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Biomedical subjects

K Burton

Publications and source records attributed to K Burton.

At least 19 recordsLinked to original sources
PubMed2000

Time-dependent impairment of mitochondrial function after storage and transplantation of rabbit kidneys.

BACKGROUND: The mitochondrial respiratory chain is implicated as a major target of kidney damage after ischemia-reperfusion. This study measures changes in integrated mitochondrial function and in the activity of enzymes of the respiratory chain after cold storage and transplantation-reperfusion in vivo. METHODS: Mitochondrial oxygen consumption and activities of respiratory chain enzymes and citrate synthase were measured in cortical mitochondria isolated from rabbit kidneys after 1-48 hr of cold ischemia with or without transplantation-reperfusion. RESULTS: State 4 mitochondrial oxygen consumption was significantly increased after 48 hr of ischemia or 24-48 hr of ischemia with transplantation. Prolonged (24 or 48 hr) ischemic storage with and without transplantation caused a significant decrease in state 3 oxygen consumption, as did transplantation after 1, 24, and 48 hr of cold storage. Complex I and complex II-III activity decreased after 24 or 48 hr of ischemia, with transplantation having little additional effect. Complex IV activity was significantly decreased after 48 hr of ischemia, this decrease being exacerbated by transplantation-reperfusion. Complex V activity decreased significantly after 1 hr of ischemia and continued to decrease after 24-48 hr of ischemia. Transplantation after 1-24 hr (but not 48 hr) of ischemia resulted in partial recovery of complex V activity. Citrate synthase activity was decreased significantly only after 48 hr of ischemia and reperfusion, consistent with the loss of mitochondrial membrane integrity seen in electron micrographs of the transplanted 48-hr group. CONCLUSIONS: These data suggest that individual rabbit kidney mitochondrial complexes have different susceptibilities to cold ischemic and reperfusion damage.

Animals↗
PubMed2000

Smokers ages 50+: who gets physician advice to quit?

BACKGROUND: Smoking-related morbidity and mortality, and benefits associated with quitting, extend across the life span. Health care provider interventions enhance quitting. The present study examined perceived influence of physician advice to quit and characteristics of subjects receiving this advice. METHODS: Subjects were 1,454 smokers ages 50+ with at least one physician visit in the past year. Subjects were surveyed at baseline for receipt of and reactions to physician advice to quit and for smoking, health, and demographic characteristics. RESULTS: Over half of subjects welcomed physician advice to quit, about half said the advice influenced their quitting decision "extremely" or "quite a lot," and about one-third indicated that it increased their confidence in quitting. Physicians were more likely to advise sicker patients, indicated by poorer health status, at least one past year hospitalization, and presence of cardiovascular, cerebrovascular, or respiratory diseases. CONCLUSIONS: Midlife and older smokers reacted generally favorably to physician advice to quit. Physicians were more likely to advise patients with commonly recognized smoking-related diseases. Discrepancies were noted in advice given to sicker vs healthier patients. Additional physician training in less commonly recognized smoking-related illnesses, intervening with healthier patients to prevent disease, and enhancing patients' confidence in quitting may improve outcomes.

Aged↗
PubMed2000

Polymer and microsphere blending to alter the release of a peptide from PLGA microspheres.

The objective of this study was to evaluate the effect of polymer and microsphere blending in achieving both a sufficient initial release and a desired continuous release of a peptide from poly(D, L-lactide-co-glycolide) microspheres. Leuprolide acetate loaded hydrophilic 50:50 PLGA microspheres were prepared by a solvent-extraction/evaporation process and were characterized for their drug load, bulk density, size distribution, surface area, surface morphology, in vitro drug release, and in vivo efficacy. Combining PLGA polymers that varied in their molecular weights in various ratios yielded microspheres with varied drug release profiles commensurate with the hydration tendencies of the polymers. Increasing the component of lower molecular weight 50:50 hydrophilic PLGA polymer, 8.6 kDa increased the initial drug release. A similar microsphere formulation prepared instead with blending microspheres from individual polymers showed a similar increase. In an animal model, microspheres obtained from polymer or microsphere blends attained a faster onset of testosterone suppression as compared to microspheres from higher molecular weight 50:50 hydrophilic PLGA polymer, 28.3 kDa, alone. These studies illustrated the feasibility of blending polymers or microspheres of varied characteristics in achieving modified drug release. In particular the increased initial release of the peptide could help avoid the therapeutic lag phase usually observed with microencapsulated macromolecules.

