Serum markers for fibrosis and plasma transforming growth factor-β1 in patients with hepatocellular carcinoma in comparison with patients with liver cirrhosis

In order to elucidate collagen metabolism in hepatocellular carcinoma (HCC) tissue, we compared levels of different potential markers of collagen metabolism and plasma transforming growth factor-β₁ in patients with HCC and in patients with liver cirrhosis. Serum levels of prolyl hydroxylase and the tissue inhibitor of metalloproteinase-1 in patients with HCC were significantly higher than those in patients with liver cirrhosis and increased with the size of the HCC tumour, whereas the serum levels of procollagen type III propeptide and type IV collagen 7S domain were similar in the two groups. In HCC, the increased plasma transforming growth factor-β₁ levels were closely correlated with serum levels of prolyl hydroxylase and the tissue inhibitor of metalloproteinase-1. These findings suggest that, in HCC tissue, the intracellular biosynthesis of collagen is enhanced, whereas the secretion of procollagen is disturbed and the degradation of collagen is suppressed by the excess production of the tissue inhibitor of metalloproteinase-1. The results also suggest that plasma transforming growth factor-β₁ plays an important role in the altered metabolism of collagen in HCC.     

Microvascular disturbances in the colonic mucosa in antibiotic-associated haemorrhagic colitis: Involvement of platelet aggregation

An ultrastructural study of the colonic mucosa was performed in four patients with antibiotic-associated haemorrhagic colitis and new findings are reported. Colonoscopy was performed and biopsy specimens were obtained within 24 h of the onset of bloody diarrhoea. Colonoscopy demonstrated diffuse oedematous and haemorrhagic mucosa with erosions and white coat. Light microscopy revealed mucosal haemorrhage and inflammatory cell infiltration. Ultrastructurally, platelet aggregation was frequently present in the lumina of colonic mucosal capillaries, causing engorgement of red blood cells in adjacent microvessels. Mild to severe damage was observed in capillary endothelial cells, including discontinuity of basement membranes, gaps between endothelial cells and the destruction of capillaries. There was no evidence of microvascular spasm. In conclusion, our findings suggest that antibiotics directly or indirectly cause microcirculatory disturbances, which result in tissue damage and haemorrhage, in the colonic mucosa.     

Relationship between severity and symptoms of reflux oesophagitis in elderly patients in Japan

Since information concerning reflux oesophagitis in the elderly is limited, particularly in Japan, the severity and symptomatic profiles of reflux oesophagitis in elderly patients were investigated. One hundred and nineteen patients with reflux oesophagitis found among 2278 endoscopy cases between 1993 and 1996 were investigated in this study. The patients were divided into two groups, elderly and non-elderly. The severity of reflux oesophagitis was estimated by the Los Angeles classification. The presence or absence of typical symptoms (heartburn and regurgitation) was determined by interview. Reflux oesophagitis was not only more frequently found in the elderly group, but was more severe than in the non-elderly. Although the degree of manifestation of typical symptoms was similar between the elderly and the non-elderly with high-grade oesophagitis, the elderly patients with mild reflux oesophagitis were less symptomatic than the non-elderly. Mild reflux oesophagitis in the elderly may be missed due to its rarity of typical reflux symptoms and a substantial number of elderly persons might have subclinical reflux oesophagitis.     

Twenty-four hour monitoring of blood pressure and heart rate in patients with chronic renal failure or renal transplant recipients: Analysis by the cosinor method

Hypertension is a major problem of patients with chronic renal failure or renal transplant recipients. To clarify the characteristics of blood pressure, heart rate, and circadian rhythms of these patients we used an ambulatory blood pressure monitor (ABPM) for 24 h monitoring and analyzed the data by the cosinor method. In eight chronic renal failure patients without dialysis the midline estimating statistic of rhythm (MESOR) of diastolic blood pressure was higher than in controls, but the MESOR of systolic blood pressure was not. Of 11 patients on dialysis some had hypertension and some had hypotension. In 14 renal transplant recipients, especially those with chronic graft rejection, the MESOR of systolic and diastolic pressures were higher than controls, and the increase of blood pressure MESOR had a significant correlation with the elevation of serum creatinine levels. Circadian rhythms of blood pressure were frequently absent in the patients on dialysis, but circadian rhythms of heart rate were not. The use of an ABPM is a non-invasive method to monitor patients and allowed us to know changes of blood pressure and heart rate in the daytime as well as during the night. For the control of hypertension in chronic renal failure, monitoring with an ABPM seems to provide invaluable information.     

