High incidence of autoimmune gastritis in patients misdiagnosed with two or more failures of H. pylori eradication.

BACKGROUND: Although autoimmune gastritis (AIG) is generally considered relatively rare, we frequently encounter AIG among patients at to our hospital who have experienced at least two episodes of Helicobacter pylori eradication failure. AIMS: We investigated the incidence of AIG in consecutive patients who consulted our department for H. pylori eradication with reference to eradication history. METHODS: A total of 404 consecutive patients who visited the H. pylori-specific out-patient unit of our hospital from June 2015 to June 2017 were enrolled. Of these, 137 were treatment-naive, 47 had failed treatment once (single failure), and 220 had failed treatment twice or more (multiple failures) by 13 C-UBT. Gastroscopy was performed in all patients. Culture tests of gastric mucosal samples were performed for H. pylori and other bacteria positive for urease activity. Anti-parietal cell antibody (APCA) was measured. Patients with severe atrophy in the gastric corpus and positivity for APCA were diagnosed as having AIG. RESULTS: A total of 43 patients were diagnosed as having AIG, of whom two were treatment-naive (1.5%, 2/137), 1 failed eradication once (2.1% 1/47), and 40 failed treatment at least twice (18.2%, 40/220). The incidence of AIG was significantly higher in the multiple failure group than in the single failure or treatment-naive groups. Urease-positive bacteria, such as Klebsiella pneumoniae and alpha-streptococcus, were identified in 33 of the 35 AIG patients who underwent culture testing. CONCLUSION: AIG patients were often misdiagnosed as refractory to eradication therapy, probably because achlorhydria in AIG might allow urease-positive bacteria other than H. pylori to colonise the stomach, causing positive 13 C-UBT results.

Potent acid inhibition by vonoprazan in comparison with esomeprazole, with reference to CYP2C19 genotype.

BACKGROUND: Acid inhibitory effects of proton pump inhibitors (PPIs) are influenced by CYP2C19 genotype. In contrast, the potent acid inhibition of vonoprazan is not influenced by CYP2C19 genotype. AIM: To compare the acid inhibitory effects of vonoprazan and esomeprazole in relation to CYP2C19 genotype. METHODS: Twenty-eight healthy Japanese volunteers [7 CYP2C19 poor metabolisers (PMs), 11 intermediate metabolisers (IMs) and 10 rapid metabolisers (RMs)] received four different regimens in a randomised crossover manner: (i) vonoprazan 20 mg twice daily (b.d.), (ii) vonoprazan 20 mg daily, (iii) esomeprazole 20 mg b.d. and (iv) esomeprazole 20 mg daily. The timing of each dosing was 1 h before a meal. Twenty-four-hour intragastric pH monitoring was performed on day 7 on each regimen. RESULTS: In the overall genotype group, pH ≥4 holding time ratios (pH 4 HTRs) with vonoprazan b.d., vonoprazan daily, esomeprazole b.d. and esomeprazole daily were 100%, 95%, 91%, and 68% respectively. pH 5 HTRs were 99%, 91%, 84% and 54% respectively. Vonoprazan b.d. potently suppressed acid for 24 h, and was significantly superior to other regimens irrespective of CYP2C19 genotype. Vonoprazan daily was equivalent to esomeprazole b.d. in IMs and PMs, but superior in RMs. CYP2C19 genotype-dependent differences were observed in esomeprazole daily but not in vonoprazan b.d. or daily. CONCLUSION: Vonoprazan 20 mg b.d. inhibits acid irrespective of CYP2C19 genotype, more potently than esomeprazole 20 mg b.d., pH 4 and 5 holding time ratios reached 100% and 99%, respectively.

Anomalous doping variation of the nodal low-energy feature of superconducting (Bi,Pb)2(Sr,La)2CuO(6+δ) crystals revealed by laser-based angle-resolved photoemission spectroscopy.

The nodal band dispersion in (Bi,Pb)(2)(Sr,La)(2)CuO(6+δ) (Bi2201) is investigated over a wide range of doping by using 7-eV laser-based angle-resolved photoemission spectroscopy. We find that the low-energy band renormalization ("kink"), recently discovered in Bi(2)Sr(2)CaCu(2)O(8+δ) (Bi2212), also occurs in Bi2201, but at a binding energy around half that in Bi2212. Surprisingly, the coupling energy dramatically increases with a decrease of carrier concentration, showing a sharp enhancement across the optimal doping. These properties (material and doping dependence of the coupling energy) demonstrate the significant correlation among the mode coupling, the energy gap close to the node, and the strong electron correlation. Our results suggest forward scattering arising from the interplay between the electrons and in-plane polarized acoustic phonon branch as the origin of the low-energy renormalization.

