Sustained Viral Response Is Rarely Achieved in Patients with High Viral Load of HCV RNA by Excessive Interferon Therapy

Adequate dosing of interferon (IFN) and its cost-effectiveness for sustained virological response were evaluated in relation to viral load and subtype. Prospective analysis of IFN therapy on 326 patients with chronic hepatitis C free from cirrhosis was performed using 9 or 6 million unit (MU) of IFN for six months daily and/or three times a week. Sustained virological response was achieved in 50–94% of patients with 2 × 10⁴ copies/ml (competitive RT-PCR) or <100 × 10³ copies/ml (Amplicor monitor) of HCV RNA by 468–1206 MU of IFN, but response was only 0–25% of the patients with 2 × 10^5.5 copies/ml (competitive RT-PCR) or >200 × 10³ copies/ml (Amplicor monitor), even with 468–1206 MU of IFN. A high sustained rate was demonstrated in patients with 100–200 × 10³ copies/ml of HCV RNA by 901–1206 MU of IFN, in comparison to that with 900 MU of IFN. Multivariate analysis showed that IFN dose had a significant value for the efficacy of IFN therapy in patients presenting 100–200 × 10³ copies/ml of HCV RNA. Cost efficacy analysis indicated that it cost approximately $10,000, $26,000, and $50,000–227,000 for one person-viral eradication in the patients with <100, 100–200, and >200 × 10³ copies/ml, respectively. High-dose IFN is only cost effective in patients with intermediate viral loads, and IFN therapy could be recommended in patients with <200 × 10³ copies/ml of HCV RNA.     

Early Triple Carcinomas Metachronously Involving the Sigmoid Colon, Stomach and Gallbladder Report of a Case

We present a case of early triple carcinomas metachronously involving the sigmoid colon, stomach and gallbladder in order to emphasize that a mass screening is useful in the detection of early cancer of the alimentary tract. A 61-year-old male was admitted to the hospital for investigation of a flat elevated lesion of the sigmoid colon. The patient received partial resection of the sigmoid colon with the diagnosis of carcinoma. Pathologic findings showed adenocarcinoma confined to the mucosa. Sixteen months after surgery, a depressed stomach lesion was found through a mass screening. Distal gastrectomy was performed because of carcinoma, which was histologically confined to the mucosa. Sixty-five months later, he underwent cholecystectomy because of a polypoid lesion of the gallbladder. Pathologic findings disclosed adenocarcinoma infiltrated into the muscular layer of the gallbladder. The patient is currently in good health about 4 years after undergoing cholecystectomy. Zusammenfassung Wir berichten über einen Fall von drei Frühkarzinomen, die metachron in Sigmoid, Magen und Gallenblase auftraten, um darauf hinzuweisen, dass ein Massenscreenig zur Entdeckung von Frühkarzinomen des Verdauungstraktes sinnvoll ist. Ein 61-jähriger Mann wurde zur Abklä,rung einer flach erhöhten Läsion des Sigmoids stationär aufgenommen. Der Patient unterzog sich einer Teilresektion des Sigmoids mit der Diagnose eines Karzinoms. Die pathologische Aufarbeitung ergab ein Adenokarzinom, das auf die Mukosa beschränkt war. 16 Monate nach der Operation zeigte sich bei einer Reihenuntersuchung eine indurierte Magenläsion. Es folgte eine distale Gastrektomie aufgrund eines Karzinoms, das auf die Mukosa begrenzt war. 65 Monate später musste sich der Patient wegen einer polypoiden Läsion der Gallenblase einer Cholezystektomie unterziehen. Die pathologischen Befunde ergaben ein Adenokarzinom, das die Muskelschicht der Gallenblase infiltriert hatte. Der Patient is zur Zeit, etwa vier Jahre nach der Cholezystektomie, bei guter Gesundheit.     

