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Biomedical subjects

J Mestre

Publications and source records attributed to J Mestre.

At least 19 recordsLinked to original sources

Evaluation of linkage and association of HPC2/ELAC2 in patients with familial or sporadic prostate cancer.

To investigate the relationship between HPC2/ELAC2 and prostate cancer risk, we performed the following analyses: (1) a linkage study of six markers in and around the HPC2/ELAC2 gene at 17p11 in 159 pedigrees with hereditary prostate cancer (HPC); (2) a mutation-screening analysis of all coding exons of the gene in 93 probands with HPC; (3) family-based and population-based association study of common HPC2/ELAC2 missense variants in 159 probands with HPC, 249 patients with sporadic prostate cancer, and 222 unaffected male control subjects. No evidence for linkage was found in the total sample, nor in any subset of pedigrees based on characteristics that included age at onset, number of affected members, male-to-male disease transmission, or race. Furthermore, only the two previously reported missense changes (Ser217Leu and Ala541Thr) were identified by mutational analysis of all HPC2/ELAC exons in 93 probands with HPC. In association analyses, family-based tests did not reveal excess transmission of the Leu217 and/or Thr541 alleles to affected offspring, and population-based tests failed to reveal any statistically significant difference in the allele frequencies of the two polymorphisms between patients with prostate cancer and control subjects. The results of this study lead us to reject the three alternative hypotheses of (1) a highly penetrant, major prostate cancer-susceptibility gene at 17p11, (2) the allelic variants Leu217 or Thr541 of HPC2/ELAC2 as high-penetrance mutations, and (3) the variants Leu217 or Thr541 as low-penetrance, risk-modifying alleles. However, we did observe a trend of higher Leu217 homozygous carrier rates in patients than in control subjects. Considering the impact of genetic heterogeneity, phenocopies, and incomplete penetrance on the linkage and association studies of prostate cancer and on the power to detect linkage and association in our study sample, our results cannot rule out the possibility of a highly penetrant prostate cancer gene at this locus that only segregates in a small number of pedigrees. Nor can we rule out a prostate cancer-modifier gene that confers a lower-than-reported risk. Additional larger studies are needed to more fully evaluate the role of this gene in prostate cancer risk.

Age of Onset↗

Aspirin prevents tumors in a murine model of familial adenomatous polyposis.

BACKGROUND: Both human and murine studies suggest that anti-inflammatory drugs prevent intestinal neoplasia. The purpose of this study was to investigate the role of aspirin as a chemopreventive agent for colorectal cancer. METHODS: We administered aspirin to the Min/+ mouse, an animal with a germline mutation in Apc, a gene that is essential for normal epithelial cell growth and differentiation. Apc mutation increases cytoplasmic beta-catenin, a regulatory protein associated with the cytoskeleton. Min/+ mice develop multiple intestinal adenomas and exhibit altered cell growth in the preneoplastic intestinal epithelium. RESULTS: Aspirin decreased the rate of tumor formation in Min/+ mice by 44%. Aspirin also normalized enterocyte growth by increasing apoptosis and proliferation in the preneoplastic intestinal mucosa. Finally, aspirin produced a decrease in intracellular beta-catenin levels, suggesting that modulation of this protein is associated with tumor prevention. CONCLUSIONS: These data confirm a role for aspirin in suppression of Apc-associated intestinal carcinogenesis.

Adenomatous Polyposis Coli↗

Development and validation of an indirect enzyme immunoassay for detection of ovine antibody to Brucella ovis.

