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Biomedical subjects

S Navarro

Publications and source records attributed to S Navarro.

At least 37 records · Page 2Linked to original sources

Treatment of oesophageal cancer with preoperative chemoradiotherapy may increase operative mortality.

AIMS: This phase II multicentric study evaluates a modified preoperative chemoradiotherapy schedule. METHODS: Patients <75 years with potentially resectable neoplasm were eligible. Treatment included an initial course of CDDP 100 mg/m2 (Day 1) and 5-FU CI 5000 mg/m2 (Days 1-5) followed by 45 Gy (Days 28-63) and 5-FU CI 5000 mg/m2 (Days 28-33), CDDP 75 mg/m2 (Day 56) and 5-FU CI 3750 mg/m2 (Days 56-61). Regional lymph nodes were irradiated. RESULTS: Nineteen patients were studied. Oesophagectomy was performed in 17. Clear margins were achieved in 16 of these. Eight patients showed a pathologic complete response (pCR). One patient died of infection during the preoperative treatment and four died due to acute surgical complications. The study was closed prematurely because of excessive mortality. Median follow-up was 19 months. Local and regional relapse occurred in one and three patients, respectively. Median time and actuarial 3-year of overall survival and progression free rates were 18.6 months and 28%, and 12.7 months and 10.4%, respectively. CONCLUSIONS: This schedule showed a high pCR, resectability and local control rate. Treatment-related mortality limits its clinical applicability, but further investigations are warranted.

Adenocarcinoma↗

Outcome of laparoscopic pancreatic surgery: endocrine and nonendocrine tumors.

Laparoscopic pancreatic surgery (LapPS) for management of benign pancreatic tumors has still not been defined. This paper evaluates the feasibility and outcome of LapPS in patients with endocrine pancreatic tumors (EPTs) and cystic neoplasms of the pancreas (CyNP). Eighteen patients with benign pancreatic tumors underwent LapPS between January 1998 and May 2001. The indications were 10 EPTs (6 sporadic insulinomas, 1 multiple insulinoma of multiple endocrine neoplasia type 1, 2 nonfunctioning tumors, 1 VIPoma) and 8 CyNPs (3 serous cystadenomas, 5 mucinous cystic neoplasms). The laparoscopic procedure was performed using four ports with patients in the half-lateral position. Laparoscopic ultrasonography (LapUS) was used in all cases. Laparoscopic enucleation (LapE) was planned in five patients and performed in four (one conversion for tumor not found during laparoscopy). Laparoscopic pancreatic resection (LapPR) with spleen salvage was planned in 13 patients and performed in 12 (one conversion for metastatic VIPoma), with splenic vessel preservation in 11 patients and short gastric vessel preservation in 1. The average operating time was 3.5 hours after enucleation, 4.0 hours after distal pancreatectomy, and 5.0 hours after subtotal pancreatectomy. Pancreatic fistula was observed in two patients after LapE and in three patients after LapPR. Splenectomy for splenic abscess was performed 1 week after surgery in a patient with short gastric vessel splenic preservation. The average hospital stay was 5 days. We concluded that LapPS is a safe method for removing EPTs and CyNPs, although the incidence of pancreatic fistulas remains high. In selected patients LapPS offers significant benefit to patients: reduced trauma to the abdominal wall, short hospital stay, and a quick postoperative recovery.

Adult↗

Laparoscopic pancreatic surgery in patients with chronic pancreatitis.

