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Left ventricular assist device (LVAD) was utilized for the treatment of postcardiotomy heart failure in two patients with Marfan's syndrome. Patient 1 (a 22-year-old) with annuloaortic ectasia (AAE) and DeBakey type II dissection had been supported by LVAD for 87h after composite graft replacement of the ascending aorta and aortic valve. Patient 2 (a 52-year-old) with AAE and DeBakey type I dissection had been supported by LVAD for 91 h after aortic valve replacement. During the assist, both patients complicated bleeding from the fragile left atria near the sites of cannulation. Patient 1 died of multiple organ failure on the 62nd postoperative day, but patient 2 returned to work after surgery.

"Free" iron, a potentially radical-generating low mass iron, and not found in normal human blood, was increased in the serum of blood-transfused thalassemia major patients seen in the Yangon General Hospital, Yangon, Myanmar (Burma). The low mass iron was detected by the bleomycin assay. Fifty-one blood samples were analyzed (from 28 males and 23 females). High "free" iron was detected in 47 sera samples from thalassemia patients. Serum ferritin, which reflects the body store iron, was higher than the normal range (10-200 ng/ml) in 49 patients. On the other hand, serum iron of 39 sera samples fell within the normal range (50-150 micrograms/dl). Four were less than 50 micrograms/dl and eight were more than 150 micrograms/dl. Almost all the patients' sera of normal or higher serum iron level contained "free" iron. Thus, almost all the sera from thalassemic patients from Myanmar contain bleomycin-detectable iron, even when serum iron is within the normal range. In developing countries where undernutrition is prevalent (serum albumin in these patients was 3.6 +/- 0.4 g/dl, P < 0.0001 vs. control value of 4.0 - 4.8 g/dl), normal serum iron does not preclude the presence of free iron in the serum.

To study the virological and serological characteristics of asymptomatic hepatitis C virus (HCV) carriers, 165 blood donors positive for antibody against HCV proteins by the second generation assay, were analyzed for their clinical backgrounds, serological reactivity against antigens derived from HCV by recombinant immunoblot assay, and the amount and genotype of HCV by the polymerase chain reaction. Compared with blood donors having abnormal levels of alanine aminotransferase (ALT), sera from the donors with normal levels of ALT reacted less frequently against NS4 antigens (anti-5-1-1: 34.4% vs. 54.5%, P = 0.0609; anti-c100-3: 34.4% vs. 56.1%, P < 0.05). Also the positivity for antibodies against these antigens were more frequent in sera from donors with genotype 1b HCV-RNA than other genotypes (anti-5-1-1: 61.0% vs. 23.5%, P < 0.01; anti-c 100-3: 61.0% vs. 26.5%, P < 0.01). The prevalence of each genotype in blood donors with normal ALT levels was different from that in patients with advanced liver disease (P < 0.05), genotype 1b being less and genotype 2a being more frequent. The number of HCV-RNA copies/0.5 ml in donors with normal ALT was 10(7.9 +/- 1.0) (n = 27) and that in patients with chronic liver disease was 10(7.4 +/- 0.8) (n = 116), the difference being statistically significant (P < 0.05). In conclusion, the results of this study suggest that asymptomatic blood donors carrying HCV have the serological and virological characteristics different from the patients with advanced liver disease.

To find an effective way to handle wheelchairs, 3-dimensional floor reactions of the hand and angular deviation of the elbow and wrist joints during push-up motion were studied in 10 healthy men. The push-up was carried out using 3 hand positions (fist, finger and palm) and a push-up device. In all hand positions, anteroposterior force (Fx) and the mediolateral force (Fy) appeared after the vertical force (Fz). The end point of Fx and Fy was observed before that of Fz. Among the 4 different hand positions, Fx and Fy appeared first in the palm, followed by the finger and fist positions, and lastly in the push-up devices. The results indicate that the more unstable pushing-up the body is, the earlier and longer Fx and Fy are. Thus, Fx and Fy are considered to be good indicators of body balance during the push-up motion. The elbow joint showed a hyperextended position only when using the palm position in the maintenance phase. The wrist joint showed palmar flexion only when using the fist position.

