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1.
Maddalena Giannella Enrico Maria Trecarichi Daniele Roberto Giacobbe Francesco Giuseppe De Rosa Matteo Bassetti Alessandro Bartoloni Michele Bartoletti Angela Raffaella Losito Valerio del Bono Silvia Corcione Sara Tedeschi Francesca Raffaelli Carolina Saffioti Teresa Spanu Gian Maria Rossolini Anna Marchese Simone Ambretti Roberto Cauda Mario Tumbarello 《International journal of antimicrobial agents》2018,51(2):244-248
Objectives
To evaluate the impact of high-dose (HD) carbapenem-based combination therapy on clinical outcome in patients with monomicrobial carbapenem-resistant Klebsiella pneumoniae (CR-KP) bloodstream-infection (BSI).Methods
Post hoc analysis of all adult patients with CR-KP BSI who were treated with a combination antibiotic regimen, collected over a six-year period in six large Italian teaching hospitals. To control for confounding effects of HD carbapenem combination on 14-day mortality, a multivariate Cox regression analysis was performed. Due to imbalances between patients, a propensity score for receiving HD carbapenem was added to the model.Results
595 patients with CR-KP BSI were analysed, 77% of isolates showed a carbapenem MIC ≥16?mg/L, 428 (71.9%) received HD carbapenem-based combination therapy. Overall, 127 patients (21.3%) died within 14 days after BSI onset. Multivariate analysis showed the Charlson comorbidity index (HR 1.31, 95%CI 1.20–1.43, P?<0.001), septic shock at BSI onset (HR 3.14, 95%CI 2.19–4.50, P?<0.001), and colistin-resistant strain (HR 1.52, 95%CI 1.02–2.24, P?=?0.03) were independently associated with 14-day mortality, whereas admission to surgical ward (HR 0.44, 95%CI 0.25–0.78, P?=?0.005) and HD carbapenem use (HR 0.69, 95%CI 0.47–1.00, P?=?0.05) were protective factors. When adjusted for the propensity score, HD carbapenem use showed a greater protective effect (HR 0.64, 95%CI 0.43–0.95, P?=?0.03). Stratifying the model for carbapenem MIC, the benefit of HD carbapenem was also observed for strains with carbapenem MIC ≥16?mg/L.Conclusions
In patients receiving combination therapy for CR-KP BSI, the use of HD carbapenem seems to be associated with better outcome, even in the presence of high-level carbapenem resistance. 相似文献2.
Mohammad H. Aljawadi Abdullah T. Khoja Abdullah M. Alhammad Azzam D. AlOtaibi Sulaiman A. Al-Shammari Tawfik A. Khoja 《Saudi Pharmaceutical Journal》2018,26(8):1112-1119
Purpose
First, to determine benzodiazepines prevalence (BDZs) among Saudi older adults (SOA); Second, to quantify the association between BDZs use and falls among SOA. Third, to determine falls effect on all-cause mortality among SOA.Methods
This is a cross-sectional study that used the Saudi National Survey for Elderly Health; a nationally-representative, population-based survey. Participants were asked about BDZs use and falls history during the 12?months prior to the interview. Demographics, medications, comorbidities and housing conditions were used as covariates. Multiple imputation was used to impute missing data. Modified poisson multivariable regression was used to study the association between BDZs and falls. Cox- proportional hazard regression was used to determine falls effect on mortality over nine years period.Results
Among 2946 SOA, BDZs prevalence was 4%. Around 13% reported falls. In the multivariable regression, relative risk (RR) of falls was 2 comparing BDZs users to non-users (95CI%: 1.02–3.99). Antidepressants (RR?=?1.72; 95%CI: 1.10–2.74), laxatives (RR?=?1.38; 95%CI: 1.11–1.7), low body mass index (RR?=?1.94; 95%CI: 1.33–2.84), mild cognitive impairment (RR?=?1.56; 95%CI: 1.21–2.03), high door steps (RR?=?1.54; 95%CI: 1.23–1.93) and insufficient illumination (RR?=?1.38; 95%CI: 1.11–1.71) increased falls risk. Lastly, the hazard ratio of falls on death was 1.48 (95%CI: 1.17, 1.89) over nine years.Conclusion
Despite the recommendation against BDZs use among older adults, still there were subjects who were prescribed these drugs. falls are common among SOA. Preventive strategies such medication therapy management, nutrition improvement, elderly-friendly housing structures can reduce the prevalence of falls and consequent increase in mortality among SOA. 相似文献3.
