[Aortitis by Aspergillus spp. in an immunocompetent patient].
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Aged↗
Biomedical subjects
R Molina
Publications and source records attributed to R Molina.
Prognostic significance of CA 125 and TPS levels after chemotherapy in ovarian cancer patients.
The analysis of survival data of patients with epithelial ovarian cancer proved that both CA 125 and TPS were good markers for clinical outcome prediction. Patients receiving chemotherapy were analyzed for 2-year overall survival (OS). Kaplan-Meier survival analysis showed highly significant differences in OS between patients with stage I+II (survival for 2 years 68%) and stage III+IV (survival for 2 years 33%; p = 0.0008). CA 125 levels above or below 35 kU/I and TPS levels above or below 80 U/l after 3 chemotherapy courses were not significantly correlated with OS in stage I+II patients (p = 0.06 respectively 0.07). However, in the subgroup of patients with stage III+IV the cut-off levels of CA 125 and TPS were excellent discriminators of OS: With CA 125 levels below the cut-off 52% of the patients survived, while with CA 125 levels above the cut-off only 13% survived (p < 0.0001). With TPS levels below the cut-off 49% of the patients survived, while with levels above the cut-off only 19% of the patients survived (p < 0.0001). In the subset of patients with CA 125 levels less than 35 kU/I after 3 chemotherapy courses (n = 50) analysis of their TPS levels allowed further discrimination of the prognostic significance. With TPS levels below the cut-off 63% of the patients survived, while 35% of the patients survived with TPS levels above the cut-off. The sum value of CA 125 and TPS cut-off values (115) as discriminator correlated even better with survival rate: With levels below this sum value 63% of the patients survived, while this was only 17% with sum values above the summed cut-off level (p = 0.0004). The extent to which the tumor was removed at operation also correlated with the 2 years survival rate. None of the patients with a staging laparotomy (n = 10) showed a 2-years survival. The difference in OS between patients with complete debulking and partial debulking was significant: OS 51% versus 23% (p = 0.027). Prognosis was not significantly correlated with histological type.
Antineoplastic Combined Chemotherapy Protocols↗
C-erbB-2, CEA and CA 15.3 serum levels in the early diagnosis of recurrence of breast cancer patients.
UNLABELLED: C-erbB-2, CEA and CA 15.3 serial serum determinations were performed in 250 patients (follow-up: 1-4 years, mean 2.5 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Ninety-five patients developed metastases during follow-up. RESULTS: Abnormal c-erbB-2, CEA and CA 15.3 serum levels (> 20 U/ml, > 10 ng/ml or > 60 U/ml, respectively) prior to diagnosis were found in 28.4%, 31.6% and 46.3% of the 95 patients with recurrence, with a lead time of 4.2 +/- 2.4, 5.0 +/- 2.5 and 4.6 +/- 2.7 months, respectively. One of the tumor markers was the first sign of recurrence in 69.5% of the patients. Tumor marker specificity was 100% with levels lower than the cut-point in all 155 patients without recurrence. Tumor marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver or bone metastases. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (10/12, 83.3%) than in those without overexpression (1/34, 2.9%) (p = 0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PgR+ patients (CA 15.3) or in PgR- patients (C-erbB-2) (p < 0.015). In conclusion, tumor markers are useful tools for the early diagnosis of metastases, being the first sign of recurrence in 69.5% of patients with relapse (76.3% in patients with metastases).
Biomarkers, Tumor↗
Carcinoembryonic antigen in tissue and serum from breast cancer patients relationship with steroid receptors and clinical applications in the prognosis and early diagnosis of relapse.
From July 1982 to August 1994, CEA levels were determined in 298 mammary tissue samples (30 benign, 242 primary breast cancer and 26 metastatic breast cancer). CEA serum levels were also evaluated in 30 patients with benign diseases, 153 patients with primary breast cancer and 26 patients with metastases. CEA tissue levels in both pellet and cytosol were significantly higher in samples from cancerous than from non malignant tissues (p < 0.0001), and higher in the pellet than in the cytosol (p < 0.0001). CEA in the pellet and cytosol were related to steroid receptors, with the highest levels being observed in ER+/PR+ tumors (p < 0.001). They were, however, not related to other pathological parameters such as tumor size or nodes. There was a correlation between CEA pellet and CEA serum in both patients with primary or metastatic tumors, with significantly higher CEA serum levels in patients with CEA pellet positivity than in those with CEA pellet negativity. CEA serum levels were a prognostic factor (DFS and OS) in the whole group as well as in node-positive and node-negative breast cancer patients. This prognostic value was only found in patients with CEA pellet positivity. In the follow-up of 143 NED patients, abnormal CEA serum levels rose prior to the diagnosis of relapse in 73% (29/40) of CEA pellet+ patients with distant recurrences but in only 9% (2/22) of CEA pellet- cases (p < 0.0001). In summary, CEA evaluation in tissue improves the CEA clinical application, selecting those patients whose serum CEA will be useful in the prognosis and early diagnosis of recurrence.
