bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Association Between Cognition and Histamine‐2 Receptor Antagonists in African Americans
Authors: Boustani Malaz , Hall Kathleen S. , Lane Kathleen A. , Aljadhey Hisham , Gao Sujuan , Unverzagt Frederick , Murray Michael D. , Ogunniyi Adesola , Hendrie Hugh 
Published: June 2007

OBJECTIVES: To evaluate the association between histamine‐2 receptor antagonist (H2A) exposure and incident cognitive impairment in a community‐based sample of African Americans.DESIGN: Five‐year longitudinal observational study.PARTICIPANTS: A sample of 1,558 community‐dwelling African Americans aged 65 and older with no baseline cognitive impairment living in Indianapolis, Indiana.OUTCOME MEASURE: Incident cognitive impairment, defined as incident dementia, cognitive impairment without dementia, or poor cognitive performance, as determined using combined cognitive assessments that included the Community Screening Instrument for Dementia, a comprehensive clinical assessment including informant interview, and neuropsychological testing.EXPOSURE: Trained interviewers assessed the use of prescription and over‐the‐counter H2As using in‐home inspection of medications and report of participants and informants.RESULTS: Incident cognitive impairment occurred in 275 (17.7%) participants. After controlling for age, education, baseline cognitive score, the use of anticholinergics, and history of diabetes mellitus and depression, continuous use of H2As was associated with greater risk of incident cognitive impairment than for nonusers (odds ratio=2.42; 95% confidence interval=1.17–5.04).CONCLUSION: H2As might be a risk factor for the development of cognitive impairment in African Americans. This finding requires confirmation from future studies.
China: The Aging Giant
Authors: Flaherty Joseph Henry , Liu Mei Lin , Ding Lei , Dong Birong , Ding Qunfang , Li Xia , Xiao Shifu 
Published: June 2007

This article examines the changing demographics of China, with particular attention paid to the effect of the one‐child policy in relation to long‐term care of older people. It also examines the current state of health care for older people. Long‐term stays characterize hospital care. Most geriatric syndromes are less common in hospitalized older people (e.g., delirium, falls), but some (e.g., polypharmacy) are more common. A high volume of patients and brief targeted visits characterize outpatient care. Nursing homes exist in China, but relatively fewer than in the most developed countries.Geriatric departments in university‐based hospitals primarily have developed out of a need to care for retired government officials and workers. There are no formal geriatric fellowships or national board certifications in geriatricsHealth care is primarily based on fee for service. Not all elderly have healthcare insurance. Although costs of health care and medications are less expensive than in the United States, they are relatively high for lower‐and middle‐class Chinese and have increased more quickly than has the standard of living in the past 20 years.Family and community support for older people is strong in China. Some older people have one‐to‐one care from a baomu (literally “protection” (bao) “mother” (mu)), a type of live‐in maid who also provides care for the older person. Some of the challenges facing China in the care of its aging population are how to increase geriatric research and training, how to care for the uninsured or underinsured, and how to handle the inevitable growth of disabled and frail older people.
Bleomycin Treatment for Verrucae
Authors: Price Norman M. 
Published: June 2007

Background.

The treatment of verrucae with bleomycin injections has not become a routinely adopted form of therapy in dermatologic practice since its use was originally described in 1980 because of the adverse effects and complications that have been associated with it.
Objectives.

The goal of this study was to demonstrate the results and the incidence of adverse effects from the use of bleomycin in clinical practice in a retrospective study of patients presenting with verrucae and to demonstrate the convenience and ease of the methodology that was used in obtaining these results.
Methods.

Patients' lesions were injected with bleomycin every 3 to 4 weeks until the lesions had been eliminated or the injections were discontinued because of adverse effects or complications.
Results.