BACKGROUND: In recent years, technological advances and technical refinements to laparoscopic instruments have encouraged some surgeons to explore the application of laparoscopic methods to benign disorders of the pancreas. The aim of this report was to evaluate the feasibility and outcome of laparoscopic pancreatic surgery in patients with chronic pancreatitis. METHODS: One group of five patients with disease of nonalcoholic origin localized in the body-tail of the pancreas underwent distal pancreatectomy with preservation of the splenic vessels; a second group of six patients with symptomatic pancreatic pseudocysts (alcoholic origin in four cases and idiopathic in two cases) underwent laparoscopic transgastric drainage. For distal pancreatectomy and spleen salvage, the patient's positioning was half-lateral decubitus with the left side up. Four ports were used. A comparison was made with 41 patients with chronic, pancreatitis who underwent conventional open distal pancreatectomy. For the patients with laparoscopic distal pancreatectomy, the mean operative time was 4 h (range 3-5). RESULTS: There were no pancreatic-related complications, but one patient was reoperated for perforation of duodenal ulcer. The mean hospital stay was 6 days and the mean time to resume normal daily activities was 3 weeks. Laparoscopic pseudocyst drainage was performed in four patients via laparoscopic anterior gastrostomy and two patients via laparoscopic intraluminal cystogastrostomy. The mean operative time was 100 min (range 60-160). There was no morbidity. The mean hospital stay was 5 days, and the mean time to resume normal daily activities was 2 weeks. CONCLUSION: This study provides information about the possibilities of performing laparoscopic surgery in patients with chronic pancreatitis. Laparoscopic distal pancreatectomy with preservation of the splenic vessels and laparoscopic transgastric drainage are feasible and safe techniques. They offer obvious advantages, such as reduction of the parietal damage to the abdomen, a shorter hospital stay, and an earlier postoperative recovery than can be obtained with conventional open pancreatic resection.

Adult↗

Changes in molecular forms of prostate-specific antigen during treatment with finasteride.

OBJECTIVE: To study the influence of finasteride treatment on the molecular forms of prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Total PSA, free PSA and PSA complexed to alpha1-antichymotrypsin (PSA-alpha1ACT) were measured in plasma and serum from 40 men with BPH and a total PSA of < 20 ng/mL, using in-house and commercial immunoassays, before and during treatment with finasteride (30 men) or placebo (10 men). RESULTS: The baseline values were not significantly different between the groups, with mean (sd) total plasma PSA levels of 3.6 (4.3) and 4.8 (5.9) ng/mL in the finasteride and placebo groups, respectively. Finasteride, but not placebo, induced a significant reduction in total PSA, free PSA and PSA-alpha1ACT levels in plasma and serum (P < 0.001). However, complexed-to-total (c/t) and free-to-total (f/t) PSA ratios remained constant in both groups, both in plasma and serum, during the follow-up. CONCLUSION: The decrease in total PSA after finasteride treatment results from a proportional reduction in its two major molecular forms, free PSA and PSA-alpha1ACT, which explains why the c/t and f/tPSA ratios do not change significantly despite treatment. This suggests that routine analysis of molecular forms of PSA could improve the utility of the change in total PSA associated with finasteride for the early diagnosis of prostate cancer. It also suggests that any subsequent change in both ratios, particularly an increase in c/tPSA or a decrease in f/tPSA ratio, could be considered an early sign of neoplastic degeneration rather than a therapeutic consequence.

Aged↗

Atypical pleomorphic extraosseous ewing tumor/peripheral primitive neuroectodermal tumor with unusual phenotypic/genotypic profile.

A pleomorphic undifferentiated tumor primarily located in the retroperitoneum with a phenotype compatible with an extraosseous Ewing tumor/peripheral primitive neuroectodermal tumor (ET/pPNET) pattern and unusual molecular features is described. Immunohistochemically, HBA-71 (CD99/mic2) and several neural markers were intensively expressed together with scattered cells expressing carcinoembryonic antigen (CEA). Short-term culture showed biphasic neuroblastic and epithelioid cell populations, with the latter expressing germ cell markers (CEA, alpha-fetoprotein, and the beta-subunit of chorionic gonadotrophin). Conventional cytogenetics displayed several chromosomic rearrangements, especially a complex translocation t(17,2,22,13) (q21::q11-->q33::q12-->q13::q14). These structural abnormalities were confirmed using fluorescence in situ hybridization analysis. Molecular studies revealed EWS-FEV fusion transcripts (exon 7 of the EWS gene and exon 2 of the FEV gene). In addition, a new p53 mutation not previously reported in ET/pPNET involving exon 5 codon 138: GCC to GAC (Ala/Asp) was detected. In our case, we emphasize the presence of atypical features not only from the phenotypic point of view but also at the genetic level as well as the value of detecting such markers in the differential diagnosis with other abdominal pleomorphic tumors.

Adult↗

Outcome of high-risk neuroblastoma using a dose intensity approach: improvement in initial but not in long-term results.

