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Heather Smith

Publications and source records attributed to Heather Smith.

12 recordsLinked to original sources
PubMed2004

Hepatitis B virus genotype A and D and clinical outcomes of liver transplantation for HBV-related disease.

Hepatitis B virus (HBV) genotypes have been associated with specific patterns of disease and response to antiviral therapy. We investigated the effect of HBV genotype on HBV recurrence and mortality after liver transplantation (LT). Pretransplant sera of 45 hepatitis B surface antigen (HBsAg) positive adults were submitted for HBV genotyping by a reverse-phase hybridization line probe assay with genotype-specific probes. Data were correlated with clinical outcomes after transplantation. Genotype A (n =15), D (n = 13) and A/D (n = 12) accounted for 89% of all genotypes. Coinfection with two HBV genotypes was encountered in 14 (31.1%) patients. Eighteen patients (40 %) developed HBV recurrence at a median of 10 months posttransplant (range, 1-53) and 10 patients (22 %) died at a median of 24 months (range, 3-63). Genotype D patients were more likely to develop HBV recurrence or die compared with genotype A patients, although this did not reach statistical significance. Dual infection with genotype A/D resulted in mortality similar to that of genotype A but recurrence similar to that of genotype D. Active viral replication at time of transplantation was the only independent factor (P = 0.03) that predicted HBV recurrence. In conclusion, HBV genotype A and D did not have a significant impact on clinical outcomes of LT for HBV-related liver disease in patients of European origin. These data do not support routine HBV genotyping in liver transplantation.

Adolescent↗
PubMed2004

Evaluation of the Rhodes Index of Nausea and Vomiting for ambulatory surgery patients.

BACKGROUND: The Index of Nausea and Vomiting (INV), developed by Rhodes and others in 1984, measures three dimensions of upper gastrointestinal distress: nausea, vomiting and retching (NVR). While the revised version has been tested with a variety of high-risk populations, there are no data suggesting that it can be used to assess upper gastrointestinal distress among the growing numbers of ambulatory or day surgery patients. AIM: The aim of this study was to evaluate a modified version of the INV for use with ambulatory surgery patients. METHODS: A secondary analysis was conducted using data obtained from a descriptive study designed to identify risk factors for postdischarge nausea and vomiting (PDNV) among adult ambulatory surgery patients. Patients who reported PDNV (n = 190) participated via phone interview 24 hours after discharge by completing a modified Rhodes INV. FINDINGS: Reliability analysis (alpha = 0.897) indicated that the modified Rhodes INV measured upper gastrointestinal distress as a single concept in the postdischarge ambulatory surgical sample. One item of the 8-item scale was dropped. Principal component analysis extracted one factor that accounted for 67% of the variance with all items loading. CONCLUSIONS: Upper gastrointestinal distress following ambulatory surgery discharge comprises a different symptom mix than during other high-risk events such as pregnancy or chemotherapy. Further research on the differences in assessing NVR among different populations is indicated.

Adolescent↗
PubMed2003

Molecular characterization of fluoroquinolone resistant Streptococcus pneumoniae clinical isolates obtained from across Canada.

There is little published data detailing fluoroquinolone resistance in clinical isolates of S. pneumoniae. The purpose of this study was to characterize the resistance mechanisms of 34 fluoroquinolone-resistant S. pneumoniae clinical isolates obtained from medical centers in 8 of 10 Canadian provinces between 1997 and 2000. The quinolone resistance determining regions of gyrA, parC, and parE from the isolates were sequenced. The isolates were evaluated for reserpine-sensitive efflux of ciprofloxacin and the new fluoroquinolones: gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin. The isolates were typed using pulsed field gel electrophoresis. The majority of the isolates were genetically unrelated. Lower level fluoroquinolone resistance (ciprofloxacin MIC 4-8 microg/ml) was associated with amino acid substitutions in ParC, while higher level resistance (ciprofloxacin MIC > or = 16 microg/ml) was associated with amino acid substitutions in both ParC and GyrA. ParE substitutions were not associated with clinical resistance. Twelve of 34 (35%) isolates demonstrated reserpine-sensitive efflux of ciprofloxacin. Efflux alone conferred low level ciprofloxacin resistance in 3 isolates. Significant reserpine-sensitive efflux of the new fluoroquinolones was not observed.