Breast↗
Multicenter evaluation of the Elecsys CA 125 II assay.
The technical performance and clinical usefulness of the newly developed Elecsys CA 125 II assay (Boehringer Mannheim) was evaluated in a multicenter study. Imprecision studies were carried out using control sera and human pool sera with CA 125 concentrations from 11 to 1026 U/ml. Within-run CVs between 0.7 to 4.8% (median 1.7%) and between-day CVs between 2.4 to 10.9% (median 5.7%) were found. Method comparison studies with Enzymun-Test CA 125 II carried out in four laboratories yielded slopes between 0.94 to 1.07 and intercepts < 3 U/ml. A good comparability of the Elecsys CA 125 II assay was also found with one MEIA and the Centocor" IRMA. For a second MEIA and a second IRMA the slopes were 1.23 and 1.42, and the corresponding correlation coefficients were 0.987 and 0.977, respectively. The Elecys CA 125 II concentrations are clearly related to the tumor stage of ovarian carcinoma patients. The maximum of diagnostic efficiency of ovarian carcinoma patients compared with patients of benign gynecological diseases is reached at 150 U/ml with a specificity of 93% and a sensitivity of 69%. Follow-up studies of ovarian carcinoma patients reflect the status of the disease and the effect of various therapeutic applications. The technical and clinical evaluation of the Elecsys CA 125 II assay show a superior analytical performance with a broad measuring range up to 5000 U/ml and a short measuring time of 18 minutes.
Biomarkers, Tumor↗
Bcl-2 oncogene (B cell lymphoma/leukemia-2) levels correlate with systemic lupus erythematosus disease activity.
OBJECTIVE: Bcl-2 translocation or overexpression is found in many types of malignancy, possibly through alteration of the apoptosis mechanism. It has also been suggested that similar apoptotic alterations may be important in the pathogenesis of systemic lupus erythematosus (SLE). It is believed that a process of apoptosis at the stage of maturation or differentiation of lymphocytes may be related to the beginning of an autoimmune event, due to the non-elimination of autoreactive lymphocytes. The aim of this study is to test bcl-2 antigen expression in human SLE peripheral blood and to analyze its relationship with disease activity. MATERIALS AND METHODS: Serum levels of bcl-2 were studied by enzyme-linked immunoabsorbent assay in whole blood samples in 68 patients with SLE and its correlation with disease activity according to SLE disease activity index (SLEDAI). RESULTS: No significant differences were found in bcl-2 levels between all SLE patients and controls. We observed increased levels of bcl-2 in active SLE patients in relation to inactive (p = 0.0003) and controls (p = 0.02). Our results show a significant correlation between bcl-2 levels and SLEDAI values (R = 0.46, P < 0.001). CONCLUSIONS: These results suggest that bcl-2 levels are related to disease activity and that this protein may play a role in the pathogenesis of SLE.
Adolescent↗
Usefulness of urinary nuclear matrix protein 22 (NMP22) as a marker for transitional cell carcinoma of the bladder.
OBJECTIVES: The purpose of this study was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22, as a novel marker for urothelial cancer. PATIENTS AND METHODS: NMP22 values were determined for 71 patients and 21 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of entry into the study. Each sample was assayed for levels of NMP22. RESULTS: When the cut-off value was set at 10 U/ml, the positive rate for urinary NMP22 in bladder cancer was 37.8% (17 out of 45), whereas that in post-treatment cases and benign diseases was 30.8% (8 out of 26) compared to 14.3% (3 out of 21) for healthy volunteers. This cut-off value provided a sensitivity of 37.8% and a specificity of 80.9%. In the bladder cancer group, NMP22 levels were related to tumor size, shape, grade and stage. CONCLUSIONS: Despite the many reports that suggest NMP22 as a promising urinary marker for monitoring transitional cell carcinoma, this study does not support its usefulness as a substitute tool for urinary cytology in the control of bladder tumors.
Adult↗
[Biological basis of posttraumatic stress disorder].
