VIGILANCIA TECNOLÓGICA PARA LA GESTIÓN DEL RIESGO TECNOLÓGICO EN EL SECTOR SALUD ASOCIADO A LA NORMA ISO 31000 / TECHNOLOGY WATCH FOR TECHNOLOGICAL RISK MANAGEMENT IN HEALTHCARE ASSOCIATED WITH THE ISO 31000 STANDARD / VIGILÂNCIA TECNOLÓGICA PARA GERENCIAMENTO DE RISCO TECNOLÓGICO EM SAÚDE ASSOCIADO COM O PADRÃO ISO 31000

La gestión estratégica de la información científico-tecnológica resulta cada vez más importante para innovar y sobrevivir en la actualidad. Es por esto, que las instituciones hospitalarias asumen la Gestión del Riesgo Tecnológico (GRT), como parte vital de las estrategias de innovación. En el presente artículo, se reporta un estudio de Vigilancia Tecnológica para la priorización de los datos más relevantes y de la información estratégica acerca de GRT en organizaciones hospitalarias. Esto, con base en el estudio de la norma ISO 31000. Inicialmente, se determinó la ecuación de búsqueda "Risk Management AND ISO 31000", para GRT. Posteriormente, se definió el plan para el estudio de GRT, que contempla 7 fases: Análisis de los documentos por año, Análisis de los documentos según las fuentes encontradas, Análisis de los documentos por Autor, Análisis de los documentos por Afiliación, Documentos por Ciudad o Territorio, Análisis de los resultados según el tipo de documento y Documentos por área temática. Finalmente, se enuncian los resultados derivados de los documentos escritos por los autores más relevantes que hablan acerca de GRT y la norma ISO 31000, comparándolos entre sí y considerando como contribuyen estos resultados en la gestión del riesgo en entidades hospitalarias.

Strategic management of scientific and technological information is increasingly important to innovate and survive today. It is for this reason that hospitals must assume Risk Management Technology (RMT) as a vital part of innovation strategies. In this article, a study of Technology Watch prioritizing the most relevant data and strategic information about GRT in hospital organizations is reported. This has been based on the study of ISO 31000 standard. Initially, the search equation "Risk Management and ISO 31000" to RMT, was determined. Then, the plan for the study of GRT, which includes 7 phases: Analysis of documents per year, analysis of the documents per sources found, analysis of documents by author, analysis of documents by affiliation, analysis of documents by city or territory, analysis of results by document type and by subject area were defined. Finally, the results from documents written by the most important authors who speak about GRT and ISO 31000 were shared, comparing them to each other and considering how these results contribute to risk management in hospital entities.

A Gestão estratégica da informação científica e tecnológica é cada vez mais importante para inovar e sobreviver no tempo presente. É por esta razão que os hospitais devem assumir Tecnologia de Gestão de Riscos (GRT) como uma parte vital das estratégias de inovação. Neste artigo, um estudo de Vigilância Tecnológica para priorizar os dados mais relevantes e informações estratégicas sobre GRT em organizações hospitalares é relatado. Com base no Padrão 31000. Inicialmente, determinou-se a equação de pesquisa "Gestão de Riscos e ISO 31000" para GRT. Posteriormente se determinou o plano para o estudo de GRT que tem 7 fases: Análise de documentos por ano, a análise das fontes onde se encontrou documentos, análise de documentos pelo o autor, análise de documentos por filiação, documentos por cidades o território, Análise de resultados por tipo de documento e documentos por área de assunto. Finalmente, se anunciaram os resultados a partir de documentos escritos pelos autores mais importantes que falam sobre GRT e ISO 31000, comparando-os uns aos outros e considerar como estes resultados contribuem para a gestão de riscos em entidades hospitalares.

Centrilobular necrosis as a manifestation of venous outflow block in pediatric malnourished liver transplant recipients--case reports.

CLN is a frequent histological finding in biopsies after pediatric: LT, and its pathogenesis has not yet been fully clarified and has different causes. Among the vascular causes, VOB is sometimes difficult to diagnose, especially when technical variants such as split-liver, reduced-liver, or living-related LT are utilized. Three liver-transplanted malnourished children (ages 12, 20, and 28 months) developed altered LFTs and post-operative ascites with right pleural effusion (two cases) and jaundice (one case). Doppler ultrasound examinations were normal and liver biopsies showed CLN interpreted as severe ACR. There were no responses to the medical treatment. Additional investigation with CT angiography suggested obstructed hepatic vein drainage, which was confirmed by interventional radiology and angioplasty of the anastomosis between the hepatic vein and the inferior vena cava, with clinical and histological resolution. It is concluded that in malnourished children undergoing LT with technical variations, in which the occurrence of severe ACR is usually less common because of the severity of the patient condition, the finding of CLN should raise the possibility of VOB, so that excessive immunosuppression and its consequences can be avoided.

