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Biomedical subjects

E García

Publications and source records attributed to E García.

At least 109 records · Page 6Linked to original sources

Synthesis and biological activity of 4-amino-7-oxo-substituted analogues of 5-deaza-5,6,7,8-tetrahydrofolic acid and 5,10-dideaza-5, 6,7,8-tetrahydrofolic acid.

The 4-amino-7-oxo-substituted analogues of 5-deaza-5,6,7, 8-tetrahydrofolic acid (5-DATHF) and 5,10-dideaza-5,6,7, 8-tetrahydrofolic acid (DDATHF) were synthesized as potential antifolates. Treatment of the alpha,beta-unsaturated esters 11a-c, obtained in one synthetic step from commercially available para-substituted methyl benzoates (9a-c) and methyl 2-(bromomethyl)acrylate (10), with malononitrile in NaOMe/MeOH afforded the corresponding pyridones 12a-c. Formation of the pyrido[2,3-d]pyrimidines 13a-c was accomplished upon treatment of 12a-c with guanidine in methanol. After the hydrolysis of the ester group present in 13a-c, the resulting carboxylic acids 14a-c were treated with diethyl cyanophosphonate in Et3N/DMF and coupled with L-glutamic acid dimethyl ester to give 15a-c. Finally, the basic hydrolysis of 15a-c yielded the desired 4-amino-7-oxo-substituted analogues 16a-c in 20-27% overall yield. Compounds 16a-c were tested in vitro against CCRF-CEM leukemia cells. The results obtained indicated that our 4-amino-7-oxo analogues are completely devoid of any activity, the IC50 being higher than 20 microg/mL for all cases except 14c for which a value of 6.7 microg/mL was obtained. These results seem to indicate that 16a-c are inactive precisely due to the presence of the carbonyl group in position C7, the distinctive feature of our synthetic methodology.

Antimetabolites, Antineoplastic↗

Mechanisms of residual lumen stenosis after high-pressure stent implantation: a quantitative coronary angiography and intravascular ultrasound study.

BACKGROUND: Intravascular ultrasound (IVUS) studies have demonstrated that stents are frequently suboptimally expanded despite the use of high pressures for deployment. The purpose of this study was to identify the mechanisms responsible for such residual lumen stenosis. METHODS AND RESULTS: Fifty-seven lesions from 50 patients treated with high-pressure (median+/-interquartile range, 14+/-2 atm) elective (44 de novo, 13 restenotic lesions) stenting were prospectively studied (29 Wiktor, Medtronic; 28 Palmaz-Schatz, Cordis Corp). Balloon subexpansion was calculated as the difference between maximal and minimal balloon cross-sectional areas at peak pressure measured by automatic edge detection; elastic recoil was calculated as the difference between minimal measured balloon size and IVUS-derived minimal lumen area within the stent. Angiographic residual diameter stenosis was 10+/-13% (reference diameter, 3.1+/-0.7 mm; balloon to artery ratio, 1.12+/-0.23) and IVUS-derived stent expansion was 80+/-28%. However, although balloon nominal size was 9.6+/-1.3 mm2 and maximal balloon size measured inside the coronary lumen was 12.5+/-3.2 mm2, final stent minimal lumen area was only 7.1+/-2.2 mm2. Balloon subexpansion of 4.0+/-1.8 mm2 (33%) and elastic recoil of 1.6+/-2.3 mm2 (20%) (both P<0.0001) were the two mechanisms responsible for residual luminal stenosis. Wiktor stent and peak inflation pressure correlated with balloon subexpansion, whereas Wiktor stent, de novo lesion, and minimal lumen area at baseline correlated with elastic recoil. CONCLUSIONS: Despite high-pressure deployment, lumen dimensions after stenting are only 57% of maximal achievable. Inadequate balloon expansion and elastic recoil are responsible for residual lumen stenosis, suggesting that plaque characteristics and stent resistance deserve further investigation.

Aged↗

Evidence for horizontal transfer from Streptococcus to Escherichia coli of the kfiD gene encoding the K5-specific UDP-glucose dehydrogenase.

