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Biomedical subjects

E Sanchez

Publications and source records attributed to E Sanchez.

At least 19 recordsLinked to original sources

Autoinflammatory gene mutations in Behçet's disease.

BACKGROUND: Behçet's disease (BD) shares clinical features with well-recognised autoinflammatory disorders. In addition, mutations in genes for familial Mediterranean fever and tumour necrosis factor receptor-associated periodic syndrome have been reported to have increased in patients with BD. PATIENTS AND METHODS: DNA samples from 97 patients with BD and 51 matched healthy controls were analysed for the mevalonate kinase (MVK), cold-induced autoinflammatory syndrome 1 (CIAS1) and proline/serine/threonine phosphatase-interacting protein 1 (PSTPIP1) genes, responsible for mevalonate kinase deficiency (MKD), cryopyrin associated periodic syndromes (CAPS) and pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome, respectively. Over 90% of known mutations were screened using restriction fragment length polymorphism analysis and/or sequencing. RESULTS: Two patients had paired mutations in the MVK gene (genotypes V377I/V377I and V377I/S135L) and displayed typical features of BD and MKD. Another was heterozygotic for the V377I genotype. The V198M mutation in the CIAS1 gene was identified in one patient with typical BD but no symptoms of CAPS. No mutations were identified in the control group. PSTPIP1 analysis revealed a new exon 10 insertion variant (c.741+33_741+34insGT) in 2 of 97 patients and in 1 of 51 controls (p>0.05), indicating that it is a polymorphism rather than a true mutation. DISCUSSION: This study could not demonstrate any significant increases in MVK, CIAS1 or PSTPIP1 mutations in patients with BD as compared with controls.

Adaptor Proteins, Signal Transducing↗

Radio-frequency ablation of hepatocellular carcinoma before liver transplantation: a histologic and 'TUNEL' study.

BACKGROUND: Radio-frequency ablation (RFA) is an increasingly used treatment modality for hepatocellular carcinoma (HCC) in patients awaiting liver transplantation (OLTX). The current study evaluates the effectiveness of RFA in this setting based on evaluation of total cell death in explanted native livers. DESIGN: We evaluated 36 tumors from 35 patients with RFA-treated HCC who underwent OLTX at our center between 1998 and 2002. Native livers from OLTX were extensively sampled for histologic evaluation. For each HCC, an estimate ratio of necrotic tumor areas was calculated based on hematoxylin and eosin (H&E) sections. In tumors with 10% or more residual viable areas, Tdt-mediated UTP nick-end labeling (TUNEL) was further performed to assess apoptosis in the morphologically 'viable' areas. A final 'tumor cell death' (TCD) ratio was recalculated for each HCC to include areas of apoptosis identified by TUNEL. RESULTS: Based on H&E evaluation, 22/36 (61.1%) HCC revealed > or = 90% necrosis including 12/36 HCC (33.3%) showing no evidence of residual viable tumor. The overall median tumor necrosis was 79%. When TUNEL findings were added, 26/36 (72.2%) HCC revealed > or = 90% TCD including 14/36 HCC (38.8%) showing complete TCD (median TCD of 88.4%). None of our patients died of HCC while awaiting OLTX. Longer RFA-to-transplant time appears to be associated with a higher TCD rate (median of 154.5 days in patients with less than 90% TCD vs 326 days for patients with > or = 90% TCD; P = 0.019). There was no significant correlation between tumor grade or pre-RFA size of the tumors and TCD rate in RFA-treated HCC (P = 0.11). CONCLUSION: Extensive TCD (88.4% median) can be obtained using RFA for HCC in patients awaiting OLTX. Our TUNEL findings suggest that RFA-induced cell injury could be associated with apoptosis.

Adult↗

Randomized phase III trials of adjuvant FAMTX or FEMTX compared with surgery alone in resected gastric cancer. A combined analysis of the EORTC GI Group and the ICCG.

