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Biomedical subjects

J Garcia

Publications and source records attributed to J Garcia.

At least 19 recordsLinked to original sources

[Magnetic resonance imaging of lesions of the triangular carpal ligament].

The wrist is a complex anatomical joint which is frequently involved in daily activities and exposed to trauma and overuse. That is why chronic wrist pain syndrome can be somewhat difficult to assess and requires the use of several imaging modalities. Three-compartment arthrography is an invasive but well-known technique that can evaluate interosseous ligaments as well as the triangular fibrocartilage complex; however in recent years MRI has become an important diagnostic tool in imaging wrist injuries, particularly triangular fibrocartilage complex. Its overall accuracy in detecting triangular fibrocartilage complex tears varies from 80 to 95% according to several authors, and even if there is still some controversy about the imaging of the small interosseous ligaments, MRI can also depict some other associated lesions.

Humans

Efficacy, safety, and immunogenicity of a meningococcal group B (15:P1.3) outer membrane protein vaccine in Iquique, Chile. Chilean National Committee for Meningococcal Disease.

A meningococcal group B (15:P1.3) outer membrane protein vaccine was tested for efficacy in a randomized, double-blind controlled study in Iquique, Chile. A total of 40 811 volunteers, ages 1-21 years, enrolled in the study. Volunteers received two doses of vaccine six weeks apart by jet injector. Both the experimental vaccine and the control vaccine (Menomune, A, C, Y and W135 meningococcal polysaccharide vaccine) were well tolerated with minor side-effects. Active surveillance for suspected cases of meningococcal disease was conducted for 20 months in Iquique. Eighteen cases of group B meningococcal disease were confirmed during the 20 months. Efficacy was estimated to be 51% (p = 0.11) for all ages combined. In children aged 1-4 no protection was evident, but in volunteers aged 5-21 vaccine efficacy was 70% (p = 0.045). The IgG antibody response by ELISA was characterized by a large booster effect after the second dose, followed by a substantial drop in antibody levels by 6 months. The youngest children had the highest responses. The bactericidal antibody response, on the other hand, was characterized by the lack of a significant booster response, higher responses in the older children, and an increase in the geometric mean titer in the later months of the study in the older children.

Adolescent

Bilateral ocular toxocariasis demonstrated by aqueous humor enzyme-linked immunosorbent assay.

PURPOSE/METHODS: A 14-year-old girl with a history of contact with puppies and chronic bilateral panuveitis was examined. The fundus of the right eye showed an inferotemporal pars plana exudate. The fundus of the left eye showed an elevated posterior mass. RESULTS/CONCLUSION: Toxocara antibodies in the aqueous humor detected by enzyme-linked immunosorbent assay had a Goldmann-Witmer coefficient of 8.63 in the right eye and 8.94 in the left eye. Toxocariasis may be a cause of bilateral panuveitis.

Adolescent

The effects of normothermic and hypothermic cardiopulmonary bypass on defibrillation energy requirements and transmyocardial impedance. Implications for implantable cardioverter-defibrillator implantation.

The influence of normothermic and hypothermic cardiopulmonary bypass on defibrillation energy requirements and transcardiac impedance is not well characterized. However, this relationship is of clinical importance during automatic defibrillator implantation done with concomitant cardiac surgery, and there is anecdotal information that criteria for successful implantation are harder to achieve after such operations. We studied the effect of controlled hypothermia on defibrillation energy requirements and transcardiac impedance in a canine model of cardiopulmonary bypass in which 26 animals underwent right atrial and femoral arterial cannulation, as well as continuous hemodynamic and intramyocardial temperature monitoring. The defibrillation energy requirements were evaluated at 60-minute intervals with an epicardial patch system, and transcardiac impedance was measured before and after the multiple inductions and terminations of ventricular fibrillation. In group 1 (n = 10) defibrillation energy requirements were evaluated immediately after initiation of cardiopulmonary bypass at 37 degrees C (T0), after gradual cooling to 28 degrees C (T1), and after rewarming to 37 degrees C (T2). Group 2 (n = 16) comprised time controls that were identically instrumented and studied, but maintained at 37 degrees C throughout. Percent successful defibrillation was plotted against delivered energy, and the raw data fit by logistic regression. The energy at which 50% of shocks were successful (E50) was 3.23 +/- 0.89 joules at T0, 5.12 +/- 1.85 joules at T1, and 4.42 +/- 1.22 joules at T2 in group 1; this was not significantly different from the corresponding group 2 E50 values, which were 3.11 +/- 1.39 joules, 4.95 +/- 2.47 joules, and 5.59 +/- 3.18 joules, respectively. Both groups demonstrated a significant increase in E50 during the first hour of cardiopulmonary bypass (mean increase from T0 to T1 was 1.89 joules in group 1 and 1.84 joules in group 2, p < 0.05). Transmyocardial impedance fell progressively during the group 2 experiments from 73.6 +/- 12.9 omega at the beginning of the T0 shock series to 61.4 +/- 8.9 omega at the end of the T2 shock series. A similar reduction in transmyocardial impedance was observed during the course of all the group 1 experiments; however, at the beginning of the T1 shock series impedance was significantly elevated to 77.4 +/- 12.3 omega (p < 0.05 compared with group 2 and with end T0 in group 1). There was no relationship between defibrillation energy requirements and transcardiac impedance; there was also no correlation between either of these parameters and intramyocardial extracellular pH or left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Micronutrient levels in HIV-1-infected children.