Capsular polysaccharides are important virulence factors both in Gram-positive and Gram-negative bacteria. A similar cluster organization of the genes involved in the synthesis of bacterial exopolysaccharides has been postulated in both cases, suggesting that these clusters evolved by module assembly. Horizontal gene transfer has been postulated to explain the polymorphism found in these cellular polymers. The cap1 K and cap3A genes coding for the pneumococcal type 1 and type 3 UDP-glucose dehydrogenases, respectively, have been compared with other UDP-sugar dehydrogenases. We have observed that the evolutionary distance between Cap1K and Cap3A is approximately equal to that found between Cap1K (or Cap3A) and other UDP-GlcDH of families evolutionarily distant like KfiD, the dehydrogenase from Escherichia coli K5. On the basis of comparisons of G + C content, patterns of synonymous and nonsynonymous substitutions, dinucleotide frequencies, and codon usage bias, we conclude that the kfiD gene has been introduced into E. coli from an exogenous source, probably from a streptococcal species.

Bacterial Capsules↗

[Results of primary angioplasty in patients with multivessel disease].

INTRODUCTION: In patients with acute myocardial infarction treated with primary angioplasty, multivessel disease is associated with a higher mortality. However, if higher mortality is simply due to a higher prevalence of cardiogenic shock or if multivessel disease is an independent risk factor remains unclear. OBJECTIVES: To study if multivessel disease constitute an independent prognostic factor in patients with acute myocardial infarction treated with primary angioplasty, and to ascertain possible mechanisms contributing to the worse prognosis found in these patients. PATIENTS AND METHODS: Between august 1991 and october 1996, 312 patients with acute myocardial infarction were treated with primary angioplasty in our center. Characteristics and in-hospital outcome of patients with or without multivessel disease were compared. RESULTS: Patients with multivessel disease (n = 158; 51%) were older (64 +/- 11 vs 61 +/- 13 years; p = 0.017), less often smokers (60% vs. 76%; p = 0.006) and had a higher prevalence of diabetes (35% vs. 20%; p = 0.007), hypertension (54% vs. 39%; p = 0.012), prior acute myocardial infarction (29% vs. 5%; p < 0.001), prior coronary bypass (2% vs. 0%; p = 0.042) and Killip class IV at admission (19% vs. 8%; p < 0.001). Angiographic success rate was not different in patients with or without multivessel disease (89% vs. 92%; NS). Patients with multivessel disease had a higher in-hospital mortality (21% vs. 7%; p < 0.001), need of revascularization (17% vs. 3%; p < 0.001) and incidence of severe mitral regurgitation, (5% vs. 0%; p < 0.001), second or third atrioventricular blockade (10% vs. 1%; p < 0.001) and severe bleeding (4% vs. 1%; p = 0.089). After excluding patients with Killip class III or IV at admission, mortality was also higher in patients with multivessel disease (9% vs. 2%; p = 0.009). Multivariate analysis showed the following independent risk factors for mortality: age > 65 years, Killip class IV and multivessel disease. CONCLUSIONS: In patients with acute myocardial infarction treated with primary angioplasty, multivessel disease is associated with higher mortality. This is due not only to a higher prevalence of cardiogenic shock at admission, but also to a worse baseline profile, a higher incidence of complications and a more frequent need of revascularization.

Age Factors↗

Transvaginal sonography in endometrial carcinoma: preoperative assessment of the depth of myometrial invasion in 50 cases.

OBJECTIVE: A prospective study was designed for patients previously diagnosed of endometrial carcinoma to evaluate the accuracy of transvaginal sonography (TVS) in determining both the presence and the depth of myometrial invasion. Patients with advanced stage disease (III and IV) were specifically excluded from the analysis. SUBJECTS AND METHODS: Sixty patients with endometrial carcinoma underwent transvaginal ultrasonography. Ten of these patients were ruled out due to various reasons. In the remaining 50 cases, TVS findings were compared with those obtained after total abdominal hysterectomy and bilateral salpingo-oophorectomy (AHT). RESULTS: The sensitivity of TVS in detecting deep invasion, i.e. more than 50% of the myometrial thickness was 94.1%, while the specificity was 84.8% and the overall accuracy was 88%. Following the classification of the International Federation of Obstetrics and Gynecology, stage I, which divides myometrial invasion into three categories (none, superficial involvement and deep invasion) sensitivity was 66.2%, specificity was 83.1% and overall accuracy was 77.2%. CONCLUSION: These findings are consistent with those reported in literature with regard to overall accuracy of TVS. Results are similar to those obtained with magnetic resonance imaging (MRI) without contrast and slightly lower than MRI plus contrast.