There were 211 patients in the study, and 224 lesions were treated. After 1 treatment, 47.6% of the lesions were cleared; another 38.8%were cleared after 2 treatments; and another 9.8% were cleared after 3 treatments. In total, 96% of lesions were cleared after 5 treatments. A small number of temporary adverse effects were noted: 3 patients had local chemical cellulitis, 2 patients had formation of sterile abscesses, 1 patient had postinflammatory hyperpigmentation, and 1 patient had localized pain. No local or systemic complications were observed.
Conclusions.

Therapy with intralesional bleomycin is a relatively rapid and convenient form of therapy, compared with other available treatments, from the point of view of both the patient and the physician.
Low serum level of hepatitis B core‐related antigen indicates unlikely reactivation of hepatitis after cessation of lamivudine therapy
Authors: Matsumoto Akihiro , Tanaka Eiji , Minami Masahito , Okanoue Takeshi , Yatsuhashi Hiroshi , Nagaoka Shinya , Suzuki Fumitaka , Kobayashi Mariko , Chayama Kazuaki , Imamura Michio , Yotsuyanagi Hiroshi , Nakaoka Shigeru , Maki Noboru , Kawata Sumio , Kumada Hiromitsu , Iino Shiro , Kiyosawa Kendo 
Published: June 2007

Aim:  The clinical significance of hepatitis B virus (HBV) core‐related antigen (HBcrAg) in predicting the reactivation of hepatitis after halting lamivudine administration was analyzed.Methods:  A total of 34 patients with chronic hepatitis B were enrolled. Lamivudine was administered for at least 6 months before cessation, and reactivation of hepatitis was defined as elevation of alanine aminotransferase levels to more than 80 IU/L within 12 months of cessation.Results:  In total, 20 (59%) patients experienced hepatitis reactivation. Although concentrations of HBV DNA and HBcrAg in serum did not differ between the two groups of patients at the onset of lamivudine administration, HBcrAg serum levels were significantly higher (P = 0.009) in the reactivation patients (median 4.9, 25–75% range 4.7– 5.9 log unit/mL) than the non‐reactivation patients (median 3.2, 25–75% range <3.0–4.5 log unit/mL) post‐lamivudine treatment. The concentration of HBV DNA did not differ between the two groups (median <3.7, 25–75% range <3.7–<3.7 log copy/mL in the reactivation group vs. median <3.7, 25–75% range <3.7–<3.7 log copy/mL in the non‐ reactivation group). Receiver operating characteristic analysis of HBcrAg concentration showed an area under the curve of 0.764 in predicting patients without reactivation of hepatitis.Conclusion:  HBcrAg can be a useful marker to identify patients who are not at risk of reactivation of severe hepatitis after discontinuation of lamivudine administration.
Association of Saquinavir Plasma Concentrations with Side Effects but Not with Antiretroviral Outcome in Patients Infected with Protease Inhibitor-Susceptible Human Immunodeficiency Virus Type 1
Authors: Lötsch Jörn , Harder Sebastian , Stürmer Martin , Doerr Hans-Wilhelm , Geisslinger Gerd , Staszewski Schlomo , von Hentig Nils 
Published: June 2007

