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Biomedical subjects

T Hatanaka

Publications and source records attributed to T Hatanaka.

At least 109 records · Page 6Linked to original sources
PubMed1991

Influence of isosorbide dinitrate concentration on its skin permeability from adhesive matrix devices.

Adhesive matrix devices containing a model drug, isosorbide dinitrate (ISDN), were prepared with three different types of pressure sensitive adhesives (PSAs). ISDN permeation through excised hairless rat skin from the different devices was measured in vitro. For each PSA type, the steady state permeation rate of ISDN increased proportionally with an increase of ISDN concentration in the PSA and reached a maximum level at a certain concentration. Although the concentrations reaching the maximum skin permeation level varied among PSA types, the maximum rate for each PSA type was largely similar to that for ISDN aqueous suspension. The release rate of ISDN from devices was too fast to influence the skin permeation rate for all devices. In the PSA of devices showing maximum skin permeability, ISDN crystalline was observed by polarizing microscopy and differential scanning calorimetry. These results suggest that the skin permeation of ISDN from adhesive matrix devices was controlled by the thermodynamic activity of the drug in the PSAs.

Adhesiveness↗
PubMed1991

[Biphenotypic acute leukemia with Ph1 chromosome, M-BCR-, myeloperoxidase+, and CALLA+].

A 63 year-old woman was referred to our hospital because of fever and increased number of blasts in the bone marrow. On physical examination she had slight hepatomegaly but no splenomegaly. Laboratory tests disclosed a hemoglobin level of 8.5 g/dl; a WBC count of 13,200/microliter with 26% blasts; a platelet count of 51,000/microliter. A bone marrow aspirate was normocellular with 74% blasts and 37% blasts were stained positive for myeloperoxidase. Cell surface markers for HLA-DR, CD10, CD19, CD13, CD33 were positive. Karyotype analysis revealed 46, XX, t (9q+; 22q-) and 45XX, -7, t (9q+; 22q-). Southern analysis showed rearrangement of immunoglobulin heavy chain but not T cell receptor beta gene. Rearrangements in M-BCR were not detected with 5' or 3' bcr probes. After 2 courses of chemotherapy, blasts decreased to 7% with recovery of normal elements and 11 out of 20 metaphases of the bone marrow cells were normal karyotype. These findings suggest that this case was de novo Ph1 positive acute leukemia which demonstrated both lymphoid and myeloid features.

Acute Disease↗
PubMed1991

[Industrial standards of hose assemblies for use with medical gas systems: safety against collapsing loads].

We experienced troubles caused by mounting an anesthesia machine and a pump oxygenator on an oxygen pressure-resistant hose that connected the central piping system with the anesthesia machine. Therefore, we measured the resistance of 9 types of hose assemblies to collapsing loads by the method in the International Standardization Organization (ISO) 5359. Two types of hose made in the U.S. were highly resistant. On the other hand, 7 types of domestic hose tended to be obstructed with collapsing loads, and 3 of them did not fulfill ISO's criteria. To prevent anesthetic accidents, improvements in the property of hose assemblies and the establishment of their industrial standardization are urgently needed.

Accident Prevention↗
PubMed1990

Embryonic mutation as a possible cause of in utero carcinogenesis in mice revealed by postnatal treatment with 12-O-tetradecanoylphorbol-13-acetate.

