The paraoxonase enzyme (PON) gene polymorphism causes a change of methionine (M-allele) to leucine (L-allele). PON may reduce low density lipoprotein oxidation and prevent atherosclerosis. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a sensitive index of oxidative DNA damage. We have studied the association between the PON genotypes and the urinary excretion of 8-OHdG. The study population consisted of 93 Finnish type 2 diabetes patients and 106 non-diabetic control subjects. The 24-h excretion of 8-OHdG was significantly higher in diabetic patients than in control subjects (P < 0.001). In control subjects, the ratio of the 8-OHdG/glomerular filtration rate increased in order of genotype from MM to ML to LL (P < 0.0412). These results suggest that lipid peroxidation may have an effect on DNA oxidation.

8-Hydroxy-2'-Deoxyguanosine↗

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Effects of cerivastatin sodium, a new HMG-CoA reductase inhibitor, on biliary lipid metabolism in patients with hypercholesterolemia.

The use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has become common in the treatment of hypercholesterolemia. The present uncontrolled study was undertaken to determine the effect of cerivastatin sodium (BAY w 6228), a new HMG-CoA reductase inhibitor, on biliary lipid levels in patients with hypercholesterolemia. Twenty-one hypercholesterolemic patients (World Health Organization type IIa = 16 patients; type IIb = 5 patients) received placebo during a 4- to 6-week observation period, after which they received cerivastatin sodium 0.2 mg/d for 12 weeks. Fasting blood samples were drawn for the measurement of serum lipid levels early in the morning before the start of treatment and once a month for each of the 12 weeks of cerivastatin sodium treatment. Gallbladder bile samples were aspirated with a duodenal tube by cerulein stimulation to assess bile lithogenicity. Serum total cholesterol levels decreased markedly after 12 weeks. However, no significant difference was found in the molar percentage composition of biliary lipids (e.g., cholesterol, phospholipids, and total bile acids) or in individual biliary bile acids. Consequently, no significant change in bile cholesterol saturation index was found. The index values before and after 12 weeks of treatment were 0.81 +/- 0.38 and 0.80 +/- 0.47, respectively, whereas when patients were grouped by type of hypercholesterolemia, there was a tendency toward decreased lithogenicity in patients with type IIb but not type IIa hypercholesterolemia. We concluded that cerivastatin sodium was an effective cholesterol-lowering drug that did not appear to worsen biliary lipid metabolism and that may decrease lithogenicity in patients with type IIb hypercholesterolemia.

Adult↗

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Positron emission tomography using 2-[(18)F] fluoro-2-deoxy-D-glucose in the diagnosis of uterine leiomyosarcoma: a case report.

The preoperative diagnosis of uterine leiomyosarcoma (LMS) is very difficult. Magnetic resonance (MR) imaging is usually used for it; however, precise diagnosis by MR imaging is limited to typical LMS with coagulative tumor cell necrosis. We presented a case of LMS that was diagnosed preoperatively by positron emission tomography (PET) using 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG).

Aged↗

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Dobutamine-stress electrocardiographically gated positron emission tomography for detection of viable but dysfunctional myocardium.

PURPOSE: This study was performed to determine whether low-dose dobutamine stress electrocardiography (ECG)-gated fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) can assess wall motion and identify myocardium without contractile reserve despite preserved FDG uptake. METHODS: Fifty-three patients with myocardial infarction and normal sinus rhythm underwent ECG-gated FDG-PET and transthoracic echocardiography. Wall motion of 10 segments of the left ventricle was graded as normal, hypokinetic, or akinetic/dyskinetic. RESULTS: In 365 (76%) of 480 segments, assessment of wall motion was concordant between the 2 modalities. In 30 patients dobutamine-stress ECG-gated FDG-PET was performed. In 13 (50%) of 26 dysfunctional segments with normal FDG uptake, 16 (36%) of 44 dysfunctional segments with mildly reduced FDG uptake and 12 (25%) of 48 dysfunctional segments with moderately reduced FDG uptake, wall motion was improved by dobutamine infusion. CONCLUSION: Assessment of left ventricular wall motion with ECG-gated FDG-PET is feasible, and dobutamine stress ECG-gated FDG-PET can simultaneously identify metabolic viability and contractile reserve.

