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Biomedical subjects

R Morales

Publications and source records attributed to R Morales.

At least 19 recordsLinked to original sources

Potential application of GSTT1-null genotype in predicting toxicity associated to 5-fluouracil irinotecan and leucovorin regimen in advanced stage colorectal cancer patients.

Our aim was to evaluate the role of C-69T in GSTA1, Ile105Val in GSTP1, null allele in GSTT1 and GSTM1 in the prediction of toxicity in patients treated with 5-Fu/CPT-11/Lv regimens in metastatic CRC patients. Fifty-one patients with CRC metastatic disease were analysed. All patients had bidimensionally measurable disease according to WHO criteria. The gender distribution was 37 (74%) males and 13 (26%) females; age ranged from 41 to 71 years; performance status was in all patients > or = 80 (Karnofsky index). The analysis of gene polymorphism was performed in lymphocytes by using PCR-RFLP (GSTA1, GSTP1), PCR (GSTT1, GSTM1) and sequencing analysis (UGT1A1 *28). An appreciable significant association was observed between the GSTT1-null and toxicity: 57% developed gastrointestinal toxicity grade III versus 23% of patients with GSTT1-present genotype (p = 0.053). The other polymorphisms analysed did not show any significant relation with toxicity. Our data suggest that GSTT1-null is associated with a greater probability of developing toxicity to 5-Fu/CPT-11/Lv treatments, indicating a potential application of this genetic analysis in predicting adverse effects of this regimen.

Adult↗

Depth profile of uncompensated spins in an exchange bias system.

We have used the unique spatial sensitivity of polarized neutron and soft x-ray beams in reflection geometry to measure the depth dependence of magnetization across the interface between a ferromagnet and an antiferromagnet. The net uncompensated magnetization near the interface responds to applied field, while uncompensated spins in the antiferromagnet bulk are pinned, thus providing a means to establish exchange bias.

Journal Article↗

Low-grade systemic inflammation, hypoadiponectinemia and a high concentration of leptin are present in very young obese children, and correlate with metabolic syndrome.

OBJECTIVE: To determine the concentration levels of C-reactive protein (CRP), leptin and adiponectin in obese pre-pubertal children, and their possible relation with metabolic syndrome, fibrinogen and plasminogen activator inhibitor-1. METHODS: A study was carried out in 51 obese children (aged 6 to 9 years) and the same number of non-obese children (control group), matched by age and sex. (Cross-sectional study of obese children). Body mass index (BMI), waist/hip ratio (WHR) and blood pressure were determined for each child. Serum CRP, leptin, adiponectin, glucose, insulin, lipid profile, plasminogen activator inhibitor-1 (PAI-1) and fibrinogen were all measured. RESULTS: The levels of CRP serum (1.67+/-0.222 vs 0.92+/-0.16 mg/l) and leptin (15.56+/-1.27 vs 4.68+/-0.62 ng/ml) were significantly higher in obese children. The adiponectin level was significantly higher in non-obese children (11.58+/-0.63 vs 9.64+/-0.49 microg/dl). In the obese group, log. CRP showed a positive correlation with BMI, insulin, homeostasis model assessment (HOMA), triglycerides, alanine aminotransferase (ALT), uric acid, PAI-1, fibrinogen and interleukin 6 (IL-6), and correlated negatively with apolipoprotein A-I and high-density lipoprotein cholesterol (HDL-C). The leptin was positively correlated with BMI, insulin, HOMA, triglycerides and PAI-1 and negatively with Apo A-I and HDL-C. Adiponectin correlated negatively with BMI, insulin, HOMA, and triglycerides. CONCLUSIONS: Low-grade systemic inflammation, elevated leptin concentration and low adiponectin level are described in very young obese children, correlating with a range of variables of metabolic syndrome. Inflammation and adipocytokines can play an important role in the etiopathogeny of metabolic syndrome.

Adiponectin↗

Efficacy of etoricoxib 60 mg/day and diclofenac 150 mg/day in reduction of pain and disability in patients with chronic low back pain: results of a 4-week, multinational, randomized, double-blind study.

