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Biomedical subjects

S Miyazaki

Publications and source records attributed to S Miyazaki.

At least 1,009 records · Page 56Linked to original sources
PubMedDate not supplied

Acute hemodynamic effects of a new positive inotropic agent, 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212), in conscious and anesthetized dogs.

The acute hemodynamic effects of a new cardiotonic agent, OPC-8212 (a 1H-quinolinone derivative), were studied in six conscious and 11 anesthetized dogs using a pair of ultrasonic crystals to measure the left ventricular segment length and a micromanometer to measure the left ventricular pressure. In six anesthetized dogs subjected to aortic constriction, the ascending aortic flow (AoF) was measured before and after intervention. In the anesthetized state bolus injections of OPC-8212 increased the ejection indices dose dependently. Maximum effects were observed at 1 min, the mean velocity of the circumferential fiber shortening (mean Vcf) being augmented by 6.6% with 0.3 mg, by 39.7% with 1 mg, and by 67.2% with 3 mg. These changes were not accompanied by any significant alteration in heart rate. With aortic constriction, the left ventricular wall shortening was significantly reduced. Depressed pump function was dramatically improved with injection of 3 mg of OPC-8212, the dP/dt was elevated by 98%, the AoF by 46%, and the mean Vcf by 78%. In the conscious state the same doses induced the same type of changes in hemodynamics and dimensions, but the amplitude of the response was significantly less; increase in the mean Vcf was by 36% and that of dP/dt by 52%. Thus, OPC-8212 has a potent inotropic effect. The effect was greater in the anesthetized state, or in dogs with depressed ventricular function, than in the conscious state.

Anesthesia↗
PubMedDate not supplied

Clinical effects of thyrotropin-releasing hormone for severe epilepsy in childhood: a comparative study with ACTH therapy.

We investigated the effects and side effects of thyrotropin-releasing hormone (TRH) on severely epileptic children to evaluate the clinical usefulness of TRH in the treatment of epilepsy and compared them with the results of ACTH therapy. The subjects were 64 patients admitted consecutively between 1980 and 1986. Their seizures were frequent, more than one a day or more than one a week. The subjects were divided into two groups; 33 patients treated with ACTH and 31 treated with TRH. The mean follow-up periods in TRH and ACTH therapy were 8 months and 3.0 years, respectively. The daily dose of TRH-t 0.5-1 mg was administered intravenously (i.v.) or intramuscularly (i.m.) for 1-4 weeks. The follow-up periods were 3-12 months (mean 6 months). In the TRH group, complete control of seizures was achieved in 7 of 13 (53.7%) of those with infantile spasms, and marked improvement of EEGs were observed in 8 of 13 (61.5%) of them. In the ACTH group, seizure cessation was observed in 75% of infantile spasms. Of the patients who received ACTH, 66.7% had various side effects, including pneumonia, huge subcutaneous abscess, hypokalemia, cataracts, and brain shrinkage as shown on computed tomography (CT), whereas only 16.7% of the patients treated with TRH had transient reduction of urine volume without other laboratory and physical abnormalities. The results of the study indicated that some patients who received TRH had cessation of infantile spasms and improved EEG findings with no serious side effect. Because of the untoward side effects of ACTH therapy, TRH is considered a possible new treatment for children with infantile spasms.

Adolescent↗
PubMedDate not supplied

Factors influencing effectiveness of thyrotropin-releasing hormone therapy for severe epilepsy in childhood: significance of serum prolactin levels.

Various factors possibly influencing responsiveness to thyrotropin-releasing hormone (TRH) therapy were studied in 38 children (20 M, 18 F) with severe epilepsy. Mean age at treatment was 4.7 years (range; 0-18 years). Seizure type was infantile spasms (IS) in 16, generalized tonic seizures in 8, secondarily generalized partial seizures in 4, generalized tonic-clonic seizures in 2, atypical absence in 5, myoclonic seizures in 1, and atonic seizures in 2 cases. All seizure types were classified by ictal EEGs documented by simultaneous EEG-VTR according to the International Classification of seizures, except for two with atonic seizures and one with IS. Factors analyzed were sex, age, etiology, neurologic abnormality, seizure types, seizure frequency, EEGs, duration of TRH therapy, and serum hormone [human growth hormone (HGH), prolactin (PRL), thyroid-stimulating hormone (TSH)] levels before and after TRH therapy. We showed that: (a) serum PRL level was significantly correlated to effectiveness of TRH therapy (the higher the PRL, the greater the response rate); (b) serum basal PRL decreased significantly, especially in good responders; and (c) serum basal PRL was elevated especially in patients with IS, which responded more to TRH therapy. These interesting findings seen in severe epilepsy of childhood deserve further neuroendocrinologic study.

