Topical analgesia for the cutting of split-skin grafts: a multicenter comparison of two doses of a lidocaine/prilocaine cream

The topical analgesic effect of two doses of a local anesthetic cream (EMLA, Astra) in the harvesting of split-skin grafts was compared in a double-blind multicenter trial. A standardized area of 200 cm2 at the donor site of 78 patients was randomly treated with 30 or 60 gm of cream 2 to 5 hours before the operation. There was no difference in pain between the groups (p = 0.53). In each group, 92 percent of the patients rated the pain as either none or slight, and 8 percent rated it as either moderate or severe. In conclusion, with the application times of 2 to 5 hours used in this trial, a dose of 15 gm EMLA cream per 100 cm2 is sufficient to provide analgesia for the cutting of split-skin grafts.     

Optimal Dosage of Methylprednisolone for the Treatment of Sudden Hearing Loss in Geriatric Patients: A Propensity Score-Matched Analysis

We aimed to compare the treatment outcomes and the occurrence rates of adverse events associated with different steroid regimens in geriatric patients (aged 65 years or older) with unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). After thorough medical chart reviews of 109 patients with ISSNHL between May 2006 and December 2013, we performed a propensity score-matched analysis using previously known prognostic factors, steroid regimens, and other cointerventions. Patients were divided based on their steroid regimens into group I (which initially received 48 mg of methylprednisolone daily with a subsequently tapered dose) and group II (which initially received 24 mg of methylprednisolone daily with a subsequently tapered dose). We compared final hearing and the occurrence of adverse events between the two groups. As a result, 20 pairs of propensity score-matched patients (n = 40) were enrolled. Group I patients showed better final hearing levels compared with group II patients (42.00±22.35 dB and 57.38±26.40 dB, respectively), although this difference was marginally significant (p = 0.058). Based on the comparative analysis of each of the frequencies in the final audiograms, lower hearing thresholds at 2 KHz were observed in group I (p = 0.049). There was no significant difference in the occurrence of adverse effects between the two groups (p>0.05). In conclusion, conventional steroid regimens produced adverse event occurrence rates that were similar to those of low-dose treatment but may also have produced superior hearing recovery. The use of steroid dose reduction in geriatric patients with ISSNHL is not preferable to conventional steroid regimens.     

Comparison of different anaesthetic methodologies for sedation during in vitro fertilization procedures: effects on patient physiology and oocyte competence

The main goal of the present retrospective study is to compare four analgesic methodologies (EMLA cream, propofol, thiopental sodium, sevoflurane) for in vitro fertilization (IVF) oocyte retrieval. We found that most anaesthetic parameters were not significantly different among all treatments. In contrast, significant differences were revealed in all groups for total number of oocytes retrieved per patient, rate of mature oocytes at metaphase II stage (MII) and percentage of fertilization and embryo development. In the EMLA cream and thiopental sodium groups we observed the highest percentage of MII oocytes (P < 0.001). Fertilization rate in the EMLA and sevoflurane groups were similar but significantly higher than the propofol and thiopental sodium groups (P < 0.001). The highest rate of anomalous fertilization was observed in the propofol group. Rate of embryo development was similar in all groups but sevoflurane group had a lower percentage of good embryos. In conclusion, by comparing different anaesthetic techniques with different mechanisms of action and administration, potential negative effects of these drugs on the initial stages of human IVF procedure were revealed. Therefore, a local anaesthetic cream is proposed as an acceptable alternative option for anaesthesia during transvaginal oocyte retrieval.     

Topical anesthetic creams

Topical anesthetic creams have positive applications in plastic surgery. For certain procedures, they can replace injected local anesthetics. By replacing injections with a topical cream, the negative effects associated with injections, such as pain, needle anxiety, and edema at the surgical site, are eliminated. A variety of U.S. Food and Drug Administration-approved topical anesthetic creams are available for use; however, much care must be taken when prescribing and administering these drugs, as anesthetic creams compounded in nonstandard doses can result in severe toxicity and death. When used appropriately, topical anesthetic creams can provide a safe and effective alternative to other forms of anesthesia. This article provides an overview of topical anesthetic creams, including availability, composition, safety, and efficacy.     