Aplasia medular após transplante hepático em pediatria / Aplastic anemia after pediatric liver transplantation

A aplasia de medula é uma das mais raras (<1 por cento) e sérias complicações após o transplante hepático por insuficiência hepática aguda grave viral não A, não B e não C. Esta condição clínica, que acomete simultaneamente o tecido hepático e o hematopoético, foi descrita pela primeira vez em 1987, por Stock, e a fisiopatologia relacionada é uma condição imunomediada, provavelmente secundária à infecção viral desconhecida, e associada a grave prognóstico. A recuperação espontânea da aplasia medular adquirida habitualmente é muito rara e 50 por cento-70 por cento dos pacientes respondem ao tratamento imunossupressor com ciclosporina A (CsA) e glubulina antitimocítica (ATG), mesmo após o transplante hepático. Além do tratamento imunossupressor, outra opção é o transplante de medula óssea (TMO). Apresentamos o caso de uma criança com aplasia medular grave após transplante hepático, por insuficiência hepática aguda grave, que recebeu tratamento imunossupressor com CsA e ATG e evoluiu com recuperação completa das três séries do hemograma.

Aplastic anemia (AA) is one of the rarest (<1 percent) and most serious complications of liver transplantation for fulminant non-A, non-B and non-C hepatitis. It was first described in 1987 by Stock; the mechanism involved is an immunologically mediated condition secondary to an unknown viral infection. The disease is associated with a dismal prognosis. Spontaneous recovery from acquired AA is very rare however some patients (50-70 percent) recover after immunosuppressive therapy, such as Cyclosporin A (CsA) and Antithymocyte globulin (ATG), even after liver transplantation. Another treatment option is bone marrow transplantation. We report on a child who developed AA following liver transplantation for fulminant viral hepatitis that was treated with intensive immunosuppression including CsA and ATG and achieved complete recovery.

Real-time and Doppler US after pediatric segmental liver transplantation : I. Portal vein stenosis.

BACKGROUND: Accurate diagnosis of portal vein (PV) stenosis by real-time and color Doppler US (CD-US) after segmental liver transplantation in children can decrease morbidity by avoiding unnecessary biopsy, PV hypertension, thrombosis and loss of the graft. OBJECTIVE: To evaluate CD-US parameters for the prediction of PV stenosis after segmental liver transplantation in children. MATERIALS AND METHODS: We retrospectively reviewed 61 CD-US examinations measuring the diameter at the PV anastomosis, velocities at the anastomosis (PV1) and in the segment proximal to the anastomosis (PV2), and the PV1/PV2 velocity ratio. The study group comprised patients with stenosis confirmed by angiography and the control group comprised patients with a good clinical outcome. RESULTS: PV stenosis was seen in 12 CD-US examinations. The mean PV diameter was smaller in the study group (2.6 mm versus 5.7 mm) and a PV diameter of <3.5 mm was highly predictive of stenosis (sensitivity 100%, specificity 91.8%). CONCLUSION: A PV diameter of <3.5 mm is a highly predictive CD-US parameter for the detection of hemodynamically significant stenosis on angiography.

Real-time and Doppler US after pediatric segmental liver transplantation : II. Hepatic vein stenosis.

BACKGROUND: Accurate diagnosis of hepatic vein (HV) stenosis by real-time and color Doppler US (CD-US) after segmental liver transplantation in children can decrease morbidity because it allows unnecessary biopsy, obstruction or thrombosis and loss of the graft to be avoided. OBJECTIVE: To evaluate CD-US parameters to predict HV stenosis after segmental liver transplantation in children. MATERIALS AND METHODS: Retrospective review of 79 CD-US examinations measuring velocity at the HV anastomosis (HV1) and the main trunk 1-2 cm proximal to the HV/IVC anastomosis (HV2), the HV1/HV2 ratio and the spectral waveform of HV2. The study group comprised patients with stenosis confirmed by angiography. The control group comprised patients with a good clinical outcome. RESULTS: HV stenosis was seen in 12 CD-US examinations. The mean HV1/HV2 ratio was higher in the study group (6.0 versus 4.0). An HV1/HV2 ratio of >4.1 was predictive of HV stenosis (sensitivity 83%, specificity 76%). CONCLUSION: An HV1/HV2 ratio of >4.1 is a highly predictive CD-US parameter for the detection of hemodynamically significant HV stenosis on angiography.

