bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermal Contact Conductance of Non-Flat, Rough, Metallic Coated Metals
Authors: Lambert M. A. , Fletcher L. S. 
Published: July 2002

AbstractThermal contact conductance is an important consideration in such applications as nuclear reactor cooling, electronics packaging, spacecraft thermal control, and gas turbine and internal combustion engine cooling. In many instances, the highest possible thermal contact conductance is desired. For this reason, soft, high conductivity, metallic coatings are sometimes applied to contacting surfaces (often metallic) to increase thermal contact conductance. O’Callaghan et al. (1981) as well as Antonetti and Yovanovich (1985, 1988) developed theoretical models for thermal contact conductance of metallic coated metals, both of which have proven accurate for flat, rough surfaces. However, these theories often substantially overpredict the conductance of non-flat, rough, metallic coated metals. In the present investigation, a semi-empirical model for flat and non-flat, rough, uncoated metals, previously developed by Lambert and Fletcher (1996), is employed in predicting the conductance of flat and non-flat, rough, metallic coated metals. The models of Antonetti and Yovanovich (1985, 1988) and Lambert and Fletcher (1996) are compared to experimental data from a number of investigations in the literature. This entailed analyzing the results for a number of metallic coating/substrate combinations on surfaces with widely varying flatness and roughness. Both models agree well with experimental results for flat, rough, metallic coated metals. However, the semi-empirical model by Lambert and Fletcher (1996) is more conservative than the theoretical model by Antonetti and Yovanovich (1985, 1988) when compared to the majority of experimental results for non-flat, rough, metallic coated metals.
Randomized Comparison of Linezolid (PNU-100766) versus Oxacillin-Dicloxacillin for Treatment of Complicated Skin and Soft Tissue Infections
Authors: Stevens Dennis L. , Smith Leon G. , Bruss Jon B. , McConnell-Martin Maureen A. , Duvall Sue E. , Todd Wesley Mark , Hafkin Barry 
Published: July 2002

ABSTRACTThis randomized, double-blind, multicenter trial compared the efficacy and safety of linezolid, an oxazolidinone, with those of oxacillin-dicloxacillin in patients with complicated skin and soft tissue infections. A total of 826 hospitalized adult patients were randomized to receive linezolid (600 mg intravenously [i.v.]) every 12 h or oxacillin (2 g i.v.) every 6 h; following sufficient clinical improvement, patients were switched to the respective oral agents (linezolid [600 mg orally] every 12 h or dicloxacillin [500 mg orally] every 6 hours). Primary efficacy variables were clinical cure rates in both the intent-to-treat (ITT) population and clinically evaluable (CE) patients and microbiological success rate in microbiologically evaluable (ME) patients. Safety and tolerability were evaluated in the ITT population. Demographics and baseline characteristics were similar across treatment groups in the 819 ITT patients. In the ITT population, the clinical cure rates were 69.8 and 64.9% in the linezolid and oxacillin-dicloxacillin groups, respectively (P= 0.141; 95% confidence interval −1.58 to 11.25). In 298 CE linezolid-treated patients, the clinical cure rate was 88.6%, compared with a cure rate of 85.8% in 302 CE patients who received oxacillin-dicloxacillin. In 143 ME linezolid-treated patients, the microbiological success rate was 88.1%, compared with a success rate of 86.1% in 151 ME patients who received oxacillin-dicloxacillin. Both agents were well tolerated; most adverse events were of mild-to-moderate intensity. No serious drug-related adverse events were reported in the linezolid group. These data support the use of linezolid for the treatment of adults with complicated skin and soft tissue infections.
Characterization of the Tn
916
-like Transposon Tn
3872
in a Strain of
Abiotrophia defectiva
(
Streptococcus defectivus
) Causing Sequential Episodes of Endocarditis in a Child
Authors: Poyart Claire , Quesne Gilles , Acar Philippe , Berche Patrick , Trieu-Cuot Patrick 
Published: July 2002

