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Biomedical subjects

H Miyake

Publications and source records attributed to H Miyake.

At least 361 records · Page 20Linked to original sources

Central cholinergic action produces antagonism to ketamine anesthesia.

Ketamine sometimes produces posthypnotic emergency reactions, such as prolonged hallucination or delirium. In a previous paper, we showed that physostigmine, an anticholinesterase agent, counteracts the manifestation of effects of ketamine at some doses. In the present study, we investigated the mechanism of the antagonistic effect of physostigmine on ketamine anesthesia. At first, rats were given ketamine 75 mg/kg. Immediately after the loss of righting reflex, the four groups of rats were given one of the three central cholinergic agents, physostigmine 0.1 mg/kg, oxotremorine 0.05 mg/kg, 4-aminopyridine 3 mg/kg, or saline as the control. The sleeping times were 10.7 +/- 1.0, 12.3 +/- 0.9, 11.4 +/- 1.3 and 21.2 +/- 0.7 min, respectively. The three cholinergic agents antagonized ketamine anesthesia. In the other groups of rats, the central anticholinergic agent, l-hyoscyamine, 0.5 mg/kg, was given subcutaneously for premedication before the above-mentioned procedure. The sleeping times were 16.3 +/- 1.2 min in the physostigmine group, 18.7 +/- 1.0 min in the oxotremorine group and 18.6 +/- 0.8 min in the 4-aminopyridine group. The sleeping time was significantly longer in the premedicated group than in the non-premedicated group, in the case of the three central cholinergic agents. The sleeping time in the saline group, 20.0 +/- 0.4 min, was not significantly different from that of the control in the non-premedicated case. It is, therefore, considered that the central cholinergic action produces antagonism to ketamine anesthesia.

4-Aminopyridine↗

FR 113680: a novel tripeptide substance P antagonist with NK1 receptor selectivity.

1. We have discovered a novel tripeptide substance P (SP) antagonist, FR 113680 [N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N'-formyl-D- tryptophyl]-N-methyl-N-phenylmethyl-L-phenylalaninamide]. In binding experiments, FR 113680 inhibited [3H]-SP binding to guinea-pig lung membranes (NK1) in a competitive manner but had not effect on [3H]-SP binding to rat cerebral cortical membranes (NK1), [3H]-neurokinin A ([3H]-NKA) binding to rat duodenum smooth muscle membranes (NK2) and [3H]-eledoisin (Ele) binding to rat cerebral cortical membranes (NK3). 2. In bioassay experiments, FR 113680 dose-dependently inhibited SP-induced guinea-pig ileum contraction (NK1), but did not inhibit either NKA-induced rat vas deferens contraction (NK2) or neurokinin B (NKB)-induced contraction of rat portal vein (NK3). According to Schild plot analysis, the inhibitory effect of FR 113680 on SP-induced guinea-pig ileum contraction is competitive and the pA2 value is 7.53. 3. The inactivity of FR 113680 on NK1 receptors in rat compared to guinea-pig may represent species-specific forms of the NK1 receptor. 4. These findings suggest that FR 113680 interacts selectively with the NK1 neurokinin receptor.

Animals↗

Pharmacological profile of a high affinity dipeptide NK1 receptor antagonist, FK888.

1. In our search for compounds that inhibit the binding of [3H]-substance P (SP) to guinea-pig lung membranes, the dipeptide SP antagonist, FK888, was developed by chemical modification of the parent compound, (D-Pro4, D-Trp7,9,10, Phe11)SP4-11. 2. In a [3H]-SP binding assay using guinea-pig lung membranes and rat brain cortical synaptic membranes, FK888 displaced [3H]-SP binding with a Ki value of 0.69 +/- 0.13 nM and 0.45 +/- 0.17 microM, respectively, in a competitive manner. 3. FK888 inhibited the contraction of guinea-pig isolated ileum induced by SP in the presence of atropine and indomethacin (a NK1 receptor bioassay) with a pA2 value of 9.29 (8.60-9.98). 4. FK888 inhibited contractions of rat vas deferens by NKA (a NK2 receptor bioassay) and of rat portal vein by NKB (a NK3 receptor bioassay) at concentrations at least 10,000 times greater than that required to inhibit contractions of guinea-pig ileum. 5. FK888 also inhibited SP-induced airway oedema in guinea-pig after both intravenous and oral administration. 6. These data demonstrate that FK888 is a potent and selective NK1 antagonist which is active both in vitro and in vivo.

Administration, Oral↗

Time course of intraventricular pressure change in a canine model of hydrocephalus: its relationship to sagittal sinus elastance.

