Efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for Helicobacter pylori initial treatment: A randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori.@*METHODS@#This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1:1:1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed.@*RESULTS@#A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05).@*CONCLUSIONS@#The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.

Ehlers-Danlos syndrome VIII with novel C1R variant accompanying white matter changes

Ehlers-Danlos syndrome (EDS) VIII is an autosomal dominant inherited connective tissue disorder characterized by intractable periodontal inflammation, absence of gingiva, pretibial plaques, skin hyperextensibility, joint hypermobility, and tissue fragility with onset in the childhood or adolescence. In a recent report, heterozygous variants of the C1R or C1S related to the classical complement pathway were identified in families with history of EDS VIII. The current report describes a Korean 34-year-old female carrying a novel missense variant of C1R c.925T>G (p.Cys309Gly) and exhibiting early severe periodontitis, skin fragility, and joint hypermobility. The patient also had frontal, parietal, and temporal white matter brain lesions without definite vascular abnormalities on brain magnetic resonance imaging, which have not been surveyed meticulously in EDS VIII. Considering the genetic alteration of classic complement pathways in this condition, it is necessary to carefully observe multisystemic inflammation processes such as changes in brain white matter.

Relationships between ¹⁸F-THK5351 Retention and Language Functions in Primary Progressive Aphasia

BACKGROUND AND PURPOSE: There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹⁸F]-THK5351 retention across all three subtypes and determine the topography of [¹⁸F]-THK5351 retention correlated with each neurolinguistic score. METHODS: We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹⁸F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹⁸F]-THK5351 retention. RESULTS: The nfvPPA patients exhibited higher [¹⁸F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹⁸F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹⁸F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹⁸F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹⁸F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹⁸F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. CONCLUSIONS: The pattern of [¹⁸F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.

Long-Term Grey Matter Changes in First Episode Psychosis: A Systematic Review

OBJECTIVE: To determine possible progressive changes of the grey matter at the first stages of the schizophrenia spectrum disorders, and to determine what regions are involved in these changes. METHODS: We searched the literature concerning studies on longitudinal changes in grey matter in first-episode psychosis using magnetic resonance imaging, especially studies with an interval between scans of more than a year. Only articles published before 2018 were searched. We selected 19 magnetic resonance imaging longitudinal studies that used different neuroimaging analysis techniques to study changes in cerebral grey matter in a group of patients with a first episode of psychosis. RESULTS: Patients with first episode of psychosis showed a decrease over time in cortical grey matter compared with a group of control subjects in frontal, temporal (specifically in superior regions), parietal, and subcortical regions. In addition to the above, studies indicate that patients showed a grey matter decrease in cerebellum and lateral ventricles volume. CONCLUSION: The results suggest a decrease in grey matter in the years after the first episode of psychosis. Furthermore, the results of the studies showed consistency, regardless of the methods used in their analyses, as well as the time intervals between image collections.

Remnant parietal serosa detection in a cat with true diaphragmatic hernia using computed tomography / 대한수의학회지

A 4-year-old cat was referred for a suspected pulmonary mass. True diaphragmatic hernia presence was diagnosed via computed tomography (CT). There was a thin membrane covering the diaphragmatic defect. The membrane was thinner than the diaphragm. After contrast injection, the membrane was less enhanced than that of the normal diaphragm. The membrane was identified as a remnant of the parietal pleura. In addition, contrast-enhanced CT images provided clarity in viewing the herniated liver and falciform fat. A thinner membrane, covering the diaphragmatic defect, and attached to the thicker normal diaphragm, is considered a unique CT feature of true diaphragmatic hernia.

