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Biomedical subjects

A Garrido

Publications and source records attributed to A Garrido.

At least 19 recordsLinked to original sources

Comprehensive DNA methylation profiling in a human cancer genome identifies novel epigenetic targets.

Using a unique microarray platform for cytosine methylation profiling, the DNA methylation landscape of the human genome was monitored at more than 21,000 sites, including 79% of the annotated transcriptional start sites (TSS). Analysis of an oligodendroglioma derived cell line LN-18 revealed more than 4000 methylated TSS. The gene-centric analysis indicated a complex pattern of DNA methylation exists along each autosome, with a trend of increasing density approaching the telomeres. Remarkably, 2% of CpG islands (CGI) were densely methylated, and 17% had significant levels of 5 mC, whether or not they corresponded to a TSS. Substantial independent verification, obtained from 95 loci, suggested that this approach is capable of large scale detection of cytosine methylation with an accuracy approaching 90%. In addition, we detected large genomic domains that are also susceptible to DNA methylation reinforced inactivation, such as the HOX cluster on chromosome 7 (CH7). Extrapolation from the data suggests that more than 2000 genomic loci may be susceptible to methylation and associated inactivation, and most have yet to be identified. Finally, we report six new targets of epigenetic inactivation (IRX3, WNT10A, WNT6, RARalpha, BMP7 and ZGPAT). These targets displayed cell line and tumor specific differential methylation when compared with normal brain samples, suggesting they may have utility as biomarkers. Uniquely, hypermethylation of the CGI within an IRX3 exon was correlated with over-expression of IRX3 in tumor tissues and cell lines relative to normal brain samples.

Brain↗

Hepatitis C virus recurrence after liver transplantation: influence of immunosuppressive regimens on viral load and liver histology.

Cyclosporine has recently been reported to produce in vitro suppression of hepatitis C virus replication driven by blockade of cyclophilins, an effect not shown for tacrolimus. However, the clinical consequence of this in vitro finding have not been well studied in vivo. We compared viral load and fibrosis in transplanted patients receiving monotherapy with tacrolimus or cyclosporine. Patients with recurrent hepatitis C after transplantation were selected from two tertiary centers with the following inclusion criteria: monotherapy with tacrolimus or cyclosporine for more than 12 months before viral load measurement, no antiviral treatment, corticosteroids stopped within 12 months after transplantation. HIV, hepatitis B, and active infection by cytomegalovirus were excluded. Patient characteristics, viral load, and fibrosis were compared by univariate analysis between the cyclosporine and tacrolimus groups. Significant variables, viral load, and fibrosis were included in a multivariate model. Sixty-six patients were included, 46 on tacrolimus and 20 on cyclosporine. Fifty-six were male, and the mean age was 55.3 +/- 10.1 years. Fibrosis (Ishak score) was 3.9 +/- 1.9 in the cyclosporine group and 2.7 +/- 1.9 in the tacrolimus group (P = .019). Viral load (log(10)IU/mL) was 5.8 +/- 0.5 and 5.9 +/- 0.5, respectively (P = .7) and time since liver transplantation was 95.3 +/- 47.7 and 41.1 +/- 16.8 months (P = .0001). In the multivariate model, viral load (P = .65) and fibrosis (P = .24) were not significantly different and only time since transplantation remained significant (P = .0001). In conclusion, viral load was not different in patients with tacrolimus as compared with cyclosporine, and the lower fibrosis observed in the cyclosporine group lacked significance when considered together with time since liver transplantation.

Aged↗

Effect of vitamin D and calcium supplementation on bone turnover in institutionalized adults with Down's Syndrome.

