Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: A randomized clinical trial (the DREAM study).

BACKGROUND: Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. METHODS: FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). KEY RESULTS: Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016). CONCLUSION & INFERENCES: Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.

Oolong tea is useful for lens cleansing in transnasal small-caliber esophagogastroduodenoscopy.

BACKGROUND AND STUDY AIMS: Unsedated transnasal small-caliber esophagogastroduodenoscopy (EGD) has been used to examine the upper gastrointestinal tract with proven feasibility and tolerability. However, a limitation of transnasal EGD is the poor lens-cleansing function of the scope due to the small-caliber water-jet nozzle. Therefore, this trial was designed to evaluate the cleansing effect of oolong tea for transnasal small-caliber EGD. PATIENTS AND METHODS: Oolong tea (O), barley tea (B), and distilled water (W) were prepared as washing solutions for endoscopic lenses. Study I: after the lenses were soiled by lard oil, they were washed with one of the three washing solutions, and the image quality of photographs was judged. Study II: 982 patients who were due to undergo transnasal EGD were enrolled and randomly assigned to the O-, B-, or W-groups. The level of lens cleansing, the overall time required for endoscopy, and the volume of washing solution used were measured. RESULTS: Study I: the image quality of photographs taken with lenses washed with oolong tea was significantly superior to that associated with other solutions. Study II: the level of lens cleansing in the O-group was significantly superior to that of the B- and W-groups ( P < 0.001). The volume of solution used for lens cleansing in the O-group was significantly smaller than that in the W-group ( P < 0.05). Endoscopic examination times in the O-group were shorter than those in the B- and W-groups ( P < 0.05). CONCLUSIONS: In transnasal small-caliber EGD, oolong tea instead of water as a washing solution for endoscopic lens cleansing is useful to maintain good visibility.

The herbal medicine Rikkunshi-to stimulates and coordinates the gastric myoelectric activity in post-operative dyspeptic children after gastrointestinal surgery.

Rikkunshi-to (TJ-43), a gastroprotective herbal medicine, has been used for the symptomatic relief of adult patients with dyspepsia. However, its mechanism has yet to be fully elucidated. The aim of this study is to evaluate the effect of TJ-43 on the gastric myoelectric activity in post-operative dyspeptic patients, whose symptoms persisted for over 1 year after gastrointestinal surgery. Electrogastrography (EGG) recordings were performed to calculate the biomechanical parameters on the dominant peak frequency (DPF). Eight pediatric patients with dyspeptic symptoms after gastrointestinal surgery were examined and six age-matched children without any dyspeptic symptoms were used as controls, and they were compared with nine age-matched children without any dyspeptic symptoms after gastrointestinal surgery as subcontrols. All patients exhibited symptomatic relief after the administration of TJ-43, and the mean symptom score decreased significantly after the treatment of TJ-43 over a 1-month period ( P<0.0001). The variability index (VI) and the percentage of normal waves (PNW) were calculated as irregularity parameters of DPF. The power ratio (PR) was calculated as a parameter of the gastric contractile activity. There were no significant differences in the VI and PNW between the controls and patients during the postprandial state after therapy, even though significant differences existed regarding those parameters between the controls and patients before the therapy. There were no significant differences in the DPF, VI, and PNW between the controls and subcontrols. Furthermore, PR exhibited a significant increase after therapy ( P<0.05). However, there was a significant difference in the PR between the controls and subcontrols ( P<0.05). Postprandial dip was observed in all control subjects, eight patients in the subcontrols, and two patients after administration of TJ-43, respectively. An abnormal gastric electrical activity therefore seems to be an important factor in the pathophysiology of post-operative dyspeptic children. The coordinating and stimulating effect of TJ-43 on the gastric myoelectric activity therefore seems to play an important role in the reduction of dyspeptic symptoms.

Radiotherapy after hyperbaric oxygenation improves radioresponse in experimental tumor models.

We examined the effect of radiotherapy after hyperbaric oxygen (HBO) breathing in experimental tumors using a tumor growth delay assay. Tumor models used were SCCVII (radiobiological hypoxic fraction: approximately 10%) and 9L tumors (containing less hypoxic cells) subcutaneously transplanted into C3H/He mice and Fisher 344 rats, respectively. Irradiation using X-rays was locally administered to the tumors immediately after decompression. HBO breathing enhanced the radiation response in SCCVII tumors but not in 9L ones. In the next experiment using SCCVII tumors, irradiation was administered 5, 15, 30, and 90 min after decompression. A significant growth delay was seen in the treated animals within 30 min after HBO breathing, and the tumor growth delay time was prolonged 1.61 times as long as that in radiotherapy alone. We concluded that: (1) radiotherapy after HBO breathing is effective for tumors with hypoxic cells; and (2) the time lapse from decompression to irradiation is an important factor in improving radiosensitivity. Radiotherapy after HBO breathing can be used to enhance the efficacy of clinical treatments.

