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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 39 (1996), S. 252-255 
    ISSN: 1530-0358
    Keywords: Colorectal cancer follow-up ; Colonoscopy ; Metachronous neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: This study was performed to determine costeffective colonoscopy guidelines for patients with prior colorectal adenocarcinoma. METHOD: A retrospective review was performed of patients who had been treated for colorectal adenocarcinoma and later underwent follow-up colonoscopy from 1984 to 1994. RESULTS: During this study period, 389 patients previously treated for colorectal adenocarcinoma underwent follow-up colonoscopy. All patients had perioperative colon evaluation for other neoplasms. Ages ranged from 26 to 89 (mean, 65.8) years, and 46.8 percent were female. Recurrent or metachronous cancer or a neoplastic polyp constituted a positive examination. Results of 389 first follow-up colonoscopies were compared with 259 second (66.6 percent), 165 third (42.4 percent), and 83 fourth (21.3 percent) follow-up examinations. Median interval between all colonoscopies was 13 months. Positive examination rates for the first two yearly examinations were 18.3 and 18.5 percent, respectively. Slightly lower, third-year and fourth-year positive examination rates were 16.4 and 14.5 percent, respectively. Fouryear examinations yielded the following: first year-1 carcinoid, 1 new adenocarcinoma, and 100 polyps; second year-1 anastomotic recurrence and 68 polyps; third year-55 polyps; and fourth year-1 recurrent cancer and 17 polyps. CONCLUSIONS: These data suggest that 1) annual follow-up colonoscopy for two years after colorectal cancer surgery is beneficial for detecting recurrent and metachronous neoplasms and 2) the interval between subsequent examinations may be increased depending on the result of the most recent examination.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 976-979 
    ISSN: 1530-0358
    Keywords: Colonoscopy ; Polyps ; Flexible sigmoidoscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Colonoscopic surveillance is recommended for patients with adenomatous polyps. Significant cost savings would result from identification of subgroups of patients in whom less costly surveillance would suffice. This study was performed to determine the natural history of patients undergoing removal of isolated rectosigmoid adenomas and to establish whether flexible sigmoidoscopy might be adequate for follow-up. METHODS: A retrospective review of a database of 7,677 colonoscopies, from 1990 to 1996, identified patients who had a minimal follow-up of two years after removal of adenomatous polyps isolated to the rectosigmoid. Polyps detected on surveillance colonoscopy were categorized as distal (≤60 cm from anal verge), proximal (〉60 cm from anal verge), and diffuse (proximal plus distal). The risk of polyp formation was determined by actuarial analysis using the Kaplan-Meier method. RESULTS: Sixty-two patients undergoing surveillance for adenomas met inclusion criteria. At the index colonoscopy, 124 isolated rectosigmoid polyps were identified. The median polyp size was 1 cm and median frequency was one polyp. The median follow-up time for the entire cohort (N = 62) was 53 months. At follow-up surveillance colonoscopy, 105 additional adenomas were discovered and removed in 40 patients. No malignant polyps were detected. The pattern of polyps detected were proximal (n=19), rectosigmoid (n=16), and diffuse (n=5). CONCLUSIONS: The majority (65 percent) of patients with isolated rectosigmoid polyps have additional polyps on long-term surveillance, and 60 percent of patients will have these polyps located proximal to the reach of a sigmoidoscope. Therefore, flexible sigmoidoscopy is not a safe alternative for surveillance of patients with isolated rectosigmoid polyps.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Risk analysis 19 (1999), S. 711-726 
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 39 (1996), S. 806-810 
    ISSN: 1530-0358
    Keywords: Colonoscopy ; Gastrointestinal hemorrhage ; Polypectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: This study was undertaken to evaluate the incidence, diagnostic methods, and treatment of hemorrhage occurring after colonoscopic polypectomy. METHODS: A retrospective chart review was conducted of 12,058 patients who underwent colonoscopy at an academic referral center between January 1989 and July 1993. Of these, 6,365 patients required polypectomies or biopsies. RESULTS: After these procedures, 13 patients (0.2 percent) developed lower gastrointestinal hemorrhage requiring hospitalization. All bleeding episodes occurred within 12 days of polypectomy or biopsy (mean=8 days). Twelve patients (92 percent) underwent technetium-tagged red blood cell scintigraphy, which localized bleeding in four patients (31 percent). In the eight patients with normal scintigrams, hemorrhage did not recur, and no further evaluation was performed. Five patients (38 percent) underwent arteriography. Arteriogram was positive in two of four patients with positive scintigrams, and bleeding was controlled with selective vasopressin infusion. The fifth patient had arteriography without prior diagnostic studies because of massive hemorrhage; the bleeding site was identified and controlled with selective vasopressin infusion. Three patients had lower gastrointestinal endoscopy, with endoscopic identification of bleeding site in two patients, and endoscopic electrocautery controlled the bleeding in one patient. In the 13 patients with hemorrhage, cessation of bleeding occurred with intestinal rest and hydration in nine patients (69 percent), selective vasopressin infusion in three patients (23 percent), and endoscopic electrocautery in one patient (8 percent). Eight patients (62 percent) required blood transfusion with a mean of 4.8 units (excluding one patient on warfarin sodium who required 14 units of blood). No patient required surgical intervention. CONCLUSIONS: Incidence of hemorrhage after colonoscopic polypectomy or biopsy is low, and in our series, hemorrhage resolved without the need for surgical intervention. Management includes initial stabilization followed by diagnostic evaluation. Technetium-tagged red blood cell nuclear scintigraphy identifies ongoing bleeding and identifies patients in whom additional invasive procedures (arteriography, lower gastrointestinal tract endoscopy) are warranted.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1530-0358
    Keywords: Colonoscopy ; Surveillance ; Polyps