An indirect enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of Brucella ovis infection was developed. The assay uses a mouse monoclonal antibody to bovine IgG1 horseradish peroxidase (HRPO) conjugate that cross-reacts with immunoglobulin from sheep and a purified antigen from Brucella ovis. The ELISA data were read and analyzed according to a targeting procedure. The ELISA results were compared with a cold complement fixation test (CFT). Sera from 675 rams from three uninfected flocks were used to determine the ELISA cut-off value (O.D. 405 nm: 0.095) and the diagnostic specificity of the ELISA (100%) and the CFT (99.69% +/- 0.42). The ELISA cut-off value was corroborated by receiver operating characteristic (ROC) analysis. Six hundred and forty semen and serum samples from 419 rams from two naturally infected flocks were collected before and after mating-time during two consecutive years. All semen samples were cultured and Brucella ovis was isolated from 28 samples. Sera from the 28 rams with positive semen were used to determine the diagnostic sensitivity of the ELISA (96.43% +/- 6.8) and of the CFT (including suspected positive samples with titers of 1:5; 88.89% +/- 11.85). Considering the CFT suspicious and the anti-complementary reactions as positive resulted in a diagnostic sensitivity value of 89.28% +/- 11.46. Six hundred and ten serum samples from the 640 sera were used to determine relative sensitivity (excluding sera with 1:5) at: ELISA/CFT 97.26% +/- 3.74 and CFT/ELISA was 71.72% +/- 8.87. The percent agreement, beyond chance measured by the Kappa index was 79.7. Relative sensitivity ELISA/CFT (including 1:5 titers in the CFT as positive) was 94.9% +/- 4.83 and CFT/ELISA was 72.84% +/- 8.59. The Kappa index was 79.4.

Animals↗

Clinical consequences of the implementation of a weaning protocol.

OBJECTIVE: To analyze the clinical and economic consequences of the implementation of a weaning protocol in patients mechanically ventilated (MV) for more than 48 h. DESIGN: Comparative study. SETTING: General intensive care unit (ICU) in a county hospital covering 360000 inhabitants. PATIENTS: 51 patients weaned by a fixed protocol were studied prospectively and compared with 50 retrospective controls. MEASUREMENTS: The following variables were assessed: Acute Physiology and Chronic Health Evaluation (APACHE) II score, age, cause of respiratory failure, type of extubation (direct extubation or extubation using a weaning technique), number of days on MV before the weaning trial, weaning time, total duration of MV, complications (reintubations and tracheostomies), length of ICU stay, and mortality. RESULTS: The groups were comparable in terms of age, APACHE II score, and main cause of acute respiratory failure. Number of days on MV up to the weaning trial were similar in the two groups (8.4 +/- 7.7 in the protocol group vs 7.5 +/- 5.5 in the control group, NS). Most of the patients (80%) in the protocol group were directly extubated without a weaning technique, unlike the control group (10%) (p < 0.01). When a weaning technique was used, the weaning time was similar in both groups (3.5 +/- 3.9 days vs 3.6 +/- 2.2 days in the control group). Duration of MV was shorter in the protocol group (10.4 +/- 11.6 days) than in the control group (14.4 +/- 10.3 days) (p < 0.05). As a result, the ICU stay was reduced by using the weaning protocol (16.7 +/- 16.5 days vs 20.3 +/- 13.2 days in the control group, p < 0.05). We found no differences in reintubation rate (17 vs 14% in the control group) and need for tracheostomies (2 vs 8% in the control group). CONCLUSION: The implementation of a weaning protocol decreased the duration of MV and ICU stay by increasing the number of safe, direct extubations.

APACHE↗

Use of capnography to detect hypercapnic episodes during weaning from mechanical ventilation.

