[Preliminary study of calculating cerebral arterial blood oxygen saturation using MRI].

To assess whether cerebral arterial blood oxygen saturation (SaO2) can be calculated by EPI, we examined the relationship between peripheral SaO2 and T2+ signal intensity (SI) changes in the brain in three normal subjects, using 1.5 Tesla MRI. To decrease SaO2, hypoxia was induced by 100% helium-gas inhalation (60 sec). SI declined as SaO2 decreased during helium inhalation, while rapid recovery of SI to the baseline was noted with recovery from hypoxia. The differential effective transverse relaxation rate was closely correlated with SaO2 (r > 0.94). Consequently, using MRI, we were able to calculate arterial SaO2.

Preparation and properties of 2',5'-linked oligonucleotide analogues containing 3'-O,4'-C-methyleneribonucleosides.

Bicyclic nucleoside analogues, 3'-O,4'-C-methyleneuridine and -5-methyluridine, were successfully incorporated into oligonucleotides via connection with 2',5'-phosphodiester linkage, and hybridization behavior and nuclease stability of the modified oligonucleotides were investigated.

Ferric ammonium citrate-cellulose paste for opacification of the esophageal lumen on MRI.

OBJECTIVE: A new ferric ammonium citrate-cellulose mixture for use in MRI of the esophagus was evaluated for its ability to opacify the esophageal lumen. MATERIALS AND METHODS: Thirty-two patients with esophageal disorders and ten patients with normal esophagus undergoing MRI at 1.5 T were given approximately 100 ml of the newly developed high-viscosity esophageal contrast preparation. Moreover, six of the patients with esophageal cancer were subjected to a second examination after radiation therapy. A total of 48 MR imagings were performed. RESULTS: Of the patients examined, successful esophageal opacification, graded as excellent, was obtained in 84.2, 78.9, and 57.9%, of the sagittal, axial, and coronal images, respectively. In cases of extrinsic disease involving the esophagus the contrast medium administration allowed the easy differentiation of the esophagus from adjacent mass lesions and proved very useful in identifying displacement and compression. In cases of esophageal carcinoma the contrast medium administration assisted in the measurement of wall thickness and length of the lesion as well as in the identification of the site of origin of the tumor. CONCLUSION: The results indicate that this product effectively opacifies the esophageal lumen in the majority of patients. We found that it is easy to use, is well tolerated, and does not produce artifacts.

[A hemodialysis patient with HTLV-1-associated myelopathy (HAM)].

We report here a case of maintenance hemodialysis with HTLV-1 associated myelopathy (HAM). A 53-year-old female hemodialysis patient was admitted to Teikyo University Ichihara hospital because of paralytic ileus. She had a history of blood transfusion and had been under dialysis treatment for 8 years. She had experienced gait disturbance and sensory disturbance in her lower extremities for 8 years. Neurological examination revealed myelopathy and neuropathy. Laboratory data revealed that serum anti-HTLV-1-antibody was over 1260 x (PA) and liquor HTLV-1-antibody was over 160 x (PA). Her liquor revealed a cell count of 4/3 cmm, protein 22 mg/dl, glucose 45 mg/dl, chloride 125 mEq/l and no atypical cells. To the best of our knowledge this is a rare case in Japan. Our findings suggest that HAM should be taken into consideration when we diagnose a maintenance hemodialysis patient showing neuropathy and myelopathy.

[Secondary hyperparathyroidism and tertiary hyperparathyroidism chronic renal failure, uremia].

The bone histology of renal osteodystrophy is classified into osteitis fibrosa, osteomalacia, those of mixed, osteoporosis and low turnover bone. Osteitis fibrosa is the most frequent skeletal abnormality and is caused by various degrees of hyperparathyroidism. The main factors inducing hyperparathyroidism which is a well known complication in patients with renal failure include (a) phosphorus retention: 1) hypocalcemia and 2) decreased levels of 1 alpha, 25(OH)2 Vitamin D3, (b) reduced number of 1 alpha, 25(OH)2 Vitamin D3 receptors in parathyroid tissue, (c) skeletal resistance to set-point for calcium-regulated parathyroid hormone secretion. Serum or plasma levels of calcium, phosphorus, alkaline phosphatase, parathyroid hormone, calcitonin and tartrate resistant acid phosphatase are measured to evaluate hyperparathyroidism and metabolic bone disease. Dietary phosphorus restriction in chronic renal insufficiency prevents secondary hyperparathyroidism and renal osteodystrophy. Other treatment of phosphorus binders, Vitamin D metabolites or analogues, carcitonin and bisphosphonate are useful for the management of renal bone disease.

[An adult case of hemolytic uremic syndrome (HUS) after pathogenic Escherichia coli (E. coli) infection].