Adult↗

PubMedDate not supplied

Dobutamine stress electrocardiography-gated Tc-99m tetrofosmin SPECT for detection of viable but dysfunctional myocardium.

BACKGROUND: Technetium-99m-labeled myocardial perfusion tracers allow simultaneous assessment of myocardial perfusion and left ventricular function by electrocardiography-gated scan. This study was performed to determine whether dobutamine stress electrocardiography-gated tetrofosmin single photon emission computed tomography (SPECT) can identify viable (as defined by positron emission tomography [PET]) but dysfunctional myocardium with contractile reserve. METHODS AND RESULTS: Thirty-five patients with myocardial infarction underwent resting electrocardiography-gated SPECT and fluorodeoxyglucose (FDG) PET. The relative uptakes of tetrofosmin (%tetrofosmin) and FDG (%FDG) were calculated. Wall motion in 9 left ventricular segments was assessed at rest and during dobutamine stress on a 3-dimensional cine-mode display created with automatic left ventricular function analysis software. A total of 129 dysfunctional segments were analyzed. Forty-five (48.9%) of 92 segments with %tetrofosmin of 50% or greater and only 4 (10.8%) of 37 segments with %tetrofosmin less than 50% had contractile reserves (P <.0001). The sensitivity, specificity, and predictive accuracy of %tetrofosmin of 50% or greater for detecting %FDG of 50% or greater were 85.7%, 74%, and 82.9%, respectively. The incidence of the presence of contractile reserve rose with increasing magnitude of %FDG. The sensitivity, specificity, and predictive accuracy of the presence of contractile reserve for detecting %FDG of 50% or greater were 43.9%, 80.6%, and 52.7%, respectively. CONCLUSIONS: Dobutamine stress electrocardiography-gated SPECT can identify viable (as defined by PET) but dysfunctional myocardium with contractile reserve.

Adult↗

PubMedDate not supplied

PET for diagnosis of malignant lymphoma of the scalp: comparison of [11C]methyl-L-methionine and [18F]fluoro-2-deoxyglucose.

A 43-year-old woman was admitted with a tumor mass in her forehead. Two months previously, a lump in her breast had been diagnosed as mastopathy. Palpation revealed an elastically hard immobile tumor mass in her forehead. MRI detected a tumoral lesion of generally uniform contrast involving frontal subcutaneous, cranial, and intracranial regions. PET demonstrated more intensive and wider accumulation of [11C]methyl-L-methionine (Met) than of [18F]fluoro-2-deoxyglucose (FDG). Biopsy of the forehead mass was performed, which was diagnosed as B-cell-type malignant lymphoma. The tumor mass in the forehead then shrank spontaneously, as confirmed by palpation and MRI. The tumor mass in the left breast was totally extirpated and histologically diagnosed as B-cell-type malignant lymphoma, like the tumor mass in the forehead. Postoperatively, chemotherapy (VEPA) was performed. Although FDG accumulation had not been detected, postchemotherapy PET demonstrated slight Met accumulation, suggesting the presence of a residual tumor. PET served well to detect the lesion and evaluate therapeutic efficacy in malignant lymphoma. Met-PET was more sensitive to malignant lymphoma than FDG-PET.

Adult↗

PubMedDate not supplied

Portal circulation in monkeys and humans studied after ingestion of a capsule containing a radionuclide.

