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Biomedical subjects

B Burnett

Publications and source records attributed to B Burnett.

15 recordsLinked to original sources
PubMed2006

Transarterial chemoembolisation for advanced hepatocellular carcinoma: results from a North American cancer centre.

AIMS: In Asian countries, transarterial chemoembolisation (TACE) has long been used for palliation of unresectable hepatocellular carcinoma (HCC) without strong evidence of improved survival or quality of life. In 2002, a survival benefi of TACE was shown in two randomised controlled trials in Europe and Hong Kong. The effectiveness of interventions fo HCC is influenced by geographical factors related to diverse patient characteristics and protocols. Therefore, the validation of TACE as palliative modality for unresectable HCC requires confirmation in diverse patient populations. The aim of the present study was to assess the effectiveness of TACE for HCC in a North American population. MATERIALS AND METHODS: This was a single centre prospective cohort study. Child-Pugh A cirrhosis or better patients wit unresectable HCC and without radiological evidence of metastatic disease or segmental portal vein thrombosis wer assessed between November 2001 and May 2004. Of 54 patients who satisfied the inclusion criteria, 47 underwent 80 TACE sessions. Chemoembolisation was carried out using selective hepatic artery injection of 75 mg/m(2) doxorubicin and lipiodol followed by an injection of embolic particles when necessary. Repeat treatments were carried out at 2-3 month intervals for recurrent disease. The primary outcome was overall survival; secondary outcomes were morbidity and tumour response. RESULTS: The survival probabilities at 1, 2 and 3 years were 76.6, 55.5 and 50%, respectively. At 6 months after the first intervention, 31% of patients had a partial response and 60% had stable disease by RECIST criteria. Minor adverse events occurred after 39% of TACEs and major adverse events after 20% of sessions, including two treatment-related deaths (4% of patients). One patient had complete cancer remission after undergoing three TACE treatments. Further progression of tumour growth was prevented in 91% of tumours at the 6 month point after the first TACE. At 3 months, serum levels of the tumour marker alpha-feto protein were significantly reduced in patients with elevated levels before TACE. CONCLUSIONS: The survival probabilities at 1 and 2 years after TACE were comparable with results in randomised studies from Europe and Asia. Most patients tolerated TACE well, but clinicians need to be aware that moderately severe sideeffects require close monitoring and prompt intervention.

Aged↗
PubMed2000

The first mail bomb?

A news item in the newspaper, the Evening Star, for the Country, October 18, 1833, probably is the first report of a mail bomb in the United States. It is also likely to be the first defusing of a mail bomb. The device appeared to be extraordinarily sophisticated and would have likely worked had it not been for suspicions of the recipient of the bomb.

Crime↗
PubMed1998

The recruitment triangle: reasons why African Americans enroll, refuse to enroll, or voluntarily withdraw from a clinical trial. An interim report from the African-American Antiplatelet Stroke Prevention Study (AAASPS).

Recruitment and retention of study subjects are key to the success of a clinical trial. In the case of minority patients, this may be challenging as minority patients have been underserved by the medical health-care system. Furthermore, minority patients are more likely to experience barriers to entry into a clinical trial such as mistrust of the medical system, economic disadvantages, lack of awareness of study programs, and communication barriers. An open-ended questionnaire was used to determine reasons why subjects in the African-American Antiplatelet Stroke Prevention Study (AAASPS) remained in the study or voluntarily withdrew in the absence of an adverse event. Potential enrollees who refused to participate in the AAASPS also were queried. Enrollees who remained in the program consistently stated that they participated to reduce the risk of stroke recurrence and to help others by finding a "cure" for stroke. Those who withdrew or refused to participate consistently stated that they were afraid of being used as "guinea pigs." A "recruitment triangle" emerged that might predict a patient's likelihood of participation in a clinical trial. The sides of the triangle include the patient, key family members and friends, and the primary medical doctor and other medical personnel. The organizers of a clinical trial need to be aware of the "recruitment triangle" and establish strategies to heighten and maintain its integrity.

Black or African American↗
PubMed1998

The formulation of recombinant factor IX: stability, robustness, and convenience.