Disappearance of Arachnoid Cyst after Burrhole Trephination: Case Series / 대한신경손상학회지

We report 3 cases of arachnoid cysts (ACs) that completely disappeared after burr hole drainage, without cyst fenestration into the subarachnoid space or cystoperitoneal shunt. The first patient was a 21-year-old female with an AC of the right cerebral convexity, found incidentally. After endoscopic AC fenestration was performed, the patient complained of persistent headache. Two-month postoperative brain imaging revealed reaccumulated AC and associated multi-stage subdural hematoma. Burr hole drainage was performed to resolve the chronic subdural hematoma (CSDH). Three months later, brain computed tomography showed that the CSDH and the AC had disappeared. The second patient was an 11-year-old male who had a history of trauma 1 month prior to presentation at the clinic. Brain magnetic resonance imaging revealed an AC in the left sylvian fissure with CSDH. We performed burr hole drainage to treat the CSDH first. Subsequently, the AC as well as the CSDH disappeared. The third case was an AC of the right parietal convexity, found incidentally. Only burr hole drainage was performed, following which, the AC disappeared. This case series shows that an AC can disappear naturally after rupture into the subdural space by trauma or the burr hole procedure.

Fear Network Model in Panic Disorder: The Past and the Future

The core concept for pathophysiology in panic disorder (PD) is the fear network model (FNM). The alterations in FNM might be linked with disturbances in the autonomic nervous system (ANS), which is a common phenomenon in PD. The traditional FNM included the frontal and limbic regions, which were dysregulated in the feedback mechanism for cognitive control of frontal lobe over the primitive response of limbic system. The exaggerated responses of limbic system are also associated with dysregulation in the neurotransmitter system. The neuroimaging studies also corresponded to FNM concept. However, more extended areas of FNM have been discovered in recent imaging studies, such as sensory regions of occipital, parietal cortex and temporal cortex and insula. The insula might integrate the filtered sensory information via thalamus from the visuospatial and other sensory modalities related to occipital, parietal and temporal lobes. In this review article, the traditional and advanced FNM would be discussed. I would also focus on the current evidences of insula, temporal, parietal and occipital lobes in the pathophysiology. In addition, the white matter and functional connectome studies would be reviewed to support the concept of advanced FNM. An emerging dysregulation model of fronto-limbic-insula and temporooccipito-parietal areas might be revealed according to the combined results of recent neuroimaging studies. The future delineation of advanced FNM model can be beneficial from more extensive and advanced studies focusing on the additional sensory regions of occipital, parietal and temporal cortex to confirm the role of advanced FNM in the pathophysiology of PD.

Visual Hyper-vigilance But Insufficient Mental Representation in Children with Overweight/Obesity: Event-related Potential Study with Visual Go/NoGo Test / 대한소아소화기영양학회지

PURPOSE: The neural processing of children with overweight/obesity (CWO), may affect their eating behavior. We investigated the visual information processing of CWO under response control condition, by event-related potential (ERP) study, an electrophysiologic study for cognitive mechanism. METHODS: Seventeen CWO (mean age: 10.6±1.9), and 17 age-matched non-obese children (NOC), participated in the study. Neurocognitive function tests and visual ERP under Go/NoGo conditions, were implemented. Area amplitudes of major ERP components (P1, N1, P2, N2, and P3) from four scalp locations (frontal, central, parietal, and occipital), were analyzed. RESULTS: For Go and NoGo conditions, CWO had significantly greater occipital P1, fronto-central N1, and P2 amplitudes compared with NOC. P2 amplitude was significantly greater in CWO, than in NOC, at the frontal location. N2 amplitude was not significantly different, between CWO and NOC. For CWO and NOC, Go P3 amplitude was highest at the parietal location, and NoGo P3 amplitude was highest at the frontal location. In Go and NoGo conditions, P3 amplitude of CWO was significantly less than in NOC. CONCLUSION: The greater P1, N1, and P2 suggested hyper-vigilance to visual stimuli of CWO, but the smaller P3 suggested insufficient mental representation of them. Such altered visual processing, may affect the eating behavior of CWO.

