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Biomedical subjects

J D Lewis

Publications and source records attributed to J D Lewis.

At least 19 recordsLinked to original sources
PubMed1995

A computer-controlled conformal radiotherapy system. II: Sequence processor.

PURPOSE: A sequence processor (SP) is described as part of a larger computer-controlled conformal radiotherapy system (CCRS). The SP provides the means to accept and then translate highly sophisticated radiation therapy treatment plans into vendor specific instructions to control treatment delivery on a computer-controlled treatment machine. METHODS AND MATERIALS: The sequence processor (SP) is a small workstation computer that interfaces to the control computer of computer-controlled treatment machines, and to other parts of the larger CCRS system. The system reported here has been interfaced to a computer-controlled racetrack microtron with two treatment gantries, and also to other linear accelerator treatment machines equipped with multileaf collimators. An extensive design process has been used in defining the role of the SP within the context of the larger CCRS project. Flexibility and integration with various components of the project, including databases, treatment planning system, graphical simulator, were key factors in the development. In conjunction with the planned set of treatment fields, a procedural scripting language is used to define the sequence of treatment events that are performed, including operator interactions, communications to other systems such as dosimetry and portal imaging devices, and database management. RESULTS: A flexible system has been developed to allow investigation into procedural steps required for simulating and delivering complex radiation treatments. The system has been used to automate portions of the acceptance testing for the control system of the microtron, and is used for routine daily quality assurance testing. The sequence processor system described here has been used to deliver all clinical treatments performed on the microtron system in 2 years of clinical treatment (more than 200 patients treated to a variety of treatment sites). CONCLUSIONS: The sequence processor system has enabled the delivery of complex treatment using computer-controlled treatment machines. The flexibility of the system allows integration with secondary devices and modification of procedural steps, making it possible to develop effective techniques for insuring safe and efficient computer-controlled conformal radiation therapy treatments.

Computer Simulation↗
PubMed1995

A computer-controlled conformal radiotherapy system. I: Overview.

PURPOSE: Equipment developed for use with computer-controlled conformal radiotherapy (CCRT) treatment techniques, including multileaf collimators and/or computer-control systems for treatment machines, are now available. The purpose of this work is to develop a system that will allow the safe, efficient, and accurate delivery of CCRT treatments as routine clinical treatments, and permit modifications of the system so that the delivery process can be optimized. METHODS AND MATERIALS: The needs and requirements for a system that can fully support modern computer-controlled treatment machines equipped with multileaf collimators and segmental or dynamic conformal therapy capabilities have been analyzed and evaluated. This analysis has been used to design and then implement a complete approach to the delivery of CCRT treatments. RESULTS: The computer-controlled conformal radiotherapy system (CCRS) described here consists of a process for the delivery of CCRT treatments, and a complex software system that implements the treatment process. The CCRS system described here includes systems for plan transfer, treatment delivery planning, sequencing of the actual treatment delivery process, graphical simulation and verification tools, as well as an electronic chart that is an integral part of the system. The CCRS system has been implemented for use with a number of different treatment machines. The system has been used clinically for more than 2 years to perform CCRT treatments for more than 200 patients. CONCLUSIONS: A comprehensive system for the implementation and delivery of computer-controlled conformal radiation therapy (CCRT) plans has been designed and implemented for routine clinical use with multisegment, computer-controlled, multileaf-collimated conformal therapy. The CCRS system has been successfully implemented to perform these complex treatments, and is considered quite important to the clinical use of modern computer-controlled treatment techniques.

Equipment Design↗
PubMed1995

A computer-controlled conformal radiotherapy system. IV: Electronic chart.

PURPOSE: The design and implementation of a system for electronically tracking relevant plan, prescription, and treatment data for computer-controlled conformal radiation therapy is described. METHODS AND MATERIALS: The electronic charting system is implemented on a computer cluster coupled by high-speed networks to computer-controlled therapy machines. A methodical approach to the specification and design of an integrated solution has been used in developing the system. The electronic chart system is designed to allow identification and access of patient-specific data including treatment-planning data, treatment prescription information, and charting of doses. An in-house developed database system is used to provide an integrated approach to the database requirements of the design. A hierarchy of databases is used for both centralization and distribution of the treatment data for specific treatment machines. RESULTS: The basic electronic database system has been implemented and has been in use since July 1993. The system has been used to download and manage treatment data on all patients treated on our first fully computer-controlled treatment machine. To date, electronic dose charting functions have not been fully implemented clinically, requiring the continued use of paper charting for dose tracking. CONCLUSIONS: The routine clinical application of complex computer-controlled conformal treatment procedures requires the management of large quantities of information for describing and tracking treatments. An integrated and comprehensive approach to this problem has led to a full electronic chart for conformal radiation therapy treatments.

Data Display↗
PubMed1995

Percutaneous endovascular covered stenting of a distal superficial femoral artery occlusion.

Peripheral vascular disease is a common problem in the elderly population. This is commonly treated nowadays by percutaneous transluminal angioplasty (PTA). When PTA is used in the treatment of superficial femoral artery (SFA) occlusions 35% reocclude within 1 year. Endovascular stents (uncovered) have been used to try to overcome this problem; however, results have been disappointing with reocclusion rates similar to PTA. In order to try to reduce this problem covered endovascular stents have been developed. We report the first known case in the UK of one of these stents being used in the treatment of SFA disease.

