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Biomedical subjects

A Pizarro

Publications and source records attributed to A Pizarro.

At least 19 recordsLinked to original sources
PubMed2003

Maintaining data integrity in microarray data management.

Gene expression microarrays are a relatively new technology, dating back just a few years, yet they have already become a very widely used tool in biology, and have evolved to a wide range of applications well beyond their original design intent. However, while the use of microarrays has expanded, and the issues of performance optimization have been intensively studied, the fundamental issue of data integrity management has largely been ignored. Now that performance has improved so greatly, the shortcomings of data integrity control methods constitute a greater percent of the stumbling blocks for investigators. Microarray data are cumbersome, and the rule up to this point has mostly been one of hands-on transformations, leading to human errors which often have dramatic consequences. We show in this review that the time lost on such mistakes is enormous and dramatically affects results; therefore, mistakes should be mitigated in any way possible. We outline the scope of the data integrity issue, to survey some of the most common and dangerous data transformations, and their shortcomings. To illustrate, we review some case studies. We then look at the work done by the research community on this issue (which admittedly is meager up to this point). Some data integrity issues are always going to be difficult, while others will become easier-one of our goals is to expedite the use of integrity control methods. Finally, we present some preliminary guidelines and some specific approaches that we believe should be the focus of future research.

Algorithms↗
PubMed2002

[Tetrabamate-induced hepatotoxicity. Report of seven cases and literature review].

OBJECTIVES: Analysis of all cases of tetrabamate (Atrium)-induced hepatotoxicity reported in the Andalusian Registry of drug-induced liver disorders and comparison with cases reported in the literature. MATERIAL AND METHOD: Information was gathered in a structured protocol. The causal role of tetrabamate was estimated in each case using the diagnostic scale of the Council for International Organizations of Medical Sciences (CIOMS). RESULTS: Of 327 cases of hepatotoxicity, 7 (2%) were due to tetrabamate. The mean age was 57 years (4 men). In 57% of the cases, the presenting symptom was tremor. The latency period was between 15 and 730 days. Liver damage was mainly cytolytic without signs of hypersensitivity. In all cases outcome was favorable with complete recovery between 60 and 120 days. The CIOMS diagnostic scale rated a causal role of tetrabamate as highly probable in six cases and as probable in one. CONCLUSION: Tetrabamate can induce hepatotoxicity, probably due to an idiosyncratic metabolic mechanism. Because of this finding and the existence of more appropriate therapeutic alternatives, tetrabamate should not be used in the treatment of alcohol withdrawal.

Adult↗
PubMed2002

[Comparative study of prognostic and risk factors for mortality in polymicrobial bacteremia-fungemia in a university hospital: development over 10 years].

OBJECTIVE: Eighty-two episodes of polymicrobial bacteremia in two time periods, 1986-87 and 1996-97, were compared to assess differences in risk factors and outcome to mortality. METHODS: A prospective, concurrent, anterograde study with univariate analysis of all episodes of polymicrobial bacteremia was performed in Hospital de la Princesa. Logistic regression analysis was applied to all significant variables (p < 0.05) in the univariate analysis in either of the two time periods. RESULTS: Variables showing statistically significant differences in incidence between the two time periods included the following: hospital acquired bacteremia; previous use of antibiotics; genitourinary, respiratory and cardiovascular manipulations; septic metastases; and absence of leukocytosis. These factors were more frequently present during 1986-87 than during 1996-97. The overall RR of outcome to mortality was five-fold greater during the first period than the second: RR 5.6 (CI 1.76-17.56) p < 0.001. The clinical characteristics at the onset of bacteremia associated with mortality in the first period were: underlying disease - < RR 2.20 (CI 1.18-4.08), steroid treatment - < RR 4.24 (CI 0.68-26.59), hypotension - < RR 2.05 (CI 1.0-4.17), and disseminated intravascular coagulation - < RR 2.31 (CI 1.69-3.35). Clinical characteristics at the onset of bacteremia associated with mortality in the second period were: hypotension - < RR 1.44 (CI 1.01-2.08), underlying disease - < RR 1.16 (CI 1.02-1.34), and disseminated intravascular coagulation - < RR 6.40 (CI 1.15-35.69). The variables independently associated with mortality in polymicrobial bacteremia were: period - < RR 2.05 (CI 1.50-2.10), underlying disease - < RR 7.05 (CI 2.68-7.50), hypotension - < RR 7.06 (CI 3.80-7.29), and (probably) vascular manipulations - < RR 3.41 (CI 0.85-4.53). CONCLUSION: Polymicrobial bacteremia-associated mortality was five-fold greater in 1986-87 than in 1996-97. The variables independently associated with mortality risk were underlying disease, hypotension, the period studied (which would include a number of variables not analyzed in this work) and, probably, vascular manipulations.