Nonrotation of the midgut with appendiceal mucocele in an adult.

Nonrotation of the midgut in adults and appendiceal mucocele are both rare pathological conditions. We report here the first case of nonrotation of the midgut associated with appendiceal mucocele. The patient was a 51-year-old man admitted to hospital with ileus. An upper gastrointestinal series and a barium enema revealed nonrotation of the midgut without midgut volvulus and with a mass in the ileocecal area. Laparotomy revealed an appendiceal mucocele adhering to the urinary bladder and the rectum. The mucocele had partly ruptured; yellowish mucinous material had entered the abdominal cavity, resulting in pseudomyxoma peritonei. Histological examination revealed a mucinous tumor of the appendix with borderline malignancy. In this patient, the ileus was caused by the appendiceal mucocele rather than being caused by nonrotation of the midgut.

[Unusual MR findings of Wernicke encephalopathy with cortical involvement].

We report a 48-year-old chronic alcoholic man, who developed consciousness disturbance, oculomotor paresis, and flaccid tetraplegia. His dietary habit was very poor since one month prior to the present admission and he was drinking alcoholic beverage. On admission on April 19, 1999, he showed disturbance of consciousness, tetraparesis without sensory disturbance, gaze paresis, and vertical nystagmus on downward gaze. His blood thiamine level was 12 ng/ml (normal range: 23.8-45.9). MRI demonstrated symmetric hyperintense lesions in the motor and premotor cortices bilaterally, in addition to other changes indicating Wernicke's encephalopathy. His motor weakness and oculomotor disturbance improved after treatment with intravenous thiamine. His cortical MRI also normalized. We believe that his cortical abnormality was responsible for his motor paresis and this is an unusual and unique finding for Wernicke's encephalopathy.

Modulation of aromatase expression in human breast tissue.

Aromatase plays an important role in breast cancer development through its role in the synthesis of estrogen. Aromatase expression in breast tissue can be regulated by several mechanisms. The major promoter usage for aromatase expression in breast tumors (i.e. cAMP-stimulated promoters I.3 and II) is different from that in normal breast tissue (i.e. glucocorticoid-stimulated promoter I.4). Recent characterization of transcription factors that interact with the two important regulatory elements near promoters I.3 and II, i.e. S1 and CREaro, helps us better understand the mechanism of the switch of promoter usage between normal breast tissue and cancer tissue. It is thought that in normal breast tissue, the function of promoters I.3 and II is suppressed through the binding of EAR-2, COUP-TFI, and EARgamma to S1, and through the binding of Snail/Slug proteins to their binding site that quenchs the CREaro activity. In cancer tissue, the expression levels of EAR-2, COUP-TFI, EARgamma, Snail, and Slug decrease, and aromatase expression is then up regulated through the binding of ERRalpha-1 to S1 and the binding of CREB or related factors to CREaro. Results from this and other laboratories reveal that aromatase activity in aromatase expressing cells can also be modified by treatment with aromatase inhibitors and the antiestrogen ICI 182, 780. While aromatase inhibitors are used to treat breast cancer, the treatment has been found to increase the level of aromatase in the breast tissue of some patients. The enhancement of aromatase activity by aromatase inhibitors is thought to be due to a decrease of aromatase protein degradation by enzyme-inhibitor complex formation, up-regulation of the aromatase gene transcription through a cAMP-mediated mechanism, and an induction of aromatase expression by gonadtropins that are released from the pituitary in response to a reduction of estrogen levels in circulation in premenopausal women. Antiestrogen ICI 182, 780 has been found to suppress aromatase expression, but the mechanism has not yet been determined. In addition, aromatase activity and expression can be affected by environmental chemicals. A detailed structure-function study has revealed that flavones, but not isoflavones, are inhibitors of aromatase. It was found that flavones bind to the active site of aromatase in an orientation in which their rings-A and -C mimic rings-D and -C of the androgen substrate. The modulation of aromatase expression by endocrine disrupting chemicals is exemplified by two organochlorine pesticides (i.e. toxaphene and chlordane) that have been found to be antagonists of ERRalpha-1 orphan receptor. These compounds reduce ERRalpha-1 activity, resulting in a suppression of aromatase expression.

