Detection of potential target genes in silico?
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Biomedical subjects
Publications and source records attributed to A Wagner.
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This article describes the methods adopted by the International Quality of Life Assessment (IQOLA) project to translate the SF-36 Health Survey. Translation methods included the production of forward and backward translations, use of difficulty and quality ratings, pilot testing, and cross-cultural comparison of the translation work. Experience to date suggests that the SF-36 can be adapted for use in other countries with relatively minor changes to the content of the form, providing support for the use of these translations in multinational clinical trials and other studies. The most difficult items to translate were physical functioning items, which used examples of activities and distances that are not common outside of the United States; items that used colloquial expressions such as pep or blue; and the social functioning items. Quality ratings were uniformly high across countries. While the IQOLA approach to translation and validation was developed for use with the SF-36, it is applicable to other translation efforts.
In a prospective study, a new biodegradable osteosynthesis material for the facial skeleton has been used in 27 patients with zygomatic fractures. In the six-month follow-up period, the first ten patients showed clinically and radiologically uneventful healing of bone. There were no implant-related complications. The main advantages of the new material are its malleability when heated, enabling fast adaptation to the bone surface, and the avoidance of a second operation for implant removal.
High precision anatomical facsimile models of the patient's skull, individually produced by stereolithography, have been used in the preoperative planning in 16 patients with acute craniomaxillofacial trauma. In late primary repair, when open reduction and internal fixation had to wait for a decrease in facial swelling or cerebral oedema, computer-aided surgery has proven to be useful in terms of facilitating anatomical reduction, minimizing surgical approaches, saving operating time and leading to improved postoperative results, which may reduce the number of secondary corrections of post-traumatic deformities.
High-precision anatomical facsimile models of the patients' skulls, individually produced by colour stereolithography, were used in the preoperative planning for seven patients with complex maxillofacial tumours. Selectively coloured models facilitated the management of ablative surgery and reconstructive procedures as well. The indicators for preoperative colour stereolithographic model planning concerning maxillofacial tumour surgery are discussed.
An increase in the regularity of blood donation is desirable for two main reasons. First, the lower incidence of viral disease markers in regular donors when compared to first donors could help to reduce risks of transmissible diseases. Second, a higher frequency of donation could contribute to a more satisfactory supply of blood products. Two measures implemented with the aim of increasing the regularity of blood donation were evaluated: (i) an increase in the annual frequency of blood collection by mobile teams at collection sites, and (ii) a "next donation document" given to each donor indicating the earliest possible date of the next donation. The regularity index was calculated as the mean number of cellular donations (whole blood and platelet apheresis) per donor per year, over two consecutive periods: 1-7-1993-30-6-1994 (P1) and 1-7-1994-30-6-1995 (P2). The junction of these two periods corresponded to the date of introduction of the "next donation document" and to the time of reinforcement of the mobile collection frequency. First donors in either period were not taken into account in the study. A significant relationship was observed between the annual frequency of mobile collection and the average number of donations per donor (comparison test of two means on large samples, p < 0.001 in all the cases excepted those of stable mobile collection numbers). Thus, in the first period, the average donation rate was the lowest on sites having only one mobile collection per year (M: 1.55, W: 1.38) and the highest on sites with five mobile collections per year (M: 2.05, W: 1.71). These average numbers significantly increased in the second period as compared to the first (M: +4.8%, W: +1.8%; comparison test of two means from paired series, p < 0.001), as did the yearly frequency of mobile blood collections (+9.2%). On the other hand, the "next donation document" was not associated to any change in the regularity index. The results of this study therefore showed an increase in the frequency of visits of mobile collection teams to be the main factor leading to an improvement in the regularity of blood donation. Moreover, this evolution was associated with a decrease in the incidence of viral markers detected at donation.