BACKGROUND: Stage 4 and MYCN amplified (MNA) neuroblastoma in children have a poor prognosis. Our aim was to increase initial and long-term response in this population. PROCEDURE: High-risk children were studied according to the International Neuroblastoma Staging System, then treated with high-dose cyclophosphamide and high-dose carboplatin, followed by surgery and autologous stem cell transplant or maintenance chemotherapy. RESULTS: From June 1992 to December 1998, 83 children were admitted in the study (72 stage 4> 1 year, 5 stage 4 MNA infants, and 6 MNA stage 3 children); tumor tissue was obtained from 73, MYCN was performed in 65, being amplified in 21 (32%). Induction chemotherapy was administered in the expected time in 35% of patients. Its toxicity was mainly hematologic followed by infections, and there were 3 chemotherapy-related deaths. Delayed surgery was performed on 60 patients with complete or >90% resection in 80% of cases. Chemotherapy plus surgery produced some response in 90% of patients, 53% were in CR/VGPR; 49 children received autologous SCT, and 16 received maintenance chemotherapy for 9 months. Follow-up ranges are 1-87 months, mean 30 months. S and EFS at 4 years are 0.33 (SD 0.02). CONCLUSIONS: High-dose cyclophosphamide and high-dose carboplatin are effective in the initial treatment of neuroblastoma; combined with surgery they produce some response in most patients. Nevertheless, the CR/VGPR rate reaches only 53%. Survival time has also been prolonged but most patients relapse with metastases.

Adolescent↗

Heterogeneous lack of expression of the tumour suppressor PTEN protein in human neoplastic tissues.

PTEN, a tumour suppressor gene located at chromosome 10q23 and commonly mutated or deleted in a variety of tumours, encodes a dual-specific/phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase. We report the generation of an anti-PTEN monoclonal antibody (MAb) that recognises an epitope at the C-terminus of PTEN, and describe the heterogeneous lack of expression of the PTEN protein in human tumour tissues, as demonstrated by immunohistochemical methods. Our anti-PTEN MAb provides a useful tool for the study of PTEN protein expression in tumour samples, in the search for tumour prognostic molecular markers.

Animals↗

Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells.

Erythropoietic protoporphyria is characterized clinically by skin photosensitivity and biochemically by a ferrochelatase deficiency resulting in an excessive accumulation of photoreactive protoporphyrin in erythrocytes, plasma and other organs. The availability of the Fech(m1Pas)/Fech(m1Pas) murine model allowed us to test a gene therapy protocol to correct the porphyric phenotype. Gene therapy was performed by ex vivo transfer of human ferrochelatase cDNA with a retroviral vector to deficient hematopoietic cells, followed by re-injection of the transduced cells with or without selection in the porphyric mouse. Genetically corrected cells were separated by FACS from deficient ones by the absence of fluorescence when illuminated under ultraviolet light. Five months after transplantation, the number of fluorescent erythrocytes decreased from 61% (EPP mice) to 19% for EPP mice engrafted with low fluorescent selected BM cells. Absence of skin photosensitivity was observed in mice with less than 20% of fluorescent RBC. A partial phenotypic correction was found for animals with 20 to 40% of fluorescent RBC. In conclusion, a partial correction of bone marrow cells is sufficient to reverse the porphyric phenotype and restore normal hematopoiesis. This selection system represents a rapid and efficient procedure and an excellent alternative to the use of potentially harmful gene markers in retroviral vectors.

Animals↗

Evaluation of the impact and acceptance of a nutrition program in an HIV community clinic.

The present paper describes the evaluation of a nutrition service and research model for human immunodeficiency virus (HIV)-positive clients within a community based HIV acquired immune deficiency syndrome (AIDS) medical clinic. This program was designed to develop an effective, practical, replicable model for the delivery of nutrition services in the ambulatory HIV care setting. The objectives of evaluating the model were to define the ways that nutrition services in HIV/AIDS impacted clients, the clinic, and referral sources, and to continually refine the model by determining what services provide greatest benefit to clients, especially in view of the changing landscape of HIV therapy. Four evaluation activities completed during the study period of 5 years are described. These included a focus group and semistructured interview with clients, a semistructured interview with workers from the local network of service referral agencies and a client satisfaction survey at study "close-out." These evaluation processes confirmed or prompted programmatic modifications that improved access, confidentiality, and the relevance of specific components for clients. Providers/stakeholder's concerns were addressed through more frequent communication about clients' specific nutrition issues, clearer and easier referral and cooperation in recruiting patients. Also, the evaluation activities provided a platform for the communication of general and specific information about the program and for outreach. Although clients' and workers' priorities differed in some details of program implementation, there was strong agreement on the value of addressing nutrition concerns in HIV. Favorable feedback about the program gave impetus to continue nutrition services in the clinic after the project period ended and supports its application in other sites and settings.