ABSTRACTThe objective of this study was to identify parameters among saquinavir pharmacokinetics, patients' demographics or comedications, to be addressed for improved personalized therapy. The presence of human immunodeficiency virus type 1 (HIV-1) RNA at therapy week 48 (principal target parameter), CD4 cell count at week 48, infections and side effects during 48 weeks, indicators of liver toxicity and lipid abnormalities at week 48, and a 12-h saquinavir plasma concentration-versus-time profile were assessed in 56 patients receiving saquinavir-ritonavir (1,000 and 100 mg, respectively) twice daily (44 therapy-naïve and 12 antiretrovirally pretreated patients) for association with saquinavir plasma concentrations, demographics, baseline values of target parameters, and coadministered antiretrovirals. Antiretroviral failure was observed in 8 of the 56 patients in whom HIV-1 RNA was detectable at week 48. This therapeutic failure was not associated with individual saquinavir pharmacokinetics. More likely, therapeutic failure was related to incidences interfering with antiretroviral therapy, causing therapy interruptions or incompliance. Weak associations were, however, seen between high maximum saquinavir plasma concentrations and both CD4 counts of ≥200 cells μl−1at week 48 (P= 0.014) and constitutional side effects during 48 weeks (P= 0.002). However, patients with high CD4 counts and constitutional side effects were not identical (P= 0.53). Saquinavir therapeutic drug monitoring in patients infected with protease inhibitor-susceptible HIV-1 taking saquinavir-ritonavir (1,000 and 100 mg, respectively) is not demanded for improving the antiretroviral effect. It may be contemplated in cases with constitutional side effects or low CD4 counts with weak immune responses.
Antiviral and Anti-Inflammatory Effects of Rosmarinic Acid in an Experimental Murine Model of Japanese Encephalitis
Authors: Swarup Vivek , Ghosh Joydeep , Ghosh Soumya , Saxena Amit , Basu Anirban 
Published: June 2007

ABSTRACT

Rosmarinic acid (RA) reduced the mortality of mice infected with Japanese encephalitis virus (JEV). Significant decreases in viral loads (
P
< 0.001) and proinflammatory cytokine levels (
P
< 0.001) were observed in JEV-infected animals treated with RA compared to levels in infected mice without treatment, at 8 to 9 days postinfection.
Pneumococcal LytA Autolysin, a Potent Therapeutic Agent in Experimental Peritonitis-Sepsis Caused by Highly β-Lactam-Resistant
Streptococcus pneumoniae
Authors: Rodríguez-Cerrato Violeta , García Pedro , Huelves Lorena , García Ernesto , del Prado Gema , Gracia Matilde , Ponte Carmen , López Rubens , Soriano Francisco 
Published: June 2007

ABSTRACT

The in vitro and in vivo antipneumococcal activities of the main pneumococcal autolysin (LytA) and Cpl-1, a lysozyme encoded by phage Cp-1, were studied. Intraperitoneal therapy with LytA or high-dose Cpl-1 remarkably reduced peritoneal bacterial counts (>5 log
10
CFU/ml) compared with those for the controls. After intravenous injection, LytA was the most effective treatment.
RSV604, a Novel Inhibitor of Respiratory Syncytial Virus Replication
Authors: Chapman Joanna , Abbott Elizabeth , Alber Dagmar G. , Baxter Robert C. , Bithell Sian K. , Henderson Elisa A. , Carter Malcolm C. , Chambers Phil , Chubb Ann , Cockerill G. Stuart , Collins Peter L. , Dowdell Verity C. L. , Keegan Sally J. , Kelsey Richard D. , Lockyer Michael J. , Luongo Cindy , Najarro Pilar , Pickles Raymond J. , Simmonds Mark , Taylor Debbie , Tyms Stan , Wilson Lara J. , Powell Kenneth L. 
Published: June 2007

ABSTRACT
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections worldwide, yet no effective vaccine or antiviral treatment is available. Here we report the discovery and initial development of RSV604, a novel benzodiazepine with submicromolar anti-RSV activity. It proved to be equipotent against all clinical isolates tested of both the A and B subtypes of the virus. The compound has a low rate of in vitro resistance development. Sequencing revealed that the resistant virus had mutations within the nucleocapsid protein. This is a novel mechanism of action for anti-RSV compounds. In a three-dimensional human airway epithelial cell model, RSV604 was able to pass from the basolateral side of the epithelium effectively to inhibit virus replication after mucosal inoculation. RSV604, which is currently in phase II clinical trials, represents the first in a new class of RSV inhibitors and may have significant potential for the effective treatment of RSV disease.
Update to the Multiplex PCR Strategy for Assignment of
mec
Element Types in
Staphylococcus aureus
Authors: Milheiriço Catarina , Oliveira Duarte C. , de Lencastre Hermínia 
Published: June 2007