Factors that contribute to faecal cyclooxygenase-2 mRNA expression in subjects with colorectal cancer.

BACKGROUND: We previously reported that a faecal cyclooxygenase-2 (COX-2) mRNA assay was useful for identifying colorectal cancer (CRC). This study sought to investigate the factors that contribute to faecal COX-2 mRNA expression in subjects with CRC. METHODS: The study cohort comprised 78 patients with CRC and 36 control subjects. The expressions of COX-2, beta-2-microglobulin (B2M), carcinoembryonic antigen (CEA), E-cadherin (E-cad), and CD45 mRNA in faeces and COX-2 mRNA expression in tissue were determined by quantitative real-time RT-PCR. RESULTS: The level of faecal expression of COX-2 mRNA in CRC was significantly higher than that in controls. A significant correlation was found between faecal COX-2 mRNA expression and faecal B2M, CEA, E-cad, or CD45 mRNAs, markers of exfoliated total cells, colonocytes, and leukocytes, respectively. A significant correlation was found between the expression of COX-2 mRNA in faeces and tumour surface area, COX-2 mRNA expression in primary tumour. There was no difference in faecal COX-2 mRNA expression between proximal CRC and distal CRC. CONCLUSION: COX-2 mRNA expression in faeces seems to originate from tumour lesion and to be affected by factors such as the number of exfoliated cells, exfoliation of inflammatory cells, COX-2 mRNA expression in tumour, and tumour size.

Epidural morphine injection after combined spinal and epidural anaesthesia.

BACKGROUND AND OBJECTIVE: Although combined spinal and epidural anaesthesia is efficient and easy to perform, the technique can be a double-edged sword having the potential risk that an increased flux of drugs across the meninges through the hole made in it may lead to severe adverse effects. The aim was to compare the incidence of adverse events when an epidural injection of morphine was given after combined spinal and epidural anaesthesia or after epidural anaesthesia. METHODS: Fifteen patients had an epidural catheter inserted at the L2-3 interspace, and then a spinal block administered via the L3-4 interspace. Another 15 patients only had an epidural catheter inserted. After the onset of spinal or epidural anaesthesia had been confirmed, morphine 2 mg was injected into the epidural space, and a continuous epidural infusion of morphine was started. At the end of the operation and at 4, 8 and 12 h after the administration of epidural morphine and on the next day, the following variables were examined: blood pressure, heart rate, respiratory rate, arterial blood-gas analysis, visual analogue scale pain scores, nausea/vomiting scores, and pruritus scores. RESULTS: In the study population, the epidural injection of morphine was not associated with a significantly higher incidence of adverse events when given after spinal anaesthesia than after epidural anaesthesia. CONCLUSIONS: The adverse effects associated with epidural morphine given after spinal anaesthesia did not increase significantly when a 27-G Whitacre needle was used. Thus, the morphine flux through the meningeal hole into the cerebrospinal fluid was trivial.

Clonidine premedication reduces maternal requirement for intravenous morphine after cesarean delivery without affecting newborn's outcome.

BACKGROUND AND OBJECTIVES: The alpha(2)-agonist clonidine has several benefits for patients undergoing surgery. During and after elective cesarean delivery (C-section), we assessed the condition of parturient and neonate when one half of the parturients were pretreated with oral clonidine. METHODS: Forty-six consenting parturients were studied in a randomized, double-blinded manner. Preanesthetic medication was atropine and famotidine with or without clonidine 4 microg/kg. After baseline measurements in parturients and fetuses, combined spinal and epidural anesthesia was established (1.6 mL of 0.5% tetracaine diluted with 10% dextrose in water). C-section was performed while breathing oxygen spontaneously (3 L/min) through a facemask. After delivery, neonates were assessed at 1 and 5 minutes, and the condition of mother and neonate was observed for 48 hours. RESULTS: Parturients receiving clonidine showed no hemodynamic instability during and after C-section, and while their visual analog scale (VAS) scores, verbal descriptive scale (VDS) scores, and sedation scores did not differ from those without clonidine, they needed significantly less patient-controlled analgesia (PCA) morphine for postoperative pain for the first 2 days (P < .01). Fetal heart rate, umbilical artery and vein pH and gas tensions, and the Apgar-scores of the newborns showed no intergroup differences. No neonatal depression or bradycardia was observed for 48 hours after delivery. CONCLUSION: The present results indicate that oral clonidine reduces the PCA morphine requirement after C-section without compromising the condition of the fetus or newborn. Further study including larger number of patients would be needed before we conclude that oral clonidine for parturients is safe for their newborns.