Konstantinos Z. Vardakas Georgios L. Voulgaris George Samonis Matthew E. Falagas 《International journal of antimicrobial agents》2018,51(1):1-9
Background
Inhaled colistin is becoming increasingly popular against respiratory tract infections caused by multidrug resistant (MDR) Gram-negative bacteria because it may overcome the problems associated with intravenous (IV) administration.Objective
To investigate the effectiveness and safety of inhaled colistin as monotherapy (without concomitant IV administration of colistin) in the treatment of respiratory tract infections caused by MDR or colistin–only susceptible Gram–negative bacteria.Methods
PubMed and Scopus databases were searched. A systematic review and meta-analysis were conducted.Results
Twelve studies (373 patients receiving inhaled colistin for respiratory tract infection) were included. Ten studies evaluated patients with pneumonia (including 8 studies with ventilator-associated pneumonia) and 2 studies evaluated patients with ventilator-associated tracheobronchitis. Patients with infections due to MDR Acinetobacter baumannii and Pseudomonas aeruginosa were mainly studied. Daily dose of inhaled colistin and treatment duration varied in the individual studies. The pooled all-cause mortality was 33.8% (95% CI 24.6% – 43.6%), clinical success was 70.4% (58.5% – 81.1%) and eradication of Gram-negative bacteria was shown in 71.3% (57.6% – 83.2%) of cases.Conclusions
Inhaled colistin monotherapy may deserve further consideration as a mode for colistin administration for the treatment of respiratory tract infections caused by MDR A. baumannii and P. aeruginosa. 相似文献4.
Eyal Kleinhendler Matan J. Cohen Allon E. Moses Ora Paltiel Jacob Strahilevitz Amos Cahan 《International journal of antimicrobial agents》2018,51(1):71-76
Background
There are several empiric antibiotic treatment options for febrile neutropenia, yet there is no universally-accepted initial protocol. We aimed to assess the performance of a protocol (piperacillin, gentamicin and cefazolin) introduced over 40 years ago and compare its coverage against bacteria isolated from blood of neutropenic patients with that of various commonly used antibiotic treatment protocols.Methods
Adults with neutropenia admitted between 2003 and 2012 to the hemato-oncologic departments and in whom blood cultures were taken on admission were included. Appropriateness of several common antibiotic protocols was assessed based on the susceptibility of the blood isolates. Crude mortality rates were computed by the susceptibility of bacteria isolated from patients' blood to the actual treatment given.Results
In total, 180 admissions of neutropenic patients (95 in patients who had fever above 38?°C) with positive blood cultures were analyzed. The actual antibiotic regimen prescribed was deemed appropriate in 82% of bacteremia episodes. The recommended institutional protocol was used in 62% of bacteremia episodes in neutropenic patients. This protocol would have been appropriate in 85% of all neutropenic bacteremia episodes and 89% of episodes in febrile neutropenia patients compared with piperacillin/tazobactam (79%, P?=?0.13 and 76%, P?=?0.002, respectively) and imipenem (93%, P?=?0.004 and 92%, P?=?0.74, respectively). Isolation of bacteria resistant to the actual antibiotic treatment given was associated with higher mortality at one week and at 30 days.Conclusion
Common current antibiotic regimens provide similar coverage among febrile neutropenic patients, whereas broad spectrum antibiotic combinations maximize coverage among neutropenic patients. 相似文献5.
