bluuebunny/crossref_metadata_2025_split huggingface dataset:
Instruments for the Assessment of Pain in Older Persons with Cognitive Impairment
Authors: Stolee Paul , Hillier Loretta M. , Esbaugh Jacquelin , Bol Nancy , McKellar Laurie , Gauthier Nicole 
Published: January 2005

Pain in older persons with cognitive impairment is often unrecognized and inadequately treated. A major problem associated with this undertreatment is the challenging nature of pain assessment and in particular the selection of accurate and useful assessment instruments. The purpose of this study was to review pain measurement instruments for acute and chronic pain suggested for use with cognitively impaired older persons and to summarize available evidence on their reliability and validity. A systematic search for pain instruments was conducted using several bibliographic databases, supplemented by a manual search of the bibliographies of retrieved articles and review chapters and by articles received from experts and clinicians in the field. Instruments were retained for review when the pain instrument was used or recommended for use with older persons with cognitive impairment.Thirty‐nine instruments were reviewed; nine were excluded for various reasons. Of the remaining 30, 18 were self‐report and 12 were staff administered. There were no instruments for which all major tests of reliability or validity were reported. Reliability and validity data were basic or unavailable for many instruments. One instrument had excellent validity but no reliability data. The remaining instruments had weak or adequate reliability and validity.The authors conclude that there is a need for further rigorous development and testing of pain instruments for use with cognitively impaired older persons. An adequate instrument would be one component of an effective program for assessment and management of pain in this population.
Creating a Teaching Geriatric Service: Ten Important Lessons
Authors: Siegler Eugenia L. , Capello Carol F. 
Published: January 2005

The restructuring of The Medical Service at the Weill/Cornell campus of the New York Presbyterian Hospital, coupled with funding from the Donald W. Reynolds Foundation to strengthen physicians' training in geriatrics, enabled the creation of a geriatrics inpatient team and a 17‐bed Acute Care for Elders unit. It has also allowed a program to be designed that exposes residents to the fundamental principles of geriatric care, offers them opportunities to follow older patients in multiple venues, and provides a chance to enhance their skills and gain experience in interdisciplinary care.In creating the service, a number of mistakes were made, but a few lessons were also learned in the process. After a brief description of the program, 10 lessons that highlight the pitfalls and potential of an inpatient geriatrics teaching service are shared.
Mi Casa o Su Casa? Assessing Function and Values in the Home
Authors: Medina‐Walpole Annette , Heppard Brian , Clark Nancy S. , Markakis Kathryn , Tripler Scott , Quill Timothy 
Published: January 2005

Clinical instruction for medical students traditionally occurs in hospitals and offices, whereas patients and families face many health issues in their homes. This is particularly true for frail older adults, those with chronic illness, and patients at the end of life. The authors sought to incorporate geriatrics, primary care, and palliative care into house calls for medical students by integrating a home visit experience into their ambulatory clerkship. Using a guide jointly developed by geriatrics, primary care, and palliative care faculty, students conduct three home visits with a patient from their community preceptor's practice. The first visit focused on medical diagnoses and symptoms, the second on functional assessment/geriatric syndromes, and the third on social/cultural and end‐of‐life values. Students completed a 2,000‐word write‐up, including a narrative using the “voice” of the patient. Students presented the cases in small groups facilitated by geriatric and palliative care faculty.Eighty‐three percent of students reported positive feedback about the experience. Based on write‐ups and program evaluation, students voiced improved knowledge of functional assessment, geriatric syndromes, and progression of chronic illness. Students also poignantly expressed advantages of home visits in exploring psychosocial aspects of medicine, including affirming the humanity of medicine, understanding family systems, providing patient‐centered care, and understanding patient beliefs. Several students expressed pursuing a house calls career.A longitudinal home visit experience for medical students can successfully enhance the geriatric, ambulatory care, and palliative care curricular content of undergraduate education and positively affect student's attitudes toward the chronically ill and homebound.
Alterations in DNA Gyrase and Topoisomerase IV in Resistant Mutants of
Clostridium perfringens
Found after In Vitro Treatment with Fluoroquinolones
Authors: Rafii Fatemeh , Park Miseon , Novak John S. 
Published: January 2005

