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Biomedical subjects

R Sierra

Publications and source records attributed to R Sierra.

At least 19 recordsLinked to original sources

Tumor growth models to generate pathologies for surgical training simulators.

Many virtual reality based surgical training simulators have been presented in the last few years. These systems promise to alleviate the lack of realistic training possibilities common to minimally invasive procedures. Virtual reality allows for riskless training on a wide range of findings in a condensed period of time. We investigated different methods for the generation of tumor models suitable for surgical training simulators. The goal of our research is a high fidelity hysteroscopy simulator which provides an individual surgical scene for every training. Emphasis was placed on the modeling of growth processes leading to the generation of macroscopically realistic findings of the most common pathologies in hysteroscopy, namely polyps and myomas found in the uterine cavity. Both a cellular automaton and a particle based tumor growth model are presented and discussed.

Cell Proliferation↗

Generation of variable anatomical models for surgical training simulators.

The generation of variable surgical scenes is a key element for effective training with surgery simulators. Our current research aims at a high fidelity hysteroscopy simulator which challenges the trainee with a new surgical scene in every training session. We previously reported on methods able to generate a broad range of pathologies within an existing healthy organ model. This paper presents the methods necessary to produce variable models of the healthy organ. In order to build a database of uteri, a volunteer study was conducted. The segmentation was carried out interactively, also covering the establishment of an anatomically meaningful correspondence between the individual organs. The variability of the shape parameters has been characterized by principal component analysis. A new method has been developed and tested, allowing the derivation of realistic new instances based on the stochastic model and complying with non-linear shape constraints which are defined and interactively controlled by medical experts.

Computer Graphics↗

Association of serum pepsinogen with atrophic body gastritis in Costa Rica.

Individuals with atrophic gastritis (AG), especially atrophic body gastritis (ABG), are at increased risk of developing gastric cancer. Serum concentrations of pepsinogens (PG) have been proposed as markers for ABG. The aim of this study was to determine the risk factors for AG and ABG and the potential of using serum PG concentrations to detect ABG in a dyspeptic population in Costa Rica, which is one of the countries with the highest incidence and mortality rates of gastric cancer in the world. Seven biopsy specimens, a fasting blood sample and a questionnaire concerning sociodemographic factors were obtained from 501 consecutive dyspeptic patients. The serum PGI level and the PGI/PGII ratios were significantly lower in patients with ABG than in other groups (P<0.000). A cut-off point of 3.4 led to a sensitivity of 91.2% in identifying ABG, a negative predictive value of 98.1%, but a positive predictive value of only 11.2%. Helicobacter pylori were present in 93% of the patients and all those with peptic ulcers were positive. AG was associated with increased age, lower body mass index, high alcohol intake and low fruit consumption. ABG was associated with age, alcohol consumption and PGI/PGII<3.4. In dyspeptic patients with a high prevalence of H. pylori infection, serum PG levels provide an assessment of ABG but it is necessary to introduce other serological and genetic markers in order to achieve a better specificity. Those markers could be serum antibodies to H. pylori-CagA, cytokine gene polymorphisms or others.

Costa Rica↗

Construct and face validity of MIST-VR, Endotower, and CELTS: are we ready for skills assessment using simulators?

BACKGROUND: Video trainers may best offer visually realistic laparoscopic simulation, whereas virtual reality (VR) modules may best provide multidimensional objective measures of performance. This study compares the construct and face validity of three different laparoscopic simulators. METHODS: Subjects were voluntarily enrolled at the Learning Center during the 2004 SAGES annual meeting. Each subject completed two repetitions of a single task on each of three simulators, MIST-VR, Endotower, and CELTS; performance scores were automatically generated and recorded. Scores of individuals with various levels of experience were compared to determine construct validity for each simulator. Experience was defined according to four parameters: (a) PGY level, (b) fellowship training, (c) basic laparoscopic cases, and (d) advanced laparoscopic cases. Subjects rated each simulator regarding six face validity (realism of simulation) parameters using a 10-point Likert scale (10 = best rating) and participant scores were compared to previously established expert scores (proficiency goals for training). RESULTS: Ninety-one attendees completed the study. Construct validity was demonstrated for all three simulators; significant differences in scores were detected according to one parameter for MIST-VR, two parameters for Endotower, and all four parameters for CELTS. Face validity was rated as good to excellent for all three simulators (7.0 +/- 0.3 for MIST-VR, 7.9 +/- 0.3 for Endotower [p < 0.001 vs MIST-VR], and 8.7 +/- 0.1 for CELTS [p = 0.001 vs MIST-VR, p = 0.01 vs Endotower]); 6%, 0%, and 36% of "expert" participants obtained expert scores on MIST-VR, Endotower, and CELTS, respectively. CONCLUSIONS: All three simulators demonstrated significant construct and reasonable face validity. Although virtual reality holds great promise to expand the scope of laparoscopic simulation, current interfaces may limit their utility for assessment. Computer-enhanced video trainers may offer an improved interface while incorporating useful multidimensional metrics. Further work is needed to establish standards for appropriate skills assessment methods and performance levels using simulators.