BACKGROUND AND METHODS: The efficacy and safety of etoricoxib 60 mg/day in patients with established chronic low back pain (CLBP) were compared with those of diclofenac 150 mg/day in a 4-week, multicentre, randomized, double-blind, parallel-group trial. Four hundred and forty-six adult patients with CLBP (Quebec Task Force on Spinal Disorders Class 1 or 2) and with worsening pain upon discontinuation of pre-study analgesic medication were enrolled in the study. The study primary efficacy endpoint was change from baseline in Low Back Pain Intensity Scale (LBP-IS) score over the 4-week treatment period. Secondary and other efficacy endpoints included: changes in Roland and Morris Disability Questionnaire (RMDQ), Patient Global Assessment of Response to Therapy (PGART) and Low Back Pain Bothersomeness Scale (LBP-BS) scores. Early efficacy was assessed using PGART and LBP-IS scores 4 h after the first dose on the mornings of Days 1, 2 and 3. The overall safety and tolerability of etoricoxib 60 mg/day during 4 weeks of treatment were also assessed. RESULTS: The least-squares mean time-weighted change from baseline LBP-IS score over 4 weeks was -32.94 mm (95% CI -36.25, -29.63) for etoricoxib, indicating substantial efficacy in relief of pain. The treatment difference for the primary outcome was 2.51 mm (95% CI -1.50, 6.51), fulfilling the prespecified equivalence criterion of 95% confidence interval wholly within +/- 10 mm. Etoricoxib improved all secondary and other efficacy outcomes. There were no statistically significant between-group differences in the proportion of patients with one or more clinical adverse events (AEs) (etoricoxib 35%, diclofenac 39%), or the proportion of patients who discontinued due to AEs (etoricoxib 7%, diclofenac 5%). CONCLUSIONS: The results of this study confirm that, for adult patients with CLBP, etoricoxib 60 mg once daily over 4 weeks is effective for relief of pain and improvement of physical function and comparable to high-dose diclofenac 150 mg daily.

Adult↗

DYS19 and DYS199 loci in a Chilean population of mixed ancestry.

The current Chilean population originated from admixture between aboriginal populations (Amerindians) and Spanish conquerors of European origin. Consequently, the unions that gave rise to the Chilean population were chiefly between Spanish males and aboriginal females, and not the converse. To test the hypothesis that the Y chromosome of the Chilean population is mainly of Spanish origin, while the other chromosomes are from mixed (European and aboriginal) origin, we studied the DYS19 and DYS199 loci in two samples. One sample was obtained from a high socioeconomic stratum, while a second sample was from a low stratum. We studied male blood donors (N = 187) from Santiago, the capital of the country. Subjects were typed for the autosomal ABO and Rh (locus D) blood groups, and for the Y-linked DYS19 and the DYS199 loci, reported as Y-chromosome haplotypes. The aboriginal admixture was estimated for each genetic marker. The percentage of aboriginal admixture was 38.17% for the ABO system and 31.28% for the Rh system in the low socioeconomic stratum and 19.22% and 22.5%, respectively, in the high stratum. Y-chromosome haplotype frequencies constructed from the DYS19 and DYS199 loci demonstrated that the main haplotypes were DYS19*14/DYS199 C, as is often the case with many European populations, and DYS19*13/DYS199 C. The aboriginal admixture from Y-haplotype frequencies was estimated to be 15.83% in the low socioeconomic stratum and 6.91% in the high stratum. These values are lower than the values found using autosomal genetic markers, and are consistent with the historical background of the population studied. This study highlights the population genetic consequences of the asymmetric pattern of genome admixture between two ancestral populations (European and Amerindian).

Chile↗

Bioelectrical impedance vector analysis in haemodialysis patients: relation between oedema and mortality.

