environment, manipulations that facilitate cross-infection are the most relevant in the acquisition of the micro-organism and risk increases throughout hospitalization.

Adult↗

Stability study of epirubicin in NaCl 0.9% injection.

OBJECTIVE: To determine the stability of epirubicin in NaCl 0.9% injection under hospital storage conditions. METHODS: NaCl 0.9% solution was added to epirubicin lyophilized powder to make a final concentration of 1 mg/mL to study the degradation kinetics and 2 mg/mL to study the stability in polypropylene syringes under hospital conditions. SETTING: Physical chemistry laboratory, Unitat de Fisicoquímica, Universitat de Barcelona. MAIN OUTCOME MEASURES: Solutions of epirubicin at 2 mg/mL in NaCl 0.9% solutions stored in plastic syringes were studied under hospital conditions at room temperature (25 +/- 1 degrees C) and under refrigeration (4 +/- 1 degrees C) both protected from light and exposed to room light (approximately 50 lumens/m2). All samples were studied in triplicate and epirubicin concentrations were obtained periodically throughout each storage/time condition via a specific stability-indicating HPLC method. To determine the degradation kinetics, solutions of epirubicin in NaCl 0.9% at 1 mg/mL were stored at different temperatures (40, 50, and 60 degrees C) to obtain the rate degradation constant and the shelf life at room temperature and under refrigeration. RESULTS: The degradation of epirubicin in NaCl 0.9% solutions follows first-order kinetics. The shelf life was defined as the time by which the epirubicin concentration had decreased by 10% from the initial concentration. In this study, epirubicin was stable in NaCl 0.9% injection stored in polypropylene containers for all time periods and all conditions. That results in a shelf life of at least 14 and 180 days at 25 and 4 degrees C, respectively. The maximum decrease in epirubicin concentration observed at 25 degrees C and 14 days was 4%, and at 4 degrees C and 180 days was 8%. The predicted shelf life obtained from the Arrhenius equation was 72.9 +/- 0.2 and 3070 +/- 15 days at 25 and 4 degrees C, respectively, in both dark and illuminated conditions. CONCLUSIONS: Solutions of epirubicin in NaCl 0.9% at 2 mg/mL are chemically stable when they are stored in polypropylene syringes under hospital storage conditions. No special precaution is necessary to protect epirubicin solutions (2 mg/mL) from light.

Antibiotics, Antineoplastic↗