Anti-Bacterial Agents↗
PubMed2003

Liver histology and progression of fibrosis in individuals with chronic hepatitis C and persistently normal ALT.

OBJECTIVE: The natural history of hepatitis C virus (HCV) infection in patients with normal liver biochemistry remains poorly characterized. We performed a retrospective review of patients with chronic HCV infection and persistently normal ALT to compare clinical and histological features with those in patients with abnormal liver biochemistry. METHODS: Ninety-one HCV RNA-positive patients with persistently normal ALT who had a liver biopsy between 1993 and 1999 were identified. Clinical, histological, and epidemiological features in this group were compared with those found in 94 patients with abnormal ALT. Biopsies were assessed using Ishak's scoring system and fibrosis progression rate calculated from the likely time of infection. RESULTS: Although overall necroinflammatory score and fibrosis were significantly lower in those with normal ALT, none had normal liver histology, and 15 (16%) patients with normal ALT were found to have significant necroinflammation with a score of 5 or greater and/or significant fibrosis staged at 3 or 4. No clinical, epidemiological, or virological predictors of severe histological disease were found. CONCLUSIONS: One in six patients with HCV infection and persistently normal ALT will have evidence of significant, progressive liver disease that can only be identified on liver biopsy.

Adolescent↗
PubMed2003

Seasonal activity, size, and parity of Culicoides occidentalis (Diptera: Ceratopogonidae) in a coastal southern California salt marsh.

Adult female Culicoides occidentalis Wirth and Jones were collected in a coastal salt marsh habitat in southern California over a period of 15 mo using CO2-baited suction traps. Adults were active year-round. Adult females overall were large based on wing length (1.86 mm). Because of coastal influences, daily and seasonal changes in air temperatures were greatly buffered, and mean temperatures ranged from 10 to 15 degrees C in winter to 19-21 degrees C in summer. Wing lengths varied inversely with air temperatures, with an average of 2.13 mm (February) to 1.6 mm (July). Parity was consistently low (3.6% overall) and may reflect poor host availability in this isolated salt marsh habitat.

Animals↗
PubMed2002

Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 1. Discovery and optimization of salicylaldehyde thiosemicarbazone thrombopoietin mimics.

High-throughput screening has resulted in the discovery of thiosemicarbazone thrombopoietin mimics. A shared pharmacophore hypothesis between this series and a previously identified class, the pyrazol-4-ylidenehydrazines, led to the rapid optimization of both potency and efficacy of the thiosemicarbazones. The application of high-throughput chemistry and purification techniques allowed for the rapid elucidation of structure-activity relationships.

Aldehydes↗
PubMed2002

Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 2. Rational design of naphtho[1,2-d]imidazole thrombopoietin mimics.

The invention of a new class of naphtho[1,2-d]imidazole thrombopoietin mimics based on a pharmacophore hypothesis for small-molecule thrombopoietic agonists is discussed. Parallel array synthesis and purification techniques allowed for the rapid exploration of structure-activity relationships within this class and for the improvement in TPO mimetic potencies and efficacies.

Antigens, CD34↗
PubMed2002

Molecular characterization of meiotic recombination across the 140-kb multigenic a1-sh2 interval of maize.

