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Biomedical subjects

Michael Flanigan

Publications and source records attributed to Michael Flanigan.

7 recordsLinked to original sources

ThurGood: evaluating assembly-to-assembly mapping.

The alignment and mapping of large genomic sequences is the focus of much recent research. However, relatively little has been done so far about testing and validating alignment methods. We introduce criteria and new tools we have developed for alignment evaluation. These tools have already proved useful in the evaluation and ranking of several methods for assembly-to-assembly mapping, which were recently used to map multiple versions of the human genome to each other (Istrail et aL, 2004).

Algorithms↗

Insulin is protein-anabolic in chronic renal failure patients.

To examine the protein anabolic actions of insulin in chronic renal failure, the authors measured four sets of whole body leucine fluxes during insulin alone and insulin with amino acid infusion in nine uremic patients before hemodialysis (B-HD). Seven were restudied 8 wk after initiation of maintenance hemodialysis (HD). Six normal subjects served as control (N). All values ( micro mol/kg/h, mean +/- SEM) are presented in the sequence of B-HD, HD, and N, and only P < 0.05 are listed. During Flux 1 (baseline), D (leucine release from body protein degradation) were 114 +/- 7, 126 +/- 4, and 116 +/- 6, respectively. C (leucine oxidation rates) were 18 +/- 2, 17 +/- 2, and 21 +/- 3, respectively. S (leucine disappearance into body protein [index of protein synthesis]) were 96 +/- 6, 107 +/- 4, and 94 +/- 4, respectively, and balances (net leucine flux into protein [values were negative during fasting]) were -18 +/- 2, -17 +/- 2, and -21 +/- 3, respectively. During Flux 2 (low-dose insulin infusion), D were 89 +/- 3, 98 +/- 6, and 94 +/- 5, respectively; C were 12 +/- 1, 11 +/- 2, and 18 +/- 1, respectively (P = 0.02); S were 77 +/- 4, 87 +/- 5, and 76 +/- 5, respectively, and balances were -12 +/- 1, -11 +/- 2, and -18 +/- 1, respectively (P = 0.02). During Flux 3 (high-dose insulin infusion): D were 77 +/- 3, 82 +/- 7, and 84 +/- 5, respectively; C were 9 +/- 1, 8 +/- 1, and 14 +/- 1, respectively (P = 0.005); S were 68 +/- 4, 74 +/- 6, and 70 +/- 5, respectively, and balances were -9 +/- 1, -8 +/- 1, and -14 +/- 1, respectively (P = 0.005). In Flux 4 (insulin infused with amino acids): D were 73 +/- 3, 107 +/- 18, and 85 +/- 7, respectively; C were 35 +/- 4, 29 +/- 5, and 39 +/- 3, respectively; S were 105 +/- 5, 145 +/- 15, and 113 +/- 6, respectively (P = 0.02), and balances were 32 +/- 4, 38 +/- 5, and 27 +/- 3, respectively. These data show that B-HD and HD patients were as sensitive as normal subjects to the protein anabolic actions of insulin. Insulin alone reduced proteolysis and leucine oxidation, and insulin given with amino acids increased net protein synthesis.

Adolescent↗

Near-infrared spectroscopic measurement of urea in dialysate samples collected during hemodialysis treatments.

Single-beam spectra were collected over the combination region of the near-infrared spectrum for 80 samples collected from 15 people over a two-week period. Partial least-squares (PLS) regression was used to generate an optimized calibration model for urea. PLS calibration models accurately measure urea in the spent dialysate matrix. Prediction errors are on the order of 0.15 mM, which is sufficient for the clinical assessment of the dialysis process. In addition, the feasibility of a global calibration model is demonstrated by generating a calibration model from samples and spectra obtained from 12 people to predict the level of urea in samples collected from 3 different people. In this case, the standard error of prediction is 0.09 mM. Spectra were modified in order to systematically examine the impact of resolution and noise. Little impact is observed by altering the spectral resolution from 4 to 32 cm-1. Spectral noise, however, plays an important role in the accuracy of these calibration models. Increasing the magnitude of the spectral noise increases the prediction errors and increases the width of the spectral range necessary for extracting the analytical information. The utility of the method is demonstrated by analyzing dialysate samples collected during actual dialysis treatments. In addition, the necessary resolution and spectral quality necessary for reliable on-line urea monitoring is identified. These findings indicate that a dedicated, on-line urea spectrometer must posses a resolution of 16 cm-1 coupled with a sample thickness of 1.5 mm and spectral noise levels on the order of 25 micro-absorbance units when measured as the root-mean-square (RMS) noise of 100% lines.