Marjan Wouthuyzen-Bakker Eduard Tornero Laura Morata Prashant V. Nannan Panday Paul C. Jutte Guillem Bori Greetje A. Kampinga Alex Soriano 《International journal of antimicrobial agents》2018,51(1):38-42
Objectives
The combination of a fluoroquinolone with rifampin is one of the cornerstones in the treatment of prosthetic joint infections (PJI) caused by staphylococci. Moxifloxacin is highly active against methicillin–susceptible Staphylococcus aureus (MSSA) and, therefore, is an attractive agent to use. However, several studies reported a lowering in serum moxifloxacin levels when combined with rifampin. The clinical relevance remains unclear. We determined the outcome of patients with early acute PJI caused by MSSA treated with either moxifloxacin/rifampin or levofloxacin/rifampin.Methods
Medical files of patients treated with moxifloxacin/rifampin (University Medical Centre Groningen) or levofloxacin/rifampin (Hospital Clinic Barcelona) were retrospectively reviewed (2005–2015). Treatment failure was defined as the need for revision surgery and/or suppressive therapy, death by infection or a relapse of infection during follow-up.Results
Differences in baseline characteristics between the two cohorts were observed, but prognostic parameters for failure, as defined by the KLIC-score (Kidney failure, Liver cirrhosis, Index surgery, C–reactive protein and Cemented prosthesis), were similar in the two groups (2.9 [1.5 SD] for the moxifloxacin group vs. 2.2 [1.2 SD] for the levofloxacin group [P?=?0.16]). With a mean follow-up of 50 months (36 SD) in the moxifloxacin group, and 67 months (50 SD) in the levofloxacin group (P?=?0.36), treatment was successful in 89% vs. 87.5%, respectively (P?=?0.89). None of the failures in the moxifloxacin group were due to rifampin– or moxifloxacin–resistant S. aureus strains.Conclusion
Our data indicate that moxifloxacin combined with rifampin is as clinically effective as levofloxacin/rifampin for early acute PJI caused by MSSA. 相似文献6.
Barbara A. Santevecchi Tiffeny T. Smith Shawn H. MacVane 《International journal of antimicrobial agents》2018,51(4):629-635
Background
Ceftazidime/avibactam is a newly approved β-lactam/β-lactamase inhibitor combination with activity against antibiotic-resistant Gram-negative organisms, including many carbapenem-resistant strains. Although this agent may offer a promising treatment option for serious infections with limited alternatives available, clinical experience with ceftazidime/avibactam in treatment of infections caused by multidrug-resistant Gram-negative organisms other than Klebsiella pneumoniae is limited.Methods
A retrospective case series was performed to evaluate patients treated with ceftazidime/avibactam for infections caused by organisms other than K. pneumoniae at our institution over a 1-year period. Patients aged at least 18 years who received at least one dose of ceftazidime/avibactam were eligible for inclusion. Clinical and microbiological data were collected, and investigators assessed adverse effects, microbiological cure, clinical success, and 30-day in-hospital mortality following completion of ceftazidime/avibactam therapy.Results
Ten patients were included. The most common index infection was pneumonia (n?=?6/13, 46%) and the most frequently isolated organism was Pseudomonas aeruginosa (n?=?8/21, 38%). Fifty percent of patients received ceftazidime/avibactam as monotherapy. Microbiological cure was achieved in 67% (n?=?6/9) of patients and 70% (n?=?7/10) of patients met criteria for clinical success. The 30-day in-hospital mortality rate was 30%. No patients experienced adverse events because of ceftazidime/avibactam therapy.Conclusions
For infections caused by antibiotic-resistant Gram-negative organisms other than K. pneumoniae, clinical and microbiological success rates for patients treated with ceftazidime/avibactam were similar to those that have been reported for K. pneumoniae. Ceftazidime/avibactam appears to be a promising treatment option for infections caused by a variety of resistant Gram-negative organisms when limited alternatives exist. 相似文献7.