OBJECTIVE: Micronutrients (zinc, copper, selenium, vitamin A, E, and carotenoids) are essential for the integrity of host defences. This study was designed to determine the prevalence of abnormalities of the micronutrient levels in HIV-1-seropositive children. DESIGN: Prospective study. SETTING: The study was performed on HIV-1-infected children at the Paediatric Haematology and Oncology Unit of Toulouse Hospital, France. PATIENTS: Twenty-one children, suffering from HIV-1 infection and 21 control subjects of similar age (2-9 years) were included in the study. In the HIV-1-infected children, two subgroups were considered according to stage (non-AIDS or AIDS), based on the Centers for Disease Control and Prevention 1987 criteria. RESULTS: The first statistically significant deficiencies occurred at non-AIDS stage and were confirmed at AIDS stage: P < 0.05 for lycopene, retinol, tocopherol and P < 0.001 for transthyretin and serum albumin. Levels of copper (40%) and long-chain polyunsaturated fatty acids (21%) were higher in the non-AIDS group than the controls. CONCLUSION: Biological impairing of the micronutrient levels was observed in the non-AIDS stage without clinical sign. This information is useful in delineating eventual and well considered nutritional intervention strategies that may improve the clinical status of HIV-1-infected children and perhaps alter the course of their disease.

Carotenoids

E-4695, a new C-7 azetidinyl fluoronaphthyridine with enhanced activity against gram-positive and anaerobic pathogens.

E-4695, (-)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-cyclopropyl-1,4- dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid, is a new fluorinated naphthyridine with an azetidine moiety. The MICs of E-4695 at which 90% of the isolates were inhibited (MIC90s) were 0.06 to 0.5 microgram/ml for gram-positive cocci, including species of the genera Staphylococcus, Streptococcus, and Enterococcus, and the MIC90s against gram-negative pathogens such as members of the family Enterobacteriaceae (with the exception of Providencia spp. [MIC90, 8 micrograms/ml]) and Pseudomonas aeruginosa were 0.015 to 0.5 microgram/ml. E-4695 inhibited 90% of the Clostridium perfringens and Bacteroides fragilis isolates at 0.25 and 4 micrograms/ml, respectively. Against gram-positive cocci the potency of E-4695 was 2- to 8-fold higher than that of ciprofloxacin, 4- to 8-fold higher than that of ofloxacin, and 8- to 16-fold higher than that of fleroxacin. Against enteric bacteria and P. aeruginosa the potency of E-4695 was, in general, similar to that of ciprofloxacin and eightfold higher than those of ofloxacin and fleroxacin. E-4695 was four- and eightfold more potent than ciprofloxacin against C. perfringens and B. fragilis isolates, respectively. E-4695 and ciprofloxacin showed similar properties when the effects of pH or magnesium concentration were tested on them. E-4695 and ciprofloxacin had substantial reductions of activity only when pH decreased below 4.8. E-4695 and ciprofloxacin activities were not markedly affected by the presence of 5 or 10 mM Mg2+. The presence of serum and human urine at pH 7.2 decreased the activity of E-4695 between two- and fourfold. After an oral dose of 50 mg/kg of body weight, the maximum level in serum, the biological half-life, and the area under the concentration-time curve from 0 to 10 h for E-4695 were 13.2 microgram/ml, 3.3 h, and 45.6 microgram . h/ml, respectively. The area under the concentration-time curve from 0 to 4 h for ciprofloxacin was 2.3 microgram . h/ml at the same dose. Fifty-percent effective doses (ED50S) against Staphylococcus aureus HS-93 infections in mice were 4.5 mg/kg with E-4695 and 37.6 mg/kg with ciprofloxacin. Infection with Streptococcus pneumoniae 29206 was more effectively treated with E-4695 (ED50, 41,2 mg/kg) than with ciprofloxacin (ED50, 200 mg/kg). The ED50 of E-4695 for infections with Streptococcus pneumoniae 1625 was 132.2 mg/kg; ciprofloxacin was ineffective at 400 mg/kg against this strain. E-4695 was also more potent than ciprofloxacin in treatment of infections caused by gram-negative organisms such as Escherichia coli HM-42 (ED50S, 1.0 and 3.9 mg/kg, respectively). The ED50S of E-4695 and ciprofloxacin were 33.0 and 145.5 mg/kg against P. aeruginosa HS-116 and 9.6 and 18.9 mg/kg against P. aeruginosa B-120, respectively. The therapeutic efficacy of E-4695 may depend not only on its in vitro activity but also on its improved pharmacokinetic properties.

