bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I study of paclitaxel plus irinotecan combination therapy for patients with refractory and advanced gastric cancer
Authors: KOBAYASHI T. , SAKAGAMI T. , KOIZUKA H. , YAMAMOTO N. , SASAKI T. , MAEDA Y. , OMURO Y. , OKAMOTO R. , MIKOSHIBA M. , SASAKI E. , MATSUMOTO T. , MIWA H. 
Published: June 2006

SummaryBackgroundNo adequate second‐line chemotherapy regimen for advanced gastric cancer is available.AimsTo determine the safety and optimal dose of paclitaxel/irinotecan as a second‐line chemotherapy for patients with advanced and recurrent gastric cancer.Patients and methodsSixteen patients with refractory and advanced measurable gastric cancer who were resistant to 5‐FU plus cis‐diamminedichloroplatinum (CDDP) therapy (FP) were enrolled. Paclitaxel/irinotecan was given intravenously on days 1, 8, and 15 in repeated 4‐week cycles. Paclitaxel/irinotecan doses were escalated in a stepwise fashion as follows: 50/40 mg/m2, 50/50 mg/m2, 50/60 mg/m2, 60/60 mg/m2, 60/70 mg/m2 in levels I, II, III, IV and V, respectively.ResultsBecause of one patient with Grade 3 febrile neutropenia at level I, three more patients were enrolled in level I. Doses were consequently escalated, and in level IV, Grade 3 febrile neutropenia occurred in one patient. Since an additional patient in level IV had grade 4 neutropenia, Level IV was judged as the maximum tolerated dose (MTD). The recommended dose and schedule for phase II study is paclitaxel 50 mg/m2 and irinotecan 60 mg/m2 on days 1, 8, and 15 every 4 weeks. Partial response was observed in 4 of 16 patients.ConclusionPaclitaxel/irinotecan combination regimen at the level III dosage was safe and well tolerated.
Discrimination between gastric ectopic pancreas and mesenchymal tumours, including GIST – from 12 years‘ surgical experience in one institute
Authors: OTANI Y. , YOSHIDA M. , SAIKAWA Y. , WADA N. , KUBOTA T. , KUMAI K. , SUGINO Y. , MUKAI M. , KAMEYAMA K. , KITAJIMA M. 
Published: June 2006

SummaryBackgroundAlthough recent immunochemical analysis enabled the discrimination of gastrointestinal stromal tumour (GIST) to other mesenchymal tumours, preoperative diagnosis of these tumours is not always easy.AimTo discriminate between ectopic pancreas (EP) and mesenchymal tumours, including GIST, 12 years surgical experience at Keio University Hospital was reviewed.MethodsClinicopathological findings were analysed for 131 patients with gastric submucosal tumours (SMT), including GIST (67 cases), myogenic tumour (21 cases), Schwannoma (11 cases), EP (12 cases) and others (20 cases) surgically treated at Keio University Hospital since 1993.ResultsAnalysis of clinicopathological findings of these tumours showed that GIST, myogenic tumour and Schwannoma mimic each other from the standpoint of size and location of the tumour. In contrast, comparison of mesenchymal tumours showed that, compared with gastrointestinal mesenchymal tumour, EP tends to exist at middle or lower third of the stomach (P = 0.004), and the tumour size was smaller than 3 cm (P = 0.0006). All EPs were laparoscopically resected and no malignant features were evident.ConclusionTo avoid unnecessary surgery for EP, SMT smaller than 3 cm occurring in the middle or lower third of the stomach should be carefully selected as a candidate of surgical resection.
Twelve years’ progress in surgery for perforated gastric and duodenal ulcers: a retrospective study of indications for laparoscopic surgery, post‐operative course and the influence of Candida infection
Authors: NAKAMURA T. , YOSHIDA M. , OTANI Y. , KAMEYAMA K. , ISHIKAWA H. , KUMAI K. , KUBOTA T. , SAIKAWA Y. , KITAJIMA M. 
Published: June 2006