The catabolite control protein CcpA is the central regulator of carbon catabolite repression in Bacilli and other Gram-positive bacteria. A comparison of 12 CcpA-like sequences with regulators from the LacI/GalR family defines a CcpA subfamily based on extensive similarities found among CcpAs and not in 32 other members of the family. These amino acids are clustered in three blocks in the CcpA sequence. Their interpretation, assuming a PurR-like fold, reveals that almost all of them are surface exposed and form a continuous patch on the N-terminal subdomain of the protein core extending into the DNA reading head. We introduced nine single amino acid exchanges in the subfamily specific residues of CcpA from Bacillus megaterium. Six mutants, namely CcpA47RS, 79AE, 89YE, 295YR, 299YE and 303RD, are inactive or severely impaired in catabolite repression, underlining their relevance for CcpA function. They are negatively transdominant over wild-type CcpA demonstrating their ability to correctly fold for dimerization. Five of them are unable or impaired in binding HPr-Ser-46-P in vitro, establishing a correlation between catabolite repression efficiency and HPr-Ser-46-P binding. These results support the hypothesis that the conserved region in CcpA is the HPr-Ser-46-P binding site.
PURPOSE: To investigate interactive MR-assisted bile duct drainage in pigs with the passive visualization technique using near real-time imaging. METHODS: 8 bile duct drainages were placed in an open low-field MR system (0.2 Tesla) in 4 pigs with surgically induced cholestasis. After planning the intervention with magnetic resonance cholangiography (MRC), both the puncture and catheter placement were interactively guided using a fast T2-weighted true FISP sequence. RESULTS: MRC enabled interventional planning in all puncture attempts. Punctures were unproblematic in all attempts, the bile ducts were punctured 6 times after the first and twice after the second attempt. Placement of the passively visible catheter was successful in all animals. The applied sequence enables interactive fluoroscopy-like positioning of the devices. CONCLUSION: The procedure introduced here enables reliable and fast placement of a bile duct drainage in an animal model using a low-field MR system.
The purpose of the present study was to analyze the morphology of the sella turcica in children born with myelomeningocele. Profile radiographs from 16 children (nine females and seven males) born with myelomeningocele were analysed. The contour of the anterior wall of the sella turcica in myelomeningocele patients, instead of following the normal cranio-caudal direction, was always in an obliquely antero-posterior direction. The sella turcica thus appeared broad cranially with a diverging anterior wall, or with both diverging anterior and posterior walls. This appearance gave and impression of a wide sella turcica in myelomeningocele with less depth than normal. The investigation has drawn attention to the fact that congenital malformations in the axial skeleton, even though, as in the case of myelomeningocele, they are located far from the cranial base, may have manifested themselves in the cranial base as well. The pathogenetic relationship between these manifestations is to be found in the early embryonic structure, the notochord. With the concept of embryological developmental fields, defined as areas with a common developmental origin, such as the notochordal field involved in myelomeningocele, new ways seem to be emerging for an improvement of aetiologically based diagnosis and treatment.
OBJECTIVE: To assess the amount of additional information provided by measurements derived from pulmonary artery catheter (PAC) use beyond that derived from clinical evaluation by intensive care residents. METHODS: One hundred forty-nine consecutive patients undergoing right-heart catheterization were prospectively included in the study. Before inserting a PAC, physicians had to predict pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), systemic vascular resistance index (SVRI), cardiac index (CI), mixed venous oxygen saturation (SvO2), oxygen delivery (DO2), oxygen consumption (VO2), and pulmonary shunt fraction (Qs/Qt) by selecting a given option on a questionnaire. Ranges of options were chosen to create clear clinical differences among them. RESULTS: The correct value was predicted in a median of 50% of cases (range, 45-63%). PAP was predicted correctly in 55%, PCWP in 46%, SVRI in 63%, CI in 62%, SvO2 in 45%, DO2 in 45%, VO2 in 51%, and Qs/Qt in 51%. A significant difference was found between estimated and measured values for all parameters (p < 0.01). No significant differences were detected between more and less experienced physicians. There was no significant difference between estimated and measured values with respect to the different courses of intensive care unit admissions or the different indications for PAC insertion. CONCLUSION: In a selected group of critically ill patients, the PAC adds valuable and clinically relevant information to clinical assessment in about 50% of cases. Its use should not be withheld in patients with unclear hemodynamic and metabolic profiles.
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INTRODUCTION: In abdominal tumors in childhood, staging laparotomy is usually an essential diagnostic tool to obtain information about the histology and the extension of the tumor, when less invasive methods do not reach to clarify the process. PATIENTS: In fourteen children between 3 months and 17 years a laparoscopical procedure was performed. MATERIAL AND METHOD: Only in patients without a clear diagnosis after noninvasive exploration were submitted to an explorative laparoscopy in order to define the histology, the extension of the illness or to locate it. The laparoscopical instrumentarium used was from Dufner, adapted to children. RESULTS: The patients tolerated well this procedure, the posoperative period was short (mean 2.07 days), no complications after the operation are reported. Only one case of hemorrhage lead to a conversion after biopsy of a neuroblastoma. In all cases the diagnosis and staging was achieved. CONCLUSIONS: When non invasive diagnostic methods are not conclusive an explorative laparoscopy should be performed because it offers a lot of advantages over a laparotomy.