A review of tribromoethanol anesthesia for production of genetically engineered mice and rats

Tribromoethanol (TBE) is easy and inexpensive to make in the laboratory from readily available reagents, requires no special equipment for its administration, and is not subject to federal or state drug enforcement agency regulations. Intraperitoneal (i.p.) injection of TBE results in the simple and rapid induction of short-term surgical anesthesia; however, recent adverse reports about the efficacy and safety of TBE make its continued routine use as a rodent anesthetic controversial. The authors review the history and use of TBE as an animal anesthetic and conclude that TBE should be relegated to acute terminal studies when administered i.p.     

The use of lignocaine-prilocaine local anaesthetic cream for pain-free venepuncture in laboratory animals

An assessment was made of the effects of topical application of a eutectic mixture of local anaesthetics (EMLA cream) in a number of species of laboratory animals. Application of EMLA cream enabled percutaneous insertion of catheters into the cephalic vein in dogs and cats and the marginal ear vein in rabbits without causing any detectable pain or discomfort. Application to the tail in rats prior to percutaneous cannulation of the lateral tail vein did not produce a significant reduction in the behavioural responses to venepuncture. EMLA cream represents a useful refinement of current techniques for intravenous injection in some species, and is especially valuable when the procedure is to be undertaken by an inexperienced operator.     

Does the Type of Anesthetic Technique Affect In-Hospital and One-Year Outcomes after Off-Pump Coronary Arterial Bypass Surgery?

Despite numerous previous studies, there is little data on the effects of anesthetics on clinical outcome after off-pump coronary arterial bypass grafting (OPCAB). Therefore, we retrospectively compared the effects of anesthetic choice on in-hospital major adverse events (MAEs) and one-year major adverse cardiovascular and cerebral events (MACCEs) in patients undergoing OPCAB. Electronic medical records were reviewed in 192 patients who received propofol-remifenanil total intravenous anesthesia (TIVA) and propensity score-matched 662 patients who received isoflurane anesthesia. The primary endpoints were in-hospital MAEs and one-year MACCEs. The components of in-hospital MAEs were in-hospital death, myocardial infarction (MI), coronary revascularization, stroke, renal failure, prolonged mechanical ventilation longer than 72 h, and postoperative new cardiac arrhythmia requiring treatment. One-year MACCEs was defined as a composite of all-cause mortality, MI, coronary revascularization, and stroke. There was no significant difference in risk of in-hospital MAEs (OR = 1.29, 95% CI = 0.88–1.88, P = 0.20) or one-year MACCEs (OR = 0.81; 95% CI = 0.46–1.42, P = 0.46) between the groups. The risk of postoperative new arrhythmia including new atrial fibrillation significantly increased in the TIVA group compared to the isoflurane anesthesia group (OR = 1.72, 95% CI = 1.12–2.63, P = 0.01). In conclusion, the choice between propofol-remifentanil TIVA and isoflurane anesthesia did not show differences in incidence of in-hospital MAEs or one-year MACCEs in patients undergoing OPCAB. However, further studies on the effects of anesthetics on development of in-hospital new arrhythmia will be needed.     

Effects of an anesthetic mixture of medetomidine,midazolam, and butorphanol in rats—strain difference and antagonism by atipamezole