SummaryBackgroundTwelve years has passed since we introduced laparoscopic surgery for gastroduodenal perforation.AimTo list problems and to investigate the feasibility of our clinical protocol for treatment of gastroduodenal ulcer perforation.MethodsCase records of 62 patients and histology samples of 9 patients undergoing surgery for gastroduodenal perforation were retrospectively reviewed.ResultsLaparoscopic omental implantation is feasible for some cases of perforated peptic ulcer in patients who have either stenosis or massive perforations. In patients undergoing laparoscopic omental implantation, oral ingestion of water was started at 3.3 ± 0.5 post‐operative days. Helicobacter pylori was positive in 27 of 35 patients (77%). Of 22 cases in whom intraoperative ascitic culture was taken, Candida was positive in nine (41%), and in six of eight cases involving wound infection or intraperitoneal abscess. Histological examination of resected stomach revealed the fungi with hypha formation at the base of the ulcer in 44% of patients.ConclusionsLaparoscopic omental implantation was more feasible than in the past. The possibility of Candida infection and subsequent abscess formation must be considered in patients with gastroduodenal ulcer perforation.
Endoscopic classifications as diagnostic factors of peptic ulcer and early gastric cancer – a possible reason why Helicobacter pylori infection causes gastric ulcers along lesser curvature
Authors: YOSHIDA M. , SAIKAWA Y. , HOSODA S. , KUMAI K. , KUBOTA T. , ISHIKAWA H. , NAKAMURA T. , NAKAMURA R. , KAMEYAMA K. , TAKAHASHI S. , KURIHARA N. , KITAJIMA M. 
Published: June 2006

SummaryBackgroundEndoscopic classifications were reported to reflect the pathophysiology of gastric mucosa. However, relationship between gastric lesions and classifications has not been examined well.AimTo investigate the relationship between endoscopic classifications and cancers or ulcers.MethodsIn this study, 487 patients undergoing upper gastrointestinal endoscopy in Takahashi Clinic and 257 patients with early gastric cancer in Keio University Hospital were enrolled.ResultsIncidence of reflux oesophagitis was higher in Helicobacter pylori‐negative patients. K‐form was better in the H. pylori‐positive patients. Most cancers in the patients with the closed‐type or reflux oesophagitis were of undifferentiated types. Incidences of ulcers were highest in C‐2 and C‐3 in which the borders of atrophy cross the medial oblique muscle bundle, the border circular muscle bundle or both, and 94% of ulcers in C‐2 and C‐3 stomach were located along the lesser curvature.ConclusionThe predominant existence of undifferentiated types in patients with reflux oesophagitis or closed‐type stomach can be useful information for early diagnosis of cancers. The relationship between the Kimura–Takemoto classification and ulcer location may explain why H. pylori infection is related to ulcer formation along the lesser curvature.
Review article: comparative pharmacodynamic review of rabeprazole – focus on day 1 data
Authors: ROBINSON M. , BARONE J. 
Published: June 2006

SummaryProton pump inhibitors have become the preferred therapy for gastro‐oesophageal reflux disease and other acid‐related disorders. Without clear‐cut clinical data to help clinicians differentiate the impact of the five currently available proton pump inhibitors on early symptom relief and health‐related quality of life, we can explore potentially relevant differences in pharmacodynamic profiles of these proton pump inhibitors.In general, rabeprazole 10 and 20 mg achieve greater gastric pH >4 and >3 holding times and area under gastric pH–time curves on day 1 of treatment compared with other proton pump inhibitors.Superiority in day 1 pharmacodynamic measures corroborates fast antisecretory onset, and supports the premise that rabeprazole will be especially suitable for on‐demand use. In particular, comparisons with omeprazole and esomeprazole suggest better day 1 nocturnal acid control with rabeprazole.
Review article: understanding the pharmacodynamic and pharmacokinetic differences between proton pump inhibitors – focus on pKa and metabolism
Authors: HORN J. 
Published: June 2006