Adult↗

Tooth enamel defects in mice with a deletion at the Arhgap 6/Amel X locus.

The amelogenin proteins regulate enamel mineral formation in the developing tooth. The human AMELX gene, which encodes the amelogenin proteins, is located within an intron of the Arhgap 6 gene. ARHGAP 6 encodes a Rho GAP, which regulates activity of Rho A, a small G protein involved in intracellular signal transduction. Mice were generated in which the entire ARHGAP 6 gene was deleted by Cre-mediated recombination, which also removed the nested Amel X gene. Enamel from these mice appeared chalky white, and the molars showed excessive wear. The enamel layer was hypoplastic and non-prismatic, whereas other dental tissues had normal morphology. This phenotype is similar to that reported for Amel X null mice, which have a short deletion that removed the region surrounding the translation initiation site, and resembles some forms of X-linked amelogenesis imperfecta in humans. Analysis of the enamel from the Arhgap 6/Amel X-deleted mice verifies that the Amel X gene is nested within the murine Arhgap 6 gene and shows that removal of the entire Amel X gene leads to a phenotype similar to the earlier Amel X null mouse results, in which no amelogenin protein was detected. However, an unusual layer of aprismatic enamel covers the enamel surface, which may be related to the 1.1-Mb deletion, which included Arhgap 6 in these mice.

Amelogenesis Imperfecta↗

Hydrometra simulation for VR-based hysteroscopy training.

During hysteroscopy a hydrometra is maintained, i.e. the uterus is distended with liquid media to access and visualize the uterine cavity. The pressure and flow induced by the liquid are crucial tools for he gynecologists during surgery to obtain a clear view of the operation site. This paper presents two different aspects of hydrometra simulation, namely the distension of the uterine muscle and the liquid flow simulation in the cavity. The deformation of the organ's shape is computed offline based on finite element calculations whereas the flow is approximated on the fly by solving the simplified Navier-Stokes equations. The real-time capabilities of the presented algorithms as well as the level of fidelity achieved by the proposed methods are discussed.

Body Fluids↗

Association of interleukin-1B and interleukin-1RN polymorphisms with gastric cancer in a high-risk population of Costa Rica.

Several risk factors have been associated with gastric cancer, among them Helicobacter pylori infection. This bacterium yields inflammation, the degree of which depends on the bacterial strain and the severity of the host response. The inflammatory response involves a complex cytokine network. Recently, polymorphisms of the genes coding for interleukin-1beta (IL-1B), interleukin-1Ra (ILRN) and interleukin-10 have been associated with an increased risk of gastric cancer. In order to determine the association of the IL-1B, IL-1RN and IL-10 polymorphisms with gastric cancer in a high-risk Costa Rican population, we analysed purified DNA of 58 gastric cancer patients, 99 controls and 41 patients classified as group I or II, according to the Japanese classification. Genotyping was carried out by PCR, PCR-RFLP and pyrosequencing analysis. We did not find any association of the IL-1B-31, IL-1B-511 and IL-10 polymorphisms with the risk for developing gastric cancer in the studied population. Carriers of the IL-1B+3954T/- had an increased risk for developing gastric cancer (OR 3.7; 95%CI: 1.34-10.2). Also we found an increased risk for developing gastric cancer for allele 2 heterozygotes of the IL-1RN (OR 2.94; 95%CI: 1.09-7.93). This is the first time that IL-1B+3954 has been associated with gastric cancer. This is one of the first studies trying to describe the role played by IL-1B, IL-1RN and IL-10 genetic polymorphisms in gastric cancer in one of the highest risk American countries. Further investigation on American countries is needed.

Aged↗

Development and transferability of a cost-effective laparoscopic camera navigation simulator.