OBJECTIVE: To evaluate the relationship between PaCO2 and end-tidal CO2 tension (PetCO2) before weaning and during a weaning trial and to determine the ability of PetCO2 to identify clinically relevant episodes of hypercapnia. DESIGN: Open, prospective study. SETTING: General intensive care unit. PATIENTS: 30 critically ill patients (mean age 63 +/- 2 years; Acute Physiology And Chronic Health Evaluation (APACHE) II of 18.4 +/- 3) who underwent a weaning trial during the recovery phase of acute respiratory failure requiring mechanical ventilation (MV) (8.9 +/- 1 days on MV). INTERVENTIONS: Weaning trial consisted of 2 h breathing on 5 cmH2O of Continuous Positive Airway Pressure (CPAP). MEASUREMENTS AND RESULTS: Arterial blood gas values, PetCO2 register and pulse oximetry determinations were recorded in assist/control ventilation before CPAP, after 1 h on CPAP and after 2 h on CPAP (immediately before extubation) or immediately before returning to assist/control mode in patients who failed the weaning trial. Clinically relevant hypercapnic episodes were described as: (1) an increment in PaCO2 > 42 mm Hg in previously normocapnic patients and (2) an increment of > 8 mm Hg from previous PaCO2 in previously hypercapnic patients. Changes in PaCO2 and changes in PetCO2 between MV and the first and second hour of CPAP showed a significant correlation (r = 0.74; p < 0.01). Clinically relevant hypercapnic episodes were detected by increments of > 3 mm Hg in PetCO2 with a sensitivity of 82%, a specificity of 76% and a negative predictive value of 94%. The area under the receiver operating characteristic curve for increments in PetCO2 was 0.90. CONCLUSIONS: Capnography provided good assessment of hypercapnic episodes during weaning, although the high number of false positives may result in arterial blood sampling in patients who do not present with ventilation failure.

APACHE↗

Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia.

OBJECTIVE: To determine whether continuous subglottic aspiration prevents nosocomial pneumonia in mechanically ventilated patients. DESIGN: A randomized, controlled, blinded study. SETTING: Medical-surgical intensive care unit. PATIENTS: 190 patients who were admitted to the intensive care unit during a 33-month period and whose condition suggested the need for prolonged intubation (> 3 days). INTERVENTION: 76 patients were randomly allocated to receive continuous aspiration of subglottic secretions, and 77 control patients were allocated to receive usual care. MEASUREMENTS: The numbers of cases of ventilator-associated pneumonia, ventilated days, days in intensive care unit, and deaths were recorded. The amount of subglottic secretions aspirated daily and surveillance cultures in the subglottic secretions were also obtained periodically. Etiologic diagnosis was based on the quantitative culture of secretions obtained by protected specimen brush or bronchoalveolar lavage. RESULTS: The incidence rate of ventilator-associated pneumonia was 19.9 episodes/1000 ventilator days in the patients receiving continuous aspiration of subglottic secretions and 39.6 episodes/1000 ventilator days in the control patients (relative risk, 1.98; 95% CI, 1.03 to 3.82). This difference was due to a significant (P < 0.03) reduction in the number of gram-positive cocci and Haemophilus influenzae organisms in the patients receiving continuous aspiration. However, no differences were observed in the number of Pseudomonas aeruginosa or Enterobacteriaceae organisms. Episodes of ventilator-associated pneumonia occurred later in patients receiving continuous aspiration (12.0 +/- 7.1 days) than in the control patients (5.9 +/- 2.1 days) (P = 0.003). The same microorganisms isolated from protected specimen brush or bronchoalveolar lavage cultures in patients with ventilator-associated pneumonia were previously isolated from cultures of subglottic secretions in 85% of cases. No significant differences in outcome were found. CONCLUSIONS: The incidence of nosocomial pneumonia in mechanically ventilated patients can be significantly reduced by using a simple method that decreases the chronic microaspirations through the cuff of endotracheal tubes.

Aged↗

Termination of pregnancy in dogs by oral administration of dexamethasone.

Dexamethasone was administered orally for 7.5 or 10 d to each of 20 pregnant bitches beginning at an estimated 28 to 51 d of gestation, using 1 of 2 dose regimens. Five bitches were given dexamethasone 3 times a day for 10 d, with the highest dose of 0.2 mg/kg for 5 d and then at progressively decreasing doses of 0.16-0.02 mg/kg for 5 d. The 15 remaining bitches were given dexamethasone 2 times a day for 7.5 d, increasing from 0.1 to 0.2 mg/kg over the first 3 administrations, then remaining at 0.2 mg/kg on Days 2 to 5, and decreasing from 0.16 to 0.02 mg/kg over the last 5 administrations. The side effects, including mild polydipsia and polyuria, disappeared when treatment was discontinued. Depending on the stage of pregnancy, uterine contents were either resorbed or aborted, or both. Pregnancy was terminated within 2 to 16 d after the start of treatment in all treated bitches, at 2 to 5 d of treatment in 2 of 3 bitches treated at 40 to 51 d of pregnancy, and at 0 to 4 d after the end of treatment in most of the 17 bitches treated at 28 to 35 days of pregnancy. Oral administration of dexamethasone appears to be a potentially useful pharmacologic treatment for the termination of unwanted pregnancy in the bitch.

