Low section of the rectum during laparoscopic total mesorectal excision using the Contour device. Technical report.
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Biomedical subjects
Publications and source records attributed to C Martinez.
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Director of a blood transfusion service in Concepción, Chili, Dr. Christina Martinez reports on her experience in this centre and the actions undertaken in order to find resources and supports, to guarantee the operation of the centre and to enhance voluntary blood donation.
It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n=124), lung cancer (n=116) and myeloid leukemia (n=169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P<0.001, mean CVC of 6.60, P=0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C>T (mean prediction error of 22%, P<0.001, mean CVC consistency of 7.40, P<0.037). For leukemia, a 3-loci model including RAD52-2259C>T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P<0.001) and a maximum CVC of 4.40 (P=0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.
OBJECTIVE: The aim of this study was to examine the relationship of diet with serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in women. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: The population are 2109 women who were control subjects in a case-control study of breast cancer nested in the European Prospective Investigation into Cancer and Nutrition. Control subjects were randomly chosen among risk sets consisting of female cohort members alive and free of cancer (except non-melanoma skin cancer) at the time of diagnosis of the index case. Matching criteria were age at enrolment, follow-up time, time of the day of blood collection and study centre. Diet was measured through validated questionnaires. Serum hormone concentrations were measured by enzyme-linked immunosorbent assays. The relationship between serum IGF-I, IGFBP-3, and intake of nutrients and foods was explored by linear regression in models adjusted for energy intake, age, body mass index, smoking, physical activity, centre and laboratory batch. RESULTS: Serum IGF-I levels were positively related to protein intake (P(trend)<0.001), but not related to energy, fat or carbohydrate intake. Positive relationships were observed with the intake of milk (P(trend)=0.007), calcium (P(trend)<0.001), magnesium (P(trend)=0.003), phosphorus (P(trend)<0.001), potassium (P(trend)=0.002), vitamin B6 (P(trend)=0.03), vitamin B2 (P(trend)=0.001) and inverse relationships with vegetables (P(trend)=0.02) and beta-carotene (P(trend)=0.02). IGFBP-3 was not related with most of the nutrients and foods in this study. CONCLUSIONS: In this population, circulating IGF-I is modestly related with the intake of protein and minerals, and with milk and cheese, while IGFBP-3 does not appear to be related with diet.
BACKGROUND: Laparoscopic splenectomy (LS) offers better short-term results than open surgery for the treatment of immune thrombocytopenic purpura (ITP), but long-term follow-up is required to ensure its efficacy. The remission rate after splenectomy ranges from 49 to 86% and the factors that predict a successful response to surgical management have not been clearly defined. The goal of this study was to determine the preoperative factors that predict a successful outcome following LS. METHODS: From February 1993 to December 2003, LS was consecutively performed in a series of 119 nonselected patients diagnosed with ITP (34 men and 85 women; mean age, 41 years), and clinical results were prospectively recorded. Postoperative follow-up was based on clinical records, follow-up data provided by the referring hematologist, and a phone interview with the patient and/or relative. Univariate and multivariate analyses were performed for clinical preoperative variables to identify predictive factors of success following LS. RESULTS: Over a mean period of 33 months, 103 patients (84%) were available for follow-up with a remission rate of 89% (92 patients, 77 with complete remission with platelet count > 150,000). Eleven patients did not respond to surgery (platelet count < 50,000). Mortality during follow-up was 2.5% (two cases not related to hematological pathology and one case without response to splenectomy). Preoperative clinical variables evaluated to identify predictive factors of response to surgery were sex, age, treatment (corticoids alone or associated with Ig or chemotherapy), other immune pathology, duration of disease, and preoperative platelet count. In a subgroup of 52 patients, we also evaluated the type of autoantibodies and corticoid doses required to maintain a platelet count > 50,000. Multivariate analysis showed that none of the variables evaluated could be considered as predictive factors of response to LS due to the high standard error. CONCLUSION: Long-term clinical results show that LS is a safe and effective therapy for ITP. However, a higher number of nonresponders is needed to determine which variables predict response to LS for ITP.
We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case-case-control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (OR(adj) for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (OR(adj) 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (OR(adj) 2.6 for more than 7000 lifelong hours) and BCC (OR(adj) 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (OR(adj) 2.2 for more than 6000 lifelong hours). In the case-case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma.