OBJECTIVE: To assess the status of vitamin D and the effects of calcium and vitamin D3 supplementation on the bone metabolism in a group of adults with Down's syndrome (DS). DESIGN: Randomized, parallel, controlled and open clinical trial. SETTING: Institution for mentally handicapped: Fundación Uliazpi, Diputación Foral de Guipúzcoa, San Sebastián, Spain. SUBJECTS: A total of 23 persons with DS, residents at the Uliazpi Foundation were recruited and all completed the study. INTERVENTION: In all, 12 participants were randomly allocated to receive 1 g of calcium and 800 IU of vitamin D once daily for 1 year while 11 were assigned to the control group, receiving no supplementation. RESULTS: We found no differences between groups regarding serum calcium and phosphorous levels. The remaining parameters showed differences between the two groups consistent with a beneficial effect of the intervention: serum levels of parathyroid hormone, osteocalcin and crosslaps diminished while serum 25 OH vitamin D3 level increased. CONCLUSIONS: The results obtained allow to include people with DS as a risk group with regards to vitamin D deficit, which that can be corrected with vitamin D and calcium supplementation, and giving rise to an improvement of the biochemical markers related to the phospho-calcium metabolism and bone remodelling.

Adult↗

Transfusion requirements in patients with gastrointestinal bleeding: a study in a Blood Unit at a referral hospital.

OBJECTIVES: 1. To study transfusion requirements in the Department of Gastroenterology of a Tertiary Referral Hospital, and their evolution over the last seven years. 2. To analyze risk factors associated with greater erythrocyte transfusion requirements. PATIENTS AND METHODS: erythrocyte transfusion requirements were compared for patients admitted to the Department of Gastroenterology at Hospital Virgen del Rocío, Seville, from 1999 to 2005. Clinical data of interest have been analyzed in order to determine factors associated with greater transfusion requirements. RESULTS: 1,611 patients with a mean age of 60.45 years (59.7-61.2) were included in this study; 76.41% were males. Gastric ulcers were the cause of bleeding in 18.4% of cases (with 69% requiring transfusions); duodenal ulcers caused 22.2% of cases (with 52.9% requiring transfusions), and portal hypertension caused 33.6% of cases (with 90.2% requiring transfusions). Upper and lower gastrointestinal bleeding of unknown origin requires transfusions in 88.9 and 96.2% of cases, respectively.A multivariate logistic regression analysis showed that clinical presentations such as hematemesis (odds ratio = 3.12), hematochezia (odds ratio = 33.17), gastrointestinal hemorrhage of unknown origin (odds ratio = 6.57), and hemorrhage as a result of portal hypertension (odds ratio = 3.43) were associated with greater transfusion requirements for erythrocyte concentrates. No significant differences were observed between the percentages of patients who received transfusions from 1999 to 2005. CONCLUSIONS: 1. No differences have been observed between the percentages of patients who received transfusions over the last seven years at our Department of Gastroenterology. 2. Patients presenting with hematemesis or hematochezia, in addition to those with bleeding of unknown origin or from portal hypertension, are prone to have greater transfusion requirements.

Erythrocyte Transfusion↗

A comparison of raloxifene and calcium plus vitamin D on vaginal atrophy after discontinuation of long-standing postmenopausal hormone therapy in osteoporotic women. A randomized, masked-evaluator, one-year, prospective study.

OBJECTIVES: We assessed the effects of the discontinuation of long-standing transdermal estrogen replacement therapy (>4 years) and substitution of this treatment by calcium or raloxifene on the vaginal epithelium and climateric symptoms in a study population of osteoporotic women. METHODS: A total of 136 women (mean age 55.5 years) were randomized to calcium (500 mg elemental calcium, 400 IU Vitamin D3) (n=40), raloxifene (60 mg/day) (n=48), or estrogen patches (3.9 mg estradiol) and progesterone (100 mg/day) (n=48). Treatment was given for 1 year. The vaginal maturation value (VMV), serum estradiol levels, and climateric symptoms using a 12-item modification of the SF-36 quality of life questionnaire were evaluated at baseline and at 6 and 12 months. RESULTS: At 6 months, mean VMV decreased significantly (P<0.001) in the calcium (-51.8%) and raloxifene (-18.6%) groups compared with baseline and the estrogen/progesterone group. At 12 months, significant decreases of mean VMV in the calcium (-38.7%) and raloxifene groups (-32%) (P<0.001) were also observed. Serum estradiol levels and changes of VMV correlated significantly at 6 months (rho=0.361, P<0.01) and at 12 months (rho=0.269, P<0.035). A significantly higher number of patients complained of hot flushes and palpitations in the calcium and raloxifene groups than in the estrogen/progesterone group. Raloxifene-treated women reported a significantly higher number of adverse events at 6 months compared to the other treatment groups. CONCLUSIONS: Withdrawal and change of long-standing transdermal hormone replacement therapy by treatment with calcium or raloxifene resulted in worsening of vaginal atrophy assessed by the VMV, although it was not clinically perceived by the patients. However, increases in dyspareunia and urinary leaks were reported. Menopausal complaints related to vasomotor symptoms worsened in the calcium- and raloxifene-treated groups and persisted throughout the study period.