Hydrocephalus was induced in adult greyhounds by intracisternal kaolin. Intraventricular pressure (IVP) was monitored in the conscious animal for 2 weeks using a small implantable sensor, and the time-course of IVP change was characterized. Intraventricular pressure increased significantly within 36 h of kaolin infusion and gradually subsided to normal values within 1 week. Enlargement of the lateral ventricles was not observed during the early phase of intracranial hypertension (less than 2 days). Evolving hydrocephalus and intracranial hypertension increased the elasticity (dP/dV) of the sagittal sinus. This effect was statistically significant (p < 0.05) and is possibly reversible in the acute stage. Normotensive hydrocephalus (1 and 2 weeks after kaolin) was associated with an irreversible increase in resistance to outflow (i.e., increased sagittal sinus elasticity). Sagittal sinus venography of animals with obvious ventricular enlargement (at least 1 week after kaolin) showed development of venous collaterals and atypical outflow pathways.

Animals↗

Giant air cell of the petrous apex: a possible cause of facial hypalgesia.

A giant air cell of the left petrous apex was found in a 23-year-old man with ipsilateral facial hypalgesia. The size of the giant air cell depicted on computed tomography was 1.5 x 2.0 x 2.0 cm. A coronal T1-weighted magnetic resonance image showed that the trigeminal nerve was compressed superomedially by a large signal void area that was probably a result of excessive pneumatization of the petrous apex. It is suggested that the facial hypalgesia was caused by the compression by the giant air cell of the petrous apex on the trigeminal nerve.

Adult↗

An index for proportion of head size to body mass during infancy.

The index "head circumference (cm)3/body weight (g)" gave an almost constant average (about 10) and standard deviation (about 1) in more than 2000 children at birth and at 4, 10, and 18 months. Application of this index to the data previously published confirms that the average is almost constant throughout the period from birth to 18 months, irrespective of sex or race. Head circumference cubed and body weight correlate significantly. This index seems to be useful to assess the proportion of head size to body mass during infancy, and to contribute to early diagnosis of diseases such as hydrocephalus or microcephaly.

Body Mass Index↗

Effects of nitric oxide synthase inhibitors on gastric alkaline secretion in rats.

The effects of NG-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on gastric HCO3- secretion were examined in anesthetized rats. Intravenous administration of L-NAME (1, 2.5, 5 mg/kg) increased HCO3- secretion in a dose-related manner. This effect of L-NAME was mimicked by NG-mono-methyl-L-arginine (50 mg/kg, i.v.) and was antagonized significantly by concurrent administration of L-arginine but not D-arginine (200 mg/kg, i.v.). These results indicate that gastric HCO3- secretion is stimulated by inhibition of NO biosynthesis.

Amino Acid Oxidoreductases↗

Localized fat collection adjacent to the intrahepatic portion of the inferior vena cava: a normal variant on CT.

We describe a normal focal collection of fat that has the appearance of a mass on CT scans. The fat is adjacent to the intrahepatic portion of the inferior vena cava and is contiguous to the fat around the subdiaphragmatic portion of the esophagus. This finding occurred in 11 (0.5%) of 2227 patients who had CT scans at our institution. The fat collections did not change in size or shape on follow-up CT scans obtained 2 to 29 months later (mean, 14 months). The localized fat collections were at the level of or above the confluence of the hepatic veins and the inferior vena cava, and were medial to the inferior vena cava. They were less than 22 mm in length, oval, and had attenuation values ranging from -113 H to -23 H on unenhanced CT scans. The collections enhanced slightly on scans obtained after contrast administration. T1-weighted (600/15) MR images obtained in three cases showed a high-intensity mass that was contiguous to high-intensity fat around the esophagus, medial to the intrahepatic portion of the inferior vena cava. Our experience suggests that a masslike fat collection adjacent to the intrahepatic portion of the inferior vena cava is a normal variant on CT scans and should not be mistaken for an abnormality.

Adipose Tissue↗

Antihypertensive effects of MPC-1304, a novel calcium antagonist, in experimental hypertensive rats and dogs.