Endometrial Neoplasms↗

Analysis of airborne radon in an ultra-low background experiment.

The contribution of 222Rn to the background in a low background experiment with a germanium detector has been estimated. We have also checked the efficacy of a standard radon cleaning system. The cleaning reduces the radon concentration two orders of magnitude with respect to the air in the laboratory. The residual 222Rn represents at most 12.5% of the background in the low energy region, a value low enough for the purpose of our experiment. A detailed study of the radioactive background is presented.

Air Pollutants, Radioactive↗

Prevention of peritonitis with disconnect systems in CAPD: a randomized controlled trial. The Mexican Nephrology Collaborative Study Group.

BACKGROUND: Recently, disconnect systems for CAPD that are associated with a reduced frequency of peritonitis have been introduced. Our objective was to compare the incidence of peritonitis using three current CAPD systems in a high-risk population with low educational and socioeconomic levels, and high prevalence of malnutrition. METHODS: In a prospective controlled trial, 147 patients commencing CAPD were randomly assigned to one of three groups: 29 to the conventional, 57 to the Y-set, and 61 to the twin bag systems. The number of peritonitis episodes was registered, and patients were followed up for an average of 11.3 months. RESULTS: The average peritonitis-free interval for the conventional group was 6.1 months, for the Y system was 12.0 months, and for the twin bag was 24.8 months (P < 0.001). By multivariate analysis, the only factor associated with peritonitis was the CAPD system. Peritonitis-related hospitalization was 5.3 +/- 2.0, 2.7 +/- 1.0, and 1.5 +/- 0.9 days/patient/year in the conventional, Y system, and twin bag groups, respectively. The cost per bag was similar for the conventional and Y system, but higher for the twin bag. However, the total costs of treatment (pesos/patient/year) were lower for twin bag (62,159 for the conventional, 70,275 for the Y system, and 54,387 for the twin bag), due to the lower peritonitis incidence and associated hospitalizations. CONCLUSIONS: Y system and twin bag use was associated with a reduction of 50 and 75% peritonitis incidence, respectively, in patients on CAPD. The cost of the twin bag was actually lower, because of savings from a decreased usage of antibiotics and fewer hospitalizations.

Adult↗

Severe experimental uraemia does not decrease the population of rat pituitary somatotrophs.

BACKGROUND: Growth hormone (GH) secretion by the anterior pituitary has been shown to be depressed in severely uraemic rats. Changes in the population of pituitary somatotrophs might be partially responsible for this decrease. METHODS: To analyse the population of pituitary somatotrophs in severe uraemia, immunocytochemical detection and quantification of GH-producing cells were carried out on paraffin sections from young rats either 5/6 nephrectomized, sham-operated fed ad libitum or sham-operated pair-fed with the nephrectomized animals. RESULTS: Nephrectomized rats were severely uraemic and growth retarded. The overall cell density (total pituitary cells/mm2) was higher in 5/6 nephrectomized animals in comparison with the two sham-operated groups. Thus, although the percentage of GH cells was slightly lower in nephrectomized than in control rats, no difference in either the density (cells/mm2) or the cross-sectional area of GH cells was found among groups. CONCLUSIONS: These results suggest that severe experimental uraemia interferes with the maturation process of the pituitary gland and support the contention that differences in either the number or the size of pituitary somatotrophs cannot explain the reduced GH secretion previously reported in severely uraemic rats.

Animals↗

The significance of lipoproteins in serum binding variations of propofol.