Animals↗
PubMed2000

Using unconditional and conditional standard deviation scores of fetal abdominal area measurements in the prediction of intrauterine growth restriction.

OBJECTIVE: To compare the performance of unconditional and conditional standard deviation scores (Z scores) of fetal abdominal area (FAA) measurements in the antenatal identification of infants born with anthropometric features of intrauterine growth restriction. METHODS: A prospective observational study, involving 274 low-risk women participating in a longitudinal study of serial ultrasound in pregnancy. Conditional Z scores were established for the last FAA prior to delivery with reference to measurements made both 28 and 56 days previously. Unconditional Z scores (size) were calculated from the last FAA measurement prior to delivery. Receiver-operator characteristics curves were employed to determine an optimal cut-off point for Z scores to predict intrauterine malnourishment. The main outcome measures were: likelihood ratios (LR) for conditional and unconditional Z scores of FAA in the prediction of infants with skinfold thickness < 10th percentile; ponderal index < 25th percentile or mid-arm circumference to occipitofrontal circumference ratio (MAC/OFC) of < -1 SD. An LR of > 10 generates significant changes in the pretest probability of growth restriction, whereas an LR of 5-10 generates only moderate changes. RESULTS: Conditional Z scores with 28- and 56-day separations predicted growth restriction with LR 7.5 (95% confidence interval [CI], 3.7-14.7) and 4.8 (95% CI, 2.8-7.8) for ponderal index but did not usefully predict skinfold thickness or MAC/OFC. Unconditional Z scores did not usefully predict any of the parameters of growth restriction. CONCLUSIONS: Quantifying third trimester fetal growth by means of FAA conditional Z scores is moderately useful in predicting infants with a low ponderal index and is superior to unconditional FAA Z scores in late pregnancy.

Abdomen↗
PubMed2000

Recruitment strategies and success in a multi-county smoking cessation study.

The current paper focuses on the process evaluation of recruitment strategies and success in a large study of self-help smoking interventions with mid-life and older smokers in a 15-county area. Recruitment 'channels' were examined: (1) multiple paid newspaper advertisements, (2) free media (i.e., TV and radio), (3) referrals, (4) HMO newsletters, (5) targeted mailings, (6) face-to-face, and (7) passive recruitment. Data were analyzed to determine (1) which channels produced the greatest numbers of information requests, or initial 'recruits', and (2) which produced the greatest number of enrolled subjects. Overall, four channels resulted in the enrollment of 96.4% of the final sample of 1972 subjects. The most reliable, cost-controlled channel was paid newspaper advertisements ($18-19 per enrolled subject), while face-to-face recruitment was inefficient and costly (over $140 per subject). Results can be used to help guide other studies in selecting recruitment strategies for large, geographically diverse, smoking intervention trials.

Aged↗
PubMed2000

Valence-dependent modulation of psychophysiological measures: is there consistency across repeated testing?

The present study used the picture perception paradigm to examine the extent to which three well-documented psychophysiological measures demonstrate consistency across time in response to emotional stimuli. The three measures were the eye-blink startle response and the activation in two facial muscle regions (zygomatic and corrugator). Twenty-seven young women were assessed on two occasions, 2 weeks apart. Whereas activation in the corrugator and zygomatic muscle regions demonstrated the predicted patterns at both assessments (with some attenuation in the zygomatic muscle regions), the startle response had limited consistency across the two assessments. The startle response revealed the predicted linear pattern of valence modulation during the first assessment. During the second assessment, startle magnitude response was a quadratic function of valence ratings and a linear function of arousal ratings. The unexpected pattern of startle response during the second session appeared to be related to the content of the pleasant slides, with action slides generating quadratic valence modulation and erotic slides continuing to exhibit the expected linear valence modulation.

Adult↗
PubMed1999

Keratocytes generate traction forces in two phases.

Forces generated by goldfish keratocytes and Swiss 3T3 fibroblasts have been measured with nanonewton precision and submicrometer spatial resolution. Differential interference contrast microscopy was used to visualize deformations produced by traction forces in elastic substrata, and interference reflection microscopy revealed sites of cell-substratum adhesions. Force ranged from a few nanonewtons at submicrometer spots under the lamellipodium to several hundred nanonewtons under the cell body. As cells moved forward, centripetal forces were applied by lamellipodia at sites that remained stationary on the substratum. Force increased and abruptly became lateral at the boundary of the lamellipodium and the cell body. When the cell retracted at its posterior margin, cell-substratum contact area decreased more rapidly than force, so that stress (force divided by area) increased as the cell pulled away. An increase in lateral force was associated with widening of the cell body. These mechanical data suggest an integrated, two-phase mechanism of cell motility: (1) low forces in the lamellipodium are applied in the direction of cortical flow and cause the cell body to be pulled forward; and (2) a component of force at the flanks pulls the rear margins forward toward the advancing cell body, whereas a large lateral component contributes to detachment of adhesions without greatly perturbing forward movement.