Takeshi Ide Yoshio Takesue Kazuro Ikawa Norifumi Morikawa Takashi Ueda Yoshiko Takahashi Kazuhiko Nakajima Kenta Takeda Shinichi Nishi 《International journal of antimicrobial agents》2018,51(5):745-751
Purpose
The purpose of this study was to identify the optimum dosing regimen of linezolid in sepsis patients with and without renal dysfunction and sepsis patients on low-dose continuous renal replacement therapy (CRRT) using a pharmacokinetics/pharmacokinetics (PK/PD) approach.Methods
Sepsis patients with and without renal dysfunction (creatinine clearance?<?50?mL/min), and sepsis patients on low-dose CRRT (dose: 800?mL/h) were studied. The PK data were modeled using a two-compartment model, and then used for simulation. The target PK/PD was the 24-h area under the concentration-time curve to minimum inhibitory concentration ratio of?≥?80. Dosing regimens were evaluated using cumulative fraction of response (CFR) and safety probability (trough level?<?7?µg/mL) by Monte Carlo simulation.Results
Twenty-seven patients, including 8 patients with preserved renal function, 9 patients with renal dysfunction, and 10 patients on CRRT, were studied. The proposed regimen to attain CFR?≥?90% was 800?mg every 12?h (safety probability 82.4%) for patients with preserved renal function. By contrast, the target CFR was attained with a decreased regimen in patients with renal dysfunction and those on CRRT [600?mg every 24h (safety probability 68.6%) and 800?mg every 24h (42.1%)].Conclusions
We identified different dosage strategies to achieve target linezolid concentrations according to renal function and use of CRRT in sepsis patients. Because of unassured safety probability in patients without preserved renal function, dosing regimens should be adjusted based on the therapeutic drug monitoring. 相似文献8.
Short-term low-dose pantoprazole-based triple therapy for cure of Helicobacter pylori infection in duodenal ulcer patients 总被引：2，自引：0，他引：2
Pazzi Scagliarini Gamberini Matarese Rizzo & Gullini 《Alimentary pharmacology & therapeutics》1998,12(8):731-734
Background:
The eradication of Helicobacter pylori infection has been achieved using various therapy regimens, but the efficacy of the proton-pump inhibitor pantoprazole as part of these regimens has not yet been widely tested.Aim:
To evaluate the efficacy and tolerability of a 1-week low-dose pantoprazole-based triple therapy in patients with H. pylori-positive duodenal ulcer.Methods:
In an open single-centre prospective study, 71 patients with endoscopically proven active duodenal ulcer and H. pylori infection received pantoprazole 40 mg o.m. for 4 weeks, and during the first week a combination antimicrobial treatment comprising tinidazole 500 mg b.d. plus clarithomycin 250 mg b.d. H.?pylori eradication was defined as concordant negative histology and rapid urease test performed at endoscopy 4–6 weeks after the end of treatment, confirmed 4 weeks later by 13C-urea breath test.Results:
Sixty-six patients (93%) completed the trial and five patients were lost to follow-up. H. pylori infection was cured in 61 out of the 66 patients who completed the trial (per-protocol analysis: 92.4%, 95% CI: 83.2–97.5%; intention-to-treat analysis: 85.9%, 95% CI: 75.7–93.0%). At final endoscopy, 65 out of 66 patients had healed ulcer (98.5%). Mild adverse events occurred in six patients (9.1%).Conclusions:
One-week low-dose pantoprazole-based triple therapy is a simple, effective and well-tolerated regimen for ulcer healing and H. pylori eradication in patients with duodenal ulcer.9.
10.
