High serum levels of granulocyte-macrophage colony-stimulating factor in patients with liver cirrhosis and granulocytopenia

Summary Leucopenia is often observed in patients with liver cirrhosis. We measured levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with liver cirrhosis by a sensitive enzyme linked immunosorbent assay. Eight out of 22 patients with liver cirrhosis had detectable serum GM-CSF (range, 55 to 245 pg/ml:mean, 135 pg/ml). Serum GM-CSF was detected in all patients with a granulocyte count below 2.0 × 10⁹/l, but in only one patient with a granulocyte count above 2.0 × 10⁹/l. Haemoglobin concentration, platelet count, serum albumin, total bilirubin and aminotransferase levels did not correlate with serum GM-CSF levels. These findings may reflect a feedback mechanism between the number of circulating granulocytes and serum GM-CSF levels in patients with cirrhosis.     

Clinical significance of hepatitis G virus infection in patients on long-term haemodialysis

Infection with the newly discovered hepatitis G virus (HGV) was analysed in 163 patients on long-term haemodialysis to clarify its prevalence and clinical significance. Hepatitis G virus RNA in serum was measured by polymerase chain reaction with primers corresponding to the putative non-structural 5’ region. Of the 163 patients, three (1.8%) were positive for hepatitis B surface antigen, 40 (24.5%) were positive for hepatitis C virus (HCV)-RNA and 16 (9.8%) were positive for HGV-RNA. Five of the 16 patients with HGV-RNA were also positive for HCV-RNA. Patients with HCV and HGV coinfection had undergone a longer duration of haemodialysis (P=0.001) and had higher units of transfusion (P=0.031) compared with those without hepatitis virus infection. Transfusion history was significantly higher (P=0.039) in patients with only HGV infection than in those without hepatitis virus infection. Hepatitis C virus RNA concentration was higher (P=0.032) in patients with HCV and HGV coinfection than in those with HCV infection only, but alanine aminotransferase (ALT) levels were similar between these two groups. In conclusion, about 10% of patients on haemodialysis were infected with HGV and the infection was closely associated with transfusion history.     

Pneumoperitoneum complicating mechanical ventilation in congenital myotonic dystrophy

Pneumoperitoneum is known as a disease caused by perforation of the gastrointestinal tract, but it has also been reported as a complication of mechanical ventilation. In a case of congenital myotonic dystrophy (CMyD), mechanical ventilation was performed to treat severe respiratory distress starting at birth, and then pneumomediastinum and pneumoperitoneum developed as complications 5 days after birth. The fact that the pneumoperitoneum improved when the ventilation pressure was reduced and the patient's course was observed, allowed us to rule out gastrointestinal perforation. It appeared that hypoplasia of the diaphragm may have been involved in the progression of pneumomediastinum to pneumoperitoneum in this patient. Mechanical ventilation is performed on many occasions in CMyD, and the development of pneumoperitoneum secondary to pulmonary air leak should always be borne in mind.     

Importance of recall and follow-up screening for chronic hepatitis C in children receiving blood products prior to 1990 in Japan

The objective was to detect chronic hepatitis C virus infection in recipients of blood products using retrospective analysis by recall and enrollment of recipients. 226 patients who received blood products for open heart surgery from January 1983 to June 1992 were examined for HCV antibody by using a second generation assay and liver function test. 22 (14%) of the 161 patients who received blood products before November 1989 had detectable HCV antibody, but none of the 65 recipients receiving blood products after 1990, the year the Japanese blood bank began to screen for HCV-antibody. Abnormal alanine aminotransferase (ALT) levels, more than 25 iu/L, during the chronic phase of HCV infection was recognized in nine of 22 (41%) seropositive patients. The liver function test and second generation HCV antibody in the serum are effective markers to screen for chronic hepatitis C in blood product recipients transfused before 1990.     

Origin of neovascular structure in an early stage of hepatocellular carcinoma: Study of alpha-smooth muscle actin immunohistochemistry in serial thin sections of surgically resected cancer

