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J M Garcia

Publications and source records attributed to J M Garcia.

At least 37 records · Page 2Linked to original sources
PubMed2001

Detection of epithelial messenger RNA in the plasma of breast cancer patients is associated with poor prognosis tumor characteristics.

PURPOSE: Free plasma RNA has been scarcely studied in patients with cancer. Here we examine the presence of RNA from epithelial tumors in plasma from a series of breast cancer patients and its correlation with tumor characteristics and circulating tumor cells. EXPERIMENTAL DESIGN: beta-actin mRNA was analyzed to check the viability of plasma RNA in samples from 45 patients with breast cancer and 25 controls. Nested primers were used to detect the presence of cytokeratin 19 (CK19) and Mammaglobin in the same samples. Eleven clinicopathological parameters were studied and correlated with molecular parameters. Additionally, we looked for circulating tumor cells in 16 of these patients and in 10 of the controls. RESULTS: All samples showed detectable quantities of beta-actin RNA. In controls, 3 cases (12%) were positive for Mammaglobin, and 5 (20%) were positive for CK19 RNA; of the 45 patients, 27 cases (60%) were positive for Mammaglobin, and 22 (49%) were positive for CK19. These differences were statistically significant (P = 0.001). Tumor size (P = 0.01) and proliferative index (P = 0.02) were associated with the presence of Mammaglobin, CK19, or both RNAs in plasma. Pathological stage (P = 0.06) was close to significance. Although a statistical relationship was not demonstrated, 9 of the 10 patients with circulating tumor cells showed epithelial mRNAs in plasma. CONCLUSIONS: We conclude that epithelial tumor RNA is detectable in plasma from breast cancer patients and that this finding is associated with a probable poor prognosis and circulating tumor cells.

Actins↗
PubMed2000

DNA damage after chemotherapy correlates with tumor response and survival in small cell lung cancer patients.

To explore the induction of chemotherapy (CT) DNA damage and its correlation with tumor response and patient survival, we undertook the present study in 20 small cell lung cancer (SCLC) patients. All patients underwent the same treatment based on CT courses of carboplatin and etoposide. Blood samples were taken before and immediately after CT and every 12 weeks during follow-up. Nuclear DNA damage was determined through the variations in three mitochondrial pseudogene mutations in DNA of peripheral blood mononuclear cells. They were detected by mutation-specific PCR and assessed by a semiquantitative method. The relative level of mutation rose after chemotherapy in all cases. Among the 11 patients (55%) with higher relative levels of mutations, 9 (82%) of them achieved a complete response. In contrast, of the 9 patients (45%) with lower relative levels of mutations, only 2 (18%) achieved a complete response, displaying a statistically significant difference (P=0.02). The overall survival for patients with marked genomic damage was 18 months (range 10-24), and for patients with low degree of DNA damage, it was 12 months (range 5-15) (P=0.002). Genomic damage detected after chemotherapy treatment correlates positively with tumor response and patient survival.

Adult↗
PubMed2000

Atrial fibrillation after beating heart surgery.

Postoperative atrial fibrillation (AF) is a frequent adverse event after coronary artery bypass grafting (CABG) and may negatively affect the early clinical outcome. We sought to investigate the risk factors, prevalence, and prognostic implications of postoperative AF in patients submitted to CABG without cardiopulmonary bypass (off-pump). The study population comprised 969 patients, 645 men (67%) and 324 women (33%) who had off-pump CABG at the Washington Hospital Center from January 1987 to May 1999. Preoperative AF patients were excluded (n = 15). Two hundred six patients (age 69 +/- 10 years, 137 men [66%]) developed AF, whereas 763 patients (age 61 +/- 12 years, 508 men [67%]) did not. Predictors of AF included age >75 years (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.9 to 4.5; p <0.001), history of stroke (OR 2.1, CI 1.2 to 3.7; p = 0. 007), postoperative pleural effusion requiring thoracentesis (OR 3.2, CI 1.0 to 9.4; p = 0.03), and postoperative pulmonary edema (OR 5.1, CI 1.2 to 21; p = 0.02). Minimally invasive direct CABG was associated with a lower incidence of AF (OR 0.4, CI 0.3 to 0.7; p <0. 001). AF was associated with a prolonged postoperative hospital stay (9 +/- 6 days AF vs 6 +/- 5 days no AF, p <0.001). In-hospital mortality was significantly higher in AF patients (3% AF vs 1% no AF, p = 0.009). Patients with persistent AF had a higher postoperative in-hospital stroke rate than patients without persistent AF (9% vs 0. 6%, p <0.001). AF after beating heart surgery is associated with a higher in-hospital morbidity, mortality, and prolonged hospital stay. A minimally invasive surgical approach (minimally invasive direct CABG) is associated with a lower risk of AF.