Mycophenolate mofetil promotes prolonged improvement of renal dysfunction after pediatric liver transplantation: experience of a single center.

Few studies have evaluated the long-term use of MMF in liver transplanted children with renal dysfunction. The aim of this study is to report the experience of a pediatric transplantation center on the efficacy and security of long-term use of a MMF immunosuppressant protocol with reduced doses of CNIs in stable liver transplanted children with renal dysfunction secondary to prolonged use of CsA or Tac. Between 1988 and 2003, 191 children underwent OLT and 11 patients developed renal dysfunction secondary to CNIs toxicity as evaluated by biochemical renal function parameters. The interval between liver transplantation and the introduction of the protocol varied from one to 12 yr. Renal function was evaluated by biochemical parameters in five phases: immediately prior to MMF administration; 3, 6, 12 and 24 months after the introduction of MMF. Among the patients, nine of them (82%) showed improvement of renal function parameters in comparison with the pretreatment values. The two patients that did not show any improvement were patients in whom the interval of time between OLT and the introduction of MMF was longer. All parameters of liver function remained unchanged. No episodes of acute or chronic rejection or increases in infection rates during the period were detected. Two patients developed transitory diarrhea and leukopenia that were reverted with reduction of MMF dosage. In conclusion, in liver transplanted pediatric patients with CNI-induced chronic renal dysfunction, the administration of MMF in addition to reduced doses of CNIs promotes long-term improvement in renal function parameters with no additional risks.

Dental caries in HIV-infected children versus household peers: two-year findings.

PURPOSE: This report will present a two-year comparison of the incidence and baseline prevalence of dental caries found in both the primary and permanent dentition among a cohort of HIV-infected children as compared to household peer control subjects who were not HIV-infected. METHODS: The subjects in this report were from an initial cohort of 171 children (104 HIV positive and 67 HIV negative), who were participants in the Children's Hospital AIDS Program in Newark, New Jersey, from 1993-1995. This two year analysis reports the findings on the children who completed baseline through Year 02 examinations (N = 121), aged 2-15 years old (68 HIV positive, 53 HIV negative). RESULTS: While the DMFS incidence at Year 02 among the 6-11 year old control subjects was 17% higher than that of the HIV-infected cases (2.1 vs. 1.8, respectively) this same incidence was eight-fold higher for the control subjects among the 12-15 year olds (e.g., 8.1 vs. 1.0, respectively). The mean cumulative dmfs score to date for HIV-infected cases was higher than for the control subjects for both the 2-5 year olds and the 6-11 year olds, (11.0 vs. 7.0) and (10.0 vs. 4.0, P = .02), respectively. In all three age groups, HIV-infected cases had a greater number of primary teeth and fewer number of permanent teeth than the control subjects (P < .01). CONCLUSION: Given that HIV-infected cases had lower DMFS scores and higher dmfs scores than their household peer controls, the fewer mean number of permanent teeth among the HIV-infected cases suggests that this delayed tooth eruption pattern in permanent teeth contributed to the lower DMFS scores seen in the HIV-infected cases.

Regulation of mRNA entry into polysomes. Parameters affecting polysome size and the fraction of mRNA in polysomes.

The kinetics of labeled histone mRNA entry into polysomes was studied in nuclease-treated reticulocyte lysates. Added mRNA rapidly bound 1 or 2 ribosomes. However, the formation of full size polysomes required at least 16 min. The amount of mRNA bound to ribosomes reached a maximum (73%) within 2 min after mRNA addition and then declined slowly for the remainder of the experiment. Two initiation inhibitors, aurintricarboxylic acid and 7-methylguanosine 5'-triphosphate, were found to affect polysome size and the fraction of mRNA in polysomes in an opposite manner. These results suggest that initiation and reinitiation events may be intrinsically different. The relatively long time period required for the formation of large polysomes can be explained by large polysomes having higher initiation and/or reinitiation rates or slower elongation rates. These possibilities are not mutually exclusive. The results suggest that there exist several levels of control which can regulate polysome size and the fraction of mRNA in polysomes.

