Metastasis of hepatocellular carcinoma to the right colon manifested by gastrointestinal bleeding

An 82-year-old black woman with a history of hepatocellular carcinoma presented with gastrointestinal bleeding. Barium enema and fibrocolonoscopy revealed a 4-cm polypoid mass at the level of the ascending colon with evidence of active bleeding. Biopsies of the lesion proved it to be metastatic hepatocellular carcinoma. Exploratory laparotomy revealed no further dissemination of the tumor, and the patient underwent an ileocolectomy. The serosal side of the colonic lesion was free from tumor, and there was no peritoneal implantation, direct extension, or lymph node involvement. This case represents an extremely rare presentation of metastatic hepatocellular carcinoma.     

A case of crossed fused kidney with simple ureterocele

A 32-year-old man consulted Osaka National hospital with chief complaints of dysuria and macrohematuria. DIP and CT revealed that the right kidney deviated to the lower pole of the left kidney and they fused together. The right ureter crossed over the supine. The calcified shadow existed in the lower end of the left ureter with cobra head image. He had no external anomalies. Under diagnosing crossed fused kidney (inverted L shaped) complicated the left ureterocele with a stone, transurethral incision of ureterocele (TUI) was performed. We made transverse incision and extracted stone, 7 mm in size (calcium oxalate 96% and calcium phosphate 4%). Three months later after the operation, IVP, CG and VCG revealed the down-sized ureterocele and no VUR. Crossed renal ectopia complicated many anomalies about 50%. Among them anomalies of the urinary tract was most frequent about 30%. But crossed renal ectopia with ureterocele wasn't reported so far in Japanese literature.     

Highly sensitive analysis for N-myc amplification in neuroblastoma based on fluorescence in situ hybridization

BACKGROUND/PURPOSE: The N-myc amplification status in neuroblastoma has been evaluated previously for the whole tumor by the Southern blot method. The aim of this study is to evaluate the effectiveness of the fluorescence in situ hybridization (FISH) method to analyze N-myc amplification in neuroblastoma and compare the findings with those using the Southern blot method. METHODS: In 26 neuroblastoma primary tumors and metastatic lesions, the N-myc amplification status was evaluated by both the Southern blot method and FISH method. RESULTS: Of the 22 samples with no N-myc amplification using Southern blot, no cells with N-myc amplification using FISH were present in 21 of the samples. However, one metastatic liver lesion showed 16% of the nuclei to display more than 10 copies of N-myc based on FISH analysis. In the 4 remaining samples with N-myc amplification using the Southern blot method (17 copies, 15 copies, 6 copies, and 3 copies), the rates of cells with more than 10 copies of N-myc based on a FISH analysis were 79%, 68%, 94%, and 9%, respectively. CONCLUSIONS: The FISH method can detect more accurately N-myc amplification than the Southern blot method either when the rate of cells with N-myc amplification is low or intratumor heterogeneity is present.     

Excitability of spinal cord and gracile nucleus neurons in rats with chronically injured sciatic nerve examined by c-fos expression

Low-threshold sensory pathways have been suggested to have an important role in the formation and maintenance of sensory abnormalities which are observed after peripheral nerve injury. Fos-like immunoreactive (Fos-LI) neurons are expressed in spinal cord laminae III-IV and the gracile nucleus by electrically stimulating the injured nerves at Abeta strength after sciatic nerve transection in rats. This suggests that the excitability of these neurons is increased by nerve injury. In this study, we investigated which receptors are involved in the regulation of the increased excitability in spinal and gracile nucleus neurons. The sciatic nerve of Sprague-Dawley rats (150 g) was transected 7 days before the experiment day. The rats were administered morphine, muscimol, baclofen, MK-801, CNQX, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) or clonidine i.p., and then electrically stimulated at 0.1 mA to the proximal region to the nerve injury site under urethane anesthesia. Two hours after the stimulation, Fos-LI expression was increased in the spinal cord dorsal horn and the gracile nucleus in control rats. Baclofen inhibited the Fos-LI expression both in the spinal cord and the gracile nucleus. Morphine inhibited only the Fos-LI expression in the posterior cutaneous (PC) nerve territory of laminae I-II, but not in the sciatic nerve (SC) territory, laminae III-IV nor the gracile nucleus. MK-801 had an inhibitory but complicated effect in laminae I-II and the gracile nucleus. The other drugs were not effective on Fos-LI expression. It is suggested that the GABA(B) receptor has a pivotal role in the regulation of Fos-LI expression after electrical stimulation to the injured low-threshold sensory fibers, and other receptors have little effect on the Fos-LI expression.     