In this work, bioelectrical impedance vector analysis (BIVA) method is used in a sample of haemodialysis patients in stable (without oedema) and critical (hyperhydrated and malnutrition) states, in order to establish the relation between hyperhydration (oedema) and mortality. The measurements obtained were single frequency (50 kHz), tetrapolar (hand-foot) complex impedance measurements (vector components are: resistance R and reactance Xc). The impedance components were standardized by the height H of the subjects, (R/H and Xc/H) to obtain de impedance vector Z/H, that is represented in the RXc plot (abscise R/H, ordinate Xc/H). Measurements were performed on a sample of 74 patients (30 men and 44 women, 18-70 year, body mass index (BMI), 19-30 kg m(-2)) at the Saturnino Lora University Hospital in Santiago de Cuba. The 46 stable patients comprised 28 men and 18 women; the 28 critical patients 16 men and 12 women. The reference population consisted of 1196 healthy adult subjects living in Santiago de Cuba (689 men and 507 women, 18-70 year, BMI 19-30 kg m(-2)). We used the RXc plot with the BIVA method to characterize the reference population using the 50%, 75% and 95% tolerance ellipses. Student's t-test and Hotelling's T2-test were used to analyse the separation of groups obtained by means of clinical diagnosis and those obtained by BIVA. We obtained a significant difference (P < 0.05) in R/H, Xc/H and phase angle (PA) in men as in women between the location of Z/H vectors in the RXc graph and the separation made by the doctors between stable and critical patients. Critical (hyperhydrated) patients were located below the inferior pole of the 75% tolerance ellipse, whereas stable patients were within the tolerance ellipses. Some cases classified as stable by the clinic were classified as hyperhydrated by BIVA with 100% sensitivity and 48% specificity. In conclusion, the BIVA method could be used to classify patients by hydration state and to predict survival. Advantages of the method are its simplicity, objectivity and that it does not require the definition of patient dry weight.

Adolescent↗

Childhood obesity and hormonal abnormalities associated with cancer risk.

There is growing evidence that overweight and obesity increase the risk of certain cancers. Studies in adults support the role of insulin-like growth factors (IGFs) and oestrogens in the pathogeneses of several cancers. We propose that hormone alterations described as risk factors for cancer in obese adults are present in prepubertal obese children. A group of obese children aged 6-9 years (n=40), and control group paired for age and sex, were used for the study. The obese children presented a significantly high level of IGF-I (P=0.0173) and insulin (P=0.0250), with a drop in sex hormone-binding globulin (SHBG) (P=0.0282). The 17 beta-oestradiol (E2)/SHBG ratio increase in obese subjects was marginally significant (P=0.0635). Grouping together all the children in quartiles for insulin and body mass index, the upper quartiles showed a rise in IGF-I and E2/SHBG. In a multivariant correlation analysis, only height (partial r=0.2464) and insulin (partial r=0.3002) were independent prediction variables for IGF-I concentration. The only variables statistically correlated with the E2/SHBG ratio were insulin (r=0.2879) and IGF-I (r=0.4140). The obese children in our study showed hormone changes described as risk factors for cancer in obese adults. These changes were significantly associated with the hyperinsulinaemia. We hypothesize that this potential risk should be taken into account given the long period of exposure involved in the presence of hormone alterations at such early ages.

Adult↗

Direct phasing at low resolution of a protein copurified with human paraoxonase (PON1).

In this paper, the low-resolution structure of a previously unknown protein copurified with human paraoxonase (PON1) is reported. The structure of this protein was very difficult to solve using classical crystallographic methods. Progress was made using a new phasing method based on topological analysis. From the experimental point of view, this method has the advantage of requiring only a simple low-resolution X-ray data set. The program used and the different steps of the data-processing and phasing procedure are described. The results provided an insight into the failure of previous molecular-replacement attempts. The low-resolution shape of the protein which was presented with confidence is compared with and confirmed by the structure at 1.8 A solved subsequently using classical methods. This work shows that this direct-phasing method could be used systematically in difficult cases: it provides low-resolution structural information comparable with that obtainable by electron microscopy.

Aryldialkylphosphatase↗

Chromatographic removal combined with heat, acid and chaotropic inactivation of four model viruses.

The virus removal of protein A affinity chromatography, inactivation capacity, acid pH and a combination of high temperature with a chaotropic agent was determined in this work. The model viruses studied were sendaivirus, human immunodeficency virus (HIV-IIIb), human poliovirus type-II, human herpesvirus I and canine parvovirus. The protein A affinity chromatography showed a maximum reduction factor of 8 logs in the case of viruses larger than 120 nm size, while for small viruses (18-30 nm) the maximum reduction factor was about 5 logs. Non viral inactivation was observed during the monoclonal antibody elution step. Low pH treatment showed a maximum inactivation factor of 7.1 logs for enveloped viruses. However, a weak inactivation factor (3.4 logs) was obtained for DNA nonenveloped viruses. The combination of high temperature with 3 M KSCN showed a high inactivation factor for all of the viruses studied. The total clearance factor was 23.1, 15.1, 13.6, 20.0 and 16.0 logs for sendaivirus, HIV-IIIb, human poliovirus type-II, human herpesvirus I and canine parvovirus, respectively.