BACKGROUND: Laparoscopic camera navigation (LCN) is vital for the successful performance of laparoscopic operations, yet little time is spent on training. This study aimed to develop an inexpensive LCN simulator, to design a structured curriculum, and to determine the transferability of skills acquired. METHODS: In this study, 0 degrees and 30 degrees LCN simulators were developed for use on a videotrainer platform. Transferability was tested by enrolling 20 medical students in an institutional review board-approved, randomized, controlled, blinded protocol. Subjects viewed a video tutorial and were pretested in LCN on a porcine Nissen model. Procedures were videotaped and the LCN performance was scored by a blinded rater according to the number of standardized verbal cues required and the percentage of time an optimal surgical view (%OSV) was obtained. Procedure time also was recorded. Subjects were stratified and randomized. The trained group practiced on the LCN simulator until competency was demonstrated. The control group received no training. Both groups were posttested on the porcine Nissen model. RESULTS: The constructed simulators required 35 man hours for development, cost $25 per board for materials, and proved to be durable. The trained group demonstrated significant improvement in verbal cues (p = 0.001), %OSV (p < 0.001), and procedure time (p = 0.001), whereas the control group showed improvement only in verbal cues (p < 0.02). At posttesting, the training group demonstrated significantly better scores for verbal cues (2.1 vs 8.0; p = 0.02) and %OSV (64% vs 45% p = 0.01) than the control group. CONCLUSION: These data suggest that the LCN simulator is cost effective and provides trainees with skills that translate to the operating room.

Adult↗

Incidental paraduodenal hernia found during laparoscopic colectomy.

This paper describes a rare right paraduodenal hernia discovered during an elective laparoscopic colon resection. Our patient was a 60-year-old Asian man with a history of multiple bouts of diverticulitis and a lifelong history of mild constipation and postprandial abdominal pain. Prior CT scans and preoperative barium enema confirmed the diagnosis of diverticular disease, and no other abnormalities were appreciated. At laparoscopic exploration, a right paraduodenal hernia was found with complete herniation of the small intestine under the ascending colon and hepatic flexure. The unclear anatomy prompted conversion to an open laparotomy. This allowed safe reduction of the hernia and sac excision. Adhesions were lysed to relieve a partial duodenal obstruction, and a Ladd's procedure was performed to correct the incomplete rotation. Additionally, a sigmoid colectomy was performed. After prolonged ileus, the patient was discharged on postoperative day 14. At 6-month follow-up, the patient was asymptomatic and doing well.

Colectomy↗

Stability studies of tablets containing 5 mg of policosanol.

The stability studies of tablets containing 5 mg of policosanol, a new cholesterol lowering drug, were conducted to predict an expiration date and to search the appearance of putative degradation products. All quality parameters such as colour, moisture content, hardness, disintegration, policosanol content and microbiological limits of the tablets were assessed. The effect of extreme treatments such as acid and basic hydrolysis, oxidative and photolytic degradation as well as thermal degradation, on the policosanol content was studied. In addition, studies under extreme conditions of storage [(40 +/- 2) degree C and (75 +/- 5)% R.H.] as well as 37, 45, 55 and 60 degrees C combined with 50, 75 and 92% R.H.) and under ambient conditions of storage for climatic zones II and IV were performed. These studies demonstrate that these tablets are a stable pharmaceutical formulation, without significant changes in their quality criteria at the stressed conditions used, so that policosanol content remains unchanged during the entire studies. The chromatographic profile of the samples after 9 months of thermal degradation shows chromatographic peaks that corresponds to the palmitate and stearate esters of octacosanoyl, triacontanoyl and hexacosanoyl, being the only degradation products observed on these studies.

Anticholesteremic Agents↗

Physico-mechanical characterization of policosanol, a novel hypocholesterolemic drug.

As part of the formulation studies of policosanol, a new hypocholesterolemic drug, a physico-mechanical characterization was developed. Thermal analysis, using differential scanning calorimetry was used to evaluate the purity of policosanol from batch to batch and, also, the particle size distribution. The degree of wettability of policosanol was studied by measuring the contact angle and solubility in different solvents. The compressibility and cohesion of particles were evaluated using a profile of compression forces, ranging between 6.5 kN and 39.0 kN. Also, other properties such as flow properties, true density, and tapped and bulk density were measured. The industrial batches of policosanol that were studied show an adequate purity and a uniform distribution of the particle sizes. Policosanol shows good flow properties, compressibility, and cohesion as well as a low solubility in the majority of the solvents used in the pharmaceutical industry, and its solubility in water or in aqueous solutions was, mainly, null. The wettability of policosanol in the different solvents shows the following order: methylene chloride > ethanol > acetone >> water.