BACKGROUND: In patients who underwent radical resection for gastric cancer, we investigate the relative efficacy of combined 5-fluorouracil+adriamycin or epirubicin and methotrexate with leucovorin rescue (FAMTX or FEMTX) compared with a control arm. PATIENTS AND METHODS: This report is a prospective combined analysis of two randomized clinical trials conducted on patients who underwent radical resection for histologically proven adenocarcinoma of the stomach or esophago-gastric junction. Three hundred and ninety-seven untreated patients, 206 from 23 European Organization for Research and Treatment of Cancer (EORTC) institutions and 191 from 16 International Collaborative Cancer Group (ICCG) institutions, were randomized. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and the treatments were compared for these end-points by means of the log-rank test, retrospectively stratified by trial. RESULTS: In a planned combined analysis of the two trials, no significant differences were found between the treatment and control arms for either DFS (hazards ratio: 0.98, P=0.87) or OS (hazards ratio: 0.98, P=0.86). The 5-year OS was 43% in the treatment arm and 44% in the control arm and the 5-year DFS was 41% and 42%, respectively. CONCLUSION: Neither FAMTX nor FEMTX can be advocated as adjuvant treatment in patients who undergo resection for gastric cancer.

Adenocarcinoma↗

Inducible but not endothelial nitric oxide synthase polymorphism is associated with susceptibility to rheumatoid arthritis in northwest Spain.

OBJECTIVE: To assess the influence of inducible and endothelial nitric oxide synthase (iNOS and eNOS) polymorphisms in susceptibility to rheumatoid arthritis (RA). METHODS: Two hundred RA patients fulfilling the 1987 American College of Rheumatology classification criteria followed at the out-patient rheumatology clinic of the Hospital Xeral-Calde (Lugo, Spain) and 251 ethnically matched controls were studied. Patients and controls were genotyped by PCR-based techniques for a multiallelic (CCTTT)(n) repeat in the promoter region of the iNOS gene and for a T/C polymorphism at position -786 in the promoter region and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the eNOS gene. RESULTS: No significant difference in allele or genotype frequencies for either polymorphism in the eNOS gene was observed between RA patients and controls. The overall iNOS CCTTT(n) allelic or genotypic distribution did not show statistical significant differences between RA patients and controls. Interestingly, when we stratified the iNOS alleles into short (8-11) and long (12-16) repeats, significant differences were observed between RA patients and controls (P = 0.021; odds ratio = 1.37, 95% confidence interval 1.04-1.81). Of note, individuals carrying two alleles with a repeat number less than 12 (fewer than 196 base pairs) exhibited a double risk of developing RA (P = 0.005, odds ratio 2.26, 95% confidence interval 1.25-4.08). CONCLUSIONS: Significant differences in the iNOS promoter polymorphism genotype frequency between northwest Spanish RA patients and controls suggest a potential role for this polymorphism in susceptibility to RA.

Arthritis, Rheumatoid↗

Synthesis of quinolinyl chalcones and evaluation of their antimalarial activity.

Quinolinyl chalcones were synthesized and evaluated for their inhibition of the Plasmodium falciparum cystein protease falcipain and their activity against cultured P. falciparum parasites. They were also tested for in vivo efficacy in a rodent P. berghei model. Their activity against falcipain and as antimalarials was moderate, but antimalarial activity was probably not due to the inhibition of falcipain and may follow a different mechanism. 1-(2,4-Dichlorophenyl)-3-[3-(2-chloro-6,7-dimethoxiquinolinyl)]-2-propen-1-one 3j was the most promising compound among those here reported (IC50 19.0 microM).

Animals↗

Five-year results of deep sclerectomy with collagen implant.

