Biomedical subjects
Publications and source records attributed to K Kamiya.
A 26-year-old primipara with a cerebral venous angioma suffered an intracerebral hemorrhage just after delivery. Venous thrombosis was considered a possible cause of the intracerebral hemorrhage on the basis of the neuroradiological findings.
Two antifungal antibiotics maniwamycins A and B were isolated from the culture broth of a strain of actinomycetes, which were classified as Streptomyces prasinopilosus. These antibiotics were isolated by resin absorption and extraction with EtOAc and purified by column chromatography. Both antibiotics were found to be new azoxy substances from their physico-chemical properties. They showed broad antifungal spectra.
The effects of recainam (Wy 42,362) on transmembrane action potentials were examined in isolated rabbit right ventricular papillary muscles. Recainam (3 x 10(-5) to 3 x 10(-4) M) caused a concentration-dependent decrease in the Vmax of the action potential. At 3 x 10(-4) M, there was a slight decrease in the amplitude of the action potential. The resting potential and the action potential duration were not affected. Use-dependent block of Vmax was tested over a wide range of pacing frequencies (from 0.1 to 3.0 Hz). At 1.0 Hz, recainam 10(-4) M produced exponential decreases in Vmax with a rate constant of 0.17 per action potential and 39.8% reduction at steady state. This use-dependent block was augmented at the higher stimulation frequencies. The time constant for the recovery of Vmax from use-dependent block (offset) was 17.2 s. In papillary muscles depolarized with 10 mM [K+]0, the use-dependent block was augmented but tonic block and the rates of onset and offset of the use-dependent block were similar to those in normally polarized preparations in 4 mM [K+]0. The curves relating membrane potential and Vmax in preparations stimulated at a low frequency (0.01 Hz) were not shifted by 10(-4) M recainam. These findings suggest that recainam is a specific sodium-channel blocker and has kinetically slow but potent affinity for the channel during action potentials. This selective binding during action potential was further augmented by depolarization and is likely to play a significant role in the control of ventricular arrhythmias by the drug.
It is well known that vasodilating antihypertensive drugs induce intracranial hypertension. A considerable number of papers have reported nitroglycerin-induced ICP elevation during anesthetized operations. However, except for Gagnon's report, most papers dealt with normal patients. Our study, using an extradural pressure transducer clinically, deals with the nitroglycerin drip infusion and its effect on high ICP state. Mean ICP value before infusion was 42 mmHg+ 14.8 (N = 10). Three cases out of ten showed ICP elevation corresponding with blood pressure depression. Six cases out of ten revealed ICP depression corresponding with blood pressure depression. One case did not show any difference in ICP. There was a statistically significant difference between the ICP elevated group and the depressed group. These results suggest that very high ICP state, like vasomotor paralysis, does not have a potential to open the vascular bed in the cranium and blood pressure depression induced by nitroglycerin infusion causes ICP depression. We would like to conclude that nitroglycerin can be used for postoperative blood pressure control even in the neurosurgical field.
Clinical course, response to various modes of treatment and changes in in vitro marrow culture assay were studied in two patients with congenital pure red cell aplasia (Diamond-Blackfan syndrome) who were followed up for a long period. Patient 1, whose diagnosis was made at 8 months of age, was refractory to prednisolone and anabolic steroid. Bolus methylprednisolone, cyclophosphamide, ALG and high-dose intravenous immunoglobulin were given but none were effective. Particularly, hemolysis occurred during high-dose intravenous immunoglobulin therapy. In colony assay, CFU-E and BFU-E were found to be extremely decreased throughout the course, and colony formation was not corrected by adding prednisolone to the assay system. However, coculture of normal bone marrow cells with the patient's peripheral mononuclear cells resulted in reduction in CFU-E and BFU-E colonies. It was interesting that CFU-E and BFU-E were normalized after high-dose intravenous immunoglobulin therapy. Patient 2, whose diagnosis was made at 3 months of age, responded to prednisolone treatment at the early phase but became dependent on it thereafter. Thus, bolus methylprednisolone and high-dose intravenous immunoglobulin were given, without effect. Unlike patient 1, bolus methylprednisolone therapy induced reticulocytosis once. During high-dose intravenous immunoglobulin therapy, hemolysis was also observed. In colony assay, CFU-E and BFU-E decreased during the course, but were not corrected by adding prednisolone to the assay system. These findings suggest that in vitro colony assay is not always correlated with response to various therapies, and congenital pure red cell aplasia seems to be a heterogeneous disorder. The indication for high-dose intravenous immunoglobulin therapy for this disorder is limited because of hemolysis complicating the therapy.
