Kenjiro Inoue

Reduced regional cerebral blood flow in aged noninsulin-dependent diabetic patients with no history of cerebrovascular disease: Evaluation by N-lsopropyl-123I-p-iodoamphetamine with single-photon emission computed tomography

Regional cerebral blood flow was measured using N-isopropyl-123I-iodoamphetamine with single-photon emission computed tomography (CT) in 16 aged patients with noninsulin-dependent diabetes mellitus (NIDDM, average age 72.8 years, average fasting plasma glucose 7.7 mmol/L), and 12 nondiabetic subjects (71.6 years, 5.3 mmol/L). None had any history of a cerebrovascular accident. Systolic blood pressure (SBP), total cholesterol, and triglyceride levels did not differ between groups. Areas of hypoperfusion were observed in 14 diabetic patients (12 patients had multiple lesions) and in 6 nondiabetic subjects (3 had multiple lesions). Areas where radioactivity was greater than or equal to 65% of the maximum count of the slice was defined as a region with normal cerebral blood flow (region of interest A, ROI-A), and areas where the count was greater than or equal to 45% were defined as brain tissue regions other than ventricles (ROI-B). The average ROI-A/B ratio of 16 slices was used as a semiquantitative indicator of normal cerebral blood flow throughout the entire brain. Mean ROI-A/B ratio was 49.6 +/- 1.7% in the diabetic group, significantly lower than the 57.9 +/- 1.6% at the nondiabetic group (p less than 0.005). The ratio was inversely correlated with SBP (r = -0.61, p less than 0.05), total cholesterol (r = -0.51, p less than 0.05), and atherogenic index (r = -0.64, p less than 0.01), and was positively correlated with high-density lipoprotein (HDL) cholesterol (r = 0.51, p less than 0.05) in the diabetic, but not the nondiabetic group. These observations suggest that the age-related reduction in cerebral blood flow may be accelerated by a combination of hyperglycemia plus other risk factors for atherosclerosis.

Predominant T3 synthesis in the metastatic thyroid carcinoma in a patient with T3-toxicosis

A metastatic mixed papillary and follicular thyroid carcinoma synthesizing predominantly triiodothyronine (T3) producing thyrotoxicosis is described. There was a concentration of 131I in numerous masses on the lung as well as a mass in the neck. BMR was +38%. Serum T4, T3-RU and T3 were 6.6 microgram/100 ml, 35.1% and 9.0 ng/ml, respectively. Serum TSH was not detectable and was not increased by the injection of 500 microgram of synthetic TRH. Decompressive surgery, performed while the patient was receiving no thyroid medication, yielded tumor tissue for chemical analysis. The mass measured 4.5 cm X 4.0 cm X 3.0 cm. The normal thyroid tissue was found to be atrophic. Sedimentation pattern of the soluble protein revealed a small peak at 18 S without a 27 S peak, suggesting an accelerated hydrolysis of thyroglobulin (Tg). Both the Tg content of the tumor and the degree of iodination of the Tg were low, 0.53% (based on wet weight of tissue) and 0.07%, respectively. DIT-I, MIT-I, T4-I, and T3-I in hydrolysate of the tumor tissue were 17.8%, 29.1%, 7.1%, and 41.7%, respectively. Therefore, the high T3 in the serum in this case seems to arise mainly from the cancer tissue. Possible mechanisms for this predominant T3 production are discussed.

Defective iodide transport and normal organification of iodide in cold nodules of the thyroid.

Eleven thyroid follicular adenomas, cold on scintigram were analysed to determine whether defect in iodide organification or iodide transport causes low iodide uptake in cold nodules of the thyroid. The results were compared with perinodular tissue samples used as controls.

Cardiac involvement of progressive muscular dystrophy (Becker type, Limb-girdle type and Fukuyama type) evaluated by radionuclide method.

Tl-201 SPECT and Tc-99m-Human serum albumin (HSA) multigated radionuclide ventriculography were performed on 11 patients with progressive muscular dystrophy (Becker type 2, Fukuyama type 2, Limb-girdle type 7) to evaluate myocardial involvement. Hypoperfusion was detected in 8 patients on Tl-201 SPECT. Decreases in both systolic function (left ventricular ejection fraction; LVEF) and diastolic function (peak filling rate; PFR) were also seen in these patients. A high incidence of myocardial involvement of these kinds of progressive muscular dystrophy was suggested.

Posterior tibial somatosensory evoked potentials in Duchenne-type progressive muscular dystrophy

Posterior tibial somatosensory evoked potentials were recorded from 10 patients with Duchenne-type progressive muscular dystrophy (DMD). The results of the patients were compared with age-matched controls. The ratio of height to latency (H/P38 and H/N22-P38) decreased significantly in DMD, which indicated central conduction disturbances in DMD.