Aged↗
PubMed2000

Size-specific defensive structures in a horned weevil confirm a classic battle plan: avoid fights with larger opponents.

A rigid sheath that extends deep into the prothorax of male Parisoschoenus expositus serves to receive the horns of opponents in battles over females. The male cannot use his own horn unless he receives his opponent's horn in his sheath. The length of a male's sheath is always approximately equal to the length of his own horns, so his body design is appropriate only for horn-locking battles with males whose horns are equal to or shorter than his own. Horn length and sheath length are dimorphic with respect to each other and to an indicator of body size. The switch points between morphs are very nearly the same for several relationships, so the different aspects of fighting morphology are tightly coordinated.

Aggression↗
PubMed2000

Absence of point mutations at codon 17 of the mdm2 gene (serine 17) in human primary tumors.

Mdm2 is a phosphoprotein that interacts with protein p53, inhibiting its activity. A serine located in position 17 of Mdm2, has been implicated in its phosphorylation process. We hypothesize that point mutations at serine 17 could block its phosphorylation and thereby increase the p53-Mdm2 interaction. This mechanism could increase the p53 degradation and cause a loss of the protective effect of p53 against tumorigenesis. This hypothesis was based on recent studies in vitro, demonstrating that when serine 17 is mutated, the DNA-dependent protein kinase, activated by genomic damage, is unable to phosphorylate it. Thus, we investigated whether structural point mutations at exon 3 of the Mdm2 gene, affecting codon 17, were present in 162 human primary tumors, 70 breast carcinomas, 14 bladder tumors, 18 colon adenocarcinomas and 60 testicular tumors. Direct sequencing of a fragment (204 bp) of exon 3 of the Mdm2 gene that contains the codon 17 showed no mutations at this position, independently of the presence or absence of p53 gene mutations in the same tumors. These results do not support the hypothesis that mutations in the Mdm2 gene at this level are involved in the tumorigenic process of human cancers.

Codon↗
PubMed2000

Spectroscopy of nanoscopic semiconductor rings.

Making use of self-assembly techniques, we realize nanoscopic semiconductor quantum rings in which the electronic states are in the true quantum limit. We employ two complementary spectroscopic techniques to investigate both the ground states and the excitations of these rings. Applying a magnetic field perpendicular to the plane of the rings, we find that, when approximately one flux quantum threads the interior of each ring, a change in the ground state from angular momentum l = 0 to l = -1 takes place. This ground state transition is revealed both by a drastic modification of the excitation spectrum and by a change in the magnetic-field dispersion of the single-electron charging energy.

Journal Article↗
PubMed2000

Mitochondrial genotype segregation and effects during mammalian development: applications to biotechnology.

Mitochondria are endosymbiotic organelles responsible for energy production in practically every eukaryotic cell. Their uniparental fashion of inheritance, maternally inherited in mammals, and the homogeneity of mitochondrial DNA (mtDNA) within individuals and matrilineages, are biological phenomena that remain unexplained. This paper reviews some of the recent findings on mitochondrial influences on the manner in which embryos develop and how their genotypes are inherited in mammals, with particular emphasis on the genetic "bottleneck" effect. Animal models carrying a mix of mtDNAs (heteroplasmic) have been produced by karyoplast and cytoplast transplantation to analyze the segregation patterns at different stages during embryogenesis, in fetuses and offspring. Comparisons performed between murine and bovine reveal interesting changes in segregation and replication of transplanted mtDNAs. We have recently obtained Bos indicus and Bos taurus fetuses and calves from embryos reconstructed using enucleated polymorphic oocytes of Bos taurus origin. These and other findings on mitochondrial biology will have important implications in determining the cytoplasmic genotype of clones and in the preservation of endangered breeds and species.