Anticholesteremic Agents↗

[Cefotaxime, twenty years later. Observational study in critically ill patients].

OBJECTIVE: Afer twenty years of commercial availability of cefotaxime, the objective of this study was to know the reasons and modes of use, administration dosage as well as its effectiveness and tolerance in critically ill patients admitted to Intensive Care Units (ICU) in our country. DESIGN: Open, prospective, observational, multicenter study. SUBJECTS: All patients who had cefotaxime administered in monotherapy or in combination with other antibiotics were included as cases in this study. RESULTS: A total of 624 patients were included in 44 ICUs (average 14 cases). Cefotaxime was indicated for therapy of 274 community-acquired infections (43.9%), 194 prophylaxis (31.1%), and 156 nosocomial infections (25.0%). Both community-acquired pneumonia (149, 34.7%) and mechanical ventilation associated pneumonia (62, 14.4%) predominated, followed by trachebronchitis (60, 13.9%) and central nervous system infections (42, 9.8%). Over half of infections (222, 51.6%) presented as systemic inflammatory response syndrome (SIRS), 133 (30.9%) as severe sepsis, and 75 (17.4%) as septic shock. In 374 (87.0%) out of the 430 cases of infection treatment, cefotaxime wan prescribed on an empirical basis and in 150 of them (40.1%) a further confirmation of the causative agent was obtained. In 120 (27.9%) cases, cefotaxime was administered as monotherapy and in the remaining cases in association with one or more antibiotics.The use of cefotaxime as prophylaxis was evaluated as failure in 31 (16.0%) of the cases, whereas in treatment it was considered as failure in 98 (22.8%) of the 430 cases, 51 community-acquired infections, 27 (27.3%) of ICU-acquired infections, and 20 (35.1%) nosocomial infections acquired outside the ICU. In 127 (29.5%) of the 430 infection treatments the initial treatment was changed. The reasons for the change included clinical failure (36, 28.3%), recovery of an uncovered pathogen with the antibiotic (40, 31.5%), emergence of multi-resistant pathogens (28, 22.0%), to decrease the therapeutic spectrum (7, 5.5%), and other reasons (16). Cefotoxime was also changed in 21 (6.0%) of the 194 cases in which it was used as prophylaxis. In 32 (5.1%) patients 37 adverse effects were noted which were associated with a possible or likely use of cefotaxime. Most notably, diarrhoea in 15 (2.4%) occasions and skin rash in 6 cases (1.0%). CONCLUSIONS: Cefotaxime is still one of the therapies of choice for community-acquired and nosocomial infections as well as in different prophylactic modes. It is mostly used on an empirical basis and associated with other antibiotics. Clinical and microbiological efficiency is high whereas adverse effects related to its use have been scarce.

Antibiotic Prophylaxis↗

Composition and gene expression of the cag pathogenicity island in Helicobacter pylori strains isolated from gastric carcinoma and gastritis patients in Costa Rica.

The composition and in vitro expression of the cag pathogenicity island genes in a group of Helicobacter pylori strains obtained from patients suffering from chronic gastritis-associated dyspepsia (n = 26) or gastric carcinoma (n = 17) were analyzed. No significant difference in the distribution of the 10 studied regions was found between the cases and the controls. Nine strains did not harbor any of the selected regions: eight (30.8%) isolated from patients with gastritis only and one (5.9%) from a patient with gastric carcinoma. No association was found between the number of repeated sequences at the 3' end of the cagA gene or the presence of tyrosine phosphorylation motifs and the clinical origin of the strains. The virB10 homolog gene was the sole gene studied to be significantly expressed more often in cancer strains than in gastritis strains (P = 0.03).

Antigens, Bacterial↗

Distribution of open reading frames of plasticity region of strain J99 in Helicobacter pylori strains isolated from gastric carcinoma and gastritis patients in Costa Rica.

The plasticity region of Helicobacter pylori strain J99 is a large chromosomal segment containing 33 strain-specific open reading frames (ORFs) with characteristics of a pathogenicity island. To study the diversity of the plasticity region, 22 probes corresponding to 20 ORFs inside the plasticity region and two ORFs on its boundaries were hybridized to genomic DNA isolated from clinical strains of H. pylori from patients with gastritis or gastric adenocarcinoma. Highly variable hybridization patterns were observed. The majority of the clinical strains presented a hybridization profile similar to that of J99; thus, these ORFs are not J99 strain specific. No association was found between a particular hybridization pattern and the clinical origin of the strain. Nevertheless, two single ORFs (JHP940 and JHP947) were more likely to be found in gastric cancer strains. They may be new pathogenicity markers. An in vitro expression study of these ORFs was also performed for the J99 strain, under different conditions. Thirteen ORFs were consistently expressed, six were consistently shut off, and three were expressed differentially. Most of the constitutionally expressed genes were located on the 3' part of the plasticity region. Our results show that the plasticity region, rather than being considered a pathogenicity island per se, should be considered a genomic island, which represents a large fragment of foreign DNA integrated into the genome and not necessarily implicated in the pathogenic capacity of the strain.

