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Attempted induction of chronic portal venous hypertension with polyvinyl alcohol particles in swine.

PURPOSE: Creation of presinusoidal chronic portal venous hypertension by means of repeated portal vein (PV) embolization was explored in an attempt to improve a porcine model of transjugular intrahepatic portosystemic shunt (TIPS) patency. MATERIALS AND METHODS: Six microswine underwent weekly PV embolization for 5 weeks with a total of 10.4-12.6 g of polyvinyl alcohol (PVA) particles (0.149-0.250 mm in size). Portography, liver function tests, pressure measurement in the PV and inferior vena cava (IVC) before and after PV embolization, and histopathologic evaluation of the livers were performed. RESULTS: Transhepatic portal venography performed after each embolization demonstrated diffuse PV branch occlusion in all cases. At weekly follow-up, reconstitution of flow was demonstrated in these branches; permanent occlusion of PV branches was not achieved. The mean PV pressure elevated acutely from 17.3 mm Hg +/- 0.9 to 24.5 mm Hg +/- 4.2 (P < .01) after each embolization. However, the pressure always returned to baseline on the follow-up studies 1 week later. Liver function tests were normal. Histopathologic evaluation of the liver showed, in multiple PV branches, central plugs of PVA with peripheral recanalization. The liver parenchyma was otherwise normal. CONCLUSION: Massive embolizations of PV with PVA at weekly intervals failed to create permanent portal hypertension or induce hepatic fibrosis.

Animals↗

Abnormal placental cord insertion may induce intrauterine growth restriction in IVF-twin pregnancies.

BACKGROUND: This study determined whether twins conceived through assisted reproduction technology (ART) have an increased risk of perinatal complications compared with natural twin pregnancies and investigated potential associated major risk factors. METHODS: This retrospective study consisted of 199 twins born between 1994 and 2003. There were four groups according to conception modalities: 97 twins after spontaneous pregnancy, 24 after induced ovulation, 28 after intrauterine insemination (IUI) and 50 after IVF with embryo transfer. Analysis included preterm birth, Caesarean delivery, weight discordance, intrauterine growth restriction (IUGR), low-birth-weight, Apgar score, chorionicity, gross placental pathology and placental umbilical cord insertion (UCI) site. RESULTS: A significant difference was found in IUGR between the IVF group (7.0%) and spontaneous pregnancy group (14.9%). When maternal age was >30 years there was a 2.86-fold increase in the risk of IUGR. There was a 3.69-fold increased risk of IUGR in the presence of abnormal UCI (odds ratio 3.69, 95% CI 1.62-8.42) and a 2.18-fold increased risk of abnormal UCI in monochorionic twins when compared with dichorionic twins (odds ratio 2.18, 95% CI 1.30-3.66). CONCLUSION: Twins conceived through ART are not at an increased risk of perinatal complications. A relationship has been found between abnormal UCI and IUGR.

Diseases in Twins↗

Administration of oral charcoal adsorbent (AST-120) suppresses low-turnover bone progression in uraemic rats.

BACKGROUND: Using a rat model of renal failure with normal parathyroid hormone levels, we had demonstrated previously that bone formation decreased depending on the degree of renal dysfunction, and hypothesized that uraemic toxins (UTx) are associated with the development of low-turnover bone development, complicating renal failure. In this study, focusing on indoxyl sulphate (IS) as a representative UTx, we analysed the effect of an oral charcoal adsorbent AST-120, which removes uraemic toxins and their precursors from the gastrointestinal tract, on bone turnover. METHODS: AST-120 or vehicle was administered orally to model rats with uraemia and low turnover bone. Bone turnover was analysed by histomorphometry. Expression of osteoblast-related genes and oat-3 gene was analysed by reverse transcription polymerase chain reaction. RESULTS: In rats treated with vehicle, serum IS level increased with time after renal dysfunction, while bone formation decreased accompanied by down-regulation of the parathyroid/parathyroid-related peptide hormone receptor, alkaline phosphatase and osteocalcin genes. Administration of AST-120 inhibited the accumulation of IS in blood and ameliorated bone formation. Bone formation rate was 2.4 +/- 1.7 microm(3)/m(2)/year in controls given vehicle and was 11.7 +/- 2.4 microm(3)/m(2)/year in rats administered with AST-120 (P < 0.05). AST-120 treatment also reversed the down-regulation of osteoblast-related genes. Gene expression of oat-3 was detected in the tibia of rats. CONCLUSION: Administration of the oral charcoal adsorbent AST-120 decreases the osteoblast cytotoxicity of UTx including IS, and suppresses progression of low bone turnover in uraemic rats.