Animals↗
PubMed2000

Beating heart versus conventional single-vessel reoperative coronary artery bypass.

BACKGROUND: Reoperative (redo) coronary artery bypass grafting (CABG) with cardiopulmonary bypass (on-pump) is associated with a higher morbidity and mortality than first-time CABG. It is unknown, however, whether CABG without cardiopulmonary bypass (off-pump) may yield an improved clinical outcome over conventional on-pump redo CABG. METHODS: We compared the perioperative outcomes of patients with single-vessel disease who underwent on-pump (n = 41) versus off-pump (n = 91) redo CABG between April 1992 and July 1999. The two groups were similar with respect to baseline characteristics and risk stratification: mean Parsonnet scores were 26 +/- 9 for on-pump versus 24 +/- 8 for off-pump patients (p = nonsignificant). RESULTS: On-pump redo patients had a higher rate of postoperative transfusions (58% on-pump versus 27% off-pump, p = 0.001), prolonged ventilatory support (17% on-pump versus 4% off-pump, p = 0.03), and a higher rate of postoperative atrial fibrillation (29% on-pump versus 14% off-pump, p = 0.04). On-pump redo CABG was also associated with prolonged postoperative length of stay (8 +/- 4 days on-pump versus 5 +/- 2 days off-pump, p < 0.001). In-hospital mortality was significantly higher in on-pump than in off-pump patients (10% versus 1%, p = 0.03). CONCLUSIONS: Single-vessel off-pump redo CABG can be performed safely with a lower operative morbidity and mortality than on-pump CABG and an abbreviated hospital stay compared with conventional on-pump redo CABG.

Aged↗
PubMed2000

Coronary revascularization of the circumflex system: different approaches and long-term outcome.

BACKGROUND: Minimally invasive direct coronary artery bypass, without cardiopulmonary bypass, through a left lateral thoracotomy approach (lateral MIDCAB), is a safe alternative to coronary artery bypass surgery using cardiopulmonary bypass (on-pump CABG) of the circumflex system via median sternotomy. However, it is unknown whether lateral MIDCAB may yield an improved long-term outcome over the conventional on-pump median sternotomy approach. METHODS: We compared the perioperative outcomes of patients undergoing lateral MIDCAB (n = 34) versus conventional on-pump CABG of the circumflex system (n = 16) from June 1996 to July 1999. The two groups were similar with respect to baseline characteristics and risk stratification. Patients who required only one or two grafts for complete revascularization were included. RESULTS: Lateral MIDCAB patients had a lower need than on-pump CABG patients for intraoperative (12% MIDCAB vs 43% on-pump CABG, p = 0.03) and postoperative transfusions (29% vs 69%, p = 0.01), had fewer neuropsychologic changes (0% vs 19%, p = 0.03), and had a lower rate of postoperative atrial fibrillation (12% vs 44%, p = 0.02). Lateral MIDCAB was also associated with a significantly lower postoperative length of stay (5 +/- 2 vs 7 +/- 3 days, p = 0.02). Actuarial survival at a mean period of follow-up of 19 +/- 11 months was 97% for the lateral MIDCAB versus 88% for the on-pump CABG group (p = 0.6). Event-free survival was 88% for lateral MIDCAB versus 81% for on-pump CABG (p = 0.1). CONCLUSIONS: Lateral MIDCAB may safely be performed in patients with isolated coronary artery disease of the circumflex system with improved early morbidity and an abbreviated hospital stay compared with conventional median sternotomy on-pump CABG.

Aged↗
PubMed2000

Beating heart surgery in octogenarians: perioperative outcome and comparison with younger age groups.