Konstantinos Z. Vardakas Andreas D. Mavroudis Maria Georgiou Matthew E. Falagas 《International journal of antimicrobial agents》2018,51(4):535-547
Background
To evaluate whether intravenous colistin in combination with other antibiotics (IVCC) is associated with lower mortality compared with intravenous colistin monotherapy (IVCM), and to identify factors influencing study outcomes.Methods
PubMed and Scopus were searched up to November 2016. Studies were included if they evaluated adult patients with multi-drug-resistant (MDR) or extensively-drug-resistant Gram-negative infections, and reported comparative mortality data (adjusted and unadjusted) for patients receiving IVCC vs. IVCM. Random effects meta-analyses were performed.Findings
Thirty-two studies (29 observational, three randomized) were included. The overall quality of data was low to very low, and studies were characterized by the lack of adjusted data. The majority of studies were not designed to evaluate the outcome of the meta-analysis, and focused mainly on infections due to Acinetobacter baumannii and Klebsiella pneumoniae. Colistin was administered at variable doses, with or without a loading dose, and in combination with several antibiotics. Overall, IVCC was not associated with lower mortality than IVCM [32 studies, 2328 patients, risk ratio (RR) 0.91, 95% confidence interval (CI) 0.81–1.02, I2 8%]. A significant difference was observed in favour of IVCC when high-dose (>6 million international units) colistin was used (RR 0.80, 95% CI 0.69–0.93), in studies conducted in Asia (RR 0.82, 95% CI 0.71–0.95), in patients with bacteraemia (RR 0.75, 95% CI 0.57–0.98) and in patients with acinetobacter infections (RR 0.88, 95% CI 0.78–1.00).Interpretation
Overall, low-quality data suggest that IVCC did not lower mortality in patients with MDR Gram-negative infections. However, there is some evidence for a benefit observed with high intravenous doses of colistin. 相似文献11.
Background
Rates of Clostridium difficile diarrhoea have recently been rising, with the elderly being at highest risk.Aim
To compare the incidence of C. difficile colonization and diarrhoea in elderly patients treated for presumed infection with either empirical cefotaxime (CTX) or piperacillin–tazobactam (PT).Methods
A prospective, ward-based, crossover study was carried out on two well-matched care of the elderly wards at a UK tertiary care hospital, in patients requiring empirical broad-spectrum antibiotic treatment.Results
There was a highly significant increased incidence of C. difficile colonization (26/34 vs. 3/14, P = 0.001) and diarrhoea (18/34 vs. 1/14, P = 0.006) in patients who received CTX as opposed to PT. DNA fingerprinting suggested that most infections arose from strains acquired from the hospital environment.Conclusions
Elderly patients are significantly less likely to develop C. difficile diarrhoea after treatment with PT than after CTX. The source of C. difficile appears to be predominantly from the ward environment.12.
J. Nicholas O&#x;Donnell Nathaniel J. Rhodes Cristina M. Miglis Lejla Catovic Jiajun Liu Cameron Cluff Gwendolyn Pais Sean Avedissian Medha D. Joshi Brooke Griffin Walter Prozialeck Anil Gulati Thomas P. Lodise Marc H. Scheetz 《International journal of antimicrobial agents》2018,51(2):239-243
Background
Although the exposure-dependent efficacy thresholds of vancomycin have been probed, less is known about acute kidney injury (AKI) thresholds for this drug. Sensitive urinary biomarkers, such as kidney injury molecule 1 (KIM-1), have shown high sensitivity and specificity for vancomycin-associated AKI. The aims of the study were to determine if there were dose–response curves with urinary KIM-1, and to evaluate the impact of therapy duration and sex on observed relationships.Methods
A systematic review was conducted via PubMed/MEDLINE. Data were compiled from preclinical studies that reported individual subject data for urinary KIM-1 concentrations, vancomycin dose (mg/kg), duration of treatment, and sex. Sigmoidal Hill-type models were fit to the individual dose-response data.Results
A total of 15 studies were identified, 6 of which reported vancomycin dose and KIM-1 data. Of these, three included individual animal-level data suitable for analysis. For all pooled rats, increasing total daily vancomycin doses displayed a dose-response curve with urinary KIM-1 concentrations (50% maximal toxic response=130.4?mg/kg/day). Dose-response curves were shifted left for females vs. males (P?=?0.05) and for long (i.e. ≥7 days) vs. short (i.e. <4 days) duration of vancomycin therapy (P=0.02).Conclusions
The collective findings demonstrate a clear dose–response relationship between vancomycin dose and AKI. As these analyses focused exclusively on dose-response relationships, additional preclinical data are needed to more clearly define vancomycin exposures that predict the onset of AKI. 相似文献13.