Medial-Vowel Writing Difficulty in Korean Syllabic Writing: A Characteristic Sign of Alzheimer's Disease

BACKGROUND AND PURPOSE: Korean-speaking patients with a brain injury may show agraphia that differs from that of English-speaking patients due to the unique features of Hangul syllabic writing. Each grapheme in Hangul must be arranged from left to right and/or top to bottom within a square space to form a syllable, which requires greater visuospatial abilities than when writing the letters constituting an alphabetic writing system. Among the Hangul grapheme positions within a syllable, the position of a vowel is important because it determines the writing direction and the whole configuration in Korean syllabic writing. Due to the visuospatial characteristics of the Hangul vowel, individuals with early-onset Alzheimer's disease (EOAD) may experiences differences between the difficulties of writing Hangul vowels and consonants due to prominent visuospatial dysfunctions caused by parietal lesions. METHODS: Eighteen patients with EOAD and 18 age-and-education-matched healthy adults participated in this study. The participants were requested to listen to and write 30 monosyllabic characters that consisted of an initial consonant, medial vowel, and final consonant with a one-to-one phoneme-to-grapheme correspondence. We measured the writing time for each grapheme, the pause time between writing the initial consonant and the medial vowel (P1), and the pause time between writing the medial vowel and the final consonant (P2). RESULTS: All grapheme writing and pause times were significantly longer in the EOAD group than in the controls. P1 was also significantly longer than P2 in the EOAD group. CONCLUSIONS: Patients with EOAD might require a higher judgment ability and longer processing time for determining the visuospatial grapheme position before writing medial vowels. This finding suggests that a longer pause time before writing medial vowels is an early marker of visuospatial dysfunction in patients with EOAD.

Essential Anatomy of the Anorectum for Colorectal Surgeons Focused on the Gross Anatomy and Histologic Findings

The anorectum is a region with a very complex structure, and surgery for benign or malignant disease of the anorectum is impossible without accurate anatomical knowledge. The conjoined longitudinal muscle consists of smooth muscle from the longitudinal muscle of the rectum and the striate muscle from the levator ani and helps maintain continence; the rectourethralis muscle is connected directly to the conjoined longitudinal muscle at the top of the external anal sphincter. Preserving the rectourethralis muscle without damage to the carvernous nerve or veins passing through it when the abdominoperineal resection is implemented is important. The mesorectal fascia is a multi-layered membrane that surrounds the mesorectum. Because the autonomic nerves also pass between the mesorectal fascia and the parietal fascia, a sharp pelvic dissection must be made along the anatomic fascial plane. With the development of pelvic structure anatomy, we can understand better how we can remove the tumor and the surrounding metastatic lymph nodes without damaging the neural structure. However, because the anorectal anatomy is not yet fully understood, we hope that additional studies of anatomy will enable anorectal surgery to be performed based on complete anatomical knowledge.

The Efficacy of Bismuth-containing Quadruple Therapy after Moxifloxacin-based Sequential Therapy Failure in Helicobacter pylori Eradication / 대한소화기학회지

BACKGROUND/AIMS: Moxifloxacin-based sequential therapy showed an excellent eradication rate as the first line treatment of Helicobacter pylori (H. pylori) infection. However, to the best of our knowledge, there were only a few studies on the treatment of those with failed moxifloxacin-based sequential therapy. Hence, this study was to investigate the efficacy of bismuth-containing quadruple therapy in those with failed moxifloxacin-based sequential or reverse sequential therapy for H. pylori eradication. METHODS: Between January 2013 and March 2016, we retrospectively analyzed patients who failed to eradicate H. pylori using moxifloxacin-based sequential (rabeprazole 20 mg bid and amoxicillin 1 g bid for 5–7 days, followed by rabeprazole 20 mg bid, metronidazole 500 mg bid, and moxifloxacin 400 mg qd for 5–7 days) and 10 days moxifloxacin-based reverse sequential therapy as the first line treatment. Then we investigated the eradication rates of bismuth-containing quadruple therapy as the second line treatment. All subjects had no history of H. pylori eradication before. Eradication rates were described as intention-to-treat (ITT) and per-protocol (PP) analyses. H. pylori status was evaluated by 13C-urea breath test 6 weeks after the end of the treatment. Moreover, we examined any side effects that caused discontinuation of therapy. RESULTS: Twenty-three patients received bismuth-containing quadruple therapy as the second line treatment. The overall eradication rates by ITT and PP analyses were 60.87% (n=14/23) and 73.68% (n=14/19). All the patients showed good compliance, and there were no serious adverse events. CONCLUSIONS: Bismuth-containing quadruple therapy is insufficient as the second line eradication treatment after a failed attempt of moxifloxacin-based sequential or reverse sequential therapy. Large-scale clinical trials should be performed to establish better clinical evidence.