SummaryProton pump inhibitors (PPIs) have been shown to be clinically more effective than other antisecretory agents, including H2‐receptor antagonists, in the treatment of acid‐related disorders and are recognized as the treatment of choice in gastro‐oesophageal reflux disease (GERD).1Five PPIs are currently available in the United States: omeprazole, its S‐enantiomer esomeprazole, lansoprazole, pantoprazole and rabeprazole. PPIs are effective in suppressing gastric acid, controlling GERD symptoms and healing erosive oesophagitis and ulcers.There are differences in pharmacodynamic and pharmacokinetic profiles among PPIs, including the onset of gastric acid suppression, routes of metabolism and specific drug–drug interactions. Some of these differences may affect the clinical utility of these agents, at least in certain clinical settings. Using rabeprazole as an example, this article investigates some of the pharmacodynamic and pharmacokinetic properties among PPIs, specifically pKa, routes of metabolism and the effect of food.In addition to reviewing the results of studies with PPIs concerning these factors, this article will define and more fully describe these measures/mechanisms to further our understanding of their impact. Finally, this article discusses the potential clinical significance of these pharmacological properties.
Low-Level Resistance of
Staphylococcus aureus
to Thrombin-Induced Platelet Microbicidal Protein 1 In Vitro Associated with
qacA
Gene Carriage Is Independent of Multidrug Efflux Pump Activity
Authors: Bayer A. S. , Kupferwasser L. I. , Brown M. H. , Skurray R. A. , Grkovic S. , Jones T. , Mukhopadhay K. , Yeaman M. R. 
Published: June 2006

ABSTRACT

Thrombin-induced platelet microbial protein 1 (tPMP-1), a cationic antimicrobial polypeptide released from thrombin-stimulated rabbit platelets, targets the
Staphylococcus aureus
cytoplasmic membrane to initiate its microbicidal effects. In vitro resistance to tPMP-1 correlates with survival advantages in vivo. In
S. aureus
, the plasmid-carried
qacA
gene encodes a multidrug transporter, conferring resistance to organic cations (e.g., ethidium [Et]) via proton motive force (PMF)-energized export. We previously showed that
qacA
also confers a tPMP-1-resistant (tPMP-1
r
) phenotype in vitro. The current study evaluated whether (i) transporters encoded by the
qacB
and
qacC
multidrug resistance genes also confer tPMP-1
r
and (ii) tPMP-1
r
mediated by
qacA
is dependent on efflux pump activity. In contrast to tPMP-1
r
qacA-
bearing strains, the parental strain and its isogenic
qacB
- and
qacC
-containing strains were tPMP-1 susceptible (tPMP-1
s
). Efflux pump inhibition by cyanide
m
-chlorophenylhydrazone abrogated Et
r
, but not tPMP-1
r
, in the
qacA-
bearing strain. In synergy assays, exposure of the
qacA
-bearing strain to tPMP-1 did not affect the susceptibility of Et (ruling out Et-tPMP-1 cotransport). The following cytoplasmic membrane parameters did not differ significantly between the
qacA
-bearing and parental strains: contents of the major phospholipids; asymmetric distributions of the positively charged species, lysyl-phosphotidylglycerol; fatty acid composition; and relative surface charge. Of note, the
qacA
-bearing strain exhibited greater membrane fluidity than that of the parental,
qacB
-, or
qacC
-bearing strain. In conclusion, among these families of efflux pumps, only the multidrug transporter encoded by
qacA
conferred a tPMP-1
r
phenotype. These data suggest that
qacA
-encoded tPMP-1
r
results from the impact of a specific transporter upon membrane structure or function unrelated to PMF-dependent peptide efflux.
Risk Factors for Selection of the L74I Reverse Transcriptase Mutation in Human Immunodeficiency Virus Type 1-Infected Patients
Authors: Wirden Marc , Roquebert Bénédicte , Derache Anne , Simon Anne , Duvivier Claudine , Ghosn Jade , Dominguez Stephanie , Boutonnet Véronique , Ait-Arkoub Zaina , Katlama Christine , Calvez Vincent , Marcelin Anne-Genevieve 
Published: June 2006