Animals↗

Stirrer tank: an appropriate technology to immobilize the CB.Hep-1 monoclonal antibody for immunoaffinity purification.

The CB.Hep-1 monoclonal antibody was coupled to CNBr-activated Sepharose CL 4B at three different immobilization scales for purification of recombinant hepatitis B surface antigen. Standard laboratory apparatus to obtain immunosorbents of 1 l (scale I) and 3 l (scale II) as well as a stirrer tank to prepare 6 l immunosorbents (scale III) were used. The binding capacity at scale III was 2- and 1.5-fold higher with respect to the scales II and I, while a reduction in the ligand leakage of 5- and 2-folds was observed. Immunosorbents from scale II showed a significantly reduced adsorption, and an increased ligand leakage. Differences in the coupling efficiency were not observed. Antigen purity eluted from the immunosorbents was always above 85%.

Antibodies, Monoclonal↗

Synthesis and antiparasitic activity of 2-(trifluoromethyl)-benzimidazole derivatives.

2-(Trifluoromethyl)benzimidazole derivatives substituted at the 1-, 5-, and 6-positions have been synthesized and in vitro tested against the protozoa Giardia lamblia, Entamnoeha histolytica. and the helminth Trichinella spiralis. Results indicate that all the compounds tested are more active as antiprotozoal agents than Albendazole and Metronidazole. One compound (20) was as active as Albendazole against T. spiralis. These compounds were also tested for their effect on tubulin polymerization and none inhibited tubulin polymerization.

Animals↗

Staged reconstruction after gunshot wounds to the abdomen.

Immediate closure of abdominal incisions after exploration and treatment of gunshot wounds is not always feasible or advisable. Significant bowel edema after massive fluid resuscitation might preclude primary closure, whereas any attempt to close under tension might result in complications ranging from wound dehiscence, infection, and necrosis to the abdominal compartment syndrome with abdominal, cardiopulmonary, and renal complications. For these difficult cases, the open technique has been recommended. The abdomen is left open and is closed when the patient's condition permits. When immediate wound approximation is not possible, temporary coverage can be achieved with a mesh, patch, or a split-thickness skin graft and the definitive reconstruction is deferred for a more optimal time. The purpose of this retrospective study is to report the authors' experience with staged abdominal wall reconstruction after gunshot wounds. From 1989 to 1998, 1933 patients underwent exploratory laparotomy for penetrating wounds to the abdomen. Twenty-nine patients in grave condition and with multiple medical problems were comanaged by the Trauma and Plastic Surgery Services at Cook County Hospital with the following protocol: The abdomen was initially left open and exposed viscera were covered with a variety of methods, including a Gore-Tex patch (W. L. Gore and Associates, Inc., Flagstaff, Ariz.). A split-thickness graft was subsequently placed on the granulation tissue over viscera at an average of 14 days after the last laparotomy. These planned ventral hernias were definitively treated at an average of 7 months after the skin grafting procedure, primarily using the components separation technique. In 24 patients, the fascia was closed primarily without tension, while five patients required the use of synthetic mesh to restore fascial continuity. Nine patients underwent closure of a colostomy or repair of fistulas simultaneously with abdominal wall reconstruction. One patient developed a postoperative hernia, two developed superficial wound dehiscence that healed without further surgery, and one required re-exploration for a failed anastomosis after colostomy closure. All but one patient maintained a stable abdominal wall after the reconstruction. The authors concluded that staged abdominal wall reconstruction should be primarily recommended for patients with complex abdominal wounds and a compromised general condition that precludes primary closure. With this treatment protocol, patients can recover faster from their trauma surgery and the risk of perioperative complications can be reduced. After final reconstruction, the continuity, stability, and strength of the abdominal wall are maintained in the vast majority of cases with the use of autogenous tissue and without the need for alloplastic material. With close cooperation between the trauma team and the plastic surgeon and appropriate timing and planning of each stage, the success rate of the technique is high and the incidence of complications limited.

Abdominal Injuries↗

Outcome of liver disease in a large cohort of histologically proven chronic hepatitis C: influence of HCV genotype.