Unilateral Posterior Reversible Encephalopathy Syndrome Secondary to Renal Artery Obstruction: A Case Report / 대한소아신경학회지

Posterior reversible encephalopathy syndrome (PRES, or posterior leukoencephalopahty syndrome) is a neurological condition caused by reversible cortical/subcortical vasogenic brain edema secondary to hypertension, cytotoxic drugs, immunosuppressants, autoimmune diseases, renal disease, eclampsia or pre-eclampsia. It is characterized by acute neurological symptoms such as headache, seizures, visual disturbances, and impaired levels of consciousness. Brain imaging usually reveals bilateral, cortical/subcortical vasogenic edema. Completely unilateral PRES constituted only 2.6% of the cases in a previous study. Here we report the case of a pediatric patient with completely unilateral PRES. A 13-year-old boy was admitted with acute gastroenteritis. On the fourth day of hospitalization, he started to complain of headache and vomiting. He then developed generalized tonic-clonic seizure 3 times. His blood pressure was 180/121 mmHg during the first seizure, 188/112 mmHg during the second seizure and 152/92 mmHg during the third seizure. T2-weighted imaging with fluid attenuation by inversion recovery (T2 FLAIR) demonstrated high-signal intensity in the cortical gyri of the left frontal, parietal, and occipital lobes. Follow-up magnetic resonance imaging (MRI) was performed 2 weeks after the seizure onset, which indicated a significant improvement in the patient's condition. Abdominal pelvic computed tomography (CT) and renal CT angiography showed abnormal narrowing of the left renal artery. In summary, we present a case report of unilateral PRES secondary to renovascular hypertension due to left renal arterial obstruction.

Magnified Endoscopic Findings of Multiple White Flat Lesions: A New Subtype of Gastric Hyperplastic Polyps in the Stomach

BACKGROUND/AIMS:: While the occurrence of multiple whitish flat elevated lesions (MWFL) was first reported in 2007, no studies on MWFL have been published to date. The present retrospective observational study aimed to clarify the endoscopic findings and clinicopathological features of MWFL. METHODS:: Subjects were consecutive patients who underwent upper gastrointestinal endoscopy as part of routine screening between April 2014 and March 2015. The conventional white-light, non-magnifying and magnifying narrow-band images were reviewed. Clinical features were compared between patients with and without MWFL. RESULTS:: The conventional endoscopic findings of MWFL include multiple whitish, flat, and slightly elevated lesions of various sizes, mainly located in the gastric body and fundus. Narrow-band imaging enhanced the contrast of MWFL and background mucosa, and magnifying narrow-band imaging depicted a uniformly long, narrow, and elliptical marginal crypt epithelium with an unclear microvascular pattern. Histopathological findings revealed hyperplastic changes of the foveolar epithelium, and parietal cell protrusions and oxyntic gland dilatations were observed in the fundic glands, without any intestinal metaplasia. The rate of acid-reducing drug use was significantly higher in patients with MWFL than in those without (100% [13/13] vs. 53.7% [88/164], p < 0.001). CONCLUSIONS:: The present study indicated a relationship between the presence and endoscopic features of MWFL and history of acidreducing drug use.