Differences in cardiovascular response to airway stimulation at different sites and blockade of the responses by lidocaine.

BACKGROUND: Mechanical stimulation of the airways elicits abrupt cardiovascular responses (CVR) in anesthetized humans. We examined a potential difference in such responses by comparing changes in heart rate (HR) and arterial blood pressure (AP) responses to mechanical stimulation of three different parts of the airways, as well as the effects of localized airway anesthesia with lidocaine on these responses. METHODS: After induction of general anesthesia, the larynx under laryngeal mask insertion (L, n = 20), the trachea-carina under tracheal intubation (T, n = 20), or the bronchus under bronchial intubation (B, N = 20) of each patient was mechanically stimulated in a similar manner. The same stimulation was repeated in 15 patients in each group after 5 ml of 4% lidocaine had been sprayed onto the part of the airway being stimulated. To test the systemic effect, intravenous lidocaine 1 mg/kg was given to five patients in each group, followed by the same airway stimulation. Consequent changes in HR and AP were continuously recorded and analyzed. RESULTS: Significant increases in HR and AP in response to airway tactile stimulation differed in magnitude according to the stimulated sites (L > T > or = B). These responses were completely blocked by topical application of lidocaine and partially blocked by intravenous lidocaine. CONCLUSIONS: We found that CVRs to tactile stimulation differ in their magnitude at three different sites within the airways, and localized anesthesia with lidocaine can abolish these responses in humans. The inhibition of lidocaine could be mainly due to direct blockade of the mechanoreceptors of the airways and partly to its systemic effect.

The effects of pentobarbital, isoflurane, and propofol on immediate-early gene expression in the vital organs of the rat.

General anesthetics are known to transiently increase the expression of messenger ribonucleic acids (mRNAs) of immediate-early genes in the brain. We investigated whether the expression of two immediate-early genes in vital organs were modulated by various anesthetics. Inhaled isoflurane (n = 20), intraperitoneal pentobarbital (n = 20), and IV propofol (n = 20) were administered to male Sprague-Dawley rats, and five from each group were decapitated at 5, 30, 60, or 120 min after the induction of anesthesia. Control, nonanesthetized rats (n = 5) were handled gently and then decapitated. Reverse transcriptase-polymerase chain reactions were performed on total RNA from samples of the brain, heart, liver, and kidney to detect the expressions of c-fos and c-jun mRNAs. As internal control, cyclophilin mRNA was amplified simultaneously. The products were separated by electrophoresis, and the optical density of the bands was quantified. The expression of c-fos mRNA was transiently increased in the brain, and more strikingly and for longer times, in the kidney with all three anesthetics; the expression of c-fos mRNA was decreased in the heart with isoflurane and pentobarbital and increased in the liver with isoflurane and propofol. The expression of c-jun mRNA was increased in the heart, liver, and kidney with isoflurane, increased in the heart and kidney with pentobarbital, increased in the heart, liver, and kidney with propofol, and decreased in the brain with pentobarbital. Our results suggest that the appropriate anesthetics to be used to anesthetize animals differ in accord with the target organs in which the expressions of immediate-early genes in response to stimuli were studied.

Localized airway anesthesia with lidocaine partially suppresses cardiovascular responses To lung inflation.