PURPOSE: To study prospectively the success rate and complications of deep sclerectomy with collagen implant (DSCI), a nonpenetrating filtration procedure. SETTING: Glaucoma Unit, Department of Ophthalmology, Hôpital Ophtalmique Jules Gonin, University of Lausanne, Lausanne, Switzerland. METHODS: This nonrandomized prospective trial comprised 105 eyes of 105 patients with medically uncontrolled primary or secondary open-angle glaucoma. Visual acuity, intraocular pressure (IOP), and slitlamp examinations were performed before and after surgery at 1 and 7 days and 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, 54, 60, and 66 months. Visual field examinations were repeated every 6 months. A qualified success was defined as IOP below 21 mm Hg with or without medication. A complete success was defined as IOP lower than 21 mm Hg without medication. RESULTS: The mean follow-up was 43.2 months +/- 14.3 (SD). The mean IOP was 26.8 +/- 7 mm Hg preoperatively, 5.1 +/- 3 mm Hg 1 day postoperatively, and 11.8 +/- 3 mm Hg 60 months postoperatively. At 60 months, the qualified success rate was 94.8% and the complete success rate, 61.9%. The IOP was lower than 21 mm Hg with medication in 32.1% of patients at 60 months; 48 patients (45.7%) had an IOP of 15 mm Hg or lower without medication. No patient developed a shallow or flat anterior chamber, endophthalmitis, or surgery-induced cataract. However, 23 (21.9%) had progression of a preexisting senile cataract. Injections of 5-fluorouracil were given to 25 patients (23.8%) who had DSCI to salvage encysted blebs. The mean number of medications per patient was reduced from 2.30 +/- 0.76 to 0.49 +/- 0.72. CONCLUSION: Deep sclerectomy with collagen implant provided reasonable IOP over a long-term follow-up with few immediate postoperative complications.

Aged↗

Protein intake, control of serum phosphorus, and relatively low levels of parathyroid hormone in elderly hemodialysis patients.

In maintenance hemodialysis (MHD) patients, advanced age is a factor associated with relative hypoparathyroidism and an adynamic bone. However, the underlying mechanism remains elusive. The aim of the present study was to analyze whether the observed spontaneous decrease in protein intake in the elderly favors a better control of serum phosphorus (P) and parathyroid hormone (PTH) levels. A cross-sectional study including 207 MHD patients (mean age, 60 +/- 14; 59% males; time on dialysis, 61 +/- 55 months) dialyzed 3.5 to 4.5 hours 3 times a week using bicarbonate hemodialysis from 6 Spanish hemodialysis centers was performed. In 95 patients, the nutrient intake was recorded over a 5-day period, and average daily ingestion of nutrients was calculated using a computerized diet analysis system. One-way analysis of variance showed that serum phosphorus and intact PTH decreased with age. In addition, patients with serum phosphorus lower than 4 mg/dL as compared with those with serum phosphorus greater than 4 mg/dL were older (68 +/- 9 v 58 +/- 15 years, P < 0.001), had a lower protein (0.86 +/- 0.3 v 1.05 +/- 0.4 g/kg body weight, P < 0.01) and caloric intake (21.9 +/- 7.4 v 25.7 +/- 8.3 kcal/Kg body weight, P < 0.01), and had lower PTH levels (102 +/- 155 v 290 +/- 345 pg/mL, P < 0.001). An inverse and significant correlation was observed between age and protein intake (r = -0.48; P < 0.01), caloric intake (r = -0.37, P < 0.01), serum phosphorus concentration (r = -0.40; P < 0.01), and PTH levels (r = -0.26; P < 0.01). Additionally, a significant positive correlation was found between serum phosphorus and PTH levels (r = 0.40; P < 0.01). The results obtained in the present study suggest that a lower serum phosphorus level due to spontaneous reduction of protein intake might contribute to the relative low PTH levels observed in elderly hemodialysis patients.

Age Factors↗

Nifedipine-activated Ca(2+) permeability in newborn rat cortical collecting duct cells in primary culture.