Antihypertensive effects of a novel calcium antagonist, MPC-1304, (+-)-methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5- pyridine-dicarboxylate and its active metabolites were investigated in experimental hypertensive rats and dogs and compared with those of other dihydropyridine derivatives (nifedipine, nisoldipine, nicardipine, and nitrendipine). MPC-1304 had a dose-related antihypertensive effect with a slight increase in heart rate (HR) in rats. The antihypertensive effects of MPC-1304 were more potent than those of other dihydropyridines, and its active metabolites had antihypertensive effects comparable to those of other dihydropyridines. The hypotensive effects of MPC-1304 were stronger in hypertensive rats than in normotensive rats. During repeated oral administration of MPC-1304 to spontaneously hypertensive rats (SHR, once daily for 4 weeks, 0.3-3 mg/kg), dose-response curves of the antihypertensive effect did not change and body weight gain was equal to that of the vehicle-treated group. When given orally to conscious renal hypertensive dogs, MPC-1304 0.1-0.3 mg/kg had a potency and duration of antihypertensive action comparable to that of nitrendipine (1-3 mg/kg). MPC-1304 increased coronary blood flow (CBF) and aortic blood flow (ABF) in conscious normotensive dogs. In conclusion, MPC-1304 and its active metabolites have potent antihypertensive effects and cause slight tachycardia, and they may be useful in treating hypertension.

Administration, Oral↗

Mass screening of neuroblastoma in Sapporo City, Japan.

In Sapporo City a mass screening program for neuroblastoma aiming at 6-month-old infants has been performed since April 1981. By March 1990, 136,001 infants were screened; 26 true-positive cases of neuroblastoma and six false-negative cases were detected. The sensitivity of the mass screening method was about 80% throughout the 9 years. During the 9-year period, a total of nine children with neuroblastoma who were not screened were also identified. Clinical stage, age at diagnosis, and survival rate for the 32 patients who were screened (26 true positives and six false negatives) were much more favorable than those for the nine patients who were not screened. A remarkable decrease in the incidence of cases of neuroblastoma with advanced clinical stages over 1 year of age, especially among children 1-4 years of age, was noted after the start of the mass screening. The mortality from this tumor in children up to 4 years of age significantly decreased after the start of the urinary screening program. Rescreening at 14 months of age was begun in April, 1991 in Sapporo City. Performing two screening examinations decreases the probability of overlooking a patient. Thus, it is expected that tumors missed on the first screening would be detected by the second screening.

Biomarkers, Tumor↗

[Study of recombinant human erythropoietin treatment on the anemia of predialysis patients].

We conducted a multiple-center joint study on the effects of recombinant human erythropoietin (rEPO) for predialysis patients. rEPO was intravenously administered to 42 predialysis patients (13 males and 29 females) with hematocrit (Ht) levels of less than 30%. The subjects were divided into group A (28 cases) in which rEPO was administered twice a week, and group B (14 cases) with rEPO administration once a week. The initial administration dosage was 6000IU/week. The Ht levels were 22.6 +/- 3.3% for group A and 23.2 +/- 2.7% for group B before the administration of rEPO, and increased to 31.0 +/- 4.0% and 27.7 +/- 3.7% respectively twelve weeks after initiating administration. The levels of effective improvement on anemia included 'markedly effective' in 17 cases (80.9%) and 'effective' in 2 cases (9.5%) in group A, and 'markedly effective' in 5 cases (41.7%) and 'effective' in 3 cases (25.0%) in group B. No significant change was seen in serum creatinine (Cr) levels during the study period. In the evaluation of renal function by reciprocal serum creatinine (1/Cr), a consistent tendency was not recognized; thus, suggesting that the rEPO administration had no effect on the renal function. No variation of blood pressure was seen. As far as side effects were concerned, headache and heavy headedness were recognized in four cases. There were, however, no cases in which the severity of the side effects dictated the discontinuation of the rEPO administration. In conclusion, rEPO was judged to be a safe and effective treatment for the anemia of predialysis patients.

Adult↗

[A case of progressive systemic sclerosis complicated by crescentic glomerulonephritis and diffuse pulmonary hemorrhage].