Pathogenic mutations in the leucine-rich repeat kinase 2 gene (LRRK2; PARK8) have been implicated in autosomal dominant, late-onset parkinsonism. The LRRK2 6055G > A (G2019S) mutation is the most common reported to date, and has been observed in a number of different European populations. So far, only the LRRK2 4321C > G (R1441G) mutation has been identified in the Spanish population. Herein we have assessed the frequency of G2019S in a referral-based series of 225 patients with Parkinson's disease (PD) from the region of Asturias, Northern Spain. The mutant allele was identified in five (2.7%) of the sporadic late-onset patients and was not present in control subjects. All carriers displayed genetic profiles consistent with the same haplotype, as previously reported for Lrrk2 G2019S-positive subjects. None of these patients presented with a family history of parkinsonism at the time of diagnosis. Thus, approximately 5% of sporadic patients with PD from the North of Spain have either Lrrk2 G2019S or R1441G substitutions.
BACKGROUND: Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) was first described by Kennedy et al. in 1990; currently, accumulated evidence shows that topical PDT is effective in the treatment of actinic keratoses, Bowen's disease and superficial basal cell carcinoma, being potentially advantageous where size, anatomical location or number of lesions limit the efficacy and/or the acceptability of conventional therapies. It involves the use of photosensitizing drugs and the administration of an appropriate light source to activate the sensitizing agent, which leads to the production of activated oxygen species for tissue destruction. The topically administered prodrug 5-ALA is converted within cells into the active photosensitizer protoporphyrin IX, via haem cycle, with preferential accumulation in tumour cells. METHODS: The authors describe their experience with topical PDT, using 20% 5-ALA and two different incoherent light sources, 'Waldman 1200 L' and 'VersaLight', in the treatment of non-melanoma skin cancer and precursor lesions. More than 100 patients were treated since 1997, with up to a 7-year follow-up period. RESULTS: Cases are illustrated and results are presented and discussed in the light of the relevant Literature. CONCLUSION: The study suggests that 5-ALA PDT is effective in the treatment of superficial skin cancer and premalignant lesions.
Our research about VIP/PACAP and the immune system goes back to 1990 when our group described the expression of VIP on lymphocytes for the first time. Since this year, using three models of disease, septic shock, rheumathoid arthritis, and Crohn's disease, we are trying to contribute with new pieces to the puzzle of immunity to approach the use of VIP/PACAP system as a therapeutic agent. In 1999 we established that the first step in the beneficial effect of the VIP/PACAP system exerts consists in its potent anti-inflammatory action. Thus, VIP and PACAP inhibit the expression and release of proinflammatory cytokines and chemokines, and enhance the production of the anti-inflammatory factors. These effects were reported both in vitro and in vivo, are mediated by the presence of PAC1, VPAC1, and VPAC2 receptors, in the three models of diseases used. The next step was that the system favors Th2 responses versus Th1 contributing to the remission of illness as rheumatoid arthritis or Crohn's disease by blocking the autoimmune component of these diseases. Because it appears that inflammatory processes requires more than blockade of a single mediator, new therapies blocking several components of both the infection- and the autoimmunity-induced inflammation cascades should be an interesting focus of attention. In this sense, at present we are trying to dissect new aspects of the potential therapeutic of the VIP/PACAP system in the control of CC and CXC chemokine and their receptors, coagulation factors, adhesion molecules, acute phase proteins, and osteoclastogenesis mediators as well as in the modulation of the expression of Toll-like receptors. Our more recent data open a hopeful door for the therapeutic use of VIP/PACAP in humans.
Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent with immunoregulatory properties, skewing the immune response to a Th2 pattern of cytokine production. Here, we studied the effect of treatment with VIP in the development of diabetes in nonobese diabetic (NOD) mice, an animal model of type 1 diabetes. Mice treated with VIP from 4 weeks of age did not develop diabetes and showed milder insulitis than nontreated mice. The protective mechanism of VIP was associated with a reduction in the circulating levels of Th1 cytokines. In the pancreas of VIP-treated animals, regulatory T cell markers predominate, as indicated by the upregulation of FoxP3 and transforming growth factor-beta (TGF-beta), and the downregulation of the transcription factor, T-bet. These findings indicate that VIP restores tolerance to pancreatic islets by promoting the local differentiation and function of regulatory T cells.