Adolescent↗
PubMedDate not supplied

Epilepsy in Angelman syndrome associated with chromosome 15q deletion.

We report eight sporadic cases of typical Angelman syndrome (AS) associated with chromosome 15q12 deletion. Age at first visit was 3-35 months (average 18 months), and follow-up period was 4-20 years (average 14.1 years). The characteristic features of epilepsy in AS are (a) seizure onset in early childhood (8 of 8); (b) evolution of seizure type with age (8 of 8); (c) EEG abnormality changes from high-voltage slow bursts (HVS) in infancy to diffuse spike and waves in middle childhood (4 of 5); (d) atypical absence seizures (8 of 8), often occurring as atypical absence status (4 of 8); and (e) diminution of seizure discharges and clinical seizures after puberty (7 of 7). We believe that AS may frequently exist in the intractable epilepsies of childhood with severe mental retardation. We stress the importance of AS as one of the main etiologic background diseases of the intractable epilepsies with infantile onset such as West syndrome, Lennox-Gastaut syndrome, and others.

Angelman Syndrome↗
PubMedDate not supplied

Prenatal diagnosis of the hemodynamics of fetal renal disease by color Doppler ultrasound.

OBJECTIVE: Hemodynamic analysis of the fetal renal artery elucidated the function of the renal glomerulus and renal tubule in normal growth fetus and was weighed against fetal renal disease. DESIGN: The subjects were fetuses from pregnant women who gave informed consent. There were 6 cases of polycystic kidney, 4 cases of hydronephrosis and 33 cases of fetuses presenting with normal growth. A longitudinal study was performed for normal growth fetuses. Using maximum systolic velocity (V(max)), pulsatility index (PI) and resistance index (RI), the blood flow was measured initially at 20-24 weeks of pregnancy and every 4 weeks thereafter. The measurement was performed 5 times in total. Also, for fetal renal disease, the measurement was performed using the same indexes. RESULTS: In 2 cases of polycystic kidney, which led to death due to postpartum afunctional kidney, V(max) indicated the lower level of less than mean -1.5 SD. In 1 case of single hydronephrosis, the single afunctional kidney was observed postpartum due to blood flow disruption. In 7 cases of normal renal function after birth, it indicated the lower level in some gestational ages but was generally in the normal range. CONCLUSIONS: Using indexes to evaluate the glomerulus and renal tubule of fetal renal disease, mean -1.5 SD of V(max) can be considered to be the lower limit in the normal range and expected to be an important factor for the final outcome.

Female↗
PubMedDate not supplied

In vitro and in vivo activity of DQ-2556, a new cephalosporin.

The antibacterial activity of DQ-2556, a new cephalosporin, was compared with that of cefepime, cefpirome, and other antibiotics. DQ-2556 was more active than cefepime and less active than cefpirome against gram-positive bacteria. DQ-2556 was the most active compound against most members of the Enterobacteriaceae, such as Escherichia coli, Klebsiella, Proteus, Salmonella spp., and Shigella spp., and Haemophilus influenzae and Neisseria gonorrhoeae. In vivo, treatment with DQ-2556 was as or more efficacious than that with reference compounds in both systemic and respiratory tract infections in mice. DQ-2556 achieved higher concentrations than cefepime and cefpirome in lungs and kidney of mice.

Animals↗
PubMedDate not supplied

In vitro and in vivo antibacterial activities of Q-35, a novel fluoroquinolone.

Q-35, a new fluoroquinolone, was evaluated for its in vitro and in vivo antibacterial activities. In vitro antibacterial activity against gram-positive bacteria was almost equal to that of sparfloxacin or tosufloxacin, but its activity against gram-negative bacteria was 2 times or more lower than that of other quinolones tested. In experimental septicemia, the in vivo activity of Q-35 reflected its in vitro antibacterial activity. In respiratory tract infections with Streptococcus pneumoniae TMS-3 in mice, Q-35 showed a therapeutic effect similar to sparfloxacin and tosufloxacin. Q-35 showed almost the same activity as that of ofloxacin in mice with pyelonephritic infection due to Escherichia coli TMS-3. The peak levels of Q-35 in murine serum, lungs and kidneys after a single oral administration were intermediate compared to those of tested quinolones.

Animals↗
PubMedDate not supplied

Role of kinins in the acute antihypertensive effect of the converting enzyme inhibitor, captopril.