Background: To elucidate the origin of the neovascular structure found in well‐differentiated hepatocellular carcinoma (HCC), an immunohistochemical study was performed on sequential thin section specimens. Method: Eleven surgically resected specimens of well‐differentiated HCC were analyzed for neovascular structure using monoclonal alpha‐smooth muscle actin (α‐SMA) antibody. Each paraffin specimen was serially sliced to a thickness of 3 µm for immunohistochemistry. When a ring‐shaped structure was found unrelated to portal triads on α‐SMA staining, it was regarded as abnormal neovascularity (non‐triadal vessel or unaccompanied vessel). Results: All of the 11 liver cancers had thin‐walled, round‐ or oval‐shaped non‐triadal vessels in their well‐differentiated parts. Immunohistochemistry of serial thin sections of HCC showed that these non‐triadal vessels were connected to portal veins in portal triads in well‐differentiated cancer in a total of nine patients (81.8%). This type of neovascular structure found in a well‐differentiated cancer seemed to be a surviving portal vein among diminishing and disappearing arteries and bile ducts. All 11 tumors showed isovascular staining on ordinary digital subtraction angiography, and four of the tumors showed negative enhancement on intra‐arterial carbon dioxide‐enhanced ultrasonography or computerized tomographic (CT) hepatic arteriography, suggesting a relative arterial blood scarcity in the tumor nodules. Conclusion: At an early stage of HCC, non‐triadal vessels originate from ordinary portal veins in intratumoral portal triads. This fact sufficiently explains the reason why a well‐differentiated liver cancer can sometimes show arterial blood paucity on CT arteriography or enhanced ultrasonography.     

Pseudo-clitoromegaly associated with congenital prepubic sinus

We operated on a 12-year-old girl who had clitoromegaly and a sinus on the midline prepubic area congenitally. The prepubic sinus appeared to point to the clitoris on the preoperative magnetic resonance image, but the relation between the sinus and clitoromegaly was unclear. Gray-brown discharge was emitted at the site of dissection between the prepuce and clitoris and the size of the clitoris became normal. The sinus was excised, revealing a tract 1.5 cm long that extended to the retropubic sinus, and ended in a fibrous tract that was linked to the clitoris. This suggested pseudo-hypertrophy because of the discharge collected in the end of the prepubic sinus.     

Anti-hypertensive Effect of Oral Controlled-release Microspheres Containing an ACE Inhibitor (Delapril Hydrochloride) in Rats

Abstract— An oral controlled-release drug delivery system based on microspheres of polyglycerol esters of fatty acids (PGEFs), was applied to an anti-hypertensive, delapril hydrochloride. The in-vitro release profile was controlled by selecting a PGEF with an appropriate hydrophilic-lipophilic balance value for the matrix. The microspheres from which 80% of the drug was released in 6 h were orally administered to rats. The plasma concentration of the active metabolite was sustained after administration of the microspheres in comparison with administration of a solution. The in-vivo release profile was in good agreement with the in-vitro release profile. When the microspheres were administered, the pharmacological effect of delapril hydrochloride on the angiotensin I-induced pressor response was also sustained showing consistency with the plasma concentration-time curve.     

Gastric mucosal energy metabolism and intracellular mucin content changes in patients with liver cirrhosis

Biopsy samples from patients with liver cirrhosis were investigated for changes in gastric mucosal energy metabolism and intracellular mucin content using high performance liquid chromatography and an image analysing system. The test group consisted of eight non-cirrhotic patients with endoscopically normal mucosa (controls) and eight cirrhotic patients with oesophageal varices. The amount of ATP, energy charge level and intracellular mucin content were all significantly decreased in cirrhotic patients when compared with those of the controls. The decrease in energy charge also correlated well with the decrease in intracellular mucin content in the gastric mucosa. The results indicate that gastric mucosal energy metabolism is impaired in cirrhotic patients concomitantly with a decrease in the intracellular mucin content in the gastric mucosa. These changes may weaken defensive mechanisms against acid and NSAID, resulting in gastric mucosal injury in cirrhotic patients.     

Economic evaluation of Helicobacter pylori eradication for the treatment of duodenal ulcer disease in Japan: A decision analysis to assess eradication strategy in comparison with a conventional strategy

To evaluate the socio-economic effects of Helicobacter pylori eradication in the treatment of duodenal ulcer disease in Japan, a clinical decision analysis was performed to assess H. pylori eradication therapy compared with the conventional strategy of maintenance with histamine-2 receptor antagonists. A decision tree-based state transition model (Markov chain approach) implemented to simulate a 5 year period of follow up was constructed. The H. pylori eradication strategy was found to be superior to the conventional maintenance strategy with regard to clinical effectiveness and other dimensions of a patient’s outcome. Furthermore, in a long-term perspective, the eradication strategy was less costly than the maintenance strategy. Helicobacter pylori eradication should be recommended as the ?rst choice treatment of H. pylori-positive duodenal ulcer patients. The clinical implication of H. pylori eradication entails an improvement in clinical effectiveness and other dimensions of a patient’s outcome and a signi?cant reduction in the costs of duodenal ulcer treatment. The long-term total costs do not depend on the initial drug cost of an eradication regimen. Pursuing a high eradication rate of H. pylori is essential in improving the patient’s outcome and the cost-effectiveness of treatment.