ABSTRACT
We analyzed 3,475 human immunodeficiency virus sequences and 241 therapeutic histories. The L74I mutation was carried by 7% of viruses. L74I was strongly associated with T215F, K70R, and V75M/S/T/A mutations and increased with the number of thymidine analog mutations. It seemed to be linked to the use of abacavir or efavirenz.
Intracellular Metabolism and In Vitro Activity of Tenofovir against Hepatitis B Virus
Authors: Delaney William E. , Ray Adrian S. , Yang Huiling , Qi Xiaoping , Xiong Shelly , Zhu Yuao , Miller Michael D. 
Published: June 2006

ABSTRACTTenofovir is an acyclic nucleotide analog with activity against human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Tenofovir disoproxil fumarate (tenofovir DF), a bis-alkoxyester prodrug of tenofovir, is approved for the treatment of HIV and is currently being developed to treat chronic hepatitis B. In this report, we further characterize the in vitro activity of tenofovir against HBV as well as its metabolism in hepatic cells. We show that tenofovir is efficiently phosphorylated to tenofovir diphosphate (TFV-DP) in both HepG2 cells and primary human hepatocytes. TFV-DP has a long intracellular half-life (95 h) and is a potent and competitive inhibitor of HBV polymerase (Ki= 0.18 μM). Tenofovir has a 50% effective concentration of 1.1 μM against HBV in cell-based assays, and potency is improved >50-fold by the addition of bis-isoproxil progroups. Tenofovir has previously demonstrated full activity against lamivudine-resistant HBV in vitro and clinically. Here we show that the major adefovir resistance mutation, rtN236T, confers three- to fourfold-reduced susceptibility to tenofovir in cell culture; the clinical significance of this susceptibility shift has not yet been determined. The rtA194T HBV polymerase mutation recently identified in tenofovir DF-treated HIV/HBV-coinfected patients did not confer in vitro resistance to tenofovir as a single mutation or in a lamivudine-resistant viral background. Overall, the antiviral and metabolic profile of tenofovir supports its development for the treatment of chronic hepatitis B.
Emergence of a
Candida krusei
Isolate with Reduced Susceptibility to Caspofungin during Therapy
Authors: Hakki Morgan , Staab Janet F. , Marr Kieren A. 
Published: June 2006

ABSTRACT

Clinical failure associated with reduced susceptibility to caspofungin has been described in
Candida albicans
and
C. parapsilosis
. We report a case of
Candida krusei
infection that progressed despite caspofungin therapy. Reduced microbial susceptibility to all three echinocandins (caspofungin, anidulafungin, and micafungin) was noted but was not associated with mutations in
FKS1
.
Multiple
cis
-Acting Sequences Mediate Upregulation of the
MDR1
Efflux Pump in a Fluconazole-Resistant Clinical
Candida albicans
Isolate
Authors: Hiller Davina , Stahl Stephanie , Morschhäuser Joachim 
Published: June 2006

ABSTRACT

Overexpression of the
MDR1
gene, which encodes a multidrug efflux pump of the major facilitator superfamily, is a frequent cause of resistance to the antimycotic agent fluconazole and other metabolic inhibitors in clinical
Candida albicans
strains. Constitutive
MDR1
overexpression in such strains is caused by mutations in as yet unknown
trans
-regulatory factors. In order to identify the
cis
-acting sequences in the
MDR1
regulatory region that mediate constitutive
MDR1
upregulation, we performed a promoter deletion analysis in the genetic background of an
MDR1
-overexpressing clinical
C. albicans
isolate. We found that several different regions in the
MDR1
promoter can mediate
MDR1
overexpression in this isolate. In contrast, deletion of one of these regions abolished benomyl-induced
MDR1
expression in a
C. albicans
laboratory strain. These results suggest that multiple transcription factors control expression of the
MDR1
efflux pump in
C. albicans
and that the mutation(s) that causes constitutive
MDR1
overexpression and drug resistance in clinical
C. albicans
isolates affects the activities of several of these transcription factors.
Risk Factors for Isolation of Strains Susceptible Only to Polymyxin among Patients with
Pseudomonas aeruginosa
Bacteremia
Authors: Falagas Matthew E. , Koletsi Patra K. , Kopterides Petros , Michalopoulos Argyris 
Published: June 2006

