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Biomedical subjects

G Ortega

Publications and source records attributed to G Ortega.

At least 19 recordsLinked to original sources

Preliminary clinical experience using a newly developed minimal-invasive reference base in computer assisted foot surgery.

In recent years, many new tools and techniques have been developed in computer assisted orthopaedic surgery primarily with an industry led effort in software innovation and development. Only a few research and clinical projects have focused on intraoperative difficulties. A common operative challenge in computer assisted orthopaedic surgery is the positioning of the reference base. Rigid fixation of a dynamic reference base is essential in navigated surgery of the extremities. The aim of this study was to develop a minimal-invasive screw which could be placed effectively and efficiently with rotational stability during computer assisted orthopaedic surgery. The minimal-invasive screw was initially evaluated in an artificial bone experiment. After successful results with the artificial bone experiment, it underwent testing in seven human cadaver thighs with ISO-C3D navigated drilling. Finally the screw was transferred into a clinical application during five foot surgeries. In 10 ISO-C3D navigated drillings, the lesions were targeted 100% of the drillings. A screw dislocation was not observed. In comparison to conventional one or two pin fixation systems, the newly designed small screw did not have any observed side effects such as artifacts. In addition, the screw generated less heterodyning than a conventional fixation system. The small screw design is an advantage in theatre. We believe the minimally-invasive screw allows the surgeon to use a tool that helps avoid common pitfalls from conventional fixation systems, and it may improve efficiency.

Bone Screws↗

Prevalence, resource utilization and costs of vascular dementia compared to Alzheimer's dementia in a population setting.

OBJECTIVES: To determine the prevalence of dementia and to measure the monetary impact and health resources utilization of vascular dementia (VD) compared to Alzheimer's dementia (AD) in persons aged over 64 years in a population setting. METHODS: Retrospective, cross-sectional study. In the initial phase, information was obtained on specific clinical characteristics from the subjects with an active diagnosis of dementia. The second phase consisted of a clinical evaluation and validation of the cases. Mini-Mental State Examination was used to assess cognitive impairment. Dementia and its subtypes were determined using established diagnostic criteria. Information was obtained on the use of health care resources (direct costs) and the number of hours devoted by the primary caregiver (indirect costs) for patients with a documented diagnosis of AD or VD within the last 6 months prior to the interview. A multiple logistic regression analysis was performed to correct the model. RESULTS: A total of 6,004 subjects were analyzed, 258 with diagnosis of dementia (overall prevalence: 4.3%). An evaluation was made of 224 patients, and gross prevalence of AD and VD was 2.4 and 1.0%, respectively. Cost per patient per semester was EUR 8,086 for AD and EUR 11,039 for VD (p = 0.016). 85.5% of the cost was attributable to primary caregiver time in AD and 84.4% in VD. CONCLUSIONS: The prevalence of AD and VD increases with age. No sociodemographic differences were seen between AD and VD. Costs associated with health care resource and primary caregiver utilization were high, being higher in VD than in AD.

Age Distribution↗

The genomic organization of the murine Mlc1 (Wkl1, KIAA0027) gene.

The human MLC1( WKL1, KIAA0027) gene encodes a putative transmembrane protein expressed exclusively in brain. Recessive mutations within this gene cause megalencephalic leukoencephalopathy with subcortical cysts (MLC, MIM 604004, 605908). Furthermore, a missense mutation in this gene is suggestively linked with hereditary catatonic schizophrenia in a large pedigree. The murine gene Mlc1is composed of 12 exons spanning approximately 20 kb, and all exon-intron boundaries conform to the GT/AG consensus. The single copy transcript after splicing is approximately 2.8 kb in length, it contains 496 bp of 5' untranslated region (5'-UTR) and 1143 bp of 3'-UTR, and encodes a protein of 382 amino acids. Potential binding sites for transcription factors including CCAAT-boxes are present in the 5'-flanking region. Fluorescent in situ hybridization localizes the gene to mouse chromosome 15E-F, a region syntenic to human chromosome 22q13. The characterization of the genomic structure of the murine gene will facilitate studies of gene function and physiological properties of the encoded protein in transgenic mouse models.

Amino Acid Sequence↗

Effects of fluctuations on electrical properties of gap-junction connected cells in the turtle retina.