ABSTRACT

To compare mutations in the DNA gyrase (
gyrA
and
gyrB
) and topoisomerase IV (
parC
and
parE
) genes of
Clostridium perfringens
, which are associated with in vitro exposure to fluoroquinolones, resistant mutants were selected from eight strains by serial passage in the presence of increasing concentrations of norfloxacin, ciprofloxacin, gatifloxacin, or trovafloxacin. The nucleotide sequences of the entire
gyrA
,
gyrB
,
parC
, and
parE
genes of 42 mutants were determined. DNA gyrase was the primary target for each fluoroquinolone, and topoisomerase IV was the secondary target. Most mutations appeared in the quinolone resistance-determining regions of
gyrA
(resulting in changes of Asp-87 to Tyr or Gly-81 to Cys) and
parC
(resulting in changes of Asp-93 or Asp-88 to Tyr or Ser-89 to Ile); only two mutations were found in
gyrB
, and only two mutations were found in
parE
. More mutants with multiple
gyrA
and
parC
mutations were produced with gatifloxacin than with the other fluoroquinolones tested. Allelic diversity was observed among the resistant mutants, for which the drug MICs increased 2- to 256-fold. Both the structures of the drugs and their concentrations influenced the selection of mutants.
Potent Plasmodicidal Activity of a Heat-Induced Reformulation of Deoxycholate-Amphotericin B (Fungizone) against
Plasmodium falciparum
Authors: Hatabu Toshimitsu , Takada Tsuyoshi , Taguchi Nao , Suzuki Mamoru , Sato Kumiko , Kano Shigeyuki 
Published: January 2005

ABSTRACT

The emergence and spread of drug-resistant
Plasmodium falciparum
continue to pose problems in malaria chemotherapy. Therefore, it is necessary to identify new antimalarial drugs and therapeutic strategies. In the present study, the activity of a heat-treated form of amphotericin B (HT-AMB) against
P. falciparum
was evaluated. The efficacy and toxicity of HT-AMB were also compared with those of the standard formulation (AMB). HT-AMB showed significant activity against a chloroquine-resistant strain (strain K-1) and a chloroquine-susceptible strain (strain FCR-3) in vitro. The 50% inhibitory concentrations of HT-AMB were 0.32 ± 0.03 μg/ml for strain K-1 and 0.33 ± 0.03 μg/ml for strain FCR-3. In the presence of 1.0 μg of HT-AMB per ml, only pyknotic parasites were observed after 24 h of incubation of early trophozoites (ring forms). However, when late trophozoites and schizonts were cultured with 1.0 μg of HT-AMB per ml, those forms multiplied to ring forms but the number of infected erythrocytes did not increase. These results indicate that HT-AMB possesses potent antiplasmodial activity and that the drug is more effective against the ring-form stage than against the late trophozoite and schizont stages. HT-AMB was observed to have little cytotoxic effect against a human liver cell line (Chang liver cells). In conclusion, the results suggest that HT-AMB has promising properties and merits further in vivo investigations as a treatment for falciparum malaria.
Efficacy of Micafungin in Combination with Other Drugs in a Murine Model of Disseminated Trichosporonosis
Authors: Serena Carolina , Pastor F. Javier , Gilgado Félix , Mayayo Emilio , Guarro Josep 
Published: January 2005

ABSTRACT

Using a murine model of disseminated infection caused by
Trichosporon asahii
, we have evaluated the efficacies of amphotericin B (AMB; 1 mg/kg of body weight/day), fluconazole (FLC; 20 mg/kg/twice a day), and micafungin (MFG; 5 mg/kg/twice a day). We tested these drugs alone and in combination (MFG with AMB and MFG with FLC). MFG with AMB showed a synergistic effect and demonstrated a higher degree of efficacy in prolonging survival and reducing the kidney fungal burden than either agent alone. The combination MFG with FLC was able to reduce significantly the kidney fungal burden in comparison to that achieved with either drug administered alone.
Antifungal Susceptibilities of Clinical Isolates of
Candida
Species,
Cryptococcus neoformans
, and
Aspergillus
Species from Taiwan: Surveillance of Multicenter Antimicrobial Resistance in Taiwan Program Data from 2003
Authors: Hsueh Po-Ren , Lau Yeu-Jun , Chuang Yin-Ching , Wan Jen-Hsien , Huang Wen-Kuei , Shyr Jainn-Ming , Yan Jing-Jou , Yu Kwok-Woon , Wu Jiunn-Jong , Ko Wen-Chien , Yang Yi-Chueh , Liu Yung-Ching , Teng Lee-Jene , Liu Cheng-Yi , Luh Kwen-Tay 
Published: January 2005