We examined the effect of intravenous enalaprilat on the course of PAI-1 plasma levels in 23 patients with acute myocardial infarction undergoing thrombolytic therapy. All patients received 100 mg aspirin, 1000 IU/h heparin, thrombolysis with 100 mg rt-PA within 90 min, and betablockers. Eleven out of 23 patients received 5 mg enalaprilat intravenously prior to thrombolysis. Blood samples for determination of PAI-1 plasma levels were collected on admission, 2, 4, 6, 12, and 24 h after thrombolysis. PAI-1 plasma levels in patients receiving enalaprilat were similar to those of the control patients before thrombolysis (5 ng/ml, 95% confidence interval: 2-10 vs. 7 ng/ml, 95% confidence interval: 2-10; p = 0.5). The PAI-1AUC was 9 ng/ml/h (95% confidence interval: 5-10) in the enalaprilat group and 19 ng/ml/h (95% confidence interval: 13-26) in the control group (p = 0.0006). The maximum difference was observed 6 h after thrombolysis (enalaprilat: 13 ng/ml, 95% confidence interval: 5-25, control: 42 ng/ml, 95% confidence interval: 18-55; p = 0.003). Our study clearly demonstrates that application of intravenous enalaprilat prior to thrombolysis attenuates the thrombolysis-related increase of PAI-1. This finding may suggest a possible therapeutic approach to influence the fibrinolytic system in patients with acute myocardial infarction after thrombolysis.
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Inhalative nitric oxide (NO) has recently been included in the therapeutic armament for the treatment of ARDS. We evaluated the effect of inhalative NO on hemodynamic and oxygen transport parameters in 30 internal intensive care patients suffering from ARDS. All patients received a pulmonary artery catheter. Hemodynamics were assessed prior to NO therapy and after 1, 6, 12, and 24 h. 80% (n = 24) of the patients were classified as therapy responders. The median NO dose was 15 ppm (range 5 to 40 ppm). The PaO2/FiO2--ratio increased significantly after initiation of NO (p = 0.0002) while the pulmonary shunt fraction (Qs/Qt) decreased significantly (p = 0.0019). All other measured or calculated parameters including arterial and pulmonary arterial blood pressure remained unchanged. No negative effects of the therapy could be observed. Inhalative NO improves oxygenation in most intensive care patients with ARDS and thus offers the possibility to reduce invasiveness of mechanical ventilation.
To delineate the astronomical number of possible interactions of all genes in a genome is a task for which conventional experimental techniques are ill-suited. Sorely needed are rapid and inexpensive methods that identify candidates for interacting genes, candidates that can be further investigated by experiment. The subject of this paper is the application of a novel method to the genome of the yeast Saccharomyces cerevisiae. The method applies to an important class of gene interactions, that is, transcriptional regulation via transcription factors (TFs) that bind to specific enhancer or silencer sites on DNA. The method addresses the question: which of the genes in a genome are likely to be regulated by one or more TFs with known DNA binding specificity? It takes advantage of the fact that many TFs show cooperativity in transcriptional activation which manifests itself in closely spaced TF binding sites. Such "clusters" of binding sites are very unlikely to occur by chance alone, as opposed to individual sites, which are often abundant both in the genome and in promoter regions. Statistical information about binding site clusters in the genome, can be complemented by information about (i) known biochemical functions of the TF, (ii) the structure of its binding site, and (iii) function of the genes near the cluster, to identify genes likely to be regulated by a given transcription factor. Previously, binding sites of well characterized transcription factors in Saccharomyces cerevisiae were analyzed. Here, the method is applied to a somewhat different situation: the yeast DNA binding activity yE2F, similar to the mammalian transcription factor E2F. yE2F has a DNA binding specificity identical to E2F, and its binding site shows UAS activity in a GAL1-based promoter construct. However, despite its high conservation, the in vivo function of yE2F is unknown. The analysis carried out the here suggests candidate genes for regulation by yE2F.