An anesthetic mixture of medetomidine (MED), midazolam (MID), and butorphanol (BUT) has been used in laboratory animals. We previously reported that this anesthetic mixture produced closely similar anesthetic effects in BALB/c and C57BL/6J strains. We also demonstrated the efficacy of atipamezole (ATI), an antagonist of MED that produced quick recovery from anesthesia in mice. Anesthetics have various anesthetic effects among animal strains. However, the differences in the effects of anesthetic mixtures in rats are unclear. In the present study, we first examined effects of the abovementioned anesthetic mixture using three different rat strains: Wistar (WST), Sprague-Dawley (SD), and Fischer 344 (F344). Second, we examined how different dosages and optimum injection timing of ATI affected recovery from anesthesia in rats. We used the anesthetic score to measure anesthetic duration and a pulse oximeter to monitor vital signs. We found no significant differences in anesthetic duration among the three different strains. However, recovery from anesthesia in the SD strain took significantly longer than in the other strains. The antagonistic effects of ATI (0.15 mg/kg and 0.75 mg/kg) were equivalent when administered at 30 min after anesthetic mixture administration. The antagonistic effects of ATI 0.75 mg/kg were stronger than those of ATI 0.15 mg/kg at 10 min after anesthetic mixture administration. This anesthetic mixture is a useful drug that can induce similar anesthetic effects in three different strains and has an antagonist, ATI, that makes rats quickly recover from anesthesia. These results may contribute to the welfare of laboratory animals.     

Meta-analysis of randomized controlled trials on the efficacy of thoracic epidural anesthesia in preventing atrial fibrillation after coronary artery bypass grafting

ABSTRACT: BACKGROUND: Postoperative atrial fibrillation (POAF) is one of the most common complications in patients undergoing coronary artery bypass grafting (CABG). The goal of this meta-analysis was to evaluate the efficacy of thoracic epidural anesthesia (TEA) in preventing POAF in adult patients undergoing CABG. METHODS: MEDLINE and EMBASE were searched to identify randomized controlled trails in adult patients undergoing CABG who were randomly assigned to receive general anesthesia plus thoracic epidural anesthesia (GA + TEA) or general anesthesia only (GA). Two authors independently extracted data using a standardized Excel file. The primary outcome measure was the incidence of POAF. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95 % confidence intervals. RESULTS: Five studies involving 540 patients met our inclusion criteria. No significant difference in the incidence of POAF was observed between the two groups (risk ratio, 0.61; 95 % confidence interval, 0.33 to 1.12; P = 0.11), with significant heterogeneity among the studies (I2 = 73 %, P = 0.005). Sensitivity analyses by primary endpoint, methodological quality and surgical technique yielded similar results. CONCLUSIONS: The limited evidence suggests that TEA shows no beneficial efficacy in preventing POAF in adult patients undergoing CABG. However, the results of this meta-analysis should be interpreted with caution due to significant heterogeneity of the studies included. Thus, the potential infuence of TEA on the incidence of atrial fibrillation following CABG warrants further investigation.     

Readmissions after Hospitalization for Heart Failure,Acute Myocardial Infarction,or Pneumonia among Young and Middle-Aged Adults: A Retrospective Observational Cohort Study

Background

Patients aged ≥65 years are vulnerable to readmissions due to a transient period of generalized risk after hospitalization. However, whether young and middle-aged adults share a similar risk pattern is uncertain. We compared the rate, timing, and readmission diagnoses following hospitalization for heart failure (HF), acute myocardial infarction (AMI), and pneumonia among patients aged 18–64 years with patients aged ≥65 years.

Methods and Findings

We used an all-payer administrative dataset from California consisting of all hospitalizations for HF (n = 206,141), AMI (n = 107,256), and pneumonia (n = 199,620) from 2007–2009. The primary outcomes were unplanned 30-day readmission rate, timing of readmission, and readmission diagnoses. Our findings show that the readmission rate among patients aged 18–64 years exceeded the readmission rate in patients aged ≥65 years in the HF cohort (23.4% vs. 22.0%, p<0.001), but was lower in the AMI (11.2% vs. 17.5%, p<0.001) and pneumonia (14.4% vs. 17.3%, p<0.001) cohorts. When adjusted for sex, race, comorbidities, and payer status, the 30-day readmission risk in patients aged 18–64 years was similar to patients ≥65 years in the HF (HR 0.99; 95%CI 0.97–1.02) and pneumonia (HR 0.97; 95%CI 0.94–1.01) cohorts and was marginally lower in the AMI cohort (HR 0.92; 95%CI 0.87–0.96). For all cohorts, the timing of readmission was similar; readmission risks were highest between days 2 and 5 and declined thereafter across all age groups. Diagnoses other than the index admission diagnosis accounted for a substantial proportion of readmissions among age groups <65 years; a non-cardiac diagnosis represented 39–44% of readmissions in the HF cohort and 37–45% of readmissions in the AMI cohort, while a non-pulmonary diagnosis represented 61–64% of patients in the pneumonia cohort.