A lyophilized recombinant factor IX (rFIX) formulation has been developed that is stable and contains no preservatives. No blood or plasma products are used in the production or formulation of rFIX. The formulation contains 10 mmol/L histidine, 0.26 mol/L glycine, 1% sucrose, and 0.005% polysorbate-80 (pH 6.8). Polysorbate-80 acts as a protectant for the protein from freezing-induced damage (eg, aggregation). Sucrose provides protection to the protein in the freeze-dried state. Glycine provides for a high-quality cake morphology. Histidine provides optimal buffering stability at the desired pH and minimizes aggregate formation upon storage in the lyophilized state. This optimized combination of excipients provides a high degree of long-term stability, as demonstrated by a variety of analytical methods, including clotting assays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing (IEF), size-exclusion chromatography (SEC), peptide mapping, oligosaccharide fingerprinting, and reverse-phase high-performance liquid chromatography (HPLC). The rFIX product is easy to reconstitute and demonstrates excellent stability in solution after reconstitution.

Chemistry, Pharmaceutical↗
PubMed1997

Hippocampal volume in normal aging and traumatic brain injury.

PURPOSE: To present a normative database of hippocampal and temporal horn volume and to clarify the relationship between these measures and cognitive outcome in patients with traumatic brain injury. METHODS: Ninety-six healthy volunteers and 94 patients with traumatic brain injury were examined with coronal intermediate and T2-weighted MR imaging. Multispectral segmentation and volume analyses were performed. The volumetry of the hippocampus and temporal horn was characterized in the control subjects. Volumetric measures in a group of patients with traumatic brain injury who had received MR imaging 3 months or less after injury were compared with measurements in other patients in the chronic phase of recovery. The relationship between neuropsychological testing and volumetric measures was analyzed with particular emphasis on the correlation between cognitive outcome and hippocampal and temporal horn volumes. RESULTS: No significant age group differences were found in the normative group from age 16 to 65. Left and right hippocampal volumes were interrelated and did not differ from each other. This was also true for the temporal horns. Hippocampal and temporal horn volumes were not significantly related. Women had larger hippocampi relative to cranial volume. Comparisons between patients with traumatic brain injury and control subjects showed significant yet modest bilateral atrophic changes in hippocampal and temporal horn enlargement in the patients with brain injury. Hippocampal and temporal horn volumes correlated significantly with each other in the group with traumatic brain injury. Cognitive outcome was modestly related to hippocampal and temporal horn volumes. However, in a specific subgroup whose images were acquired between 71 and 210 days after injury, strong correlations were noted in which temporal horn volume correlated highly with IQ and hippocampal volume correlated with verbal memory function. CONCLUSION: Hippocampal and temporal horn volumes appear to be independent variables in healthy control subjects. Traumatic brain injury results in significant hippocampal atrophy and temporal horn enlargement. The hippocampus and temporal horn volumes were inversely correlated in the group with traumatic brain injury, suggesting a differential relationship of these structures in patients with brain injury as compared with control subjects. In the subacute phase, the volume of the temporal horn may be indicative of intellectual outcome and that of the hippocampus appears to be indicative of verbal memory function.

Adolescent↗
PubMed1995

Uptake and processing of duplex DNA by RecA nucleoprotein filaments: insights provided by a mixed population of dynamic and static intermediates.

In the polarized strand exchange that is promoted by Escherichia coli RecA protein, when the initiating end of a duplex DNA molecule is blocked by heterology, the homologous distal end nonetheless forms a joint with single-stranded DNA, but strand exchange in that joint cannot be completed because the strand that would otherwise be displaced lacks a free 5' end. Instead, 2/3 to 3/4 of such distal joints cyclically form and dissociate. Dissociation requires the hydrolysis of ATP (Burnett et al., 1994). Observations on DNase protection revealed that consistent with their dynamic nature, these joints were heterogeneous in length, extending from the labeled distal end of the duplex up to 600 base pairs within the homologous region. Switching of base pairs was undetectable in this fraction of distal joints. However, the other 1/3 to 1/4 of distal joints, which did not cycle, were as long as the entire homologous region (6 kb), and underwent complete switching of base pairs. The formation of these static joints occurred at a rate in excess of 100 bp per second, without requiring hydrolysis of ATP. These and earlier observations suggest that the RecA filament containing single-stranded DNA rapidly incorporates duplex DNA into a coaxial three-stranded helix by a passive process, whereas additional energy is required to convert the three-stranded intermediate into products or back into substrates, both of which involve the unwinding of many turns of three-stranded helix.