ABSTRACT

The susceptibilities of nonduplicate isolates to six antifungal agents were determined for 391 blood isolates of seven
Candida
species, 70 clinical isolates (from blood or cerebrospinal fluid) of
Cryptococcus neoformans
, and 96 clinical isolates of four
Aspergillus
species, which were collected in seven different hospitals in Taiwan (as part of the 2003 program of the study group Surveillance of Multicenter Antimicrobial Resistance in Taiwan). All isolates of
Candida
species other than
C. glabrata
and
C. krusei
were susceptible to fluconazole. Among the 59
C. glabrata
isolates, 16 (27%) were not susceptible to fluconazole, and all were dose-dependently susceptible or resistant to itraconazole. For three (5.1%)
C. glabrata
isolates, voriconazole MICs were 2 to 4 μg/ml, and for all other
Candida
species isolates, voriconazole MICs were ≤0.5 μg/ml. The proportions of isolates for which amphotericin B MICs were ≥2 μg/ml were 100% (3 isolates) for
C. krusei
, 11% (23 of 207 isolates) for
Candida albicans
, 3.0% (2 of 67 isolates) for
Candida tropicalis
, 20% (12 of 59 isolates) for
C. glabrata
, and 0% for both
Candida parapsilosis
and
Candida lusitaniae
. For three (4%)
Cryptococcus neoformans
isolates, fluconazole MICs were ≥16 μg/ml, and two (3%) isolates were not inhibited by 1 μg of amphotericin B/ml. For four (4.2%) of the
Aspergillus
isolates, itraconazole MICs were 8 μg/ml.
Aspergillus flavus
was less susceptible to amphotericin B, with the MICs at which 50% (1 μg/ml) and 90% (2 μg/ml)
nsrsid417869\delrsid7301351
of isolates were inhibited being twofold greater than those for
Aspergillus fumigatus
and
Aspergillus niger
. All
Aspergillus
isolates were inhibited by ≤1 μg of voriconazole/ml, including isolates with increased resistance to amphotericin B and itraconazole. This study revealed the emergence in Taiwan of decreased susceptibilities of
Candida
species to amphotericin B and of
C. neoformans
to fluconazole and amphotericin B. Voriconazole was the most potent agent against the fungal isolates tested, including fluconazole- and amphotericin B-nonsusceptible strains.
Cholesterol Import by
Aspergillus fumigatus
and Its Influence on Antifungal Potency of Sterol Biosynthesis Inhibitors
Authors: Xiong Quanbo , Hassan Saad A. , Wilson William K. , Han Xiang Y. , May Gregory S. , Tarrand Jeffrey J. , Matsuda Seiichi P. T. 
Published: January 2005

ABSTRACT

High mortality rates from invasive aspergillosis in immunocompromised patients are prompting research toward improved antifungal therapy and better understanding of fungal physiology. Herein we show that
Aspergillus fumigatus
, the major pathogen in aspergillosis, imports exogenous cholesterol under aerobic conditions and thus compromises the antifungal potency of sterol biosynthesis inhibitors. Adding serum to RPMI medium led to enhanced growth of
A. fumigatus
and extensive import of cholesterol, most of which was stored as ester. Growth enhancement and sterol import also occurred when the medium was supplemented with purified cholesterol instead of serum. Cells cultured in RPMI medium with the sterol biosynthesis inhibitors itraconazole or voriconazole showed retarded growth, a dose-dependent decrease in ergosterol levels, and accumulation of aberrant sterol intermediates. Adding serum or cholesterol to the medium partially rescued the cells from the drug-induced growth inhibition. We conclude that cholesterol import attenuates the potency of sterol biosynthesis inhibitors, perhaps in part by providing a substitute for membrane ergosterol. Our findings establish significant differences in sterol homeostasis between filamentous fungi and yeast. These differences indicate the potential value of screening aspergillosis antifungal agents in serum or other cholesterol-containing medium. Our results also suggest an explanation for the antagonism between itraconazole and amphotericin B, the potential use of
Aspergillus
as a model for sterol trafficking, and new insights for antifungal drug development.
Bayesian Parameter Estimates of Nelfinavir and Its Active Metabolite, Hydroxy-tert-Butylamide, in Infants Perinatally Infected with Human Immunodeficiency Virus Type 1
Authors: Payen Salomé , Faye Albert , Compagnucci Alexandra , Giaquinto Carlo , Gibbs Diana , Gomeni Roberto , Bressolle Françoise , Jacqz-Aigrain Evelyne 
Published: January 2005