In recent years, it has been revealed that verocytotoxin-producing E. coli (VTEC) infection is one of the leading causes of HUS and the molecular aspects of its pathophysiology have also been studied extensively. We report a case of a 56-year-old man who developed HUS after E. coli (O 26 strain) infection with diarrhea. The characteristic laboratory findings in this case included hypergammaglobulinemia, hypocomplementemia and a high level of immune complex in addition to the common findings of HUS. The light microscopic findings of the first renal biopsy performed before treatment revealed extensive interstitial changes with remarkable mononuclear cell infiltrations as well as mild mesangial proliferation with crescent formation. Subendothelial electron-dense deposits within the glomerular capillary walls and mesangial area were also detected by electron microscopic examination. The diagnostic possibilities of infectious endocarditis and collagen diseases, such as Sjögren syndrome, were reasonably ruled out by the appropriate examinations. After 2-month prednisolone therapy, proteinuria and deteriorated renal functions as well as the abnormal immunological parameters described above were remarkably improved. The second renal biopsy after treatments showed clearly diminished subendothelial deposits and interstitial mononuclear cell infiltrations. This case report might provide information on the unique features of renal interstitial damage and immunological abnormalities in VTEC-induced adult HUS.

[New development of cellulose-ferric ammonium citrate solution as a contrast-enhancement agent for magnetic resonance imaging of esophageal diseases].

For magnetic resonance imaging (MRI) of esophageal diseases, we have developed a new contrast-enhancement agent, cellulose-ferric ammonium citrate solution. Using this agent, the esophageal lumen is easily identified. This agent is expected to play a role in the MRI diagnosis of esophageal cancer and to help determine the indications for radical surgery and/or intracavitary irradiation.

[Thrombotic thrombocytopenic purpura (TTP) with a low level of apolipoprotein A-I (Apo A-I) which responded to combination of vincristine and beraprost].

A 51-year-old man was admitted to the psychiatric ward because of increasing confusion and irrational behavior. He was later transferred to our department due to anemia and thrombocytopenia. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was made based on the presence of thrombocytopenic purpura, microangiopathic hemolytic anemia, neurological symptoms and fever. Corticosteroids, plasma exchange (PE), dextrans, dipyridamole and vincristine (VCR) were given without satisfactory response. Beraprost sodium was prescribed followed by a dramatic improvement and complete remission. A number of reports indicated that prostacyclin metabolism was involved in the pathogenesis of TTP. Recently Apo A-I was identified to be a prostacyclin-stabilizing factor, which was initially low in this patient. If patients do not respond to either PE or VCR, consideration should be given to treatment with beraprost, especially when the level of Apo A-I is low.

Percutaneous treatments for biliary diseases.

Percutaneous treatment of biliary disease was administered in 173 cases, mainly among high-risk or elderly patients. Diagnosis was acute cholecystitis in 32 cases, acute cholangitis in 16, hepatic abscess in five, gallbladder stones in 28, common bile duct stones in 11, intrahepatic stones in five, malignant obstructive jaundice in 61, and benign biliary stenosis in 15. The treatment was successful in 158 of 173 cases (91.3%). Complications were encountered in 17 (9.8%). Most of these occurred during the initial period and were mild and controllable with conservative treatments. There were two deaths (1.2% of patients); one was not related to the procedure. These data suggest that percutaneous treatments are safe and effective even among elderly or high-risk patients with biliary diseases.

[Thrombotic thrombocytopenic purpura which was effectively treated by plasma exchange therapy--involvement of vWF and endothelial cell injury].

A 49-year-old man with a one-week history of general fatigue and several other symptoms, including hematuria, numbness of the mouth, anemia and thrombocytopenia, was admitted because of an episode of convulsions and unconsciousness after blood transfusion. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was then made, and treatment with steroids, anti-platelet agents, transfusion of fresh frozen plasma was started. However, since no improvement was seen, on the third day of admission, treatment with plasma exchange was instituted (total plasma exchange volume was 18.1 iota), and his clinical and hematological conditions improved markedly. Since then, he has been in a remission state for about three years. Laboratory examinations during the acute phase showed increase of vWf: Ag, decrease of RCof/vWf: Ag, increase of vWf large multimers and a high endothelial cell injury activity by the patient's serum. In the next day following the plasma exchange therapy, RCof/vWf: Ag improved, but not to the normal range. One and a half years later, while in the remission phase, the vWf multimers and endothelial cell injury activity normalized. Thus, these findings show further evidence on the involvement of endothelial cell injury and vWf in the pathogenesis of TTP.

Role of endogenous arginine vasopressin in potentiating corticotropin-releasing hormone-stimulated corticotropin secretion in man.