The 140-kb a1-sh2 interval of the maize genome contains at least four genes (a1, yz1, x1, and sh2). Partial sequence analysis of two haplotypes has revealed many single nucleotide polymorphisms and InDel polymorphisms, including several large structural polymorphisms. The physical positions of 101 meiotic recombination breakpoints are not distributed uniformly across the interval and are instead concentrated within three recombination hot spots. Two of these recombination hot spots are genic (a1 and yz1) and one is apparently nongenic. The x1 gene is not a recombination hot spot. Thus, these results suggest that not all hot spots are genes and indicate that not all genes are hot spots. Two of the 101 recombination events arose by means of either noncrossover events involving conversion tract lengths of at least 17 kb or double-crossover events. Only one recombination breakpoint mapped to the approximately 80-kb distal portion of the a1-sh2 interval that contains large amounts of repetitive DNA including retrotransposons; in this region the ratio of genetic to physical distance is less than 0.5% of the genome's average. These results establish that the retrotransposon faction of the maize genome is relatively inert recombinationally.

Alleles↗
PubMed2002

Pharmacodynamic activity of fluoroquinolones against ciprofloxacin-resistant Streptococcus pneumoniae.

The susceptibility and pharmacodynamic activity of ciprofloxacin and new fluoroquinolones were studied against low-level (MIC 4 mg/L) and high-level (MIC 16 mg/L) ciprofloxacin-resistant Streptococcus pneumoniae. An in vitro pharmacodynamic model simulating free fluoroquinolone (protein unbound) serum concentrations, using Cp(max) and AUC(0-24) achieved (in healthy volunteers) after standard oral doses that are used for community-acquired respiratory infections, was used to compare bacterial killing by five fluoroquinolones against six ciprofloxacin-resistant S. pneumoniae isolates (four different resistance mutant phenotypes: ParC, efflux, ParC with efflux, and ParC and GyrA) obtained from an ongoing Canadian respiratory organism surveillance study. The potency (MIC only) of fluoroquinolones was gemifloxacin > moxifloxacin > gatifloxacin > levofloxacin > ciprofloxacin. Ciprofloxacin (free AUC(0-24)/MIC 0.9-3.5) produced no reduction of growth at 6, 24 or 48 h compared with the initial inoculum in all six strains. Levofloxacin (free AUC(0-24)/MIC 18-35) was bactericidal (> or = 3 log(10) killing) at 6, 24 and 48 h for the ParC as well as the efflux mutants, but only bactericidal at 24 h for the ParC with efflux strain. Levofloxacin (free AUC(0-24)/MIC 4.4) demonstrated no reduction of growth relative to the initial inoculum against the ParC and GyrA mutants. Gatifloxacin and moxifloxacin (free AUC(0-24)/MIC 48 and 60, respectively) were bactericidal at 6, 24 and 48 h against the ParC, efflux, and ParC with efflux mutants, but demonstrated little to no growth reduction (free AUC(0-24)/MIC 6 and 7.5, respectively) in ParC and GyrA mutants. Gemifloxacin (free AUC(0-24)/MIC 67-133) was bactericidal (> or = 3 log(10) killing) at 6, 24 and 48 h in all low-level ciprofloxacin-resistant S. pneumoniae mutants. Against two of the ParC and GyrA mutants, gemifloxacin (free AUC(0-24)/MIC 32) was bactericidal at 6, 24 and 48 h but against one ParC and GyrA mutant (free AUC(0-24)/MIC 16) gemifloxacin demonstrated reduced activity with initial killing at 24 h but with subsequent regrowth. These data indicate that ciprofloxacin produces no inhibition of growth of low- or high-level ciprofloxacin-resistant S. pneumoniae, whereas gatifloxacin, levofloxacin and moxifloxacin (moxifloxacin>gatifloxacin>levofloxacin) were bactericidal for low-level resistant strains but produced little or no inhibition of high-level resistant strains. Gemifloxacin at simulated free AUC(0-24)/MIC > or = 32, was bactericidal against low- and high-level resistant strains. When simulated free AUC(0-24)/ MIC was <16, gemifloxacin allowed regrowth of high-level ciprofloxacin-resistant strains.