The postraumatic psychobiological stress disorder (PTSD) remains unclear although it is suggested that many systems are implicated. In this article, the PTSD biological aspects are reviewed, providing an exposition of main changes which are taking place in both the hypothalamic pituitary adrenal (HPA) and sympathetic nervous system (SNS). There are also some other mechanisms which are involved into human stress response such as thyroid function, neuropeptide Y, substance P and the opiod and glutamatergic system. Finally, we remark some changes which were found in neuroimaging techniques.
Humans↗
Serum levels of CA 125 and TPS during treatment of ovarian cancer.
Two hundred and sixty ovarian cancer patients (including all FIGO stages) were enrolled in a prospective multicentre study. In this interim study we analyzed 206 patients receiving combined chemotherapy for at least 3 courses for two-year overall survival (OS). CA 125 and TPS were applied for monitoring treatment and the relationship between marker levels, marker changes and clinical assessments was established. Preoperative CA 125 or TPS levels were not correlated with OS in FIGO stage I and II patients. After 3 chemotherapy courses the marker levels were not correlated with OS in stage I and II. Partial debulking in stage II patients was a bad prognostic factor. CA 125 or TPS levels (using a CA 125 discrimination level of 25 kU/l and a TPS discrimination level of 100 U/l) after 3 courses of chemotherapy were highly significantly correlated with OS in FIGO stages III and IV patients: CA 125 two-year OS 67% versus 26% (p < 0.0001) and TPS two-year OS 55% versus 22% (p < 0.0001). The prognostic value of CA 125 levels after 3 chemotherapy courses could be further increased by combining CA 125 and TPS levels. When both CA 125 and TPS levels were below their respective discrimination levels, the two-year overall survival was 75%. When both levels were above the discrimination level, the two-year overall survival was only 17%.
Antineoplastic Agents↗
Relationship of oncogenes (sFas, Bcl-2) and cytokines (IL-10, alfa-TNF) with the activity of systemic lupus erythematosus.
BACKGROUND: Different oncogenes (Fas and bcl-2) and diverse cytokines (IL-10 and alfa-TNF) may have an effect on the regulation of apoptosis. The majority of studies to date have evaluated only one or two of these elements independently and it is difficult to obtain a global view of apoptosis disregulation in the pathogenesis of systemic lupus erythematosus (SLE) and their role in disease activity. The aim of this study was to evaluate serum levels of sFas, bcl-2, IL-10 and alfa-TNF in human SLE patients and to analyze their relationship with disease activity and with regulation of the apoptotic process. PATIENTS AND METHODS: Serum levels of sFas and cytokines IL-10 and alfa-TNF were studied by enzyme-linked immunoabsorbent assay. Bcl-2 antigen expression was analyzed in lysated lymphocytes from 51 SLE patients. The disease activity was analyzed according to the SLE disease activity index (SLEDAI). RESULTS: SLE patients had higher levels of sFas (p=0.0006) and alfa-TNF (p<0.0001) than the control group. No relationship was found between the levels of bcl-2 and IL-10 from SLE patients and the control group. However, there was a significant correlation between SLEDAI and bcl-2 (p<0.001) and IL-10 levels (p=0.004). In contrast, we found that sFas and alfa-TNF were not related with disease activity. A significant correlation of sFas with alfa-TNF serum levels (p=0.003, R= +0.41) and bcl-2 antigen expression (p=0.02, R=+0.32) was observed. CONCLUSION: sFas and alfa-TNF serum levels are increased in SLE patients. sFas levels seems to be secondary to alfa-TNF action, which is enhanced in inflammatory conditions such as SLE. Bcl-2 antigen expression and IL-10 serum levels are related to the maintenance of SLE activity. These alterations may interfere with the apoptotic process, promoting lymphocyte hyperactivity secondary to increased cytokine levels, and causing the characteristic features of SLE.
Adolescent↗
Free to complexed PSA ratio in differentiating benign prostate hyperplasia from prostate cancer.