Aged↗
PubMed1995

Intestinal and hepatobiliary diseases in HIV-infected children.

Children with HIV disease and gastrointestinal disease should be evaluated for enteric pathogens. Bacterial, protozoal, and viral agents can cause chronic diarrhea, abdominal pain, gastrointestinal bleeding, and contribute to growth retardation. This article presents an approach to the evaluation of the HIV-infected child with gastrointestinal symptoms. Therapeutic and nutritional interventions are discussed with emphasis on the multidisciplinary approach required to initiate successful management.

AIDS-Related Opportunistic Infections↗
PubMed1994

Nutrition support in inflammatory bowel disease.

The mechanisms of nutritional therapy in inflammatory bowel disease have not been thoroughly established. It is likely that a further understanding of the underlying disease process will allow better understanding of these forms of therapy, with a sounder rationale for the construction of specific diet constituents for therapy. Regardless, nutritional therapy is likely to be multidimensional, and various forms may affect different aspects of the disease process. Decreased inflammatory factors, decreased antigenic stimuli, provision of essential nutrients, improved immune function, and other factors may all be of varying importance in different patients with inflammatory bowel disease. Little work has been done on the role of diet therapy in the long-term treatment of patients with inflammatory bowel disease as a method of preventing relapse. Parenteral nutrition and elemental diets appear to have limited roles in this area. Some investigation has been done to see if minor modifications of the normal diet can prolong remission periods. Low-fiber diets are frequently recommended for patients with strictures. Whether this has any significant effect on symptoms, inflammation, or complications is unclear. Heaton et al suggested that a high-fiber, unrefined carbohydrate diet resulted in fewer and shorter hospitalizations. In a prospective follow-up study by Ritchie et al, however, these results were not able to be reproduced. Exclusion diets have also been suggested as a means of reducing relapse rates in patients with Crohn's disease. In a small, randomized, controlled trial of an exclusion diet versus an unrefined carbohydrate, fiber-rich diet, there were significantly fewer relapses among the patients treated with the exclusion diet at 6 months. These diets require intensive patient cooperation, but the potential side effects are minimal. Clearly, these findings need to be reproduced in large, prospective, randomized, controlled studies before widespread use can be advocated. A great deal of data exists on the use of nutritional supplementation in the treatment of inflammatory bowel disease, although little of it is in the form of large, randomized, controlled studies. Nutritional manipulation currently has a limited role in patients with ulcerative colitis; a much broader role exists in patients with Crohn's disease. The mechanisms by which nutritional therapy affects these diseases may include a combination of factors--decreased antigenic exposure, improved immune function, and provision of essential nutrients and calories needed for bowel regeneration.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1993

Common and unique transcription factor requirements of human U1 and U6 snRNA genes.

The human U1 and U6 genes have similar basal promoter structures. A first analysis of the factor requirements for the transcription of a human U1 gene by RNA polymerase II in vitro has been undertaken, and these requirements compared with those of human U6 gene transcription by RNA polymerase III in the same extracts. Fractions containing PSE-binding protein (PBP) are shown to be essential for transcription of both genes, and further evidence that PBP itself is required for U1 as well as U6 transcription is presented. On the other hand, the two genes have distinct requirements for TATA-binding protein (TBP). On the basis of chromatographic and functional properties, the TBP, or TBP complex, required for U1 transcription appears to differ from previously described complexes required for RNA polymerase I, II or III transcription. The different TBP requirements of the U1 and U6 promoters are reflected by specific association with either TFIIB or TFIIIB respectively, thus providing a basis for differential RNA polymerase selection.

Base Sequence↗
PubMed1992

Cofractionation of the TATA-binding protein with the RNA polymerase III transcription factor TFIIIB.

We have investigated the requirement for TBP (TATA-binding protein) in transcription mediated by RNA polymerase III (pol III) in fractionated HeLa cell extracts. Two activities, TFIIIB and TFIIIC, found in phosphocellulose fractions PC B and PC C respectively, have been defined as necessary and sufficient, with pol III, for in vitro transcription of tRNA genes. Depletion of TBP from PC B, using antibodies raised against human TBP, is shown to inhibit the pol III transcriptional activity of the fraction. Furthermore, TBP is present in fractions with human TFIIIB activity, and a proportion of TBP cofractionates with TFIIIB over four chromatographic purification steps. TFIIIB fractions are capable of supplying TBP in the form necessary for pol III transcription, and cannot be substituted by fractions containing other TBP complexes or TBP alone. The use of a 5S RNA gene and two tRNA templates supports the general relevance of our findings for pol III gene transcription. Purified TFIIIB activity can also support pol II-mediated transcription, and is found in a complex of approximately 230kD, suggesting that TFIIIB may be the same as the previously characterized B-TFIID complex (1,2). We suggest that transcription by the three RNA polymerases is mediated by distinct TBP-TAF complexes: SL1 and D-TFIID for pol I and pol II respectively, and TFIIIB for pol III.

