Long-term administration of natural interferon-α in patients with chronic hepatitis C: Relationship to serum RNA concentration, HCV-RNA genotypes, histological changes and hepatitis C virus

To virologically assess the efficacy of interferon therapy in chronic hepatitis C, either 5 or 10 MU/day natural interferon-α (IFNα) was administered to 57 patients with chronic hepatitis C for 38 weeks. A complete and sustained response (CR-SR), as evidenced by the absence of serum hepatitis C virus (HCV)-RNA during the administration period and at 6 months after the final administration of IFNα and a normal GPT level at 6 months after final administration, occurred in 42.6% (23/54) of subjects. Liver tissue was histologically evaluated using the histological activity index (HAI) score before and after the administration period. In CR-SR cases, significant improvements (P <0.01) occurred in periportal necrosis, intralobular necrosis, portal inflammation and total score. A comparison, by HCV genotypes, revealed that CR-SR occurred in 60% (9/15) of subjects with type 2a and 30.3% (10/33) of subjects with type Ib. A comparison by virus concentration revealed that CR-SR occurred in 71.4% (15/21) of those subjects having a virus concentration of < 10⁵ copies/mL, but in only 24.2% (8/33) of those having a virus concentration of > 10⁵ copies/mL. Analysis by a multiple logistic model revealed a strong correlation between the therapeutic effect of interferon therapy and the pre-administration virus concentration (P=0.0061) and genotype (P=0.0015). These results suggest that the preadministration virus concentration and genotype are both key factors affecting the therapeutic effect of interferon therapy in chronic hepatitis C and that the therapeutic effect of interferon is satisfactorily high, irrespective of virus concentration, in subjects with type 2a HCV, but varies depending on virus concentration in subjects with type 1b.     

Clinical evaluation of titration of hepatitis C virus core antibody and its subclasses

Abstract Titrations of anti-hepatitis C core (anti-HCc) immunoglobulin G (IgG) antibodies and its subclasses were studied in 90 patients with acute and chronic hepatitis C virus (HCV) infection, including 27 patients who underwent interferon (IFN) therapy. The positivity rates for each anti-HCc subclass were as follows: 95.2% for IgG1, 12.0% for IgG2, 69.9% for IgG3 and 19.3% for IgG4. The total anti-HCc IgG titre correlated well with the IgG1 titre, indicating that IgG1 was the main virus-specific IgG. Changes of IgG1 production mainly contributed to fluctuations of the anti-HCc IgG titre and corresponded well to positivity for HCV-RNA during and after IFN therapy. IgG3 was detected prior to IgG1 during the early phase of acute hepatitis in some cases and also appeared with relapse after IFN therapy. The serial assay of anti-HCc subclasses showed the patients' humoral immune response to HCV infection, and might be useful for evaluation of anti-viral immunity influenced by IFN therapy.     

Ganglioneuroma of left adrenal gland in a patient with Turner syndrome during growth hormone therapy

We report on a Japanese girl with Turner syndrome (45,XO) who developed ganglioneuroma of the left adrenal gland during growth hormone (GH) therapy. She had received GH replacement therapy from the age of 6.8 years. At the age of 10.3 years, abdominal ultrasonography revealed a mass which occupied the upper area of her left kidney. Computed tomography and magnetic resonance imaging of the abdomen showed a low density mass with a smooth surface located between the upper portion of the left renal vein and the pancreas. Microscopic examination resulted in a diagnosis of ganglioneuroma of the left adrenal gland. At present we cannot conclude that patients who have received GH replacement therapy are at higher risk for developing tumors compared to those without GH replacement therapy.     