Administration, Oral↗

Urinary response to an oxalic acid load is influenced by the timing of calcium loading in rats.

PURPOSE: Dietary intake of calcium or dairy products has been shown to decrease urinary oxalate excretion by limiting its intestinal absorption. However, not enough attention has been given to whether there is any benefit from altering the schedule of ingesting calcium and oxalate. Therefore, we investigated the effects of changes in the timing of calcium and oxalate loading on urinary oxalate excretion. MATERIALS AND METHODS: Male Wistar rats weighing 180 to 200 gm were fasted and randomized into several groups. They were then administered normal saline or oxalic acid with or without calcium or milk. Calcium or milk was given immediately, or 5, 10, 15 or 30 minutes before or after the oxalate load. All treatments were given via gastrostomy. Urine samples were collected by bladder puncture just before administration and at hourly intervals up to 5 hours afterward. Urinary oxalate was measured by capillary electrophoresis. RESULTS: Urinary oxalate increased after the administration of oxalate alone, while it decreased when oxalate was combined with calcium or milk. Urinary oxalate showed a smaller increment when calcium or milk was given before than after oxalate loading, and it was much smaller when calcium or milk was given immediately before oxalate. CONCLUSIONS: Prior calcium loading appears to have a positive influence on decreasing oxalic acid absorption from the intestinal tract. Therefore, calcium or dairy products should always be ingested before a meal rich in oxalate to prevent oxalate absorption and decrease urinary oxalate excretion.

Analysis of Variance↗

Histochemical investigation of criteria for the distinction between monoamine oxidase A and B in various species.

The superior cervical ganglion (SCG), pineal body (PB), and liver (L) of the rat, rabbit and cat were stained for monoamine oxidase (MAO) A and B by the tetranitro blue tetrazolium (TNBT) and coupled peroxidase ( PerOx ) methods, using 5-hydroxytryptamine (5HT), tryptamine ( Tryp ), tyramine (Tyr), and benzylamine (Bz) as substrates, and clorgyline (Cl) and deprenyl (Dep), both at 10(-7) M, as selective inhibitors. The nodose ganglion (NG) and dorsal root ganglion (DRG) of the rabbit and cat were also studied. The results with rat tissues were consistent with published quantitative findings (SCG, MAO-A much greater than B; PB, MAO-A less than or equal to B; L, MAO-A = B). In the rabbit, the findings with the SCG were similar; the MAO activities of the PB were relatively resistant to both inhibitors; the MAO of the liver required 10(-4) M concentrations of both inhibitors to produce near total inhibition, suggesting that the liver contains an MAO distinct from MAO A and B. All cat tissues examined appeared to contain almost exclusively MAO-B. In this species 5HT, which is generally considered a selective substrate for MAO-A, was oxidized by MAO-B. The findings indicate that criteria for MAO-A, -B, and other subgroups must be defined for each species and tissue.

Animals↗

Imaging of cauda equina edema in lumbar canal stenosis by using gadolinium-enhanced MR imaging: experimental constriction injury.