Conclusion

When adjusted for differences in patient characteristics, young and middle-aged adults have 30-day readmission rates that are similar to elderly patients for HF, AMI, and pneumonia. A generalized risk after hospitalization is present regardless of age. Please see later in the article for the Editors'' Summary     

Contribution from geriatric medicine within acute medical wards.

In 1977 a scheme of attachment to acute medical wards of consultants in geriatric medicine and associated junior medical staff was instituted in a large Edinburgh teaching hospital. The effect on admissions of patients aged 65 and over was examined for comparable periods before and during this arrangement. Mean and median stays were reduced for both sexes but more noticeably for women. The mean stay for all women aged over 65 was reduced from 25 to 16 days and for women aged over 85 from 50 to 19 days. The proportion staying under two weeks was significantly increased in both sexes, and the proportion discharged home also increased, correspondingly fewer patients being transferred to convalescent wards. These changes were not accompanied by increased transfers to the geriatric department, and probably the skills and extra resources available to the geriatric service were the factors mainly responsible for the changes in performance.     

Efficacy and Safety of Ideglira in Older Patients with Type 2 Diabetes

Objective: The efficacy and safety of insulin degludec/liraglutide (IDegLira) in older patients has not yet been reported. This analysis aimed to evaluate the efficacy and safety of IDegLira in patients aged ≥65 years.Methods: A post hoc analysis compared results of patients aged ≥65 versus <65 years from DUAL II, III, and V. These were 26-week, phase 3, randomized, twoarm parallel, treat-to-target trials in patients already taking injectable glucose-lowering agents. We evaluated 311 patients aged <65 and 87 patients aged ≥65 years from DUAL II, 326 patients <65 years and 112 patients ≥65 years from DUAL III, and 412 patients <65 years and 145 patients ≥65 years from DUAL V. Patients were randomized to IDegLira or insulin degludec (DUAL II), IDegLira or unchanged glucagon-like peptide 1–receptor agonist (GLP-1RA) (DUAL III), or IDegLira or IGlar U100 (DUAL V).Results: In patients ≥65 years, hemoglobin A1C decreased to a greater extent with IDegLira than with comparators (estimated treatment differences, -1.0% &lsqb;-1.5; -0.6]_{95% confidence interval &lsqb;CI]}, -0.8% &lsqb;-1.0; -0.5]_{95% CI}, and -0.9% &lsqb;-1.3; -0.6]95%CI) for DUAL II, V, and III, respectively; all P<.001). These mirrored results of patients <65 years of age. Hypoglycemia rates were lower with IDegLira versus basal insulin and higher versus unchanged GLP-1RA (estimated rate ratios, 0.5 &lsqb;0.2; 1.6]_{95% CI} &lsqb;P = .242]; 0.3 &lsqb;0.1; 0.5]_{95% CI} &lsqb;P<.001], and 11.8 &lsqb;3.3; 42.8]_{95% CI} &lsqb;P<.001] for DUAL II, V, and III, respectively).Conclusion: Patients aged ≥65 years on basal insulin or GLP-1RA can improve glycemic control with IDegLira, and it is well tolerated overall.Abbreviations: A1C = hemoglobin A1C; AE = adverse event; CI = confidence interval; Degludec = insulin degludec; EOT = end of trial; ETD = estimated treatment difference; FPG = fasting plasma glucose; GLP-1RA = glucagon-like peptide 1 receptor agonist; IDegLira = insulin degludec/liraglutide; IGlar U100 = insulin glargine 100 U/mL; SU = sulfonylurea; T2D = type 2 diabetes     

Adjunctive subantimicrobial dose doxycycline in the management of institutionalised geriatric patients with chronic periodontitis