Serial changes of FPA, FPB beta 15-42, FN, XIIIa, and alpha 2PI were investigated for the study on wound healing, blood coagulation, and fibrinolysis during gastric cancer surgery. For a control, we compared the preoperative values with the postoperative ones. These results also were compared with the values in healthy volunteers and in patients with cholelithiasis or myoma uteri. Our findings were as follows; 1) Compared with the control values, a statistically significant elevation of FPA, FPB beta 15-42 and FPA/FPB beta 15-42 ratios in patients with gastric cancer was noticed after operation. 2) Compared with the control values, a statistically marked decrease of FN, XIIIa and alpha 2PI in patients with gastric cancer was observed after operation. 3) The preoperative FPA and FPB beta 15-42 levels of gastric cancer patients were appreciably greater than those of normal healthy volunteers. Compared with patients with cholelithiasis or myoma uteri, however, the only preoperative FPA of gastric cancer patients showed significantly high levels. 4) FN and alpha 2PI revealed a notable positive correlation. These results suggest (1) increase of coagulation activity (thrombin formation) in gastric cancer patients; (2) increase of intravascular coagulation and fibrinolytic activity (thrombin and plasmin formation) during gastric cancer surgery; and, (3) depression of FN, XIIIa and alpha 2PI during surgery was due to sequestration at the site of tissue injury.
We studied the therapeutic effects of human urinary trypsin inhibitor (UTI) in 5 cases with acute renal failure, resulting from traumatic shock in 1 case, post-operative shock in 2 cases, septic shock in 1 case, and dehydration in 1 case. We administered 300,000 u/day of UTI intravenously at the initial phase of acute renal failure for 7 days. We measured the activities of urinary N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP) and the activities of serum beta-glucuronidase, PMN-elastase serially. As a control, we also studied same markers in 5 cases with acute renal failure without the administration of UTI. We could obtain the following results. 1) Urinary activities of NAG and AAP were already elevated markedly at the onset phase of acute renal failure. 2) The administration of UTI caused a significant decrease of the activities of NAG and AAP in the urine as compared with those in the controls. 3) The administration of UTI caused also the significant suppression of the activities of beta-glucuronidase and PMN-elastase in the serum. These results suggested that UTI has the protective effects on the tubular epithelial cell injuries in cases of acute renal failure.
On Day 0, young adult female F344 rats were adrenalectomized and intrasplenically implanted with a pituitary gland and capsule containing estrone. All were thereafter given 2.5 mg deoxycorticosterone per week and the choice of saline or tap water. This treatment yields high prolactin levels and glucocorticoid deficiency (Prl+/Glc-). On Day +48, total recoverable mammary DNA was increased by more than sevenfold, tritiated thymidine uptake by nearly fourfold, and total mammary clonogens by about fivefold. Irradiation with 4, 40, and 80 cGy X rays on Day +48 increased total mammary carcinomas per rat day at risk linearly with dose, and 40 and 80 cGy significantly decreased first carcinoma latency. A dose of 40 cGy X rays on Day -1 yielded tumor latencies and frequencies insignificantly different from unirradiated controls and significantly different from the dose on Day +48. Total carcinomas per rat day at risk were better fit by a function of dose to the power 0.4 than by a linear function after exposure to 1, 10, and 20 cGy fission neutrons, and 10 and 20 cGy significantly shortened the time to appearance of the first cancer. In contrast to results with X rays, 10 cGy neutrons on Day -1 yielded tumor frequencies and latencies insignificantly different from 10 cGy neutrons on Day +48. The carcinogenic action of X rays was thus influenced by total clonogen numbers and/or proliferation rates; that of neutrons was not.