Animals

Effects of inotropic stimulation on energy metabolism and systolic function of ischemic right ventricle.

This study determined whether dobutamine enhances regional systolic function in the ischemic right ventricle (RV) at the cost of adverse effects on regional energy metabolism. Seventeen alpha-chloralose-anesthetized, open-chest pigs were studied under four conditions: 1) control; 2) dobutamine infusion (mean dose 9 micrograms.kg-1.min-1); 3) RV ischemia (45 +/- 5% reduction in RV free wall blood flow for 100 min); and 4) continued ischemia with dobutamine. Regional RV free wall high-energy phosphate metabolites were measured by 31P nuclear magnetic resonance (NMR) spectroscopy or by high-speed drill biopsies of the RV free wall. Regional RV free wall substrate and O2 consumption were measured using coronary venous blood sampling. Global RV systolic function was assessed by the maximal first derivative of RV pressure (dP/dtmax), and regional RV free wall systolic function was assessed by systolic segment shortening in the ischemic zone. Right coronary artery constriction caused markedly depressed regional RV systolic function, net lactate production, and coronary venous acidosis. Surprisingly, high-energy phosphates were unchanged compared with control. Addition of dobutamine caused a further decline in coronary venous pH and continued lactate production but did not reduce high-energy phosphates. While dobutamine markedly enhanced global RV systolic function (RV dP/dtmax 201 +/- 19% of control), systolic shortening in the ischemic RV free wall remained severely depressed (47 +/- 18% of control) despite dobutamine. The mechanism of high-energy phosphate preservation is likely due to diminished consumption of ATP in the hypocontractile ischemic region.

Animals

Suppression of the skin reaction to histamine by ebastine.

BACKGROUND: Ebastine is a nonsedating histamine H-1 antagonist undergoing evaluation for treatment of allergic rhinitis and urticaria. OBJECTIVE: To compare the suppression of prick and intradermal skin reactions to histamine over a period of 24 hours produced by a single dose of ebastine. Also to record side effects and assess changes in the electrocardiogram, particularly the QTc interval. METHOD: Single doses of 1, 3, 10, and 30 mg of ebastine or placebo were administered double-blind at approximately 8 AM after baseline measurement of the reaction to intradermal testing with 5 micrograms histamine base and prick skin testing with three concentrations of histamine. Intradermal testing with histamine was repeated hourly for four hours, every two hours for eight hours, and after 24 hours. Titrated prick skin testing with histamine was performed at 6, 12, and 24 hours. Potential side effects were recorded each time skin testing was performed. Electrocardiograms were repeated at 4 and 24 hours. RESULTS: Intradermal skin test reactions were suppressed between 4 and 24 hours and prick skin tests to 10 mg/mL histamine base were suppressed between 6 and 24 hours with all doses of ebastine. Prick skin test reactions were significantly smaller at 12 and 24 hours in the group receiving the 30 mg dose of ebastine than in all other groups. CONCLUSION: Ebastine is a potent antihistamine that suppresses skin reactions to histamine for 24 hours following single doses in the doses tested (1 to 30 mg). No differences from placebo were noted in either the incidence of side effects or in the QTc intervals of serial electrocardiograms.

Adult

Design of molecules that specifically recognize and cleave apurinic sites in DNA.