To characterize Ca(2+) transport in newborn rat cortical collecting duct (CCD) cells, we used nifedipine, which in adult rat distal tubules inhibits the intracellular Ca(2+) concentration ([Ca(2+)](i)) increase in response to hormonal activation. We found that the dihydropyridine (DHP) nifedipine (20 microM) produced an increase in [Ca(2+)](i) from 87.6 +/- 3.3 nM to 389.9 +/- 29.0 nM in 65% of the cells. Similar effects of other DHP (BAY K 8644, isradipine) were also observed. Conversely, DHPs did not induce any increase in [Ca(2+)](i) in cells obtained from proximal convoluted tubule. In CCD cells, neither verapamil nor diltiazem induced any rise in [Ca(2+)](i). Experiments in the presence of EGTA showed that external Ca(2+) was required for the nifedipine effect, while lanthanum (20 microM), gadolinium (100 microM), and diltiazem (20 microM) inhibited the effect. Experiments done in the presence of valinomycin resulted in the same nifedipine effect, showing that K(+) channels were not involved in the nifedipine-induced [Ca(2+)](i) rise. H(2)O(2) also triggered [Ca(2+)](i) rise. However, nifedipine-induced [Ca(2+)](i) increase was not affected by protamine. In conclusion, the present results indicate that 1) primary cultures of cells from terminal nephron of newborn rats are a useful tool for investigating Ca(2+) transport mechanisms during growth, and 2) newborn rat CCD cells in primary culture exhibit a new apical nifedipine-activated Ca(2+) channel of capacitive type (either transient receptor potential or leak channel).

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Occurrence of serious adverse effects in patients receiving community-based therapy for multidrug-resistant tuberculosis.

SETTING: A community-based treatment program for multidrug-resistant tuberculosis (MDR-TB) in an urban shantytown of Lima, Peru. OBJECTIVES: To ascertain the occurrence of serious adverse effects associated with therapy for MDR-TB in northern Lima, Peru, where therapy was individualized according to drug-susceptibility testing of patients' infecting strains and delivered through a community-based program. DESIGN: A retrospective record review of 60 patients who had received individualized therapy for MDR-TB between September 1996 and October 1998. RESULTS: Although adverse effects were common, they occurred less frequently than previously reported in the literature and were rarely life-threatening. Effects occurring most frequently in this population included: mild gastritis (100%), dermatological effects (43.3%), peripheral neuropathy (16.7%), depression (18.3%), and anxiety (11.7%). These effects never resulted in the discontinuation of anti-tuberculosis therapy, and only occasionally resulted in the suspension of an agent (11.7%). CONCLUSION: In young patients with little comorbid disease, multidrug, long-course regimens rarely caused life-threatening adverse effects. Common side effects may be managed successfully on an out-patient basis through a community-based treatment program in conjunction with MDR-TB experts, even in resource-poor settings. The very low rate of default in this cohort offers hope that strategies to manage the adverse effects may reduce the incidence of abandonment of therapy and increase rates of cure.

Adolescent↗

In search of the elusive zonal flow using cross-bicoherence analysis

We show that the modulational instability growth rate of zonal flows is determined directly from the quasilinear wave kinetic equation. We also demonstrate the relation between zonal-flow growth and the cross bispectrum of the high-frequency drift-wave-driven Reynolds stress and the low-frequency plasma potential by explicit calculation. Experimental measurements of the spatiotemporal evolution of the spectrum integrated bicoherence at the L-->H transition near the edge shear layer indicate a modification in the nonlinear phase coupling, which might be linked to the generation of sheared ExB flows.

Journal Article↗

The Spanish National Reference Database for Ionizing Radiations (BANDRRI)

The Spanish National Reference Database for Ionizing Radiations (BANDRRI) is being implemented by a reasearch team in the frame of a joint project between CIEMAT (Unidad de Metrologia de Radiaciones Ionizantes and Direccion de Informatica) and the Universidad Nacional de Educacion a Distancia (UNED, Departamento de Mecanica y Departamento de Fisica de Materiales). This paper presents the main objectives of BANDRRI, its dynamic and relational data base structure, interactive Web accessibility and its main radionuclide-related contents at this moment.

Journal Article↗

Microbial study of farmhouse ewe cheese during storage in olive oil.

