[Complete resection for giant thymic carcinoma after simultaneous combination chemotherapy].

A 19-year-old man visited our hospital complaining of dyspnea. Chest X-ray and computed tomography (CT) showed a huge mass in the right anterior mediastinum. We diagnosed this as invasive thymoma by microscopic examination of specimens obtained by echo-guided needle biopsy. The patient underwent 6 courses chemotherapy [1st course : carboplatin (CBDCA) + doxorubicin hydrochloride (DXR) + vincristine sulfate (VCR) + cyclophosphamide (CPA), 2nd, 3rd-6th course : cisplatin (CDDP) + ADM + VCR + CPA]. At achievement of partial response (the reduction rate of the tumor size : 91.4%), the tumor was completely resected. The pathological examination of the resected specimens yielded a diagnosis of large cell carcinoma. Preoperative chemotherapy with ADOC regimen may be effective in advanced thymic carcinoma.

Pharmacokinetics of roxatidine acetate in patients with chronic liver disease.

BACKGROUND AND AIM: Patients with liver disease are prone to develop peptic ulceration and often receive H(2)-receptor antagonists. Therefore, it is important to clarify whether the pharmacokinetics of H(2)-receptor antagonists is affected by hepatic function. However, pharmacokinetics of a new H(2)-receptor antagonist, roxatidine acetate, in chronic liver disease has not been well known. In this study, we analyzed the pharmacokinetics of roxatidine in patients with liver disease. METHODS: Blood samples were obtained from 11 patients with chronic hepatitis, 11 patients with cirrhosis and six healthy subjects. Under fasting conditions, 75 mg of roxatidine acetate was administered orally, and plasma roxatidine levels were determined sequentially from 3 to 12 h. Relationships between pharmacokinetic variables and each parameter related to hepatic functions were also investigated. RESULTS: There was no difference in the pharmacokinetic variables and serum levels of roxatidine between chronic hepatitis and healthy controls. In contrast, in cirrhosis, serum roxatidine levels were significantly higher than those in chronic hepatitis and normal control. Half-life, the area under the plasma concentration-time curve and clearance in cirrhosis were also significantly longer, bigger and smaller than those in chronic hepatitis and healthy controls, respectively. The half-life became longer and the clearance became smaller in parallel with the progression of liver disease. Serum levels of hyaluronate and gamma-glutamyl transpeptidase showed a good correlation with half-life, clearance and elimination rate. A good correlation between creatinine clearance and elimination rate was found. CONCLUSION: Pharmacokinetics of roxatidine acetate is affected by hepatic function, and the dosage of roxatidine acetate for patients with liver disease, especially cirrhosis, should be modified.

Esophagogastrostomy reconstruction after limited proximal gastrectomy.

BACKGROUND/AIMS: Recent advances in diagnostic techniques have led to the detection of an increasing number of early gastric cancers in the upper third of the stomach. The objective of this study was to determine the most appropriate surgical treatment for these cancers. METHODOLOGY: The clinicopathologic characteristics of 35 patients with early gastric cancer in the upper third of the stomach who underwent three different types of gastrectomies were reviewed retrospectively from hospital records between January 1992 and August 1999. RESULTS: Patients undergoing limited proximal gastrectomy with esophagogastrostomy reconstruction had shorter operation times and less blood loss than those for patients undergoing total gastrectomy or proximal gastrectomy with jejunal interposition. No lymph node metastasis was identified in any of these patients. Heartburn due to reflux esophagitis was seen in a few patients of each group, but they were successfully treated by antacids. The extreme reduction in food intake volume was more frequently experienced in patients with total gastrectomy than those with both proximal gastrectomies. When mortality due to other disease was excluded, all patients survived without recurrence. CONCLUSIONS: A limited proximal gastrectomy with esophagogastrostomy reconstruction decreased surgical risk and realized preservation of maximal function.