We have prepared a series of tailor-made molecules that recognize and cleave DNA at apurinic sites in vitro. These molecules incorporate in their structure different units designed for specific function: an intercalator for DNA binding, a nucleic base for abasic site recognition and a linking chain of variable length and nature (including amino and/or amido functions). The cleavage efficiency of the molecules can be modulated by varying successively the nature of the intercalating agent, the nucleic base and the chain. All molecules bind to native calf thymus DNA with binding constants ranging from 10(4) to 10(6) M-1. Their cleavage activity was determined on plasmid DNA (pBR 322) containing 1.8 AP-sites per DNA-molecule. The minimum requirements for cleavage are the presence of the three units, the intercalator, the nucleic base and at least one amino function in the chain. The most efficient molecules cleave plasmid DNA at nanomolar concentrations. Enzymatic experiments on the termini generated after cleavage of AP-DNA suggest a strand break induced by a beta-elimination reaction. In order to get insight into the mode of action (efficiency, selectivity, interaction), we have used synthetic oligonucleotides containing either a true abasic site at a determined position to analyse the cleavage parameters of the synthetic molecules by HPLC or a chemically stable analog (tetrahydrofuran) of the abasic site for high field 1H NMR spectrometry and footprinting experiments. All results are consistent with a beta-elimination mechanism in which each constituent of the molecule exerts a specific function as indicated in the scheme: DNA targeting, abasic site recognition, phosphate binding and beta-elimination catalysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Effects of regional myocardial lidocaine infusion on high energy phosphates.

High energy phosphates [phosphocreatine (PCr) and adenosine triphosphate (ATP)] are maintained in the heart under conditions of altered myocardial contractility and under certain conditions of maintained in the heart under conditions of altered myocardial contractility and under certain conditions of myocardial ischemia (such as hibernating myocardium). However, the metabolic consequences of reduced regional contractility have not been investigated. This study was designed to test the hypotheses that (1) under conditions of normal blood flow, reduction in regional contractility does not result in changes in PCr or ATP and (2) under conditions of reduced blood flow, reduction in regional contractility prevents the expected decline in high energy phosphates usually seen in regional ischemia. An in situ open chest swine preparation was used in which regional contractility was reduced with the administration of intracoronary lidocaine. High energy phosphates were measured using phosphorus-31 magnetic resonance spectroscopy (NMR) under conditions of normal flow and reduced flow. Intracoronary lidocaine infusion in 9 animals did not change blood flow from basal levels, but significantly reduced regional segment shortening from 0.16 +/- 0.02 to 0.02 +/- 0.01. The ratio of PCr/ATP did not change with lidocaine infusion (control: 1.53 +/- 0.09; lidocaine: 1.59 +/- 0.11), but oxygen content in the anterior interventricular vein increased from 8.25 +/- 0.69 to 9.83 +/- 0.91 ml/O2/100 ml blood in parallel studies (P = 0.04). While the lidocaine infusion was maintained, subsequent coronary stenosis significantly reduced subendocardial blood flow from 0.91 +/- 0.06 to 0.41 +/- 0.06 ml/min/g without significantly altering high energy phosphates (PCr/ATP = 1.51 +/- 0.15). In contrast to the 29% decline in PCr previously seen with regional ischemia, PCr was unchanged with this degree of flow reduction in the presence of lidocaine. Thus, PCr and ATP are unchanged under conditions of reduced contractility, consistent with equilibrium of energy synthesis and utilization. In addition, factors which reduce myocardial contractility, either pharmacologically or endogenously, protect against the metabolic consequences of reduced flow by reducing MVO2.

Adenosine Triphosphate

Radicular compression by gas in a spinal extra dural cyst. Report on two cases.

The authors describe two cases of secondary sciatica due to radicular compression by a gas containing cyst in the extra dural space. The diagnosis was realized with CT-Scan and magnetic resonance imaging. In both cases removal of the cyst provided relief. The pathogenesis of the presence of epidural gas is discussed and the literature reviewed.

Cysts

[Imaging of the spine].

Modern imaging techniques allow early and precise diagnosis of spinal diseases. Their sensitivity and specificity are variable, but in general they are more complementary than competitive. After emphasizing the different patterns which characterize the late evolution of diagnostic imaging, the author reviews the indications and limits of plain films, bone scintigraphy, computed tomography, and in particular of magnetic resonance, in trauma, degenerative lesions, inflammations, infections and tumors of the spine.

Diagnostic Imaging