Adult↗

Translocation (10;11;22)(p14;q24;q12) characterized by fluorescence in situ hybridization in a case of Ewing's tumor.

It is well recognized that the identification by classic cytogenetics of t(11;22)(q24;q12) is a useful aid in the accurate diagnosis of Ewing's sarcoma and related tumors. This translocation induces the EWS/FLI-1 fusion transcript, which can be detected by reverse transcription-polymerase chain reaction. Recent studies have also used fluorescence in situ hybridization (FISH) to demonstrate the translocation. The authors coupled classic cytogenetics and FISH on tumor cells from the original specimen, the local recurrence, and the pulmonary metastasis as well as from the xenografted tumors in a case of extraosseous Ewing's sarcoma. FISH analysis not only confirmed the cytogenetic results but also allowed the identification of a tumor-specific chromosome change, consistent with a complex translocation, t(10;11;22), as well as revealed other chromosomal rearrangements on both metaphases and interphase nuclei of each material. In addition this technique served to identify, in the interphase nuclei of the original tumor, the clone that became dominant, from the cytogenetic point of view, in the lung metastasis and in the nude mice xenografted tumors. Current results indicate that the use of FISH on metaphases and interphase nuclei is an easy and reliable approach to complement or even to substitute classic cytogenetic studies for the detection of specific chromosomal rearrangements, especially for determining complex translocations and for describing tumoral clones with different cytogenetic markers.

Bone Neoplasms↗

Immunohistochemical detection of EWS and FLI-1 proteinss in Ewing sarcoma and primitive neuroectodermal tumors: comparative analysis with CD99 (MIC-2) expression.

The molecular analysis of the t(11;22) rearrangement involving EWS/FLI-1 genes is likely to be of diagnostic value in Ewing sarcoma (ES) and primitive neuroectodermal tumors (PNET). The objective of the current study was to analyze the immunohistochemical expression of the EWS and FLI-1 proteins in a group of small round-cell tumors (SRCT) to determine their specificity and relevance in their differential diagnosis. Forty-eight cases-10 conventional ES, 4 large-cell ES, 5 PNET, 9 neuroblastomas (NB), 6 undifferentiated synovial sarcomas (SS), 5 rhabdomyosarcomas (RB), 5 non-Hodgkin lymphomas (NHL), 1 round-cell liposarcoma, and 3 mesenchymal chondrosarcomas-were analyzed. Immunocytochemistry was performed on paraffin sections after the LSAB method and antigen retrieval using ethylenediaminetetraacetic acid buffer (pH 6). Primary antibodies included FLI-1 (C-19), EWS (N-18), EWS (C-19), and CD99 (MIC-2). As expected, CD-99 expression was found in 100% of ES/PNET cases, in 2 cases of RB, 2 SS, and 1 NHL. FLI-1 protein was observed as nuclear staining in 16 cases of ES/PNET (84%) and in 4 cases of NHL, 2 NB, and 3 SS. Normal endothelial cells and lymphocytes also were positive. EWS expression (both proteins N-18 and C-19) was detected not only in 95% of ES/PNET cases but also in more than 50% of cases from the other tumoral types (4 of 9 and 7 of 9 NB, 5 of 6 and 6 of 6 SS, 3 of 5 and 5 of 5 RB, and 2 of 5 and 3 of 5 NHL, respectively). Whereas EWS expression does not appear specific for ES/PNET, analysis of FLI-1 expression together with CD-99 is a powerful marker for ES/PNET and important factors in the differential diagnosis of SRCT.