OBJECTIVES: Vasoactive intestinal peptide (VIP) has demonstrated therapeutic effects in arthritis by inhibiting both innate and acquired immune responses. We investigated the potential effects of VIP in the regulation of Toll-like receptor (TLR) expression and function in synovial fibroblasts from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Cultured fibroblast-like synoviocytes (FLS) were obtained from patients with RA and OA. The effects of VIP on basal or TNF-alpha or lipopolysaccharide (LPS)-induced TLR2, TLR4 and MyD88 expression and its effects on TLR4-mediated CCL2 and CXCL8 chemokine production were studied by reverse transcription-polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. RESULTS: TLR2, TLR4 and MyD88 mRNA expression was increased in RA FLS compared with OA FLS. The largest increase was observed for TLR4 and there was also overexpression at the protein level in RA FLS. TLR4 and MyD88 mRNA and proteins were induced by LPS and TNF-alpha in RA FLS. VIP down-regulated the induced but not the constitutive expression of TLR4 and MyD88 in RA FLS. VIP treatment decreased CCL2 and CXCL8 chemokine production in response to TLR4 activation with LPS in RA FLS. CONCLUSIONS: We demonstrate that VIP down-regulates LPS and TNF-alpha activation of TLR4 expression and the TLR4 functional response in terms of proinflammatory chemokine production. These studies suggest that the pleiotropic anti-inflammatory actions of VIP involve inhibitory effects on TLR4 expression and signalling.
Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral-pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case-control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16-4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27-0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05-0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02-6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02-1.61), bladder cancer (OR = 1.38, 95% CI = 1.06-1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.
Fermentation of wine is a complex microbial reaction, which involves the sequential development of various species of yeasts and lactic acid bacteria. Of these, yeasts are the main group responsible for alcoholic fermentation. The aim of this work was to study, under industrial conditions, the evolution of yeast populations and to describe the individual evolution of the most important yeasts during three spontaneous fermentations of Malbec musts from Argentina. This work shows the significant participation of non-Saccharomyces yeasts during spontaneous fermentation of musts, with the ubiquitous presence of three main species: Kloeckera apiculata, Candida stellata and Metschnikowia pulcherrima.
AIMS: The aims of this work were to evaluate different pre-isolation treatments applied to complete yeast extraction from grapes and to identify the yeast microflora associated to Malbec grapes from two vineyards located in Mendoza, Argentina. METHODS AND RESULTS: The pre-isolation treatments evaluated were shaking, jet streaming with pressurized water and grape blending. The overall results clearly indicated that when a more vigorous and disruptive pre-isolation treatment was applied; larger numbers of yeast species were recovered. The yeast population on healthy and ripe Malbec grapes was in the order of 10(5)-10(6) CFU g(-1). Eight different yeast species were isolated from berries, including Kloeckera apiculata, Metschnikowia pulcherrima, Pichia membranifaciens, Saccharomycodes ludwigii, Candida species (Candida stellata and Candida raghi), Issatchenkia orientalis and Rhodotorula spp. CONCLUSIONS: Grape blending gave the highest yeast counts. Rainfall near grape harvest time quantitatively and qualitatively modifies the yeast microflora. The yeast species identified on ripe grapes from the Mendoza region, partially match those previously documented in different parts of the world related. S. ludwigii has not been previously reported in grapes. SIGNIFICANCE AND IMPACT OF THE STUDY: The report is on yeast microbiota in grapes from Mendoza, Argentina. Saccharomycodes ludwigii was found in high percentage (17%), this species has not been described before on grapes surface. The importance of pre-isolation steps to the recovery of high number of yeasts was shown. Influence of climatic conditions near harvest time on microflora was confirmed.
This paper presents the profile and competences for the European Dentist as approved by the General Assembly of the Association for Dental Education in Europe at its annual meeting held in Cardiff in September 2004. A task-force drafted the document, which was then sent to all European Dental Schools. Reactions received were used to amend the document. European dental schools are expected to adhere to the profile and the 17 major competences but the supporting competences may vary in detail between schools. The document will be reviewed in 5 years time. This paper will be disseminated to ministries of health, national dental associations and dental specialty associations or societies in Europe and these organisations will be asked to offer their comments. This information will be used in the reviewing process to be started in 2007. It is hoped that the availability of this document will assist dental schools in Europe to further harmonize and improve the quality of their curricula.