Electrical properties of gap-junction connected cells (input voltage and length constant) are shown to depend strongly on fluctuations in membrane and contact conductances. This opens new possibilities and incorporates a further difficulty to the analysis of electrophysiological data, since four, instead of two, parameters (the average values and the magnitude of fluctuations of the two conductances) have to be used in fitting the experimental data. The discussion is illustrated by investigating the effects of dopamine on signal spreading in horizontal cells of turtle retina, assuming a linear cell arrangement. It is shown that while a standard fitting with the average values of the two conductances leads to the conclusion that both are equally affected by dopamine, including fluctuations allows fitting the data by varying just the average contact conductance plus the magnitude of fluctuations.

Animals↗

Exclusion of the neuronal nicotinic acetylcholine receptor alpha7 subunit gene as a candidate for catatonic schizophrenia in a large family supporting the chromosome 15q13-22 locus.

The gene encoding the neuronal nicotinic acetylcholine receptor alpha7 subunit (CHRNA7) is located on chromosome 15q13.2. This region was suggested to be involved in the etiopathogenesis of: (a) schizophrenia combined with a neurophysiological deficit; (b) lithium-responsive bipolar disorder; and (c) familial catatonic schizophrenia (periodic catatonia). Therefore, members of a large family with periodic catatonia strongly supporting the chromosome 15q13-22 region were genotyped with polymorphic markers localized around the CHRNA7 locus. A recombination event distally of marker D15S144 leading to the exclusion of the CHRNA7 locus from this candidate region was detected in one branch of the pedigree. This result provides strong evidence that a gene located telomeric to CHRNA7 is causative for the pathogenesis of catatonic schizophrenia in this family.

Chromosomes, Human, Pair 15↗

Gap junctional channels regulate acid secretion in the mammalian gastric gland.

Gap junction channels are regarded as a primary pathway for intercellular message transfer, including calcium wave propagation. Our study identified two gap junctional proteins, connexin26 and connexin32, in rat gastric glands by RT-PCR, Western blot analysis, and immunofluorescence. We demonstrated a potential physiological role of the gap junctional channels in the acid secretory process using the calcium indicator fluo-3, and microinjection of Lucifer Yellow. Application of gastrin (10-7 m) to the basolateral membrane resulted in the induction of uniphasic calcium signals in adjacent parietal cells. In addition, single parietal cell microinjections in intact glands with the cell-impermeant dye Lucifer Yellow resulted in a transfer of dye from the injected cell to the adjacent parietal cell following gastrin stimulation, demonstrating gastrin-induced cell-to-cell communication. Both calcium wave propagation and Lucifer Yellow transfer were blocked by the gap junction inhibitor 18alpha-glycyrrhetinic acid. Our studies demonstrate that functional gap junction channels in gastric glands provide an effective means for rapid cell-to-cell communication and allow for the rapid onset of acid secretion.

Animals↗

Paclitaxel and gemcitabine chemotherapy for advanced transitional-cell carcinoma of the urothelial tract: a phase II trial of the Minnie pearl cancer research network.

PURPOSE: To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel and gemcitabine in patients with advanced transitional-cell carcinoma of the urothelial tract. PATIENTS AND METHODS: Fifty-four patients with advanced unresectable urothelial carcinoma entered this multi-centered, community-based, phase II trial between May 1997 and December 1999. All patients were treated with paclitaxel 200 mg/m(2) by 1-hour intravenous (IV) infusion on day 1 and gemcitabine 1,000 mg/m(2) IV on days 1, 8, and 15; courses were repeated every 21 days. Patients who had objective response or stable disease continued treatment for six courses. RESULTS: Twenty-nine of 54 patients (54%; 95% confidence interval, 40% to 67%) had major responses to treatment, including 7% complete responses. With a median follow-up of 24 months, 16 patients (30%) remain alive and nine (17%) are progression-free. The median survival for the entire group was 14.4 months; 1- and 2-year actuarial survival rates were 57% and 25%, respectively. Seven (47%) of 15 patients previously treated with platinum-based chemotherapy responded to paclitaxel/gemcitabine. Grade 3/4 toxicity was primarily hematologic, including leukopenia (46%), thrombocytopenia (13%), and anemia (28%). Ten patients (19%) required hospitalization for neutropenia and fever, and one patient had treatment-related septic death. CONCLUSION: The combination of paclitaxel and gemcitabine is active and well tolerated in the first- or second-line treatment of patients with advanced transitional-cell carcinoma of the urothelial tract. Response rate and duration compare favorably with those produced by other active, first-line regimens. This regimen should be further evaluated in phase II and III studies, as well as in patients with compromised renal function.