ABSTRACT

Clinical blood isolates from three sequential episodes of endocarditis occurring over a 6-month period in a child with a malformative cardiopathy were investigated. All isolates identified as
Abiotrophia defectiva
were resistant to erythromycin-clindamycin and to tetracycline-minocycline, due to the presence of sequences homologous to the erythromycin resistance gene
ermB
and to the tetracycline resistance gene
tet
(M), respectively. These resistance genes were located on a chromosomally borne composite Tn
916
-related transposon. These results demonstrate the involvement of conjugative transposons in the dissemination of antibiotic resistance in the genus
Abiotrophia
.
Dihydropteroate Synthase of
Mycobacterium leprae
and Dapsone Resistance
Authors: Williams Diana L. , Spring Laynette , Harris Eugene , Roche Paul , Gillis Thomas P. 
Published: July 2002

ABSTRACT

Two
Mycobacterium leprae
genes,
folP1
and
folP2
, encoding putative dihydropteroate synthases (DHPS), were studied for enzymatic activity and for the presence of mutations associated with dapsone resistance. Each gene was cloned and expressed in a
folP
knockout mutant of
Escherichia coli
(C600Δ
folP
::Km
r
). Expression of
M. leprae folP1
in C600Δ
folP
::Km
r
conferred growth on a folate-deficient medium, and bacterial lysates exhibited DHPS activity. This recombinant displayed a 256-fold-greater sensitivity to dapsone (measured by the MIC) than wild-type
E. coli
C600, and 50-fold less dapsone was required to block (expressed as the 50% inhibitory concentration [IC
50
]) the DHPS activity of this recombinant. When the
folP1
genes of several dapsone-resistant
M. leprae
clinical isolates were sequenced, two missense mutations were identified. One mutation occurred at codon 53, substituting an isoleucine for a threonine residue (T53I) in the DHPS-1, and a second mutation occurred in codon 55, substituting an arginine for a proline residue (P55R). Transformation of the C600Δ
folP
::Km
r
knockout with plasmids carrying either the T53I or the P55R mutant allele did not substantially alter the DHPS activity compared to levels produced by recombinants containing wild-type
M. leprae folP1
. However, both mutations increased dapsone resistance, with P55R having the greatest affect on dapsone resistance by increasing the MIC 64-fold and the IC
50
68-fold. These results prove that the
folP1
of
M. leprae
encodes a functional DHPS and that mutations within this gene are associated with the development of dapsone resistance in clinical isolates of
M. leprae
. Transformants created with
M. leprae folP2
did not confer growth on the C600Δ
folP
::Km
r
knockout strain, and DNA sequences of
folP2
from dapsone-susceptible and -resistant
M. leprae
strains were identical, indicating that this gene does not encode a functional DHPS and is not involved in dapsone resistance in
M. leprae
.
Disposition of Intravenous Pyrimethamine in Healthy Volunteers
Authors: Almond D. S. , Szwandt I. S. F. , Edwards G. , Lee M. G. , Winstanley P. A. 
Published: July 2002

ABSTRACTA proportion of patients with AIDS and toxoplasmic encephalitis (TE) sustain low plasma pyrimethamine concentrations during oral treatment, possibly because of incomplete and variable bioavailability. We wanted to develop a safe, practicable intravenous (i.v.) formulation of pyrimethamine and characterize its disposition in healthy volunteers. A neutral, aqueous, sterile solution of pyrimethamine was produced and presented in sealed glass ampoules. Pyrimethamine (1 mg/kg) was given to eight healthy male volunteers by i.v. infusion over 2 h, and blood was sampled over a 2 week period. Pyrimethamine levels in plasma were measured by high-performance liquid chromatography. The drug was well tolerated by all volunteers, and there were no changes in vital signs, electrocardiogram, hematology, or biochemical parameters. The maximum pyrimethamine concentration of 2,089 ± 565 ng ml−1(mean ± standard deviation) was achieved shortly after the end of the infusion; thereafter, concentrations declined in a log-linear manner, with a half-life of 140 ± 31 h.
Efficacies of Sordarin Derivatives GM193663, GM211676, and GM237354 in a Murine Model of Systemic Coccidioidomycosis
Authors: Clemons Karl V. , Stevens David A. 
Published: July 2002