12E7 Antigen↗

Usefulness of carbohydrate-deficient transferrin and trypsin activity in the diagnosis of acute alcoholic pancreatitis.

OBJECTIVE: The aim of this study was to assess if carbohydrate-deficient transferrin (CDT) and trypsin activity differentiate acute alcoholic pancreatitis from nonalcohol-related pancreatitis, and as a secondary goal to evaluate its use in comparison to healthy controls. METHODS: Serum levels of CDT and trypsin activity were measured in frozen sera from 70 nonconsecutive patients with acute pancreatitis and in 16 healthy controls. RESULTS: Causes of pancreatitis were gallstones in 51%, chronic alcoholism in 23%, and other or unknown causes in 26% of the patients. Serum CDT was significantly higher in alcoholic pancreatitis than in the nonalcoholic disease (p < 0.0001) with a median (interquartile range) of 30.8 U/L (23.6-41.7 U/L) in chronic alcoholism, 16.7 U/L (13.05-21.1 U/L) in gallstones, 17.5 U/L (15.9-21.6 U/L) in unknown cause, 19.3 U/L (15.1-27.7 U/L) in other etiologies, and 16.1 U/L (12.1-18.8 U/L) in controls. At a cutoff over 22.5 U/L, CDT showed a sensitivity of 87.5% and a specificity of 85.2%. Serum levels of trypsin activity were significantly higher (p = 0.0007) in alcoholic pancreatitis, median 165 U/L (76-405 U/L) than in nonalcoholic pancreatitis, median 73 U/L (46.5-100.5 U/L). At a cutoff value over 152 U/L, the sensitivity of trypsin activity was 60% with a specificity of 100%. In the multivariate analysis, patient's age (< or = 44 yr), CDT (>22.5 U/L), and trypsin activity (>152 U/L) enabled correct prediction of acute alcoholic pancreatitis in 98% of the cases. CONCLUSION: Serum CDT and trypsin activity are of clinical utility in differentiating alcoholic from nonalcoholic acute pancreatitis.

Acute Disease↗

Malignant granular cell tumor of soft tissues: a study of two new cases.

We describe 2 cases of malignant granular cell tumor. A marked discrepancy exists concerning the criteria of malignancy of this rare entity, which was diagnosed in male patients aged 41 and 52 years, respectively. They presented with tumors measuring more then 3.5 cm; one arose in the dermis and subcutaneous tissue in the region of the scapula, whereas the other was situated in deeper soft tissue in the pelvis. One case, with previous diagnosis of benign granular cell tumor, presented local recurrence 2 years after the initial diagnosis. The other case presented a fascicular pattern of growth invading adjacent muscular tissue. Both neoplasms were composed of polygonal and spindle cells, showing abundant cytoplasm, vesicular nuclei with large nucleoli, high nuclear-to-cytoplasmic ratio, and pleomorphism. Immunohistochemically, the neoplastic cells of both cases were positive for vimentin, S100 protein, neuron-specific enolase (NSE), and CD68. In addition, high expression of p53 and MiB1 (Ki67) was detected. Herein, we discuss the morphologic and immunohistochemical criteria of malignancy of granular cell tumors. Int J Surg Pathol 9(3):255-259, 2001

Adult↗

Primitive neuroectodermal tumor of the uterus. A case report.

BACKGROUND: Primitive neuroectodermal tumors (PNETs) of the uterus are very rare. Even preoperative curettage specimen morphology does not permit establishing a proper histogenetic diagnosis. CASE: A 16-year-old woman was admitted to the hospital because of metrorrhagia of three months' duration. The curettage specimen was interpreted as poorly differentiated sarcoma. The patient was operated on, and a total abdominal hysterectomy with bilateral salpingo-oophorectomy with omentectomy was performed. Histologically the tumor was composed of uniform, rounded, oval and sometimes spindle shaped cells with a narrow rim of eosinophilic cytoplasm. The cells were positive for neurogenic marker protein gene product, neuron-specific enolase and Ewing's sarcoma-related HBA-71. All cells were uniformly negative for Ber EP4 monoclonal antibody recognizing an epithelium-specific surface antigen. A diagnosis of PNET was rendered. The patient received combined therapy, external radiation to the pelvis and chemotherapy. Four years later she was alive, without signs of recurrent tumor. CONCLUSION: In spite of the generally recognized aggressive behavior of PNET, it can have a long disease-free survival rate when appropriately treated.