ABSTRACT

We conducted a case-control study to identify risk factors associated with the isolation of
Pseudomonas aeruginosa
strains susceptible only to polymyxin from blood by comparing data between 16 patients with blood isolates that were susceptible only to polymyxins and 40 patients with blood isolates that were susceptible to carbapenems. The multivariable analysis showed that exposure to carbapenems was associated with the development of
P. aeruginosa
bacteremia susceptible only to polymyxin (odds ratio, 9.0; 95% confidence interval, 2.4 to 34.3;
P
= 0.001).
Intrinsic Macrolide Resistance of the
Mycobacterium tuberculosis
Complex Is Inducible
Authors: Andini Nadya , Nash Kevin A. 
Published: June 2006

ABSTRACT

Mycobacterium tuberculosis
is intrinsically resistant to macrolides, a characteristic associated with expression of the
erm
(37) gene. This intrinsic resistance was found to be inducible with clarithromycin and the ketolide HMR3004. Furthermore, underlying the phenotypic induction was an increase in
erm
(37) mRNA levels.
Characterizing the Effects of Caspofungin on
Candida albicans
,
Candida parapsilosis
, and
Candida glabrata
Isolates by Simultaneous Time-Kill and Postantifungal-Effect Experiments
Authors: Clancy Cornelius J. , Huang Hong , Cheng Shaoji , Derendorf Hartmut , Nguyen M. Hong 
Published: June 2006

ABSTRACT

We measured time-kills and postantifungal effects (PAFEs) of caspofungin against
Candida albicans
,
C. parapsilosis
, and
C. glabrata
isolates. One-hour exposure to caspofungin during PAFE experiments accounted for the majority of killing during time-kill experiments. Regrowth of all isolates was inhibited for at least 24 h following drug washout.
Common Region CR1 for Expression of Antibiotic Resistance Genes
Authors: Rodriguez-Martinez Jose-Manuel , Poirel Laurent , Canton Rafael , Nordmann Patrice 
Published: June 2006

ABSTRACT

The CR1 element defined by an
orf513
gene encoding a putative recombinase and a recombination crossover site has been identified upstream of several antibiotic resistance genes in
Enterobacteriaceae
. This CR1 element was shown to bring promoter sequences that play a role in the expression of unrelated antibiotic resistance genes.
Absence of Cochleotoxicity Measured by Standard and High-Frequency Pure Tone Audiometry in a Trial of Once- versus Three-Times-Daily Tobramycin in Cystic Fibrosis Patients
Authors: Mulheran Michael , Hyman-Taylor Pauline , Tan Kelvin H.-V. , Lewis Sarah , Stableforth David , Knox Alan , Smyth Alan 
Published: June 2006

ABSTRACTWe undertook assessment of hearing in patients with cystic fibrosis who were taking part in a large randomized controlled trial of once- versus three-times-daily tobramycin for pulmonary exacerbations of cystic fibrosis (the TOPIC study). All patients were eligible to have standard pure tone audiometry performed across the frequency range of 0.25 to 8 kHz. High-frequency pure tone audiometry over 10 to 16 kHz was also performed with a subset of patients. Audiometry was undertaken at the start of tobramycin treatment, at the end of a 14-day course of treatment, and at follow-up 6 to 8 weeks later. We enrolled 244 patients, of whom 219 (125 children and 94 adults) completed treatment. Nineteen patients were excluded from analysis due to abnormal baseline audiometry. Complete pre- and posttreatment standard audiological data were obtained for 168/219 patients. We found no significant differences in hearing thresholds when they were assessed at the baseline, at the end of treatment, and at follow-up 6 to 8 weeks later were compared. In addition, no significant differences in hearing thresholds were detected between treatment regimens. Similar results were obtained for the subset of 63/168 patients who underwent high-frequency audiometry. We conclude that for a single 14-day course of tobramycin treatment in patients with cystic fibrosis with no preexisiting auditory deficit, no measurable effect on hearing was apparent with either once- or three-times-daily treatment. Estimation of the cumulative cochleotoxic risk in cystic fibrosis patients due to repeated aminoglycoside therapy, as evidenced by the patients excluded from this study due to hearing loss, also requires further characterization.
Polyphenols Reduce Gastritis Induced by
Helicobacter pylori
Infection or VacA Toxin Administration in Mice
Authors: Ruggiero P. , Tombola F. , Rossi G. , Pancotto L. , Lauretti L. , Del Giudice G. , Zoratti M. 
Published: June 2006