ABSTRACT

Sordarin derivatives (Glaxo Wellcome) are a new class of compounds that selectively inhibit fungal protein synthesis and have a broad spectrum of activity. Systemic coccidioidomycosis was established in female CD-1 mice infected with
Coccidioides immitis
, and therapy was begun on day 4 with either GM193663, GM211676, GM237354, fluconazole, or no treatment; compounds were given twice daily orally for 19 days at 20 or 100 mg/kg/day. The serum pharmacokinetics of the compounds were studied in uninfected mice. The MICs of GM193663, GM211676, and GM237354 for
C. immitis
were 1.56, 0.39, and 0.39 μg/ml, respectively, and the minimum fungicidal concentrations were 6.25, 3.13, and 0.39 μg/ml, respectively. Peak serum levels (sampled at 1 to 2 h) after a single 50-mg/kg dose were 9.8 μg/ml for GM193663, 13 μg/ml for GM211676, and 6.0 μg/ml for GM237354. No accumulation occurred after 19 days of dosing, and peak levels were lower at 3.2 μg/ml for GM193663, 4.0 μg/ml for GM211676, and <2.5 μg/ml for GM237354. We estimate that the
t
1/2
for each compound in serum is <2 h. In vivo, all compounds showed dose-responsive efficacy, significantly prolonging survival over the control groups (100% lethal dose); 80 to 100% of the mice given the 100-mg/kg doses of fluconazole or a GM drug survived. All 100-mg/kg/day regimens were equivalent. At 20 mg/kg/day, GM211676 was equivalent to 100 mg of fluconazole/kg/day, indicating that GM211676 was ∼5-fold more efficacious. No mice surviving the 49 days of the experiment were free of infection. All drugs dose responsively reduced the fungal burden in the spleen, liver, and lungs, and GM237354 at 100 mg/kg/day was superior to all of the other regimens in the reduction of burden in all organs.
C. immitis
was susceptible both in vitro and in vivo to the GM compounds, which were found to be equivalent or superior to fluconazole. These results are encouraging, indicating that further testing in other models of fungal disease is warranted.
Antiviral Activities of Oral 1-O-Hexadecylpropanediol-3-Phosphoacyclovir and Acyclovir in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection
Authors: Hostetler Karl Y. , Beadle James R. , Hornbuckle William E. , Bellezza Christine A. , Tochkov Ilia A. , Cote Paul J. , Gerin John L. , Korba Brent E. , Tennant Bud C. 
Published: July 2002

ABSTRACTAcyclovir triphosphate is a potent inhibitor of hepatitis B virus DNA polymerase, but acyclovir treatment provides no benefit in patients with hepatitis B virus infection. This is due in part to the fact that hepatitis B virus, unlike herpes simplex virus, does not code for a viral thymidine kinase which catalyzes the initial phosphorylation of acyclovir. We synthesized 1-O-octadecyl-sn-glycero-3-phospho (3-P)-acyclovir and found that it was highly active in reducing hepatitis B virus replication in 2.2.15 cells, while acyclovir was inactive. The greater antiviral activity of 1-O-octadecyl-sn-glycero-3-P-acyclovir appeared to be due to liver cell metabolism of the compound to acyclovir monophosphate (K. Y. Hostetler et al., Biochem. Pharmacol. 53:1815–1822, 1997). However, a closely related compound without a hydroxyl group at thesn-2 position of glycerol, 1-O-hexadecylpropanediol-3-P-acyclovir, was more active and selective in 2.2.15 cells in vitro. In this study, we treated woodchucks chronically infected with woodchuck hepatitis virus with increasing oral doses of 1-O-hexadecylpropanediol-3-P-acyclovir and assessed the response to therapy versus acyclovir or a placebo. At a dosage of 10 mg/kg of body weight twice a day, the test compound significantly inhibited viral replication in vivo, as indicated by a 95% reduction in serum woodchuck hepatitis virus DNA levels and by a 54% reduction in levels of woodchuck hepatitis virus replicative intermediates in the liver. Higher doses were somewhat less effective. In contrast, 20 mg of acyclovir/kg twice daily, a 5.3-fold-higher molar dosage, had no demonstrable activity against woodchuck hepatitis virus. Oral 1-O-hexadecylpropanediol-3-P-acyclovir appeared to be safe and effective in chronic woodchuck hepatitis virus infection.
Tilmicosin Induces Apoptosis in Bovine Peripheral Neutrophils in the Presence or in the Absence ofPasteurella haemolyticaand Promotes Neutrophil Phagocytosis by Macrophages
Authors: Chin Alex C. , Lee Wilson D. , Murrin Katherine A. , Morck Douglas W. , Merrill John K. , Dick Paul , Buret Andre G. 
Published: July 2002