BACKGROUND: Octogenarians have higher morbidity and mortality rates (9% to 16%) after coronary artery bypass grafting with cardiopulmonary bypass, compared with younger patients. METHODS: We compared the perioperative outcome and hospital stay after coronary artery bypass grafting without cardiopulmonary bypass (off-pump) from January 1987 to May 1999, among patients older than 80 years (n = 71), patients between 70 and 79 years (n = 228), and patients whose age ranged from 60 to 69 years (n = 296). In comparison with younger patients, more octogenarians were female (51% versus 39% in patients aged 70 to 79 years and 35% in those aged 60 to 69 years, p = 0.04), they had previous myocardial infarction more frequently (48% versus 47% versus 34%, respectively, p = 0.008), and were operated on urgently (69% versus 56% versus 52%, respectively, p = 0.04). RESULTS: Postoperative complications that were significantly higher in octogenarians compared with younger groups included pneumonia (6% in octogenarians versus 2% in patients aged 70 to 79 years and 0% in patients aged 60 to 69 years, p = 0.001) and atrial fibrillation (47% versus 32% versus 21%, respectively, p<0.001). By multivariate logistic regression analysis, age over 80 years was an independent predictor of prolonged hospital stay (odds ratio = 2.7, 95% confidence interval, 1.4 to 5, p<0.001). The in-hospital mortality rate was higher in octogenarians (6% versus 3% for 70 to 79 year-olds and 0.3% for 60 to 69 year-olds, p = 0.006). CONCLUSIONS: When appropriately applied in patients older than 80 years, off-pump coronary artery bypass grafting can be done with acceptable postoperative morbidity, mortality, and hospital stay.

Age Factors↗
PubMed2000

Clinicopathological characteristics of breast carcinomas with allelic loss in the p73 region.

p73, a new member of the p53 family, has been mapped to chromosome 1p 36, a region where loss of heterozygosity (LOH) is frequently observed in primary human tumors. Allelic loss studies involving the 1p arm in breast carcinomas offer rates ranging from 13% to 75%, depending on the genetic interval being studied. We investigated LOH in an intragenic microsatellite marker, and those centromerically flanking the p73 gene, at 1p 36, and their correlations with patient age and 10 pathologic parameters in a series of 193 breast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, using the five markers of the 1p 36 region (p73P1, D1S2694, D1S214, D1S2666 and D1S450). LOH was found in at least one of these markers in 27% of tumors. When we established the comparison between tumors with and without LOH and the distribution of the 10 pathologic parameters considered, we observed statistically significant differences in association with higher histologic grade (p = 0.02), more advanced pathological stage (p = 0.02), peritumoral vessel involvement (p = 0.04) and poorly differentiated carcinomas (p = 0.01), as well as in tumors that concomitantly exhibited lymph node metastases, peritumoral vessel involvement and absence of steroid receptors (p = 0.02). These data suggest that LOH in the p73 region could be pathogenically related to breast cancer and possibly to a poor tumor prognosis.

Adult↗
PubMed2000

Microsatellite alterations and TP53 mutations in plasma DNA of small-cell lung cancer patients: follow-up study and prognostic significance.

BACKGROUND: Small-cell lung cancer (SCLC), one of the major types of lung cancer, is associated with many different somatic molecular genetic changes. These alterations, observed in tumor DNA, have also been identified in the plasma DNA of patients. We undertook the present study to make a prospective investigation into the correlation between abnormal plasma DNA and patient survival. PATIENTS AND METHODS: Thirty-five patients with SCLC were selected after histological diagnosis. Polymorphic markers (ACTBP2, UT762 and AR) were chosen for their reported high rate of alterations in SCLC and analyzed in tumor tissue, normal blood cells and plasma DNA. Furthermore, we looked for mutations of the TP53 gene in tumor and plasma DNA. RESULTS: In 25 patients (71%) at least one molecular change precisely matching that of the primary tumor was detected in the plasma DNA. No difference in survival was observed between patients with aberrant plasma DNA and patients without plasma DNA alterations. However, patients with microsatellite modifications and TP53 mutations concomitantly, showed a significant difference (P = 0.02) in survival compared with patients bearing only one of these molecular changes. In 15 cases it was possible to find a correlation either between tumor response and disappearance of abnormal plasma DNA, or tumor progression and persistence of plasma DNA alterations. CONCLUSIONS: Free plasma DNA with molecular alterations is present to a high degree in plasma DNA of SCLC patients and may have a role as a prognostic factor.