Open channel block of NMDA receptors by conformationally restricted analogs of milnacipran and their protective effect against NMDA-induced neurotoxicity

We investigated the blocking effect of the conformationally restricted analogs of milnacipran on NMDA receptors by recording the whole-cell currents of Xenopus oocytes injected with rat brain mRNA and the single channel currents of cultured hippocampal neurons under voltage-clamp conditions. Their protective effect against excitotoxicity was also investigated on cultured cortex neurons. All conformationally restricted analogs examined blocked activated NMDA receptors, though their structures were quite different from known NMDA receptor blockers. The analogs with a (1S, 2R, 1'S)-configuration such as PPDC ((1S, 2R)-1-phenyl-2[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide+ ++) had lower IC50 values than those with other configurations. The empirical Hill coefficients for each compound were close to unity, indicating a 1:1 stoichiometry for the block. PPDC decreased the maximum responses to both N-methyl D-aspartate (NMDA) and glycine without altering their dissociation constants. The blocking effect was enhanced on hyperpolarization. PPDC had no effects on other glutamate receptor subtypes (AMPA, kainate, and metabotropic glutamate receptors) or other neurotransmitter receptors (GABA(A), 5HT2C, and AChM1 receptors) produced by the oocytes. PPDC decreased the mean open time of NMDA receptors without decreasing their elementary conductance. The microscopic blocking rate constant was 2.8x10(7) M(-1)s(-1). The macroscopic unblocking rate constant of PPDC was much faster than that of MK-801. Only the analogs with the (1S, 2R, 1'S)-configuration protected the cultures against NMDA-induced neurotoxicity, though they failed to protect against kainate-induced neurotoxicity. These results show that conformationally restricted analogs, at least PPDC, selectively blocked open channels of NMDA receptors.     

Paradoxical effect of L-arginine on nitric oxide (NO) synthesis and histopathological changes in 5/6 nephrectomized SD rats

Whether L-Arginine (L-ARG) ameliorates or aggravates renal function and histopathological changes in several models of renal disease remains controversial as L-ARG is the substrate for nitric oxide (NO) synthase as well as the precursor of proline and polyamines which cause renal fibrosis. These ambiguous results might be attributed to differences in the dose and period of L-ARG administration and the animal model used in each observation. Therefore, we tested the dose-dependent effect of L-ARG on mean blood pressure (MBP), 24-hour urinary excretion of protein (UP), NO metabolites (NO2(-) + NO3-) and cyclic GMP (cGMP), plasma asymmetrical dimethylarginine (ADMA), glomerular sclerosis index (SI) and % interstitial fibrosis area (%INT) in 5/6 nephrectomized SD rats. These 5/6 nephrectomized SD rats were divided into 4 groups: 1. L-ARG 0.2 g/kg/day (0.2 g ARG), 2. L-ARG 1 g/kg/day (1 g ARG), 3. L-ARG 2 g/kg/day (2 g ARG), 4. No administration of L-ARG(ARG(-)). Compared with ARG(-)MBP, UP and ADMA were significantly decreased and NO2(-) + NO3-, cGMP were significantly increased in the 0.2 g ARG. SI group and %INT were significantly increased in the 2 g ARG group and decreased in the 0.2 g ARG group. A small dose of L-ARG ameliorated glomerulosclerosis and interstitial fibrosis while a larger dose did not. SI, %INT and ADMA were inversely correlated with NO2(-) + NO3-. These data suggested that renal NO synthesis might attenuate glomerulosclerosis and interstitial fibrosis and the rise in ADMA and L-ARG might cause the decrease in NO.     

