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Biomedical subjects

K Dohmen

Publications and source records attributed to K Dohmen.

At least 19 recordsLinked to original sources

Ultrasound evaluation of the fibrosis stage in chronic liver disease by the simultaneous use of low and high frequency probes.

A liver biopsy is currently considered the definitive diagnostic modality for establishing the severity of hepatic fibrosis. We analysed the diagnostic sensitivity and accuracy of ultrasound (US) using both low frequency and high frequency probes as a repeatable, inexpensive, and reliable method to determine the fibrosis stage in chronic liver disease and then compared our results with the histological findings. A total of 103 patients with chronic liver disease (60 males and 43 females, average age 51 years old) who had undergone both a liver biopsy and US with 2-5 MHz frequency and 5-12 MHz frequency probes were prospectively evaluated in this study. An US scoring system using both the low frequency and high frequency probes was performed by evaluating the edge, surface and parenchymal texture of the liver. Each score was obtained by evaluating three parameters; the bluntness of the liver edge, the irregularity of the surface and the coarseness of the parenchymal texture were evaluated and then compared with the histological findings. The US scores of the liver edge (rs: 0.6668), liver surface (rs: 0.9007) and liver parenchymal texture (rs: 0.8853) correlated significantly with the fibrosis stage obtained based on the biopsy findings. The accumulated US scores of these three parameters, however, was found to be the most reliable indicator (rs: 0.9524). Patients with an accumulated score of 6.5 or more were all found to have fibrosis stage 4 in which the accuracy of our scoring system for correctly predicting cirrhosis was found to be 100% sensitive. When an accumulated US score of 3 was interpreted to indicate mild fibrosis (a fibrosis score of 0 or 1), all 42 patients with stage 0 or 1 fibrosis were found to have an accumulated US score of 3 or less (a probability of 100%) and 42 of 53 patients with a score of 3 or less were found to have stage 0 or 1 fibrosis (specificity of 79.2%). An ultrasound evaluation of the liver fibrosis stage based on the scoring system using both low and high frequency probes was found to be a reliable and effective alternative to the histological staging in chronic liver diseases.

Biopsy↗

Gender differences in pharmacokinetics of alcohol.

BACKGROUND: The enhanced vulnerability of women to develop alcohol-related diseases may be due to their higher blood alcohol levels after drinking, but the mechanism for this effect is debated. METHODS: Sixty-five healthy volunteers of both genders drank 0.3 g of ethanol/kg of body weight (as 5%, 10%, or 40% solutions) postprandially. Blood alcohol concentrations were monitored by breath analysis and compared with those after intravenous infusion of the same dose. First-pass metabolism was quantified (using Michaelis-Menten kinetics) as the route-dependent difference in the amount of ethanol reaching the systemic blood. Gastric emptying was assessed by nuclear scanning after intake of 300 microCurie of technetium-labeled diethylene triamine pentacetic acid in 10% ethanol. The activities of alcohol dehydrogenase isozymes were assessed in 58 gastric biopsies, using preferred substrates for gamma-ADH (acetaldehyde) and for final sigma-ADH (m-nitrobenzaldehyde) and a specific reaction of chi-ADH (glutathione-dependent formaldehyde dehydrogenase). RESULTS: Women had less first-pass metabolism than men when given 10% or 40%, but not 5%, alcohol. This was associated with lower gastric chi-ADH activity; its low affinity for ethanol could explain the greater gender difference in first-pass metabolism with high rather than with low concentrations of imbibed alcohol. Alcohol gastric emptying was 42% slower and hepatic oxidation was 10% higher in women. A 7.3% smaller volume of alcohol distribution contributed to the higher ethanol levels in women, but it did not account for the route-dependent effects. CONCLUSIONS: The gender difference in alcohol levels is due mainly to a smaller gastric metabolism in females (because of a significantly lesser activity of chi-ADH), rather than to differences in gastric emptying or in hepatic oxidation of ethanol. The concentration-dependency of these effects may explain earlier discrepancies. The combined pharmacokinetic differences may increase the vulnerability of women to the effects of ethanol.

Adult↗

Manifestation of cutaneous polyarteritis nodosa during interferon therapy for chronic hepatitis C associated with primary biliary cirrhosis.

