A sensitive enzyme immunoassay for anti-thyroglobulin antibody using Fab'-horseradish peroxidase conjugate. Evaluation of in vitro anti-thyroglobulin antibody synthesis by lymphocytes from patients with autoimmune thyroid disease.

A sensitive enzyme immunoassay (EIA) for the detection of anti-thyroglobulin (Tg) antibodies was developed using Fab'-horseradish peroxidase (HRP) conjugate. Anti-Tg antibody was assayed by incubation with a thyroglobulin-coated polystyrene ball and then with affinity-purified anti-IgG Fab'-HRP conjugate. The HRP activity was assayed fluorimetrically. The sensitivity was 625 amol/tube and anti-Tg antibody levels between 0.5 and 200 ng/ml could be determined. The recoveries of anti-Tg antibody added to human sera at three different concentrations were 94.2-101.0%. Both within- and between-assay coefficients of variation were below 10%. Significant correlation was observed between values by the EIA and TGHA method (Kendall's rank correlation coefficient = 0.712, P less than 0.001). The present EIA for anti-Tg antibody is sensitive enough to determine anti-Tg antibody synthesized in vitro by the lymphocytes from patients with autoimmune thyroid disease and normal subjects. The amounts of anti-Tg antibody synthesized by peripheral lymphocytes from patients with Hashimoto's disease were significantly greater than those from patients with Graves' disease, although serum levels of anti-Tg antibody were usually elevated in both groups of patients. The results obtained suggest that anti-Tg antibody is synthesized in a different manner in patients with Hashimoto's disease and in patients with Graves' disease.

A prospective analysis of subacute thyroid dysfunction after neck irradiation.

PURPOSE: Exposure of the thyroid to therapeutic doses of external irradiation has been demonstrated to induce thyroid dysfunction. This study was designed to assess the relationship between irradiation and early thyroid dysfunction, prospectively. METHODS AND MATERIALS: Twenty patients in whom the thyroid was incidentally exposed to therapeutic doses of irradiation were studied. The dose given to the thyroid was 40-54 Gy over 4-7 weeks. Thyroid function tests, including serum thyroid stimulating hormone (TSH), free thyroxine (free T4), free triiodothyronine (free T3), antithyroglobulin antibody, and antimicrosomal antibody, were performed prior to irradiation and at 3, 6, and 12 months after radiotherapy. RESULTS: Serum TSH levels did not change significantly at 3 months after irradiation (mean TSH level: 1.33 microU/ml before irradiation, 1.74 microU/ml at 3 months, p = 0.11). However, a significant elevation was noted at 6 months (mean TSH: 3.50 microU/ml at 6 months, p = 0.0001, vs. preirradiation), when TSH levels were higher than preirradiation levels in 19 of 20 patients. After irradiation, 13 patients remained in a euthyroid state (euthyroid group), while in the other 7 patients hypothyroidism occurred (hypothyroid group) and thyroid hormone-replacement therapy was performed. After 6 months, elevation of TSH was less significant in the euthyroid group, whereas elevation of TSH persisted continuously and exponentially in the hypothyroid group. Thyroid autoantibodies did not turn positive in any patient during follow-up. CONCLUSIONS: Damage of the thyroid develops in most patients when the organ is exposed to radiation. This radiation-induced damage is initially manifested within 6 months after irradiation.

Acute radiation thyroiditis.

