Biomedical subjects

R Malone

Publications and source records attributed to R Malone.

At least 19 recordsLinked to original sources

PubMed2006

Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation.

BACKGROUND: Warfarin is a mainstay of therapy for conditions associated with an increased risk of thromboembolic events. However, the use of this common agent is fraught with complications and little is known regarding inter-individual variation in warfarin response. OBJECTIVE: We tested for association between single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 and average weekly warfarin dose required to maintain patients at their desired anticoagulation target. METHODS: The sample consisted of 93 European-American patients from anticoagulation clinics at the University of North Carolina at Chapel Hill. Data on mean weekly warfarin dose were collected over a mean treatment period of 20.6 months. ANCOVA models were used and haplotype analysis was performed. RESULTS: Three of six VKORC1 SNPs were found to be very strongly associated with the average warfarin dose required to achieve the target international normalised ratio (INR; p<0.0001). The mean weekly dose by genotype ranged from approximately 27 to 47 mg. There was no evidence for an association between either of the two CYP2C9 polymorphisms studied, CYP2C9*2 and CYP2C9*3. CYP2C9*3 was significantly (p = 0.05) associated with average warfarin dosage after adjustment for VKORC1*1173. CONCLUSIONS: These results are of considerable clinical interest and confirm recently published results regarding the role of these two genes in modifying warfarin metabolism and maintenance dosage. The consistent findings regarding the role of VKORC1 and CYP2C9 in warfarin metabolism and maintenance dosage represent a clinically useful proof of principal for the use of pharmacogenomic information in medicine and may lead to improved understanding of warfarin's actions.

Adult↗

PubMed2006

Effect of refined soy oil or whole soybeans on intake, methane output, and performance of young bulls.

An experiment was conducted to establish the effects of feeding refined soy oil (RSO) or whole soybeans (WSB) containing soy oil on DMI, animal performance, and enteric methane (CH4) emissions in young bulls. Thirty-six Charolais and Limousin cross-bred, young beef bulls (338 +/- 27 kg of BW, 218 +/- 17 d of age at the beginning of the experiment) were blocked by BW, age, and breed before being assigned in a randomized complete block design to 1 of 3 experimental treatments (n = 12). The experimental period lasted for 103 d, with enteric CH4 output recorded for 2 periods of 5 consecutive days on d 37 to 41 and d 79 to 83. The 3 dietary treatments consisted of a barley/soybean meal-based concentrate with 0 g/d of RSO; oil from WSB as 6% of DMI (WSB treatment); and oil from RSO as 6% of DMI (RSO treatment). Each diet had a 10:90 forage:concentrate ratio, using barley straw as the forage source. Diet affected DMI (P < or = 0.001) and GE intake (P < 0.05 during the CH4 measurement periods), with the WSB treatment producing the lowest values. The addition of WSB decreased ADG (P < 0.05) compared with the RSO treatment. The WSB treatment also decreased (P < 0.05) average daily carcass gain (ADCG). Both the RSO and WSB concentrates decreased (P < 0.05 to P < 0.001) daily enteric CH4 output when expressed in terms of liters per day, liters per kilogram of DMI, percentage of GE intake, liters per kilogram of ADG, and liters per kilogram of ADCG. Diet had no effect (P = 0.557) on ruminal protozoal numbers. The reductions in enteric CH4 were achieved at relatively high oil inclusion levels. Such oil levels have previously been reported to decrease DMI of high-forage diets, although no effect on DMI was noted with the low-forage diets fed in this experiment. This impact on DMI of high-forage diets may limit the range of diets for which this CH4 reduction strategy may be applicable. The inclusion level of WSB in the current experiment (27%) was beyond the palatability threshold of the bulls used and resulted in a marked decline in intake and performance. Therefore, WSB may have a role to play in ruminant diets, but only at a reduced inclusion rate.

Animal Feed↗

PubMed2003

Properties of the ultrashort gain length, self-amplified spontaneous emission free-electron laser in the linear regime and saturation.

VISA (Visible to Infrared SASE Amplifier) is a high-gain self-amplified spontaneous emission (SASE) free-electron laser (FEL), which achieved saturation at 840 nm within a single-pass 4-m undulator. The experiment was performed at the Accelerator Test Facility at BNL, using a high brightness 70-MeV electron beam. A gain length shorter than 18 cm has been obtained, yielding a total gain of 2 x 10(8) at saturation. The FEL performance, including the spectral, angular, and statistical properties of SASE radiation, has been characterized for different electron beam conditions. Results are compared to the three-dimensional SASE FEL theory and start-to-end numerical simulations of the entire injector, transport, and FEL systems. An agreement between simulations and experimental results has been obtained at an unprecedented level of detail.

Journal Article↗

PubMed2003

Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of adult acute myelogenous leukemia in first complete remission.

