Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: A biomarker corroboration study

AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma(HCC) patients compared to cirrhosis patients and controls. METHODS: Urine samples from 42 Bangladeshi patients with HCC(39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance(NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis(PCA) and orthogonal partial leastsquared discriminant analysis(OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLSDA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance(ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the MannWhitney U test was used to compare metabolite levels depending on hepatitis B e-antigen(HBe Ag) status and treatment with anti-viral therapy. A BenjaminiHochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P 0.05.RESULTS: There were significant differences in age(P 0.001), weight(P 0.001), and body mass index(P 0.001) across the four clinical subgroups. Serum alanine aminotransferase(ALT) was significantly higher in the HCC group compared to controls(P 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group(P = 0.004). A threefactor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, creatine, creatinine, dimethyamine(DMA), formate, glycine, hippurate, and trimethylamine-N-oxide(TMAO). A comparison of relative metabolite levels confirmed that carnitine was significantly increased in HCC; and creatinine, hippurate, and TMAO were significantly reduced in HCC compared to the other subgroups. HBe Ag negative patients showed a significant increase in creatinine(P = 0.001) compared to HBe Ag positive patients in the chronic hepatitis B subgroup, whilst HBe Ag negative patients showed a significant decrease in DMA(P = 0.004) in the cirrhosis subgroup compared to HBe Ag positive patients. There were no differences in metabolite levels in HCC patients who did or did not receive antiviral treatment. CONCLUSION: Urinary NMR changes in Bangladeshi HCC were identified, corroborating previous findings from Egypt and West Africa. These findings could form the basis for the development of a cost-effective HCC dipstick screening test.     

Evaluation of three psychologic interventions to reduce anxiety during MR imaging

The authors compared the effectiveness of three anxiety-reducing interventions for patients undergoing magnetic resonance imaging. Each of 50 subjects was randomly assigned to one of the interventions. Intervention 1 involved provision of information about the imager and nature of the examination. Intervention 2 included information and counseling. Intervention 3 included information and a 12-minute relaxation exercise. Anxiety levels were measured by means of a 20-item questionnaire before and after imaging. The latter provided a retrospective report of anxiety experienced during imaging. Patients in intervention group 3 showed significantly less increase in anxiety compared with those in groups 1 and 2. Overall, only patients who participated in intervention 1 showed a significant increase in anxiety during imaging. When anxiety levels experienced before and during the examination were compared, with the focus on each questionnaire item for each group, those in group 1 showed a significant increase in anxiety on eight of 20 items; those in group 2, three items; and those in group 3, none. Psychologic preparation that includes relaxation strategies is more effective than provision of information alone.     

Fast-field-echo MR imaging with Gd-DTPA: physiologic evaluation of the kidney and liver

To determine if magnetic resonance imaging with Gd-DTPA could be used to assess renal and hepatic perfusion and possibly function, a fast-field-echo technique was used to perform sequential imaging of the kidney and liver of five subjects. Sixteen 3-second images of the same section were obtained at 13-second intervals immediately after Gd-DTPA administration, and again at 30 or 50 minutes after injection. From these images, curves of renal and hepatic signal versus time were generated. In each case the renal signal intensity peaked within 2 minutes and decreased to 60% or less by 3.4 minutes, and 35% or less by 50 minutes. Hepatic curves peaked within 2 minutes and approached initial levels by 30 minutes. These results suggest that transit and clearance of the contrast agent can be imaged by this technique.     

Autoimmune hemolytic anemia associated with anti-Sc1

A case of autoimmune hemolytic anemia (AIHA) in a young child is described. The hemolysis was resistant to steroid therapy but responded to splenectomy and intravenous immunoglobulin. The autoantibody was shown to be anti-Sc1 by both serologic and immunoblotting techniques. This seems to be the first report of an autoanti-Sc1 detected by immunoblotting and the first example of AIHA in a child caused by autoanti-Sc1.     

Ng-nitro-L-arginine reduces nonadrenergic, noncholinergic relaxations of human gut.

The aim of this study was to determine whether nonadrenergic, noncholinergic inhibitory neurotransmission in human circular sigmoid colonic and internal anal sphincter muscle involves release of a nitric oxide-like substance. Colonic and sphincter muscle respond to electrical field stimulation by giving nonadrenergic, noncholinergic relaxations. After-contractions always occur in colonic muscle but only sometimes in sphincter muscle. Ng-Nitro-L-arginine abolished relaxations of sphincter muscle and partially reduced those of colonic muscle. After-contractions were undiminished as were relaxations of sphincter muscle to sodium nitroprusside. The effects of Ng-nitro-L-arginine were reversed by L-arginine. The results suggest that nitric oxide is possibly the neurotransmitter mediating nonadrenergic, noncholinergic relaxations of the human internal anal sphincter muscle.