UNLABELLED: Lung inflation causes cardiovascular suppression via an increase in intrathoracic pressure and neural mechanisms. To examine the mechanisms involved, we mea-sured the heart rate (HR) and arterial blood pressure (AP) responses to lung inflation before and after spraying the bronchi with lidocaine to suppress airway reflex. Thirty women participated in the study. One group (n = 20, Group BT) had their tracheas intubated by using double-lumen tubes. The other group (n = 10, Group TT) received an ordinary endotracheal tube. They were all studied under general anesthesia by using nitrous oxide, isoflurane, and muscle relaxation after a thiopental induction. In each patient, airway pressure was increased for 3 s, and changes in HR and AP were measured. Lung inflation was repeated after 5 mL of 4% lidocaine had been sprayed into the main bronchi unilaterally in Group BT or bilaterally in Group TT. There were no significant differences in cardiovascular responses between left and right lung inflation with the pressure at 20 and 30 cm H(2)O. Both lungs inflated at 20 cm H(2)O caused an increase in HR with a significantly greater decrease in AP than with unilateral inflation. Anesthesia of the bronchi abolished the HR increase, but not the AP decrease. Lung inflation at 30 cm H(2)O caused significant decreases in HR and AP which were not affected with topical anesthesia. These results indicate that the cardiovascular responses elicited by lung inflation in anesthetized humans are predominantly the direct effect of the increase in intrathoracic pressure, although sympathetic afferent activity induced via stimulation of mechanoreceptors in the airways contributes. IMPLICATIONS: Localized airway anesthesia with lidocaine is unlikely to suppress the cardiovascular responses to lung inflation. This suggests that a limited number of neurogenic mechanisms are involved in the cardiovascular responses to lung inflation in anesthetized humans.

Pulmonary arterial and right ventricular responses to prophylactic albumin administration before aortic unclamping during abdominal aortic aneurysmectomy.

UNLABELLED: During abdominal aortic aneurysmectomy (AAAectomy) and before aortic unclamping (XU), we studied the effects of albumin administration on pulmonary arterial and right ventricular responses in 39 anesthetized patients using a modified thermodilution technique. Group 1 patients (n = 18) were given no extra IV fluids. Group 2 patients (n = 21) were given additional albumin administration (5% albumin at 10 mL/kg) before XU. After XU, mean arterial blood pressure (MAP) decreased significantly in each group, and MAP and stroke volume index (SVI) were not significantly higher in Group 2 than in Group 1. At 5 min after XU, the patients in Group 2 had a higher mean pulmonary arterial pressure and pulmonary vascular resistance index and a lower right ventricular ejection fraction than those in Group 1 (P < 0.05), but their SVIs were well maintained. These results indicate that albumin administration before XU may not always prevent post-XU hypotension. It caused a significant increase in right ventricular afterload and a significant dilation of the right ventricular cavity; however, right ventricular function was almost equally maintained in both groups. However, because SVI did not increase in some patients (Group 2) with the increase in right ventricular end-diastolic volume index after XU, albumin administration should be performed carefully before XU during AAAectomy. IMPLICATIONS: We studied the effects of albumin administration before aortic unclamping on pulmonary arterial and right ventricular responses during abdominal aortic aneurysmectomy using a modified thermodilution technique. Albumin administration before aortic unclamping may not always prevent hypotension, and it may cause a higher pulmonary arterial pressure than in patients without albumin administration.

Diuretic effect of clonidine during isoflurane, nitrous oxide, and oxygen anesthesia.

BACKGROUND: Because clonidine, a relative selective alpha 2-agonist, inhibits the action of arginine vasopressin (AVP), the authors examined whether clonidine as an oral preanesthetic medication would induce diuresis and also would affect AVP release and its action during general anesthesia. METHODS: Fifty-seven patients (aged 18-65 yr) randomly received oral clonidine either approximately 5 micrograms.kg-1 (n = 19), approximately 2.5 micrograms.kg-1 (n = 19), or none (n = 19) in addition to oral famotidine 20 mg, 90 min before arrival at operating room. Urine volume, urine osmolality, and amount of sodium and potassium excreted into urine were examined every hour for 3 h during minor surgery under general anesthesia with isoflurane and nitrous oxide in oxygen. For 5 patients of each group, plasma AVP and atrial natriuretic peptide concentrations and urine cyclic adenosine monophosphate concentrations as an index of AVP action were also assayed. RESULTS: Urine output indices (calculated as hourly urine output [milliliters per hour] divided by body weight [kilograms]) were significantly greater in the all periods (P < or = 0.035) after the initiation of anesthesia in the patients receiving clonidine 5 micrograms.kg-1 and only in the 3rd h in those receiving clonidine 2.5 micrograms.kg-1 (P = 0.047) as compared with those in the patients given famotidine alone. The peak effects of diuresis and natriuresis induced by oral clonidine 5 micrograms.kg-1 were both observed at the 2nd h (mean +/- SEM, 2.4 +/- 0.4 ml.kg-1.h-1 and 5.7 +/- 1.5 mEq.h-1 vs. 0.6 +/- 0.1 ml.kg-1.h-1 and 2.2 +/- 0.5 mEq.h-1 in the control subjects; P = 0.001 and P = 0.049). Kaliuresis also increased in the patients receiving clonidine 5 micrograms.kg-1 in the 2nd and 3rd h (P < or = 0.003). Urine osmolality showed a significant reduction over time in patients given clonidine but not in the control subjects. However, plasma AVP and atrial natriuretic peptide levels, and urine cyclic adenosine monophosphate concentrations did not significantly differ among the three groups. CONCLUSIONS: Oral preanesthetic medication of clonidine 2.5 or 5 micrograms.kg-1 caused a significant diuretic effect during surgery under general anesthesia, though it did not apparently relate to AVP action. This effect of clonidine could be related to its pharmacological action as an alpha 2-adrenoceptor agonist not necessarily restricted to the kidney. The diuretic effect of clonidine implicates its clinical importance in the management of patients during anesthesia.