ABSTRACT

Staphylococcal cassette chromosome
mec
(SCC
mec
) typing is important for the identification and definition of methicillin-resistant
Staphylococcus aureus
clones, and for routine purposes, multiplex PCR assays are the most adequate for SCC
mec
typing. Here, we describe an update to the multiplex PCR strategy for SCC
mec
typing that we described in 2002 so that SCC
mec
types IV and V may be properly identified.
Distribution of Suramin, an Antitrypanosomal Drug, across the Blood-Brain and Blood-Cerebrospinal Fluid Interfaces in Wild-Type and P-Glycoprotein Transporter-Deficient Mice
Authors: Sanderson Lisa , Khan Adil , Thomas Sarah 
Published: June 2007

ABSTRACTAlthough 60 million people are exposed to human African trypanosomiasis, drug companies have not been interested in developing new drugs due to the lack of financial reward. No new drugs will be available for several years. A clearer understanding of the distribution of existing drugs into the brains of sleeping sickness patients is needed if we are to use the treatments that are available more safely and effectively. This proposal addresses this issue by using established animal models. Using in situ brain perfusion and isolated incubated choroid plexus techniques, we investigated the distribution of [3H]suramin into the central nervous systems (CNSs) of male BALB/c, FVB (wild-type), and P-glycoprotein-deficient (Mdr1a/Mdr1b-targeted mutation) mice. There was no difference in the [3H]suramin distributions between the three strains of mice. [3H]suramin had a distribution similar to that of the vascular marker, [14C]sucrose, into the regions of the brain parenchyma that have a blood-brain barrier. However, the association of [3H]suramin with the circumventricular organ samples, including the choroid plexus, was higher than that of [14C]sucrose. The association of [3H]suramin with the choroid plexus was also sensitive to phenylarsine oxide, an inhibitor of endocytosis. The distribution of [3H]suramin to the brain was not affected by the presence of other antitrypanosomal drugs or the P-glycoprotein efflux transporter. Overall, the results confirm that [3H]suramin would be unlikely to treat the second or CNS stage of sleeping sickness.
Predictive Genotypic Algorithm for Virologic Response to Lopinavir-Ritonavir in Protease Inhibitor-Experienced Patients
Authors: King Martin S. , Rode Richard , Cohen-Codar Isabelle , Calvez Vincent , Marcelin Anne-Geneviève , Hanna George J. , Kempf Dale J. 
Published: June 2007

ABSTRACTSeveral genotypic resistance algorithms have been proposed for quantitation of the degree of phenotypic resistance to the human immunodeficiency virus (HIV) protease inhibitor (PI) lopinavir (LPV), including the original LPV mutation score. In this study, we retrospectively evaluated 21 codons in HIV protease known to be associated with PI resistance in a large antiretroviral agent-experienced observational patient cohort, “Autorisation Temporaire d'Utilization” (ATU), to assess whether a more optimal algorithm could be derived by using virologic response data from patients treated with LPV in combination with ritonavir (LPV/r). Five of the 11 mutations constituting the LPV mutation score were not associated with a virologic response, while 4 additional mutations not included in this score demonstrated an association. Therefore, the LPV ATU score, which includes mutations at codons 10, 20, 24, 33, 36, 47, 48, 54, 82, and 84, was constructed and shown in two different types of multivariable analyses of the ATU cohort to be a better predictor of the virologic response than the LPV mutation score. The LPV ATU score was also more strongly associated with a virologic response when it was applied to independent clinical trial populations of PI-experienced patients receiving LPV/r. This study provides the basis for a new genotypic resistance algorithm that is useful for predicting the antiviral activities of LPV/r-based regimens in PI-experienced patients. The refined algorithm may be useful in making clinical treatment decisions and in refining genetic and pharmacologic methods for assessing the activity of LPV/r.
Efflux-Related Resistance to Norfloxacin, Dyes, and Biocides in Bloodstream Isolates ofStaphylococcus aureus
Authors: DeMarco Carmen E. , Cushing Laurel A. , Frempong-Manso Emmanuel , Seo Susan M. , Jaravaza Tinevimbo A. A. , Kaatz Glenn W. 
Published: June 2007