Actuarial Analysis↗

A missense mutation in a novel gene encoding a putative cation channel is associated with catatonic schizophrenia in a large pedigree.

Schizophrenia is a common and etiologically heterogeneous disorder. Although inheritance of schizophrenic syndromes is complex with genetic and environmental factors contributing to the clinical phenotype, periodic catatonia, a familial subtype of catatonic schizophrenia, appears to be transmitted in an autosomal dominant manner. We report here that a Leu309Met mutation in WKL1, a positional candidate gene on chromosome 22q13.33 encoding a putative non-selective cation channel expressed exclusively in brain, co-segregates with periodic catatonia in an extended pedigree. Structural analyses revealed that this missense mutation results in conformational changes of the mutant protein. Our results not only underscore the importance of genetic mechanisms in the etiology of schizophrenic syndromes, but also provide a better understanding of the pathogenesis and incapacitating course of catatonic schizophrenia and related disorders.

Amino Acid Sequence↗

Mutational analysis of the neuronal cadherin gene CELSR1 and exclusion as a candidate for catatonic schizophrenia in a large family.

The cadherin gene CELSR1 is specifically expressed in the brain and located on chromosome 22q13.33, a region that has recently been shown to be involved in the etiopathogenesis of familial catatonic schizophrenia. The gene is a strong positional candidate and was considered for mutational analysis. A total of 17 allelic variants of CELSR1 was found by sequencing all 35 exons, intron-exon junctions, and the putative promoter region by screening two patients from a large family mainly supporting this locus, and three control subjects in a first step. No variant exclusively co-segregates with the disease in the large pedigree, providing evidence that CELSR1 is not causative for the pathogenesis of catatonic schizophrenia in this family.

Alleles↗

Role of architecture in determining passive electrical properties in gap junction-connected cells.

The electrical properties of gap junction-connected cells were analysed in terms of their architectural organization. Two major architectural categories were considered: trees and rings. Trees are described by means of Bethe lattices (lattices with no rings) with arbitrary co-ordination and rings by two-dimensional periodic lattices with fourfold (square) or sixfold (triangular) co-ordination. The Bethe lattice is solved analytically by the transfer constant method, which allows the introduction of several physiologically relevant effects in a very simple manner. The experimental data for the length constant and the input resistance were fitted by varying the coupling and membrane resistances for various morphologies. The large variations in the length constant observed experimentally in two systems (turtle retina horizontal cells with and without dopamine and pancreatic beta-cells in the active and silent phases) could not be explained by means of the Bethe lattice, indicating that the cell arrangements form rings. Subsequent analysis by means of a linear chain and the square and triangular lattices showed the crucial relevance of architecture in deriving the electrical characteristics of gap junction-connected cells from experimental data.

Animals↗

Phylogenetic comparison of the DEN-2 Mexican isolate with other flaviviruses.

Recent attention has focused on the geographic variation of dengue viruses, since major epidemies may follow introduction of a new virus strain into susceptible populations. We cloned and sequenced a very interesting Mexican isolate (200787/1983) which is antigenically unique by signature analysis with respect to all other dengue-2 topotype viruses. This strain is also unique in biological behavior (neurotropism) and is of epidemiological significance in Mexico. The dengue-2 Mexican isolate sequence information was compared with that of other flaviviruses, analyzing the branching structure of the phylogenetic tree reconstructed from the E gene amino acid sequences. The E glycoprotein, is target for neutralizing antibodies and T-cell responses, and defines the tropism and virulence of flaviviruses. In the phylogram, our strain was located in the position of greatest dissimilarity within serotype-2. Also, frequency analysis of amino acids revealed a very different signature pattern from that found in viral serotype-2.

Amino Acid Sequence↗

Are neurons multifractals?

In the last few years, fractal analysis has found widespread application in the field of neuroscience and some investigators are starting to use multifractals as a methodology that may provide information about the distribution of fractal dimensions in biological structures. This is so, despite of the technical difficulties of multifractal analysis. In this paper, we investigate the theoretical and practical aspects of studying and measuring the multifractal dimensions of neurons. Patterns were analysed by means of the standard box-counting method and a generalised sand-box method. Our results show that odd behaviours of Dq reported in the literature are a consequence of numerical deficiencies of the box-counting method and cannot be associated to peculiar geometrical characteristics of neurons. Instead the sand-box method gives a Dq which monotonically decreases with q. Although this result may indicate that neurons are multifractals, it is argued that size effects may in fact be the origin of this apparent multifractality.

Animals↗