SAVARINO ZENTILIN BISSO PIVARI BILARDI BIAGINI MELE MANSI TERMINI VIGNERI & CELLE 《Alimentary pharmacology & therapeutics》1999,13(1):43-47
Background:
Ranitidine bismuth citrate (RBC) co-prescribed with clarithromycin and metronidazole for 1 week has been shown to be an effective eradicating regimen for Helicobacter pylori.Aim:
To determine the optimal duration of this regimen.Methods:
A series of 165 dyspeptic patients were recruited for this randomized, open, parallel-group study. They were subdivided into three groups receiving RBC 400 mg b.d. plus clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. for three different periods (4, 7 and 10 days). H. pylori infection was assessed by the concomitant positivity of CLO-test and histology performed at the pre-entry endoscopy. The bacterium was considered eradicated on the basis of a negative 13C-urea breath test performed at least 28 days after the completion of treatment.Results:
The three subgroups were well matched and 16 patients dropped out of the study for many reasons (six in the 4-day, five in the 7-day and five in the 10-day treatment regimens). Intention-to-treat cure rates were 60%, 84% and 85%, and the per-protocol rates 67%, 92% and 94% in the 4-day, 7-day and 10-day treatment regimens, respectively. There was a significant difference, P = 0.003?0.006 on intention-to-treat and P = 0.001?0.002 on per protocol analysis between the 4-day and the 7-day and the 4-day and the 10-day periods, respectively. The 7-day and 10-day periods did not differ from each other. Side-effects were reported in 9%, 14% and 20% of the 4-, 7- and 10-day regimens. They led to stopping treatment in four cases (one in the 7-day and three in the 10-day period). There was no statistical difference among them.Conclusions:
Reducing the duration of RBC-based triple therapy to 4 days provides a low and unacceptable rate of H. pylori eradication. As there is no difference between 7 and 10 days of treatment, 1 week represents the optimal time period for this kind of treatment, based on RBC plus two antibiotics.14.
G. Massimo Claar Monaco C. Del Veccho Blanco Capurso Fusillo & Annibale 《Alimentary pharmacology & therapeutics》1998,12(5):463-468
Background
Non-steroidal anti-inflammatory drugs (NSAIDs) are strongly associated with gastroduodenal ulcers, and the management of patients with NSAID-associated ulcers represents a common clinical dilemma.Aim
To assess NSAID-associated ulcer healing during treatment with either standard (20 mg) or high dosage (40 mg) omeprazole.Methods
One hundred and sixty-nine patients chronically ingesting diclofenac, ketoprofen, indome-thacin or naproxen for osteoarthritis or rheumatoid arthritis, who had abdominal pain and an endoscopically proven gastroduodenal ulcer, were evaluated in a randomized, double-blind, dose regimen trial with omeprazole 20 mg o.m. (n = 81) or omeprazole 40 mg o.m. (n = 88). Ulcer healing was assessed endoscopically at 4 and 8 weeks in the case of unhealed ulcers. Patients continued their usual daily dose of anti-inflammatory medication throughout the study period.Results
One hundred and fifty-six patients completed the study (77 patients taking 20 mg omeprazole and 79 patients taking 40 mg omeprazole); 12 patients were lost during follow-up and one patient reported an adverse event. Cumulative ulcer intention-to-treat healing rates at 8 weeks were 88% (95% confidence interval (CI) = 79–95%) for the 20 mg omeprazole group and 96.2% (95% CI = 89–99%) for the 40 mg group, and 97.1% (95% CI = 90–100%) for the 20 mg omeprazole group and 98.6% (95% CI = 93–100%) for the 40 mg group by per protocol analysis. There were no statistically significant differences between the two groups. Symptom relief did not differ significantly between the two treatment groups.Conclusion
Both standard and high doses of omeprazole are equally safe and effective regimens for the treatment of NSAID-induced gastroduodenal ulcers when anti-inflammatory treatment is not discontinued.15.