A persistent problem in orthotopic liver transplantation is primary nonfunction (PNF) of the hepatic allograft. In an attempt to reduce the incidence of graft failure, the feasibility of pretransplant assessment of graft viability was investigated by 31P nuclear magnetic resonance (NMR) spectroscopy. The level of adenosine triphosphate (ATP) was measured as an indicator of liver function by 31P NMR spectroscopy after a 30 min normothermic reperfusion following cold-storage in University of Wisconsin (UW) solution. The mean +/- SD beta-ATP/Pi ratio after preservation for 0, 12, 24 or 48 h was 1.40 +/- 0.34, 0.85 +/- 0.27, 0.64 +/- 0.14 and 0.38 +/- 0.09, respectively. Significance was observed between 12h and 24h and between 12h and 48h of preservation. These results correlated well with the morphological changes in endothelial cells and sinusoidal lining cells examined by transmission electron microscopy. It is suggested strongly that microcirculatory disturbances due to endothelial cell injury impairs the recovery of ATP levels after reperfusion, and that ATP determination by 31P NMR spectroscopy, as a non-invasive modality, may help in the prediction of PNF after liver transplantation.

The presence of high-risk types of human papillomavirus (HPV) 16, 18 and 33 in cell lines established from several malignancies including 5 of cervical cancer and 6 of head and neck cancer was studied. HPV DNA, either type 16 or 18, was detected by polymerase chain reaction, and by Southern blot hybridization in all of the cell lines derived from cervical cancers. The hybridization patterns of HPV DNA after endonuclease digestion differed among cell lines, suggesting that all of these cell lines were independent isolates. Accordingly, high-risk types of HPV DNA seem to be ubiquitous in cervical cancer. HPV DNA was not detected in the cell lines derived from head and neck cancers or from any other malignancies besides cervical cancer in this study.

Monoclonal antibodies were raised against urine proteins from diabetic patients. An antibody, YO-2, stained three protein bands with apparent molecular weights of 66, 49, and 36 kDa. These bands were not reactive with an anti-human albumin antibody. The urine levels of YO-2-reactive antigen in the normal control were 0.97 +/- 0.37 U/g-Cr (units per gram of urine creatinine) (mean +/- SD). Those of the normo-, micro-, and macroalbuminuric diabetic patients, respectively, were 1.38 +/- 1.36, 2.87 +/- 2.07, and 3.92 +/- 3.33 U/g-Cr. They were significantly higher in the micro- and macroalbuminuric patients. The urine levels of YO-2-reactive antigen had no significant correlation with the urine albumin levels and hemoglobin A1c. We concluded that; a) monoclonal antibody YO-2 recognized a non-albumin urine antigen increasingly excreted in diabetic patients with nephropathy, b) recent glycemic control of diabetes would not significantly affect the urinary excretion rate of YO-2-reactive antigen, and c) the excretion rate and probably the mechanism of YO-2-reactive protein differed from those of albumin. The urine levels of YO-2-reactive antigen could be a clinical marker of diabetic nephropathy.

In this study, we established the surgical procedure and postoperative care of multivisceral transplantation (MVTX) in pigs, and examined the functional changes and rejection pattern of transplanted organs in MVTX. Twenty-two MVTXs were performed without immunosuppression, and nine cases (41%) that survived for 5 days or more after MVTX were used for evaluation. Rejection in grafts including the liver, pancreas, and gastrointestinal tract were assessed histopathologically. On day 5 after transplantation, the duodenum and small bowel already showed signs of mild rejection. On the other hand, in the liver, pancreas and stomach, rejection occurred later and was still mild on day 16. Hepatic rejection in MVTX appeared to occur later than in simple liver transplantation (LTX). These results showed that the susceptibility to rejection of individual visceral organs varies.

The effect of cigarette smoke on organ weights, lipid peroxidation and plasma biochemical parameters was investigated in male Wistar rats. Daily exposure (for 20 min twice a day) to cigarette smoke for 27 days caused a significant decrease in liver weight and a significant increase in lung weight. The smoke-exposure group showed increased lipid peroxidation in the liver, but not in the lung. In the smoke-exposure group, the GOT, gamma-GTP, total bilirubin and LDH values were significantly higher than those in the control group, while the plasma glucose value was significantly lower. These results suggest that cigarette smoking might induce liver injury by enhancing lipid peroxidation.