Adenosine Triphosphate↗
PubMed1994

Resolution of the three-stranded recombination intermediate made by RecA protein. An essential role of ATP hydrolysis.

Previous work has shown that triplex DNA is an intermediate in homologous pairing and strand exchange promoted by RecA protein. Heterology at the proximal end of duplex DNA blocks strand exchange, but triplex joints form nonetheless at the homologous distal end. Experiments on the formation and processing of distal joints revealed that the yield of distal joints depends critically on the concentration of RecA-coated single strands and the adequacy of the ATP-regeneration system, and reflects a steady state. Distal joints reversibly formed and dissociated, as shown by several methods, including a chase with unlabeled duplex DNA. Controls excluded a contribution of exonucleolytic nibbling to the formation of distal joints and the stability of the deproteinized product. RecA protein was bound preferentially by putative triplex sites both in isolated proximal and distal joints. These high affinity sites disappeared from proximal joints as strand exchange progressed, and disappeared from distal joints as the joints dissociated. Dissociation of distal joints under all conditions, however, was completely arrested by the addition of ATP gamma S. Distal triplex joints can be as long as six kilobases. The observed inhibition of the dissociation of such long non-productive triplex intermediates by ATP gamma S leads us to propose that an essential role of ATP hydrolysis in RecA recombinational exchanges may be to ensure that no potentially troublesome triplex DNA remains in the cell.

Adenosine Triphosphate↗
PubMed1992

A partially deficient mutant, recA1730, that fails to form normal nucleoprotein filaments.

The phenotype of the recA1730 mutant is highly dependent on the level of expression of the RecA1730 protein. If the recA1730 gene was expressed from its own promoter, the cells were deficient in recombination and SOS induction. In contrast, when the recA1730 gene was expressed under the control of recAo98, a constitutive operator that increased the RecA1730 concentration 20-fold, cells became proficient in recombination and SOS induction. Likewise, in crude extracts, fivefold more RecA1730 than RecAwt was required to produce full cleavage of LexA protein. The requirement for a high RecA1730 concentration for recombination and LexA cleavage suggests that the recA1730 defect alters a common reaction step. In fact, in vitro data show that the impaired assembly of RecA1730 protein on single-stranded DNA (ssDNA) can account for the mutant phenotype. Purified RecA1730 protein was assayed in vitro for ssDNA binding and ATPase activities. RecA1730, like RecAwt, retained ssDNA equally well on nitrocellulose filters; this activity was specifically inhibited by a monoclonal anti-RecA antibody. However, RecA1730 protein did not form complete filaments on ssDNA, as shown by two observations: (i) most of the protein did not elute with ssDNA during gel filtration; and (ii) binding of RecA1730 to ssDNA did not protect it from being digested by DNaseI. RecA1730 hydrolysed ATP in high salt but was defective in ssDNA-dependent ATP hydrolysis. These results strongly suggest that RecA1730 binds to ATP and ssDNA but does not form normal nucleoprotein filaments.

Adenosine Triphosphatases↗
PubMed1988

Equivalent potency and pharmacokinetics of recombinant human growth hormones with or without an N-terminal methionine.