Usefulness of autologous blood transfusion for avoiding allogenic transfusion and infectious complications after esophageal cancer resection.

BACKGROUND: A retrospective investigation was conducted to determine whether autologous blood collection could reduce allogenic transfusion after resection of esophageal cancer and whether allogenic transfusion influenced postoperative infection. METHODS: Patients (n = 100) who met the criteria for hemoglobin, age, body weight, and serum protein donated 800 mL of autologous blood from May 1994 to December 1997. The control group (n = 248) was selected from patients who met the same criteria and did not donate autologous blood over the 10 years before the start of autologous blood collection. RESULTS: Only three patients (3%) from the autologous group required allogenic transfusion versus 84 patients (33.7%) from the control group. Sixteen of the 26 patients who received more than 4 units of allogenic blood contracted postoperative infections compared with 25 of 165 patients who did not (P < .0001). Autologous blood transfusion significantly increased the probability of avoiding allogenic transfusion (odds ratio, 27.58), and allogenic transfusion was significantly related to postoperative infection (odds ratio, 1.19), according to logistic regression analysis. CONCLUSIONS: Autologous blood collection reduces the need for allogenic transfusion in patients undergoing resection of esophageal cancer, and avoidance of allogenic transfusion may reduce the risk of postoperative infection.

Preservation of tumour oxygen after hyperbaric oxygenation monitored by magnetic resonance imaging.

Hyperbaric oxygen (HBO) has been proposed to reduce tumour hypoxia by increasing the dissolved molecular oxygen in tissue. Using a non-invasive magnetic resonance imaging (MRI) technique, we monitored the changes in MRI signal intensity after HBO exposure because dissolved paramagnetic molecular oxygen itself shortens the T1 relation time. SCCVII tumour cells transplanted in mice were used. The molecular oxygen-enhanced MR images were acquired using an inversion recovery-preparation fast low angle shot (IR-FLASH) sequence sensitizing the paramagnetic effects of molecular oxygen using a 4.7 tesla MR system. MR signal of muscles decreased rapidly and returned to the control level within 40 min after decompression, whereas that of tumours decreased gradually and remained at a high level 60 min after HBO exposure. In contrast, the signal from the tumours in the normobaric oxygen group showed no significant change. Our data suggested that MR signal changes of tumours and muscles represent an alternation of extravascular oxygenation. The preserving tumour oxygen concentration after HBO exposure may be important regarding adjuvant therapy for cancer patients.

Effects of radiotherapy after hyperbaric oxygenation on malignant gliomas.

The purpose of this non-randomized trial was to evaluate the efficacy of radiotherapy combined with hyperbaric oxygen (HBO) in patients with malignant glioma. Between 1987 and 1997, 29 patients in whom computerized tomography (CT) or magnetic resonance imaging (MRI) scans showed post-operative residual tumours were locally irradiated with nitrosourea-based chemotherapy. Treatments were consecutively combined with HBO at two institutions since 1991 and 1993. Fifteen patients were irradiated daily after HBO, and the periods of time from decompression to irradiation were within 15 and 30 min in 11 and four patients respectively. Fourteen other patients were treated without HBO. Tumour responses were assessed by CT or MRI scans and survival times were compared between the treated groups. In the HBO group, 11 of 15 patients (73%) showed > or = 50% tumour regression. All responders were irradiated within 15 min after decompression. In the non-HBO group, four of 14 patients (29%) showed tumour regression. The median survivals in patients with and without HBO were 24 and 12 months, respectively, and were significantly different (P < 0.05). No serious side-effects were observed in the HBO patients. In conclusion, irradiation after HBO seems to be a useful form of treatment for malignant gliomas, but irradiation should be administered immediately after decompression.

Enhanced expression in seminoma of human zinc finger genes located on chromosome 19.

Six Krüppel-type zinc finger (ZF) genes were cloned from a seminoma cDNA library. One, ZFS-1, showed high sequence homology to the ZNF91 KRAB (Krüppel-associated box) ZF gene family and also the same chromosomal assignment. Interestingly, Northern blot analyses using ZFS-1 and ZNF91 revealed that multiple ZF genes on chromosome 19 were predominantly expressed in seminomas. In addition, the testis and the seminoma showed specific expression of 2.3 kb transcript. Our results suggest that ZF genes on chromosome 19 may be implicated in the development and/or growth of seminomas.

A successfully treated case of multiple liver abscesses accompanied by portal venous gas.