High density collimated beams of relativistic ions produced by petawatt laser pulses in plasmas

Under optimal interaction conditions ions can be accelerated up to relativistic energies by a petawatt laser pulse in both underdense and overdense plasmas. Two-dimensional particle in cell simulations show that the laser pulse drills a channel through an underdense plasma slab due to relativistic self-focusing. Both ions and electrons are accelerated in the head region of the channel. However, ion acceleration is more effective at the end of the slab. Here electrons from the channel expand in vacuum and are followed by the ions dragged by the Coulomb force arising from charge separation. A similar mechanism of ion acceleration occurs when a superintense laser pulse interacts with a thin slab of overdense plasma and the pulse ponderomotive pressure moves all the electrons away from a finite-diameter spot.

[Study of how to continue peak flow monitoring for patients with bronchial asthma: questionnaire to continuation and interruption patients].

Since 1993, our hospital has actively pursuing introduction of peak flow monitoring for patients with bronchial asthma. However, a number of patients are found to discontinue PEF monitoring. In order to determine the causes, a comparative analysis of recognition between patients who continued PEF monitoring (continuation group, hereafter) and those who discontinued PEF monitoring (interruption group, hereafter) was conducted through a questionnaire survey. The number of patients with bronchial asthma who responded to the questionnaire was 120; among them, the number of cases who continued and interrupted PEF monitoring were 68 and 52, respectively. The percentage of patients whose symptoms improved after the introduction of PEF monitoring was higher in the continuation group than in the interruption group. Approximately half of the patients in the interruption group commented that PEF monitoring was valid. The percentage of patients who believed that PEF monitoring is valid was higher in the group of patients who experienced reduction in the severity of symptom after introduction of PEF monitoring compared with those who did not. From these results, to keep high compliance of PEF monitoring, we propose that introduction of PEF monitoring and education of self-management should be positively stated for patients in unstable state. Furthermore, we found that some of the patients in the interruption group expressed interest in restarting PEF monitoring, indicating that each patient should be dealt with on a case by case basis. Appeals from doctors, patients education and advice of relatively few measurements, were found to be especially important in motivating patients to use PEF monitoring.

Study of mitochondrial DNA deletion in alcoholics.

BACKGROUND: Recently, it has been reported that single or multiple mitochondrial DNA (Mt-DNA) deletions have been observed frequently in liver tissue and white blood cells (WBC) obtained from patients with alcoholic liver disease (ALD). In this study, we investigated the deletion of the Mt-DNA encoding adenosine triphosphatase (ATPase) region in WBC to clarify whether Mt-DNA heteroplasmy caused by alcohol drinking is reversible. METHODS: Blood samples were obtained from 4 healthy volunteers, 56 patients with ALD, and 106 nonalcoholic healthy controls. The Mt-DNA encoded ATPase region was amplified by polymerase chain reaction (PCR) by using two primers: forward primer, 5'-AACCAACACCTCTTACAGTGA; and reverse primer; 5'-TTGGTGGGTCATTATGTGTTGT. RESULTS: Heteroplasmy was observed in one volunteer on day 3 and in the remaining persons on day 4 after the start of alcohol consumption. Heteroplasmy was observed for another 6 days after alcohol consumption stopped, but on the 7th day it had disappeared in all volunteers. In WBC Mt-DNA obtained from ALD patients within 3 days of abstinence, heteroplasmy was observed in 38 of the 56 patients (67.9%), whereas heteroplasmy was not detected in any healthy subjects. In 10 of the 18 ALD patients (56%) who had heteroplasmy within 3 days of abstinence, heteroplasmy disappeared after 4 weeks of abstinence. CONCLUSION: An acquired mutation of Mt-DNA, at least in the encoding ATPase region, may result from alcohol drinking and may be reversed by stopping drinking.

Immunohistochemical study of hyaluronate receptor (CD44) in alcoholic liver disease.