In vivo mapping of DNA topoisomerase II-specific cleavage sites on SV40 chromatin.

The antitumor drug, m-AMSA (4'-(9-acridinylamino)-methanesulfon-m-anisidide), is known to interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II by blocking the enzyme-DNA complex in its putative cleavable state. Treatment of SV40 virus infected monkey cells with m-AMSA resulted in both single- and double-stranded breaks on SV40 viral chromatin. These strand breaks are unusual because they are covalently associated with protein. Immunoprecipitation results suggest that the covalently linked protein is DNA topoisomerase II. These results are consistent with the proposal that the drug action in vivo involves the stabilization of a cleavable complex between topoisomerase II and DNA in chromatin. Mapping of these double-stranded breaks on SV40 viral DNA revealed multiple topoisomerase II cleavage sites. A major topoisomerase II cleavage site was preferentially induced during late infection and was mapped in the DNAase I hypersensitive region of SV40 chromatin.

Serum estradiol-17beta concentrations during spontaneous silent estrus and after prostaglandin treatment in the mare.

Serum estradiol-17beta concentrations were determined during silent estrus in the mare. Relationships between serum estradiol-17beta concentration, corpus luteum regression, follicular development, ovulation, prostaglandin treatment and behavioral estrus were investigated. The expression of behavioral estrus was found to be related to the patterns of progesterone and estradiol-17beta secretion during the periovulatory period. When compared to normal estrous cycles, silent estrus was accompanied by a significantly lower maximum serum estradiol-17beta concentration (47.8 vs 34.6 pg/ml), a significantly longer interval from maximum estradiol-17beta concentration to ovulation (1.7 vs 4.0 days), and a significantly shorter interval from corpus luteum regression to ovulation (5.3 vs 2.8 days). Silent estrus following prostaglandin treatment was related to a significantly shorter interval from prostaglandin treatment to ovulation (3.6 +/- 0.4 days) than from normal corpus luteum regression to ovulation (5.3 +/- 0.3 days). Silent estrus appeared to be related to changes in follicular estradiol-17beta secretion and to the pattern of its secretion as related to regression of the corpus luteum. There appeared to be not only less estradiol-17beta present, but also less time available after luteal regression for it to interact with the central nervous system to elicit the changes necessary to cause behavioral estrus. There fore, unusual relationships between luteal function and folliculogenesis can result in one type of silent estrus. Significant correlations (P<0.05) were found between follicle size and serum estradiol-17beta concentration whenever behavioral estrus occurred [follicle diameter in mm = 0.96 (serum estradiol-17beta in pg/ml) + 6.08 and 0.73 (serum estradiol-17beta + 13.32 for control and normal estrus following prostaglandin treatment groups, respectively]. During silent estrus, however, no significant correlations between follicle size and serum estradiol-17beta concentration were observed.

Multiple levels of regulation of protein synthesis at fertilization in sea urchin eggs.

Fertilization of sea urchin eggs results in a large stimulation of protein synthesis. This increase in protein synthesis is mediated by the mobilization of stored maternal mRNA (mRNPs) into polysomes, but the details of the molecular mechanisms which regulate this process are not well understood. Using a sea urchin egg cell-free translation system, evidence has been obtained which indicates that the capacity to initiate protein synthesis on new mRNAs is limited. Addition of exogenous mRNAs failed to stimulate overall protein synthesis, whereas supplementing the system with a nuclease-treated reticulocyte lysate, an S-100 supernatant fraction, or purified eIF-2 stimulated nearly twofold. In addition, the levels of 43 S preinitiation complexes containing a 40 S ribosomal subunit and methionyl-tRNA were increased at pH 7.4 compared to pH 6.9, or when reticulocyte S-100 was added. However, other experiments showed clearly that mRNA availability may also regulate translation in the sea urchin egg. Sea urchin lysates only stimulated poorly the nuclease-treated reticulocyte lysate system, and the mRNPs in the sea urchin lysate did not bind to reticulocyte 43 S preinitiation complexes. Since purified sea urchin egg mRNA was active in both assays, the bulk of sea urchin mRNA must be masked in the egg, and remain masked in the in vitro assays. Thus, protein synthesis appears to be regulated at both the level of mRNA availability and the activity of components of the translational machinery.

Intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II.