Adolescent↗

Goodpasture antigen-binding protein, the kinase that phosphorylates the goodpasture antigen, is an alternatively spliced variant implicated in autoimmune pathogenesis.

The non-collagenous C-terminal domain of the alpha(3) chain of collagen IV is the autoantigen in Goodpasture disease, an autoimmune disorder described only in humans. Specific N-terminal phosphorylation is a biological feature unique to the human domain when compared with other homologous domains lacking immunopathogenic potential. We have recently cloned from a HeLa-derived cDNA library a novel serine/threonine kinase (Goodpasture antigen-binding protein (GPBP)) that phosphorylates the N-terminal region of the human domain (Raya, A. Revert, F, Navarro, S. and Saus J. (1999) J. Biol. Chem. 274, 12642-12649). We show here that the pre-mRNA of GPBP is alternatively spliced in human tissues and that the most common transcript found encodes GPBPDelta26, a molecular isoform devoid of a 26-residue serine-rich motif. Recombinantly expressed GPBPDelta26 exhibits lower activity than GPBP, due at least in part to a reduced ability of GPBPDelta26 to interact and to form very active high molecular weight aggregates. In human tissues, GPBP shows a more limited expression than GPBPDelta26 but displays a remarkable preference for the small vessels and for histological structures targeted by natural autoimmune responses including alveolar and glomerular basement membranes, the two main targets in Goodpasture disease. GPBP expression is, in turn, up-regulated in the striated muscle of a Goodpasture patient and in other autoimmune conditions including cutaneous lupus erythematosus, pemphigoid, and lichen planus.

Alternative Splicing↗

Comparisons of energy reserves among strains of Tribolium castaneum selected for resistance to hypoxia and hypercarbia, and the unselected strain.

The quantities of energy reserves and their utilization were examined in adults of three strains of Tribolium castaneum (Herbst) before and during exposure to two modified atmospheres. It was shown that a strain selected for resistance to high carbon dioxide (CO(2)) content (HCC) contained significantly greater triacylglycerol (TG) reserves than a strain selected for resistance to low oxygen (O(2)) concentration (LOC) and an unselected strain. During exposure to HCC (65% CO(2), 20% O(2), balance nitrogen), the major energy sources were TGs, most of which were consumed during exposure; TG utilization by the unselected strain was more rapid than that by the HCC-selected strain. During exposure to LOC (0.5% O(2), 99.5% nitrogen), TGs were also utilized, but to a lesser extent, revealing an indication of more attenuated mobilization of energy reserves. Here, too, TG utilization by the unselected strain was more rapid than by the LOC-selected strain. The function of TGs in enabling the insects to maintain their water balance during exposure was considered.Concentrations of polysaccharides and glucose were low in all strains and although they decreased during exposure to MAs, their contribution to metabolic energy supply during exposure was small.

Journal Article↗

Multiresidue method for the rapid determination of organophosphorus insecticides in grapes, must and wine.

A rapid multiresidue gas chromatographic method for determining 12 insecticides in grapes, must and wine is described. A simple on-line microextraction method for isolating frequently applied insecticides on vineyard is used. The matrix, once extracted with an acetone-dichloromethane (1:1, v/v) mixture, was filtered and concentrated. Nitrogen-phosphorus detection (NPD) and electron-capture detection (ECD) were used to identify and quantify the insecticides, the findings being confirmed using mass spectrometric detection (MSD). No clean-up was necessary for either NPD or ECD. The regression coefficients relating to linearity were at least 0.99. Recoveries from spiked grape, must and wine samples ranged from 80 to 108% and relative standard deviations were no higher than 16% in the most unfavourable case. Individual detection limits were in the range 0.02-0.1 ng. Limits of quantification varied from 0.01 to 0.05 mg kg(-1), which are below the maximum residue limits set by the legislation of the main wine-producing countries of the European Union. Only in the case of methidathion and quinalphos were the limits of quantification equivalent to the maximum residue limits (0.05 mg kg(-1)) established by Spanish and French legislation, respectively.

Insecticides↗