In order to improve leukemia-free survival (LFS) without the treatment-related morbidity of allogeneic bone marrow transplantation or multiple prolonged cycles of consolidation chemotherapy, we evaluated the long-term outcome of autologous transplantation of peripheral blood progenitor cells (PBPCs) as postremission therapy in 129 patients aged 18-71 years (median 49 years) with newly diagnosed acute myelogenous leukemia (AML) in first complete remission (CR1). The median follow-up from remission for surviving patients was 62.2 months (range 3.7-127.9 months). A total of 57 patients were alive and leukemia free at the end of the study. The LFS and overall survival 5 years from remission were 40.2% (+/-9.2%) and 41.4% (+/-9.4%), respectively. The median LFS and overall survival are 17.3 and 23.3 months, respectively. Multivariate analysis identified age as the most significant predictor for both LFS and overall survival. Karyotype was also found to be predictive of outcome. Our results show that autologous transplantation of PBPC procured after a single cycle of high-dose cytarabine-based consolidation chemotherapy for a population of adult patients with AML in CR1 produces a high likelihood of long-term LFS, offering a state of clinical minimal residual disease for the investigation of future therapeutic approaches.

Adolescent↗

PubMed2002

Surface-roughness wakefield measurements at brookhaven accelerator test facility.

An experiment has been carried out at the Brookhaven Accelerator Test Facility to investigate the effect of a surface-roughness wakefield in narrow beam tubes with artificially created bumps. The measurements show that the synchronous modes decay significantly due to the randomization of the roughness pattern. It is pointed out that this decay mechanism has not been investigated in the previous experiment at DESY and the investigators' conclusion does not apply for surface-roughness wakefields in real surfaces.

Journal Article↗

PubMed2002

Fundamental and harmonic microbunching in a high-gain self-amplified spontaneous-emission free-electron laser.

Electron beam microbunching in both the fundamental and second harmonic in a high-gain self-amplified spontaneous emission free-electron laser (SASE FEL) was experimentally characterized using coherent transition radiation. The microbunching factors for both modes (b(1) and b(2)) approach unity, an indication of FEL saturation. These measurements are compared to the predictions of FEL simulations. The simultaneous capture of the microbunching and SASE radiation for individual micropulses correlate the longitudinal electron beam structure with the FEL gain.

Journal Article↗

PubMed2002

Experimental characterization of nonlinear harmonic radiation from a visible self-amplified spontaneous emission free-electron laser at saturation.

Nonlinear harmonic radiation was observed using the VISA self-amplified, spontaneous emission (SASE) free-electron laser (FEL) at saturation. The gain lengths, spectra, and energies of the three lowest SASE FEL modes were experimentally characterized. The measured nonlinear harmonic gain lengths and center spectral wavelengths decrease with harmonic number, n, which is consistent with nonlinear harmonic theory. Both the second and third nonlinear harmonics energies are about 1% of the fundamental energy. These experimental results demonstrate for the first time the feasibility of using nonlinear harmonic SASE FEL radiation to produce coherent, femtosecond x rays.

Journal Article↗

PubMed2001

Characterization of a high-gain harmonic-generation free-electron laser at saturation.

We report on an experimental investigation characterizing the output of a high-gain harmonic-generation (HGHG) free-electron laser (FEL) at saturation. A seed CO2 laser at a wavelength of 10.6 microm was used to generate amplified FEL output at 5.3 microm. Measurement of the frequency spectrum, pulse duration, and correlation length of the 5.3 microm output verified that the light is longitudinally coherent. Investigation of the electron energy distribution and output harmonic energies provides evidence for saturated HGHG FEL operation.

Journal Article↗

PubMed2001

Hydrologic modeling of aquatic plant treatment systems polishing dairy lagoon effluents.

In this study, a mathematical model of the hydrologic balance of an aquatic plant treatment system (APTS) has been developed. The mass balance approach has been adopted and the major components of the water balance, such as precipitation, evapotranspiration (ET) and percolation have been incorporated into the model. For estimation of ET for duckweed and water hyacinth plants, mathematical relationships were established between ET and pan evaporation using data collected at the site. The observed ET rates of water hyacinths were up to 66% higher than the pan evaporation rates. But for duckweed, the observed ET rates were 10 to 20% lower than the pan evaporation rates. Using the available historic precipitation and pan evaporation data, several computer simulations of the model were run to estimate the HLR and HRT of the ponds under different design requirements. The results indicate that aquatic ponds with water hyacinths can operate at greater HLR's than ponds supporting duckweed. For a zero discharge system, the allowable HLR for a water hyacinth pond was found to be 5 times that of a pond containing duckweed.

Agriculture↗

PubMed2001

The cigar revival and the popular press: a content analysis, 1987-1997.