Capsules (8 x 30 mm) of technetium-99m pertechnetate were designed for measurement of portal blood flow. Most of the radionuclide entered the superior mesenteric vein. The capsule was taken orally and monitored with a collimator for scintigraphy until it reached the small intestine, when a magnetic field completed an electrical circuit in a sensor, burning a thread, releasing a spring, and discharging the preparation. A study in crab-eating monkeys (Macaca fascicularis) showed that the radionuclide in the small intestine circulated through the superior mesenteric vein to the portal vein and liver. Portal scintigraphy through the small intestine could be analysed in the same way as per-rectal portal scintigraphy, in which blood flow mostly from the inferior mesenteric vein is evaluated. A study of four volunteers showed that, after the radionuclide was released, it circulated through the superior mesenteric vein to the portal vein and liver. Use of a capsule enclosing a radioisotope was possible, and the procedure seemed to be safe. The use of the per-small intestine method plus the per-rectal method should give more accurate results than either method used alone, because the haemodynamics of both the superior and inferior mesenteric vein would be reflected.

Administration, Oral↗

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Significance of blood flow in the inferior and superior mesenteric veins for the formation of oesophageal varices.

The degree of involvement of blood flow in the superior mesenteric vein and inferior mesenteric vein in the formation of oesophageal varices is not known. We have developed a method by which the contributions of these veins to portal blood flow can be evaluated simultaneously in a relatively non-invasive way. An enteric-coated capsule containing [123I]iodoamphetamine (IMP) is given by mouth and 3 h later [123I]IMP is instilled into the rectum. The data obtained are treated by computer to calculate the portal shunt index via the inferior and superior mesenteric veins. In chronic hepatitis and cirrhosis, when varices were absent, the difference in these indices was not significant. In the presence of varices, the portal shunt index via the inferior mesenteric vein was significantly higher than that via the superior mesenteric vein. It was suggested that the contribution of blood flow in the inferior mesenteric vein the portal/splenic axis is important in the formation of varices.

Amphetamines↗

PubMedDate not supplied

Reversibility of organic anion-induced cholestasis: association with compensatory hypersecretion of biliary phospholipid and protein in the dog.

The effect of a concomitant infusion of organic anions, structurally related phthaleins, on bile flow was studied in anaesthetized dogs. A combination of rose bengal and sulfobromophthalein was found to uniquely and synergistically produce an acute, reversible form of intrahepatic cholestasis (< 10% of control level). This phenomenon was not observed with the administration of those individual organic anions at concentrations previously associated with the induction of intrahepatic cholestasis. The infusion of either a micelle forming bile salt, sodium taurocholate, or a non-micelle forming bile salt, sodium dehydrocholate, rapidly reversed the intrahepatic cholestasis (within 20 min after bile salt infusion). During the choleretic phase immediately following the bile salt infusion, a transient but marked hypersecretion, a disproportionately increased output in relation to that of bile acids, of biliary phospholipid (176% of control level by taurocholate and 138% of control level by dehydrocholate), and an even more striking amount of biliary protein hypersecretion were observed (392% of control level by taurocholate and 357% of control level by dehydrocholate). Although the significance of these new post-cholestatic observations requires clarification, it is suggested that the intrahepatic cholestasis induced by organic anions reflects a reversible defect in the mechanism(s) involved in transcellular transport.

Animals↗

PubMedDate not supplied

Relationship between endotoxin antibody levels and portal systemic shunt evaluated by per-rectal portal scintigraphy.

The reasons for the high frequency of endotoxaemia in cirrhosis, whether poor liver function or abnormal portal circulation, are not known. Accurate measurement of endotoxin itself is difficult. Instead, in this study an enzyme-linked immunosorbent assay was used to measure levels of IgA, IgG and IgM antibodies to endotoxin in patients with chronic liver disease and underlying hepatic viral infection. The relationships between the results and clinical symptoms or the presence of a portal systemic shunt were investigated. The median level of IgA antibodies was not different in patients with chronic hepatitis and those with cirrhosis, and the same was found for IgM, but the median level of IgG antibodies was significantly higher in the patients with cirrhosis. When patients with cirrhosis were grouped by the presence or absence of ascites or hepatocellular carcinoma, no significant difference was observed in any of these antibody levels. However, in cirrhotic patients with varices, the level of IgG antibodies to endotoxin was significantly higher than in patients without varices. For evaluation of the portal systemic shunt, the per-rectal portal shunt index was calculated. There was a significant correlation (R = 0.431, P < 0.001) between the per-rectal portal shunt index and the level of IgG antibodies to endotoxin. That is, the degree of abnormality in the portal haemodynamics was correlated with the level of IgG antibodies to endotoxin in patients with liver disease.