Administration, Cutaneous↗

Epidemiology of chronic inflammatory bowel disease in the Northern area of Huelva.

OBJECTIVE: To know the different epidemiologic aspects of chronic inflammatory bowel disease (IBD) in the Northern area of the province of Huelva. MATERIAL AND METHODS: we carried out a retrospective (1980-1996) and prospective (1996-2003) study of all patients diagnosed with IBD in the Northern area of Huelva, with 77,856 inhabitants. The distribution of Crohn s disease (CD) and ulcerative colitis (UC) was analyzed, as well as sex, age and smoking habit at the time of diagnosis, familial aggregation, appendicectomy rate, phenotype (anatomical site and clinical types), extraintestinal manifestations, and immunosuppressive therapy or surgical requirements. RESULTS: 70 patients with IBD were studied, 40 with UC and 30 with CD. Sex distribution was 39 (55.7%) males (55% with CD vs 56.6% with UC; NS) and 31 (44.3%) females (45% with CD vs 43.3% with UC; NS). Mean age at presentation was 44.7 +/- 19.32 years in UC vs 32.3 +/- 16.43 in CD; p < 0.001. Familial association was 7.1%. Previous appendicectomy was referred in 2.5% of patients with UC vs 36.7% of those with CD (p < 0.001), and the percentage of smokers was also higher in CD 66.7% vs CU 12.5% (p < 0.001). Anatomical site in UC was: proctitis, 20%; proctosigmoiditis/left colon, 42.5%; extensive colitis, 25%; and pancolitis, 12.5%; in CD was: terminal ileum, 43.3%; colon, 20%; and ileo-colon, 36.7%. The disease patterns were: inflammatory 56.7%, obstruction 26.7%, and fistulization 16.7%. Extraintestinal manifestations were diagnosed in 7.5% of patients with UC vs 16.6% patients with CD; surgery was performed in one patient with UC vs 10 with CD, and one patient with UC required immunosuppressive treatment vs 12 with CD. A multivariant analysis showed that younger age and smoking habit were risk factors for CD vs advanced age in UC, in which case, the smoking habit was a protective factor. The mean incidence rate of IBD starting from 1996 and expressed in cases/100,000 inhabitants/year was 5.2 for UC and 6.6 for CD. CONCLUSIONS: The mean incidence of UC in our area was 5.2 cases/100,000/inhabitants/year, and 6.6 for CD. Patients presenting with CD are diagnosed at a significantly younger age that those with UC; the smoking habit is a risk factor for CD while it protects from UC. The characteristics of IBD in our geographical area do not differ substantially from those in other regions of Spain.

Adult↗

Cutting or round-bodied needles for tendon repair.

We carried out a biomechanical study comparing tensile strength after using round-bodied or cutting needles for tendon repair. Swine tendons were repaired in three groups: Group 1 core suture repair only; group 2 core and circumferential suture repair; and group 3 isolated circumferential suture repair. The tendons were tested at longitudinal stress to failure at 5mm/minute. No significant differences were found between the round-bodied and cutting needles in any group. Equal numbers in the core suture repair group failed by suture pullout when comparing cutting and round-bodied needles. We conclude that the choice of needle has no effect on the outcome of tendon repair if there is consistency of surgeon's skill and experience.

Animals↗

HLA class I expression in bladder carcinomas.