Actins↗
PubMed1997

Measurements of tissue viability in transplantation.

Near-infrared spectroscopy has primarily been used in monitoring changes in cerebral haemoglobin oxygenation and haemodynamics. However its use as a method for the assessment of tissue viability following transplantation has recently been explored experimentally in our laboratory. The ability to measure changes in oxygenation and perfusion during harvesting and following transplantation of organs or transfer of free and pedicled flaps potentially important in reconstructive surgery. We have found that near-infrared spectroscopy is extremely useful in detecting vaso-occlusive events and can accurately and reliably distinguish between arterial, venous or total occlusions. Venous congestion indicated by raised levels of deoxygenated haemoglobin with a concomitant increase in blood volume and the presence and magnitude of reactive hyperaemia are both easily recognizable features by near-infrared spectroscopy. We have shown that near-infrared spectroscopy measurements of venous congestion in kidneys (and other tissues) following prolonged storage correlate with medullary vascular congestion confirmed by angiographical and histological analysis of intrarenal perfusion. Clinically we have shown that flap perfusion can be improved by altering fluid replacement regimes and the addition of ionotropes. Cerebral near-infrared spectroscopy measurements in a liver transplant model showed statistically significant differences within minutes after the anhepatic phase in cerebral perfusion and oxygenation, between animals transplanted with ischaemically damaged livers compared to those isografted with minimally stored livers. Similarly we have found that near-infrared spectroscopy can be used as a monitor to assess the adequacy of fluid or blood replacement in haemorrhagic and hypovolaemic models. We believe that near-infrared spectroscopy provides a sensitive and reliable postoperative method for the assessment of tissue viability following the transfer of free and pedicled flaps and organs.

Animals↗
PubMed1997

Traction forces of cytokinesis measured with optically modified elastic substrata.

Animal cells dividing in culture undergo a dramatic sequence of morphological changes, characterized by cytoskeletal disassembly as cells round up, redistribution of actin, myosins and other cytoplasmic and surface molecules into the cleavage furrow, and respreading, before daughter cells finally separate at the mid-body. Knowledge of forces governing these movements is critical to understanding their mechanisms, including whether formation of the cleavage furrow results from increased force generation at the equator or relaxation at the poles, and whether traction force subsequently mediates cytofission of the intercellular bridge. We have quantitatively mapped traction forces in dividing cells, by extending the silicone-rubber substratum method to detect forces of nanonewtons to micronewtons. We used a new silicone polymer to fabricate substrata whose compliance can be adjusted precisely by ultraviolet irradiation. We show that traction force appears locally at the furrow in the absence of relaxation at the poles during cleavage. Force also rises as connected daughter cells respread and attempt to separate, suggesting that tension contributes to the severing of the intercellular bridge when cytokinesis is completed.

3T3 Cells↗
PubMed1995

Donor-specific transfusions have long-term beneficial effects for human renal allografts.

From April, 1980 to November, 1988, 163 one or two haplotype-mismatch living related (LR) or living unrelated (LUR) potential renal transplant recipients received three 200 ml aliquots of donor specific transfusion (DST) at biweekly intervals with concomitant azathioprine (2 mg/kg/day). Following transplantation, only prednisone and azathioprine were given for immunosuppression. The results for the DST group are compared with those for HLA identical living recipients (57 patients) transplanted during this same interval (1980-1988). Comparison is also made with a group of one or two haplotype-mismatched living donor recipients (54 patients) not treated with DST but with triple drug therapy (prednisone, azathioprine, cyclosporine) and antithymocyte globulin (ATG) or OKT-3 induction. Permanent T cell crossmatch sensitization occurred in 11 of 163 patients (7%). Successful DST donor transplants were performed between 121 one HLA haplotype-mismatched, 14 two HLA haplotype-mismatched LR, and 7 two haplotype-mismatched LUR pairs. Actual one- and five-year graft survivals were 94%, 100%, 100%, and 72%, 85%, and 71%, respectively, for these three subgroups of DST treated patients. The graft survival for all DST pretreated recipients at one, five, and ten years was comparable to the HLA-identical group (94%, 79%, 64% vs. 91%, 80% and 77%). At a mean follow-up of 10 1/2 years, 54% (80 patients) of the entire group of 147 patients transplanted after DST have functioning transplants with a mean serum creatinine of 1.7 mg/dl. Fifteen percent of DST patients (21 patients) died with a functioning graft 2 to 132 months after transplantation, 26% (37 patients) rejected the DST graft after 1 to 128 months, and 6% (9 patients) were lost for nonimmunological reasons. No lymphoproliferative disease developed in the DST group and the incidence of cytomegalovirus sepsis was only 2% (3 patients). The long-term beneficial effects of DST on renal allograft survival and function and the lower incidence of the complications of nonspecific immunosuppression should encourage increased utilization of DST in renal transplantation.