Two forms of human GH (hGH) have been produced by recombinant DNA technology. One form has an amino acid sequence identical to that of the natural pituitary hormone (rhGH) and the other form has an additional N-terminal methionine (Met-hGH). The biological potencies of these 2 polypeptides have been compared in hypophysectomized rats in a multidose study measuring body weights and several long bone growth parameters. The pharmacokinetic profiles after iv and sc injection were determined in cynomolgus monkeys in a 4-period cross-over study. All of the measured parameters in all the studies indicated that there was no difference in the two forms of hGH. Measurements taken after 27 daily injections of rhGH or Met-hGH (30-500 micrograms/kg.day) indicated that femur length and width of the proliferative zone in the tibial epiphysis showed dose-related effects for both forms of hGH but no difference between them. The relative potency, based on body weight gain, was calculated using a parallel line bioassay. Weight gain after 8 daily injections in the 5-dose long bone growth study indicated a rhGH potency of 0.80 (95% confidence interval, 0.5-1.23) relative to Met-hGH. It was concluded that the presence of an N-terminal methionine on hGH has no effect on potency in this model. The pharmacokinetic parameters after iv administration were estimated by fitting serum concentration-time data to a 2-compartment model. Parameters after sc injection were computed by compartment-independent methods. Met-hGH and rhGH had very similar pharmacokinetic profiles after both routes of administration. Comparison of the pharmacokinetic parameters indicated that the clearance after iv administration (rhGH, 15 ml/min; Met-hGH, 13 ml/min) and the sc bioavailability (rhGH, 0.72 +/- 0.21; Met-hGH, 0.59 +/- 0.21) were not significantly different for the 2 forms of hGH. It was concluded that rhGH and Met-hGH have equivalent bioavailability and pharmacokinetics in cynomolgus monkeys.

Amino Acid Sequence↗
PubMed1988

Pharmacokinetics of recombinant human interferon-gamma in the rhesus monkey after intravenous, intramuscular, and subcutaneous administration.

The pharmacokinetics of recombinant human interferon-gamma (rIFN-gamma) were studied in rhesus monkeys. Intravenous administration of 0.1 mg/kg yielded half-lives of 12.3-13.4 min and 130 min. Clearance after intravenous administration was 18.7 ml/min/kg, and the steady-state volume of distribution (Vdss) was 510 ml/kg. The peak serum concentrations after intramuscular and subcutaneous administration of 0.25 mg/kg rIFN-gamma were 50.7 and 52.3 ng/ml, respectively. The time to reach the peak serum concentration was 480 min for both routes. The mean bioavailabilities after intramuscular and subcutaneous administration were 109 and 90%, respectively. Intravenous administration of 0.25 mg/kg rIFN-gamma resulted in no significant change in the clearance, half-life, or Vdss, suggesting that the kinetics of rIFN-gamma are linear over the range of doses tested. Nearly all of the animals developed antibodies to rIFN-gamma after three doses. The presence of nonneutralizing antibodies to rIFN-gamma had no discernible effect on the calculated pharmacokinetic parameters.

Animals↗
PubMed1986

Cardiovascular findings in quadriplegic and paraplegic patients and in normal subjects.

Seven normal, 7 paraplegic and 7 quadriplegic patients underwent cross-sectional cardiovascular evaluation, including recording of sitting heart rate, blood pressure and echocardiography. Quadriplegic patients had a 26% lower left ventricular (LV) mass index (75 +/- 13 g/m2, p less than 0.01) compared with normal volunteers (102 +/- 16 g/m2) or paraplegic patients (110 +/- 26 g/m2). Six quadriplegic patients and 3 paraplegic patients had an unusual pattern of LV posterior wall asynergy, which was associated with a significant rightward shift of the frontal-plane QRS axis (92 +/- 22 degrees vs 42 +/- 41 degrees, p less than 0.005) and smaller left atrial dimensions (2.4 +/- 0.4 vs 3.0 +/- 0.3 cm, p less than 0.005). The quadriplegic group was characterized by a significantly reduced mean blood pressure (67 +/- 7 vs 88 +/- 8 mm Hg in normal subjects, p less than 0.002), high normal peripheral resistances (22 +/- 5 vs 17 +/- 5 units in normal subjects, difference not significant) and a markedly reduced calculated cardiac output (3.2 +/- 0.6 vs 5.4 +/- 1.4 liters/min in normal subjects, p less than 0.01). Hemodynamic data for the paraplegic patients were similar to those in the normal group. A decrease in LV wall stress, mediated primarily by a decrease in venous return, appeared to result in the "adaptive" cardiac atrophy seen in these quadriplegic patients. LV asynergy was common and also may be related to a decrease in cardiac filling.

Adolescent↗