Thyroid blood flow related with thyroid function is of great importance in diagnosing thyroid gland disease. However, there has no report on such observations of thyroid blood flow dynamics, especially non-invasively and quantitatively. In this study new developed ultrasound duplex scanning system was used to measure the superior thyroid blood flow and analyze the hemodynamics in 105 cases of solitary thyroid tumors, including 30 cases of thyroid cancers. Superior thyroid blood flows on afferent portion obviously increased both in benign and malignant tumor cases, but clear difference between them could not be found. On the other hand, in concern with the blood flows on inafferent portions, malignant thyroid tumor cases showed remarkable increase with statistical difference. The blood flow ratio between afferent and inafferent portions was considered to distinguish between benign and malignant thyroid tumors as quantitative criteria. The assumption that the tumors whose blood flow rate was below 3.0 is malignant led the fine result that accuracy was 79.8%, sensitivity; 71.5%, specificity; 81.5%. This quantitative criterion requires no surgical technique, therefore, this is useful for the tissue characterization of thyroid tumors.
Two-dimensional transesophageal echocardiography (2D-TEE) facilitates clear imaging of the thoracic aorta, and we have already reported the diagnostic value of this procedure for detecting dissecting aortic aneurysm (DAA). Recently, we performed preoperative and postoperative 2D-TEE in nine surgically treated patients with DAA (Debakey type I: 2 cases, type II: 1 case, type IIIa: 2 cases, type IIIb: 4 cases), and repeated 2D-TEE in six medically treated patients (DeBakey type IIIa: 2 cases, type IIIb: 4 cases), and the usefulness of 2D-TEE in the follow-up study of DAA was evaluated. Two types of ultrasound probe (radial scan type, and sector type with a color-Doppler system) were used in this study. Of the surgically treated patients, four of nine cases in which the initial tears were excised or repaired showed neither leakage nor pseudoaneurysm at the site of graft insertion. Other surgically treated patients showed residual intimal tears and continued to harbor patent false lumen. One patient with type I dissection demonstrated localized saccular aneurysm in the proximal arch of the aorta, but no evidence of aortic regurgitation. Of the six medically treated patients, further extension of the initial dissection was observed in one of the two type IIIa cases. False lumen narrowing was recognizable in three of the four type IIIb patients, and complete obliteration of false lumen was observed at necropsy in one of these three cases. Double-channeled aorta was seen in another case of type IIIb dissection.(ABSTRACT TRUNCATED AT 250 WORDS)
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A successfully treated case of infantile medulloblastoma is presented that was associated with omphalocele, malrotation of the intestine, and extrophy of the bladder. A 5-month-old boy was admitted due to disturbance of consciousness and was diagnosed by computed tomography as having a medulloblastoma. Ventricular drainage, subduralperitoneal shunt, and removal of the tumor were performed, and postoperatively radiation therapy was administrated with 4,000 rad to the whole brain. He was discharged in good condition and no evidence of recurrence was observed at the 14th post-operative month. Medulloblastomas associated with congenital anomaly of the abdomen have been only rarely reported. The authors postulate that between the second and third month of gestation an intrinsic or extrinsic factor may have caused the development of the medulloblastoma, as well as anomalies of the abdomen such as omphalocele, malrotation of the intestine, and extrophy of the bladder.
The acute and chronic cellular electrophysiologic actions of ketanserin, a selective blocker of 5-hydroxytriptamine (5-HT2) receptor, were examined in the isolated rabbit ventricular muscle. This work was prompted by the recent observations that small numbers of patients treated with hypertension develop QTc prolongation, rarely associated with torsades de pointes. At 1.0 Hz stimulation, ketanserin, 10(-5) and 10(-4) M, prolonged the action potential duration (APD) (by 20% and 29%, respectively) and voltage-dependent refractoriness. At 10(-4) M, the maximal rate of rise of phase 0 of the action potential (Vmax) decreased 11%. Action potential amplitude and resting membrane potential were not affected by either concentration of ketanserin used (10(-6) to 10(-4) M). Trains of stimuli at rates of 1.0 Hz or higher led to an exponential decline in Vmax to a new plateau level. The time constant for the recovery of Vmax from the use-dependent block was 1.3 second. Chronic administration of ketanserin (40 mg/kg/day, intramuscularly) caused a significant prolongation of APD (106%; p less than 0.01) and voltage-dependent refractoriness without effects on the action potential amplitude, resting membrane potential, and Vmax. These data indicate that ketanserin exerts significant class I effects with mild class III effects when superfused acutely, whereas chronic administration of ketanserin exhibits marked class III effects. Both effects of the drug are likely to exert significant antiarrhythmic actions.