BACKGROUND AND PURPOSE: It has been reported that disturbance of blood flow arising from circumferential compression of the cauda equina by surrounding tissue plays a major role in the appearance of neurogenic intermittent claudication (NIC) associated with lumbar spinal canal stenosis (LSCS). We created a model of LSCS to clarify the mechanism of enhancement within the cauda equina on gadolinium-enhanced MR images from patients with LSCS. METHODS: In 20 dogs, a lumbar laminectomy was performed by applying circumferential constriction to the cauda equina by using a silicon tube, to produce 30% stenosis of the circumferential diameter of the dural tube. After 1 and 3 weeks, gadolinium and Evans blue albumin were injected intravenously at the same time. The sections were used to investigate the status of the blood-nerve barrier function under a fluorescence microscope and we compared gadolinium-enhanced MR images with Evans blue albumin distribution in the nerve. The other sections were used for light and transmission electron microscopic study. RESULTS: In this model, histologic examination showed congestion and dilation in many of the intraradicular veins, as well as inflammatory cell infiltration. The intraradicular edema caused by venous congestion and Wallerian degeneration can also occur at sites that are not subject to mechanical compression. Enhanced MR imaging showed enhancement of the cauda equina at the stenosed region, demonstrating the presence of edema. CONCLUSION: Gadolinium-enhanced MR imaging may be a useful tool for the diagnosis of microcirculatory disorders of the cauda equina associated with LSCS.

Animals↗

[A novel method of dural repair using polyglycolic acid non-woven fabric and fibrin glue: clinical results of 140 cases].

This paper presents a report based on the results obtained from clinical applications of a biocompatible dural substitute made of polyglycolic acid non-woven fabric and fibrin glue. The cases subjected to this study were the ones needing reconstruction of dura mater which had become defective due to injury or brain tumor and the ones in which primary suture of the dura mater was considered to be too difficult or inadequate with ordinary methods. The dural substitute was used in 140 cases during the period between June, 2001 and July, 2005. The operations were performed using the supratentorial approach in 66 cases and infratentorial approach in 74 cases. Among these procedures, 39 cases were indicated for microvascular decompression, the commonest operation performed, then cranial base surgery in 27 cases and tumor resection in 24 cases, and so on. Lumber spinal fluid drainage or re-operation was required in 3 cases (2.1%) due to formation of post-operative cerebrospinal fluid leakage or subcutaneous accumulation of cerebrospinal fluid. With the dural substitute no infection was observed as a complication in any of the cases. Among the 140 cases presented this time, 27 cases were cranial base surgery and 74 cases were performed, using the infratentorial approach. Nevertheless, the study showed that the closing ability of the dural substitute was adequate even in actual clinical settings it is reported above that the incidence rate of post-operative cerebrospinal fluid leakage or subcutaneous accumulation of cerebrospinal fluid which require additional intervention was only 2.1%.

Adult↗

Expression of hepatitis B virus surface antigen in adult rat liver. Co-introduction of DNA and nuclear protein by a simplified liposome method.

We established a simple and efficient method for gene transfer in vitro (to cultured cells) and in vivo (to an adult organ) using liposomes. Plasmid DNA and proteins were efficiently co-encapsulated in liposomes by agitation and sonication, and were co-introduced into cells by hemagglutinating virus of Japan (HVJ)-mediated membrane fusion. Introduction of the Escherichia coli beta-galactosidase gene with non-histone chromosomal protein high mobility group 1 (HMG1) into LLCMK2 cells resulted in about 3 times higher beta-galactosidase activity than that on introduction of the gene alone. Two days after injection of HVJ-liposomes containing the beta-galactosidase gene and HMG1 under the perisplanchnic membrane of adult rat liver, hepatic cells near the injection site were found by 5-bromo-4-chloro-3-indolyl beta-D-galactoside staining to have beta-galactosidase activity. After similar injection of HVJ-liposomes containing the hepatitis B virus surface antigen (HBsAg) gene and HMG1, HBsAg was detected in the serum for 9 days with a maximum of 25-45 ng/ml on day 2 after the injection.

Animals↗

Prognostic significance of Ki-67 reactivity in soft tissue sarcomas.

Proliferative activity of soft tissue sarcomas (STS) in 34 cases was estimated by immunohistochemical procedures (avidin-biotin complex [ABC] method) with monoclonal antibody Ki-67 which reacts with a nuclear antigen expressed in all phases of cell cycle except G0. In 20 of 34 cases (59%), varying numbers of Ki-67-positive tumor cells were detected with a range from 5 to 382 per 10 high power fields (HPF) (mean 57.2/10 HPF). Ki-67 index (the number of Ki-67-positive tumor cells/10 HPF) positively correlated with mitotic count (r = 0.428, P less than 0.02), cellularity (r = 0.447, P less than 0.01), and histologic grade (r = 0.473, P less than 0.01). The Ki-67 low index group (less than 50/10 HPF) showed more favorable prognosis than the high index group (more than 50/10 HPF) (P less than 0.005). Three cases with low mitotic count and unfavorable prognosis were proved to be the Ki-67 high index group (142-382/10 HPF). These results indicated that reactivity of tumor cells for Ki-67 is a useful prognostic marker in the patients with STS, and might be used as one of the histologic factors for the grading of STS.