BACKGROUND: It has been suggested that the elevation of serum hyaluronate (HA) levels in liver diseases may be due to increased synthesis of HA by hepatic stellate cells or decreased degradation by sinusoidal endothelial cells. The increase in serum HA levels in patients with cirrhosis is thought to be a response to a reduction in HA receptors (CD44) in hepatic sinusoidal endothelial cells. To learn more about how alcohol affects the number and distribution of HA receptors of hepatic sinusoidal endothelial cells, we immunohistochemically studied CD44 levels in liver biopsy obtained from patients with alcoholic liver disease (ALD patients) and also from patients with nonalcoholic liver disease (non-ALD); ALD patients were evaluated when they were currently drinking and again after they became abstinent. Normal liver tissue obtained from three autopsy cases served as a control. METHODS: Liver biopsy specimens were obtained from 18 ALD patients and 12 non-ALD patients. In ALD patients, liver biopsy was performed twice within 3 days and 4 to 8 weeks after abstinence when serum levels of aspartate aminotransferase and alanine aminotransferase became normal. CD44 in liver specimens was stained with anti-CD44 antibody by streptavidine-biotin-peroxidase complex. The intensity of the staining of CD44 in liver tissue was determined by a computer-assisted imaging analyzer. We also measured serum levels of CD44 in both ALD and non-ALD patients. RESULTS: The intensity and the number of CD44 staining increased in both ALD and non-ALD patients compared with those in normal liver, which was negative. The staining intensity of CD44 in liver specimens obtained from patients with ALD who were active in alcohol consumption were significantly higher when compared with patients with ALD after abstinence. Serum levels of CD44 in patients with liver disease increased compared with those of healthy subjects. CONCLUSIONS: The results suggest that HA receptors may increase to degrade the increased HA in serum and/or liver.

[Thymic carcinoma successfully treated by a combination of intra-arterial infusion chemotherapy and surgery].

A 47-year-old man with thymic carcinoma that had invaded the inner pericardium and adhered to the superior vena cava and right atrium at first operation was treated with intra-arterial infusion chemotherapy (nedaplatin and adriamycin) through the internal thoracic artery. After 2 courses of modified ADOC therapy (nedaplatin, adriamycin, vincristine, and cyclophosphamide), chest computed tomographic (CT) scans revealed a 47% reduction in tumor size. No adverse effects due to the anticancer drugs were observed. Resection of the tumor included part of the upper lobe of the right lung and pericardium. Examination of resected tumor tissue specimens revealed viable cancer cells and extensive fibrosis. The diagnosis was thymic anaplastic carcinoma. We concluded that intra-arterial selective infusion chemotherapy utilizing an ADOC regimen can be of value as a treatment for thymic carcinoma.

Effects of a new orally active dopamine prodrug, docarpamine, on refractory ascites: a pilot study.

OBJECTIVE: Refractory ascites is a debilitating condition in patients with cirrhosis. Recently, docarpamine, an orally active dopamine prodrug, was reported to increase renal blood flow, glomerular filtration, and sodium excretion. This suggests docarpamine may be useful for the treatment of refractory ascites. METHODS: In this study, we investigated docarpamine metabolism in cirrhotic patients and its effect on refractory ascites. RESULTS: Blood samples were obtained from seven cirrhotic patients and six healthy subjects after administration of 750 mg docarpamine, and plasma levels of free dopamine were measured. In healthy subjects, maximum plasma concentration (Cmax), time taken to reach Cmax (Tmax), elimination half-life (T(1/2)), and area under the plasma concentration-time curve (AUC) of plasma free dopamine were 76.8 +/- 24.1 ng/ml, 1.3 +/- 0.2 h, 0.8 +/- 0.1 h, and 97.5 +/- 21.1 ng x h/ml, respectively. In patients with cirrhosis, Cmax (53.1 +/- 24.9 ng/ml), T(1/2) (0.8 +/- 0.1 h), and AUC (100.6 +/- 45.6 ng x h/ml) were no different from healthy subjects when comparing each parameter, whereas Tmax (2.7 +/- 0.2) was significantly longer than that of healthy subjects. We treated 10 cirrhotic patients with refractory ascites with docarpamine or placebo and the same dose of diuretics used before hospitalization. After 8 wk of docarpamine treatment, ascites disappeared completely in three of the five patients and decreased in the remainder. However, in five patients treated with placebo, ascites was not changed or increased. Side effects were not observed in any case. CONCLUSIONS: Docarpamine was found to metabolize in cirrhotic patients as well as in normal subjects and may be an effective treatment for refractory ascites.