Blotting, Southern↗

A 5' splice site-proximal enhancer binds SF1 and activates exon bridging of a microexon.

Internal exon size in vertebrates occurs over a narrow size range. Experimentally, exons shorter than 50 nucleotides are poorly included in mRNA unless accompanied by strengthened splice sites or accessory sequences that act as splicing enhancers, suggesting steric interference between snRNPs and other splicing factors binding simultaneously to the 3' and 5' splice sites of microexons. Despite these problems, very small naturally occurring exons exist. Here we studied the factors and mechanism involved in recognizing a constitutively included six-nucleotide exon from the cardiac troponin T gene. Inclusion of this exon is dependent on an enhancer located downstream of the 5' splice site. This enhancer contains six copies of the simple sequence GGGGCUG. The enhancer activates heterologous microexons and will work when located either upstream or downstream of the target exon, suggesting an ability to bind factors that bridge splicing units. A single copy of this sequence is sufficient for in vivo exon inclusion and is the binding site for the known bridging mammalian splicing factor 1 (SF1). The enhancer and its bound SF1 act to increase recognition of the upstream exon during exon definition, such that competition of in vitro reactions with RNAs containing the GGGGCUG repeated sequence depress splicing of the upstream intron, assembly of the spliceosome on the 3' splice site of the exon, and cross-linking of SF1. These results suggest a model in which SF1 bridges the small exon during initial assembly, thereby effectively extending the domain of the exon.

5' Untranslated Regions↗

Malignant myoepithelioma of the salivary glands: clinicopathological and immunohistochemical features.

Malignant myoepitheliomas (myoepithelial carcinomas) are uncommon, and we know of only 29 reported cases. We present a new case together with its clinical, histological, and immunohistochemical features. The tumour was located in the inferior vestibular sulcus of a 64-year-old woman. She was treated by wide local resection. Malignant myoepitheliomas are distinguished from benign myoepithelial neoplasms by their infiltrating and destructive growth. The tumour cells may be spindle-shaped or more rounded (plasmacytoid cells) and contain cellular pleomorphism and mitotic activity. The clinical and biological behaviour of this tumour is not yet known and there is little information about treatment and prognosis.

Diagnosis, Differential↗

Bone turnover and mineral metabolism in the last trimester of pregnancy: effect of multiple gestation.

OBJECTIVE: To test the hypothesis that maternal bone turnover and mineral stress are greater in multiple pregnancy than in singleton pregnancy. METHODS: We measured serum markers of bone turnover and mineral stress in 17 multiple and 30 singleton pregnancies during the third trimester. RESULTS: Serum 25(OH) vitamin D, a marker of vitamin D intake, was higher (61 +/- 5 versus 39 +/- 2 ng/mL, P < .001), and 1,25(OH)2 vitamin D was lower (50 [95% confidence interval (CI) 24-102] versus 64 pg/mL [95% CI 30-135], P = .03) in multiple than in singleton pregnancy. Carboxyterminal telopeptide of type I collagen, a marker of bone resorption, increased with gestational duration and was higher in multiple gestation (5.8 [95% CI 3.3-10.1] versus 4.4 ng/mL [95% CI 2.5-7.8], P = .005). Carboxyl-terminal propeptide of type 1 procollagen, a marker of bone formation, increased with gestational duration and was not different between groups (110 [95% CI 36-337] versus 99 ng/mL [95% CI 34-286], P = .5). Calcitonin increased with gestational duration and was not different between groups (7.0 [95% CI 3.7-13.0] versus 7.8 pg/mL [95% CI 4.0-15.4], P = .37). Parathyroid hormone was not different between groups and decreased with increasing maternal age. CONCLUSION: Bone turnover indices increased with gestational duration. The bone resorption index was greater in multiple than in singleton gestation. Serum 25(OH) vitamin D was greater and 1,25(OH)2 vitamin D was lower in multiple gestation, presumably because of greater consumption of vitamin D and minerals by women carrying more than one fetus.

Adult↗