ABSTRACTEfflux is an important resistance mechanism inStaphylococcus aureus, but its frequency in patients with bacteremia is unknown. Nonreplicate bloodstream isolates were collected over an 8-month period, and MICs of four common efflux pump substrates, with and without the broad-spectrum efflux pump inhibitor reserpine, were determined (n= 232). A reserpine-associated fourfold decrease in MIC was considered indicative of efflux. Strains exhibiting efflux of at least two of the four substrates were identified (“effluxing strains” [n= 114]). For these strains, MICs with or without reserpine for an array of typical substrates and the expression ofmepA,mdeA,norA,norB,norC, andqacA/Bwere determined using quantitative real-time reverse transcription-PCR (qRT-PCR). A fourfold or greater increase in gene expression was considered significant. The most commonly effluxed substrates were ethidium bromide and chlorhexidine (100 and 96% of effluxing strains, respectively). qRT-PCR identified strains overexpressingmepA(5 [4.4%]),mdeA(13 [11.4%]),norA(26 [22.8%]),norB(29 [25.4%]), andnorC(19 [16.7%]); 23 strains overexpressed two or more genes. Mutations probably associated with increased gene expression included a MepR-inactivating substitution andnorApromoter region insertions or deletions. Mutations possibly associated with increased expression of the other analyzed genes were also observed. Effluxing strains comprised 49% of all strains studied (114/232 strains), with nearly half of these overexpressing genes encoding MepA, MdeA, and/or NorABC (54/114 strains). Reduced susceptibility to biocides may contribute to persistence on environmental surfaces, and efflux of drugs such as fluoroquinolones may predispose strains to high-level target-based resistance.
High Prevalence of Metallo-β-Lactamase and 16S rRNA Methylase Coproduction among Imipenem-ResistantPseudomonas aeruginosaIsolates in Brazil
Authors: Doi Yohei , Ghilardi Angela C. R. , Adams Jennifer , de Oliveira Garcia Doroti , Paterson David L. 
Published: June 2007

ABSTRACTRates of metallo-β-lactamase and 16S rRNA methylase production were investigated in 51 imipenem-resistantPseudomonas aeruginosaclinical isolates collected from hospitals in São Paulo, Brazil. Of them, 57% and 75% produced SPM-1 and RmtD, respectively. Of note, 51% produced both enzymes, suggesting that their coproduction is already common in this geographic area.
In Vitro Susceptibility to Posaconazole of 1,903 Yeast Isolates Recovered in France from 2003 to 2006 and Tested by the Method of the European Committee on Antimicrobial Susceptibility Testing
Authors: Lortholary Olivier , Dannaoui Eric , Raoux Dorothée , Hoinard Damien , Datry Annick , Paugam André , Poirot Jean-Louis , Lacroix Claire , Dromer Françoise 
Published: June 2007

ABSTRACT

The posaconazole MIC
90
for 1,903 yeast isolates from France was 1 μg/ml (range, ≤0.015 to 8 μg/ml). Ninety percent of isolates with fluconazole MICs of ≥8 μg/ml (
n
= 509) and 90% of those with voriconazole MICs of ≥2 μg/ml (
n
= 80) were inhibited by 2 and 8 μg/ml of posaconazole, respectively.
In Vivo Efficacy and Pharmacokinetics of Voriconazole in an Animal Model of Dermatophytosis
Authors: Saunte D. M. , Simmel F. , Frimodt-Moller N. , Stolle L. B. , Svejgaard E. L. , Haedersdal M. , Kloft C. , Arendrup M. C. 
Published: June 2007