HLA class I molecules are frequently lost in a large variety of human carcinomas, possibly because of T-cell immune selection of major histocompatibility complex class I deficient tumor variants. We report that this phenomenon is also a frequent event in bladder carcinomas. Of a total of 72 bladder carcinomas, 72% of the tumors had at least one alteration in HLA class I expression. These altered HLA class I phenotypes were classified as total HLA class I loss (25%; phenotype I); HLA-A or/and HLA-B locus-specific loss (12%; phenotype III); and HLA class I allelic loss (35%; phenotype II or IV). Comparison of histopathological parameters with HLA class I expression showed a statistically significant relationship with the degree of differentiation and tumor recurrence.

Carcinoma↗

[Diagnosis and treatment of refractory sprue].

Celiac disease is a gluten-sensitive enteropathy characterized by villous atrophy that is reversed by gluten withdrawal. A minority of these patients is resistant to a gluten-free diet or, after a period of remission, they experience relapse despite continued adherence to treatment, which is called unclassified sprue or refractory sprue.The prognosis of refractory sprue may be poor: patients may die of severe malabsorption or from the development of an enteropathy-associated T-cell lymphoma. We report a 72-year-old-woman with a diagnosis of refractory sprue who responded well to treatment with corticosteroids and a gluten-free diet.

Aged↗

Reconstruction of the natal cleft with a perforator-based flap.

Recurrent chronic conditions of the natal cleft, such as pilonidal sinuses, are difficult problems to treat. The deep natal cleft and the rolling effect of one buttock surface over the other contribute to the high recurrence rate. Wide excision of the affected area is the treatment of choice; to cover the defect many techniques have been described that flatten the natal cleft and shift the suture line away from the midline to try to reduce recurrence. These techniques include Z-plasties, rhomboid flaps, V-Y flaps, gluteus maximus myocutaneous flaps and others. Five patients with recurrent natal-cleft problems were operated on over a 1 year period. After wide excision of the natal cleft, the defect was reconstructed with a parasacral perforator-based flap. Preoperatively, a perforator situated superolaterally to the defect is identified with a Doppler probe; the flap is then designed horizontally around the perforator and, after elevation, is rotated 908 over the defect. The mean hospital stay was 5 days. Follow-up ranged from 3 months to 15 months, with no signs of recurrence. We believe this to be a simple and reliable technique, with the advantages of placing the scars away from the midline and flattening the natal cleft - factors that help to prevent recurrence.

Adult↗

Acid hydrolysis of secoiridoid aglycons during storage of virgin olive oil.

The main change found in the phenolic composition of virgin olive oils of Arbequina, Hojiblanca, and Picual varieties during storage in darkness at 30 degrees C was the hydrolysis of the secoiridoid aglycons. This reaction gave rise to an increase in the free phenolics hydroxytyrosol and tyrosol in the oil. Filtration of oil and acidity influenced the hydrolysis to a large extent. Thus, the addition of commercial oleic acid to Hojiblanca and Picual oils increased the hydrolysis rate of the secoiridoid aglycons. In contrast, the concentration of lignans 1-acetoxypinoresinol and pinoresinol remained constant during storage. It must also be stressed that the total molar concentration of the phenolic compounds analyzed in the oils changed slightly (<20% reduction) after one year of storage, which is important from a nutritional point of view. However, the transformation of the secoiridoid aglycons into free phenolics may have consequences on oil taste and antioxidant capacity.

Acids↗

HLA class II allele distribution in the Gypsy community of Andalusia, southern Spain.

We have studied the allele distribution of DRB1, DQB1 and DPB1 loci in 80 unrelated Gypsies living in different eastern areas of the Andalusian province of Granada (southern Spain). The frequency distribution of HLA class II alleles and the genetic distance of Andalusian Gypsies from several Caucasian populations indicate a marked similarity - but not total - of the former with the Gypsy population previously studied in Madrid (central Spain), which suggests that both groups migrated together out of India. In terms of genetic distance, both Gypsy groups are more like the Czech Gypsies and the Northern Indian groups than their neighbouring Caucasian non-Gypsy populations. In summary our data support the hypothesis of a common anthropological origin of all three European Gypsy groups, which probably split up after their arrival in Europe.

Alleles↗