Factors Influencing Transfused Platelet Recovery and Survival, With Special Reference to Antiplatelet Antibody

Factors influencing platelet increment, recovery and survivalwere analyzed in 103 transfusions given to 33 thrombocytopenicpatients, with special reference to the antiplatelet antibodywhich was examined by the mixed passive hemoagglutination methodrecently developed by Shibata et al., (1976). The results demonstratedthat platelet increment, recovery and survival were significantlyreduced in the patients with post-transfusion fever or antiplateletantibody. Platelet recovery seemed to decrease with the increasein the number of HLA mismatched antigens, but the changes inpercent recovery among every HLA mismatched grades were notstatistically significant. The presence of the antiplateletantibody rather than the lymphocytotoxic antibody, HLA mismatchedgrades or post-transfusion fever established the presence ofthe poorer platelet recovery and survival and the more refractorystate. Post-transfusion fever was significantly associated withthe presence of antibodies against platelets and/or lymphocytes.Hemorrhage was arrested after transfusion in 81.1% out of the33 patients that had clinical hemorrhage prior to transfusion,but not in six cases (18.2%), all which had poor platelet recoveryand post-transfusion fever. The detection of antiplatelet antibodyand platelet cross-match test using the mixed passive hemoagglutinationmethod was of primary importance for selecting the adequatedonor for platelet transfusion. Platelet typing must be donein the near future.     

Two Cases of Ventricular Parasystole Associated with Ventricular Tachycardia

In two patients, ventricular pamsystole (VP) was associated with ventricular tachycardia (VT), and in one patient, catheter ablation was successful. In patient 1, with dilated cardiomyopathy, VP led to VT, which converted to ventricular fibrillation. In patient 2, VP led to symptomatic nonsustained polymorphic VT. The origin of parasystolic focus was determined byendocardial mapping, and a radiofrequency current was delivered to patient 2. Both VP and VT disappeared immediately, and no recurrence has been observed during a follow-up of 8 months. Catheter ablation to the parasystolic focus was effective and a relationship between VP and VT was strongly suggested.     

Hypertensive crisis after discontinuation of an angiotensin-converting enzyme inhibitor in a patient with renal dysfunction

SUMMARY: A 54-year-old woman with hypertension treated for 2 years with enalapril, 10 mg daily, was admitted to hospital because of progressively worsening renal function. There was no evidence of scleroderma, except for the presence of anticentromere antibodies. to prevent hyperkalaemia and further deterioration of renal function, enalapril was abruptly withdrawn and replaced with a calcium antagonist on the second hospital day, but hypertensive crisis developed. Renal failure requiring haemodialysis developed 2 weeks after admission. Findings of a renal biopsy were consistent with scleroderma kidney. Scleroderma is difficult to diagnose in the absence of cutaneous symptoms. Therefore, angiotensin-converting enzyme inhibitors should only be discontinued with care in patients with renal dysfunction if there is the possibility of scleroderma without skin changes.     

Acute Changes in Left Atrial and Left Ventricular Diameters After Physiological Pacing

The present study examined alterations in left atria! diameter (LAD) and diastolic left ventricular diameter (LVDd) in 37 patients (72.2 ± 9.8 years old) who received physiological pacemakers; 22 with atrioventricular (AV) block and 15 with sick sinus syndrome (SSS). After pacemaker implantation, LAD and LVDd were serially measured using echocardiography, and their diameters ware expressed per body surface area (LADI and LVDdl; mm/m). Pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were measured in ten patients with SSS and ten with AV block during both right ventricular and AV sequential pacing. After AV sequential pacing, CO increased in 19 of 20 patients (3.2 ± 0.9 L/min to 3.9 ± 1.0 L/min: P < 0.001). LADI decreased from 24.9 ± 4.2 mm/m² to 21.8 ± 4.4 mm/m² (P < 0.001) in 22 patients with AV block and from 24.1 ± 3.4 mm/m² to 20.4 ± 3.8 mm/m² (P < 0.001) in 15 SSS patients. However, LVDdl did not change significantly in either group of patients. The changes in LAD after the implantation of a physiological pacemaker occurred rapidly, i.e. LAD began to decrease within 1 minute after the procedure, and then reached a plateau. This plateau phase continued for at least 7 days during physiological pacing. There was a positive correlation between the changes in LADI after pacemaker implantation and those in PCWP observed during the AV sequential pacing performed prim- to the implantation (r = 0.86; P < 0.001). The reduction in LAD following pacemaker implantation was rapid and seemed to be accompanied by improvement of cardiac function. Thus, it is suggested that the serial measurement of LADI is useful to predict the efficacy of physiological pacemaker implantation.