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Biomedical subjects

J Ruiz

Publications and source records attributed to J Ruiz.

At least 181 records · Page 10Linked to original sources

Video-laparoscopic staging of gastric cancer. A prospective multicenter comparison with noninvasive techniques.

BACKGROUND: The high proportion of gastric carcinomas present in an unresectable stage, together with the emergence of multimodal treatments, increases the usefulness of objective staging methods that avoid unnecessary laparotomies. METHODS: A prospective evaluation of the accuracy of laparoscopy in the staging of 71 patients with gastric adenocarcinoma is presented. Serosal infiltration, retroperitoneal fixation, metastasis to lymph nodes, peritoneal and liver metastasis, and ascites were determined in the staging workup. Sensitivity, specificity, and predictive values were calculated and compared with those obtained with ultrasonography (US) and computed tomography (CT). RESULTS: The diagnostic accuracy of laparoscopy in the determination of resectability was 98.6%. Consequently, over 40% of patients were spared unnecessary laparotomies. Laparoscopy yielded diagnostic indices superior to US and CT for all the tumoral attributes studied. Our technique permits accurate assessment and pathologic verification of liver and the peritoneal and retroperitoneal extent of tumor invasion in the majority of patients. CONCLUSIONS: Laparoscopy in gastric adenocarcinoma is a reliable technique that provides accurate assessment of resectability and stage, thus avoiding unnecessary laparotomies in patients in whom surgical palliation is not indicated. A stepwise diagnostic workup combining imaging and minimally invasive techniques is proposed.

Adenocarcinoma↗

Association of poorly controlled diabetes with low serum leptin in morbid obesity.

OBJECTIVES: Leptin may be involved in the regulation of body weight, food intake, and energy expenditure. In view of a possible link between leptin concentrations and diabetes that has been suggested in obese rodents, we investigated the potential relationship between serum leptin concentrations and hyperglycaemia in French patients with morbid obesity. SUBJECTS: Fasting leptin concentrations were measured in 241 morbidly obese patients with various degrees of glucose tolerance in a cross-sectional study. RESULTS: Fasting serum leptin concentrations did not differ between normoglycaemia (NG, 61.5 +/- 24.0 ng/ml) and glucose intolerant morbidly obese subjects (IGT, 56.5 +/- 18.5 ng/ml) and were slightly lower in those with controlled diabetes (55.1 +/- 30.3 ng/ml, P = 0.06 when compared to NG subjects). In contrast, leptin concentrations were 30% lower in patients with poorly controlled diabetes (43.0 +/- 22.2 ng/ml, P = 0.001 vs NG subjects). Leptin concentrations were negatively correlated with fasting glucose in all groups combined (p = -0.24, P = 0.0001) and particularly in NIDDM subjects (p = 0.31, P = 0.0054). Although leptin concentrations were higher in women than in men, similar significant correlation with fasting glucose was found when females were analyzed separately. A positive correlation was found with BMI (p = 0.25, P = 0.0001) in all groups. Multivariate analysis revealed that fasting glucose was independently associated with serum leptin concentrations (F = 12.5, P = 0.0005). Sex, age, BMI, waist/hip ratio, fasting glucose and insulin, total cholesterol and triglycerides, tested in the model, explained 42% of the leptin variability in this population. CONCLUSIONS: Poorly controlled diabetes was accompanied by a significant reduction of serum leptin concentrations in morbidly obese subjects. We suggest that a relative leptin deficiency (lower than expected for the BMI) associated with insulin deficiency in this population might contribute to a vicious cycle maintaining (or even worsening) obesity itself and/or its metabolic complications.

Adult↗

Quinolone-resistance mutations in the topoisomerase IV parC gene of Acinetobacter baumannii.

Mutations in the parC gene, which encodes a subunit of topoisomerase IV, were determined in 21 epidemiologically unrelated clinical isolates of Acinetobacter baumannii. Our studies highlight the conserved sequences in the quinolone-resistance-determining region of the parC gene from A. baumannii and other bacteria. Nine of ten isolates with MICs of ciprofloxacin of > or = 32 mg/L showed a change of Ser80 to Leu and one showed a change of Glu84 to Lys. These results suggest that ParC from A. baumannii is a secondary target for quinolones and that mutations at residues Ser80 and Glu84, when combined with mutations at Ser83 of GyrA, may render A. baumannii highly resistant to quinolones.