A case with multiple liver abscess accompanied by massive portal venous gas is reported. A 61-yr-old male was admitted because of left lower abdominal pain, fever, and diarrhea. Abdominal x-ray examination demonstrated multiple branching lucencies in the liver. Computed tomography revealed multiple liver abscesses and massive gas in the portal system as well as a thickened wall of the sigmoid colon. Enema study using contrast medium revealed a perforation of the sigmoid colon with diverticulitis. The outcome was favorable after sigmoid colectomy in addition to intensive treatment with antibiotics. Bacteroides fragilis, which produces gas (H2 and NH3) by fermentation, was isolated not only from the resected specimen but also from blood samples. Although the presence of portal venous gas is a sign of poor prognosis in patients with intestinal infectious diseases, the sensitive detection of hepatic portal venous gas by computed tomography and the appropriate treatment may improve the patient's prognosis.

The expression of tumour necrosis factor in the hypothalamus after treatment with lipopolysaccharide.

To investigate the effects of tumour necrosis factor (TNF) in the hypothalamus, Wistar rats received an intravenous administration of lipopolysaccharide (LPS) at a dose of 3.0 mg/100 g. Concentrations of TNF-alpha in the cerebral liquor and blood sera rapidly increased at 30 minutes after administration of LPS, rose to the maximum level at 1 hour, and then gradually decreased. Using horse-radish peroxidase as a tracer, a transient increase in paracellular permeability throughout the tight junctions of the ependymal cell layer covering the third ventricle was observed by electron microscopy at 30 minutes and in that of the capillary endothelium at 1 hour after administration, respectively. Following LPS administration, TNF was preferentially localized by immunoelectron microscopy in the tight junctional area of the ependymal cell layer and the capillary. These data indicate that TNF, synthesized in the ependymal cell layer, induces a deterioration in the cerebrospinal fluid-brain barrier and subsequently in the blood-brain barrier. The present study suggests that oedematous changes in the hypothalamic areas determined by ultrastructural and magnetic resonance analyses were mainly due to TNF conveyed from the ependymal cell layer to the hypothalamus after administration of LPS.

Radiotherapy after hyperbaric oxygenation for malignant gliomas: a pilot study.

The results of radiotherapy combined with hyperbaric oxygen in 9 patients with malignant glioma were compared with those of radiotherapy without hyperbaric O2 in 12 patients. This is the first report of a pilot study of irradiation immediately after exposure to hyperbaric O2 in humans. All patients receiving this treatment showed more than 50% regression of the tumor, and in 4 of them, the tumors disappeared completely. Only 4 out of 12 patients without hyperbaric O2 showed decreases in tumor size, and all 12 patients died within 36 months. So far, this new regimen seems to be a useful form of radiotherapy for malignant gliomas.

Screening of tissue cultures and thalli of lichens and some of their active constituents for inhibition of tumor promoter-induced Epstein-Barr virus activation.

Inhibition of tumor promoter-induced Epstein-Barr virus (EBV) activation was screened using tissue culture and thallus extracts of lichens. Usnea longissima ACH. thallus and Cetraria ornata MULL. ARG. tissue culture showed strong inhibitory activity. We identified (+)-usnic acid (1), barbatic acid (2), diffractaic acid (3), 4-O-demethylbarbatic acid (4), and evernic acid (5) as inhibitors of EBV activation from the U. longissima thallus. Of these compounds, (+)-usnic acid exhibited the highest inhibitory activity (IC50 = 1.0 microM).

Copresence of prostaglandin EP2 and EP3 receptors on gastric enterochromaffin-like cell carcinoid in African rodents.

BACKGROUND & AIMS: Prostaglandins (PGs) have important roles in the regulation of gastric acid secretion. The aim of this study was to examine the possible presence of PG receptors on the gastric enterochromaffin-like (ECL) carcinoid of Mastomys natalensis, which might be a useful model of normal ECL cells. METHODS: A [3H]PGE2 binding experiment was performed by using the ECL tumor membrane, and intracellular signal transduction was studied in the cells. In addition, Northern blot analysis using EP2 and EP3 receptor complementary DNAs was conducted. RESULTS: [3H]PGE2 specifically bound to the tumor cell membrane, and the binding was displaced by various PGs with a potency order of PGE1 = PGE2 > enprostil > PGF2 alpha. Although PGE1 and PGE2 stimulated 5'-cyclic adenosine monophosphate (cAMP) production, neither PGF2 alpha nor enprostil had any effect. On the other hand, all of PGE1, PGE2, PGF2 alpha, and enprostil attenuated the forskolin-induced cAMP production. Moreover, enprostil inhibited histamine release induced by forskolin. However, on pertussis toxin treatment, PGE2 paradoxically enhanced the forskolin-induced increase of cAMP production. Finally, the presence of EP2 and EP3 receptor messenger RNAs was confirmed by RNA blot analysis. CONCLUSIONS: The ECL carcinoid tumor cells of Mastomys seem to possess two subtypes of PGE receptor: EP2 linked to cAMP production and EP3 coupled with inhibitory guanosine 5'-triphosphate-binding proteins mediating the inhibition of cAMP production.