PURPOSE: Radiation-induced thyroid dysfunction is considered a late effect. We prospectively assessed acute reactions of the thyroid to external neck irradiation. METHODS AND MATERIALS: This study included 22 patients in whom the thyroid was incidentally exposed to therapeutic doses of radiation. Thyroid function tests included measurements of serum thyroid stimulating hormone (TSH), free and total triiodothyronine (T3) and thyroxine (T4), thyroglobulin, and antithyroid antibodies. These tests were performed before radiotherapy (baseline values), after approximately 40 Gy had been administrated, 2 weeks after the end of radiotherapy, and 3 and 6 months after the beginning of radiotherapy. RESULTS: Mean serum levels of TSH were 1.53, 0.55, 0.78, 2.14, and 7.57 microU/ml before radiotherapy, after 40 Gy irradiation, 2 weeks after the end of radiotherapy, and 3 and 6 months after radiotherapy, respectively. Thus, levels of TSH exhibited two phases: a significant decrease during radiotherapy (thyrotoxic phase) and an increase after radiotherapy (hypothyroid phase) (baseline vs. 40 Gy: p < 0.0001, baseline vs. 6 months: p = 0.003). Increases of thyroid hormones were subtle during radiotherapy. CONCLUSIONS: We believe that radiation promotes release of excessive amounts of thyroid hormones during radiotherapy owing to suppression of TSH secretion. In addition to the late damage (hypothyroidism), thyrotoxicosis occurs when the thyroid gland receives a therapeutic doses of external radiation.

Tetramer Bence Jones protein in the immunoproliferative diseases. Angioimmunoblastic lymphadenopathy, primary amyloidosis, and multiple myeloma.

The authors report the clinical features and the results of immunochemical studies of patients with angioimmunoblastic lymphadenopathy, primary amyloidosis, and multiple myeloma, each of whom had in the serum and urine multiple forms of Bence Jones protein (BJP). The BJPs were isolated and purified and were shown by electrophoretic, gel filtration, and ultracentrifugal analyses to exist as tetramers and dimers. The components in two cases were kappa type and in one lambda type. The kappa tetramers consisted of two covalent dimers and the lambda tetramer two noncovalently bound dimers present in both serum and urine.

Geographic clustering of myeloma in Tokushima.

Between 1978-1988, seven cases of multiple myeloma were found in T Town (population 9,000), which is located at the mouth of a large river within the boundaries of Tokushima City, Japan. This is a significantly high incidence, 7.06 per 100,000 as compared with an incidence of 1.20 in Tokushima City itself and 1.53 in Japan as a whole. The clinical and laboratory features of these patients were typical of myeloma. Although the causes of this small but apparent cluster of multiple myeloma remain obscure, the fact that five of the seven patients had been working for long periods as fishermen was notable.

Renal failure caused by long-term use of a germanium preparation as an elixir.

Two Japanese women and one Japanese man, who had been taking the same germanium preparation, mainly containing inorganic germanium, as an elixir for health almost every day at 90 mg of germanium per day for 6 to 20 months, suffered from chronic renal failure. Histological examination of the kidney in one patient showed marked interstitial changes with vacuolar degeneration of the renal tubules. High germanium concentrations were found in hair and nails of the three patients, but no germanium was detected in hair or nails of normal persons. These results suggest that long-term use of a germanium preparation at high dosage can cause serious renal tubular damage and renal failure due to germanium toxicity.

Determination of germanium and some other elements in hair, nail, and toenail from persons exposed and unexposed to germanium.

Inductively coupled atomic emission spectrometry was used for the determination of germanium in hair, nail, and toenail. The levels of germanium in three individuals administered a high concentration of a germanium preparation daily for about 12-16 months were very high: 56.4-173.7; 5.4-35.0; and 14.0-15.8 micrograms g-1 in hair, nail, and toenail, respectively. The levels for normal or unexposed persons are very low and were not detected by the method.

[Clinical study on effects of cefmetazole on severe infections accompanied by hematologic diseases].

