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Biomedical subjects

K Hagan

Publications and source records attributed to K Hagan.

17 recordsLinked to original sources
PubMed2003

Comparison of gemcitabine versus the matrix metalloproteinase inhibitor BAY 12-9566 in patients with advanced or metastatic adenocarcinoma of the pancreas: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To compare the selective matrix metalloproteinase inhibitor BAY 12-9566 with the nucleoside analog gemcitabine in the treatment of advanced pancreatic cancer. METHODS: Patients with advanced pancreatic adenocarcinoma who had not previously received chemotherapy were randomly assigned to receive BAY 12-9566 800 mg orally bid continuously or gemcitabine 1,000 mg/m2 administered intravenously on days 1, 8, 15, 22, 29, 36, and 43 for the first 8 weeks, and then days 1, 8, and 15 of each subsequent 28-day cycle. The primary end point was overall survival; secondary end points were progression-free survival, tumor response, quality of life, and clinical benefit. The planned sample size of the study was 350 patients. Two formal interim analyses were planned. RESULTS: The study was closed to accrual after the second interim analysis on the basis of the recommendation of the National Cancer Institute of Canada Clinical Trials Group Data Safety Monitoring Committee. There were 277 patients enrolled onto the study, 138 in the BAY 12-9566 arm and 139 in the gemcitabine arm. The rates of serious toxicity were low in both arms. The median survival for the BAY 12-9566 arm and the gemcitabine arm was 3.74 months and 6.59 months, respectively (P <.001; stratified log-rank test). The median progression-free survival for the BAY 12-9566 and gemcitabine arms was 1.68 and 3.5 months, respectively (P <.001). Quality-of-life analysis also favored gemcitabine. CONCLUSION: Gemcitabine is significantly superior to BAY 12-9566 in advanced pancreatic cancer.

Adenocarcinoma↗
PubMed2002

Measurement of the K(L) charge asymmetry.

We present a measurement of the charge asymmetry delta(L) in the mode K(L)-->pi(+/-)e(-/+)nu based on 298 x 10(6) analyzed decays. We measure a value of delta(L) = [3322+/-58(stat)+/-47(syst)]x10(-6), in good agreement with previous measurements and 2.4 times more precise than the current best published result. The result is used to place more stringent limits on CPT and DeltaS = DeltaQ violation in the neutral kaon system.

Journal Article↗
PubMed2001

First measurement of form factors of the decay Xi(0) --> Sigma(+)e(-)nu macro(e).

We present the first measurement of the form factor ratios g(1)/f(1) (direct axial vector to vector), g(2)/f(1) (second class current), and f(2)/f(1) (weak magnetism) for the decay Xi(0)-->Sigma(+)e(-)nu macro(e) using the KTeV (E799) beam line and detector at Fermilab. From the Sigma(+) polarization measured with the decay Sigma(+)-->p pi(0) and the e(-)-nu; correlation, we measure g(1)/f(1) to be 1.32+/-(0.21)(0.17)(stat)+/-0.05(syst), assuming the SU(3)(f) (flavor) values for g(2)/f(1) and f(2)/f(1). Our results are all consistent with exact SU(3)(f) symmetry.

Journal Article↗
PubMed2001

Branching ratio measurement of the decay K(L) --> e(+)e(-)mu(+)mu(-).

We have collected a 43 event sample of the decay K(L)-->e(+)e(-)mu(+)mu(-) with negligible backgrounds and measured its branching ratio to be (2.62+/-0.40+/-0.17)x10(-9). We see no evidence for CP violation in this decay. In addition, we set the 90% confidence upper limit on the combined branching ratios for the lepton flavor violating decays K(L)-->e(+/-)e(+/-)mu(-/+)mu(-/+) at B(K(L)-->e(+/-)e(+/-)mu(-/+)mu(-/+))< or =1.23x10(-10), assuming a uniform phase space distribution.

Journal Article↗
PubMed2001

Measurement of the branching ratio and form factor of K(L)-->mu(+)mu(-)gamma.