The role of kinins in the acute antihypertensive effect of a converting enzyme inhibitor (CEI) was studied in sodium-depleted normotensive and in two-kidney, one clip chronically hypertensive rats (2K-1C). The 2K-1C were on a normal sodium diet. The acute vasodepressor effect of the CEI was determined in these two groups either after administration of normal rabbit globulins or antikinin globulins. The amount of kinin antibodies administered completely blocked the hypotensive effects of bradykinin, 400 ng/kg, and urinary kallikrein, 4 microgram/kg. After administration of CEI in the sodium-depleted rats there was no significant difference (p greater than 0.05) in the acute changes in mean blood pressure (BP) between the group pretreated with normal rabbit globulins (delta BP -32.3 +/- 3.9 mm Hg) and the group pretreated with antikinin globulins (delta BP -25 +/- 2.5 mm Hg). In the 2K-1C pretreated with normal rabbit globulins, the CEI produced a decrease in BP of -21 +/- 4.5 mm Hg. This decrease was almost completely blocked in the group pretreated with the antikinin globulins (delta BP -4 +/- 4.1 mm Hg). These differences in the changes in BP were significant (p less than 0.02). These results suggest that the acute antihypertensive effect of the CEI in the sodium-depleted rats is probably due to inhibition of the conversion of angiotensin I to II while in the 2K-1C it is due, in part, to an increase in kinin concentrations secondary to the inhibition of kininase II.

Angiotensin II↗
PubMedDate not supplied

Role of mineralocorticoid in the chronic antihypertensive effect of converting enzyme inhibitor.

The chronic antihypertensive effect of converting enzyme inhibtor (CEI) may be due to a decrease in aldosterone secretion secondary to blockade of angiotensin II formation. To study this hypothesis, changes in blood pressure (BP), in response to chronic administration of the CEI, captopril, were measured in spontaneously hypertensive (SHR) and in chronic two-kidney, one clip hypertensive (2K-1C) rats. To avoid a decrease in mineralocorticoid activity, half of the rats in these two models of hypertension were adrenalectomized and maintained with daily administrations of deoxycorticosterone acetate and hydrocortisone (steroid replacement) while the other half had the adrenal gland left in situ and no exogenous steroids administered. The doses of steroids used were devoid of hypertensive effect in Wistar Kyoto (WKY), SHR, 2K-1C, and sham-clipped rats. Chronic administration of the CEI decreased the BP to normotensive levels in the SHR with intact adrenals and no steroid replacement. However, the antihypertensive effect of the CEI was almost completely blocked in those SHR with steroid replacement. In contrast, the antihypertensive effect of the CEI in 2K-1C was similar in the rats with steroid replacement and in the rats with intact adrenals (no steroid replacement). These results suggest that the chronic antihypertensive effect of CEI in SHR is due partially to a decrease in aldosterone activity secondary to the blockade of angiotensin II formation, whereas in 2K-1C it is due to mechanisms other than lower mineralocorticoid activity.

Adrenalectomy↗
PubMedDate not supplied

Treatment of chemotherapy-induced neutropenia in children with subcutaneously administered recombinant human granulocyte colony-stimulating factor.

Fifty-six children with various malignancies were treated subcutaneously with recombinant human granulocyte colony-stimulating factor (rhG-CSF, KRN 8601) for neutropenia induced by cancer chemotherapy. Patients received the first chemotherapy without rhG-CSF (control course). In the second course, rhG-CSF was given once daily, starting 3 days after completion of identical chemotherapy (day 3) and continuing until day 12. At day 12, the white blood counts and neutrophil counts were found to be 6.8 and 30 times higher in the rhG-CSF course than in the control course (P = .0001) Nadirs of white blood counts and neutrophils were significantly elevated in the rhG-CSF course (P = .003 and .0001, respectively). rhG-CSF administration shortened the neutropenic period in the majority of patients. Children tolerated the rhG-CSF administration well and we have hereby confirmed that rhG-CSF administration is useful for proceeding with chemotherapy in children with cancer.

Adolescent↗
PubMedDate not supplied

Mechanism of thrombocytosis in hepatoblastoma: a case report.

Although thrombocytosis has long been recognized as a common finding in children with hepatoblastoma, its mechanism is still unknown. In this study, to confirm the role of thrombopoietin (Tpo) in the thrombocytosis in hepatoblastoma, the expression of Tpo mRNA in tumor cells was examined and the serum Tpo level was analyzed during the course of the disease. A 1-year, 6-month-old girl was diagnosed as having advanced hepatoblastoma. At diagnosis, she had marked thrombocytosis with 1220 x 10(9)/microL. After resection of the tumor and after four courses of chemotherapy, the level of alpha-fetoprotein normalized but the platelet count remained high. However, after the fifth course of chemotherapy, the platelet count decreased and normalized within 3 months. By enzyme-linked immunosorbent assay, the serum Tpo level was not high at diagnosis, whereas high Tpo levels were observed after chemotherapy. By polymerase chain reaction, Tpo mRNA was detected in both normal liver and tumor tissues, but the level of expression was not different between them. Therefore, in hepatoblastoma the serum Tpo level is not correlated with a high platelet count, and there is no difference in Tpo expression between normal liver and tumor tissues. Other unknown factors and their production sites to induce thrombocytosis should be examined in further studies.