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to determine the appropriate surveillance for patients with a history of adenomatous polyps whose last colonoscopic examination was normal. METHODS: This was a retrospective review of a database of 7,677 colonoscopies (1990 to 1996). In patients under colonoscopic surveillance, we reviewed cases of patients who had received three colonoscopies (an index (initial) colonoscopy positive for adenomas and 2 follow-up colonoscopies (interim and final)). The risk of adenomas and cancers at final follow-up colonoscopy was compared between patients having a normal interim colonoscopy and those with a positive interim colonoscopy. The risk at final colonoscopy was also stratified by time interval and the size and number of adenomas at the initial index colonoscopy. RESULTS: Two hundred four patients undergoing surveillance for adenomas met inclusion criteria. At index colonoscopy the median polyp size was 1 cm and median frequency was three polyps. At all follow-up colonoscopies, we detected 493 adenomas and one cancer (median follow-up, 55 months). At 36 months patients with a normal interim colonoscopy (n=91) had significantly fewer polyps than patients with a positive interim colonoscopy (n=113; 15vs. 40 percent;P=0.0001). By 40 months, adenomas were detected in more than 40 percent of patients in both groups. The risk after a normal interim colonoscopy was not affected by time interval or number or size of polyps. Adenomas found subsequent to a normal interim colonoscopy were dispersed throughout the colon in 28 patients and isolated to the rectosigmoid in 6 patients. CONCLUSIONS: In patients with a history of adenomas, a normal follow-up colonoscopy is associated with a statistically but not clinically significant reduction in the risk of subsequent colonic neoplasms. These patients require follow-up surveillance colonoscopy at a four-year to five-year interval.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of computer aided molecular design 10 (1996), S. 337-358 
    ISSN: 1573-4951
    Keywords: Genetic algorithms ; Evolutionary programming ; Evolution strategies ; Drug design ; Molecular modelling ; Protein folding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary In recent years, search and optimisation algorithms inspired by evolutionary processes have been applied with marked success to a wide variety of problems in diverse fields of study. In this review, we survey the growing application of these ‘evolutionary algorithms’ in one such area: computer-aided molecular design. In the course of the review, we seek to summarise the work to date and to indicate where evolutionary algorithms have met with success and where they have not fared so well. In addition to this, we also attempt to discern some future trends in both the basic research concerning these algorithms and their application to the elucidation, design and modelling of chemical and biochemical structures.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-4951
    Keywords: Drug design ; De novo design ; Genetic algorithms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Recently, the development of computer programs which permit the de novo design of molecular structures satisfying a set of steric and chemical constraints has become a burgeoning area of research and many operational systems have been reported in the literature. Experience with PRO_LIGAND—the de novo design methodology embodied in our in-house molecular design and simulation system PRO-METHEUS—has suggested that the addition of a genetic algorithm (GA) structure refinement procedure can ‘add value’ to an already useful tool. Starting with the set of designed molecules as an initial population, the GA can combine features from both high- and low-scoring structures and, over a number of generations, produce individuals of better score than any of the starting structures. This paper describes how we have implemented such a procedure and demonstrates its efficacy in improving two sets of molecules generated by different de novo design projects.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-4951
    Keywords: Drug design ; De novo design ; Enzyme inhibitors ; Graph theory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary An approach to de novo molecular design, PRO_LIGAND, has been developed that, in the environment of a large, integrated molecular design and simulation system, provides a unified framework for the generation of novel molecules which are either similar or complementary to a specified target. The approach is based on a methodology that has proved to be effective in other studies-placing molecular fragments upon target interaction sites-but incorporates many novel features such as the use of a rapid graph-theoretical algorithm for fragment placing, a generalised driver for structure generation which offers a large variety of fragment assembly strategies to the user and the pre-screening of library fragments. After a detailed description of the relevant modules of the package, PRO_LIGAND's efficacy in aiding rational drug design is demonstrated by its ability to design mimics of methotrexate and potential inhibitors for dihydrofolate reductase and HIV-1 protease.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of computer aided molecular design 10 (1996), S. 397-416 
    ISSN: 1573-4951
    Keywords: Drug design ; Lead generation ; Thrombin inhibitors ; Scoring function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Two new computational tools, PRO_PHARMEX and PRO_SCOPE, for use in active-site-directed searching of 3D databases are described. PRO_PHARMEX is a flexible, graphics-based program facilitating the extraction of pharmacophores from the active site of a target macromolecule. These pharmacophores can then be used to search a variety of databases for novel lead compounds. Such searches can often generate many ‘hits’ of varying quality. To aid the user in setting priorities for purchase, synthesis or testing, PRO_SCOPE can be used to dock molecules rapidly back into the active site and to assign them a score using an empirical scoring function correlated to the free energy of binding. To illustrate how these tools can add value to existing 3D database software, their use in the design of novel thrombin inhibitors is described.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 11 (1994), S. 1204-1206 
    ISSN: 1573-904X
    Keywords: phenobarbital ; pharmacokinetics ; milk ; rabbit ; neonate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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