Hemodialysis Solutions↗

The genome sequence of the malaria mosquito Anopheles gambiae.

Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency ("dual haplotypes") in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect.

Animals↗

Dialysate composition and hemodialysis hypertension.

Dialysis prescriptions have evolved to take advantage of new technology and serve a burgeoning patient population. High-sodium bicarbonate-based dialysate was first formulated in 1982 to enable short, safe, comfortable, high-efficiency hemodialysis (HD). Near-universal adaptation of these high-sodium formulas has virtually eliminated profound dialysis disequilibrium and greatly reduced dialysis discomfort, but has created a syndrome of dialysis salt loading with accentuated postdialysis thirst, interdialytic weight gain, and hypertension. Available technology will soon permit individuals to receive isonatremic dialysis with dialysate customized to the patient's serum sodium activity. Then, rather than choosing between comfortable, safe, high-efficiency dialysis with salt loading; cramps, asthenia, and symptomatic hypotension using low-sodium, high-efficiency rapid HD to control blood pressure (BP) and weight gain; or comfortable, slow, low-efficiency HD with BP control, physicians may be able to minimize symptoms and avoid dialysis salt loading while providing maximum time for rehabilitative activities. The current use of a single sodium activity for all patients ignores the inter- and intraindividual variability in serum sodium activity in our patients. This results in undesired consequences for 20-40% of patients. The application of even more severe salt loading through high-salt sodium modeling only accentuates the long-term problems of excessive thirst, weight gain, and hypertension.

Extracellular Fluid↗

Peritoneal catheters and exit-site practices toward optimum peritoneal access: a review of current developments.

OBJECTIVE: This review updates the 1998 International Society for Peritoneal Dialysis (ISPD) recommendations for peritoneal dialysis catheters and exit-site practices (Gokal R, et al. Peritoneal catheters and exit-site practices toward optimum peritonealaccess: 1998 update. Perit Dial Int 1998; 18:11-33.) DESIGN DATA SOURCES: The Ovid and PubMed search engines were used to review the Medline databases of January 1980 through June 2003. Searches were restricted to human data; primary key word searches included dialysis, peritoneal dialysis, and continuous ambulatory peritoneal dialysis cross referenced with access, catheter, dialysis catheter, peritoneal dialysis catheter, and Tenckhoff catheter. Related searches were provided via the PubMed related articles link. STUDY SELECTION: Reports were selected if they provided identifiable information on catheter design, catheter placement technique, and survival or placement complications. Reports without such data were excluded from review. Each study was then categorized by its characteristics: single-center or multicenter; retrospective or prospective; controlled trial, with or without random patient assignment; or review article. MAIN RESULTS: There are few randomized controlled evaluations testing how catheter design and/or placement influence long-term survival and function, and these are typically conducted at a single center. The majority of reports represent retrospective single-center experiences, and these are supplemented by occasional multicenter data registries. CONCLUSIONS: There is substantial variability in catheter outcomes between centers, and this variability is more closely correlated with operator and center characteristics than with catheter design. Some catheter designs appear to impact long-term catheter success, and, in some cases, specific patient characteristics and dialysis formats combine with specific catheter designs to influence catheter survival. Most reporters prefer two-cuff designs and placement of the deep cuff at an intramuscular location. Intramuscular cuff placement results in fewer pericatheter leaks and hernias, but makes catheter removal more difficult. High-risk patients (those with previous pelvic surgery) benefit from visual inspection of the peritoneum during catheter placement, and in randomized controlled trials, catheters with pre-shaped arcuate subcutaneous segments ("swan neck" designs) reduce the risk of early drainage failure via "migration."

Catheterization↗