The effect of storing farmhouse ewe cheese in oil and in vacuo over long periods of time on physicochemical properties (water activity and pH) and the microbiota of the cheese was investigated. The storage conditions were found to scarcely influence the sample pH. Also, the initial water activity (a(w) = 0.961) and its value after 9 months of storage (0.927) were both very similar to those for naturally ripened cheese. The incidence of pathogenic microbial groups was found to decrease with storage time (counts fell below 1 log CFU/g). The flora that effects proteolytic changes in cheese consisted of lactic microorganisms (viz. lactococci and lactobacilli), in addition, after 6 months of storage, of enterococci. The last are responsible for the formation of large amounts of soluble nitrogen (SN), non-protein nitrogen (NPN) and aminoacid nitrogen (NH2-N), which provide this type of cheese with very special sensory features while preventing dehydration and thus lengthening its shelf life.

Animals↗

Multiple hereditary infundibulocystic basal cell carcinomas: a genodermatosis different from nevoid basal cell carcinoma syndrome.

BACKGROUND: Infundibulocystic basal cell carcinoma is a recently described distinctive clinicopathologic variant of basal cell carcinoma. Histopathologic differential diagnosis among infundibulocystic basal cell carcinoma, trichoepithelioma, and basaloid follicular hamartoma has generated controversy in the literature. OBSERVATIONS: Members of 2 families with multiple infundibulocystic basal cell carcinomas are described. Each patient showed multiple papular lesions, mostly located on the face. No patient showed palmar pits or jaw cysts. Forty-two cutaneous lesions from 5 patients were studied histopathologically. Thirty-nine lesions were infundibulocystic basal cell carcinomas. This clinicopathologic variant of basal cell carcinoma consists of a relatively well-circumscribed basaloid neoplasm composed of buds and cords of neoplastic cells arranged in anastomosing fashion and with scant stroma. Some of the neoplastic cords contain tiny infundibular cysts filled by cornified cells with abundant melanin. Linkage analysis in family 2 was performed using polymorphic markers (D9S196, D9S280, D9S287, and D9S180), and the affected members shared the same haplotype. Loss of heterozygosity analysis was performed in 2 affected members of this family from whom tumoral DNA was available, and although these individuals were constitutively heterozygous for D9S196, they did not show loss of heterozygosity for this marker in their neoplasms. CONCLUSIONS: Multiple hereditary infundibulocystic basal cell carcinomas represent a distinctive genodermatosis different from multiple hereditary trichoepitheliomas and nevoid basal cell carcinoma syndrome. We propose clinical and histopathologic criteria to distinguish infundibulocystic basal cell carcinoma from trichoepithelioma, basaloid follicular hamartoma, and folliculocentric basaloid proliferation.

Adult↗

Variceal ligation compared with endoscopic sclerotherapy for variceal hemorrhage: prospective randomized trial.

BACKGROUND: To evaluate the safety and efficiency of variceal ligation compared with endoscopic sclerotherapy, 88 patients with cirrhosis with recent variceal bleeding were randomized to undergo either treatment. METHODS: Sclerotherapy was performed using ethanolamine and polidocanol injection at 1, 2, and 3 weeks and every 3 weeks thereafter. The Stiegmann-Goff device was used for variceal ligation at the same intervals. RESULTS: The rate of variceal eradication was the same for both groups, but eradication was accomplished sooner in patients undergoing variceal ligation (5.3+/-1.6 vs. 6.6+/-2.4 endoscopic sessions, p < 0.05) and with fewer complications (19 vs. 6, p < 0.005). The rate of recurrent bleeding was lower in patients treated by ligation (31% vs. 50%, p < 0.05). After eradication, variceal recurrence was more frequent in patients treated by variceal ligation at 1 and 3 years (47% and 92% vs. 23% and 55%, p < 0.01). Portal hypertensive gastropathy was significantly worse in the patients who had variceal ligation (17 patients vs. 6, p < 0.01). Survival and treatment failure were similar in both groups. CONCLUSIONS: Variceal ligation was superior to sclerotherapy in terms of the rate of recurrent bleeding and the occurrence of complications but worse with respect to recurrence of varices and the evolution of portal hypertensive gastropathy. Long-term follow-up studies are required to find out whether there are deleterious effects of variceal ligation.