Adolescent↗
PubMed2001

Sterically hindered cisplatin derivatives with multiple carboxylate auxiliary arms: synthesis and reactions with guanosine-5'-monophosphate and plasmid DNA.

Two novel sterically hindered cisplatin derivatives with the ligand L=NH(2)C(CH(2)CH(2)COOH)(3) were prepared: cis-PtCl(2)L(2) and cis-PtCl(2)L(NH(3)). The starting compound for the syntheses was NH(2)C(CH(2)CH(2)COOtBu)(3), also known as a building block for dendrimers. cis-PtCl(2)L(2) was prepared from K(2)PtCl(4) in an unusual two-phase reaction in water-chloroform, followed by deprotection of the tert-butyl protective groups with formic acid to yield a water-soluble complex. The mixed-ligand compound cis-PtCl(2)L(NH(3)) was prepared from [PPh(4)][PtCl(3)(NH(3))] in methanol, with subsequent deprotection in formic acid. DNA-binding properties of the two compounds were investigated using the model base guanosine-5'-monophosphate (5'-GMP) and pBR322 plasmid DNA. While cisplatin [cis-PtCl(2)(NH(3))(2)] induced an unwinding of 12 degrees in pBR322 plasmid DNA, cis-PtCl(2)L(NH(3)) induced only 3 degrees unwinding, which is indicative of a monofunctional binding mode. Remarkably, cis-PtCl(2)L(2) did not induce any distortion in plasmid DNA, which strongly suggests that the compound does not bind to DNA. Test reactions with 5'-GMP, monitored by 1H and 195Pt NMR, confirmed that cis-PtCl(2)L(2) is unable to bind to DNA, whereas cis-PtCl(2)L(NH(3)) binds only one nucleotide. Apparently, binding of platinum to nucleotides at the coordination site cis with respect to the ligand L is prevented by steric crowding. Thus, cis-PtCl(2)L(NH(3)) must bind DNA monofunctionally at the trans position. Besides, both compounds have a chloride replaced by one of the carboxylate arms, forming a a seven-membered chelate ring. In theory, cis-PtCl(2)L(2) could also form a second chelate ring, but this was not observed.

Antineoplastic Agents↗
PubMed2001

A relational schema for both array-based and SAGE gene expression experiments.

MOTIVATION AND RESULTS: A relational schema is described for capturing highly parallel gene expression experiments using different technologies. This schema grew out of efforts to build a database for collaborators working on different biological systems and using different types of platforms in their gene expression experiments as well as different types of image quantification software. The tables are conceptually organized into three categories of information: Platform, Experiment (which includes image scanning and quantification), and Data. The strengths of the schema are: (i) integrating information on array elements using a gene index; (ii) describing samples using ontologies; (iii) reducing an experiment to a single RNA source for precise descriptions yet not losing the relationships between experiments done at the same time or for the same project; and (iv) maintaining both raw and processed (e.g. cleansed and normalized) data and recording how the data is processed. The result is a novel schema, which can hold both array and non-array data, is extensible for detailed experimental descriptions that are precise and consistent, and allows for meaningful comparisons of genes between experiments.

Databases, Factual↗
PubMed1999

[A universal method to correct underreporting of communicable diseases. Real incidence of hydatidosis in Chile, 1985-1994].

BACKGROUND: There is evidence to postulate that undernotification is the reason for the great decrease in the reported incidence of hydatidosis in Chile. AIM: To develop and propose a method to assess the notification of transmissible diseases, based on observed lethality and hospital discharges. MATERIAL AND METHODS: Human hydatidosis in the period 1985-1994 was used as a model to develop the method. Official reports and mortality were analyzed first, determining the first lethality rate. A second lethality rate was calculated based on hospital discharges and a third, based on all Chilean surgical series published in the last two decades. Adjusting official notification of lethality to the true lethality according to surgical series, the number of unreported cases was calculated and the true incidence of hydatidosis was calculated, summing these cases to the official notification. RESULTS: According to this method, the real rates of human hydatidosis in the period 1985-1994, would fluctuate between 6.5 and 11.4 per 100,000. This figure is four times higher than the official notification in the analysed period. CONCLUSIONS: The correction of under notification based on hospital discharges, with or without correction for repeated hospital admissions, or real mortality of surgical series gave similar results, suggesting that both methods are correct.