Interferon alpha-2b was administered to a 50-year-old Japanese woman with chronic hepatitis C associated with primary biliary cirrhosis. Two months after the beginning of the interferon alpha-2b therapy a systemic nodular, erythematous rash developed. Histological analysis of the skin revealed typical features of necrotizing arteritis. Because there was no microhematuria, and no microaneurysms were detected on abdominal angiography, a diagnosis of cutaneous polyarteritis nodosa was made. A good outcome was achieved after interferon alpha-2b was discontinued and prednisolone was administered instead. The cutaneous polyarteritis nodosa in this patient is thus considered to have occurred as an adverse effect of interferon administration. To our knowledge, this is the first reported case of cutaneous polyarteritis nodosa which developed because of interferon therapy for chronic hepatitis C associated with primary biliary cirrhosis.

Female↗

Differences in survival based on the type of follow-up for the detection of hepatocellular carcinoma: an analysis of 547 patients.

The aim of this study was to identify any significant variables in the prognosis of 547 cases with hepatocellular carcinoma (HCC), and simultaneously confirm the survival among the different surveillance modalities for the initial detection of HCC in a closely followed-up group (regular periodic follow-up with monthly alpha-fetoprotein (AFP) and ultrasonography at least every 4 months), a not closely followed-up group (neither performed with AFP nor ultrasonography regularly) and an incidental group (incidentally discovered due to related symptoms). Five hundred and forty-seven consecutive patients with HCC diagnosed at the Internal Medicine Department of Saga Prefectural Hospital Koseikan from January 1989 to December 1998 were retrospectively analyzed. The 1-, 3- and 5-year survivals in all 547 cases were 69.7, 42.4 and 26.9%, respectively. The 1-, 3- and 5-year survivals in the cases found to have solitary HCC measuring 2 cm or less in diameter at the time of diagnosis were 97.3, 76.2 and 52.3%, respectively. Forty-seven point one percent of the closely followed-up group, which was the high-risk group were found to have solitary HCC measuring 2 cm or less in diameter (48 out of the 102 followed-up cases), while only 18.5 and 11.8% were found in the not closely followed-up group (46 out of 248 cases) and the incidental group (22 out of 186 cases), respectively. The 5-year survival in the closely followed-up, the not closely followed-up and the incidental groups were 42.9, 26.1 and 15.3%, respectively. The significant factors obtained in the closely followed-up group compared to those from the not closely followed-up group included AFP, tumor size, tumor number and portal thrombosis. These findings indicate the importance of a close follow-up for high-risk groups in order to identify HCC at an early stage, and thereby have a positive influence on survival.

Journal Article↗

Colour Doppler ultrasound for the evaluation of bowel wall thickening.

We performed colour Doppler ultrasound to evaluate bowel wall thickening and to determine the effectiveness of this modality. 42 patients (aged 8-83 years old, mean age 43.5 years) with bowel disease underwent both grey scale and colour Doppler ultrasound examinations. The diagnoses were classified into three categories: inflammation, vasculitis or ischaemia. The bowel wall thickness, wall echotexture and location of the involved portion were all recorded by grey scale ultrasound, while the presence of an intramural colour Doppler flow and arterial signal was evaluated by colour Doppler ultrasound. The colour Doppler flow was graded as "absent", "mild", or "abundant", and the resistive index was also calculated. Bowel wall thickening was observed in the bowel diseases demonstrating inflammation, vasculitis and ischaemia. Patients with ischaemia were significantly older than those with inflammation. The difference in bowel wall thickness was not significant among the disease categories. Differences in bowel wall echotexture, colour Doppler flow, arterial signal and resistive index among the disease categories were significant. The absence of a colour Doppler flow and of an arterial signal suggested ischaemia, while in younger patients, an abundant colour Doppler flow and a stratified echotexture suggested inflammation. The mean resistive index in the ischemic group was significantly higher than that in the inflammatory group. In conclusion, both grey scale and colour Doppler ultrasound are considered to provide useful information for evaluating and differentiating bowel wall thickening in various bowel diseases.

Adolescent↗

The value of colour Doppler ultrasonography for small bowel involvement of adult Henoch-Schönlein purpura.

Three patients presented with a non-thrombocytopenic purpuric rash on their upper and lower limbs, abdominal pain, diarrhoea, and arthralgia. Grey scale ultrasound showed abnormally thickened walls of the small bowel. Colour Doppler showed blood flow signals in the diseased bowel wall in all patients. Subsequent barium and endoscopic studies showed oedematous bowel loops with petechial lesions. Biopsy from the purpuric rash of the skin demonstrated vasculitis of subdermal small vessels. The clinical diagnosis of Henoch-Schönlein purpura was made in each case. This paper describes the efficacy of grey scale and colour Doppler ultrasonography in the assessment of the small bowel involvement of Henoch-Schönlein purpura.