Esophageal and Gastric Varices↗

Deep sclerectomy with collagen implant: medium term results.

AIMS: To study prospectively the success rate and complications of deep sclerectomy with collagen implant (DSCI), a new non-penetrating filtration procedure. METHODS: Non-randomised prospective trial involving consecutive patients. 100 eyes of 100 patients with medically uncontrolled primary and secondary open angle glaucoma. A superficial scleral flap was raised and a deep sclerectomy was performed in the scleral bed. Schlemm's canal was opened and dissection of the cornea was performed up to Descemet's membrane, at which point aqueous percolated through the remaining trabeculo-Descemet's membrane. A collagen implant was sutured radially in the scleral bed. Visual acuity, intraocular pressure (IOP) measurements, and slit lamp examinations were performed before surgery and after surgery at 1 and 7 days, and 1, 3, 6, 9, 12, 18, 24, 30, and 36 months. RESULTS: The mean follow up period was 17.8 (SD 8.7) months. The mean preoperative IOP was 27.8 (8.6) mm Hg; the mean postoperative IOP was 5.7 (4.0) at day 1, 11.2 (4.6) at month 1, 14.0 (3.5) at month 12, and 13.0 (3.8) at month 36. Complete success rate, defined as an IOP lower than 21 mm Hg without medication, was 44.6% at 36 months. Qualified success rate, defined as an IOP lower than 21 mm Hg with medication, was 97.7% at 36 months. Early postoperative complications included hyphaema in seven patients, would leak in 10 patients, and subtle choroidal detachment in 11 patients. Goniopuncture was performed in 41 of the patients, and 5-fluorouracil injections were made in 23 patients; cataract progression occurred in seven patients. When comparing the different types of open angle glaucoma, no difference was found in terms of reduction in IOP, number of patients requiring antiglaucoma medications, or success rate. CONCLUSIONS: Deep sclerectomy with collagen implant appears to provide reasonable control of IOP at medium term follow up, with few immediate postoperative complications.

Aged↗

Nd:Yag goniopuncture after deep sclerectomy with collagen implant.

BACKGROUND AND OBJECTIVE: To study the need, the safety and the success rate of Nd:Yag goniopuncture in eyes that underwent deep sclerectomy with collagen implant. PATIENTS AND METHODS: The first 100 patients that underwent deep sclerectomy with collagen implant were prospectively followed. Deep sclerectomy with collagen implant is a non-penetrating filtering surgery which allows filtration of aqueous from the anterior chamber to the subconjunctival space through a remaining trabeculo-Descemet's membrane without opening the anterior chamber. Goniopunctures with Nd:Yag laser were performed at the site of surgery when the filtration through the trabeculo-Descemet's membrane was considered to be insufficient with elevated intraocular pressure. The laser treatment was performed using a Lasag 15 gonioscopy contact lens (CGA1). Goniopunctures were performed using the free-running Q-switched mode with an energy ranging from 2 to 4 mJ. RESULTS: Of 100 patients who underwent deep sclerectomy with collagen implant, goniopunctures with Nd:Yag laser were performed in 41 patients (41%). The mean time between deep sclerectomy with collagen implant and goniopuncture was 9.9 months +/-1.2 months (+/-SE). The mean IOP before laser treatment was 22.2 mm +/-7.0 mm Hg and decreased to 12.5 mm +/-5.8 mm Hg immediately after laser treatment and remained stable for the next 2 years of follow-up. The immediate success rate of goniopuncture was 83%. Choroidal detachment occurred in two patients (5%). CONCLUSION: Nd:Yag goniopuncture is an efficient and safe treatment for low filtration through the trabeculo-Descemet's membrane after deep sclerectomy with collagen implant.

Aged↗