Objective: To assess the efficacy of subantimicrobial dose doxycycline (SDD; 20 mg doxycycline twice daily) as an adjunct to scaling and root planing (SRP) in the treatment of moderate‐severe chronic periodontitis (CP) in institutionalised elderly patients aged 65 years or older. Background: Previous studies have shown that SDD is of clinical benefit in the treatment of CP. However, the benefits of SDD in geriatric populations (65+ years) have not been determined. Material and methods: A 9‐month, double‐blind, randomised, placebo‐controlled pilot study was conducted. 24 institutionalised geriatric patients (65 years or older) with evidence of CP manifested by baseline clinical attachment levels (CAL) 5–9 mm, probing depths (PD) 4–9 mm and bleeding on probing (BOP) were recruited. At baseline, patients were treated by a standardised episode of SRP, and randomised to receive either adjunctive SDD or placebo. Full mouth PD and CAL were measured using the manual UNC‐15 periodontal probe at 3, 6, and 9 months post‐baseline to assess the response to treatment. Periodontal sites were stratified by baseline PD value: sites with PD 4–5 mm were considered moderately diseased and sites with PD ≥6 mm severely diseased. Results: The SRP + placebo resulted in PD reductions similar to those reported previously in the literature. At all time‐points and in both moderate and deep sites, SRP + SDD resulted in significantly greater PD reductions relative to baseline than SRP + placebo. At month 9, in moderate sites, mean PD reductions of 1.57 ± 0.11 mm were reported in the adjunctive SDD group, compared with 0.63 ± 0.11 mm in the adjunctive placebo group (p < 0.001). In deep sites at month 9, mean PD reductions of 3.22 ± 0.29 mm were reported in the adjunctive SDD group, compared with 0.98 ± 0.31 mm in the adjunctive placebo group (p < 0.05). Similar improvements were observed for CAL in the SDD group compared with the placebo group. Significantly lower BOP scores were also recorded at month 9 in the SDD group (7.5%) compared with the placebo group (71.2%) (p < 0.01). Conclusion: SDD used as an adjunct to SRP provides significant benefit for elderly patients with CP compared with SRP alone.     

全麻药物对神经发育影响的争鸣

每年有大量的婴幼儿在全身麻醉下接受各种检查和治疗,麻醉药物的安全问题也成为人们日益关注的问题,全麻药物作用于发育期大脑是否会产生持续性不可逆损伤这一问题,被学者所担忧。虽然动物研究提示了全麻药物具有神经毒性,但临床研究结论并不一致,需要有更多的研究予以探索,并通过合理的用药手段、保护手段,将麻醉药品的副作用降低到最低。本文从基础研究和临床研究方面,简述了当前全身麻醉药对神经发育影响的研究现状,介绍了现有研究的成果和局限性。分析了全麻药物神经毒性可能存在的时间依赖性和剂量依赖性。目前更多的研究趋向于单次、相对短时间的麻醉下手术对神经发育影响很小,未来期待更多的研究予以探索全麻药物神经毒性作用,特别是大剂量重复麻醉暴露对发育期神经的生长影响,从而更好地指导临床治疗。     

The reasons for tooth loss in geriatric patients attending two surgical clinics in Jerusalem,Israel.

Abstract Objectives Numerous studies around the world have been conducted in order to understand the reasons for tooth extractions in various age groups. Most studies have dealt with the general adult population but little attention has been paid to the elderly population. In Israel, as in most of the western countries, the elderly population is growing rapidly and thus demands for its dental needs are also increasing. In order to meet the dental requirements of the geriatric population, data on the main reasons of tooth mortality have been collected. Design Retrospective analysis of reasons for extraction divided into three categories: caries, periodontal disease and “other’’. Subjects The files of 302 consecutive elderly patients aged 65-95 years attending for extraction. The cause for tooth extraction was gathered from the written diagnosis described by the operator as well as from radiographs. Setting Two surgical clinics in Jerusalem serving low income residents. Results Results indicated that 30% of the extractions were due to caries, 65% were due to periodontal disease and only 6.4% related to “other’’ reasons. In both, males and females, periodontal disease was the major cause for tooth loss yet, females exhibited more extractions due to caries than males (35%vs 23% respectively). A relatively high incidence of tooth loss was documented for the 85+ age group. Of the teeth that were extracted, incisors and molars were equally the most frequent (29%) followed by premolars (26%) and canines (17%). Premolars were the teeth most frequently extracted out of the teeth removed due to caries (32%) whereas incisors were the most frequently removed within the group of teeth extracted due to periodontal disease (31%). Conclusions The results of this study point to the importance of prevention and treatment of dental diseases, particularly periodontal disease, in adults aged 0 years and above in order to prevent tooth loss in their later years.     