Adolescent↗

Horizontal inclination of the longitudinal axis of the colonic J-pouch: defining causes of evacuation difficulty.

PURPOSE: Functional outcome after low anterior resection for rectal cancer is improved by the construction of a colonic J-pouch. One disadvantage of this type of reconstruction is evacuation difficulty, which has been associated with large pouches. The purpose of this study was to elucidate the causes of evacuation difficulty in large pouches using pouchography. METHODS: The angle between the longitudinal axis of the pouch and the horizontal line (pouch-horizontal angle) on lateral pouchography was determined in 26 patients with 10-cm J-pouch reconstructions (10-J group) and 27 patients with 5-cm J-pouch reconstructions (5-J group). Measurement were made at three months, one year, and two years after surgery. Clinical function was evaluated using a questionnaire one year postoperatively. RESULTS: The pouch-horizontal angle in the 10-J group was significantly smaller than that in the 5-J group at all three time points. In both groups the pouch-horizontal angle at one year was significantly smaller than that at three months. There were no significant differences between the pouch-horizontal angles at one and two years. An evacuation difficulty was significantly more common in the 10-J group than the 5-J group. CONCLUSIONS: The evacuation difficulty observed in patients with large colonic J-pouch reconstructions may be attributed to the development of a horizontal inclination within one year of surgery.

Adult↗

Lack of intratumoral heterogeneity in DNA ploidy pattern of hepatocellular carcinoma.

BACKGROUND: From biological and clinical perspectives, it is important to clarify tumor heterogeneity. This study was aimed to investigate whether or not intratumoral heterogeneity of DNA ploidy pattern exists in hepatocellular carcinoma (HCC). METHODS: Using fresh materials resected from 31 untreated patients, DNA ploidy was analyzed at different sites of the same HCC by means of flow cytometry. The tumor size ranged from 1.7 to 25.0 cm. RESULTS: There was no case in which euploid and aneuploid HCCs coexisted in the same tumor. The DNA ploidy pattern was euploid in 15 and aneuploid in 16 instances. Of 15 euploid tumors, the areas analyzed were all diploid in 12 and tetraploid in 2 but diploid/tetraploid in 1. Among 16 aneuploid tumors, the DNA indices (DI) at different sites were similar in 9, but apparently, different aneuploid subclones coexisted in 7 cases. The incidence of DI heterogeneity in aneuploid HCCs was similar between small (< 5 cm) and large (> or = 5 cm) tumors; 3 of 7 (42.9%) versus 4 of 9 (44.4%). CONCLUSIONS: It is assumed that euploid and aneuploid HCCs develop in their own ploidy pattern and that the evolution of aneuploid subpopulations from euploid HCC is rare, but new aneuploid subclones can evolve from aneuploid HCC due to increased instability of its karyotype.

Adult↗

Interferon gamma treatment prevents procollagen gene expression without affecting transforming growth factor-beta1 expression in pig serum-induced rat liver fibrosis in vivo.

BACKGROUND/AIM: The aim of this study was to investigate the effect of interferon gamma on the synthesis of matrix proteins such as collagens with the relation to transforming growth factor-beta1 expression in vivo. METHODS: We investigated the effects of interferon gamma in a model of liver fibrosis induced by pig serum in male Wistar rats, which develops fibrosis without an increase in serum alanine aminotransferase (i.e., without hepatocyte injury). Rats were injected with 0.5 ml of pig serum twice a week for 8 weeks with or without 20,000 or 50,000 U of interferon gamma. RESULTS: Interferon gamma at doses up to 50,000 U/day prevented fibrosis, as indicated by reduced hydroxyproline content in the liver. Interferon gamma at 50,000 U/day also reduced expression of type I and III procollagen in the liver. However, the expression of transforming growth factor-beta1 mRNA and protein in the liver was not reduced by interferon gamma. Histologically, interferon gamma at 50,000 U/day also reduced the number of myofibroblast-like cells (activated stellate cells). CONCLUSIONS: These results indicate that interferon gamma can prevent fibrosis by inhibiting the activation and proliferation of stellate cells, resulting in reduced expression of procollagen without affecting transforming growth factor-beta1 expression in pig serum-induced rat liver fibrosis in vivo.