Acinetobacter↗

Analysis of the mechanism of quinolone resistance in nalidixic acid-resistant clinical isolates of Salmonella serotype Typhimurium.

Over a period of 2.5 years, 42 cases of gastro-enteritis caused by nalidixic acid-resistant Salmonella serotype Typhimurium occurred in Malaga. The epidemiological relationship among the strains involved was investigated by analysis of plasmid profile and of chromosomal DNA by pulsed-field gel electrophoresis (PFGE). Despite having different plasmid profiles, all 42 nalidixic-acid resistant Typhimurium isolates had evolved from one clone as shown by analysis of chromosomal DNA by PFGE. The mechanism of quinolone resistance in these Typhimurium isolates was also investigated. Analysis of outer-membrane proteins and lipopolysaccharide from quinolone-susceptible and resistant clinical isolates tested showed no differences. All nalidixic acid-resistant isolates had MICs for ciprofloxacin of 0.25 mg/L and for nalidixic acid of 1024 mg/L. Polymerase chain reaction fragments of 285 bp, containing the quinolone resistance-determining region of the gyrA gene, and of 237 bp, containing the region of parC homologous to the quinolone resistance-determining region of the gyrA gene, were sequenced. All resistant isolates presented a change at Ser-83 to Phe in the GyrA protein, but no changes were observed in the ParC protein. These findings indicated that this mutation in gyrA plays a major role in the acquisition of nalidixic-acid resistance in clinical isolates of Typhimurium.

Amino Acid Sequence↗

Cloning and nucleotide sequence analysis of a gene encoding an OXA-derived beta-lactamase in Acinetobacter baumannii.

A clinical strain of Acinetobacter baumannii (strain Ab41) that was resistant to all beta-lactam antibiotics tested except ceftazidime, ceftriaxone, ceftizoxime, and imipenem produced three beta-lactamases: a presumptive chromosomal cephalosporinase, a TEM-1-like beta-lactamase (pI 5.4), and a novel OXA-derived beta-lactamase named OXA-21 (pI 7.0). The gene encoding OXA-21 was located in an integron. The nucleotide sequence showed three mutations compared with the sequence of OXA-3, with two being silent; the nonsilent mutation generated a substitution of Ile-217 to Met.

Acinetobacter↗

Isolation of verotoxin-producing Escherichia coli O-rough:K1:H7 from two patients with traveler's diarrhea.

Two Escherichia coli O-rough:K1:H7 strains producing verotoxin 1 that were isolated from stool samples of two travelers with diarrhea who consulted our clinic after trips to the Indian Subcontinent and Central America were characterized. Both strains were sorbitol negative, the same phenotype presented by E. coli O157:H7, but in contrast they were beta-glucuronidase positive. Low-frequency restriction analysis of chromosomal DNA and pulsed-field gel electrophoresis and repetitive extragenic palindrome-PCR showed that both strains were epidemiologically related. The illness was self-limited in both cases but involved long-duration, watery diarrhea (10 to 50 days) accompanied by abdominal cramps and flatulence. This serotype should be taken into account as a possible cause of traveler's diarrhea.

Adult↗

Diagnosis of brucellosis by using blood cultures.

The performances of three blood culture systems, Hemoline performance diphasic medium (bioMérieux, Marcy l'Etoile, France), Bactec Plus Aerobic/F* (Becton Dickinson, Paramus, N.J.), and Vital Aer (bioMérieux), were compared for the diagnosis of 17 cases of brucellosis. By using a 5-day incubation protocol, positive results were 52.9, 82.4, and 11.8%, respectively. When the protocol was extended to 7 days, the results were 76.5, 94.1, and 47.1%, respectively. Bactec was the fastest system (P < 0.05).

Bacteriological Techniques↗

Electron microscopic microanalysis of bronchoalveolar lavage: a way to identify exposure to silica and silicate dust.