腰硬联合麻醉与局麻下施实吻合器痔上黏膜环切术麻醉效果对照研究

摘要目的：探讨局麻与腰硬联合麻醉在环状脱垂痔患者中的麻醉效果和安全性。方法：运用随机数字表法将2010年5月~2012年5月在我院治疗行吻合器痔上黏膜环切术的154例环状脱垂痔患者分为A组和B组,A组患者在腰硬联合麻醉下行吻合器痔上黏膜环切术治疗,B组患者在局麻下行吻合器痔上黏膜环切术治疗,比较两组患者麻醉效果和安全性。结果：B组患者术后15分钟、1小时、2小时、4小时和8小时视觉模拟评分（VAS）明显低于A组患者,差异有统计学意义（P〈O．05）,B组患者在恶心呕吐、皮肤瘙痒和尿潴留发生率明显低于A组,差异有统计学意义（P〈O．05）,而且B组患者对手术满意度明显高于A组,差异有统计学意义（P〈O．05）。结论：局麻下行吻合器痔上黏膜环切术治疗环状脱垂痔麻醉效果好,具有安全高效、不良反应少和疼痛程度轻等特点。     

Temporal Variations in Transcutaneous Passage of Drugs: The Example of Lidocaine in Children and in Rats

Because a eutectic mixture of lidocaine and procaine (EMLA cream) is used to treat pain in children who are undergoing venipuncture for screening clinical presurgery laboratory tests, this study was designed to investigate the influence of the time of application of EMLA cream on lidocaine transcutaneous absorption in children. The same phenomenon was also studied in rats. Local application of EMLA (right and left cubital fossae) was performed 1 hour before venipuncture in two groups of children (0.5 g/kg body weight at two sites), at 08:15 or 16.15 h; blood samples were performed 1 h later. Two groups of five rats each received 12 mg/kg lidocaine at 07:30 or 19.30 h by application to the back skin. Blood samples were collected 0.5, 1, 1.5, 2, 3, and 4 h after application. Plasma lidocaine levels were assayed according to an immunoenzymatic method (Abbott). Our data indicate that the lidocaine plasma levels were significantly different: higher in the evening for the children or in the morning for the rats. The plasma level of the local anesthetics (LA) represents an elimination route and thus may be inversely correlated to the skin amount of the LA.     

Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised,double blind,parallel group study

Objective To explore the efficacy and safety of fluticasone propionate, cream and ointment, applied twice weekly in addition to maintenance treatment with emollients, in reducing the risk of relapse of chronic recurrent atopic dermatitis.Design Randomised, double blind, parallel group study of 20 weeks'' duration.Setting Dermatology outpatient clinics (6 countries, 39 centres).Participants Adult (aged 12-65) patients with moderate to severe atopic dermatitis who were experiencing a flare.Methods Participants applied fluticasone propionate (0.05% cream or 0.005% ointment; once or twice daily) regularly for four weeks to stabilise their condition. The patients whose disease was brought under control then continued into a 16 week maintenance phase, applying emollient on a daily basis with a bath oil as needed and either the same formulation of fluticasone propionate or its placebo base (emollient alone) twice weekly to the areas that were usually affected.Main outcome measure Time to relapse of atopic dermatitis during maintenance phase.Results 376 patients entered the stabilisation phase, and 295 continued into the maintenance phase. After 16 weeks in the maintenance phase, the disease remained under control in 133 patients (87 using fluticasone propionate twice weekly, 46 using emollient alone), 135 (40 fluticasone propionate, 95 emollient) had experienced a relapse, and 27 had discontinued. Median time to relapse was six weeks for emollient alone compared with more than 16 weeks for additional fluticasone propionate. Patients who applied fluticasone propionate cream twice weekly were 5.8 times less likely (95% confidence interval 3.1 to 10.8, P < 0.001) and patients using fluticasone propionate ointment 1.9 times less likely (1.2 to 3.2, P=0.010) to have a relapse than patients applying emollient alone. The groups showed no differences in adverse events.Conclusion After atopic dermatitis had been stabilised the addition of fluticasone propionate twice weekly to maintenance treatment with emollients significantly reduced the risk of relapse.     