Journal Article↗

[Hair mercury levels in different occupational groups in a gold mining zone in the north of Colombia].

Hair mercury analysis was carried out on a sample of 219 people living in the main gold mining zone of Colombia, 27 inhabitante of Cartagena City being taken as control sample. For data analysis the sample was divided by occupation and the corresponding the hair mercury concentrations (mean +/- SD) were found to be 5.23 +/- 5.78, 2.83 +/- 3.27, 2.4 +/- 2.02 and 1.33 +/- 0.74 micrograms/g for fishermen, miners, people of various other activities and the control sample, respectively. According to variance analysis and the Newman Keuls test, there were significant differences (p < 0.01) between the mercury concentrations for fishermen and those for the other groups. No significant differences were found for hair mercury and sex, non was any correlation with age detected; however, a low positive correlation (R = 0.15, p < 0.01) with the frequency of the consumption of fish was noted. The main symptoms of mercury poinsoning observed in the persons exposed were headache, oral lesions, metalic taste, loss of memory, and irritability.

Adolescent↗

Role of bronchoalveolar lavage in mechanically ventilated patients with suspected pneumonia.

To determine the usefulness of samples obtained by bronchoalveolar lavage (BAL) in establishing the diagnosis of ventilator-associated pneumonia, quantitative cultures of BAL and protected specimen brush (PSB) samples obtained via fiberoptic bronchoscope were compared in 42 patients with suspected ventilator-associated pneumonia. Direct examination of BAL fluid was also used to identify cells with intracellular organisms. Ventilator-associated pneumonia was diagnosed in 18 patients; a total of 39 microorganisms were recovered from BAL fluid and 29 from PSB specimens. Cultures of 21 BAL and 23 PSB specimens were sterile. Quantitative BAL and PSB cultures coincided in 76% of cases. Sterile BAL and PSB cultures agreed in 87% of cases. Cultures were completely discordant in only three cases. The sensitivity of BAL for diagnosis of ventilator-associated pneumonia using bacterial counts of > or = 10(4) cfu/ml was 89%, and specificity was 100%. In 14 of the 18 patients with ventilator-associated pneumonia, the percentage of cells containing intracellular organisms in specimens recovered by BAL was 11.6% versus 0.45% in patients without pneumonia (p < 0.05). In the remaining four patients, all of whom had Pseudomonas aeruginosa pneumonia, no intracellular organisms could be detected. Using a cut-off point of > or = 5% of cells with intracellular organisms, the sensitivity and specificity for the early diagnosis of ventilator-associated pneumonia was 67% and 96%, respectively. The results confirm the usefulness of the quantitative BAL culture (with a cut-off at 10(4) cfu/ml) for the diagnosis of ventilator-associated pneumonia. The identification of intracellular organisms in BAL fluid is a good early indicator of pneumonia, but the sensitivity of this technique may be lower for Pseudomonas aeruginosa infections.

Adult↗

Hemodynamic responses to external counterbalancing of auto-positive end-expiratory pressure in mechanically ventilated patients with chronic obstructive pulmonary disease.