Certain type of chronic lung disease of newborns is associated with Ureaplasma urealyticum infection in utero

BACKGROUND: Recent studies of chronic lung disease (CLD) of newborns emphasize the contribution of antenatal infection. However, the association of Ureaplasma urealyticum infection and CLD has been controversial. The purpose of the present paper was to determine whether U. urealyticum is associated with chorioamnionitis (CAM) and a certain type of CLD. METHODS: One hundred and five infants <32 weeks of gestation who were admitted to the neonatal intensive care unit at Jichi Medical School Hospital, who underwent both histological and microbiological examinations and who survived to discharge were included. CAM was determined by histological examination. Placenta, gastric and tracheal aspirates, and nasopharyngeal swabs were cultured for Mycoplasma and other microorganisms. CLD was defined as oxygen needed at 28 days of age with symptoms of persistent respiratory distress and hazy or emphysematous and fibrous appearance upon X-ray. CLD was further divided into two subtypes according to the presence of antenatal infection. RESULTS: CAM was associated with premature rupture of membrane (odds ratio [OR], 10.19; 95% confidence interval [CI]: 3.10-33.56), placental colonization of U. urealyticum (OR 6.73, 95%CI: 1.89-23.91), neonatal colonization of other microorganisms (OR 7.33, 95%CI: 1.22-44.13) and level of IgM (OR 1.06, 95%CI: 1.01-1.11). Comparisons between CLD and non-CLD patients showed that gestational age (OR 0.43, 95%CI: 0.30-0.61) and white blood cell count (WBC) at birth (OR 1.06, 95%CI: 1.01-1.11) were risk factors for CLD, while gestational age (OR 0.38, 95%CI: 0.23-0.64), neonatal colonization of U. urealyticum (OR 5.98, 95%CI: 1.17-30.6) and WBC (OR 1.08, 95%CI: 1.01-1.15) were independent risk factors for infection-related CLD compared with non-CLD. Within CLD, infection-related CLD was associated with neonatal colonization of U. urealyticum (OR 43.7, 95%CI: 2.84-673.8) and WBC (OR 1.27, 95%CI: 1.07-1.50). CONCLUSIONS: Placental colonization of U. urealyticum was significantly related to CAM; and neonatal colonization of U. urealyticum and leukocytosis at birth were risk factors for infection-related CLD.     

Oral Tolerance Induced by Enterobacteria Altered the Process of Lymphocyte Recruitment to Intestinal Microvessels: Roles of Endothelial Cell Adhesion Molecules,TGF‐beta and Negative Regulators of TLR Signaling

Objective: Although enterobacteria are implicated in intestinal immune response, there has been no report on how intraluminal pathogens affect lymphocyte recruitment. The aim of this study was to determine how the presence of intestinal flora affects lymphocyte migration to intestine under physiological and lipopolysaccharide (LPS)‐induced inflammatory conditions. Methods: Interaction of T‐cells with ileal microvessels was monitored by using an intravital microscope in mice under germ‐free (GF) and specific pathogen‐free (SPF) conditions. LPS was administered into either the peritoneal cavity or duodenum before lymphocyte injection. Results: Adherence of T‐cells was greater in SPF than in GF mice, indicating that the presence of enterobacteria upregulated migration under physiological conditions. Intraperitoneally administered LPS significantly increased the adherence of T‐cells in both GF and SPF mice accompanied by the expression of adhesion molecules and proinflammatory cytokines. However, intraluminally administered LPS did not enhance the adherence of T‐cells in SPF mice. A significant induction of increase in mRNA expression of IRAK‐M, a negative regulator of TLR4 signaling, and transforming growth factor beta (TGF‐beta), a regulatory cytokine, was observed in SPF mice after luminal LPS treatment. Conclusions: Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK‐M and TGF‐beta.     

Long-term effect of α-glucosidase inhibitor on late dumping syndrome

Dumping syndrome commonly occurs after gastrectomy. The late dumping, which is one of the dumping syndromes, is due to postprandial hypoglycaemia caused by an excessive insulin secretion after a sharp rise in plasma glucose. Several treatments, including operation, dietary fibre and somatostatin, have been attempted to relieve dumping symptoms. These treatments take effect through modulation of plasma insulin and glucose levels, but their efficacy is still under consideration. α-Glucosidase inhibitor attenuates the postprandial increase of plasma glucose levels and is widely used for treatment of non-insulin-dependent diabetes mellitus (NIDDM). The acute effect of α-glucosidase inhibitor on late dumping syndrome has been reported by some studies with test meals. The purpose of this study was to evaluate a long-term effect of α-glucosidase inhibitor treatment with ordinary meals in late dumping patients with NIDDM because administration of α-glucosidase inhibitor is only ethically allowed for diabetic patients in Japan. Six late dumping patients with NIDDM were orally administered α-glucosidase inhibitor, acarbose (50 or 100 mg), three times a day before each meal for 1 month. Diurnal changes of plasma glucose, insulin and pancreatic glucagon levels were compared before and after the α-glucosidase inhibitor treatment. All patients had late dumping-related symptoms, such as weakness, palpitation and dizziness before the induction of α-glucosidase inhibitor treatment. Patients suffered from a rapid fall in plasma glucose levels from hyperglycaemia at the same time as dumping symptoms. These late dumping-related symptoms disappeared and a rapid change of plasma glucose and insulin levels were attenuated after the α-glucosidase inhibitor treatment. These data suggest a long-term therapeutic efficacy of α-glucosidase inhibitor for late dumping patients.