LIPID STORAGE MYOPATHY IN VON GIERKE'S DISEASE

An 18-year-old girl with von Gierkes disease associated with a lipid storage myopathy is reported. The diagnosis of von Gierkes disease was made from decreased activity in glucose-6-phosphatase in the jejunal biopsy specimen. Neurologically she showed generalized hypotonia of the muscles, atrophy of bilateral proximal muscles of the lower extremities, weakness in neck flexors, deltoid and lumbar girdle muscles, and a positive Gowers sign. Muscle biopsy from flexor femoris muscle revealed fatty deposition in type 1 fibers and atrophy of type 2 fibers and the diagnosis of an accompanying lipid storage myopathy was made. This case also had a ventricular septal defect confirmed by right cardiac catheterization.

Acid thyroglobulin protease activities in human diseased thyroid glands.

The lysosomal acid protease is thought to be a main enzyme in hydrolysis of thyroglobulin. The protease activity of lysosome‐rich fractions of various diseased thyroid glands were assayed by the sensitive and reproducible method developed in our laboratory. They included 78 diseased thyroid glands; 37 thyrotoxic goitres, five irradiated thyroids, five Hashimotos thyroiditis, one granulomatous thyroiditis, six multinodular goitres, 14‘cold’ adenomas, four‘hot’ adenomas with three paranodular tissues, and six carcinomas. Fifteen paranodular tissues of cold and solitary thyroid nodules were served as controls. The protease activities were significantly increased in thyroid tissues of thyrotoxic goitres, Hashimotos thyroiditis, adenomas and adenocarcinomas. In thyrotoxic goitres, the protease activity correlated well with the mean area size of colloid follicles. The‘hot’ adenomas had higher protease activity than‘cold’ ones. The protease activity of multinodular goitres was nearly normal. Only the irradiated thyroid glands had low protease activities. Therefore the high protease activities in hyperfunctioning goitres seem to reflect hormone secretory activities. On the other hand, cold neoplastic goitres seem to have lysosomal protease activities which are not associated with thyroidal secretory process. The assay of acid protease activity will be useful to understand the pathophysiology of lysosomal system in diseased thyroid glands.

Equilibrium radionuclide ventriculography in Duchenne's cardiomyopathy.

Myocardial dysfunction in 14 patients with Duchennes muscular dystrophy (DMD) was evaluated by Tc-99m HSA multigated radionuclide ventriculography (MGRV). Follow- up studies were performed on eight patients for 5 years. Left ventricular ejection fraction and standard deviation of the phase angle were abnormal in all patients older than 15 years. Hypokinetic changes and phase delay were recognizable in most patients older than 17 years. Peak filling rate decreased in patients older than 17 years. MGRV was considered an effective method for evaluating serial changes in cardiomyopathy of patients with DMD.

Tl-201 myocardial SPECT in patients with Duchenne's muscular dystrophy: A long-term follow-up

Tl-201 SPECT was used to evaluate myocardial involvement in 13 patients with Duchennes muscular dystrophy. Serial studies of 9 patients were done at two-year intervals. The hypoperfused areas of the left ventricle became more prominent with age and severity.

The Adverse Effects of Thioureylene Antithyroid Drugs

The aims of the present study were to investigate the incidence of adverse effects of thioureylene antithyroid drugs and to see if there were any factors related to the development of the adverse effects. Methimazole or propylthiouracil was administered to 151 patients with Graves disease; 76 untreated cases and 75 treated cases. The overall incidence was 22.4% among the 76 untreated cases. The incidences were 26.7% (13/45 cases) for methimazole and 16.1% (5/31 cases) for propylthiouracil, respectively, which were significantly higher than those previously reported. Fourteen out of 17 cases with the adverse effects were given the other thioureylene. The successive incidence of the adverse effects was 28.6% (4 cases), which was not significantly different from that under the drug of first choice. The result suggests that methimazole and propylthiouracil may not have cross-reaction each other. On the other hand, antinuclear antibody and anti-DNA antibody became positive in 2 out of the 4 cases. It would be a significant phenomenon, since antinuclear antibody was positive in only 3% of cases before the drug treatment. Thus, an immunological mechanism seemed to be involved in the problems, although there was no correlation between antithyroid autoantibodies and the development of the adverse effects. The adverse effects were observed within 2 months of administration of less than 250 tablets in total in most of the cases. The results imply that allergic mechanism rather than accumulating or toxic effect may concern the development of adverse effects of the thioureylenes.