Clinicopathological study of chronic hepatitis induced by alcohol with or without hepatitis G virus.

The concept of chronic hepatitis induced by alcohol (AL-CH) has not been widely accepted, because AL-CH may be due to non-A-E hepatitis virus in heavy drinkers. Recently, hepatitis G virus (HGV) was identified as a positive-strand RNA virus related to members of the Flaviviridae family. In this study, we determined serum HGV in patients with AL-CH and analyzed the clinicopathological changes after abstinence to evaluate whether AL-CH is caused by alcohol or not. Serum samples were obtained from 16 patients with AL-CH who had neither hepatitis B nor C virus. The diagnosis was confirmed histologically. In eight patients, liver biopsy was performed twice, within 3 days and 4 to 8 weeks after abstinence. The NS3 region of the HGV genome was detected using an reverse transcriptase-polymerase chain reaction method. Serum levels of AST, ALT and gamma-glutamyltranspeptidase were measured once a week sequentially after admission. Serum HGV-RNA was detected in only one patient with AL-CH (6.3%). In all patients, including one patient with HGV, serum levels of AST, ALT and gamma-glutamyltranspeptidase clearly decreased to normal levels after abstinence. Inflammatory activity in the periportal area of patients with actively drinking decreased or disappeared after abstinence for 4 to 8 weeks. These results suggest that HGV may not play an important role for development of AL-CH, and that AL-CH may be caused by alcohol itself, although a more larger number of patients with AL-CH are needed to obtain definitive conclusions.

Histochemical study of hyaluronate in alcoholic liver disease.

Recently, it has been reported that serum hyaluronate (hyaluronic acid; HA) concentrations increase in various liver diseases, especially in alcoholic liver disease (ALD), and serum HA concentration has been used as a marker for hepatic fibrosis. However, it is unknown whether hepatic HA contents in ALD increase by alcohol or not. In this study, we histochemically stained HA in liver biopsy specimens obtained from ALD patients while actively drinking and after abstinence to clarify the effects of alcohol on hepatic HA contents. Liver biopsy specimens were obtained from 13 patients with ALD and 10 patients with non-ALD. In ALD patients, liver biopsy was performed twice within 3 days, and 4 to 8 weeks after abstinence when serum levels of AST and ALT normalized. HA in biopsy specimens was stained histochemically with biotinylated HA binding protein. Staining intensity of HA in liver tissue was also determined by computer-assisted imaging analyzer. HA staining was clearly observed in sinusoidal wall and fibrous regions around the portal tract and central vein in liver diseases. HA staining intensities in patients actively drinking with ALD increased markedly, compared with those in patients with non-ALD, and these intensities decreased with abstinence. These results clearly suggest that hepatic HA contents in ALD may be increased by alcohol in addition to hepatic fibrosis, and, therefore, increased HA deposition in the liver may be reversible by abstinence of alcohol.

Nucleus-electron model for states changing from a liquid metal to a plasma and the Saha equation.

We extend the quantal hypernetted-chain (QHNC) method, which has been proved to yield accurate results for liquid metals, to treat a partially ionized plasma. In a plasma, the electrons change from a quantum to a classical fluid gradually with increasing temperature; the QHNC method applied to the electron gas is in fact able to provide the electron-electron correlation at an arbitrary temperature. As an illustrating example of this approach, we investigate how liquid rubidium becomes a plasma by increasing the temperature from 0 to 30 eV at a fixed normal ion density 1.03x10(22)/cm(3). The electron-ion radial distribution function (RDF) in liquid Rb has distinct inner-core and outer-core parts. Even at a temperature of 1 eV, this clear distinction remains as a characteristic of a liquid metal. At a temperature of 3 eV, this distinction disappears, and rubidium becomes a plasma with the ionization 1.21. The temperature variations of bound levels in each ion and the average ionization are calculated in Rb plasmas at the same time. Using the density-functional theory, we also derive the Saha equation applicable even to a high-density plasma at low temperatures. The QHNC method provides a procedure to solve this Saha equation with ease by using a recursive formula; the charge population of differently ionized species are obtained in Rb plasmas at several temperatures. In this way, it is shown that, with the atomic number as the only input, the QHNC method produces the average ionization, the electron-ion and ion-ion RDF's, and the charge population that are consistent with the atomic structure of each ion for a partially ionized plasma.