Animals↗

Assessment of the presence and severity of esophagogastric varices by splenic index in patients with liver cirrhosis.

PURPOSE: To determine whether spleen size is related to the severity of esophageal varices or associated gastric varices and liver functions in patients with cirrhosis. METHOD: The authors retrospectively studied spleen size on CT (splenic index [SI] = length x width x height of the spleen), liver functions, and the results of esophagogastric endoscopy in 110 patients with cirrhosis. They also analyzed SI in 112 controls. RESULTS: In controls, body weight, height, and age affected the SI. The SI in patients with uncompensated cirrhosis was greater compared with the SI in those with well-compensated disease (p = 0.0363). The SI in patients with esophageal varices was greater than in patients without esophageal varices (p<0.0001), but patients with and without gastric varices had similar SI values. The SI in patients with the red color signs (red wale marking, cherry red spot, and hematocystic spot) on esophageal varices or with risky varices (enlarged tortuous varices with beady, nodular, or tumor shape associated with red color signs) was greater than in patients without these signs (p = 0.0029 and p = 0.0030, respectively). CONCLUSION: The SI is a good indicator of the severity of esophageal varices and hepatic functional reserve in patients with cirrhosis.

Age Factors↗

Network computer-assisted transfusion-management system for accurate blood component-recipient identification at the bedside.

BACKGROUND: ABO-mismatched transfusions caused by human error are among the most serious problems in transfusion therapy. The major cause is misidentification of a recipient or a blood component at the bedside. STUDY DESIGN AND METHODS: A network computer-assisted transfusion-management system has been developed with bar coding as a fail-safe/fool-proof system for accurate component-recipient identification at the bedside, which allows us to monitor the usage of blood components in real time. The efficacy of this system was evaluated to prevent human errors by monitoring the transfusion process via the network and analyzing voluntary and mandatory reports with regard to transfusion errors over a 3-year period. The crossmatch-to-transfusion ratio for operations and outdate rate of RBCs were calculated to assess economic benefit. RESULTS: More than 60,000 blood components have been transfused perfectly to the intended recipients via the network, and one human error was prevented by the system. After establishment of the network system, the crossmatch-to-transfusion ratio for operations and outdate rate of RBCs have been gradually reduced from around 2.5 to 1.8 and from 3.9 to 0.32 percent, respectively. CONCLUSION: The network computer-assisted management system greatly contributes to safe and efficient transfusion therapy.

ABO Blood-Group System↗

Change in O2 uptake during rebreathing in hyperoxia in man.

In pertaining to PO2 dependency of the pulmonary CO diffusing capacity during rebreathing, the O2 uptake (VO2) and cardiac output (Q) were measured at three different PO2 levels between 100 and 500 Torr. Since the VO2 measured by an O2 injection method is strongly influenced in hyperoxia by a gas exchange ratio (R), a simulation method using a R-PCO2 relation during rebreathing was developed. Gas volume in the lung-bag-system needed in the computation was measured from the difference in O2 concentration between before and after injecting a known amount of O2 into the rebreathing circuit. The accuracy of the volume was checked by comparing it with the volume measured successively with a body box. The VO2 was determined by comparing the simulated O2 and CO2 concentrations in rebreathing gas with the measured ones. The VO2 significantly increased by rebreathing in hyperoxia. To analyze the VO2 increase, the Q was computed by dividing the VO2 by the arteriovenous O2 content difference, which in turn was obtained by dividing the slope of the CO2 dissociation curve by that of the R-PCO2 line. The Q was almost linearly related to the VO2. Since there was no difference in VO2 in steady state breathing between normoxia and hyperoxia, the increase in VO2 and Q seemed to occur transiently. This finding is very important in evaluating the PO2 dependency of the pulmonary diffusing capacity for CO.