Adult↗
PubMed2000

An unusual form of persistent polyclonal B lymphocytosis in an infant.

We report a case of persistent polyclonal lymphocytosis in an infant. The circulating lymphocytes were of a small to medium size and a small proportion were larger and had lymphoplasmacytoid features. The presence of either an infectious or mutagenic agent was excluded. The polyclonal B-cell nature of the lymphocyte was demonstrated by immunological markers and confirmed by Southern blot analysis and by polymerase chain reaction targeting immunoglobulin genes. In contrast to the common form of polyclonal lymphocytosis, this case was not associated with HLA-DR7 and/or abnormalities of chromosome 3, p53 or Bcl2/IgH. Whether this lymphocytosis represents a premalignant or a benign condition remains uncertain, although there has been no progression to date.

B-Lymphocytes↗
PubMed2000

Mutational status of K-ras and TP53 genes in primary sarcomas of the heart.

We investigated three patients with cardiac angiosarcomas and two with cardiac rhabdomyosarcomas, all for mutations at exons 5, 6, 7 and 8 of the p53 gene and at exon 1 of K-ras. No point mutations were observed in the p53 gene in any of the five cases; however, at exon 1 of K-ras, three patients (60%) presented the same mutation at the first base of codon 13 (G to A transition). Interestingly, this mutation was detected in both rhabdomyosarcoma and angiosarcoma histologic sarcoma types.

Adult↗
PubMed2000

Minimally invasive coronary revascularization in women: A safe approach for a high-risk group.

PURPOSE: Female gender has been shown to be an independent risk factor for mortality in coronary artery bypass graft (CABG) surgery. This report analyzes our early outcomes in 304 women who underwent off-pump coronary artery bypass (OPCAB) surgery at the Washington Hospital Center (Washington, DC) over the last 3 years to determine whether this is a safe approach for coronary bypass in women. METHODS: A retrospective review of 5528 cases of CABG bypass (on-pump) and 840 cases of OPCAB surgery, from June 1996 to July 1999, was performed. Women accounted for 1527 (27.6%) of the on-pump bypass cases and 304 (36.2%) of the OPCABs. All cases without cardiopulmonary bypass were included, with the majority of the most recent cases being multivessel revascularization. The data for analysis were obtained from our cardiac surgery database and included cases from all surgeons operating at the Washington Hospital Center, although the majority of off-pump cases were performed by only a few of these surgeons. RESULTS: The two groups were similar with respect to urgent cases, redos, and other comorbities including preoperative congestive heart failure, peripheral vascular disease, transient ischemic attack (TIA), cerebral vascular accident, and previous myocardial infarction. The mean age for the two groups was similar, 67 years for the off-pump group and 66 years for the on-pump group. The absolute number of all off-pump cases increased each year (from 175 to a total of 373), representing a corresponding increase in percentage of all coronary artery bypass procedures (from 9% to 16%). Of the total number of patients undergoing CABG, the percentage of women who underwent OPCAB doubled from 3% to 6% over the time period analyzed. The percentage of single-vessel cases in the off-pump group fell from 88% to 41% as multivessel bypasses became more routine However, the percentage of patients aged > 75 years was greater for the off-pump group (30%) than for the on-pump group (24%). Otherwise, the two groups differed only in diabetic disease (36% off-pump compared with 46% on-pump; p = 0.001) and previous transcatheter therapy (38% off-pump compared with 29% on-pump; p = 0.003). Patients who had OPCABs received fewer postoperative transfusions (40%) than the on-pump group (59%; p < 0.001). The off-pump group also had fewer neurological complications in the form of TIAs or strokes (0.3%) compared with the on-pump group (3.5%; p = 0.001). The mortality rate was 2.3% off -pump versus 4.1% on pump but did not reach statistical significance in this study (p =.12). CONCLUSION: Myocardial revascularization in women can be performed safely without cardiopulmonary bypass. In our series, the mortality for women receiving off-pump revascularization was lower than the on-pump cohorts despite an older age and higher incidence of diabetes. Although the absolute mortality rates did not reach statistical significance, we were encouraged that the mortality rate for women operated on without CPB dropped to the mortality rate typically seen in men. We also observed a favorable tendency in the off-pump group for a shorter length of stay and a lower incidences of transient ischemic attacks, strokes, post-op bleeding, and blood transfusions. A larger series of patients with multivariate analysis and/or a prospective trial will need to be analyzed in order to confirm our findings.