Meta-analysis of somatostatin, octreotide and gabexate mesilate in the therapy of acute pancreatitis 总被引：16，自引：0，他引：16
Andriulli Leandro Clemente Festa Caruso Annese Lezzi Lichino Bruno & Perri 《Alimentary pharmacology & therapeutics》1998,12(3):237-245
Background:
Autodigestion of the pancreas, secondary to the activation of digestive enzymes, is the pathogenetic mechanism of acute pancreatitis (AP).Aim:
Clinical trials in which somatostatin (SS), octreotide (OCT) and gabexate mesilate (FOY) were used to treat patients with AP, were submitted to a meta-analytical evaluation. Five end-points were evaluated: early and overall mortality, patients with complications, complication rate, and patients who needed surgery.Results:
In mild AP, no agent proved of value. In severe AP, both SS and OCT were beneficial in improving the overall mortality: the odds ratios (OR) were, respectively, 0.36 (95% CI: 0.20–0.64, P = 0.001) and 0.57 (95% CI: 0.35–0.88, P = 0.006). FOY had no effect on either early or overall mortality, but was effective in improving complication rate (OR = 0.70, 95% CI: 0.56–0.88, P = 0.02), number of patients with complications (OR = 0.61, 95% CI: 0.41–0.91, P = 0.01), and number of cases submitted to surgery (OR = 0.60, 95% CI: 0.39–0.92, P = 0.01). SS and OCT had no effect on these latter outcomes.Conclusions:
Antisecretory agents, such as SS and OCT, are able to reduce mortality without affecting complications, whereas antiproteases, such as FOY, have no effect on mortality but do reduce complications. A trial exploring the efficacy of combining antisecretory agents with antiproteases would be of great benefit in patients with severe AP.16.
Background:
H2-receptor antagonists are becoming widely available as over-the-counter medications for the treatment of heartburn and excess gastric acidity.Aim:
To determine the effects of single low doses of ranitidine on intragastric acidity.Methods:
Intragastric pH was measured for 9 h after lunch in five studies involving 24 healthy male volunteers. Antacid was given to all subjects on day 1. They then received single oral doses of a study drug 45 min after lunch on four separate occasions: placebo and either ranitidine 25 mg, 75 mg or 125 mg were given double-blind according to a predetermined randomization schedule.Results:
During both of the post-dosing time periods (0–5 h and 5–9 h) there were significant decreases in integrated intragastric acidity for each ranitidine dose compared with placebo (P < 0.0001). There was a significant linear relationship between dose and integrated intragastric acidity with a greater decrease in acidity with increasing ranitidine doses (P < 0.0001). Compared with placebo, time with pH > 3 was significantly greater for ranitidine 75 mg and 125 mg (P < 0.001), but not ranitidine 25 mg. Results with the antacid were similar to placebo.Conclusions:
Using low doses of ranitidine (25, 75 or 125 mg) there was a dose-related decrease in intragastric acidity for 9 h after dosing. A single dose of antacid did not decrease intragastric acidity significantly.17.
