Tatsuhiro Masaoka

Helicobacter pylori eradication shifts monocyte Fcγ receptor balance toward inhibitory FcγRIIB in immune thrombocytopenic purpura patients

Immune thrombocytopenia purpura (ITP) is a bleeding disorder in which platelet-specific autoantibodies cause a loss of platelets. In a subset of patients with ITP and infected with Helicobacter pylori, the number of platelets recovers after eradication of H. pylori. To examine the role of H. pylori infection in the pathogenesis of ITP, the response of 34 ITP patients to treatment with a standard H. pylori eradication regimen, irrespective of whether they were infected with H. pylori, was evaluated. Eradication of H. pylori was achieved in all H. pylori-positive patients, and a significant increase in platelets was observed in 61% of these patients. By contrast, none of the H. pylori-negative patients showed increased platelets. At baseline, monocytes from the H. pylori-positive patients exhibited an enhanced phagocytic capacity and low levels of the inhibitory Fcgamma receptor IIB (FcgammaRIIB). One week after starting the H. pylori eradication regimen, this activated monocyte phenotype was suppressed and improvements in autoimmune and platelet kinetic parameters followed. Modulation of monocyte FcgammaR balance was also found in association with H. pylori infection in individuals who did not have ITP and in mice. Our findings strongly suggest that the recovery in platelet numbers observed in ITP patients after H. pylori eradication is mediated through a change in FcgammaR balance toward the inhibitory FcgammaRIIB.

Efficacy of Buspirone, a Fundus-Relaxing Drug, in Patients With Functional Dyspepsia

BACKGROUND & AIMS Impaired accommodation and hypersensitivity to gastric distention are believed to be involved in the development of functional dyspepsia (FD). Buspirone, a 5-hydroxytryptamine 1A receptor agonist, relaxes the proximal stomach in healthy individuals. We studied the effects of buspirone on symptoms and mechanisms of FD. METHODS We performed a randomized, double-blind, placebo-controlled, crossover study of 17 patients (13 women; mean age, 38.5 ± 2.4 years). The study included 2 treatment periods of 4 weeks each, separated by a 2-week washout period. In the first period, 7 participants were given buspirone (10 mg, 3 times daily for 4 weeks) and 10 were given placebo 15 minutes before meals; patients switched groups for the second period. We assessed meal-related symptoms and severity, along with gastric sensitivity, accommodation, and emptying (by using barostat and breath tests) before and after 4 weeks of treatment. RESULTS Buspirone significantly reduced the overall severity of symptoms of dyspepsia (7.5 ± 1.3 vs 11.5 ± 1.2 for placebo; P < .005) and individual symptoms of postprandial fullness, early satiation, and upper abdominal bloating, whereas placebo had no significant effect (all P < .05). Buspirone did not alter the rate of gastric emptying of solids or sensitivity to gastric distention, but it significantly increased gastric accommodation, compared with placebo (229 ± 28 vs 141 ± 32 mL, respectively; P < .05), and delayed gastric emptying of liquids (half-life = 64 ± 5 vs 119 ± 24 minutes, respectively). Adverse events were similar when patients were given buspirone or placebo. CONCLUSIONS In patients with FD, 4 weeks of administration of buspirone significantly improved symptoms and gastric accommodation, compared with placebo, whereas gastric emptying of liquids was delayed.

Blatchford scoring system is a useful scoring system for detecting patients with upper gastrointestinal bleeding who do not need endoscopic intervention

Background and Aim:  Several scoring systems have been devised to identify patients with upper gastrointestinal (UGI) bleeding who are at a high risk of adverse outcomes. We retrospectively evaluated the accuracy of the Blatchford scoring system for assessing the need for clinical intervention in cases of UGI bleeding admitted to the emergency department (ED).

The relation between symptom improvement and gastric emptying in the treatment of diabetic and idiopathic gastroparesis

OBJECTIVES:The relationship between symptom improvement (SI) and acceleration of gastric emptying (GE) for different drugs used in the treatment of idiopathic and diabetic gastroparesis is uncertain. In this paper we examined the study-specific correlations between SI and GE, and we performed a meta-regression analysis of the association across multiple studies.METHODS:The MEDLINE database (1,946 to present) was searched, and only controlled trials or trials with an established effective comparator that compared both SI and GE were included.RESULTS:Studies were identified for metoclopramide (n=6), domperidone (n=6), cisapride (n=14), erythromycin (n=3), botulinum toxin (n=2), and levosulpiride (n=3). Even though most drugs concomitantly improved symptoms and accelerated GE, no study reported a significant correlation between SI and GE. Moreover, a correlation analysis over all studies using meta-regression did not show a significant relationship between SI and GE. Our findings need to be qualified by inconsistencies in study methods, which is a limitation but also suggests that our findings are robust to methodological factors.CONCLUSIONS:In this review, no evidence of a relationship between SI and GE was identified for different drugs used for the treatment of gastroparesis. This finding questions the use of GE measurement to direct drug development for gastroparesis.