Azathioprine↗
PubMed1995

Family history of severe cardiovascular disease in Marfan syndrome is associated with increased aortic diameter and decreased survival.

OBJECTIVES: We attempted to determine whether a family history of severe cardiovascular disease in patients with the Marfan syndrome is associated with increased aortic dilation or decreased survival, or both. BACKGROUND: The prognostic importance of a family history of severe cardiovascular disease in patients with the Marfan syndrome has been incompletely examined. We hypothesized that such a family history would correlate with increased aortic dilation and would be associated with decreased survival. METHODS: One hundred eight affected patients and 48 unaffected family members from 33 multigenerational families with the Marfan syndrome underwent echocardiographic measurement of the aortic root, arch and mid-abdominal aorta. Date of birth and age at death ascertained from family pedigrees were used to perform life table analysis and estimate survival. RESULTS: Aortic root and arch diameters were significantly greater in patients with a family history of severe cardiovascular disease than in patients without such a family history. Of subjects in the highest quartile for aortic size, > 80% had such a family history in contrast to < 10% of those in the lowest quartile (chi-square 57.37, p < 0.00001). Mean age at death and cumulative probability of survival were significantly lower in patients with such a family history. CONCLUSIONS: Among patients with the Marfan syndrome, aortic dilation is greater and life expectancy shorter in those with a family history of severe cardiovascular manifestations. These data suggest that such a family history is an important risk factor for cardiovascular events in patients with the Marfan syndrome.

Adult↗
PubMed1995

Identification of source of oscillations in apparent sarcomere length measured by laser diffraction.

The most widely used technique for dynamic estimates of sarcomere length in muscle is laser light diffraction. We have identified conditions under which artifactual oscillations can arise in apparent sarcomere length measured by this technique and report methods to reduce the effect. Altringham et al. (1984) first reported that the diffraction angle can exhibit one cycle of oscillation for each sarcomere length displacement of the illuminated portion of the fiber. We find that the amplitude of similar oscillations is strongly dependent on the intensity of light scattered from objects near the fiber and on the spacing between fiber and scatterer. The oscillations can be eliminated by minimizing scattered light and positioning the fiber a few millimeters from sources of scattering. A theoretical description shows that oscillations of this kind are expected from interference of scattered and diffracted light. Interference fringes were observed along the meridian of the pattern, and these moved during translation of either a fiber or a grating. The movement of fringes across the diffraction order shifts the centroid back and forth and, when associated with steady shortening, can give rise to "steps" and "pauses" in apparent striation spacing.

Animals↗
PubMed1995

Beneficial effects of donor-specific transfusions on long-term renal allograft function.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 163 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor-recipient combinations were at least one-haplotype disparate, and 21 were two-haplotype disparate. Transient sensitization occurred in 2% and permanent sensitization in 7%. Over a 10-year period, the DST+Aza allograft survival rate is similar to the HLA-identical sibling transplants. The CMV sepsis rate was only 2%, and there were no lymphoproliferative neoplasms. The low rate of sensitization (7%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of early rejection (3%) argues for a modification of the immunologic response.

Azathioprine↗
PubMed1994

Adenine transport in Escherichia coli.

The purP gene for energized high-affinity adenine uptake in Escherichia coli is localized to a restriction fragment between tnaB and bglR. Comparison with DNA sequence data (Burland et al. 1993) indicates the involvement of the open-reading frame f445 (86003 < 84666). A non-energized transport route of lower affinity also occurs. The purP system is known to require metabolic removal of transported adenine which would diminish futile cycling by the two transport systems and toxicity by external adenine. Analysis of a conventional kinetic model for permeases suggests that internal adenine might inhibit transport sufficiently to account for the lack of accumulation.

Adenine↗