Anti-inflammatory effect of recombinant thrombomodulin for fulminant hepatic failure.

Fulminant hepatic failure (FHF) is a critical illness that can be comorbid to primary liver damage. FHF shows a high mortality rate, and patients with FHF require intensive therapy, including plasma apheresis. However, intensive care at the present is not enough to restore the severe liver damage or promote hepatocellular reproduction, and a standard therapy for the treatment of FHF has not been established. An 86-year-old female with FHF was admitted to our hospital. Her manifestation demonstrated a clinical situation of systemic inflammatory response syndrome (SIRS) and disseminated intravascular coagulation. A diagnosis of fulminant hepatitis was made according to the definition given in the position paper of the American Association for the Study of Liver Diseases. Her serum hepatocyte growth factor (HGF) level had increased to 11.84 ng/mL. The HGF level indicated massive liver damage as seen in FHF. Recombinant thrombomodulin (rTM) was administered daily from the admission day for 1 wk at 380 U/kg. The patient's white blood cells and C-reactive protein responded to the rTM treatment within a few days. The HGF level and PT recovered to the normal range. The levels of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1ß) were suppressed by the administration of rTM. The patient's hepatic function (e.g., PT and albumin) completely recovered without plasma exchange. rTM may modulate the over-response of SIRS with the improvement of proinflammatory cytokines. The underlying mechanism is thought to be the inhibitory effect of rTM on high-mobility group box 1 (HMBG1). The pathogenesis of HMBG1 protein in fulminant hepatic failure has been already known. A novel favorable effect of rTM for SIRS would be promising for FHF, and the wide application of rTM for SIRS should be considered.

Esophageal function worsens with long duration of diabetes.

BACKGROUND: The aim of this study was to assess the relationship between the duration of diabetes and esophageal dysfunction. METHODS: We examined 66 patients with type 2 diabetes. Duration of diabetes was determined by asking patients and from their medical records. The patients were divided into three groups according to the duration of their diabetes: group A, 1-4 years, n=26; group B, 5-9 years, n=20; and group C, 10+ years, n=20. Ambulatory esophageal 24-h pH and motility were monitored, and gastroesophageal reflux and esophageal motility disorders were estimated in detail. RESULTS: When the duration of diabetes was long, the percentage of time with pH<4 tended to increase. The amplitude of esophageal peristaltic waves and the frequency of effective peristalsis were reduced when the duration of diabetes was long. A significant correlation was observed between the duration of diabetes and the frequency of effective peristalsis. The number of esophageal peristaltic waves per minute and the percentage of multipeaked peristaltic waves increased significantly in group B, and decreased when the duration of diabetes became longer. CONCLUSIONS: Gastroesophageal reflux and esophageal motility disorders worsened with long duration of diabetes. These esophageal dysfunctions should be considered in patients with long-standing diabetes.

[Gastroesophageal reflux disease in diabetic patients].

Esophageal dysfunctions occur frequently in patients with diabetic neuropathy, and the complication of gastroesophageal reflux disease(GERD) has also been reported. However, the characteristics of GERD complicated with diabetes mellitus are obscure because no detailed assessment was performed. We performed long-term ambulatory esophageal pH and motility monitoring in diabetic patients, and analyzed the data in detail. Esophageal dysfunctions including GERD were significantly related to diabetic neuropathy and duration. Although GERD was frequently complicated with diabetes mellitus, the symptoms were not apparent in diabetic patients. The average score of a questionnaire was extremely low, and no significant difference in score was observed between patients with and without gastroesophageal reflux. We should keep in mind that diabetic patients have the abnormal gastroesophageal reflux even when they do not complain of the related symptoms.

Is the questionnaire for the assessment of gastroesophageal reflux useful for diabetic patients?

OBJECTIVE: It has been suggested that the questionnaire reported by Carlsson et al. has high sensitivity in diagnosing gastroesophageal reflux disease (GERD) and is considered to be one of the most useful diagnostic tools for GERD. The aim of the present study was to evaluate the ability of the questionnaire to identify gastroesophageal reflux (GER) diagnosed by 24-h pH monitoring in diabetic patients. MATERIAL AND METHODS: Fifty-three patients with type 2 diabetes were enrolled in the present study. GER was monitored by means of an antimony electrode. Patients completed the questionnaires immediately before undergoing pH monitoring. RESULTS: Diabetic patients were found to have few symptoms, and the average score on the questionnaire was extremely low. No significant difference in scores on the questionnaire was observed between patients with and those without GER. CONCLUSIONS: The questionnaire was shown not to be useful for diagnosing GER as a complication in diabetic patients. We, therefore, should not diagnose GER as a complication in diabetes mellitus on the basis of the questionnaire.

Effect of an aldose reductase inhibitor on esophageal dysfunction in diabetic patients.

BACKGROUND/AIMS: Disorders of the digestive tract in diabetic patients are mainly ascribed to disorders of the vagus nerve. Although aldose reductase inhibitors (ARIs) have been shown to be effective against diabetic peripheral neuropathy, their effectiveness on diabetic digestive neuropathy remains to be evaluated. The aim of the present study is to examine the effect of an ARI on the esophageal dysfunction in diabetic patients by monitoring pH and motility of the esophagus. METHODOLOGY: Eight type 2 diabetic patients with peripheral neuropathy were administered with the ARI epalrestat (150 mg/day) for 90 days, and esophageal pH and motility were monitored before and after the ARI treatment. RESULTS: Parameters related to the gastroesophageal acid reflux and the esophageal motility, such as % time of pH<4, DeMeester score, duration of the longest reflux episode, reflux episodes longer than 5 min, ratios of peristaltic waves with the amplitude greater than 25 mmHg and ratios of effective peristalsis were remarkably improved by the ARI treatment. CONCLUSIONS: Because the present study clearly demonstrated the effectiveness of an ARI on the esophageal dysfunction in diabetic patients, ARI may be useful for the treatment of diabetic digestive disorders.

[Gastroesophageal reflux disease in diabetic patients].

Esophageal dysfunctions occur frequently in patients with diabetic autonomic neuropathy, and the complication of gastroesophageal reflux disease (GERD) has also been reported. However, the characteristics of the GERD complicated with diabetes are obscure, because no detail assessment was performed. We recorded esophageal motility and acid reflux simultaneously in diabetic patients, and the correlation between esophageal dysfunction and diabetic neuropathy was examined. Esophageal dysfunctions including GERD were significantly related to diabetic motor neuropathy. Although the GERD is frequently complicated with diabetes, the symptoms are not apparent in diabetic patients. Therefore, physicians treating diabetic patients should have GERD in mind regardless of the symptoms. We also examined the effect of aldose reductase inhibitor (ARI) on the esophageal dysfunction in diabetic patients. Significant improvement of gastroesophageal reflux and esophageal motility were observed in diabetic patients by ARI treatment. ARI may be useful for the treatment of GERD complicated with diabetes.