Primary carcinoid tumor of the testis with teratoma metastatic to the para-aortic lymph node

A primary testicular carcinoid tumor with teratoma metastasized to the para-aortic lymph node. After inguinal orchiectomy, serum and urinary levels of 5-hydroxyindoleacetic acid (5-HIAA) were found to be elevated. Chemotherapy consisting of cisplatin, etoposide and bleomycin was not effective on the metastatic lesions. Retroperitoneal lymphadenectomy normalized the levels of 5-HIAA. The patient is alive without recurrence 25 months after the retroperitoneal lymphadenectomy.     

13C-phenylalanine breath test correlates with liver fibrosis in postoperative biliary atresia

BACKGROUND: Values derived from the (13)C-phenylalanine breath test (PBT) may serve as an index for liver fibrosis and clinically predictive readings for liver diseases in adults. In the present study the PBT was conducted in postoperative biliary atresia (BA) children to evaluate phenylalanine metabolism in the liver, and the results based on biochemical data, especially the index on liver fibrosis, were compared with PBT findings. METHODS: Hepatofunctional evaluations were conducted in 10 postoperative BA children with moderate (group B; n = 4) and severe (group A; n = 6) liver dysfunction, and the PBT results were compared with those of 13 normal healthy children (group C). Subjects were orally given single-bolus (13)C-phenylalanine at 3.5 mg/kg (maximum dosing: 100 mg) in the morning. Time-related exhaled gas was periodically collected until 120 min after dosing. The (13)CO(2) levels were monitored with gas chromatography-mass spectrometry before and after administration, and the (13)C excretion rate, (13)C cumulative excretion and time of maximum (13)C excretion rate were monitored accordingly. RESULTS: Total bile acid, hyaluronic acid, type IV collagen 7S, total bilirubin or albumin and the PBT findings were significantly correlated. The PBT findings in group A were significantly lower those of group B, indicating that phenylalanine metabolism was markedly attenuated in the former. CONCLUSION: The PBT values correlated well with liver fibrosis in postoperative BA children. Because PBT is a non-invasive approach, results from this method may serve as a useful and reliable index for post-surgical monitoring of children operated on for liver fibrosis.     

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.     

Clinical significance of hepatitis G virus infection in patients on long-term haemodialysis

Infection with the newly discovered hepatitis G virus (HGV) was analysed in 163 patients on long-term haemodialysis to clarify its prevalence and clinical significance. Hepatitis G virus RNA in serum was measured by polymerase chain reaction with primers corresponding to the putative non-structural 5’ region. Of the 163 patients, three (1.8%) were positive for hepatitis B surface antigen, 40 (24.5%) were positive for hepatitis C virus (HCV)-RNA and 16 (9.8%) were positive for HGV-RNA. Five of the 16 patients with HGV-RNA were also positive for HCV-RNA. Patients with HCV and HGV coinfection had undergone a longer duration of haemodialysis (P=0.001) and had higher units of transfusion (P=0.031) compared with those without hepatitis virus infection. Transfusion history was significantly higher (P=0.039) in patients with only HGV infection than in those without hepatitis virus infection. Hepatitis C virus RNA concentration was higher (P=0.032) in patients with HCV and HGV coinfection than in those with HCV infection only, but alanine aminotransferase (ALT) levels were similar between these two groups. In conclusion, about 10% of patients on haemodialysis were infected with HGV and the infection was closely associated with transfusion history.     

Lack of hepatic benefit by oxygen inhalation during vasopressin infusion in patients with cirrhosis

Vasopressin has been found to impair hepatic function in patients with cirrhosis. The aim of this study was to investigate whether oxygen inhalation could improve hepatic function during vasopressin infusion. Vasopressin (0.3 iu/min) was infused into eight patients with cirrhosis for 50 min. During the first 30 min they were ventilated by room air and for the following 20 min by oxygen (approximate 50% of FiO2). The extra oxygen inhalation caused a typical increase in arterial (+7%, P less than 0.01), portal venous (+8%, P less than 0.05), and hepatic venous (+9%, P less than 0.01) oxygen content. No effect was noted in arterio-hepatic venous and portal venous-hepatic venous oxygen content difference in comparison with the values after vasopressin alone. The hepatic perfusion remained unchanged. These results suggest that the extra oxygen did not increase hepatic oxygen uptake. Similarly, intrinsic clearance of indocyanine green did not improve. It is concluded that oxygen supplement in this setting has no hepatic benefit in patients with cirrhosis.     

