Prospective study of a high-intensity interferon-alpha regimen for chronic hepatitis C virus genotype 1b infection

BACKGROUND/AIMS: To evaluate efficacy of high-intensity interferon administration for patients chronically infected with hepatitis C virus genotype 1b, we administered interferon-alpha with different regimens according to viral load. METHODOLOGY: Eighty-eight patients with hepatitis C virus genotype 1b were treated with recombinant interferon alpha-2b. The 70 patients with pretreatment hepatitis C virus RNA concentration > or = 10(6) copies/mL were given 10(7) units of interferon daily for the first 8 weeks and then three times weekly for 16 weeks (group A). The 18 patients with smaller pretreatment hepatitis C virus RNA concentration received the same dose daily for the first 2 weeks and then three times weekly for 14 weeks (group B). We analyzed tolerance of therapy, responses, and long-term outcome in the two groups. RESULTS: Fifteen of 70 patients (21.4%) in group A could not continue treatment and dropped out, while all patients in group B completed the entire course of therapy. The rate of sustained response in group A was 10.0%, being significantly less than in group B (72.2%; p < 0.0001). However, 12 patients in group A showed a biochemical sustained response despite presence of viremia. Long-term outcome did not differ between groups. CONCLUSIONS: Many patients could not tolerate high-intensity therapy, which showed the limitation of tolerance of patients receiving interferon monotherapy. High-intensity therapy could not improve eradication of hepatitis C virus in patients with high pretreatment hepatitis C virus RNA concentration. However, this therapy may increase the rate of sustained biochemical response, improving long-term outcome.     

Pulmonary thromboembolism. Evaluating the indication and effect of a vena caval filter with indium-111-platelet scintigraphy.

A 63-year-old woman complained of chest pain and was referred to hospital where she was found to have left pleural effusion and swelling, local heat and edema of the right lower leg. Initial pulmonary perfusion scintigraphy demonstrated multiple defects and pulmonary thromboembolism (PTE) was confirmed during the anticoagulant and thrombolytic therapy against thrombophlebitis. A Greenfield filter was inserted in the inferior vena cava to prevent recurrence of PTE from the thrombosis that was resistant to therapy. In-111-labeled platelet scintigraphy (platelet scintigraphy) showed abnormal uptake of platelets in the chest, femoral veins and abdomen, which suggested active thrombus formation in those regions, including the filter, and a risk of recurrent PTE. Therefore, the thrombolytic therapy was terminated and the anticoagulant therapy intensified. A computed tomography (CT) scan revealed thrombus at the filter, which was markedly decreased 1 month later on platelet scintigraphy. Pulmonary ventilation and perfusion scintigraphy revealed remarkable improvement of the PTE. In this case, platelet scintigraphy complemented CT in demonstrating the activity and localization of the thrombus and can be used to evaluate the risk of recurrence during thrombolytic therapy after insertion of a filter.     

New quinolone versus vancomycin/tobramycin for intestinal sterilization in patients who undergo allogeneic bone marrow transplantation

The frequency of infection in recipients of allogeneic bone marrow transplants (BMT) who received oral new quinolones (NQ) was compared with that in BMT recipients who were given oral vancomycin/tobramycin (V/T). Between 1984 and 1997, our hospital treated 79 patients with V/T and 90 patients with NQ. Number of febrile days, duration of intravenous antibiotics administration, and frequency of documented infections were statistically the same for both groups. However, the frequency of grampositive bacterial infections, especially staphylococcal infections, was slightly higher in patients receiving NQ than in patients receiving V/T (p = 0.12). Of the patients who received NQ, those who underwent unrelated donor BMT procedures were generally febrile for slightly longer periods than those who underwent related donor BMT procedures (p = 0.10). These results suggest that oral NQ is as effective as oral V/T for the prevention of serious gramnegative bacterial infections in patients who undergo BMTs.     

Vipoma of the Pancreas Complicating Ulcerative Colitis

We report a case of vipoma of the pancreas in conjunction with ulcerative colitis in a 20-yr-old woman. Twenty months after the onset of ulcerative colitis, the patient complained of watery diarrhea and was found to have an electrolyte disorder. A pancreatic tumor was detected by ultrasonography and computed tomography, along with an elevation of serum vasoactive intestinal polypeptide (VIP). The secretory diarrhea diminished dramatically, and the serum VIP level decreased into the normal range immediately after resection of the pancreatic tumor. Immunohistochemical staining revealed a pancreatic vipoma. Despite removal of the vipoma, she underwent restorative proctocolectomy and ileal J-pouch anal anastomosis 2 yr later due to progression of the ulcerative colitis. Postoperative course was uneventful, with excellent functional results. Knowledge of this rare condition accompanying ulcerative colitis may help in the management of the patient with an atypical clinical course.     

Successful catheter ablation of ventricular tachycardia originating from the idiopathic saccular apical left ventricular aneurysm

Left ventricular (LV) aneurysm has been recognized to frequently become a substrate of ventricular tachyarrhythmias. We report a case of a 66-year-old woman with symptomatic sustained monomorphic ventricular tachycardia (SMVT) originating from saccular apical LV aneurysm without definite underlying diseases. We performed catheter ablation using electroanatomical and conventional bipolar potential mapping. During SMVT, we found an area of fragmented potential -40 ms preceding the earliest wide QRS complex in the area of the apical LV aneurysm. Radiofrequency applications were delivered to this area. Since then, SMVT was no longer inducible by programmed electrical stimulation. The patient has remained free of VT recurrences during a subsequent 12-month follow-up period.     