Severe infections accompanied by hematopathy under granulocytopenic conditions were treated with cefmetazole (CMZ). Subject diseases mainly consisted of acute leukemia, agranulocytosis and aplastic anemia; combined infections were septicemia, pneumonia, fever of an undetermined origin, etc. As for causative organisms found in cases that could be examined, Gram-negative bacilli such as Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa and Enterobacter cloacae were isolated, as was Staphylococcus aureus. In general, 4 g of CMZ divided into 2 administrations was given per day through intravenous injection or intravenous drip infusion. On the basis of the judgement criteria for effectiveness established by Takaku et al., the efficacy rate in this study was found to be 68%, including 2 cases that showed excellent responses to treatment of infections caused by S. aureus. Cases that showed pyretolysis within 4 days had over 1,000/microliter of neutrophils, while cases with less than 1,000/microliter showed no pyretolysis. No hepatorenal dysfunctions related to the treatment with CMZ were seen as side effects except increases of transaminase in 1 case. These results indicate that CMZ is a useful drug for the treatment of infections accompanied by hematopathy under granulocytopenic condition.

[Phase II study on peplomycin for esophageal cancer].

For the purpose of verifying the effectiveness of peplomycin, one of the derivatives of bleomycin, against carcinoma of the esophagus and the safety of it, the analysis of the data for total 113 cases collected from 25 institutions in Japan was made. The results are as follows. It was effective in 19 out of 74 evaluable cases of carcinoma of the esophagus (25.7%). In case of treatment with peplomycin alone, it was effective in 6 out of 39 cases (15.4%). In case of the combination treatment with peplomycin and some other therapy, it was effective in 13 out of 35 cases (37.1%). As for the side effects, the incidence of fever was the highest in both the cases of peplomycin alone and the combination treatment such as 39.6% and 37.0%, respectively. Anorexia, nausea, vomiting, respiratory symptoms and tiredness were found in relatively many cases. In the clinical laboratory tests, the vital capacity after the treatment tended to be lower than that before the treatment, but there was little change in the hematological tests, pulmonary function test and renal function test.

[Spontaneous complete remission in a patient with acute monocytic leukemia].

A spontaneous complete remission was observed in a 47-year-old female with acute monocytic leukemia. Resolution of all abnormalities, including systemic papule, thrombocytopenia, increased numbers of immature monocytoid cells in the peripheral blood and bone marrow, elevation of serum lysozyme and LDH, and trisomy 8 on chromosome analysis, occurred without any treatment. Moreover, the remission was not associated with any infection or blood transfusion, and is persistent for 12-month duration.

[IBL-type lymphadenopathy after infection of rubella virus].

A 52-year-old woman presented slight fever, diffuse papular skin rash and painful cervical lymph node swelling. Her lymph node swelling generally up to 3 cm in diameter, with petechiae on the lower legs and hepato-splenomegaly within a few weeks. ESR was 45 mm/h, Hb 10.0 g/dl, RBC 345 x 10(4)/microliter, WBC 22,600/microliter (atypical lymphocyte 47%), PLT 1.0 x 10(4)/microliter, GPT 91 U/L, gamma-globulin 34.3%, EBV-VCA x 2,560, EBNA x 20, and anti-rubella antibody x 512. The biopsied cervical lymph node showed histologic features of effacement of nodal architecture by an exuberant vascular proliferation accompanied with infiltration of the immunoblasts, and was diagnosed as immunoblastic lymphadenopathy (IBL)-type lymphadenopathy. The pulse therapy of methylprednisolone and high dose of gamma-globulin improved lymphadenopathy, thrombocytopenia and anemia. IBL-type lymphadenopathy after infection of rubella virus may be different from true IBL, but is important to discuss the pathogenesis of IBL.

[Postoperative brain metastasis from esophageal carcinomas: report of 4 cases].

Out of 83 cases received resection of primary esophageal lesion, 4 patients were affected by metastatic brain tumor which was reported to rarely occur. All 4 patients had symptoms of central nervous system. Three of them were diagnosed by CT and the other one at autopsy. All of the primary esophageal tumors were advanced and of histological stage III or IV. They located in the middle or lower thoracic esophagus. Brain tumor of one case was removed and this case was of progression free at the last presentation. The other 3 cases were not received resection of metastatic brain tumors and died. All of 3 were autopsied and two of them had no metastasis in the lung. Therefore, it was considered that these hematogenic metastases were not through lung filtrations but through other routes, which Batson O. V. experimentally proved and designated as vertebral vein system in 1940. It is concluded that aggressive surgical intervention to metastatic brain tumors was beneficial with regard to prognosis for cases without other metastatic lesions.