ABSTRACTThe objective of the present study was to develop a population pharmacokinetic model for nelfinavir mesylate (NFV) and nelfinavir hydroxy-tert-butylamide (M8), the most abundant metabolite of NFV, in infants vertically infected with human immunodeficiency virus type 1 and participating in the Paediatric European Network for Treatment of AIDS 7 study. Plasma NFV concentrations were determined during repeated NFV administrations (two to three times a day). Eighteen infants younger that age 2 years participated in this study. The doses administered ranged from 71 to 203 mg/kg of body weight/day. Pharmacokinetic parameter estimates were obtained by a compartmental approach by using a kinetic model to simultaneously fit NFV and M8 (active metabolite) concentrations. M8 was shown to be formation rate limited and was characterized by first-order rate constants of formation and elimination. Body weight was found to be a more appropriate predictor than age of the changes in (i) the rate of metabolism, (ii) the elimination rate constant of NFV, and (iii) NFV clearance. Population parameters were computed to account for the relationship between the rate of metabolism and body weight. The estimated NFV and M8 elimination half-lives were 4.3 and 2.04 h, respectively. The estimated NFV clearance was 2.13 liters/h/kg. The M8 concentration-to-NFV concentration ratio was 0.64 ± 0.44. In conclusion, the population pharmacokinetic model describing the dispositions of NFV and M8 should facilitate the design of future studies to elucidate the relative contributions of the parent compound and M8 to the pharmacological and toxic effects of NFV therapy.
Mutations in
folP
Associated with Elevated Sulfonamide MICs for
Neisseria meningitidis
Clinical Isolates from Five Continents
Authors: Fiebelkorn K. R. , Crawford S. A. , Jorgensen J. H. 
Published: January 2005

ABSTRACT

Sulfonamide resistance in meningococci is associated with mutations in the chromosomal gene
folP
, which encodes dihydropteroate synthase. Several mutations associated with resistance have been previously described, including amino acid substitutions at codons 31 and 194, a glycine-serine insertion at codons 195 and 196, and, recently, an additional mutation at nucleotide 682 (C682A). In this study, sulfisoxazole MICs were determined for 424 geographically diverse clinical isolates of
Neisseria meningitidis
, including all major subtypes. A subset of 134 isolates with MICs ranging from 0.5 to >64 μg/ml were assayed for the C682A mutation by real-time PCR, and 25 isolates were selected for
folP
gene sequencing. All isolates for which the sulfisoxazole MIC was ≥8 possessed the C682A mutation by real-time PCR or
folP
sequencing, and 34 of 35 isolates with a MIC of ≤2 lacked this mutation. Of 16 sequenced isolates for which the sulfisoxazole MIC was ≥4, 15 possessed previously described mutations, including 10 at codon 31, 1 at codon 194, and 4 with the 2-amino-acid insertion codons 195 and 196; all 16 possessed the C682A mutation. The C682A mutation predicted elevated sulfonamides MICs for a large number of geographically diverse clinical isolates of meningococci. Detection of this mutation by real-time PCR or other methods may allow more wide-scale detection of meningococcal isolates with for which the sulfonamide MICs are elevated without resorting to multiple assays or
folP
gene sequencing, providing a simple, high-throughput screening method for use in public health and epidemiologic settings.
Genetic Analysis of a Unique Bacteriocin, Smb, Produced by
Streptococcus mutans
GS5
Authors: Yonezawa Hideo , Kuramitsu Howard K. 
Published: January 2005

ABSTRACT

A dipeptide lantibiotic, named Smb, in
Streptococcus mutans
GS5 was characterized by molecular genetic approaches. The Smb biosynthesis gene locus is encoded by a 9.5-kb region of chromosomal DNA and consists of seven genes in the order
smbM1
, -
T
, -
F
, -
M2
, -
G
, -
A
, -
B
. This operon is not present in some other strains of
S. mutans
, including strain UA159. The genes encoding Smb were identified as
smbA
and
smbB
. Inactivation of
smbM1
,
smbA
, or
smbB
attenuated the inhibition of the growth of the indicator strain RP66, confirming an essential role for these genes in Smb expression. Mature Smb likely consists of the 30-amino-acid SmbA together with the 32-amino-acid SmbB. SmbA exhibited similarity with the mature lantibiotic lacticinA2 from
Lactococcus lactis
, while SmbB was similar to the mersacidin-like peptides from
Bacillus halodurans
and
L. lactis
. We also demonstrated that Smb expression is induced by the competence-stimulating peptide (CSP) and that a com box-like sequence is located in the
smb
promoter region. These results suggest that Smb belongs to the class I bacteriocin family, and its expression is dependent on CSP-induced quorum sensing.
Generation and Characterization of Recombinant Influenza A (H1N1) Viruses Harboring Amantadine Resistance Mutations
Authors: Abed Yacine , Goyette Nathalie , Boivin Guy 
Published: January 2005