Mearadji Straathof Biemond Lamers & Masclee 《Alimentary pharmacology & therapeutics》1998,12(11):1163-1169
Background:
Somatostatin affects gastrointestinal motility and secretion and visceral sensation, but little is known about its effects on the proximal stomach.Aim:
To evaluate the effects of somatostatin on proximal gastric motor function and perception of symptoms.Methods:
Six healthy subjects participated in two experiments performed in random order during continuous intravenous infusion of saline or somatostatin (250 μg/h). Proximal gastric motor function was evaluated using a barostat. We performed pressure and volume distensions and a barostat procedure (minimal distending pressure + 2 mmHg). Symptoms were evaluated at regular intervals using visual analogue scales (VAS).Results:
Neither minimal distending pressure nor gastric fundal tone were significantly different between somatostatin and saline. Pressure–volume curves during distensions were not influenced by somatostatin. However, phasic volume waves were significantly (P < 0.001) reduced by somatostatin, and somatostatin significantly (P < 0.05) reduced symptom perception of fullness and abdominal pressure during stepwise distensions.Conclusions:
Continuous infusion of somatostatin does not influence gastric compliance but it inhibits phasic volume waves and significantly reduces visceral perception.18.
S. Bruley Des Varannes Duquesnoy Mamet Slama Galmiche & Scarpignato 《Alimentary pharmacology & therapeutics》1998,12(11):1155-1161
Background:
Because of their tolerance and safety, low doses of H2-receptor antagonists are now increasingly used in some countries for self-care medication of gastro-oesophageal reflux symptoms.Aim:
The purpose of this randomized, double-blind, placebo-controlled, five-way crossover study was to determine and to compare the effects of low doses of ranitidine and cimetidine both on gastric pH and on oesophageal acid exposure.Methods:
Gastric and oesophageal pH were simultaneously monitored in 20 healthy subjects using two glass pH electrodes, after placebo and single doses of ranitidine 75 mg and cimetidine 200 mg (effervescent and tablet forms), for 4 h before and after a meal.Results:
During the fasting period, median gastric pH rose significantly with both drugs, but more rapidly with the effervescent forms; the oesophageal acid exposure was significantly decreased by all drug regimens. After the meal, although there was no significant difference in gastric pH values, oesophageal acid exposure was significantly decreased in comparison with placebo with both forms of ranitidine (P < 0.05), and also for ranitidine tablets in comparison with cimetidine tablets (P < 0.05).Conclusions:
Low doses of ranitidine and cimetidine increase gastric pH, with a more pronounced effect for ranitidine. Effervescent formulations of both drugs induce a slightly more rapid initial increase in pH than tablets. Ranitidine demonstrates a more prolonged effect than cimetidine and decreases oesophageal acid exposure monitored after a meal ingested 4 h after the drug intake.19.
Background:
In lactose maldigesters the ingestion of food which retards gastric emptying improves tolerance to lactose.Aim:
To study the effects of the pharmacological modification of gastric emptying on the speed of development of lactose-induced symptoms.Methods:
After an overnight fast, 18 lactose maldigesters were given, in a randomized double-blind study design at 1-week intervals, either propantheline (as bromide 15 mg), metoclopramide (as hydrochloride 10 mg) or placebo, in identical capsules, 60 min before ingesting 50 g lactose coloured with 1 g carmine dye (to measure gastrointestinal transit time). Gastrointestinal symptoms, urinary galactose excretion, and breath hydrogen and blood glucose concentrations were recorded.Results:
The propantheline-induced prolongation of gastric emptying improved tolerance to lactose, as measured by reduced area under the gastrointestinal symptom score curve 0–12 h, compared to placebo (by 26%) (P < 0.05) or metoclopramide (by 30%) (P < 0.05). The total hydrogen excretion AUC (180 min follow-up) increased by 15% after metoclopra- mide as compared with placebo (P = 0.18). Propantheline decreased this variable by 15% from placebo (P = 0.17). No significant differences in blood glucose, urinary galactose or gastrointestinal transit time were found.Conclusions:
In an oral lactose tolerance test, delaying gastric emptying with propantheline improved tolerance in lactose maldigesters, as measured by diminished gastrointestinal symptoms and reduced breath hydrogen concentration.20.
The effect of cisapride on dyspepsia symptoms and the electrogastrogram in patients with non-ulcer dyspepsia 总被引：6，自引：0，他引：6