Female↗
PubMedDate not supplied

Cutaneous infiltration by leukemic cells in acute promyelocytic leukemia of a child after treatment with all-trans retinoic acid.

We describe here the first case of childhood acute promyelocytic leukemia (APL) with cutaneous infiltration of leukemic cells following treatment with all-trans retinoic acid (ATRA) confirmed by immunostaining and polymerase chain reaction for PML/RAR alpha. An 11-year-old girl was diagnosed as having APL. Chromosomal analysis demonstrated the characteristic karyotype of t(15;17). ATRA therapy was begun at a dose of 45 mg/m2 daily. During ATRA therapy, leukocytosis and retinoic acid syndrome were observed but were resolved by dexamethasone. Two months after commencement of ATRA therapy, complete remission was achieved. During the course of consolidation chemotherapy, however, multiple cutaneous nodules developed in her trunk, the size and number of which increased despite intensive chemotherapy. Histological and immunological studies of the cutaneous nodules showed infiltration of leukemic cells. PML/RAR alpha mRNA was detected in both the cutaneous nodules and bone marrow by means of polymerase chain reaction. ATRA treatment for APL may be associated with an increased incidence of extramedullary disease such as cutaneous lesions. The best available therapy for APL may be a combination of ATRA and chemotherapy, especially when a marked leukocytosis occurs during ATRA therapy.

Antineoplastic Agents↗
PubMedDate not supplied

Analysis of thrombopoietin and c-mpl expression in a child with essential thrombocythemia.

The pathogenesis of the increased number of megakaryocytes and thrombocytosis in essential thrombocythemia (ET) is still unknown. We examined the expression of c-mpl, a receptor of thrombopoietin (TPO), and its signaling molecules in a patient with ET. An 8-year-old girl showed a high platelet count and an increased number of bone marrow megakaryocytes. Neither chromosomal abnormalities nor myelofibrosis was observed. Following the diagnosis of ET, aspirin therapy was begun for the patient, with only modest improvement of symptoms. Her platelet count ranged from 1,200,000/microL to 2,200,000/microL for more than 2 years. In the analyses, the serum TPO level in the patient was 420 attomoles/mL (normal, 760 +/- 320). The level of c-mpl expression in bone marrow mononuclear cells was higher in the patient than in healthy children, while there was no difference in the level of c-mpl expression in CD34+ cells, indicating an expanded pool of megakaryocytic lineage cells. The level of Janus kinase 2 (Jak2) expression was lower in the patient than in a healthy child. These findings indicate that the signal pathway mediated by c-Mpl after binding to TPO may be impaired in ET. Further analysis is needed to clarify the mechanism underlying the development of thrombocytosis in ET patients.

Child↗
PubMedDate not supplied

Liver regeneration and restoration of liver function after partial hepatectomy: the relation of fibrosis of the liver parenchyma.

BACKGROUND/AIMS: Patients who survive partial hepatectomy sometimes have unsatisfactory liver regeneration and restoration of liver function. Although the extent of resection should be adjusted to attain favorable liver regeneration and restoration of liver function, a guiding principle for this has not been established. METHODOLOGY: Seventy patients with hepatic tumors associated with liver disorders of various severity who underwent hepatectomy were studied. We calculated the removal rate of the liver and the regeneration rate of the remnant liver using computed tomography. The liver function was investigated using ICG R-15 (retention rate of indocyanine green). Liver disorder was classified into 4 groups, according to the severity of fibrosis. RESULTS: The regeneration rates of the remnant liver indicated a significant decline in patients with severe fibrosis. In the no fibrosis and mild fibrosis groups, an increased removal rate was associated with increased regeneration rate, and post-operative ICG R-15 improved with time. However, in the moderate fibrosis and severe fibrosis groups, an increased removal rate was not associated with increased regeneration rate, and post-operative ICG R-15 showed no change or became worse with time. CONCLUSIONS: Severe fibrosis of the liver parenchyma is associated with poorer regeneration of the remnant liver leading to poor restoration of post-operative liver function. The severity of fibrosis is useful as a predictive factor for liver regeneration and restoration of liver function after partial hepatectomy.

Adult↗