Antibodies, Bacterial↗

PubMedDate not supplied

An estimation of human bile metastability: clinical application of a sensitive cholesterol crystal growth assay.

The formation of cholesterol monohydrate crystal initiates cholesterol gallstone formation. The nucleation time (NT), a light microscopy method, is used currently to estimate human bile metastability. Recently, a cholesterol crystal growth (CCG) assay utilizing photometric turbidity to quantitate cholesterol crystallization was developed using model bile systems. The object of this study was to determine whether this novel CCG assay was applicable to the quantitative assessment of native human bile metastability. Human gall-bladder bile samples were collected from patients undergoing cholecystectomy. There were five patients with cholesterol gallstone and five stone-free patients. A significant correlation between the onset time measured by the CCG assay and the NT observed by light microscopy was found in our modified assay condition where interference by bilirubin was negligible (P < 0.01). Also, the growth rate measured by the CCG assay significantly correlated with the NT (P < 0.05). These results indicate that the CCG assay is applicable to quantitative assessment of human bile metastability reflected by cholesterol crystal nucleation and that the cholesterol crystal growth is also conveniently estimated by this method.

Bile↗

PubMedDate not supplied

Immunohistochemical detection of 8-hydroxy-2'-deoxyguanosine in paraffin-embedded sections of rat liver after carbon tetrachloride treatment.

To test the applicability of an anti-8-hydroxy-2'-deoxyguanosine (8-OH-dG) antibody for immunohistochemistry using paraffin-embedded sections, carbon tetrachloride (CCl4)-induced rat liver injury was evaluated. Male rats were given a single dose of CCl4 and killed at 6 hr, 12 hr, 1, 2, 3, and 7 days thereafter. Severe centrilobular necrosis was evident at 1 day. At 2 days, moderate mononuclear cell infiltration was present in centrilobular necrotic regions. Infiltrating mononuclear cells, surrounding sinusoidal endothelial cells and hepatocytes were stained with anti-8-OH-dG antibody at 2 and 3 days. Formation of 8-OH-dG in DNA and 8-oxo-dGTPase mRNA expression were also increased at these time points, the amounts of malondialdehyde and 4-hydroxy-2-nonenal showed 2 peaks at 6 hr and 3 days. The findings suggest that the main contributory factor in the massive hepatic necrosis was increased lipid peroxidation, rather than excessive formation of 8-OH-dG, and that the observed increase in the latter was largely due to infiltrating mononuclear cells. The agreement between biochemical data and the results for immunohistochemical analysis confirms that the anti-8-OH-dG antibody is applicable for detection of cells targeted by free radicals in paraffin-embedded sections and also for investigation of the mechanisms of oxidative damage-related disease, including carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

PubMedDate not supplied

Early diagnosis and evaluation of therapy in postoperative recurrent cervical cancers by positron emission tomography.

Positron emission tomography (PET) using 2-[18F]fluoro-2 deoxy-D-glucose (FDG) was performed on two uterine cervical cancer patients in whom recurrent tumors, one pelvic and the other at the vaginal wall had not been precisely diagnosed using the usual imaging examinations. One recurrence was confirmed by the acccumulation of FDG to the pelvic mass as detected by magnetic resonance imaging (MRI). During chemotherapy, changes in FDG-PET findings were detected earlier than those in MRI. In the other, PET detected a recurrent tumor that could not be found by MRI, and was also useful for evaluating chemotherapeutic effects. These cases suggest that PET with FDG can be a useful examination not only for diagnosing recurrent cervical cancer after radical hysterectomy, especially pelvic recurrence, but also for evaluating chemotherapeutic effects on recurrent cancers.

Female↗