Combination of epidural morphine and fentanyl for postoperative analgesia.

The rapid onset of epidural fentanyl could be used to cover the latency period of epidural morphine, thus potentiating analgesia during anesthesia regression after short-acting local anesthetics and possibly extending morphine analgesia for longer duration. The object of this study is to determine whether there are clinical advantages or disadvantages of combining epidural morphine and epidural fentanyl for postoperative analgesia. Patients scheduled for gynecologic procedures were assigned to two groups (n = 54 for each): Group 1 receiving 4 mg epidural morphine, and Group 2 receiving 4 mg epidural morphine and 100 micrograms fentanyl 30 minutes before the estimated completion of the surgery using lidocaine epidural anesthesia. Comparisons were made with regard to: (1) times before the first supplemental analgesic for incisional pain, (2) numbers of supplemental analgesic during the first 48 hours postoperatively, and (3) adverse effects. The two groups were comparable. The number of patients requiring supplemental analgesics between the fourth and 17th hours was significantly greater in Group 1 (n = 10, compared to n = 0 for Group 2; p less than 0.05). The mean time before the first supplemental analgesic was significantly longer in Group 2 (p less than 0.05). The number of supplemental analgesics during the first 48 hours was significantly less in Group 2 (p less than 0.01). No significant difference was found regarding adverse side effects. The results obtained confirm the potential desirability of combining epidural morphine and epidural fentanyl for postoperative analgesia.

[Effects of epidural clonidine added to lidocaine solution upon the requirements of sedatives during epidural anesthesia].

The authors studied 34 patients undergoing abdominal total hysterectomy in order to evaluate whether epidural clonidine added to lidocaine solution could alter the requirements of sedatives during epidural anesthesia. Patients were randomly assigned to one of four groups; 18 ml of 2% lidocaine with 1:200,000 clonidine (n = 6), 1:100,000 clonidine (n = 7), 1:200,000 epinephrine (n = 13), or neither (plain, n = 8). The requirements of sedatives (diazepam, thiamylal) and analgesic (butorphanol) prior to the second epidural injection were compared among the four groups. The dose of intravenous diazepam or thiamylal required for sedation in the patients receiving lidocaine with 1:100,000 clonidine had a tendency to be smaller as compared with those in other three groups. There was a significant difference (P less than 0.05) in the requirement of diazepam between the patients given lidocaine with 1:100,000 clonidine and those given plain lidocaine. The present results suggest that the addition of clonidine to lidocaine solution could reduce the requirements of sedatives in epidural anesthesia.

Effective doses of epidural morphine for relief of postcholecystectomy pain.

Having previously established the effective dose of intrathecal morphine for relief of postcholecystectomy pain, we determined in this study the effective dose of epidural morphine for relief of postcholecystectomy pain in 154 patients given epidural injections of a placebo (group 1, n = 49), 2 mg morphine (group 2, n = 54), or 4 mg morphine (group 3, n = 51) intraoperatively mixed in 1.5% lidocaine. The percentage of patients who did not request an analgesic, 30 mg IM pentazocine, for relief of pain during the first 24 postoperative hours was significantly greater in groups 2 and 3 than in group 1. In patients who did need 30 mg IM pentazocine postoperatively, the number of times pentazocine was administered was also significantly greater in group 1 than in groups 2 and 3. The percentage of patients developing respiratory depression or vomiting in the first 48 postoperative hours was similar in the three groups. Based on the present data and those we previously reported for intrathecal morphine, we conclude that an epidural morphine dose of 2-4 mg and an intrathecal morphine dose of 0.06-0.12 mg are equipotent for relief of postcholecystectomy pain.