[A case of Hodgkin's disease exhibiting erythrodermia probably due to allergic reaction to vinca alkaloids].

A 58-year-old man with Hodgkin's disease exhibited erythrodermia due to allergic reaction to vincristine sulfate (VCR) and vindesine sulfate (VDS). However, chemotherapy could be continued by changing VCR and VDS to etoposide without allergic symptom. Clinical observation strongly suggested that erythrodermia was due to the use of vinca alkaloids in this patient. Hematological and neurological side effects have been well known for VDS and VCR, but erythrodermia has not yet been reported as being caused by these agents. It is often difficult to differentiate drugs as a cause of an allergic reaction when several drugs are used together. Therefore, it is important to collect all the cases showing the effects of drugs.

[Malignant pericardial effusion after esophageal cancer surgery successfully treated by intrapericardial instillation of CDDP].

The patient is a 63-year-old male with pericardial effusion who fell into cardiac tamponade one year and eight months following radical operation for esophageal cancer (stage IV). Because the cytological diagnosis for the punctured specimen of pericardial effusion indicated class V, we recognized it as pericardial recurrence and instilled CDDP 20 mg and 25 mg into the pericardial cavity. The pericardial effusion disappeared completely. There are many reports of CDDP instillation into the pleural cavity or the peritoneal cavity, but few into the pericardial cavity. For esophageal cancer, this is the first report in Japan. The patient is still alive at present after fourteen months have passed. It is considered that this method is effective for malignant pericardial effusion due to advanced esophageal cancer.

[Radiation therapy of esophageal cancer--radical radiotherapy and radiotherapy in combination with surgery].

The role of radical and palliative radiotherapy, and radiotherapy combined with surgery are discussed. Surgical resection and radiation therapy have been applied to curative treatment of carcinoma of esophagus. Despite of recent advances of surgery, the results are still unfavorable. Radical irradiation was applied to attempt at long term control of the local and regional disease despite dismal cure rate: doses in the range of 6000 to 7000 rad were required. Palliative irradiation is also achieved significant improvement, and dose range of 4000 to 5000 rad were required. The lesions of cervical or upper one third of the esophagus showed better prognosis by radiotherapy than the lower lesions. Prognosis was related to the size of the lesion and the depth of penetration of the esophageal wall. To improve the treated result, pre- or post operative radiotherapy was tried in combination with surgery. Preoperative irradiation has improved the surgical resectability and treatment result, which was contributed by the recent advances of surgical technique which made extended operation possible. Therefore, the role of preoperative irradiation should be re-evaluated. Postoperative prophylactic irradiation was used to control the possible improvements of mediastimun and/or neck nodes. The treatment results were better in the group of postoperative irradiation than in the group without irradiation.

[Myelodysplastic syndrome (RAEB-T) occurring after adjuvant chemotherapy for colon and rectum cancers].

A 67-year-old man was admitted to our hospital because of bleeding tendency and high fever. The patient had a past history of gastrectomy and transverse colectomy for cancer of transverse colon at age 57, and rectum resection for rectum cancer at age 59. After these operations, Tegafur 645 g, MMC 56 mg, and Ara-C 560 mg were administered for about 6 years. Hematological examinations revealed hemoglobin of 7.7 g/dl, white cell count of 9,500/microliters with 8% myeloblasts, and platelet count of 7,000/microliters. A diagnosis of myelodysplastic syndrome (RAEB-T) was made from the finding of bone marrow smear, which showed 28% myeloblasts, and neutrophils and megakaryocytes with morphologically abnormal nuclei and cytoplasms. Chromosomal banding study of the bone marrow cells revealed -5, -8, 7q- in all analyzed cells. These findings suggest that the preceding adjuvant chemotherapy is probably related to the occurrence of myelodysplastic syndrome.