OBJECTIVE: To study the effect of positive end-expiratory pressure (PEEP) on right ventricular hemodynamics and ejection fraction in patients with chronic obstructive pulmonary disease and positive alveolar pressure throughout expiration by dynamic hyperinflation (auto-PEEP). DESIGN: Open, prospective, controlled trial. SETTING: General intensive care unit of a community hospital. PATIENTS: Ten patients sedated and paralyzed with an acute exacerbation of chronic obstructive pulmonary disease undergoing mechanical ventilation. INTERVENTIONS: Insertion of a pulmonary artery catheter modified with a rapid response thermistor and a radial arterial catheter. PEEP was then increased from 0 (PEEP 0) to auto-PEEP level (PEEP = auto-PEEP) and 5 cm H2O above that (PEEP = auto-PEEP +5). MEASUREMENTS: At each level of PEEP, airway pressures, flow and volume, hemodynamic variables (including right ventricular ejection fraction by thermodilution technique), and blood gas analyses were recorded. MAIN RESULTS: The mean auto-PEEP was 6.6 +/- 2.8 cm H2O and the total PEEP reached was 12.2 +/- 2.4 cm H2O. The degree of lung inflation induced by PEEP averaged 145 +/- 87 mL with PEEP = auto-PEEP and 495 +/- 133 mL with PEEP = auto-PEEP + 5. The PEEP = auto-PEEP caused a right ventricular end-diastolic pressure increase, but there was no other significant hemodynamic change. With PEEP = auto-PEEP + 5, there was a significant increase in intravascular pressures; this amount of PEEP reduced cardiac output (from 4.40 +/- 1.38 L/min at PEEP 0 to 4.13 +/- 1.48 L/min; p < .05). The cardiac output reduction induced by PEEP = auto-PEEP + 5 was > 10% in only five cases and this group of patients had significantly lower right ventricular volumes than the group with less cardiac output variation (right ventricular end-diastolic volume: 64 +/- 9 vs. 96 +/- 26 mL/m2; right ventricular end-systolic volume: 38 +/- 6 vs. 65 +/- 21 mL/m2; p < .05) without significant difference in the other variables that were measured. Neither right ventricular ejection fraction nor right ventricle volumes changed as PEEP increased, but there were marked interpatient differences and also pronounced changes in volume between stages in individual patients. CONCLUSIONS: In the study conditions, PEEP application up to values approaching auto-PEEP did not result in the impairment of right ventricular hemodynamics, while higher levels reduced cardiac output in selected patients.

APACHE↗

Occipital encephalocele associated with a dermoid cyst.

The case of a neonate with a dermoid cyst originating within an occipital encephalocele is reported. The finding of the tumor was made during the routine repair of the meningoencephalocele. To our knowledge this is the first time that this association has been described.

Brain Neoplasms↗

[Prevalence and treatment of bacteriuria in the geriatric population].

The aim of this study was to evaluate the prevalence of asymptomatic bacteriuria and its prognostic factors in a geriatric population living in a nursing home. Seventy-eight patients (68 females, 10 males) with a mean age of 82 +/- 6 years (range: 60-94) were studied. Once symptomatic infection is ruled out and the risk factors had been analyzed, a urine culture was performed in all cases. We then identified two different population groups: asymptomatic bacteriuria without risk factors (group A), and asymptomatic bacteriuria with risk factors (group B). Overall prevalence of asymptomatic bacteriuria was 38.5% (Group A: 23%, group B: 63%; p < 0.001). Considering all patients with bacteriuria, 50% of cases (15 out of 30 patients) had urine incontinence, 40% suffer from severe limitation of movements and 70% had a past history of pregnancy. The same figures for the population with negative urine culture were 12.5%, 14.5%, and 46% respectively (p < 0.01). In group B, 79% of cases had more than one RF, including all patients with the association of urine incontinence, movement limitation and diabetes. In group A, 93% of asymptomatic bacteriuria were due to E. coli with low adhesin expression (27%) whereas in group B, E. coli was isolated in 44% asymptomatic bacteriuria cases, with high adhesin expression (71.5%), other enteric gram-negative bacilli (31%), non-fermentative gram-negative bacilli (19%) and gram-positive cocci (6%). Group A patients were treated with a single dose of ciprofloxacin (500 mg) with elimination of bacteria in urine in 91% of cases (at one week) and 73% of cases (at one month).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intussusception of the appendix in a patient with cystic fibrosis.

This case report describes the clinical presentation and the radiographic, endoscopic, and pathologic findings in a patient with cystic fibrosis (CF) and intussusception of the appendix. This is the first time that intussusception of the appendix has been documented in a patient with CF. This disorder should be considered in the CF patient with cramping lower abdominal pain or rectal bleeding.

Adolescent↗