We report on the analysis of the rare decay K(L)-->mu(+)mu(-)gamma the 1997 data from the KTeV experiment at Fermilab. A total of 9327 candidate events are observed with 2.4% background, representing a factor of 40 increase in statistics over the current world sample. We find that B(K(L)-->mu(+)mu(-)gamma) = (3.62 +/- 0.04(stat) +/- 0.08(syst)) x 10(-7). The form factor parameter alpha(K*) is measured to be alpha(K*) = -0.160(+0.026)(-0.028). In addition, we make the first measurement of the parameter alpha from the D'Ambrosio-Isidori-Portolés form factor, finding alpha = -1.54 +/- 0.10. In that model, this alpha measurement limits the Cabibbo-Kobayashi-Maskawa parameter rho>-0.2.

Journal Article↗
PubMed2001

Measurements of the rare decay K(L) --> e(+)e(-)e(+)e(-).

We observe 441 K(L)-->e(+)e(-)e(+)e(-) candidate events with a background of 4.2 events and measure B(K(L)-->e(+)e(-)e(+)e(-)) = [3.72+/-0.18(stat)+/-0.23(syst)]x10(-8) in the KTeV/E799II experiment at Fermilab. Using the distribution of the angle between the planes of the e(+)e(-) pairs, we measure the CP parameters beta(CP) = -0.23+/-0.09(stat)+/-0.02(syst) and gamma(CP) = -0.09+/-0.09(stat)+/-0.02(syst). We also present the first detailed study of the e(+)e(-) invariant mass spectrum in this decay mode.

Journal Article↗
PubMed2001

Measurement of the branching ratio and asymmetry of the decay Xi degrees -->Sigma degrees gamma.

We have studied the rare weak radiative hyperon decay Xi degrees -->Sigma degrees gamma in the KTeV experiment at Fermilab. We have identified 4045 signal events over a background of 804 events. The dominant Xi degrees -->Lambdapi degrees decay, which was used for normalization, is the only important background source. An analysis of the acceptance of both modes yields a branching ratio of B(Xi degrees -->Sigma degrees gamma)/B(Xi degrees -->Lambdapi degrees ) = (3.34+/-0.05+/-0.09)x10(-3). By analyzing the final state decay distributions, we have also determined that the Sigma degrees emission asymmetry parameter for this decay is alpha(XiSigma) = -0.63+/-0.09.

Journal Article↗
PubMed2001

Study of the K(0)(L) --> pi(+)pi(-)gamma Direct Emission Vertex.

We have performed studies of the K(0)(L)-->pi(+)pi(-)gamma direct emission ( DE) and inner Bremsstrahlung ( IB) vertices, based on data collected by KTeV during the 1996 Fermilab fixed target run. We find a(1)/a(2) = -0.737+/-0.034 GeV2 for the DE form-factor parameter in the rho-propagator parametrization, and report on fits of the form factor to linear and quadratic functions as well. We concurrently measure gamma(K(0)(L)-->pi(+)pi(-)gamma,E(*)(gamma)>20 MeV)/gamma(K(0)(L)-->pi(+)pi(-)) = (20.8+/-0.3)x10(-3), and a K(0)(L)-->pi(+)pi(-)gamma DE/(DE+IB) branching ratio of 0.683+/-0.011.

Journal Article↗
PubMed2001

Search for the decay KL --> pi(0)e+e-.

We report on a search for the decay KL-->pi(0)e+e- carried out by the KTeV/E799 experiment at Fermilab. This decay is expected to have a significant CP violating contribution and the measurement of its branching ratio could support the Cabibbo-Kobayashi-Maskawa mechanism for CP violation or could point to new physics. Two events were observed in the 1997 data with an expected background of 1.06+/-0.41 events, and we set an upper limit B(KL-->pi(0)e+e-)<5.1 x 10(-10) at the 90% confidence level.

Journal Article↗
PubMed1999

Mutations in VPS16 and MRT1 stabilize mRNAs by activating an inhibitor of the decapping enzyme.

Decapping is a rate-limiting step in the decay of many yeast mRNAs; the activity of the decapping enzyme therefore plays a significant role in determining RNA stability. Using an in vitro decapping assay, we have identified a factor, Vps16p, that regulates the activity of the yeast decapping enzyme, Dcp1p. Mutations in the VPS16 gene result in a reduction of decapping activity in vitro and in the stabilization of both wild-type and nonsense-codon-containing mRNAs in vivo. The mrt1-3 allele, previously shown to affect the turnover of wild-type mRNAs, results in a similar in vitro phenotype. Extracts from both vps16 and mrt1 mutant strains inhibit the activity of purified Flag-Dcp1p. We have identified a 70-kDa protein which copurifies with Flag-Dcp1p as the abundant Hsp70 family member Ssa1p/2p. Intriguingly, the interaction with Ssa1p/2p is enhanced in strains with mutations in vps16 or mrt1. We propose that Hsp70s may be involved in the regulation of mRNA decapping.