Hemispheric asymmetry of event-related potentials in a patient with callosal disconnection syndrome: a comparison of auditory, visual and somatosensory modalities.

To investigate whether callosal lesions affect the distribution of event-related potentials (ERP) between the two hemispheres and whether hemispheric ERP distribution differs among sensory modalities, a patient with interhemispheric disconnection syndrome and 47 controls were subjected to an oddball paradigm. High (target) and low tone bursts for auditory, red (target) and green lights for visual and electrical stimuli delivered to the index (target) or fifth finger for somatosensory ERPs were presented to the unilateral ear, visual field and hand, respectively. The subjects were instructed to press a button with the hand on the stimulated side. The results showed that the hemispheric asymmetry of the patient's auditory ERPs was not significantly different from that of the controls, regardless of which ear was stimulated. In contrast, the visual and somatosensory ERPs showed a delay of the P3 latency and an attenuation of the N1-P2 and N2-P3 amplitude over the hemisphere ipsilateral to the stimulus, regardless of the stimulated side. These findings suggest that the source of P3 generation is relatively lateralized to the hemisphere contralateral to the stimulus, and that the callosal transfer of visual and somatosensory information is involved in the P3 generation in the hemisphere ipsilateral to the stimulus.

Usnic acid and diffractaic acid as analgesic and antipyretic components of Usnea diffracta.

Diffractaic acid and usnic acid were identified as the analgesic and antipyretic components of a lichen, Usnea diffracta. Both compounds showed an analgesic effect by the acetic acid-induced writhing and tail-pressure methods in mice. Regarding the effect on normal body temperature and LPS-induced hyperthermia in mice, diffractaic acid showed a significant effect only on the former and usnic acid only on the latter.

[Comparison of the effects between standard doses of H2-blocker (famotidine 20mg b.d.) and proton pump inhibitor (omeprazole 20mg o.d.) in the treatment of refractory reflux esophagitis by ambulatory 24-hr intra-gastroesophageal pH monitoring].

Ambulatory 24-hour pH monitoring was conducted in 11 patients with H2-blocker resistant reflux esophagitis to compare the effects of standard doses of H2-blocker (famotidine 20mg twice daily) and proton pump inhibitor (omeprazole 20mg once daily) on the inhibition of intraesophageal acidity. Mean intraesophageal pH during PPI treatment was significantly higher than that during H2-blocker treatment. Proportion of abnormal intra-esophageal acidity in 24hr (%time pH < 4) during PPI treatment was significantly less than that during H2-blocker treatment (11.7 +/- 3.1% vs 31.6 +/- 4.8%). The difference of the effect was more apparent in day time (upright time) than in night time (supine time). Thus PPI is superior to H2-blocker in treatment for refractory reflux esophagitis, but proportion of abnormal intra-esophageal acidity in 24hr (%time pH < 4) could be normalized only in 4 out of 11 patients even by standard dose PPI treatment. Effects of not only long-term maintenance therapy but also high dose therapy with PPI should be examined in future studies.

Gastrin receptor genes are expressed in gastric parietal and enterochromaffin-like cells of Mastomys natalensis.

Although gastric enterochromaffin-like (ECL) carcinoid tumors are known to develop in patients with long-standing hypergastrinemia, the expression of the gastrin receptor gene in ECL cells has not yet been demonstrated. Therefore, this study was designed to examine gastrin receptor gene expression in ECL cells. Mastomys gastric mucosal cells isolated by enzyme dispersion were separated into 10 fractions (F1-10) by centrifugal elutriation. Each fraction was examined histologically to determine whether they contained ECL and/or parietal cells and Northern blot analysis was used to confirm the presence of histidine decarboxylase and H+, K(+)-ATPase gene expression. ECL cells were found only in fractions 1 and 2, whereas parietal cells were detected in fractions 6-10. Gastrin receptor gene expression was demonstrated in both parietal cell-rich and ECL cell-rich fractions. In addition, the gastrin receptor cDNA sequences obtained from the two of the fractions (F1 and 8) were identical. These results suggest that gastrin receptor genes are expressed in ECL cells as well as in parietal cells and that these receptors are identical.