ABSTRACTThe standard treatment for tinea capitis caused byMicrosporumspecies for many years has been oral griseofulvin, which is no longer universally marketed. Voriconazole has been demonstrated to inhibit growth ofMicrosporum canisin vitro. We evaluated the efficacy and tissue pharmacokinetics of oral voriconazole in a guinea pig model of dermatophytosis. Guinea pigs (n= 16) were inoculated withM. canisconidia on razed skin. Voriconazole was dosed orally at 20 mg/kg/day for 12 days (days 3 to 14). The guinea pigs were scored clinically (redness and lesion severity) and mycologically (microscopy and culture) until day 17. Voriconazole concentrations were measured day 14 in blood, skin biopsy specimens, and interstitial fluid obtained by microdialysis in selected animals. Clinically, the voriconazole-treated animals had significantly less redness and lower lesion scores than untreated animals from days 7 and 10, respectively (P< 0.05). Skin scrapings from seven of eight animals in the voriconazole-treated group were microscopy and culture negative in contrast to zero of eight animals from the untreated group at day 14. The colony counts per specimen were significantly higher in samples from untreated animals (mean colony count of 28) than in the voriconazole-treated animals (<1 in the voriconazole group [P< 0.0001]). The voriconazole concentration in microdialysate (unbound) ranged from 0.9 to 2.0 μg/ml and in the skin biopsy specimens total from 9.1 to 35.9 μg/g. In conclusion, orally administered voriconazole leads to skin concentrations greater than the necessary MICs forMicrosporumand was shown to be highly efficacious in an animal model of dermatophytosis. Voriconazole may be a future alternative for treatment of tinea capitis in humans.
Population Pharmacokinetics at Two Dose Levels and Pharmacodynamic Profiling of Flucloxacillin
Authors: Landersdorfer Cornelia B. , Kirkpatrick Carl M. J. , Kinzig-Schippers Martina , Bulitta Jürgen B. , Holzgrabe Ulrike , Drusano George L. , Sörgel Fritz 
Published: June 2007

ABSTRACT

Flucloxacillin is often used for the treatment of serious infections due to sensitive staphylococci. The pharmacokinetic (PK)-pharmacodynamic (PD) breakpoint of flucloxacillin has not been determined by the use of population PK. Targets based on the duration of non-protein-bound concentrations above the MIC (
fT
>MIC
) best correlate with clinical cure rates for beta-lactams. We compared the breakpoints for flucloxacillin between several dosage regimens. In a randomized, two-way crossover study, 10 healthy volunteers received 500 mg and 1,000 mg flucloxacillin as 5-min intravenous infusions. Drug concentrations were determined by high-pressure liquid chromatography. We used the programs WinNonlin for noncompartmental analysis and statistics and NONMEM for population PK and Monte Carlo simulation. We compared the probability of target attainment (PTA) for intermittent- and continuous-dosage regimens based on the targets of
fT
>MIC
s of ≥50% and ≥30% of the dosing interval. The clearance and the volume of distribution were very similar after the administration of 500 mg and 1,000 mg flucloxacillin. We estimated renal and nonrenal clearances of 5.37 liters/h (coefficient of variation, 19%) and 2.73 liters/h (33%). For near maximal killing (target,
fT
>MIC
of ≥50%) flucloxacillin showed a robust (≥90%) PTA up to MICs of 0.75 to 1 mg/liter (PTA of 86% at 1 mg/liter) for a continuous or a prolonged infusion of 6 g/day. Short-term infusions of 6 g/day had a lower breakpoint of 0.25 to 0.375 mg/liter. The flucloxacillin PK was linear for doses of 500 mg and 1,000 mg. Prolonged and continuous infusion at a 66% lower daily dose achieved the same PK-PD breakpoints as short-term infusions. Prolonged infusion and continuous infusion are appealing options for the treatment of serious infections caused by sensitive staphylococci.