Anti-Infective Agents↗
PubMed2002

A critical review of the fluoroquinolones: focus on respiratory infections.

The new fluoroquinolones (clinafloxacin, gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin) offer excellent activity against Gram-negative bacilli and improved Gram-positive activity (e.g. against Streptococcus pneumoniae and Staphylococcus aureus) over ciprofloxacin. Ciprofloxacin still maintains the best in vitro activity against Pseudomonas aeruginosa. Clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin display improved activity against anaerobes (e.g. Bacteroides fragilis) versus ciprofloxacin. All of the new fluoroquinolones display excellent bioavailability and have longer serum half-lives than ciprofloxacin allowing for once daily dose administration. Clinical trials comparing the new fluoroquinolones to each other or to standard therapy have demonstrated good efficacy in a variety of community-acquired respiratory infections (e.g. pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis). Limited data suggest that the new fluoroquinolones as a class may lead to better outcomes in community-acquired pneumonia and acute exacerbations of chronic bronchitis versus comparators. Several of these agents have either been withdrawn from the market, had their use severely restricted because of adverse effects (clinafloxacin because of phototoxicity and hypoglycaemia; grepafloxacin because of prolongation of the QTc and resultant torsades de pointes; sparfloxacin because of phototoxicity; and trovafloxacin because of hepatotoxicity), or were discontinued during developmental phases. The remaining fluoroquinolones such as gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin have adverse effect profiles similar to ciprofloxacin. Extensive post-marketing safety surveillance data (as are available with ciprofloxacin and levofloxacin) are required for all new fluoroquinolones before safety can be definitively established. Drug interactions are limited; however, all fluoroquinolones interact with metal ion containing drugs (eg. antacids). The new fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin) offer several advantages over ciprofloxacin and are emerging as important therapeutic agents in the treatment of community-acquired respiratory infections. Their broad spectrum of activity which includes respiratory pathogens such as penicillin and macrolide resistant S. pneumoniae, favourable pharmacokinetic parameters, good bacteriological and clinical efficacy will lead to growing use of these agents in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis. These agents may result in cost savings especially in situations where, because of their potent broad-spectrum activity and excellent bioavailability, they may be used orally in place of intravenous antibacterials. Prudent use of the new fluoroquinolones will be required to minimise the development of resistance to these agents.

Anti-Infective Agents↗
PubMedDate not supplied

Acute hepatitis A virus infection: a review of prognostic factors from 25 years experience in a tertiary referral center.

BACKGROUND/AIMS: Hepatitis A is usually a mild, self-limiting illness but can result in severe or fatal disease. We reviewed 25 years experience to determine what factors predispose to severe or fatal disease. METHODOLOGY: We identified 97 patients admitted between 1974-1999 with acute hepatitis A. Clinical, biochemical and histological data were correlated with outcome and patients were screened for evidence of hepatitis B or C virus coinfection and coexisting autoimmunity. RESULTS: Fifty-five patients had liver failure with hepatic encephalopathy of whom 29 died and 6 underwent liver transplantation. Patients with liver failure were significantly older than those without (mean age: 42.2 +/- 13.3 vs. 29.2 +/- 7.8, P = 0.0001), and liver failure patients who died were older than those surviving (47.5 +/- 12.7 vs. 36.3 +/- 11.6, P = 0.0001). Hyperacute liver failure predicted good outcome (P = 0.0001). Three patients with viral coinfection had established cirrhosis and died. Detectable autoantibodies did not correlate with outcome or severity. Patients acquiring infection abroad were more likely to have liver failure than those acquiring infection in the UK (P = 0.023). CONCLUSIONS: Age is the best predictor for outcome in patients with liver failure from hepatitis A. Underlying chronic liver disease, and the time of onset of encephalopathy are also factors affecting outcome. Infection acquired abroad has a worse prognosis.

Acute Disease↗