Total hip and knee arthroplasty for arthropathy in a hemophiliac

We evaluated the medium-term follow-up results, effectiveness, and suitability of arthroplasty for hemophilic arthropathy. We performed 26 total knee and 9 total hip arthroplasty operations on hemophilic patients between 1988 and 1998 under general anesthesia and appropriate hemostatic management. Postoperative treatment for hemophilic arthropathy is the same as that for osteoarthritis and rheumatoid arthritis. After their operations, patients experienced relief from pain and intra-articular bleeding in affected joints but only marginal improvement in the range of motion. In general, total joint arthroplasty is not indicated for young patients. However, arthropathy can have a severe impact on the active life of patients during their youth. For severe hemophilic arthritis, total knee and hip arthroplasty can lead to a pain-free and improved quality of life. We believe total knee and hip arthroplasty is a good solutions for hemophiliac arthropathy before severe deformity occurs. Although treated relatively young hemophilic patients, age was not considered to be a contraindication.     

Severe exacerbation of hepatitis after short‐term corticosteroid therapy in a patient with “latent” chronic hepatitis B

Abstract: We present a case of severe exacerbation of hepatitis after short‐term corticosteroid therapy for chronic inflammatory demyelinating polyneuropathy (CIPD) with “latent” chronic hepatitis B showing no HBV‐related antigens and antibodies. After corticosteroid pulse therapy for CIPD, the patient had severe exacerbation of hepatitis twice. Although she did not show any hepatitis B virus (HBV)‐related antigens or antibodies, sequences of HBV were detected in serum and liver by a nested polymerase chain reaction. A sequence analysis of HBV at the second exacerbation showed that the G‐to‐A point mutation at nucleotide 1896 that converted codon 28 from tryptophan (TGG) to a stop codon (TAG) in the precore region resulted in amino acid change, which has been frequently observed in fulminant hepatitis and severe hepatitis in Japan.     

Simultaneous, clonally identical T cell expansion in tonsil and synovium in a patient with rheumatoid arthritis and chronic tonsillitis

In some patients with rheumatoid arthritis (RA), the disease improves following tonsillectomy. We describe a 28-year-old woman with treatment-resistant RA and chronic tonsillitis. Initially, her arthritis had been well controlled with methotrexate and corticosteroids, but the RA activity became difficult to control in spite of addition of bucillamine to the treatment regimen and repeated arthrocentesis with infusion of corticosteroid into her swollen joints. Closer examination revealed that the period of exacerbation of her chronic tonsillitis paralleled that of the systemic arthritis, and administration of antibiotics brought transient relief of the systemic symptoms. Her arthritis was ameliorated after successful tonsillectomy and synovectomy, with marked reduction of the serum rheumatoid factor concentration. Analysis of infiltrating T cell clones in tonsil and synovium using T cell receptor V(beta) repertoire and third complementarity-determining region size distribution analysis followed by nucleotide sequencing revealed common clonal T cell expansion in both tissues. This finding suggests the possible involvement of chronic focal infection in refractory RA.     

Serum-soluble c-kit levels during mobilization of peripheral blood stem cells correlate with stem cell yield

c-Kit is expressed in hematopoietic stem cells and plays an important role in hematopoiesis. In 16 patients with malignancies, serum-soluble c-Kit levels and the expressions of c-KIT messenger RNA (mRNA) and protein in peripheral blood mononuclear cells were analyzed serially during 26 courses of peripheral blood stem cell (PBSC) mobilization after granulocyte colony-stimulating factor administration following chemotherapy for PBSC harvest. Serum-soluble c-Kit levels were significantly lower in patients than in controls (179.7+/-17.7 arbitrary units [AU]/mL versus 274.5+/-18.9 AU/mL; P < .001), decreasing after chemotherapy (167.7+/-18.2 AU/mL), increasing from day 14, and peaking at day 19 (193.3+/-16.4 AU/mL). The numbers of both c-Kit+ cells and CD34+ cells and granulocyte-macrophage colony-forming units in peripheral blood peaked at day 17, following the peak of the expression of c-KIT mRNA. Serum-soluble c-Kit levels showed a significant positive correlation with the numbers of CD34+ cells in both peripheral blood and leukapheresis products (r = 0.553, P < .01, and r = 0.640, P < .001, respectively) and changed at higher levels in patients with large numbers of PBSCs versus patients with small numbers of PBSCs (P < .05). Serum-soluble c-Kit may reflect the capacity for hematopoiesis after chemotherapy and may be useful in predicting the number of PBSCs that can be mobilized and harvested after mobilization, as well as for monitoring the timing for PBSC harvest.     