Spontaneous Remission of Pernicious Anemia / 대한내과학회지

Pernicious anemia is a macrocytic anemia that is caused by vitamin B12 deficiency, itself a result of the absence of intrinsic factors due to autoimmune destruction of parietal cells. We report here the case of a 43-year-old female with spontaneous remission of pernicious anemia. The patient presented with fatigue. Her serum vitamin B12 level was low, hemoglobin level was 7.6 g/dL, and serologic tests for anti-intrinsic factor and anti-parietal cell antibodies were positive. We diagnosed her with pernicious anemia, but did not administer vitamin B12 because her hemoglobin level increased spontaneously. Since then, the patient's hemoglobin and serum vitamin B12 levels have been within the normal range.

Clinical Efficacy of Gemifloxacin-containing Triple Therapy for First-line Treatment of Helicobacter pylori Infection: A Pilot Study

BACKGROUND/AIMS: Levofloxacin resistance is increasing rapidly, and widely limits its application in Helicobacter pylori eradication. This study aimed to evaluate the efficacy of a clarithromycin- versus gemifloxacin-containing triple therapy regimen in first-line eradication of H. pylori infection. MATERIALS AND METHODS: This was an open-label, prospective, non-randomized two-armed pilot study in which treatment-naïve subjects with active H. pylori infection received a seven-day triple therapy with rabeprazole 20 mg bid (twice daily), gemifloxacin 320 mg qd (once daily), and amoxicillin 500 mg bid (n=70) or seven-day triple therapy with rabeprazole 20 mg bid (twice daily), clarithromycin 500 mg bid (twice daily), and amoxicillin 500 mg bid (n=83). H. pylori infection status was checked in all patients at enrollment and at least 8 weeks after the end of therapy by the urea breath test. RESULTS: Intention-to-treat eradication rates were 71.1% and 74.3% for clarithromycin-containing triple therapy and gemifloxacin- containing triple therapy, respectively (P=0.398). The corresponding per-protocol eradication rates were 76.6% and 76.1% (P=0.624). The gemifloxacin-containing triple therapy was associated with a lower incidence of adverse events (2.9% vs. 18.5%, P=0.003). CONCLUSIONS: Although the seven-day gemifloxacin-containing triple therapy regimen showed a more favorable safety profile, there was no significant difference in eradication rates between the gemifloxacin-containing and clarithromycin-containing triple regimens, and both regimens had eradication rates slightly lower than acceptable efficacy for the Korean population. Therefore, the gemifloxacin-containing regimen might be useful as an alternative regimen for patients showing severe side effects of clarithromycin due to poor tolerance. Further studies on the efficacy of gemifloxacin in the Korean population are warranted.

Postoperative Subarachnoid Hemorrhage and Multipunctate Intracerebral Hemorrhages Following Evacuation of Bilateral Chronic Subdural Hematomas / 대한신경손상학회지

Chronic subdural hematoma (CSDH) can be easily treated by burr hole surgery. However, several complications including intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and acute subdural hematoma are rare after evacuation of a CSDH. A 77-year-old man was admitted with right hemiparesis and dysarthria. A brain computed tomography (CT) scan revealed a bilateral CSDH with midline shifting toward the right side. The patient got the burr hole trephination with the catheters insertion in the both sides of parietal area under the local anesthesia. After burr hole surgery immediately, he developed left side weakness and decreased level of consciousness. Repeat CT scans detected a diffuse SAH and multiple small ICHs. He was treated conservatively and fully recovered at discharge after 1 month. To avoid these complications, slow and gradual drainage of the CSDH is needed. The authors report a rare case of SAH and multipunctate ICHs in both cerebral hemispheres after evacuation of a bilateral CSDH.