INTRODUCTION: The diagnosis of patients with cognitive deterioration or dementia requires a global approach in which the neuropsychological examination is a key piece. As part of the GERMCIDE study (Group for the Study and Multicenter Registry of Incident Cases of Dementia in Spain), a protocol was designed that included an assessment of the different cognitive functions that are most frequently altered in dementias (memory, orientation, speech, praxis, abstraction capacity and executive function). METHODS: In order to obtain data in normal subjects, this neuropsychological protocol was applied to a group of persons over 50 years without cognitive deterioration or dementia. RESULTS: A total of 103 subjects whose ages ranged from 50 to 95 years (mean: 73.5; SD: 9.3 years); 39 (37.9%) men and 64 (62.1%) women were studied. The mean score on the Mini-Mental State Examination (MMSE) was 27/30 (SD: 2.0). In the speech and praxis tests, 90% of the subjects obtained the maximum value, while performances were more unequal in memory, reasoning and programming. Mean score, standard deviation and distribution in percentages for each subtest are presented. CONCLUSIONS: The values obtained in this sample of normal subjects and their distribution in percentages may be very helpful to facilitate the interpretation of the findings of the neuropsychological examination with the GERMCIDE protocol in the general neurology clinic visits and also in the specialized visits in dementia.
International rice export markets are increasing demands for rapid improvements in grain quality characteristics. The African rice Oryza glaberrima is a new potential source of genes that will enhance the eating, cooking, and milling properties of the rice grain. The objective of this research was to identify and characterize quantitative trait loci (QTLs) among 312 doubled haploid lines derived from the BC3F1 of an interspecific cross of O. sativa x O. glaberrima. Genetic material was planted in replicated plots and evaluated for ten grain quality traits in 2001 in Colombia. A linkage map was constructed with 100 polymorphic microsatellite markers using the mapdisto software program to adjust for segregation distortion. Transgressive segregation was observed for all traits. Interval and composite interval analyses identified 27 QTLs for nine characters located on 11/12 chromosomes. The chromosomal positions of QTLs for percentage amylose, alkali-spreading score, and percentage protein were in agreement with data reported by others, whereas QTL markers for percentage head rice, percentage milled rice, percentage protein, and percentage brown rice were different in our mapping population. Five major QTLs were found to be associated with improved percentage rice bran, percentage amylose, and alkali-spreading score. Seven QTLs for improved percentage rice bran, percentage milled rice, alkali-spreading score, percentage protein, and grain length/width ratio were derived from the O. glaberrima accession. Three new QTLs for percentage rice bran are reported here for the first time. Results from this study suggest that the African rice might be a valuable new source for introgression and improvement of several traits that affect quality traits demanded by the different rice export markets.
High-dose therapy (HDT) followed by autologous stem cell support is widely used as intensification treatment in patients with multiple myeloma (MM) responsive to the initial chemotherapy. However, there is growing evidence that only the subset of patients who achieve complete remission (CR) actually benefit from this approach. The aim of this study was to identify pretransplant predictors of CR in responding myeloma patients intensified with HDT. A total of 59 patients with chemosensitive disease received myeloablative therapy. The intensification regimen consisted of MEL-200 (23), MEL-140/TBI 12 Gy (21) or busulfan-based regimens (15). Serum and urine negative immunofixation were required for CR. After HDT, the CR rate increased from 8 to 37%. For the overall series, the median event-free survival (EFS) and overall survival (OS) from the initiation of therapy were 41 and 68 months, respectively. Patients who achieved CR had an EFS (median 47 vs 36 months; P=0.023) as well as an OS (median not reached vs 60 months; P=0.006) significantly longer than those attaining a lower degree of response. Finally, the pretransplant features significantly associated to CR were a low M-protein size (serum </=10 g/l and urine <0.5 g/24 h) (P=0.0003) and a proportion of bone marrow plasma cells of </=5% (P=0.02).