Estimation of stem cell fractions in peripheral blood stem cell harvest by using an SE-9000 hematology analyzer

We inquired whether stem cell fractions in peripheral blood stem cell harvest could be precisely detected by using a hematopoietic progenitor cell (HPC) counting system applied to an automated hematology analyzer, SE-9000. Although there was an apparent increase in the HPCs 20 h after storage in nondiluted conditions, samples diluted with RPMI-1640 containing 1.0 mg/ml EDTA-2K showed a relatively stable number of HPCs. There was a significant relationship between HPCs and CD34 cells (n = 75, r = 0.769). This method may represent the least expensive and most time-effective way for stem cell estimation in harvest products.     

A study of the minimum number of slices required for quantification of pulmonary emphysema by computed tomography]

We attempted to determine the minimum number of slices required for quantification of overall emphysema by computed tomography (CT). Forty-nine patients underwent CT scanning with a 15-mm slice interval, and 13 to 18 slices per patient were obtained. The percentage of low attenuation area (LAA%) per slice was measured with a method that we reported on previously, utilizing a CT program and NIH image. The average LAA% values for 1, 2, 3, and 6 slices evenly spaced through the lungs [LAA% (1), LAA% (2), LAA% (3), and LAA% (6)] were compared with those for all slices [LAA% (All)]. The correlation coefficients for LAA% (1), LAA% (2), LAA% (3), and LAA% (6) with LAA% (All) were 0.961, 0.981, 0.993, and 0.997, respectively. Mean differences +/- SD were -3.20 +/- 4.21%, -2.32 +/- 3.00, -0.20 +/- 1.84, and -0.16 +/- 1.26, respectively. From these results, we concluded that overall emphysema can be quantified by using at least three slices: one each of the upper, middle, and lower lung.     

Vascular release of plasminogen activator inhibitor-1 impairs fibrinolysis during acute arterial thrombosis in mice

The role of plasminogen activator inhibitor-1 (PAI-1) in the plasma, blood platelets, and vessel wall during acute arterial thrombus formation was investigated in gene-deficient mice. Photochemically induced thrombosis in the carotid artery was analyzed via transillumination. In comparison to thrombosis in C57BL/6J wild-type (wt) mice (113 +/- 19 x 10(6) arbitrary light units [AU] n = 15, mean +/- SEM), thrombosis in PAI-1(-/-) mice (40 +/- 10 x 10(6) AU, n = 13) was inhibited (P <.01), indicating that PAI-1 controls fibrinolysis during thrombus formation. Systemic administration of murine PAI-1 into PAI-1(-/-) mice led to a full recovery of thrombotic response. Occurrence of fibrinolytic activity was confirmed in alpha(2)-antiplasmin (alpha(2)-AP)-deficient mice. The sizes of thrombi developing in wt mice, in alpha(2)-AP(+/-) and alpha(2)-AP(-/-) mice were 102 +/- 35, 65 +/- 8.1, and 13 +/- 6.1 x 10(6) AU, respectively (n = 6 each) (P <.05), compatible with functional plasmin inhibition by alpha(2)-AP. In contrast, thrombi in wt mice, t-PA(-/-) and u-PA(-/-) mice were comparable, substantiating efficient inhibition of fibrinolysis by the combined PAI-1/alpha(2)-AP action. Platelet depletion and reconstitution confirmed a normal thrombotic response in wt mice, reconstituted with PAI-1(-/-) platelets, but weak thrombosis in PAI-1(-/-) mice reconstituted with wt platelets. Accordingly, murine (wt) PAI-1 levels in platelet lysates and releasates were 0.43 +/- 0.09 ng/10(9) platelets and plasma concentrations equaled 0.73 +/- 0.13 ng/mL. After photochemical injury, plasma PAI-1 rose to 2.9 +/- 0.7 ng/mL (n = 9, P <.01). The plasma rise was prevented by ligating the carotid artery. Hence, during acute thrombosis, fibrinolysis is efficiently prevented by plasma alpha(2)-AP, but also by vascular PAI-1, locally released into the circulation after endothelial injury.