Use of multislice helical computed tomography cholangiography in the diagnosis of biliary disease

A recent advance in computed tomography (CT) technology, multislice helical CT, has enabled production of clearer three-dimensional (3D) images and has drawn interest. We report the usefulness of CT cholangiography using a multislice helical CT scanner for the diagnosis and preoperative imaging of the biliary duct in a case of peculiarly shaped gallbladder with cholecystitis. A 34-year-old woman admitted to our hospital presented with chronic hypochondralgia. A CT scan showed that the gallbladder was normal without wall thickening or stones. However, there appeared to be a tumor, containing a stone approximately 1 cm in diameter, attached under the gallbladder in front of the right kidney and extending up to its lower level. Magnetic resonance cholangiography also depicted a normal gallbladder without wall thickening or stones. Hence, gallbladder stones were not diagnosed by previously the mentioned investigations. In contrast, a 3D image produced by multislice helical CT cholangiography was very clear. From the bottom of the gallbladder, a narrow canal continued to a stone. We diagnosed that the wall of the lower part of the long gallbladder had become thick and elongated because of chronic cholecystitis caused by a gallbladder stone, and laparoscopic cholecystectomy was performed. Macroscopically, the resected gallbladder showed an extremely thickened wall from the lower body to the fundus, in which a stone was located in the center. Multislice helical CT cholangiography has the potential to become one of the most significant examinations for diagnosis and anatomical analysis of biliary disease prior to laparoscopic cholecystectomy.     

Dihydropyrimidine dehydrogenase (DPD) activity in gastric cancer tissue and effect of DPD inhibitory fluoropyrimidines

Background

Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catabolizes 5-fluorouracil (5-FU). The effect of DPD inhibitory fluoropyrimidines (DIF) is presumably related to DPD activity. We studied the efficacy of DIF (tegafur + uracil [UFT], tegafur + gimeracil + osteracil [S-1 (TS-1^®)]) relative to DPD activity, with other fluoropyrimidines as controls.

Methods

The efficacy of DIF relative to DPD activity was evaluated in 58 gastric cancer patients who received postoperative administration of fluoropyrimidines, consisting of DIF in 42 patients (UFT in 23; S-1 in 19) and non-DIF in 16 patients.

Results

In patients with low DPD activity (under 40?U/mg protein), curative potential tended to be lower for DIF than for non-DIF, but the survival rate was the same for both. In patients with high DPD activity (40?U/mg protein or more), such a tendency was not detected. In a comparison between those treated with UFT and those treated with S-1, prognosis was better in the latter group, in spite of their predominance of lower curative potentials of B or C. In 27 patients with measurable lesions, a partial response (PR) or higher response occurred in 33% (5/15) of those with low DPD activity, and in 17% (2/12) of those with high DPD activity. In the patients with low DPD activity, non-DIF induced no change (NC) in 17% (1/6), and progressive disease (PD) in the rest. UFT induced PD in all 5 patients, while S-1 induced a response rate of 44% (7/16), with NC in 25% (4/16). In the patients with high DPD activity, on the other hand, non-DIF (n = 3) and UFT (n = 3) induced PD in all the patients, while S-1 induced PR in 33% (2/6) and NC or a higher response in 67% (4/6).

Conclusion

It is recommended to use S-1 rather than UFT in patients with high DPD activity. Measurement of DPD was useful in drug selection.

     

Early-onset multisystem mitochondrial disorder caused by a nonsense mutation in the mitochondrial DNA cytochrome C oxidase II gene

We report the first nonsense mutation (G7896A) in the mtDNA gene for subunit II of cytochrome c oxidase (COX) in a patient with early-onset multisystem disease and COX deficiency in muscle. The mutation was heteroplasmic in muscle, blood, and fibroblasts from the patient and abundantly present in COX-deficient fibers, but less abundant in COX-positive fibers; it was not found in blood samples from the patient's asymptomatic maternal relatives. Immunoblot analysis showed a reduced concentration of both COX II and COX I polypeptides, suggesting impaired assembly of COX holoenzyme.     