ABSTRACTPathogen virulence factors and inflammation are responsible for tissue injury associated with respiratory failure in bacterial pneumonia, as seen in the bovine lung infected withPasteurella haemolytica. Tilmicosin is a macrolide antibiotic used for the treatment of bovine bacterial pneumonia. Recent evidence suggests that tilmicosin-induced neutrophil apoptosis may have anti-inflammatory effects. Using bovine leukocytes, we sought to define whether liveP. haemolyticaaffected tilmicosin-induced neutrophil apoptosis, assessed the proapoptotic effects of tilmicosin in comparison with other drugs, and characterized its impact on phagocytic uptake of neutrophils by macrophages. Induction of apoptosis in the presence or absence ofP. haemolyticawas assessed by using an enzyme-linked immunosorbent assay for apoptotic nucleosomes. In addition, fluorescent annexin-V staining identified externalized phosphatidylserine in neutrophils treated with tilmicosin, penicillin, ceftiofur, oxytetracycline, or dexamethasone. Neutrophil membrane integrity was assessed by using propidium iodide and trypan blue exclusion. As phagocytic clearance of apoptotic neutrophils by macrophages contributes to the resolution of inflammation, phagocytosis of tilmicosin-treated neutrophils by esterase-positive cultured bovine macrophages was assessed with light microscopy and transmission electron microscopy. Unlike bovine neutrophils treated with penicillin, ceftiofur, oxytetracycline, or dexamethasone, neutrophils exposed to tilmicosin became apoptotic, regardless of the presence or absence ofP. haemolytica. Tilmicosin-treated apoptotic neutrophils were phagocytosed at a significantly greater rate by bovine macrophages than were control neutrophils. In conclusion, tilmicosin-induced neutrophil apoptosis occurs regardless of the presence or absence of liveP. haemolytica, exhibits at least some degree of drug specificity, and promotes phagocytic clearance of the dying inflammatory cells.
ATP Synthase Is Necessary for Microcin H47 Antibiotic Action
Authors: Trujillo Mónica , Rodrı́guez Eliana , Laviña Magela 
Published: July 2002

ABSTRACT

Microcin H47 is a gene-encoded peptide antibiotic produced by a natural
Escherichia coli
strain isolated in Uruguay. In order to identify cellular components necessary for its antibiotic action, microcin H47-resistant mutants isolated in this work, as well as previously described mutants affected in membrane proteins, were analyzed. These studies indicated that (i) receptor outer membrane proteins for ferric-catechol siderophores would be involved in microcin-specific binding to the cell surface, (ii) the TonB pathway is needed for microcin H47 uptake, and (iii) the presence of the ATP synthase complex is necessary for microcin action. The possibility that this last structure contains the antibiotic target is discussed.
Treatment of Vancomycin-Resistant Enterococcal Infections in the Immunocompromised Host: Quinupristin-Dalfopristin in Combination with Minocycline
Authors: Raad Issam , Hachem Ray , Hanna Hend , Girgawy Essam , Rolston Kenneth , Whimbey Estella , Husni Rola , Bodey Gerald 
Published: July 2002