Exogenously administered vasopressin (VP) augments ACTH secretion stimulated by CRH. This study was performed to elucidate the role of endogenous VP in potentiating CRH-induced ACTH secretion in man. Synthetic human CRH (100 micrograms) was injected iv into seven normal men after they had been water loaded (20 mL/kg; 60 and 30 min before CRH injection; WL-CRH test) and water deprived (water restriction for 18 h before CRH injection; WD-CRH test). Blood samples were obtained before and 5, 15, 30, 60, 90, and 120 min after CRH injection at 0900 h for determination of plasma ACTH, cortisol, arginine vasopressin (AVP), CRH, and catecholamine levels and osmolality. Urine was obtained immediately before and 120 min after CRH injection for determination of osmolality. The mean plasma AVP levels were significantly higher during the WD-CRH test [1.8 +/- 0.4 (+/- SE) to 1.9 +/- 0.4 pmol/L] than during the WL-CRH test (0.6 +/- 0.1 to 0.9 +/- 0.1 pmol/L). The mean plasma ACTH and cortisol levels rose significantly from basal (4.5 +/- 0.6 pmol/L and 320 +/- 20 nmol/L, respectively) to peak values of 14.0 +/- 2.1 pmol/L at 30 min and 700 +/- 50 nmol/L at 60 min, respectively, during the WD-CRH test. During the WL-CRH test, mean basal plasma ACTH and cortisol levels were 3.5 +/- 0.7 pmol/L and 420 +/- 50 nmol/L, respectively, and reached peak values of 7.7 +/- 1.1 pmol/L at 60 min and 550 +/- 40 nmol/L at 30 min, respectively. Both the mean peak levels and integrated ACTH and cortisol responses were significantly higher during the WD-CRH than during the WL-CRH test. There was no significant difference between the plasma CRH and catecholamine concentrations in both tests. These results suggest that endogenous AVP potentiates CRH-stimulated ACTH secretion and, thus, plays a physiologically significant role in regulating CRH-stimulated ACTH and cortisol secretion in man.

Effect of subcutaneous injection of a long-acting analogue of somatostatin (SMS 201-995) on plasma thyroid-stimulating hormone in normal human subjects.

SMS 201-995 (SMS), a synthetic analogue of somatostatin (SRIF) has been shown to be effective in the treatment of the hypersecretion of hormones such as in acromegaly. However, little is known about the effects of SMS on the secretion of thyroid-stimulating hormone (TSH) in normal subjects. In this study, plasma TSH was determined with a highly sensitive immunoradiometric assay, in addition to the concentration of SMS in plasma and urine with a radioimmunoassay, following subcutaneous injection of 25, 50, 100 micrograms of SMS (4 subjects/dose) or a placebo (6 subjects) to normal male subjects, at 0900 h after an overnight fast. The plasma concentrations of SMS were dose-responsive and the peak levels were 1.61 +/- 0.09, 4.91 +/- 0.30 and 8.52 +/- 1.18 ng/ml, which were observed at 30, 15 and 45 min after the injection of 25, 50 and 100 micrograms of SMS, respectively. Mean plasma disappearance half-time of SMS was estimated to be 110 +/- 3 min. Plasma TSH was suppressed in a dose dependent manner and the suppression lasted for at least 8 hours. At 8 hours after the injection of 25, 50 and 100 micrograms of SMS, the plasma TSH levels were 43.8 +/- 19.4, 33.9 +/- 9.4 and 24.9 +/- 3.2%, respectively, of the basal values. The results suggest that SMS suppresses secretion of TSH from the normal thyrotrophs in man and thus also that attention should be paid to possible hypothyroidism during the long-term treatment of patients such as those with acromegaly with this potent analogue of SRIF.

Hormonal responses to insulin-induced hypoglycemia in man.

Insulin-induced hypoglycemia is a potent stress stimulating ACTH release, but the factors responsible for this ACTH secretion are not known. In this study, several ACTH-stimulating factors, such as CRH, arginine vasopressin (AVP), epinephrine (E), norepinephrine (NE), and dopamine, in addition to ACTH, cortisol, and glucose, were simultaneously measured in plasma before and 15, 30, 60, 90, and 120 min after iv administration of 0.1 U/kg BW regular insulin to seven normal subjects. Insulin administration resulted in significant rises in the mean plasma ACTH level from 4.6 +/- 1.1 (+/- SEM) to 21.6 +/- 4.8 pmol/L at 30 min (P less than 0.01) and in plasma cortisol from 330 +/- 60 to 720 +/- 50 nmol/L at 60 min (P less than 0.01). These increases were preceded by a 41.0 +/- 1.9% (P less than 0.001) fall in blood glucose levels. The mean plasma CRH level rose significantly from 1.0 +/- 0.1 to 1.2 +/- 0.1 pmol/L (P less than 0.01) at 30 min and remained elevated until 120 min. In addition, concomitant and significant rises in plasma AVP levels (basal, 1.5 +/- 0.01; peak, 4.5 +/- 1.1 pmol/L at 30 min; P less than 0.01), E (basal, less than 50; peak, 640 +/- 130 pmol/L at 30 min; P less than 0.01), and NE (basal, 0.07 +/- 0.01; peak, 0.17 +/- 0.03 nmol/L at 60 min; P less than 0.05), but not dopamine, also occurred. These results suggest that multiple ACTH-releasing factors, such as CRH, AVP, E, and NE, are involved in ACTH secretion induced by insulin-induced hypoglycemia in man.