Many intercalative antitumor drugs have been shown to induce reversible protein-linked DNA breaks in cultured mammalian cells. Using purified mammalian DNA topoisomerase II, we have demonstrated that the antitumor drugs ellipticine and 2-methyl-9-hydroxyellipticine (2-Me-9-OH-E+) can produce reversible protein-linked DNA breaks in vitro. 2-Me-9-OH-E+ which is more cytotoxic toward L1210 cells and more active against experimental tumors than ellipticine is also more effective in stimulating DNA cleavage in vitro. Similar to the effect of 4'-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA) on topoisomerase II in vitro, the mechanism of DNA breakage induced by ellipticines is most likely due to the drug stabilization of a cleavable complex formed between topoisomerase II and DNA. Protein denaturant treatment of the cleavable complex results in DNA breakage and covalent linking of one topoisomerase II subunit to each 5'-end of the cleaved DNA. Cleavage sites on pBR322 DNA produced by ellipticine or 2-Me-9-OH-E+ treatment mapped at the same positions. However, many of these cleavage sites are distinctly different from those produced by the antitumor drug m-AMSA which also targets at topoisomerase II. Our results thus suggest that although mammalian DNA topoisomerase II may be a common target of these antitumor drugs, drug-DNA-topoisomerase interactions for different antitumor drugs may be different.

Mechanism of antitumor drug action: poisoning of mammalian DNA topoisomerase II on DNA by 4'-(9-acridinylamino)-methanesulfon-m-anisidide.

The intercalative acridine derivative 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA), but not its isomer o-AMSA, is a potent antitumor drug that in mammalian cells stimulates the formation of DNA strand breaks that are characterized by tightly bound proteins. Using purified mammalian DNA topoisomerases, we have analyzed the effects of these antitumor drugs on topoisomerase-DNA interactions. The antitumor drug m-AMSA dramatically stimulates the formation of a topoisomerase II-DNA complex that is detected on protein-denaturant treatment: both single- and double-stranded DNA breaks are produced and a topoisomerase II subunit is linked covalently to each 5' end of the broken DNA strands. The noncytotoxic isomer, o-AMSA, which does not induce significant amounts of DNA breaks in cultured cells, exhibits a correspondingly smaller effect in stimulating formation of the complex in vitro. The agreement between in vitro and in vivo studies suggests that mammalian DNA topoisomerase II may be the primary target of m-AMSA and that the drug-induced complex formation between topoisomerase II and DNA may be the cause of cytotoxicity and other effects such as DNA sequence rearrangements and sister-chromatid exchange.

Classification of DNA polymerase activities from ovaries of the frog, Xenopus laevis.

Four distinct DNA polymerase activities were isolated from ovaries of the frog Xenopus laevis. Specific assays for each activity were established. The isolated activities were characterized by molecular weight, template-primer preferences, and sensitivity to specific inhibitors as Xenopus laevis ovarian DNA polymerases-alpha 1, -alpha 2, -beta, and -gamma. All previously described Xenopus laevis DNA polymerases were classified using these properties.

DNA primase activity associated with DNA polymerase alpha from Xenopus laevis ovaries.

One of the two forms of DNA polymerase alpha from ovaries of the frog Xenopus laevis catalyzed ribonucleoside triphosphate-dependent DNA synthesis on single-stranded circular fd phage DNA templates. DNA synthesis was dependent on ATP and added template. CTP, GTP, and UTP stimulated DNA synthesis but were not required and could not substitute for ATP. DNA synthesis was not inhibited by alpha-amanitin. Neither poly(dT) nor double-stranded DNA served as template. Analysis of [32P]-dTMP-labeled product by neutral and alkaline agarose gel electrophoresis showed that 0.1- to 1-kilobase DNA fragments (average size of approximately equal to 0.25 kilobase) were synthesized. The fragments were not covalently linked to the template. Either [alpha-32P]NMP, [gamma-32P]ATP, or [gamma-32P]GTP were incorporated also into the product. Analysis of the product after hydrolysis by KOH, alkaline phosphatase, or bacteriophage T4 3' leads to 5' exonuclease showed the presence of a small oligoribonucleotide primer at the 5' end of the newly synthesized DNA. NTP-dependent DNA-synthesizing activity copurified on six columns and cosedimented during glycerol gradient centrifugation with one form of DNA polymerase alpha activity but not with the other form. These results suggest that DNA primase activity is associated with one of the two forms of X. laevis DNA polymerase alpha.