Aged↗
PubMed2000

Determinants of in-hospital mortality in women with acute myocardial infarction who underwent primary coronary angioplasty.

INTRODUCTION: According to recent data, women have a greater risk of dying from an acute coronary event. The determinants of this ominous prognosis are not completely understood. Preliminary analysis of our data suggested that this poorer prognosis is also observed in the subgroup of patients with acute myocardial infarction submitted to direct coronary angioplasty (PTCA). This finding prompted us to investigate gender differences and their determinants in this particular context. OBJECTIVE: To identify risk factors associated with the greater in-hospital mortality of women with acute infarction who underwent PTCA. METHODS: One hundred and forty-five consecutive patients with acute myocardial infarction who underwent direct PTCA in the same hospital were studied retrospectively. Data were collected from the database of the catheterisation laboratory and from clinical files. The following parameters were analysed: in-hospital mortality, age, prevalence of diabetes mellitus, history of coronary heart disease, time elapsed from beginning of symptoms to coronary intervention, peak values of CK and MB-CK, number of coronary arteries with significant disease at angiography, culprit lesion localisation, and prevalence of shock on admission. For statistical analysis, cross-tabulation (Pearson x2) and comparison of means (Student's t test) were employed when appropriate; an error of 5% was admitted for the rejection of the null hypothesis. RESULTS: Women (n = 39) represented 26.9% of sample. In hospital mortality was 28.2% (n = 11) for women and 11.3% (n = 12) for men (p = 0.014). The prevalence of coronary heart disease before the current acute event, the time elapsed from beginning of symptoms to coronary intervention, and maximum values of CK and MB-CK were similar in both genders. Differences between women and men were found as regards the following variables (women vs men): age (61.7 +/- 10 vs 56.1 +/- 12.6 years), prevalence of left main disease (15.3 vs 1.9%) and prevalence of shock (41 vs 17%) and diabetes (38.7 vs 13.6%). Considering women and men who died, only disease severity as evaluated by the number of vessels involved distinguished both genders (p = 0.05). CONCLUSIONS: In our experience, women admitted with acute myocardial infarction and treated by direct PTCA are, on average, older than men and have a greater prevalence of shock at admission, of left main disease and of diabetes, and more severe coronary artery disease. In the present series and as regard in-hospital mortality, disease severity as evaluated by the number of vessels involved is the only variable that discriminates women from men.

Age Factors↗
PubMed1999

Diagnosis of Helicobacter pylori infection with a new non-invasive antigen-based assay. HpSA European study group.

BACKGROUND: Helicobacter pylori is a common human pathogen implicated in certain gastrointestinal diseases. In the search for new non-invasive techniques to diagnose H. pylori infection, we evaluated an EIA for H. pylori antigen in stool (HpSA). METHODS: In a prospective multicentre study, stool specimens from 501 patients (276 men, 225 women; age range 17-88 years, mean 52) undergoing gastroscopy in 11 centres throughout Europe were tested with HpSA and the carbon-13-urea breath test. At endoscopy, four biopsy samples were taken for histology (haematoxylin and eosin) and H. pylori detection (giemsa in both antrum and corpus, culture and rapid urease test). Patients were defined as positive for H. pylori if histology (antrum, corpus, or both) and urease test were positive, or if culture was positive. Patients classified as having H. pylori infection received an eradication regimen; 107 were reassessed 4 weeks after therapy. FINDINGS: Of 272 patients with H. pylori infection by the predefined criteria, 256 were positive by HpSA (sensitivity 94.1% [95% CI 90.6-96.6]). Of 219 patients without infection, 201 were negative by HpSA (specificity 91.8% [87.3-95.1]). INTERPRETATION: The stool assay was a reliable and easy-to-use tool for diagnosis of H. pylori infection. The test was accurate even shortly after treatment.

Adolescent↗