OBJECTIVES: The purpose of this study was to examine print media coverage of cigars during the period 1987 to 1997. METHODS: A content analysis of 790 cigar-focused newspaper and magazine articles was conducted. RESULTS: Cigar-focused articles increased substantially over the study period, paralleling increased cigar consumption. Articles focused on cigar business (39%) and events (19%). Only 4% of articles focused on health effects. Sixty-two percent portrayed cigars favorably. The tobacco industry was mentioned in 54% of articles and portrayed positively in 78%. Forty-two percent of the individuals quoted or described in articles were affiliated with the tobacco industry; only 5% were government/public health figures. CONCLUSIONS: Print coverage of cigars failed to communicate health risk messages and contributed to positive images of cigars.

Humans↗

PubMed2000

High-gain harmonic-generation free-electron laser

A high-gain harmonic-generation free-electron laser is demonstrated. Our approach uses a laser-seeded free-electron laser to produce amplified, longitudinally coherent, Fourier transform-limited output at a harmonic of the seed laser. A seed carbon dioxide laser at a wavelength of 10.6 micrometers produced saturated, amplified free-electron laser output at the second-harmonic wavelength, 5.3 micrometers. The experiment verifies the theoretical foundation for the technique and prepares the way for the application of this technique in the vacuum ultraviolet region of the spectrum, with the ultimate goal of extending the approach to provide an intense, highly coherent source of hard x-rays.

Journal Article↗

PubMed2000

New classification and update on the quinolone antibiotics.

The newer fluoroquinolones have broad-spectrum bactericidal activity, excellent oral bioavailability, good tissue penetration and favorable safety and tolerability profiles. A new four-generation classification of the quinolone drugs takes into account the expanded antimicrobial spectrum of the more recently introduced fluoroquinolones and their clinical indications. First-generation drugs (e.g., nalidixic acid) achieve minimal serum levels. Second-generation quinolones (e.g., ciprofloxacin) have increased gram-negative and systemic activity. Third-generation drugs (e.g., levofloxacin) have expanded activity against gram-positive bacteria and atypical pathogens. Fourth-generation quinolone drugs (currently only trovafloxacin) add significant activity against anaerobes. The quinolones can be differentiated within classes based on their pharmacokinetic properties. The new classification can help family physicians prescribe these drugs appropriately.

Anti-Infective Agents↗

PubMed2000

Excellent tolerance of rituximab when given after mitoxantrone/cyclophosphamide: an effective and safe combination for indolent non-Hodgkin's lymphoma.

Treatment for extensive indolent lymphoma should provide optimization of efficacy while avoiding excessive toxicity. Rituximab may be an ideal agent to combine with chemotherapy because of its lack of classical myelotoxicity. In this study, 27 patients with a variety of histologies of indolent B-cell non-Hodgkin's lymphoma have been treated utilizing a novel three-drug combination. Nine patients had relapsed disease and 18 were previously untreated. Patients first received cyclophosphamide 800 mg/m(2) and mitoxantrone 8 mg/m(2) i.v. on day 1, every 3 weeks for 2 cycles. Subsequently, patients received rituximab 375 mg/m(2) followed by mitoxantrone 8 mg/m2 every 2 weeks for 4 cycles. This regimen and, in particular, the rituximab infusion were extremely well tolerated. Only two of 27 patients experienced a grade 1/2, infusion-related reaction during the first rituximab infusion. Grade 4 neutropenia was noted at some point in 16 patients who were then offered granulocyte-macrophage colony-stimulating factor support for improvement of neutropenia. No infections were noted. Alopecia was minimal. Of 27 patients, 19 achieved a complete response (CR), one achieved an unconfirmed CR (CRu), and five patients achieved a partial response, for an overall response rate of 92.5%. Molecular remissions were noted in seven of 12 tested patients in CR. We concluded that the cyclophosphamide/mitoxantrone/rituximab (CyMiR) regimen is effective and extremely well tolerated. Furthermore, rituximab infusion-associated morbidity is markedly reduced.

Adult↗

PubMed1999

Suppressor analysis of the Saccharomyces cerevisiae gene REC104 reveals a genetic interaction with REC102.

REC104 is a gene required for the initiation of meiotic recombination in Saccharomyces cerevisiae. To better understand the role of REC104 in meiosis, we used an in vitro mutagenesis technique to create a set of temperature-conditional mutations in REC104 and used one ts allele (rec104-8) in a screen for high-copy suppressors. An increased dosage of the early exchange gene REC102 was found to suppress the conditional recombinational reduction in rec104-8 as well as in several other conditional rec104 alleles. However, no suppression was observed for a null allele of REC104, indicating that the suppression by REC102 is not "bypass" suppression. Overexpression of the early meiotic genes REC114, RAD50, HOP1, and RED1 fails to suppress any of the rec104 conditional alleles, indicating that the suppression might be specific to REC102.

Alleles↗

PubMed1999