UNLABELLED: The protein binding of propofol was investigated in vitro in isolated lipoprotein fractions (very low-density lipoprotein [VLDL], low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) and in serum samples from the following subjects: healthy normolipemic volunteers (n = 16), hyperlipidemic subjects diagnosed with familiar polygenic hypercholesterolemia (n = 26) showing high levels of cholesterol, and elderly subjects (n = 15). Protein binding was determined by using ultrafiltration, and the concentration of unbound propofol was measured by using liquid chromatography. Levels of total cholesterol, triglycerides, VLDL cholesterol, LDL cholesterol, HDL cholesterol, albumin, and alpha1-acid glycoprotein were also measured. Propofol was extensively bound to the three lipoprotein fractions (88%+/-2% to VLDL, 93%+/-1% to LDL, and 91%+/-4% to HDL). The percentage of unbound propofol was significantly decreased (P < 0.0001) in hyperlipidemic (0.88%+/-0.20%) individuals whose levels of cholesterol and triglycerides were increased versus healthy subjects (1.26%+/-0.22%), whereas no significant difference was found in the elderly group (1.12%+/-0.23%). A positive relationship was found between serum protein binding of propofol and lipid levels. Multiple regression analysis, including all subjects, showed that changes in the levels of total cholesterol and triglycerides explained approximately 62% of the variability in the serum protein binding of propofol. These results stress the importance of triglycerides and cholesterol in the serum protein binding of propofol. We therefore suggest that these variations in lipid levels, and consequently in protein binding, may influence anesthetic practice with propofol. IMPLICATIONS: We investigated the effect of serum lipids in the protein binding of propofol. We found that propofol binds extensively to all lipoprotein fractions. Propofol binding showed a significant relationship with the serum levels of cholesterol and triglycerides.

Adult↗

Characterization of IS1515, a functional insertion sequence in Streptococcus pneumoniae.

We describe the characterization of a new insertion sequence, IS1515, identified in the genome of Streptococcus pneumoniae I41R, an unencapsulated mutant isolated many years ago (R. Austrian, H. P. Bernheimer, E. E. B. Smith, and G. T. Mills, J. Exp. Med. 110:585-602, 1959). A copy of this element located in the cap1EI41R gene was sequenced. The 871-bp-long IS1515 element possesses 12-bp perfect inverted repeats and generates a 3-bp target duplication upon insertion. The IS encodes a protein of 271 amino acid residues similar to the putative transposases of other insertion sequences, namely IS1381 from S. pneumoniae, ISL2 from Lactobacillus helveticus, IS702 from the cyanobacterium Calothrix sp. strain PCC 7601, and IS112 from Streptomyces albus G. IS1515 appears to be present in the genome of most type 1 pneumococci in a maximum of 13 copies, although it has also been found in the chromosome of pneumococcal isolates belonging to other serotypes. We have found that the unencapsulated phenotype of strain 141R is the result of both the presence of an IS1515 copy and a frameshift mutation in the cap1EI41R gene. Precise excision of the IS was observed in the type 1 encapsulated transformants isolated in experiments designed to repair the frameshift. These results reveal that IS1515 behaves quite differently from other previously described pneumococcal insertion sequences. Several copies of IS1515 were also able to excise and move to another locations in the chromosome of S. pneumoniae. To our knowledge, this is the first report of a functional IS in pneumococcus.

Amino Acid Sequence↗

[The incidence of intraoperative conciousness in emergency surgery and its possible relation to the post-traumatic stress syndrome. Presentation of three cases].

Intraoperative awakening and recall of specific events is a rare complication (0.2 to 1.3%) of surgery. The possibility of developing serious psychiatric complications, such as posttraumatic stress disorder (PTSD) makes the prevention and detection of intraoperative awareness a subject of special interest. We describe our experience with three patients in whom awareness was detected during emergency surgery under general anesthesia. We conducted two structured interviews with the patients three months after surgery in order to detect the possible development of psychiatric complications. One patient suffered insomnia and reexperience of the event during the first two weeks after surgery. Improvement was spontaneous. None of the patients suffered PTSD. Efforts to decrease the incidence of episodes of intraoperative awakening with specific recall must be based on clinical observation and exhaustive monitoring of the patient, including anesthetic gases, given that no ideal method of monitoring depth of anesthesia exists. Cases should be detected in the first few days after surgery by means of a specific test. Likewise, possible causes for the episode should be explained to the patient, who should be followed for six months so that early diagnosis of PTSD or other psychiatric complications can be made.

Adult↗

Ring1A is a transcriptional repressor that interacts with the Polycomb-M33 protein and is expressed at rhombomere boundaries in the mouse hindbrain.