Chemical Fractionation↗
PubMed1992

Venous leg ulcers: a prognostic index to predict time to healing.

OBJECTIVE: To evaluate the prognostic factors in uncomplicated venous leg ulcer healing. DESIGN: Randomised parallel group controlled trial with subjects stratified by initial ulcer diameter and four months' maximum duration of follow up. SETTING: Assessment at Northwick Park Hospital vascular unit with community based treatment. PATIENTS: 200 patients with clinical and objective evidence of uncomplicated venous leg ulceration and an initial ulcer diameter > 2 cm. MAIN OUTCOME MEASURE: Time to complete healing of the ulcer. RESULTS: In the presence of graduated compression healing occurred more rapidly in patients with a smaller initial ulcer area (relative risk of healing 1.92 associated with halving of ulcer area (95% confidence interval 1.58 to 2.33)), shorter duration of ulceration (relative risk 1.35 associated with halving duration (1.17 to 1.56)), younger age (relative risk 1.34 associated with 10 year decrease (1.12 to 1.59)), and no deep vein involvement (relative risk 1.8 (1.19 to 2.78)). CONCLUSION: These prognostic factors used in a simple scoring system predict time to healing.

Aged↗
PubMed1992

Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA.

Methylated DNA in vertebrates is associated with transcriptional repression and inactive chromatin. Two activities have been identified, MeCP1 and MeCP2, which bind specifically to DNA containing methyl-CpG pairs. In this report we characterize MeCP2. We show that it is more abundant than MeCP1, is more tightly bound in the nucleus, and is distinguishable chromatographically. The two proteins share widespread expression in somatic mammalian cells, and barely detectable expression in early embryonic cells. DNAs containing thymidine which has a methyl group at position 5 are not ligands for the MeCPs. The possible role of MeCP2 in methylation-associated gene inactivation was tested in in vitro transcription extracts. Purified MeCP2 inhibited transcription from both methylated and nonmethylated DNA templates in vitro, probably due to the presence of nonspecific DNA binding domains within the protein. We hypothesise that MeCP2 normally binds methylated DNA in the context of chromatin, contributing to the long-term repression and nuclease-resistance of methyl-CpGs.

Animals↗
PubMed1992

A six year prospective study of fibrinogen and other risk factors associated with mortality in stable claudicants.

A total of 333 patients with stable intermittent claudication at recruitment were followed up for 6 years to determine risk factors associated with subsequent mortality. Cardiovascular diseases were the underlying cause of death in 78% of the 114 patients who died. The strongest independent predictor of death during the follow-up period was the plasma fibrinogen level, an increase of 1 milligram being associated with a nearly two-fold increase in the probability of death within the next 6 years. Age, low ankle/brachial pressure index and a past history of myocardial infarction also increased the probability of death during the study period. The plasma fibrinogen level is a valuable index of those patients with stable intermittent claudication at high risk of early mortality. The results also provide further evidence for the involvement of fibrinogen in the pathogenesis of arterial disease.

Aged↗
PubMed1992

Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA.

Methylation of mammalian DNA can lead to repression of transcription and alteration of chromatin structure. Recent evidence suggests that both effects are the result of an interaction between the methylated sites and methyl-CpG-binding proteins (MeCPs). MeCP1 has previously been detected in crude nuclear extracts. Here we report the identification, purification, and cDNA cloning of a novel MeCP called MeCP2. Unlike MeCP1, the new protein is able to bind to DNA that contains a single methyl-CpG pair. By staining with an antibody, we show that the distribution of MeCP2 along the chromosomes parallels that of methyl-CpG. In mouse, for example, MeCP2 is concentrated in pericentromeric heterochromatin, which contains a large fraction (about 40%) of all genomic 5-methylcytosine.

Amino Acid Sequence↗
PubMed1990

A CT-based computerized treatment planning system for I-125 stereotactic brain implants.

A computer program has been developed at the University of California, San Francisco, as an aid in planning and evaluating stereotactic brain implants made with 125I seeds. The program allows images of seeds and catheters to be positioned in the target volume revealed by CT. It then generates and displays the resulting isodose distributions. Catheters may be changed interactively until an optimum implant is achieved. From the geometry of a stereotactic implant frame as measured by CT, the program calculates the approach angles of the catheters in the frame coordinate system. After the seeds are implanted, films made with a fiducial marker box can be used to generate true seed positions and hence true isodoses. This paper describes mathematically the geometrical transformations used by the program, and also outlines its many features and options. In its first 2 years of use the program has proved to be a valuable contributor to improved patient care.

Brachytherapy↗
PubMed1990

Episodic intermittent claudication associated with a Baker's cyst.

Baker first described synovial cysts in the leg in connection with diseases of the knee joint. Whilst the majority are asymptomatic, some present as a localised swelling behind the knee, and others either compress the popliteal vein or rupture and can be misdiagnosed as deep vein thrombosis; transmitted pulsation through the cyst can suggest the presence of a popliteal aneurysm. This paper documents a case of intermittent claudication of the lower limb secondary to compression of the popliteal artery by a Baker's cyst.

Constriction, Pathologic↗