Adenosine Triphosphatases↗
PubMed1999

Adaptation to hypoxia alters energy metabolism in rat heart.

The present study characterized metabolic changes in the heart associated with long-term exposure to hypoxia, a potent stimulus for pulmonary hypertension and right ventricular hypertrophy. When anesthetized rats adapted to chronic hypoxia spontaneously respired room air, their mean right intraventricular peak systolic pressure (RVSP) was twice that in normal control animals with the same arterial PO2. RVSP was linearly related to right ventricular mass (r = 0.78). Oxidative capacity (O2 consumption) of homogenates of right and left ventricles from both groups of rats was measured with one of the following substrates: pyruvate, glutamate, acetate, and palmitoyl-L-carnitine. Oxidation of all substrates was significantly greater in the left than in the right ventricle in normal rats but not in hypoxia-adapted animals, where it was the same, within the experimental error. O2 consumption by the left ventricle was greater in control than in experimental rats, but right ventricular O2 consumption was similar in the two groups. Maximal reaction velocity of cytochrome-c oxidase was about the same in the two ventricles, and there were no significant differences between control and hypoxia-adapted animals. HPLC analyses showed significantly higher aspartate levels and aspartate-to glutamate concentration ratios in both ventricles of hypoxic rats than in corresponding tissues from controls, indicative of a decreased flux through the malate-aspartate shuttle under conditions of O2 limitation. Myocardial glutamine levels were lower in hypoxic rats, and glutamine-to-glutamate concentration ratios decreased, although primarily in the pressure-overloaded right ventricle. These findings indicate that normal energy metabolism in the left ventricle differs from that in the right and that the differences, particularly those of amino acid metabolism, are markedly influenced by chronic exposure to hypoxia.

Adaptation, Physiological↗
PubMed1995

Placebo controlled trial of fusidic acid gel and oxytetracycline for recurrent blepharitis and rosacea.

A prospective, randomised, double blind, partial crossover, placebo controlled trial has been conducted to compare the performance of topical fusidic acid gel (Fucithalmic) and oral oxytetracycline as treatment for symptomatic chronic blepharitis. Treatment success was judged both by a reduction in symptoms and clinical examination before and after therapy. Seventy five per cent of patients with blepharitis and associated rosacea were symptomatically improved by fusidic acid gel and 50% by oxytetracycline, but fewer (35%) appeared to benefit from the combination. Patients with chronic blepharitis of other aetiologies did not respond to fusidic acid gel but 25% did benefit from oxytetracycline and 30% from the combination. Our results demonstrate the need to investigate patients with blepharitis for concomitant rosacea as they respond well to targeted therapy.

Blepharitis↗
PubMed1993

Laparoscopic insertion of the Moss feeding tube.

Placement of enteral feeding tubes is an important part of a surgeon's skill base. Surgical insertion of feeding tubes has been performed safely for many years with very few modifications. With the recent surge in interest and applicability of other laparoscopic procedures, it is well within the skills of the average laparoscopic surgeon to insert feeding tubes. We describe herein a simple technique for the insertion of the Moss feeding tube. The procedure described has a minimum of invasion, along with simplicity, safety, and accuracy.

Duodenum↗
PubMed1989

Adjunctive use of laser Doppler flowmetry for debridement of osteomyelitis.

Laser Doppler flowmetry was used intraoperatively to differentiate viable from nonviable bone during the debridement of 12 cases of chronic osteomyelitis and three cases of acute bone infection following trauma. Six weeks of i.v. antibiotic therapy were directed against two cases of gram-positive and 13 cases of gram-negative bone infection. In cases of chronic infection, free muscle flaps were added for soft tissue coverage in five cases and rotational muscle flaps in four cases. At follow-up observation, of 1 to 3 years, no recurrences were seen. Laser Doppler flowmetry is an easy-to-use adjunct to the surgical debridement of bone infection.

Adult↗