Tsutomu Yokota

The effects of a high dose, short course of interferon on hepatitis C

To shorten the period of interferon (IFN) treatment for chronic hepatitis C, we investigated the clinical efficacy of a regimen using a higher dose and a shorter treatment period. Fifty chronic hepatitis C patients who were hepatitis C virus (HCV)‐RNA positive and who were histologically diagnosed as having chronic hepatitis, took part in the study. Virus levels were measured before and 2 weeks after starting the treatment. We administered natural IFNα, 10 MU, i.m. daily for 2 consecutive weeks and then three times per week for the subsequent 14 weeks (total dose 560 MU). Patients who were HCV‐RNA negative at the completion of the therapy and 6 months later, were evaluated as sustained responders (SR; 32%). Those who were not HCV‐RNA negative at the two time points were evaluated as non‐responders. Nucleotide and clone differences in the hypervariable region (HVR) and predictive factors for prognosis were also analysed. Low virus level and HCV‐RNA genotype 2a/2b were the predictors for good prognosis, whereas the numbers of nucleotide differences and clone differences in HVR were not. Sustained responder patients became HCV‐RNA negative 2 weeks after starting the treatment at a significantly higher rate, whereas no non‐responder patients were HCV‐RNA negative at that time. The SR rate (32%) was equivalent to those reported in previous 24 week treatment studies. This IFN therapy using a higher dose and a shorter period was useful.

A Patient with Primary Hypoparathyroidism Developing Hypercalcemia Associated with Adult T-Cell Leukemia/Lymphoma

A 38-year-old woman was admitted to our hospital with symptoms and signs of hypocalcemia in 1977 and a diagnosis of primary hypoparathyroidism was made with a positive Ellsworth Howard test. She was then lost to follow up until 1992 when she returned this time with symptoms and signs of hypercalcemia. An inguinal lymph node was biopsied showing non-Hodgkins lymphoma, diffuse pleomorphic type and monoclonal integration of proviral human T-cell lymphotropic virus-1 DNA was detected in lymph node cells indicating ATLL. Serum parathyroid hormone-related peptide (PTHrP) was slightly elevated and the tumor cells were positively stained with anti-PTHrP serum. Combination chemotherapy with vincristine, adriamycin, cyclophosphamide and prednisolone was given to the patient with disappearance of the lymphadenopathy and subsequent normalization of PTHrP levels. Interestingly, the signs and symptoms of hypocalcemia reappeared after the treatment requiring replacement therapy with calcium and vitamin D.

A study on immunity in tsutsugamushi disease

The immune response in human tsutsugamushi disease (scrub typhus) was studied. Anti-rickettsial activity of sera, peripheral mononuclear cells and their culture supernatants from patients on in vitro growth of Rickettsia tsutsugamushi proliferating in normal human peripheral macrophages was examined. The results obtained were as follows. 1) Sera from patients at the early convalescent stage, which exhibited high antibody titers against R. tsutsugamushi, effectively inhibited their growth in macrophages. 2) Sera from patients after a long period from the onset showed low antibody titers and did not inhibit rickettsial growth. 3) Mononuclear cells and T cell enriched fractions suppressed rickettsial growth when they were obtained from the patients at the early convalescent stage and even after as long as 3.5 years from the onset. 4) The culture supernatants of the T cell-enriched fractions which were collected from the patients mentioned above, exhibited a similar antirickettsial activity. These findings indicate that sensitized T lymphocytes and macrophages might play a fundamental role in immunological defense mechanism in tsutsugamushi disease. And the results obtained in our experiments are compatible with those previously reported in experimental scrub typhus in laboratory animals such as mice and monkeys.

A case of porphyria cutanea tarda which was improved by phlebotomy.

症例は53歳,男性.全身倦怠感と露出部の皮膚症状を主訴として来院した.検査所見では軽度の肝機能障害ならびに尿中ポルフィリン体の排泄増加がみられた.腹腔鏡検査では肝表面に灰青色斑がみられ,生検肝は紫外線の照射によって赤色蛍光を発した.肝組織像では軽度のリンパ球浸潤,ヘモジデリンの沈着および多数の細胞質内針状結晶を認めた.症候性晩発性皮膚ポルフィリン症と診断し,昭和56年12月より4～8週おきに1回250～300ml,総量3,000mlの瀉血療法を行った.治療にほぼ平行して自覚症状の軽減,尿中ポルフィリン体排泄量の正常化がみられたが,肝機能検査成績はほとんど不変であった.治療終了6カ月後に行われた腹腔鏡検査では,肝の灰青色斑は消失し,生検肝の赤色蛍光もみられなくなったが,肝組織の炎症像および針状結晶については不変であった.本例において瀉血療法は体内の過剰な蓄積ポルフィリン体の減少と,皮膚所見および自覚症状の軽減という点では著効を示したといえよう.