Plasma fatty acids concentrations in postoperative patients with biliary atresia.

The concentrations of plasma fatty acids in postoperative patients with biliary atresia (BA) were measured to clarify whether they had essential fatty acid deficiency. Thirty-eight fasting blood samples from 14 postoperative patients with BA were studied. All of them had the hepatic portoenterostomy without any stoma. Samples were divided into three groups on the basis of liver function. The concentrations of fatty acids in the plasma fat were measured quantitatively. Non-essential fatty acids levels were increased and omega-3 fatty acids levels were decreased with the progress of deterioration of hepatic function. Regarding omega-6 fatty acids, C18:2 and 20:4 did not show any significant difference between the three groups and the control, and only C20:3 increased with the deterioration of liver dysfunction. The ratio of C20:3 (omega-6) to C20:4 (omega-6) was increased significantly with the progress of liver dysfunction. The activity of delta-5 desaturase was suspected to be suppressed in BA patients with poor liver function. The BA patients with poor bile flow did not show any decrease of omega-6 fatty acids in the plasma, but were at risk of developing omega-3 fatty acid deficiency.     

Population pharmacokinetic analysis of theophylline: relationship between serum concentrations and clinical effects in therapeutic drug monitoring

Therapeutic drug monitoring (TDM) of theophylline is essential duties at hospital pharmacy in Japan. The relationship between serum concentrations and clinical effects of theophylline has been investigated. The pharmacokinetics of theophylline was determined from the concentration of theophylline in the serum which were calculated on the basis of TDM for patients administered theophylline. The one-compartment model as a pharmacokinetic model was assumed. The relationship between clinical effects of theophylline and the predicted concentrations calculated using population parameters was evaluated. The obtained parameters are ka(h-1) = 0.223, ke(h-1) = 0.047 (1-0.0025.age(y) (p.o.) and 0.076(1-0.0025.age(y)) (d.i.v.), Vd(1/kg) = 0.733 (p.o.) and 0.830 (d.i.v.). The bioavailability is 0.732, and theophylline/aminophylline is 0.846. The model including no serum creatinine as a variational factor was considered to be best. The following three groups were used as a clinical evaluation; effective as theophylline therapy was 43%, no change of the clinical status after administration of theophylline was 42%, and aggravation after administration of theophylline was 15%. There is no relationship between the predicted concentration using parameters of the final model and these three groups. These results suggest that TDM of theophylline should be assessed in terms of clinical effects and also suggests that in should be kept monitoring from the viewpoint of the prevention of toxic effects in the theophylline therapy.     

Lower plasma levels of haloperidol in smoking than in nonsmoking schizophrenic patients.

The impact of smoking on plasma haloperidol (HAL) concentrations was investigated in 66 Japanese male schizophrenic inpatients treated orally with HAL. The subjects consisted of 22 nonsmokers and 44 smokers each smoking ten cigarettes per day. Plasma concentrations of HAL were determined by an enzyme immunoassay method. There were significant positive correlations between the plasma HAL concentration and the daily dose of HAL per kg body weight (Y = 58.1X-0.01 (r = 0.86)). Smokers had significantly lower HAL concentrations per daily dose of HAL/kg body weight than nonsmokers (smokers vs. nonsmokers = 54.3+/-16.6 vs. 70.6+/-23.2 ng/mL/mg/kg). In doses less than 0.2 mg/kg of HAL, smokers showed significantly lower HAL concentrations per daily dose of HAL/kg body weight than nonsmokers (smokers vs. nonsmokers = 55.1+/-14.4 vs. 79.5+/-27.1 ng/mL/mg/kg), whereas no significant difference in HAL concentrations per daily dose of HAL/kg body weight was observed between smokers and nonsmokers when treated with more than 0.2 mg/kg (smokers vs. nonsmokers = 52.9+/-20.7 vs. 60.0+/-11.1 ng/mL/mg/kg). Our results indicate that smoking may induce the enzyme(s) metabolizing HAL, which results in lower plasma HAL concentrations in smokers than in nonsmokers, particularly at low doses of HAL.