25 Years of Proton Pump Inhibitors: A Comprehensive Review

Proton pump inhibitors (PPIs) were clinically introduced more than 25 years ago and have since proven to be invaluable, safe, and effective agents for the management of a variety of acid-related disorders. Although all members in this class act in a similar fashion, inhibiting active parietal cell acid secretion, there are slight differences among PPIs relating to their pharmacokinetic properties, metabolism, and Food and Drug Administration (FDA)-approved clinical indications. Nevertheless, each is effective in managing gastroesophageal reflux disease and uncomplicated or complicated peptic ulcer disease. Despite their overall efficacy, PPIs do have some limitations related to their short plasma half-lives and requirement for meal-associated dosing, which can lead to breakthrough symptoms in some individuals, especially at night. Longer-acting PPIs and technology to prolong conventional PPI activity have been developed to specifically address these limitations and may improve clinical outcomes.

IL-10 Plays a Pivotal Role in Tamoxifen-Induced Spasmolytic Polypeptide-Expressing Metaplasia in Gastric Mucosa

BACKGROUND/AIMS: Gastric cancer evolves in the pathologic mucosal milieu, and its development is characterized by both the loss of acid-secreting parietal cells and mucosal cell metaplasia, called spasmolytic polypeptide-expressing metaplasia (SPEM). Cytokines, such as interleukin (IL)-10, IL-1β, and IL-6, play a key role in gastric carcinogenesis. However, changes in the cytokine profile of SPEM have not been evaluated. METHODS: To induce SPEM in mouse stomachs, C57BL/6 mice were intraperitoneally injected with tamoxifen and sacrificed at 3, 10, and 21 days after treatment. RNA-sequencing (RNA-seq) and a multiplex bead array were used to measure cytokines in the stomachs of tamoxifen-treated/control mice. RESULTS: The administration of tamoxifen led to the rapid development and histological normalization of SPEM 3 and 10 days after administration, respectively. RNA-seq revealed that the expression of IL-10 was decreased 3 days after tamoxifen administration. The multiplex assay identified a significant decline in IL-10 levels 3 days after tamoxifen treatment (58.38±34.44 pg/mL vs 94.09±4.98 pg/mL, p=0.031), which normalized at 10 and 21 days after tamoxifen treatment. Immunofluorescence staining confirmed that IL-10 expression was markedly decreased at the time of SPEM development and subsequently returned to normal, accompanied by a reversal in histologic changes. CONCLUSIONS: IL-10 may play a pivotal role in the tamoxifen-induced acute development of gastric SPEM.

The Effect of H₂ Receptor Antagonist in Acid Inhibition and Its Clinical Efficacy / 대한소화기학회지

The first histamine H₂ receptor antagonists (H₂RAs) were developed in the early 1970s. They played a dominant role in treating peptic ulcer disease and gastroesophageal reflux disease (GERD). H₂RAs block the production of acid by H⁺, K⁺-ATPase at the parietal cells and produce gastric luminal anacidity for varying periods. H₂RAs are highly selective, and they do not affect H₁ receptors. Moreover, they are not anticholinergic agents. Sequential development of H₂RAs, proton pump inhibitors (PPIs), and discovery of Helicobacter pylori infection changed the paradigm of peptic ulcer disease with marked decrease of morbidity and mortality. PPIs are known to be the most effective drugs that are currently available for suppressing gastric acid secretion. Many studies have shown its superiority over H₂RAs as a treatment for acid-related disorders, such as peptic ulcer disease, GERD, and Zollinger-Ellison syndrome. However, other studies have reported that PPIs may not be able to render stomach achlorhydric and have identified a phenomenon of increasing gastric acidity at night in individuals receiving a PPI twice daily. These nocturnal acid breakthrough episodes can be eliminated with an addition of H₂RAs at night. The effectiveness of nighttime dose of H₂RA suggests a major role of histamine in nocturnal acid secretion. H₂RAs reduce secretion of gastric acid, and each H₂RA also has specific effects. For instance, nizitidine alleviates not only symptoms of GERD, but also provokes gastric emptying, resulting in clinical symptom improvement of functional dyspepsia. The aim of this paper was to review the characteristics and role of H₂RAs and assess the future strategy and treatment of upper gastrointestinal disease, including acid related disorders.