Prognostic factors in childhood acute lymphoblastic leukemia in Japan. Japan Association of Childhood Leukemia Study

A retrospective analysis of children with acute lymphoblastic leukemia (ALL) was performed to evaluate the current status of diagnosis and treatment of ALL in Japanese children. Clinical records of 670 children with ALL were collected and analyzed; these children had been diagnosed between 1991 and 1995 at the 53 institutions in 4 areas participating in the Japan Association of Childhood Leukemia Study. It was found that T-cell ALL was significantly less frequent in Tokai and Hokkaido than in Kansai and Chu-Shikoku. The overall induction rate was 92.4%. The estimated 7-year overall survival rate and event-free survival (EFS) rate were 76.0% +/- 1.9% and 61.4% +/- 2.1%, respectively. EFS rates were significantly different among the geographic areas. In female patients with B-cell precursor (B-pre) ALL and white blood cell counts at diagnosis (WBCsdiag) below 50.0 x 10(9)/L, favorable outcomes were significant. Favorable outcomes were not significant in B-pre ALL patients with a WBCdiag above 50.0 x 10(9)/L or in T-cell ALL patients. The EFS rate for infants was significantly worse than that for patients over 1 year of age. In B-pre ALL, but not in T-cell ALL, it was found that the higher the WBCdiag, the worse the EFS rate. Multivariate analysis showed that the following factors were significantly unfavorable for EFS: the Philadelphia chromosome, an translocations associated with chromosome 11q23, an acute unclassified leukemia, mixed-lineage leukemia, a WBCdiag above 100.0 x 10(9)/L, and male gender. Hyperdiploidy (> 50 chromosomes) was significantly favorable for EFS. For further tailoring of treatment and to improve the outcome in childhood ALL, a prospective large-scale study should be undertaken in Japan.     

Relationship between histological prognosis of chronic hepatitis C and amount of hepatitis C virus core protein in serum

BACKGROUND: Hepatitis C virus (HCV) viraemia is one of the factors for histological prognosis of chronic hepatitis C. METHODS: One hundred and thirty-five patients who received hepatic biopsies twice at intervals of 5 years or longer were followed up for a mean of 9.7 +/- 4.0 years were studied retrospectively. The amount of HCV viraemia present was measured as the concentration of HCV core protein by using the fluorescence enzyme immunoassay method. RESULTS: Multiple-regression analysis, using deterioration of the histological stage as a dependent variable, showed that greater age (P = 0.041), higher stage of hepatic histology at the start of follow up (P = 0.029), and higher serum concentration of core protein (P < 0.001) were independent factors affecting the deterioration of the liver's histological stage. At follow up, no significant difference in histological stage was seen between patients with serum HCV core protein > or = 100 pg/mL (n = 60) and those with serum core protein < 100 pg/mL (n = 75). The histological grade in patients with high serum core-protein levels tended to be significantly worse and the deterioration rate of the histological stage was significantly higher than in those with low HCV core protein levels (68 vs 35%, P < 0.001). The mutation rate of the HCV envelope-2/non-structural 1 (E2/NS1) nucleotide region was compared in two patients who had high serum concentrations of HCV core protein and whose histological stage had deteriorated with two patients who had low serum concentrations of the core protein and whose histological stages remained unchanged. No significant difference in E2/NS1 mutation was found. CONCLUSIONS: The amount of HCV viraemia was suggested to be a significant factor for determining histological outcome in patients with chronic hepatitis C. The mutation rate in the E2/NS1 region did not seem to be associated with the prognosis of chronic hepatitis C.     

Agricultural soil fumigation as a source of atmospheric methyl bromide

Methyl bromide (MeBr) is used increasingly as a biocidal fumigant, primarily in agricultural soils prior to planting of crops. This usage carries potential for stratospheric ozone reduction due to Br atom catalysis, depending on how much MeBr escapes from fumigated soils to the atmosphere and on details of atmospheric chemical reactions. We present direct field measurements of MeBr escape; 87% of the applied MeBr was emitted within 7 days after a commercial fumigation. Covering the field with plastic sheets retarded MeBr escape somewhat but first-day losses were still 40%; thicker sections of sheets were relatively more effective than thin sections. We also measured gaseous MeBr concentrations versus depth in the soil column; these profiles display diffusion-like evolution. In soil, MeBr is partitioned among gas, liquid, and adsorbed solid phases. Calculated soil inventories agreed only roughly with applied amounts, probably due to nonequilibrium partitioning (during the first 30 min) and to uncertainties in partitioning coefficients. Fumigated fields may release less MeBr if they are covered by more gas-tight plastic films, if injection techniques are improved and injection is deeper, and if soil moistures, organic amounts, and densities are greater than in the soil studied here.     

Utilization for protein synthesis in individual rat organs of extracellular 2-ketoisocaproate relative to utilization of extracellular leucine

Rats were given constant intravenous infusions of [3H]-leucine plus [1-14C]-2-ketoisocaproate (KIC). Specific activities of plasma leucine and plasma KIC reached plateaus by two to three hours. 3H specific activity of KIC was 85% +/- 2% of that in leucine. 14C specific activity of leucine was 36% +/- 2% of that in KIC. The 14C/3H ratios in leucine and KIC were constant from the earliest sampling time (one hour) at 0.65 +/- 0.03 and 2.20 +/- 0.07, respectively. In various tissues, 14C/3H in free leucine and in tissue protein were approximately equal, but in most organs these ratios were significantly greater than the ratio 14C/3H in plasma leucine. From these data we estimate that the fraction of leucine incorporated into protein in individual organs derived from extracellular KIC rather than extracellular leucine varies from zero (in liver and bone marrow) to 35% to 45% (in brain and heart), and comprises 12% in the body as a whole.