ABSTRACT

The emergence of resistance to amantadine in influenza A viruses has been shown to occur rapidly during treatment as a result of single-amino-acid substitutions at position 26, 27, 30, 31, or 34 within the transmembrane domain of the matrix-(M)-2 protein. In this study, reverse genetics was used to generate and characterize recombinant influenza A (H1N1) viruses harboring L26F, V27A, A30T, S31N, G34E, and V27A/S31N mutations in the M2 gene. In plaque reduction assays, all mutations conferred amantadine resistance, with drug concentrations resulting in reduction of plaque number by 50% (IC
50
s) 154- to 3,300-fold higher than those seen for the wild type (WT). M2 mutants had no impairment in their replicative capacities in vitro on the basis of plaque size and replication kinetics experiments. In addition, all mutants were at least as virulent as the WT in experimentally infected mice, with the highest mortality rate being obtained with the recombinant harboring a double V27A/S31N mutation. These findings could help explain the frequent emergence and transmission of amantadine-resistant influenza viruses during antiviral pressure in the clinical setting.
Pharmacokinetics of the Antiviral Agent β-
l
-3′-Fluoro-2′,3′-Didehydro-2′,3′-Dideoxycytidine in Rhesus Monkeys
Authors: Asif Ghazia , Hurwitz Selwyn J. , Gumina Giuseppe , Chu Chung K. , McClure Harold M. , Schinazi Raymond F. 
Published: January 2005

ABSTRACT

β-
l
-3′-Fluoro-2′,3′-didehydro-2′,3′-dideoxycytidine (
l
-3′-Fd4C) is a potent and selective antiretroviral nucleoside with activity against lamivudine-resistant human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV) in vitro. The pharmacokinetics of
l
-3′-Fd4C were characterized in three rhesus monkeys given single intravenous and oral doses. A two-compartment open model was fitted to the plasma and urine data. Plasma concentrations declined in a biexponential fashion with an average beta half-life of 12.45 h and central and steady-state volumes of distribution of 0.43 and 1.90 liters/kg, respectively. The average systemic and renal clearance values were 0.23 and 0.08 liters/kg, respectively, and the apparent mean terminal half-life of the oral dose was 12.5 h. The serum concentrations exceeded the 90% effective concentration value for lamivudine-resistant and wild-type HIV-1 after oral administrations. A large variation was observed in the oral bioavailability, which ranged from 15 to 31%. To determine whether the bioavailability may be improved by using a basic buffer solution, the oral dose was repeated to the same animals in a sodium bicarbonate solution. The bioavailability of
l
-3′-Fd4C administered with sodium bicarbonate was not significantly different from the bioavailability when the oral dose was administered in the absence of buffer (
P
= 0.49), suggesting that further development of this compound may warrant other approaches, such as development of a prodrug to improve its oral absorption.
Use of an Efflux Pump Inhibitor To Determine the Prevalence of Efflux Pump-Mediated Fluoroquinolone Resistance and Multidrug Resistance in
Pseudomonas aeruginosa
Authors: Kriengkauykiat Jane , Porter Edith , Lomovskaya Olga , Wong-Beringer Annie 
Published: January 2005

ABSTRACT

Fluoroquinolone-resistance in
Pseudomonas aeruginosa
may be due to efflux pump overexpression (EPO) and/or target mutations. EPO can result in multidrug resistance (MDR) due to broad substrate specificity of the pumps. MC-04,124, an efflux pump inhibitor (EPI) shown to significantly potentiate activity of levofloxacin in
P. aeruginosa
, was used to examine the prevalence of EPO in clinical isolates. MICs were determined for ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin with or without EPI and for other antipseudomonal agents by using broth microdilution against
P. aeruginosa
isolates from adults (
n
= 119) and children (
n
= 24). The prevalence of the EPO phenotype (≥8-fold MIC decrease when tested with EPI) was compared among subgroups with different resistance profiles. The EPO phenotype was more prevalent among levofloxacin-resistant than levofloxacin-sensitive strains (61%, 48/79 versus 9%, 6/64). EPO was present in 60% of fluoroquinolone-resistant strains without cross-resistance, while it was present at variable frequencies among strains with cross-resistance to other agents: piperacillin-tazobactam (86%), ceftazidime (76%), cefepime (65%), imipenem (56%), gentamicin (55%), tobramycin (48%), and amikacin (27%). The magnitude of MIC decrease with an EPI paralleled the frequency of which the EPO phenotype was observed in different subgroups. EPI reduced the levofloxacin MIC by as much as 16-fold in eight strains for which MICs were 128 μg/ml. Efflux-mediated resistance appears to contribute significantly to fluoroquinolone resistance and MDR in
P. aeruginosa
. Our data support the fact that increased fluoroquinolone usage can negatively impact susceptibility of
P. aeruginosa
to multiple classes of antipseudomonal agents.