Down‐regulation of a morphogen (sonic hedgehog) gradient in the gastric epithelium of Helicobacter pylori‐infected Mongolian gerbils

Sonic hedgehog (Shh) is a morphogen involved in many aspects of patterning of the gut during embryogenesis and in gastric fundic gland homeostasis in the adult. Intestinal metaplastic change of the gastric epithelium is associated with the loss of Shh expression, and mice that lack Shh expression show intestinal transformation of the gastric mucosa. The present study was designed to investigate the alteration of Shh expression in the stomach of an experimental model of Helicobacter pylori (H. pylori) colonization. Male Mongolian gerbils were inoculated with H. pylori and examined 4 and 51 weeks later. The level of Shh mRNA expression was determined by quantitative RT‐PCR and in situ hybridization. Shh protein expression was determined by immunoblotting and immunohistochemistry. Shh was expressed in the parietal cells, zymogenic cells, and mucous neck cells of the gastric fundic glands of gerbils. Prolonged colonization by H. pylori led to extension of the inflammation from the antrum to the corpus of the stomach, with loss of Shh expression. Loss of Shh expression correlated with loss of parietal cells, disturbed maturation of the mucous neck cell–zymogenic cell lineage, and increased cellular proliferation. Shh expression is significantly reduced in H. pylori‐associated gastritis. These data show for the first time that H. pylori infection leads to down‐regulation of the expression of a morphogen with an established role (Shh) in gastric epithelial differentiation. Copyright

Enhanced plasma ghrelin levels in rats with streptozotocin-induced diabetes.

Ghrelin is a novel gastrointestinal peptide that stimulates growth hormone secretion, food intake, and body weight gain. Increased ghrelin secretion has been reported in such negative energy states as starvation and low body weight. We investigated the dynamics of ghrelin in rats with streptozotocin‐induced diabetes, because they present reduced body weight and hyperphagia. The plasma ghrelin levels and gastric preproghrelin mRNA expression levels of the diabetic rats increased significantly and their gastric ghrelin levels decreased significantly. Negative energy balance may enhance preproghrelin mRNA expression and ghrelin secretion into the bloodstream.

Improvement of gastrointestinal quality of life scores in cases of Helicobacter pylori‐positive functional dyspepsia after successful eradication therapy

Functional dyspepsia (FD) refers to a broad range of chronic upper abdominal symptoms associated with food intake. A definitive treatment for FD has not yet been established, and the effect of Helicobacter pylori (H. pylori) eradication still remains under debate. The Gastrointestinal Symptom Rating Scale (GSRS) is a specific questionnaire for patients with gastrointestinal symptoms. The present study examined the quality of life (QOL) of patients with H. pylori‐positive FD following H. pylori eradication.

Effect of dietary anti‐Helicobacter pylori‐urease immunoglobulin Y on Helicobacter pylori infection

Recently, chicken egg yolk was recognized as an inexpensive antibody source, and the therapeutic usefulness of egg yolk immunoglobulin Y (IgY) in oral passive immunization has been investigated. Although multiple antibiotic treatments eradicate most Helicobacter pylori (H. pylori) infections, therapy fails in 10–15% of cases due to the development of drug resistance. Consequently, it is important that new, more broadly based therapies for the treatment of H. pylori infection should be identified. The present study evaluated the effect, on H. pylori infection, of IgY prepared from egg yolk of hens immunized with H. pylori urease (anti‐HpU IgY). Seventeen asymptomatic volunteers diagnosed as H. pylori‐positive by the 13C‐urea breath test (UBT) were orally administered anti‐HpU IgY for 4 weeks. Four weeks later, UBT values were significantly decreased although no case showed H. pylori eradication. An H. pylori‐positive 53‐year‐old female gastritis patient administered anti‐HpU IgY plus lansoprazole for 8 weeks showed a decrease in serum pepsinogen (PG) I and UBT values as well as an increase in the PG I/II ratio. In conclusion, anti‐HpU IgY may mitigate H. pylori‐associated gastritis and partially attenuate gastric urease activity. Furthermore, anti‐HpU IgY combined with antacids appears to ameliorate gastric inflammation. These encouraging results may represent a novel approach to the management of H. pylori‐associated gastroduodenal disease.

Effect of dietary anti-urease immunoglobulin Y on Helicobacter pylori infection in Mongolian gerbils.

Background and aim.  Helicobacter pylori is known to be a major pathogenic factor in the development of gastritis, peptic ulcer disease and gastric cancer. Recently, chicken egg yolk immunoglobulin Y (IgY) has been recognized as an inexpensive antibody source for passive immunization against gastrointestinal infections. The present study was designed to investigate the effect of anti‐urease IgY on H. pylori infection in Mongolian gerbils.

Autoimmune pancreatitis with pseudocysts

A 47-year-old woman was admitted to our hospital with complaints of fever, upper abdominal pain, and back pain. The serum amylase, C-reactive protein (CRP), and IgG (especially IgG4) were elevated, and abdominal computed tomography (CT) revealed diffuse enlargement of the pancreas and pseudocysts. Endoscopic retrograde pancreatography (ERP) revealed diffuse irregular narrowing of the main pancreatic duct. Histopathological examination of the pancreatic tissue showed fibrotic change with lymphocytic infiltration. Based on these findings, we diagnosed this case as a case of autoimmune pancreatitis. This case also fully satisfied the diagnostic criteria for autoimmune pancreatitis established by the Japan Pancreas Society in 2002. Few reports have been published on cases of autoimmune pancreatitis complicated by the formation of pseudocysts in the pancreas. We, therefore, report this case here to emphasize that cases of autoimmune pancreatitis can be complicated by the development of pseudocysts.