The effect of feeding carrots on immunoglobulin E production and anaphylactic response in mice.

Carrot juice was administered orally to BALB/c mice immunized intraperitoneally with dinitrophenylated (DNP)-OVA for about 1 month. The titers of DNP-specific IgE, DNP-specific IgG, and the levels of total IgE in mouse sera were determined. The DNP-specific IgE production by mice fed carrot juice was significantly inhibited. On the other hand, the DNP-specific IgG production and the level of total IgE in mice fed carrot juice were not significantly different from those in control mice. We also examined the effect of feeding carrots on immediate-type hypersensitivity. One hour after antigen stimulation, the ears of mice fed carrots swelled less than those of control mice. Furthermore, the rise in serum histamine in the mice fed carrots under active systemic anaphylaxis was lower than in controls. We then examined the pattern of cytokine production by spleen cells from mice followed by restimulation with DNP-OVA in vitro. The spleen cells from the mice fed carrots produced more interferon-gamma than those from the control group. In contrast, the spleen cells from the mice fed carrots produced less interleukin-4 than those from the control group. Furthermore, the interleukin-12 production of the spleen cells from mice fed carrots was also higher than that of the control group. These findings suggest that feeding carrots improves the helper T cell (Th)1/Th2 balance, inhibiting specific IgE production and antigen-induced anaphylactic response.     

P-glycoprotein inhibition by membrane cholesterol modulation

P-glycoprotein (Pgp) is a transmembrane protein that actively exports lipophilic chemotherapeutics from the cells causing multidrug resistance. Pgp molecules are partially localized in TX-100-resistant rafts, and the activity of the transporter is highly sensitive to the presence of cholesterol. To better understand these relationships, the influence of membrane cholesterol content on Pgp function, as measured via calcein accumulation, was studied in correlation with changes elicited in membrane structure. Membrane cholesterol was modulated by heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DIMEB) and the cholesterol inclusion complex of DIMEB (Chol-DIMEB). Changes in membrane cholesterol level were reflected by alterations in the overall lipid packing as measured by Merocyanine 540 (MC540) staining and were also accompanied by changes in the raft association of the pump. DIMEB and Chol-DIMEB treatments have also lead to increased permeability of the cell membrane in both directions, raising the possibility that the effects on pumping efficiency reflect leakage of ATP also from the non-permeabilized cells. However, the treatments did not influence the intracellular ATP levels of the non-permeabilized cells. Our data suggest that Pgp inhibition by cyclodextrin treatments arises through modulation of its membrane microenvironment, rather than as a result of concomitant cytotoxicity.     

Retrohepatic vena cava replacement of hepatic malignancies without using total hepatic vascular exclusion or extracorporeal bypass.

Total hepatic vascular exclusion and venovenous bypass are frequently used surgical procedures when concomitant resection of the inferior vena cava is required during surgery of liver cancer involving the retrohepatic inferior vena cava close to the hepatic veins. However, the duration of total hepatic vascular exclusion is limited due to the risk of hepatic ischemia. Three patients presented with severely compressed inferior vena cava and/or hepatic veins due to liver cancer. The surgical procedure involved initial taping of the inferior vena cava just below the hepatic veins by extrahepatic division and taping of the hepatic veins. After taping the inferior vena cava, hepatectomy with caval resection was performed by simply clamping the retrohepatic inferior vena cava, without the need for total hepatic vascular exclusion or venovenous bypass. In all patients the retrohepatic inferior vena cava were safely replaced with a prosthetic graft under stable hemodynamics. Duration of the inferior vena cava clamping was 31, 66, 75 minutes, respectively. No graft-related complications occurred, but 2 of the 3 patients showed temporal renal dysfunction associated with renal congestion postoperatively. The surgical procedure described herein is effective for the treatment of retrohepatic inferior vena cava in some patients. However, when the case is complicated by chronic nephropathy or simultaneous nephrectomy is required, venovenous bypass should be performed.     