Adult↗

Obstructive jaundice due to multiple hepatic abscesses.

A 63-year-old Japanese male with diabetes mellitus developed obstructive jaundice following the onset of multiple hepatic abscesses. Percutaneous transhepatic cholangiography showed intrahepatic bile duct irregularity and dilatations accompanied by a complete obstruction of the right branch of the intrahepatic bile duct. Three kinds of organisms were cultured from the blood and the drained bile. The cholangiographic changes returned to the normal after the liver abscesses subsided following biliary drainage and the administration of intravenous antibiotics.

Bacteroides Infections↗

Ethnic differences in gastric sigma-alcohol dehydrogenase activity and ethanol first-pass metabolism.

We assessed whether the low sigma-alcohol dehydrogenase (ADH) activity in Japanese (compared with Caucasians) affects the first-pass metabolism of ethanol. ADH isozyme activities were determined in endoscopic biopsies of the gastric corpus from 24 Japanese and 41 Caucasian men by starch gel electrophoresis and by comparing the reduction of m-nitrobenzaldehyde (a preferred substrate of sigma-ADH) with that of acetaldehyde (a preferred substrate of gamma-ADH) and the glutathione-dependent formaldehyde oxidation (a specific reaction of chi-ADH). Alcohol pharmacokinetics was compared in 10 Japanese and 10 Caucasians after administration of ethanol (300 mg/kg of body weight) intravenously or orally, using 5 and 40% oral solutions. Japanese exhibited lower sigma-ADH activity than Caucasians, with no difference in the other gastric isozymes. With 5% ethanol, first-pass metabolism was strikingly lower in Japanese than in Caucasians. Blood alcohol levels were similar because of the high elimination rate in Japanese due to the hepatic beta 2-ADH variant. With 40% ethanol, the first-pass metabolism increased in both groups to comparable levels, suggesting an additional contribution by chi-ADH at high ethanol concentrations. These results indicate that sigma-ADH activity contributes significantly to gastric ethanol oxidation and its lower activity in Japanese is associated with lesser first-pass metabolism.

Alcohol Dehydrogenase↗

Rotenone, a mitochondrial NADH dehydrogenase inhibitor, induces cell surface expression of CD13 and CD38 and apoptosis in HL-60 cells.

We previously demonstrated that the mitochondrial NADH dehydrogenase subunit 2 (ND2) gene was overexpressed in human acute myelogenous leukemia (AML) cells. Since this finding suggested that ND2 gene expression was related to myeloid differentiation, we here investigated the effects of rotenone, a specific NADH dehydrogenase inhibitor, on HL-60 cell growth, differentiation and death. Fifty nM rotenone inhibited the growth of HL-60 cells and caused an increase in the cell population in the G(2) +M phase. In the quantitative comparison of myeloid antigen, the expression of CD13 and CD38 were relatively increased in the rotenone-treated cells. These findings suggest that the inhibition of NADH dehydrogenase changes the cell cycle and induces some specific surface antigens of HL-60 cells. On the other hand, the expression of ND2 gene remained unchanged after the rotenone treatment, suggesting the rotenone-mediated mitochondrial inhibition did not affect the mitochondrial gene expression. Five mu M rotenone strongly inhibited the cellular proliferation. Electron microscopy and an electrophoretic analysis of DNA showed that the majority of the HL-60 cells were induced into typical apoptosis within 24-48 hours. On the basis of this and other studies, we believe that mitochondrial function is directly involved in both cellular differentiation and apoptotic cell death.

ADP-ribosyl Cyclase↗

[Association of cirrhosis and hepatocellular carcinoma with porphyria cutanea tarda].

A common characteristic of patients with porphyria cutanea tarda (PCT) is liver dysfunction. The degree of liver damage is usually mild but liver cirrhosis is a common associated finding. Hepatic iron overload is a characteristic feature but the role of iron in the pathogenesis of the condition has not yet been clarified. Heavy alcohol consumption is a frequent precipitant of PCT. A strong association with markers of past hepatitis B virus infection was first demonstrated but a high prevalence of hepatitis C virus markers is now noted. Although the potential to give rise to hepatocellular carcinoma (HCC) in PCT patients with cirrhosis is well recognized, HCC itself has a risk of developing PCT. HCV or the cirrhotic change itself has been attributed as the risk factor for the occurrence of HCC.

Alcoholism↗