OBJECTIVE: To assess the influence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2,307 patients. RESULTS: The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P< 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P< 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P< 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2,307 patients, only genotype 1b was associated significantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P< 0.01) and a lower cumulative hazard for HCC (P< 0.01). CONCLUSIONS: Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not confirm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.

Adolescent↗

Is (99m)Tc-sestamibi scintimammography complementary to conventional mammography for detecting breast cancer in patients with palpable masses?

UNLABELLED: The aim of this trial was to evaluate in developing countries from different regions the diagnostic performance of (99m)Tc-sestamibi scintimammography (SM) in palpable breast lesions and to verify the clinical usefulness of a joint evaluation with mammography and SM. METHODS: From 10 countries, a total of 238 patients with palpable breast masses (n = 245) were included in this prospective multicenter trial. Prone SM was performed 10 min and 60-90 min (157 patients) after injection using an isotime acquisition of 10 min. Mammography was assessed by the same dedicated imaging radiologist according to breast imaging reporting and data system (BI-RADS) categories for malignancy and breast density. Masked SM findings and mammography findings were checked for a correlation with histopathology findings for excisional biopsy samples. Diagnostic values for breast cancer detection were calculated per lesion. RESULTS: Histopathology revealed 189 cancerous lesions and 56 benign lesions. The sensitivity and specificity of SM were 0.83 and 0.77, respectively. SM diagnostic values did not depend on the incidence of breast cancer in the country of origin or on the timing of imaging (early vs. delayed scans). On mammography, the technique yielded a sensitivity and specificity of 0.85 and 0.66, with 27 mammograms classified as BI-RADS category 1, 33 as category 2, 5 as category 3, 56 as category 4, and 124 as category 5. Thirty-seven lesions were considered to show increased radiologic density. No significant difference was found in SM diagnostic values among different BI-RADS categories or between the groups with low and high breast density. A sensitivity of 96% was calculated when SM and mammography results were combined, with 75% of all false-negative mammography findings classified as true-positive results by SM. CONCLUSION: SM complements mammography in patients with palpable masses and negative mammography findings.

Adult↗

Quality indicators in ambulatory surgery. A prospective study.

Introduction: Ambulatory Surgery has emerged and developed in Spain in a similar way as in other occidental countries. Once established as a model for surgical care, results must be improved using objective quality indicators to assure minimal morbidity, efficient use of resources and satisfaction of patients and family. Objective: To provide a list of quality assessment indicators in Ambulatory Surgery and to discuss the necessity of obtaining a general consensus regarding the complexity of both the operations and the patients undergoing surgery. Design: Prospective and descriptive study. Patients and Methods: The study was performed on 833 ambulatory patients operated on in the Ambulatory Surgical Unit of the Can Misses Hospital of Ibiza. Surgical specialities involved were General Surgery, Ophthalmology, Orthopaedics, Urology, Gynaecology, and E.N.T. All diagnoses and proceedings were classified according to the CIE-9 and DGR systems, showing as an example the codes related to the General Surgery department. Quality Indicators evaluated were: (a) unplanned admission index; (b) re-admission index; (c) emergency department consultations; (d) cancellation index; (e) substitution index; and (f) postoperative pain evaluation. Results: Specialities involved were: Ophthalmology 277 patients (33.2%), General Surgery 189 (22.8%), Orthopaedics 142 (17%), Urology 90 (10.8%), E.N.T. 79 (9.5%) and Gynaecology 56 (6.7%). Unplanned Admission Index was 7.2%; Re-Admission Index 0.4%; Emergency department consultation 1.6%; Cancellation Index 3.3% and Substitution Index 70%. The reasons for unplanned admission were due to specific complications in 36 cases (60.1%), followed by those secondary to an inadequate selection of the patient in 22 cases (36.6%). Conclusions: It is necessary to apply a series of Quality Indicators in Ambulatory Surgery. Their systematic evaluation may help us define national standards in order to continuously improve our results.

Journal Article↗

Porphyria cutanea tarda affecting lower lip.

In porphyria cutanea tarda, the most common type of porphyria, blisters of the skin occur because of high sensitivity to sunlight. This case report describes porphyria cutanea tarda of the lower lip mimicking an actinic cheilitis in a 62-year-old man with a history of Hodgkin's lymphoma.

Administration, Topical↗