Ion explosion and multi-mega-electron-volt ion generation from an underdense plasma layer irradiated by a relativistically intense short-pulse laser.

Ion acceleration and expansion in the interaction of a relativistically intense short-pulse laser with an underdense plasma layer are investigated. Ion and electron dynamics are studied by a two-dimensional particle-in-cell simulation with the real mass ratio. It is shown that the longitudinal electric field induced by electron evacuation due to a large ponderomotive force or light pressure can accelerate ions to several MeV in the direction of the laser propagation. It is after the laser completely passes through the plasma layer that the ion explosion starts to be significant.

Characteristics of serum hyaluronate concentrations in patients with alcoholic liver disease.

It has been reported that serum hyaluronate [hyaluronic acid (HA)] concentrations are increased in liver diseases, especially in alcoholic liver disease (ALD). However, the characteristics of serum HA concentration in patients with ALD have not been studied. In this study, first, we measured serum HA concentrations in patients with different stages of both ALD and non-ALD to clarify the characteristics of serum HA concentration in patients with ALD. Second, we measured serum HA concentrations in patients with ALD sequentially after abstinence. We also measured serum HA concentrations in patients with chronic type C hepatitis before and after treatment with interferon. Finally, we analyzed the relationship between serum HA concentrations and the contents of type IV collagen and laminin in the livers of both ALD and non-ALD patients. Serum HA concentrations in liver disease were higher than the cut-off value, and increased significantly (p < 0.001) in parallel with the progression of hepatic fibrosis in both ALD and non-ALD patients. Serum HA concentrations in patients actively drinking with ALD were significantly higher (p < 0.001) than those in non-ALD. After 4 weeks of abstinence, these concentrations fell to the levels of non-ALD. Although serum ALT levels were decreased in 80% of patients treated with interferon, serum HA concentrations were not changed or increased. A significant correlation between serum HA concentrations and hepatic type IV collagen and laminin content was present in ALD, but not in non-ALD. These results clearly suggest that the increase of serum HA concentrations in ALD may be associated with not only hepatic fibrosis, but also alcohol drinking.

Clinical significance of hepatitis GB virus C infection in alcoholic liver disease.

Recently, hepatitis GB virus C (HGBV-C) has been recovered from patients with non-A-E hepatitis. However, it has been unclear whether HGBV-C may be related to the development of alcoholic liver disease (ALD) or not. In this study, we determined HGBV-C RNA in sera from alcoholic patients without markers for hepatitis C and B viruses to evaluate the role of HGBV-C in ALD. Serum samples were obtained from 68 patients with ALD and 40 nonalcoholic patients with chronic type C liver disease. HGBV-C RNA was detected in only 3 of 68 (4.4%) patients with ALD, in 2 of 27 patients with hepatic fibrosis, and in 1 of 5 patients with chronic hepatitis. There was no HGBV-C RNA in sera from patients with fatty liver, alcoholic hepatitis, or cirrhosis. Serum levels of AST, ALT, and gamma-glutamyltranspeptidase in alcoholic patients with, as well as without, HGBV-C RNA decreased to normal levels after abstinence. In addition, an inflammatory change was not observed in liver biopsy specimens obtained from two HGBV-C-positive patients with alcoholic hepatic fibrosis. Our results clearly suggest that the prevalence of HGBV-C infection in patients with ALD is rare and that HGBV-C may not play an important role in the development of liver disease in alcoholics.