ABSTRACT

Helicobacter pylori
colonizes the human gastric mucosa, causing inflammation that leads to atrophic gastritis, and it can cause peptic ulcer and gastric cancer. We show that polyphenol administration to mice experimentally infected by
H. pylori
or treated with VacA toxin can limit gastric epithelium damage, an effect that may be linked to VacA inhibition.
The Antimalarial Artemisinin Synergizes with Antibiotics To Protect against Lethal LiveEscherichia coliChallenge by Decreasing Proinflammatory Cytokine Release
Authors: Wang Jun , Zhou Hong , Zheng Jiang , Cheng Juan , Liu Wei , Ding Guofu , Wang Liangxi , Luo Ping , Lu Yongling , Cao Hongwei , Yu Shuangjiang , Li Bin , Zhang Lezhi 
Published: June 2006

ABSTRACTIn the present study artemisinin (ART) was found to have potent anti-inflammatory effects in animal models of sepsis induced by CpG-containing oligodeoxy-nucleotides (CpG ODN), lipopolysaccharide (LPS), heat-killedEscherichia coli35218 or liveE. coli. Furthermore, we found that ART protected mice from a lethal challenge by CpG ODN, LPS, or heat-killedE. coliin a dose-dependent manner and that the protection was related to a reduction in serum tumor necrosis factor alpha (TNF-α). More significantly, the administration of ART together with ampicillin or unasyn (a complex of ampicillin and sulbactam) decreased mortality from 100 to 66.7% or 33.3%, respectively, in mice subjected to a lethal liveE. colichallenge. Together with the observation that ART alone does not inhibit bacterial growth, this result suggests that ART protection is achieved as a result of its anti-inflammatory activity rather than an antimicrobial effect. In RAW264.7 cells, pretreatment with ART potently inhibited TNF-α and interleukin-6 release induced by CpG ODN, LPS, or heat-killedE. coliin a dose- and time-dependent manner. Experiments utilizing affinity sensor technology revealed no direct binding of ART with CpG ODN or LPS. Flow cytometry further showed that ART did not alter binding of CpG ODN to cell surfaces or the internalization of CpG ODN. In addition, upregulated levels of TLR9 and TLR4 mRNA were not attenuated by ART treatment. ART treatment did, however, block the NF-κB activation induced by CpG ODN, LPS, or heat-killedE. coli. These findings provide compelling evidence that ART may be an important potential drug for sepsis treatment.
Prospective Determination of Plasma Imipenem Concentrations in Critically Ill Children
Authors: Giannoni Eric , Moreillon Philippe , Cotting Jacques , Moessinger Adrien , Bille Jacques , Décosterd Laurent , Zanetti Giorgio , Majcherczyk Paul , Bugnon Denis 
Published: June 2006

ABSTRACT
Plasma imipenem concentrations were measured in 19 critically ill children (median age, 0.8 year; range, 0.02 to 12.9 years). Wide interindividual variations (2 to 4× at peak and >10× at trough concentrations) resulted in unpredictable plasma levels in several children. To avoid subtherapeutic drug levels, we recommend treatment with at least 100 mg/kg of body weight/day of imipenem-cilastatin for critically ill children requiring such therapy.