Determination of anesthetic molecule environments by infrared spectroscopy. II. Multiple sites for nitrous oxide in proteins, lipids, and brain tissue

The presence of molecules of the general anesthetic nitrous oxide (N2O) in oils, esters, proteins, red cells, cream, lipid vesicles, and brain tissue upon exposure to the gas was observed by infrared spectroscopy. Analysis of the N-N-O antisymmetric stretch band reveals a distribution of N2O molecules among several sites of differing polarity in these solutions and tissues. The sensitivity of the band intensity and frequency to the number and strength of the dipoles in the solvating molecules is demonstrated by the resolution of N2O-ester and N2O-alkane interactions in acetic acid ethyl ester and oleic acid methyl ester. In all aqueous solutions and in all tissues a population of N2O molecules in water is observed. At least two sites of N2O-protein interaction are observed in purified hemoglobin A and packed red cells; multiple N2O sites may also be present in bovine serum albumin. Two sites of N2O-lipid interaction are observed in whipping cream and in an aqueous suspension of phosphatidylcholine vesicles. The sites providing the least polar immediate environment to N2O in hemoglobin, cream, and vesicles give similar band frequencies to those found in pure alkane solvents. Infrared spectra of bovine brain tissue, upon exposure to N2O, show N2O molecules present in water and in two less-polar environments. Analysis of spectra of N2O in cerebellum tissue removed from a dog under halothane-N2O anesthesia reveals, in addition to N2O in water, a single population of N2O molecules in an alkane-like environment. Infrared spectroscopy provides a unique means of probing the structure of the environment of N2O and should prove useful in correlating anesthetic potency with anesthetic environment under physiological conditions.     

Efficacy of 2-week, second-line Helicobacter pylori eradication therapy using rabeprazole, amoxicillin, and metronidazole for the Japanese population

Background: Following the failure of first‐line Helicobacter pylori eradication therapy using a proton pump inhibitor, amoxicillin, and clarithromycin, second‐line therapy is conducted for 1 week using metronidazole instead of clarithromycin in Japan. Recent studies indicate that metronidazole‐containing therapy has a higher eradication rate with prolonged treatment duration, even with metronidazole resistance. The aim of this study was to reveal the efficacy of 2‐week metronidazole‐containing second‐line therapy. Methods: Eighty‐two consecutive outpatients who had failed in the first‐line eradication therapy were enrolled and second‐line therapy was initiated with 10 mg rabeprazole, 750 mg amoxicillin, and 250 mg metronidazole twice daily. After they had been screened by hematological examination 1 week after initiation, the treatment was continued for 2 weeks after initiation in patients without hematological abnormality. Cure was essentially confirmed by the urea breath test. Results: After one patient was lost, hematological examination showed elevated serum aminotransferase in 14 of 81 patients. Although it was mild without clinical issues, they were ethically excluded from this study. In the remaining 67 patients and the lost patient, the eradication rate with 2‐week therapy was 65/68 (96%, 95% confidence interval: 88–98%) by intention to treat analysis and 65/65 (100%, 94–100%) by per protocol analysis. The main adverse event was soft stools (39%), and no serious adverse event was observed. Conclusion: This 2‐week metronidazole‐containing second‐line therapy provides high efficacy in Japan where metronidazole resistance is rare.