Changes in hepatic metabolism through simulated weightlessness: decrease of glycogen and increase of lipids following prolonged immobilization in the rat

The effect of simulated weightlessness on hepatic metabolisms of carbohydrates and lipids was investigated in rats that were chronically immobilized by means of a suspension harness. During the 10-day period of the suspension, the animals showed a substantial decrease in the hepatic glycogen content, whereas the content of hepatic total lipids was markedly elevated. Similar results were obtained when the “suspended” animals were provided with a regular amount of nutrients by a force-feeding procedure. In the suspended animals, hepatic parenchymal cells were filled with large fat droplets, and hepatic triglyceride contents were elevated. The prolonged immobilization led to a slight, but significant, increase in glucose-6-phosphatase activity in the liver, suggesting that an increased glycogen breakdown might have occurred in the suspended animals. However, it was unlikely that the increased amount of glucose produced by the glycogen breakdown was utilized as a substrate for the lipogenesis in the liver, because hepatic lipogenic enzyme activities were unaffected by the suspension. The results suggest that the hepatic lipids accumulate in animals exposed to a prolonged immobilization state, presumably due to a decreased lipolysis and/or a suppressed lipoprotein mobilization from the liver into the blood stream.     

The AB Portable Driver Generates Higher Drive‐Line Pressures Possibly Leading to Accelerated Hemolysis

The AB5000 Circulatory Support System is paracorporeal pulsatile ventricular assist device. The AB Portable Driver is a portable console for this system. We experienced two cases with accelerated hemolysis while receiving support by the AB Portable Driver. The purpose of this study was to clarify the mechanical differences associated with the hemolysis between the AB5000 console and the AB Portable Driver. The mock circulatory system modeled by an AB5000 ventricle and a blood sampling bag of vinyl chloride was run with an AB5000 console or AB Portable Driver. The peak drive‐line pressure, the mean arterial cannula pressure and the pumping rate of the VAD were recorded. The AB5000 console generated a peak drive‐line pressure of 280–300 mm Hg in LVAD mode and 210–220 mm Hg in RVAD mode, approximately 100 mm Hg lower than officially documented. In contrast, the AB Portable Driver generated pressures of 310–330 mm Hg in LVAD mode and 230–250 mm Hg in RVAD mode, 65–95 mm Hg higher than officially documented. The AB Portable Driver console generates higher drive‐line pressures than the AB5000 console, possibly explaining the accelerated hemolysis.     

Hierarchical Bayesian estimation for MEG inverse problem

Source current estimation from MEG measurement is an ill-posed problem that requires prior assumptions about brain activity and an efficient estimation algorithm. In this article, we propose a new hierarchical Bayesian method introducing a hierarchical prior that can effectively incorporate both structural and functional MRI data. In our method, the variance of the source current at each source location is considered an unknown parameter and estimated from the observed MEG data and prior information by using the Variational Bayesian method. The fMRI information can be imposed as prior information on the variance distribution rather than the variance itself so that it gives a soft constraint on the variance. A spatial smoothness constraint, that the neural activity within a few millimeter radius tends to be similar due to the neural connections, can also be implemented as a hierarchical prior. The proposed method provides a unified theory to deal with the following three situations: (1) MEG with no other data, (2) MEG with structural MRI data on cortical surfaces, and (3) MEG with both structural MRI and fMRI data. We investigated the performance of our method and conventional linear inverse methods under these three conditions. Simulation results indicate that our method has better accuracy and spatial resolution than the conventional linear inverse methods under all three conditions. It is also shown that accuracy of our method improves as MRI and fMRI information becomes available. Simulation results demonstrate that our method appropriately resolves the inverse problem even if fMRI data convey inaccurate information, while the Wiener filter method is seriously deteriorated by inaccurate fMRI information.