Adult↗

[Compared studies of antimicrobial agents against E. coli, Klebsiella, Citrobacter and Proteus isolated from urinary tract infections].

In vitro activities of antibacterial agents against E. coli, Klebsiella, Citrobacter and Proteus which were isolated from patients urinary tract infections at 8 hospitals in Japan, were investigated by agar dilution method from July to October in 1979. The summarized results are as follows. 1. Among oral antibacterial agents, MPC and PPA have showed potent antibacterial activities against E. coli and Klebsiella. Among parenteral antibiotics, CTM was the most active against E. coli and Klebsiella. However, ABPC-resistant E. coli and Klebsiella have appeared to occupy about 40% and 96% of bacteria isolated from urinary tract infections, respectively. 2. In vitro activities of antibacterial agents against Proteus and Citrobacter showed not so potent. 3. Causative organisms in female patients with simple urinary tract infections were mainly E. coli and Klebsiella. 4. Among oral antibacterial agents, PPA have shown similar antimicrobial activities against E. coli isolated from simple and complicated urinary tract infections. ABPC and MPC have been influenced in some degree by these factors. However, parenteral antibiotics are not influenced by these factors. On the other hand, in vitro activities of antibacterial agents against Klebsiella isolated from simple and complicated urinary tract infections were similar.

Adult↗

A new method for continuous measurement of regional cerebral blood flow using laser Doppler flowmetry in a conscious rat.

We have developed a new system to continuously measure regional cerebral blood flow (rCBF) in the cortex of a conscious animal. For this purpose, we used rats and laser Doppler flowmetry. Under pentobarbital anesthesia, the animal's skull was opened making a small square hole 3 mm x 3 mm in size. A transparent acrylic plate was placed over the hole in the skull. A polyethylene cannula (inner diameter 1.0 mm, length 5.0 mm) was fixed on the plate as a guide for the laser Doppler flowmeter (LDF) probe (outer diameter 1.0 mm, length 5.5 mm). Both the plate and guide cannula were fixed to the skull by dental cement. Every day for the following two weeks after surgery, the conscious animal was placed in a hammock for recording rCBF. A LDF probe was freely attachable to the plate above the cortex via the guide cannula during measurement of rCBF. The rats were kept in a hammock with their legs firmly touching the floor during measurement of rCBF. It was possible to measure rCBF every day for about two weeks, and rCBF responded consistently to inhalation of 7% CO2 when the responses were expressed as percentages of the prestimulus control rCBF values. This system is recommended for the continuous measurement of rCBF in a conscious animal.

Animals↗

A late cutaneous response in actively sensitized rats: a new method for evaluating the efficacy of antiallergic drugs.

We established a new and facile model to investigate allergic mechanism and assess the effect of antiallergic compounds. Male Wistar rats were actively or passively sensitized. Active sensitization was performed by injection of both dinitrophenylated-ovalbumin (DNP-OA) and Bordetella pertussis. Nine days later, DNP-OA was injected into the right hind footpad. This antigen challenge induced a biphasic footpad swelling that consisted of an early-phase (EPR) and a late-phase response (LPR). In rats passively sensitized with rat anti-DNP-OA serum, DNP-OA induced only EPR. The EPR was suppressed by disodium cromoglycate, a mast cell stabilizer, but not by cyclosporin A, an immunosuppressant, while the LPR was suppressed by cyclosporin A. Furthermore, to investigate these two allergic responses determined by the interactions between the hapten and the carrier proteins, two distinct haptenated antigens were created. DNP-Ascaris (DNP-As) induced a marked EPR and LPR in DNP-As-sensitized rats. However, DNP-As induced only EPR in DNP-OA-sensitized rats, indicating that the usage of the same carrier protein in both sensitization and challenge was necessary for induction of LPR. These data suggest that this actively sensitization model in which EPR and LPR are functionally distinguishable should be useful for evaluating the efficacy of antiallergic compounds.

Aminopyridines↗