Chile↗
PubMed1998

Low-frequency electromagnetic fields alter the replication cycle of MS2 bacteriophage.

The effect of exposure to 60-Hz electromagnetic fields (EMFs) on RNA coliphage MS2 replication was studied. EMF exposure commenced when the bacterial cultures were inoculated with the phage (t = 0). In 12 experiments in which the strength of the field was 5 G, a significant delay in phage yield was found in the EMF-exposed cultures 45-65 min after inoculation, compared with control cultures. However, the EMF did not alter the final phage concentration. Experiments at 25 G (N = 5) suggested that the stronger field resulted in both impeded phage replication and increased phage yield. No differences between test groups were found in experiments involving sham-EMF exposure, thereby indicating that the results obtained with the EMFs were not due to systematic error. It appears that MS2, which codes for only four proteins, is the simplest biological system in which an EMF-induced effect has been demonstrated. The MS2 system is, therefore, conducive to follow-up studies aimed at understanding the level and nature of the underlying interaction process, and perhaps to biophysical modeling of the interaction process.

Electromagnetic Fields↗
PubMed1998

Small-cell lung carcinoma: an analysis of 194 consecutive patients.

The treatment of small-cell lung carcinoma (SCLC) requires the careful combination of chemotherapy and radiation therapy. To understand the factors involved in the outcome of these patients, the authors undertook a study of patients treated for limited stage SCLC. The charts of 194 consecutive patients treated at our facilities between 1986 and 1994 were reviewed. All patients underwent thoracic radiation therapy (TRT), 50% received prophylactic cranial irradiation (PCI), and all but one received chemotherapy. The probability of survival at 5 years was 14%, and the disease-free survival (DFS) was 17%. Patients receiving a combination of platinum and etoposide (PE) and Cytoxan (Bristol-Myers, Evansville, IN, U.S.A.), Adriamycin (Adria Laboratories, Dublin, OH, U.S.A.), and Vincristine (Eli Lilly, Indianapolis, IN, U.S.A.) (CAV) experienced a DFS at 3 years of 31%, versus 14% for CAV only and 18% for PE only (p = 0.004). In a multivariate survival analysis, only PCI (p = 0.001), having received PE and CAV (p = 0.01), and response to treatment (p = 0.001) were significant. Radiation dose and field size did not influence outcome. The combination of PE and CAV chemotherapy produced the best results in our series. Unanswered questions regarding the optimal TRT dose, field size, and timing of TRT await the results of ongoing randomized trials.

Adult↗
PubMed1998

Inhibition of phosphodiesterase type IV suppresses human immunodeficiency virus type 1 replication and cytokine production in primary T cells: involvement of NF-kappaB and NFAT.

Rolipram, a phosphosdiesterase type IV-specific inhibitor, prevented p24 antigen release from anti-CD3-activated human immunodeficiency virus (HIV)-infected T cells and CD4(+)-cell depletion associated with viral replication in a dose-responsive manner but minimally inhibited T-cell proliferation. Moreover, rolipram reduced the production of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) by HIV-infected T cells. The transcriptional ability of a luciferase reporter gene under control of the HIV long terminal repeat, induced by phorbol myristic acetate plus ionomycin or by TNF-alpha, in primary T and Jurkat cells was also inhibited by rolipram. Rolipram inhibited NF-kappaB and NFAT activation induced by T-cell activation in Jurkat and primary T cells, as measured by transient transfection of reporter genes and electrophoretic mobility shift assays. Exogenous addition of TNF-alpha in the presence of rolipram restored NF-kappaB but not NFAT activation or p24 release. Addition of dibutyryl-cyclic AMP (dBcAMP) mimicked the effects of rolipram on p24 antigen release, NF-kappaB activation, and TNF-alpha secretion, but it did not affect NFAT activation or IL-10 production. The protein kinase A inhibitor KT5720 prevented the inhibition of TNF-alpha secretion but not that of HIV type 1 (HIV-1) replication caused by rolipram. Our data indicate that blockade of phosphodiesterase type IV could be of benefit against HIV-1 disease by modulating cytokine secretion and transcriptional regulation of HIV replication, and they suggest an important role of NFAT in HIV replication in primary T cells. Some of those activities cannot be ascribed solely to its ability to increase cAMP.

Cells, Cultured↗