A 38-year-old man was hospitalized for proteinuria, and pitting edema. He had noticed Raynaud's phenomenon at about age fifteen. One month prior to admission, his urine contained protein and the serum creatinine was 3.0 mg/dl. On admission, sclerodactylia, digital pitting scar of fingertips, digital bone absorption and pulmonary fibrosis were observed and a diagnosis of progressive systemic sclerosis (PSS) was made. Laboratory investigations revealed: 24-hour urine protein excretion 3 g; serum creatinine 5.6 mg/dl; creatinine clearance 13.5 ml/min; antinuclear factor strongly positive in a speckled pattern; antibodies to nRNP positive with a titer of 1: 20, 480; antibodies to DNA, Sm, SS-A, SS-B, Scl-70, centromere and Jo-1 negative; serum complement normal. A renal biopsy revealed focal and segmental necrotizing glomerulonephritis with 70% crescents but no vascular changes. Circulating antiglomerular basement membrane antibodies were negative. Immunofluorescence disclosed granular deposits of IgM and C3 in the mesangium and along the capillary walls. Treatment was begun with methylprednisolone pulse therapy. After 5 month, serum creatine and creatinine clearance were 1.9 mg/dl and 35 ml/min, respectively. A year after the discharge, he was readmitted for hemoptysis and worsening of proteinuria and microhematuria. A chest radiograph demonstrated bilateral alveolar consolidation. Serum creatinine was elevated to 3.5 mg/dl. The continuous hemoptysis resulted in a severe dyspnea associated with a rapid fall in the hemoglobin. On the fourth hospital day, the PaO2 was 41 Torr on oxygen by mask that necessitated mechanical ventilation and pulse therapy was started. However, the patient died on the ninth hospital day of respiratory failure due to pulmonary hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Unsuspected painless subacute thyroiditis detected by radiogallium scintigraphy].

Two cases of painless subacute thyroiditis were presented in whom fever, fatigue and arthralgia except for thyroidal pain and swelling were complained. Until a intense uptake of the thyroid was found on radiogallium scintigraphy, the examinations of the thyroid had not been done. Laboratory data showed increased erythrocyte sedimentation rate, C-reactive protein and serum alkaline phosphatase, and mild leukocytosis. Skeletal, hepatic and biliary diseases were denied. In patients who have fever, increased erythrocyte sedimentation rate and serum alkaline phosphatase elevation without apparent sources, thyroid function should be evaluated because subacute thyroiditis can be associated with elevation of the serum alkaline phosphatase.

Gallium Radioisotopes↗

[Ototoxicity of cis-diammine glycolato platinum, 254-S].

Ototoxicity of cis-diammine glycolato platinum, 254-S, was evaluated from the results obtained in phase II studies for head & neck cancer, lung cancer, breast cancer, gastrointestinal cancer, urogenital cancer and gynecological cancer at 114 institutions, and in randomized comparative study of 254-S plus vindesine vs. cisplatin plus vindesine for advanced non-small cell lung cancer conducted at 41 institutions. In these studies, 254-S was administered at doses ranging from 80 to 100 mg/m2, repeated at least 2 times at 4-week intervals. Impaired hearing was examined in a hearing audiometry test before and after 254-S administration. The incidence of impaired hearing was 25.8% (16/62) in the 254-S phase II studies. The incidences in the randomized comparative study were 17.6% (3/17) for the 254-S/vindesine group and 20.0% (3/15) for the cisplatin/vindesine group. From these results, the ototoxicity of 254-S was thought to be similar to that of cisplatin in incidence and type.

Aged↗

[Effect of glycerol and mannitol on the distribution of brain tissue water determined by differential calorimetric scanning analysis].

To further clarify their mechanisms as "dehydrators", the effect of glycerol and mannitol on the distribution of tissue water was studied by using differential scanning calorimetry. In normal rat brain, glycerol, 30 minutes after infusion, reduced, by a certain amount, the free water contents. However, mannitol had no effect on the amount of tissue water. In the focal ischemic model, produced by Tamura's method, glycerol reduced the free water contents in the perifocal brain tissue. As for the contralateral brain tissue, mannitol not glycerol, reduced the total water contents. Above findings suggest that the effect of glycerol is mainly to decrease free water fraction in the non ischemic brain tissue, while mannitol shows its effect through the decrease it produces in the extra-brain water fraction.

Animals↗

[A phase I study of DWA2114R].

Phase I study of DWA2114R, a new platinum analogue, was conducted in 39 patients with various tumor types by a group of 13 institutions. Of the 39 patients entered in this study, 35 were evaluable. The starting dose was 40 mg/m2 (1N) and the drug was administered i.v. for 20-30 min, escalating stepwisely up to 1,000 mg/m2 (25 N). The dose limiting factor (DLF) was leukocytopenia, especially neutrocytopenia, and the maximum tolerated dose (MTD) was more than 1,000 mg/m2. Major clinical toxicity was gastrointestinal. Hepatotoxicity and nephrotoxicity were mild. Following administration of the drug, plasma concentrations of total and filterable platinum (Pt) showed a triphasic and biphasic decays. Excretion into urine within 24 hours was in the range of 54.2% to 92.2% of the administered platinum. The recommended dose of phase II study was 800-1,000 mg/m2, repeating every 3-4 weeks.

Adult↗