In Drosophila, the products of the Polycomb group (Pc-G) of genes act as chromatin-associated multimeric protein complexes that repress expression of homeotic genes. Vertebrate Pc-G homologues have been identified, but the nature of the complexes they form and the mechanisms of their action are largely unknown. The Polycomb homologue M33 is implicated in mesoderm patterning in the mouse and here we show that it acts as a transcriptional repressor in transiently transfected cells. Furthermore, we have identified two murine proteins, Ring1A and Ring1B, that interact directly with the repressor domain of M33. Ring1A and Ring1B display blocks of similarity throughout their sequences, including an N-terminal RING finger domain. However, the interaction with M33 occurs through a region at the C-terminus. Ring1A represses transcription through sequences not involved in M33 binding. Ring1A protein co-localizes in nuclear domains with M33 and other Pc-G homologues, such as Bmi1. The expression of Ring1A at early stages of development is restricted to the neural tube, whereas M33 is expressed ubiquitously. Within the neural tube, Ring1A RNA is located at the rhombomere boundaries of the hindbrain. Taken together, these data suggest that Ring1A may contribute to a tissue-specific function of Pc-G-protein complexes during mammalian development.

3T3 Cells↗

Molecular biology of the capsular genes of Streptococcus pneumoniae.

The polysaccharide capsule of Streptococcus pneumoniae is the main virulence factor of this microorganism. Although the study of the genes responsible for the synthesis of the pneumococcal capsule enabled genetic and molecular analysis, the precise structure, organization, and functioning of these genes have only been investigated very recently. The genes implicated in the production of the type 3 capsule have been sequenced, expressed and their corresponding products biochemically characterized. In addition, partial information on the genes responsible for the biosynthesis of the capsules of pneumococcal types 1, 14 or 19 F is currently available.

Bacterial Capsules↗

Esophageal obstruction by solidification of the enteral feed: a complication to be prevented.

We report three cases of esophageal obstruction due to solidification of enteral feed refluxed from the stomach in patients being fed through a nasogastric tube. All three patients were administered sucralfate continuously by tube. The few previous descriptions of this rare complication have also implicated sucralfate with its pathogenesis. Given its clinical importance and the growing use of long-term enteral nutrition, this adverse event needs to be considered.

Adult↗

[The syndrome of mid-ventricular obstruction with apical aneurysm in hypertrophic myocardiopathy: presentation of a case].

We report an 81-year-old woman with hypertrophic cardiomyopathy, midventricular obstruction and associated apical aneurysm partially dyskinetic. At admission she showed a lateral acute myocardial infarction with sustained episodes of uniform ventricular tachycardia and subtle cardiac physical findings. Old apical infarction was suggested by resting thallium defects in the absence of obstructive coronary disease. The ECG revealed persistent ST elevation in the anteroapical leads without Q waves at discharge. This case report represents a rare example, in a previously asymptomatic elderly woman, of a distinct syndrome within the wide clinical spectrum of hypertrophic cardiomyopathy.

Aged↗

[Registry of activities of the Hemodynamics and Interventional Cardiology Section in the year 1996].

The results of the Spanish Registry of Hemodynamic and Interventional Cardiology in 1996 are presented. The Registry collects the activity of 81 centers which constitutes all of the cardiac catheterization laboratories in Spain. The main activity was adult cardiac catheterization in 73 centers and exclusively pediatric cardiac catheterization in 8. A total of 63,961 diagnostic catheterization procedures were performed, which represents a 10.7% increase compared to 1995. This was mainly due to the increase in coronary angiographies. Coronary interventions increased by 21.4%, for a total number of 15,009 procedures. The ratio of coronary interventions per million inhabitants was 375. Success rates of coronary interventions (94%) and complications (2.9%) were similar to those registered in preceding years. In the specific field of revascularization devices, there has been a sustained and spectacular increase in the use of intracoronary stents in the last 3 years. In 1996, coronary stents were employed in 7,104 cases (47.3% of all coronary revascularization procedures) and 8,873 prosthesis were implanted, increasing two-fold the activity in that field when compared to 1995. Stent implantation was elective in 58% cases, and the complication rate was very low (1% subacute closure; 1.8% myocardial infarction and 0.9% mortality). Directional coronary atherectomy decreased by 47% in the last year whereas rotational atherectomy increased by 10% despite a reduction in the number of centers performing this technique. As in previous years, a slight decrease in adult valvuloplasties was noted. Pediatric interventional procedures (607) increased by 30% compared to the 1995 Registry.

Adult↗