OBJECTIVES: The diagnostic implications of finding non-fibrous inorganic particles in bronchoalveolar lavage (BAL) fluid has not been fully assessed. The aim of this study has been to measure the silica and non-fibrous silicates in BAL fluid from populations with different exposures to inorganic dust, and to find whether such measurement is useful for diagnostic purposes. MATERIALS AND METHODS: BAL samples from 19 subjects with only environmental exposure to inorganic dust (group A, mean (SD) age 50.7 (15.2)), 23 subjects with normal chest x ray films exposed to silica or silicates at work (group B, mean (SD) age 52.0 (12.4)), and 15 subjects with a previous diagnosis of silicosis (group C, mean (SD) age 68.0 (6.5)) were studied. Absolute and relative cell counts were found, and the samples were prepared for microanalysis by electron microscopy (EM). Firstly, semiquantitative x ray microanalysis was performed to find the level of silicon (Si) (peak/background Si) and this was followed by microanalysis of individual particles by EM. Variables related to the level of Si detected were assessed with multivariate analysis. RESULTS: Detected levels were higher in group B (2.09, 95% confidence interval (95% CI) 1.56 to 2.82) and C (1.50, 95% CI 1.07 to 2.12) than in group A (0.87, 95% CI 0.66 to 1.16) (P < 0.05, Dunett t test). A first multivariate analysis showed that exposure to silica or silicates was the only determinant of the level of Si expressed as log peak/background Si, when adjusted for age, sex, smoking habit, and cell count. A second multivariate analysis with microanalysis of individual particles as an independent variable showed the silica count to be the main predictor of detected concentration of Si. Silica and non-aluminium silicates together explain 55.5% (R2) of the variation in detected levels of Si. CONCLUSIONS: Detected levels of Si in BAL fluid depend on silica count and are higher in subjects with exposure to inorganic dust at work, but will not discriminate between exposed subjects with and without silicosis. Because semiquantitative x ray microanalysis does not accurately define exposure to non-silica inorganic particles, this measurement must be followed by EM microanalysis of individual particles in most cases, especially when exposure to silicates or metal dust is suspected.

Adult↗

CYP2D6 polymorphism is not associated with essential tremor.

Recent reports have shown an association between cytochrome P450IID6 (CYP2D6) polymorphism and Parkinson's disease. We investigated the association between this polymorphism and the risk for developing essential tremor (ET). Leukocytic DNA from 91 unrelated ET patients and a control group of 258 unrelated healthy individuals was studied for the occurrence of eight different CYP2D6 allelic variants by using allele-specific PCR amplification Xbal and EcoRI-RFLP's analyses. The prevalence for these allelic variants in the ET and control groups were, respectively: CYP2D6*1 76.9 and 78.7%, CYP2D6*2 0.5 and 0.2%, CYP2D6*3 0 and 1%, CYP2D6*4 12.1 and 12.2%, CYP2D6*5 1.6 and 1.7%, CYP2D6*9 4.4 and 2.9%, CYP2D6*2x2 4.4 and 3.2%. The prevalence of subjects with absent CYP2D6 activity (those carrying two defect genes) was 1.1 and 3.1% in ET and control groups, respectively. Both groups studied were in Hardy-Weinberg equilibrium. These results indicate that mutations at the CYP2D6 gene do not seem to be a major factor in determining susceptibility to ET, and reinforces the view that ET and parkinsonism are distinct conditions.

Adolescent↗

Effectiveness of immunomodulating treatment (thymostimulin) in chronic obstructive pulmonary disease.

We conducted a prospective randomized study to assess the effect of thymostimulin in patients with long-standing chronic obstructive pulmonary disease (COPD) during a 1-year follow-up. A total of 38 patients in the intervention group and 40 in the control group received standard treatment for COPD. Patients in the intervention group were also given thymostimulin intramuscularly (1 mg/kg day for the 1st week followed by once a week for 6 months). At the end of the study period, patients treated with thymostimulin showed a statistically significant lower number of exacerbations and hospital admissions as compared with controls. However, there were no changes in the number of patients with severe or moderate impairment of respiratory function throughout the study period. No significant differences were found by Multitest or in serum concentrations of immunoglobulins and T-cell subsets before and after thymostimulin treatment. We conclude that treatment with thymostimulin is effective in the prevention of COPD exacerbations acting on the cellular immune response involved in bronchopulmonary defense.

Adjuvants, Immunologic↗

Pancoast's syndrome due to chronic pneumonia by Pasteurella multocida.

Infectious causes of Pancoast's syndrome are extremely rare. We describe the case of a patient with Pancoast's syndrome due to chronic pneumonia resulting from Pasteurella multocida. The patient was not immunosuppressed and had had no contact with animals. The diagnosis was made by transthoracic needle aspiration and institution of therapy with cefuroxime-axetil resulted in resolution of his symptoms.

Adult↗

Design and preparation of a multimeric self-cleaving hammerhead ribozyme.