During acute superfusion studies by means of the standard microelectrode technique, we previously showed that both amiodarone and its major metabolite, desethylamiodarone, had a modest effect on the lengthening of the action potential duration (APD) at high drug concentrations and produced a rate-dependent block of the sodium channel in cardiac muscle. In this study the comparative electrophysiologic effects of the two compounds in rabbits treated chronically with these compounds were determined with particular reference to repolarization and sinus node automaticity. The changes were correlated with those in serum and tissue drug levels and in thyroid hormone indices. After 1 week neither compound had a significant effect on atrial or sinus nodal potentials; after 3 weeks, amiodarone increased the atrial APD at 90% repolarization time by 10.5% (p less than 0.05) and the effective refractory period (ERP) by 6.7% (p less than 0.05). The corresponding figures for desethylamiodarone were 13% (NS) and 18% (NS). The sinus cycle length was increased 12% (NS) by amiodarone and 27.9% (p less than 0.05) after the metabolite. In animals treated for 6 weeks, amiodarone increased the ventricular APD at 90% repolarization by 58.8% (p less than 0.01) and desethylamiodarone by 42.0% the corresponding figures for the ERP were 63.4% (p less than 0.01 and 47.4% (p less than 0.01), respectively. At the stimulation frequency used, neither compound exerted a significant effect on Vmax. Both amiodarone and desethylamiodarone significantly decreased serum triiodothyronine and increased reverse triiodothyronine levels but had no effect on thyroxine.(ABSTRACT TRUNCATED AT 250 WORDS)
A report is presented on a case of teratoma with a malignant component arising from the septum pellucidum 7 years after total surgical removal of a mature teratoma in the pineal region. The patient was successfully treated with radiotherapy and total surgical resection of the second tumor. The case is characterized by the development of a second malignant tumor and by the long interval from complete resection of the primary tumor to the occurrence of the second tumor. Our case is not considered to be a recurrence of the mature teratoma of the pineal region but to be a multiple tumor of germ-cell tumor having multicentricity and a different temporal variety.
Recainam (Wy 42,362) is a new antiarrhythmic agent undergoing clinical evaluation, but its electrophysiologic effects in cardiac muscle are poorly defined. With microelectrode techniques, its profile in isolated preparations of dog and rabbit hearts was determined using drug concentrations of 10 to 300 microM. Recainam induced a concentration- and frequency-dependent decrease in the maximal rate of rise of the phase 0 of the action potential (Vmax), action potential amplitude and overshoot potential, with little or no change in the effective refractory period except in Purkinje fibers, in which it was markedly reduced. At a 300 microM concentration, Vmax was reduced 51% (p less than 0.001) in ventricular muscle and 44% (p less than 0.001) in atrial muscle, with no change in action potential duration or effective refractory period. At the same drug concentration in Purkinje fibers, Vmax was decreased by 41% (p less than 0.01), action potential duration at 90% repolarization by 36% (p less than 0.01) and effective refractory period by 34% (p less than 0.01). Recainam had no significant effect on the sinoatrial node, but it depressed phase 4 depolarization in isoproterenol-induced automaticity in Purkinje fibers. The drug had no effect on slow channel potentials induced by high concentrations of potassium and isoproterenol. The data indicate that the electrophysiologic profile of recainam in isolated cardiac muscle is consistent with the overall effects of class IC agents without having an effect on the slow calcium channel. Its major action is to depress Vmax, with little effect on refractoriness.(ABSTRACT TRUNCATED AT 250 WORDS)
The synthetic design and the biological activities of structurally new angiotensin converting enzyme (ACE) inhibitors, (R)-3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid derivatives, are described. A number of compounds in this series showed potent ACE inhibitory activity in vitro and in vivo. Structure-activity studies indicated that a piperidyl moiety on the amino group at the 3-position in this series conferred long-lasting ACE inhibitory activity and that the duration of activity depended on the length of the carbon chain in the 1-carboxy-omega-(4-piperidyl)alkyl group. (R)-3-[(S)-1-carboxy-5-(4-piperidyl)-pentyl]amino-4-oxo-2,3,4,5-tetrahydro- 1,5-benzothiazepine-5-acetic acid (CV-5975) was selected as the most promising ACE inhibitor for further studies because of its marked inhibitory activity.
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