ABSTRACT
Between February 1994 and November 1998, 56 oncology patients infected with vancomycin-resistant enterococci (VRE) were treated with quinopristin-dalfopristin (Q-D) plus minocycline (MIN). Infections included bacteremia, urinary tract infection, pneumonia, and wound infection. The response rate was 68%, and the most frequent adverse event was arthralgia or myalgia (36%). Q-D–MIN is effective for VRE infection in cancer patients but is associated with a substantial frequency of arthralgia or myalgia.
Activities of a New Fluoroketolide, HMR 3787, and Its (Des)-Fluor Derivative RU 64399 Compared to Those of Telithromycin, Erythromycin A, Azithromycin, Clarithromycin, and Clindamycin against Macrolide-Susceptible or -Resistant
Streptococcus pneumoniae
and
S. pyogenes
Authors: Nagai Kensuke , Davies Todd A. , Ednie Lois M. , Bryskier Andre , Palavecino Elizabeth , Jacobs Michael R. , Appelbaum Peter C. 
Published: July 2002

ABSTRACT

Activities of HMR 3787 and RU 64399 were compared to those of three macrolides, telithromycin, and clindamycin against 175
Streptococcus pneumoniae
isolates and 121
Streptococcus pyogenes
isolates. HMR3787 and telithromycin were the most active compounds tested against pneumococci. Telithromycin and RU 64399 were equally active against macrolide-susceptible (MICs, 0.008 to 0.06 μg/ml) and -resistant
S. pyogenes
isolates, but HMR 3787 had lower MICs for
ermB
strains.
Susceptibilities of
Eikenella corrodens
,
Prevotella intermedia
, and
Prevotella nigrescens
Clinical Isolates to Amoxicillin and Tetracycline
Authors: Luong N. , Tsai J. , Chen C. 
Published: July 2002

ABSTRACT

The AB Biodisk Etest showed that 106 (100%) and 98 (92%) isolates of
Eikenella corrodens
were susceptible to amoxicillin and tetracycline, respectively. Twenty-three (68%)
Prevotella intermedia
isolates and 14 (67%)
Prevotella nigrescens
isolates were susceptible to amoxicillin. Seventy-nine percent of the
P. intermedia
isolates and 67% of the
P. nigrescens
isolates were susceptible to tetracycline. A higher percentage of β-lactamase-producing isolates of
P. intermedia
and
P. nigrescens
were identified with selective agar containing amoxicillin than with nonselective agar.
In Vitro and In Vivo Activities of Aminoadamantane and Aminoalkylcyclohexane Derivatives againstTrypanosoma brucei
Authors: Kelly John M. , Quack Guenter , Miles Michael M. 
Published: July 2002

ABSTRACTWe reported recently that the bloodstream form of the African trypanosome,Trypanosoma brucei, is sensitive to the anti-influenza virus drug rimantadine. In the present report we describe the trypanocidal properties of a further 62 aminoadamantane and aminoalkylcyclohexane derivatives. Seventeen of the compounds were found to be more active than rimantadine, with four inhibiting growth in vitro ofT. bruceiby >90% at concentrations of 1 μM. The most active derivative (1-adamantyl-4-amino-cyclohexane) was about 20 to 25 times more effective than rimantadine. We observed a correlation between structural features of the derivatives and their trypanocidal properties; hydrophobic substitutions to the adamantane or cyclohexane rings generally enhanced activity. As with rimantadine, the activity in vitro varied with the pH.T. bruceiwas more sensitive in an alkaline environment (including a normal bloodstream pH of 7.4) and less sensitive under acidic conditions. Tests for activity in vivo were carried out with a mouse model of infection with a virulent strain ofT. brucei. Although the parasitemia was not eliminated, it could be transiently suppressed by >98% with the most active compounds tested. These results suggest that aminoadamantane derivatives could have potential as a new class of trypanocidal agents.
In Vitro Characterization of A-315675, a Highly Potent Inhibitor of A and B Strain Influenza Virus Neuraminidases and Influenza Virus Replication
Authors: Kati Warren M. , Montgomery Debra , Carrick Robert , Gubareva Larisa , Maring Clarence , McDaniel Keith , Steffy Kevin , Molla Akhteruzzaman , Hayden Frederick , Kempf Dale , Kohlbrenner William 
Published: July 2002