Serum markers for hepatic fibrosis in alcoholic liver disease: which is the best marker, type III procollagen, type IV collagen, laminin, tissue inhibitor of metalloproteinase, or prolyl hydroxylase?

Although various serum markers for the evaluation of hepatic fibrosis have been introduced, it remains unclear which is the best marker to evaluate the hepatic fibrosis observed in alcoholic liver disease (ALD). In this study, we measured serum concentrations of the immunoreactive beta-subunit of prolyl hydroxylase, procollagen type III peptide, the 7S domain (7S-IV) and triple-helix domain (TH-IV) of type IV collagen, laminin, and tissue inhibitor of metalloproteinase (TIMP) in patients with and without ALD (non-ALD), and controls to evaluate the best serum marker reflecting the characteristic histologic features of ALD. After Azan-Mallory and silver-impregnated reticulin staining, histologic specimens were examined; and the degree of hepatic fibrosis was classified as mild, moderate, or severe. Although serum concentrations of all markers, except for TIMP, in patients with each type and stage of liver disease were higher than cut-off values and these concentrations increases with the progression of liver disease, statistical analyses indicate that serum TH-IV concentration is the best marker to distinguish ALD from non-ALD. A good correlation was also found between the hepatic type IV collagen content and serum TH-IV, but not serum 7S-IV concentration. Moreover, after abstinence from alcohol, serum concentrations of TH-IV decreased more quickly than other serum markers. These results clearly suggest that, compared with other markers, serum concentration of TH-IV may more strongly reflect the histologic features of ALD. However, other serum markers, except for TIMP, may be useful in evaluating the degree of hepatic fibrosis.

Acetaminophen metabolism in patients with different cytochrome P-4502E1 genotypes.

Cytochrome P-450 (CYP) 2E1 is the major ethanol-oxidizing enzyme of the nonalcohol dehydrogenase metabolic pathway in the liver. Recently, the presence of genetic polymorphisms of this enzyme was confirmed. In this study, to clarify the influence of CYP2E1 genotype on alcohol metabolism, we analyzed acetaminophen metabolism in subjects with different CYP2E1 genotypes. In normal subjects, a half-life of acetaminophen from blood was the longest in type A (c1/c1) and was the shortest in type C (c2/c2). The elimination rate in type C was more than twice that of type A and type B (c1/c2). In type A, both half-life and elimination rate of acetaminophen were not different between patients with noncirrhotic alcoholic liver disease within 1 week after abstinence and in normal subjects. In one patient with minimal change, there were no differences in both half-life and elimination rate within 1 and 6 weeks after abstinence. On the other hand, in type B, half-life was shorter and the elimination rate was greater in alcoholic noncirrhotic patients within 1 week after abstinence than in alcoholic patients with type A and in normal subjects with type B. In type B, half-lives were shorter, and the elimination rates were greater in patients with alcoholic liver disease within 1 week after abstinence than 4 to 6 weeks after abstinence. These results suggest the possibility that alcohol metabolism in individuals with the c2 gene may be greater than those with the c1 gene, and that the induction of CYP2E1 by ethanol in type B may occur more markedly than that in type A, although the sample number is too small to obtain final conclusions.

Noninvasive analysis of water movement in rat testis using deuterium magnetic resonance imaging.

To measure water movement in the testis without the effects from the blood-testis barrier, we performed in vivo deuterium magnetic resonance imaging (2H MRI) of rats administered with deuterated saline. Alcohol was injected into one testis of each animal and the other was administered with normal saline as a control. Dynamic 2H MRI was obtained at 2 T by FLASH pulse sequence (TR, 300 ms; TE, 10 ms; alpha = 90 degrees) using a surface coil (3 cm in diameter). The variation in 2H signal intensity between the two testes as a function of time after deuterated saline injection was examined every 1.1 min up to 20 min. The signal intensity in the testis receiving the alcohol treatment was lower than that in the normal control. Thus, deuterium MRI can be used to analyze functional disorders of the testis.