The possible role of nitric oxide (NO) and vasoactive intestinal polypeptide on isoprenaline-induced relaxation of the mouse longitudinal gastric fundal strips precontracted with 5.4 x 10(-7) M carbachol was investigated. Isoprenaline (5 x 10(-7) M, 10(-6) M and 5 x 10(-6) M) produced a concentration-dependent relaxations. NG-nitro L-arginine (10(-4) M) partly inhibited isoprenaline-induced relaxation. The inhibitory action of NG-nitro L-arginine was reversed by 4 x 10(-4) M L-arginine but not by 4 x 10(-4) M D-arginine. NG-nitro L-arginine (10(-4) M) did not affect the relaxation caused by sodium nitroprusside (10(-6) M). Vasoactive intestinal polypeptide antibody 7913 (1:160 dilution) partly inhibited isoprenaline-induced relaxation. This inhibition was greater on the response to the higher isoprenaline concentration (5 x 10(-6) M) than to the lower concentration (10(-6) M). The combination of vasoactive intestinal polypeptide antibody and NG-nitro L-arginine significantly enhanced the inhibition on 10(-6) M isoprenaline action. These results suggest that nitric oxide and vasoactive intestinal polypeptide may partly contribute to the relaxation induced by isoprenaline in the mouse gastric fundus precontracted with carbachol.

<p>To assess the role of the kidney dopamine system on the diuretic state induced by angiotensin-converting enzyme (ACE) inhibitors, we examined the changes in urinary excretion and plasma level of dopamine, and kidney dopamine receptors in spontaneously hypertensive rats (SHR) treated with cilazapril, an ACE inhibitor. We administered cilazapril 10 mg/kg orally to 13-week-old SHR daily for 21 days (CILAZA group). Systolic blood pressure was significantly decreased in the CILAZA group on Day 6 compared with that in vehicle-treated SHR (control group). The urine volume was three- to fivefold higher in the CILAZA group, and total urinary dopamine secretion was also increased compared with the control group. There was no significant difference in affinity and number of kidney dopamine receptors between the CILAZA and the control groups. In conclusion, the diuretic effect caused by cilazapril is partly mediated by inhibition of the water reabsorption via the increase of dopamine production in the kidney.</p>

The antitumor effects of indomethacin and interleukin 2 (IL-2) were studied in C3H/HeJ mice inoculated with MH134 hepatoma cells. Combined treatment with indomethacin and IL-2 augmented natural killer (NK) cells in mice with MH134-induced peritoneal carcinomatosis, and the survival of the treated mice was significantly longer than the non-treated mice. In animals with subcutaneous MH134 tumors, the combined therapy with indomethacin and IL-2 significantly suppressed tumor growth and induced complete regression of the tumor in three out of five mice. These results suggest that indomethacin and IL-2 therapy could be effective on human gastrointestinal cancer cells as well.

We examined the pharmacokinetics of phenobarbital before and during pregnancy in rats. Animals were divided into four groups: (a) control, (b) pregnant, (c) phenobarbital-treated, and (d) phenobarbital-treated pregnant groups. The increase in body weight of nonpregnant or pregnant rats was not influenced by long-term phenobarbital treatment. Plasma phenobarbital concentrations during the period of long-term phenobarbital treatment with a fixed dosage by body weight were not significantly affected by pregnancy. Furthermore, pregnancy did not affect pharmacokinetic parameters of phenobarbital between 0.25 and 24h after administration. These results suggest that pregnancy does not influence on the pharmacokinetics of long-term phenobarbital treatment at a fixed dosage by body weight.

Eighty-one adult Nigerians with essential hypertension were randomly allocated to receive doxazosin, hydrochlorothiazide/amloride, or amlodipine. In each group, the patients were further classified as obese and non-obese, and total cholesterol as well as high density lipoprotein (HDL) cholesterol was determined before and after the 3-month treatment period. The total cholesterol level was significantly reduced in the non-obese patients, but did not show any significant change in the obese patients after doxazosin therapy, indicating the beneficial effects of doxazosin therapy in non-obese patients. The levels of total cholesterol increased and HDL cholesterol decreased in both the obese and the non-obese patients after hydrochlorothiazide/amloride therapy. Amlodipine treatment did not cause any significant change in the total and HDL cholesterol levels in both the obese and non-obese patients. These findings are worthy of consideration by clinicians and researchers when selecting the most appropriate drug for antihypertensive pharmacotherapy.