BACKGROUND: The description of the different forms of circulating PSA has opened a new strategy in the diagnosis of prostate cancer. The aim of our study was to assess the diagnostic potential of PSA and the PSA fractions in the diagnosis of benign prostate hyperplasia (BPH) and prostate cancer. PATIENTS AND METHODS: We measured the serum levels of PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany), complexed PSA (Immuno 1 system, Bayer, Tarrytown, NY USA) and free PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany) in 178 patients with BPH and 44 patients with prostate cancer. RESULTS: ROC curves were used for comparison of the diagnostic utility of the tests assessed. The biggest areas under the curve were obtained for the ratios between free/complexed PSA and free/total PSA (0.887 and 0.872, respectively). When choosing the cut-off values to obtain a 90% sensibility, we found that the specificity for the free/total PSA ratio was 59% and for the free/complexed PSA ratio 72%. CONCLUSION: Our results suggest that replacement of the measurement of total PSA by complexed PSA in prostate cancer diagnosis may be interesting. Nevertheless, as this is a retrospective study limited to a small number of patients, it is obvious that we need more data to make a final decision with regard to this subject.
Diagnosis, Differential↗
BTA TRAK urine test increases the efficacy of cytology in the diagnosis of low-grade transitional cell carcinoma of the bladder.
BACKGROUND: Among urinary tumor markers we studied the utility of the BTA TRAK assay to diagnose transitional cell carcinoma of the bladder in highly suspiscious patients, in comparison to urine cytology. MATERIALS AND METHODS: A preliminary study of 65 patients was made (21 transitional cell carcinoma (TCC), 36 without TCC and 8 excluded patients who received BCG therapy, endocavitary mytomicin or radiotherapy), using the BTA TRAK, cytology and cystoscopy. RESULTS: 12 out of the 21 selected patients were pTa (9 G1and 3 G2), 2 carcinoma in situ (CIS), 2pT1 (1 G2 and 1 G3) and 5 muscle invasive tumors (all of them G3). Setting our cut-off at 18 U/ml, a sensitivity of 52.3% and a specificity of 88.9% was reached. BTA TRAK detected 11 out of 21 of the tumors as well as urine cytology. However, BTA TRAK was more sensitive in the detection of low grade tumors (p<0.05). When considering both tests as complementary, a combined sensitivity of 80.9% and specificity of 88.5% were obtained. CONCLUSION: BTA TRAK is a valid test for the diagnosis of TCC of the bladder, which is not superior to urine cytology but complementary. More extensive prospective studies are required to validate this application and others of the BTA TRAK assay used either alone or in combination with urinary cytology in the management of bladder cancerpatients.
Antigens, Neoplasm↗
[Sexuality in adolescents].
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Adolescent↗
Glutathione S-transferase (GSTM1 and GSTT1)-dependent risk for colorectal cancer.
BACKGROUND: The deleted GSTT1 and GSTM1 genotypes (null genotypes) resulting in loss of transferase activity are found in 10-20% and 50-60% of the population, respectively. PATIENTS AND METHODS: The GSTT1- and GSTM1-dependent risk for sporadic colorectal cancer (CRC) was studied in 247 incident CRC cases and 296 hospital-based controls. RESULTS: The GSTT1-null genotype was found to be 1.5 times more prevalent in CRC patients (17.4%) compared with controls (11.1%) (crude OR 1.6; p = 0.03). The GSTM1-null genotype was found to be equally prevalent in cases and controls (53%). Multivariate analysis showed a significant 1.7-fold risk for CRC associated with the GSTT1-null genotypes (p = 0.04) and this increased to 2.9 for smokers (p = 0.02). CONCLUSION: This study provides evidence of gene-environment interaction and illustrates the importance of further research into the role of genetic susceptibility for CRC.
Aged↗
[Enhanced suppression of cortisol after dexamethasone in borderline personality disorder. A pilot study].
INTRODUCTION: Some studies have suggested the etiological role of childhood traumatic events in borderline personality disorder (BPD), involving the stress response mechanisms and the activity of hypothalamic-pituitary adrenal (HPA) axis. Recent preliminary results show that BPD, similar to that found in post-traumatic stress disorder (PSD), might have a hypersensitive response to the dexamethasone test. METHODS: Fourteen BPD patients, diagnosed according to DSM-IV criteria, without a major depressive episode or history of bipolar or psychotic disorder, were compared with 10 patients with other personality disorders (OPD). Plasma cortisol was measured at baseline and following an oral test with 0.25 mg of dexamethasone. RESULTS: Nine out of 14 (64%) BPD patients were cortisol suppressors in the test versus only 2 out of 10 (20%) patients with other personality disorders (chi square 4.6, degree factors [df] 18, p<0.05). The degree of cortisol suppression was significantly greater for BPD patients (73% ) than for patients with other personality disorder (34 %). Baseline cortisol concentrations, although lower in BPD patients, were not significantly different among groups. CONCLUSIONS: BPD could be associated with hypersensitivity of feedback mechanisms of the HPA axis similar to PSD, which suggests a possible role for traumatic experiences in the pathogenesis of the disorder.