The activity of a ribozyme can be impaired by additional sequences at the 5' and 3' termini of the catalytic sequence. To approach this problem, a system was designed that minimizes sequences upstream and downstream from active regions of a hammerhead ribozyme and allows delivery of a large number of active molecules. A self-cleavable multimeric molecule was prepared by placing a ribozyme target sequence (derived from the core region of the hepatitis B virus [HBV]) upstream and downstream from the catalytic sequence. This construct was cloned in tandem into in vitro expression vectors. 32P-UTP-labeled transcripts of the multimeric construct, as well as non-self-cleaved monomeric ribozyme controls, and substrate were synthesized. The multimeric ribozyme molecule efficiently self-cleaved to release monomeric ribozymes lacking any extra upstream and downstream sequences. In addition, monomers were substantially more active against the HBV target RNA than the non-self-cleavable ribozymes. Up to 80% degradation of the target RNA was achieved by a tenfold molar excess of a pentameric construct. We conclude that ribozymes can be produced as a multimeric tandem of self-cleavable molecules, the monomers of which are more active than monomeric ribozymes and highly efficient in cleavage of target transcripts.

Base Sequence↗

Diagnostic heterogeneity of diabetes in lean young adults: classification based on immunological and genetic parameters.

The aim of our study was to investigate the relative prevalence of the different forms of diabetes in young adults and their respective clinical characteristics. Included were 51 nonobese patients (BMI < 27 kg/m2) with diabetes diagnosed before age 40, excluding typical IDDM. Each patient was subjected to screening for glucokinase gene (MODY2) and mitochondrial DNA (at nucleotide 3243) mutations, to HLA class II genotyping, and screening for the presence of islet cell antibodies (ICAs) and anti-GAD antibodies. Informative families were analyzed for linkage of diabetes to chromosome 12q (MODY3). Based on clinical criteria, patients were subdivided into MODY (n = 19) and non-MODY (n = 32). In the MODY group, we identified three patients with MODY2, one with the 3243 mitochondrial mutation, and another with autoimmune diabetes. One of the five MODY families available for linkage study was shown to have MODY3. In the non-MODY group, we found five patients with autoimmune diabetes and one with MODY2. No clinical parameter was helpful to classify patients in one of these subclasses of diabetes; however, the glucagon-stimulated C-peptide was useful to discriminate between MODY2 patients and the others. In conclusion, young and lean non-insulin-dependent diabetic patients constitute a very heterogeneous group, although they present similar clinical characteristics. The clinical distinction of MODY and non-MODY patients allows correct classification in, at most, 75% of the patients and thus is not sufficient to predict clinical course. However, immunological and genetic parameters allowed us to classify only 25% of the patients in specific diagnostic classes.

Adult↗

Diabetes mellitus and the late complications: influence of the genetic factors.

Epidemiological, population and familial studies have revealed the multifactorial aspect of diabetes mellitus. Several mutations implicated in the pathogenesis of diabetes have been described over the last decade. These mutations are localised within genes associated with glucose metabolism, providing a molecular basis for the heterogeneity in the clinical presentation of diabetes mellitus. However, chronic hyperglycaemia associated with other vascular risk factors can only partly explain the incidence of micro and macrovascular complications. Familial studies have revealed the presence of a familial susceptibility for some vascular complications as nephropathy and coronary heart disease. In addition, these two vascular complications of diabetes mellitus are frequently associated in the same individual. This familial susceptibility could not be exclusively explained by environmental factors. Consequently the quest for susceptibility genes of vascular complications appears as a logical approach. The study of genes associated with an increased cardiovascular risk like the renin angiotensin system, the hemostasis cascade or the lipoproteins, may constitute the first step in this new research avenue. Moreover, glycation and oxidation pathways seem to play a role in the development of vascular complications. For example, the paraoxonase genes are good candidates for an increased vascular risk. This enzyme is entirely bound to HDL-cholesterol and could explain its anti-oxidant capacity. The natural substrate of this enzyme is unknown but there is some evidence suggesting that it may participate in the oxidated phospholipids degradation. Functional studies of paraoxonase with other exogenous substrates have revealed different phenotypes associated with different catalytic activities. In addition, varying enzymatic activities seem to be associated with different polymorphisms of the paraoxonase gene recently described (at position 192 and 55 of the paraoxonase gene), and these two polymorphisms have been recently studied in relation with coronary heart disease in non insulin dependent diabetic patients. The two polymorphisms were associated with coronary heart disease. But these initial results still await confirmation in different populations. Such studies will likely open the way to novel approach of vascular complications in diabetes mellitus.

Age of Onset↗