Seventy-six patients with ulnar neuropathy at the elbow were divided into 3 classes (Grades I, II, and III) according to their clinical features and the maximal motor nerve conduction velocity (MCV), and the amplitude ratios at the across-elbow segment were retrospectively analyzed. To determine the criteria for abnormality, a control study was conducted on 150 healthy volunteers ranging in age from 20 to 89 years (6 age groups). The normal value for MCV could be set for two age groups: those under 60 and those over 60 years old. The 95% confidence limit was 54m/s for the former and 50m/s for the latter. There was no statistically significant difference in the amplitude ratio among the age groups. The confidence limit was set uniformly at 0.82 (above elbow/below elbow). An abnormality in either MCV or the amplitude ratio was found in 66.7% of Grade I (recent and mild symptoms), 89.7% of Grade II (persistent symptoms), and 100% of Grade III cases (marked intrinsic muscle atrophy). Evaluation using the combination of MCV and the amplitude ratio, considering the age-related normal value, appeared to be useful in establishing a differential diagnosis of ulnar neuropathy at the elbow.

The reduced hepatic blood flow calculated from hepatic scintigram with 198Au colloid was elucidated as the primary responsible factor for postoperative hepatic insufficiency. However 198Au colloid is no longer in use because of the high levels of radiation. Although 99mTc-phytate behaves similarly to 198Au on imaging, there were discrepancies between the hepatic blood flow index (KL) value and the severity of cirrhosis determined by laboratory data or by histology. In the measurement of hepatic blood flow using a radioactive colloid, factors like organ distribution, stability and uniformity of the colloid particles influence the values. In the present study, a 111In colloid was prepared and administered to rats to investigate the usefulness: as much as 95.4 (0.8) [Mean (+/- SD)]% of the colloid accumulated in the liver at pH 6.8. The distribution of particle diameter was within a relatively narrow range with the peak at 0.2 to 0.4 microns. Moreover, the KL values were not affected by condition of the reticuloendothelial system. The values showed a significant correlation with the measurements of the hepatic tissue blood flow obtained by the hydrogen gas clearance method (gamma = 0.83, P < 0.001). Thus, the 111In colloid can be clinically used as a substitute for 198Au colloid in the preoperative examination for estimation of the limit of resection.

The medical records of 16 consecutive patients with Crohn's disease surgically treated in our department from 1978 to 1993 were retrospectively reviewed. The indication for surgery was obstructive symptoms due to Crohn's strictures that were unresponsive to conservative therapy. The types of operations performed were classified into five categories. Nine patients (56.3%) had small bowel resection only, 4 (25.0%) underwent an ileocolonic resection, 1 (6.3%) had a total colectomy, 1 (6.3%) had Mile's operation and 1 (6.3%) had subtotal gastrectomy with gastrojejunostomy and antral mucosectomy. Of these 16 patients, 13 (81.3%) had resection with a single anastomosis and strictureplasty was concomitantly performed in only 2 cases (12.5%). Crohn's disease recurred in 3 patients (18.8%), 1 of whom required a second operation.

In situ hybridization of slide-mounted brain sections from rats subjected to acute and chronic phencyclidine treatment was carried out using synthetic oligonucleotides complementary to dopamine D2-receptor and non-N-methyl-D-aspartate (NMDA) glutamate-receptor-subunit (GluR-1) mRNAs. There was no significant difference in either the D2-receptor or the GluR-1 mRNA levels in any brain region of the acute phencyclidine (10 mg/kg)-treated and control groups. However, chronic administration of phencyclidine (10 mg/kg/day, 14 days) significantly decreased the dopamine D2-receptor mRNA level in the caudate-putamen (by 27%, P < 0.01) and significantly increased the GluR-1 mRNA level in the prefrontal cortex (by 29%, P < 0.001). These results suggest that the chronic pharmaco-behavioral effects of phencyclidine may involve expression of both dopamine- and non-NMDA glutamate-receptor mRNAs.

We administered a biological response modifier Picibanil (OK-432), attenuated Streptococcus pyogenes, via the dorsal vein of the penis after 70% hepatectomy in rats, and clarified the scavenging effect of Picibanil on free radicals generated in the regenerating liver. A group of 5 rats was intravenously administered with 25 KE/kg of OK-432 after hepatectomy, while the control group was given saline after hepatectomy. Serum levels of aspartate aminotransferase and alanine aminotransferase and the value of thiobarbituric acid-reactive substances in serum and hepatic tissue after hepatectomy were serially measured, and these values were significantly lower in Picibanil treated animals than in control animals. Free radical production in the regenerating liver was also measured by electron spin resonance spectrometry, and OK-432 injection significantly reduced free radical production. These results suggested that OK-432 reduced hepatocellular damage in regenerating liver by inhibiting lipid peroxidation.