Administration, Oral↗
Prospective evaluation of CEA and CA 15.3 in patients with locoregional breast cancer.
The tumor markers, CEA and CA 15.3, were prospectively studied in the sera of 1057 untreated patients with locoregional breast cancer diagnosed from 1983 to 2001. Abnormal CEA and CA 15.3 serum levels were found in 13% and 18.8% of the patients, respectively. One tumor marker or another was abnormal in 22.8% of the patients. Both tumor markers were correlated with tumor size and nodal involvement, with significantly higher concentrations in patients with larger tumors or in patients with nodal involvement. CEA was also related to the histological type and CA 15.3 with the histological grade. Univariate prognostic evaluation showed that tumor size, nodal involvement, histological grade, steroid receptors, adjuvant treatment, CEA, CA 15.3 and treatment before surgery were prognostic factors in both disease-free survival (DFS) and overall survival (OS). Similar results were obtained in node-positive patients, with the same factors being prognostic, excluding adjuvant treatment and CA 15.3, in both DFS and OS. Multivariate analysis showed that tumor size, nodal involvement, histological grade, ER and CEA were independent prognostic factors in both DFS and OS in the whole group as well as in node-positive patients. In contrast, tumor size was the only useful parameter in the prognosis of node-negative patients. CA 15.3 was useful for prognosis (OS) in node-negative patients. In summary, tumor markers are useful tools in the prognostic evaluation of patients with breast cancer.
Analysis of Variance↗
Prospective evaluation of tumor markers (c-erbB-2 oncoprotein, CEA and CA 15.3) in patients with locoregional breast cancer.
Tumor markers were prospectively (CEA and CA 15.3) or retrospectively (c-erbB-2) studied in the sera of 503 untreated patients with breast cancer diagnosed from 1988 to 2001. Abnormal c-erbB-2 levels (> 15 U/ml) were found in 7%, CEA in 12% and CA 15.3 in 13% of the 503 patients. C-erbB-2 serum levels were only related to c-erbB-2 in tissue, with significantly higher concentrations in patients with positivity in tissue. All the tumor markers (c-erbB-2 only in patients with positivity in tissue) were correlated with tumor size, TNM and nodal involvement. CEA was also related to menopausal status, c-erbB-2 overexpression in tissue and ER. Univariate analysis (mean follow-up 8 years) showed that CEA and CA 15.3 were prognostic factors with significantly shorter disease-free survival (DFS) and overall survival (OS) in patients with pretreatment tumor marker positivity. Multivariate analysis in DFS and in OS showed that nodal involvement CEA and ER but not tumor size, menopausal status, histological grade, histology, CA 15.3, c-erbB-2, PgR, adjuvant treatment, p53 (345 patients) or c-erbB-2 in tissue are independent prognostic factors. In summary, tumor markers are a useful, inexpensive and reproducible tool for prognosis in breast cancer.
Adult↗
Expression of HER-2/neu oncoprotein in human breast cancer: a comparison of immunohistochemical and western blot techniques.
Three hundred and one primary breast cancers from patients with tumor infiltrated lymph nodes were analyzed for the presence of HER-2/neu oncoprotein by two procedures: Western blot (WB) and immunohistochemistry (IHC). Overexpression of this protein was found by WB in 16.6% of the tumors, and by IHC in 16.3%. Concordance between the two methods was found in 95% of tumors (286/301). In 7 cases we found HER-2/neu by IHC but not by WB, while the opposite was found in the remaining 8 patients. This discrepancy was found mainly in samples with HER-2/neu values just above the cut points and were therefore close to the sensitivity limits of the procedures used here. This study helps to define the parameters that should be considered to evaluate the immunostaining for HER-2/neu as positive (i.e., membrane staining, IHC score of 2 or more). The results obtained by both techniques were correlated with several currently used prognostic factors. Higher HER-2/neu protein expression was found in tumors lacking estrogen or progesterone receptors, in tumors with high S-phase fraction and in patients with more than 3 positive lymph nodes. In contrast, no relationship was found between overexpression of this protein and tumor size, ploidy, or age of the patient. Patients with elevated HER-2/neu expression showed a significantly worse overall survival by both methods, IHC (p = 0.05) and WB (p = 0.001). In conclusion, there is very high agreement between IHC and WB when measuring expression of HER-2/neu and both techniques showed prognostic significance.
Biomarkers, Tumor↗