ABSTRACT

A-315675 is a novel, pyrrolidine-based compound that was evaluated in this study for its ability to inhibit A and B strain influenza virus neuraminidases in enzyme assays and influenza virus replication in cell culture. A-315675 effectively inhibited influenza A N1, N2, and N9 and B strain neuraminidases with inhibitor constant (

K
i

) values between 0.024 and 0.31 nM. These values were comparable to or lower than the

K
i

values measured for oseltamivir carboxylate (GS4071), zanamivir, and BCX-1812, except for the N1 enzymes that were found to be the most sensitive to BCX-1812. The time-dependent inhibition of neuraminidase catalytic activity observed with A-315675 is likely due to its very low rate of dissociation from the active site of neuraminidase. The half times for dissociation of A-315675 from B/Memphis/3/89 and A/Tokyo/3/67 (H3N2) influenza virus neuraminidases of 10 to 12 h are significantly slower than the half times measured for oseltamivir carboxylate (33 to 60 min). A-315675 inhibited the replication of several laboratory strains of influenza virus in cell culture with potencies that were comparable or superior to those for oseltamivir carboxylate and BCX-1812, except for the A/H1N1 viruses that were found to be two- to fourfold more susceptible to BCX-1812. A-315675 and oseltamivir carboxylate exhibited comparable potencies against a panel of A/H1N1 and A/H3N2 influenza virus clinical isolates, but A-315675 was found to be significantly more potent than oseltamivir carboxylate against the B strain isolates. The favorable in vitro results relative to other clinically effective agents provide strong support for the further investigation of A-315675 as a potential therapy for influenza virus infections.
Use of IMiD3, a Thalidomide Analog, as an Adjunct to Therapy for Experimental Tuberculous Meningitis
Authors: Tsenova Liana , Mangaliso Bande , Muller George , Chen Yong , Freedman Victoria H. , Stirling David , Kaplan Gilla 
Published: July 2002

ABSTRACTTuberculous meningitis (TBM), the most severe form ofMycobacterium tuberculosisinfection in humans, is associated with significant morbidity and mortality despite successful treatment with antituberculous drugs. This is due to the irreversible brain damage subsequent to the local inflammatory response of the host toM. tuberculosis.Corticosteroids have been used in conjunction with antituberculous therapy in an attempt to modulate the inflammatory response, but this strategy has been of limited success. Therefore, we examined whether combining antituberculous drugs with the immunomodulatory drug thalidomide or with a new thalidomide analog, immunomodulatory drug 3 (IMiD3), would be effective in reducing morbidity and mortality in an experimental rabbit model of TBM. Intracisternal inoculation of 5 × 104CFU ofMycobacterium bovisRavenel in rabbits induced progressive subacute meningitis characterized by high cerebrospinal fluid (CSF) leukocytosis, protein influx, release of tumor necrosis factor (TNF), substantial meningeal inflammation, and mortality by day 28. Treatment with antituberculous drugs or with antituberculous drugs plus thalidomide improved the clinical course of disease somewhat and increased survival to about 50%. In contrast, treatment with antituberculous drugs in combination with IMiD3 limited pathological neurologic changes and resulted in marked improvement (73%) in survival. IMiD3 treatment was also associated with reduced leukocytosis in the CSF and significantly lower levels of TNF in CSF and plasma. Histologically, the meningeal inflammation in animals treated with antituberculous drugs plus IMiD3 was considerably attenuated compared to that of the other treatment groups. These results suggest a potential role for IMiD3 in the management of TBM in patients.