Gene therapy for metachromatic leukodystrophy

Metachromatic leukodystrophy (MLD) is an inherited metabolic disease which is characterized by a deficiency of arylsulfatase A (ASA). This deficiency causes progressive accumulation of cerebroside sulfate in oligodendrocytes (OL) in the brain, resulting in dysmyelination. Approaches being developed by the authors to treating MLD are based on direct delivery of ASA genes into the brain. In the present report, it has been shown that the recombinant adenovirus (Adex 1SRLacZ) was able to transduce the OL very efficiently. Moreover, primary fibroblasts from MLD patients were exposed to recombinant adenovirus expressing the ASA gene (Adex1SRASA) and the cells expressed the transgene. The influence of overexpression of ASA on the activity of other sulfatases was also tested in fibroblasts from patients with MLD using a retrovirus vector (MFG-ASA). It was demonstrated that the overexpression of ASA reduces the activity of various sulfatases by a small amount but does not induce an accumulation of glycosaminoglycan. These results indicate that the influence of ASA overexpression on other sulfatases is different from that of the N-acetygalactosamine-4-sulfatase overexpression in a previous report. It was concluded that the correction of ASA deficiency by a recombinant adenovirus that potentially could be used to transfer the gene to the brain, and gene therapy for MLD based on gene transfer of the ASA gene to mutant cells will be feasible because the overexpression of ASA in cells does not lead to profound deficiency of other sulfatases or result in a new phenotype.     

Pharmacokinetics:Pharmacokinetic Differences Between Lansoprazole Enantiomers in Rats

Because limited information is available about potential differences between the pharmacokinetics and pharmacodynamics of the enantiomers of lansoprazole, the enantioselective pharmacokinetics of the compound have been investigated in rats. There was a noticeable difference between the serum levels of the enantiomers of lansoprazole and of their metabolites, 5-hydroxylansoprazole enantiomers, after oral administration of the racemate (50 mg kg^?1) to rats. C_max (maximum serum concentration) and AUC (area under the serum concentration-time curve) for (+)-lansoprazole were 5–6 times greater than those for (—)-lansoprazole, whereas for (+)-5-hydroxylansoprazole both values were significantly smaller than those for the (—) enantiomer. CL_tot/F values (where CL_tot is total clearance and F is the fraction of the dose absorbed) for (+)-lansoprazole were significantly smaller than those for the (—) enantiomer. There was no significant difference between the absorption rate constants of the lansoprazole enantiomers in the in-situ absorption study. The in-vitro protein-binding study showed that binding of (+)-lansoprazole to rat serum proteins was significantly greater than for the (—) enantiomer. The in-vitro metabolic study showed that the mean metabolic ratio (45.9%) for (—)-lansoprazole was significantly greater than that (19.8%) for the (+) enantiomer in rat liver microsomes at 5.6 μM lansoprazole. These results show that the enantioselective disposition of lansoprazole could be a consequence of the enantioselectivity of plasma-protein binding and the hepatic metabolism of the enantiomers.     

Long-Term Survival in Patients with Small Cell Lung Cancer

Of the 66 patients with small cell lung cancer (SCLC) who weretreated by combination chemotherapy with or without radiationtherapy from July 1978 to December 1983 at the National CancerCenter Hospital, Tokyo, 12 (18%) sur vived over two years andnine (14%) have remained disease-free over three years. Thetwo-year survival rates were compared according to the patientcharacteristics of sex, performance status (PS), extent of disease,histologic subtype, regimen of the initial chemotherapy andresponse to treatment. Sex, extent of disease and response tothe initial chemotherapy were the most important prognosticfactors. The prognosis for patients with liver or bone metastasis was poor. All disease-free survivors, except for two patientswho were treated by surgical resection after chemotherapy, achievedcomplete response (CR) with chemotherapy with or without radiationtherapy. Eleven of the 12 two-year survivors achieved CR. Becauseof the small number of patients in our study, it will be necessaryto evaluate further the influence of prognostic factors in patientswith SCLC in future studies.     

Temporal and egional profiles of cytoskeletal protein accumulation in the rat brain following traumatic brain injury

Abstract To characterize the cytoskeletal aberration due to traumatic injury, temporal and regional profiles of changes in immunoreactivity of microtubule-associated protein 2 (MAP2), neurofilament heavy subunit protein (NFH) and heat shock protein 72 (HSP72) were investigated after different magnitudes of traumatic brain injury by fluid percussion. The experimental rat brain was perfusion-fixed at 1, 6 and 24 hours after traumatic brain injury. Conventional histological staining has demonstrated that the mildest traumatic brain injury (1.0 atm) induced no neuronal loss at the impact site and that neuron loss was apparent when traumatic brain injury was increased to 4.3 atm. The mildest traumatic brain injury, however, caused a significant increase in HSP72 immunoreactivity in the superficial cortical layers at the impact site as early as 1 hour after the injury. In the case of severe traumatic brain injury (4.3 atm), neuron loss was apparent in the area at the impact site, but the increase in HSP72 immunoreactivity was moderate, and it was observed only after 6 hours in the deep cortical layers under the necrotic area. The increased immunostaining of MAP2 was demonstrated in damaged axons and neuronal perikarya in the wider area surrounding the impact site at 6 and 24 hours after the injury. Six and 24 hours after the injury, perikaryal accumulation of neurofilament was observed, and the accumulated neurofilament was mostly phosphorylated. These results indicate that the severe traumatic brain injury of 4.3 atm triggers the abnormal accumulation of cytoskeletal proteins in neuronal perikarya, most probably due to an impairment of axonal transport. It is implied that the increased expression of HSP72 may be involved in the protective process of neurons after traumatic brain injury.