Although in utero irradiation at early stages induced a high incidence of somatic mutations at coat color genes in the embryos of a specified tester strain (PT x HT F1) of mice, it was not carcinogenic by itself. However, in utero-irradiated animals did develop skin tumors and hepatomas (but not leukemias) by the postnatal administration of 12-O-tetradecanoylphorbol-13-acetate. The incidence of both tumors and embryonic mutations increased with in utero doses of X-rays. Furthermore, a large reduction of tumor incidence, about 80%, was observed by low-dose-rate irradiation, similar to the 75% reduction in spot size found for embryonic mutations. The tumor nodule size was also dramatically reduced by low-dose-rate irradiation. Consequently, the induced incidence and size of tumors produced by 12-O-tetradecanoylphorbol-13-acetate treatment parallel those which are observed for coat color mutations as expected, because somatic mutations observed in the pigment cells must similarly occur in embryonic cells of other organs. The larger the clone of mutant cells, the greater their chance of becoming tumorigenic by 12-O-tetradecanoylphorbol-13-acetate posttreatment. These results strongly support the recent epidemiological survey showing that adult types of cancers, but not leukemias, are increasing in the atomic bomb survivors exposed in utero, since humans are continuously exposed to a variety of cancer-promoting agents in contrast to experimental animals reared without such exposures.

Animals↗
PubMed1990

Electrically and mechanically elicited blink reflexes in infants and children--maturation and recovery curves of blink reflex.

We studied the electrically and mechanically elicited blink reflexes in 2 groups of subjects, i.e., 237 newborn infants, 25-41 weeks of conceptional age, and 74 children, 1 month-12 years of age. In infants after 25 weeks of conceptional age we could usually induce the early response (R1) and ipsilateral late response (R2), while the contralateral late response (R2') of the electrical blink reflex became apparent after 33 weeks of conceptional age and the frequency of the appearance of R2' reached more than 60% after 38 weeks of conceptional age. After 7 months of age, R2' was usually observed. The R1 latency in full-term newborns was close to adult values, while the R2 and R2' latencies reached adult values at 7-12 years. After 1 year of age the latency of the R2 mechanical blink reflex had a tendency to be shorter than that of the electrical blink reflex. Under 35 weeks of conceptional age, the recovery curves of the blink reflex were considerably different from those of full-term infants, and premature infants showed little or no evidence of inhibition. These results indicate the absence of inhibitory interneurones in premature infants.

Blinking↗
PubMed1990

Auditory brain stem response in newborn infants--masking effect on ipsi- and contralateral recording.

Ipsilateral and contralateral auditory brain stem responses (ABR) were recorded in 10 full-term neonates. We investigated the effect of the masking level on the peak latency and amplitude on ipsi- and contralateral recordings. Clicks were presented at 85 dB HL to the ipsilateral ear and the masking white noise was presented at 75, 65, 55, 45 and 0 dB HL on the contralateral one, respectively. Masking had no significant effect on the ipsi- and contralateral recording in regard to latency and amplitude except for wave CVI (contralateral wave VI). In addition, ABR was recorded in an infant with total unilateral hearing loss. Crossover responses on both sides were observed with-out contralateral masking, but these responses were completely eliminated when 45 dB HL contralateral masking masked the 85 dB HL clicks to the dead ear. Therefore, it is suggested that such crossover responses will contribute to the ipsi- and contralaterally recorded ABR waveform when an ABR recording is carried out without contralateral masking. Our results indicate that contralateral masking is necessary and should be used in cases of unilateral hearing loss.

Audiometry, Evoked Response↗
PubMed1990

Lesch-Nyhan syndrome with delayed onset of self-mutilation: hyperactivity of interneurons at the brainstem and blink reflex.

We studied a case of Lesch-Nyhan syndrome with delayed onset of self-mutilation. Athetotic cerebral palsy and mental retardation were diagnosed at 1 year old, but the disease was not suspected until age 8 years when he began biting his lips and fingers. There was no obvious alteration of catecholamine in urine and CSF. We attempted to induce a series of blink reflexes by electric, mechanical and photic procedures. The R1 amplitude increased and the latency of the R2 shortened compared with controls. This shows that not only orbicularis motoneuron itself, but also uncrossed interneurons, are in a state of hyperexcitability. The contralateral R2 was poor which was in favour of hypoexcitability of the crossed interneurons at the brainstem. The significant large response was obtained by photic procedure which was in favour of hyperexcitability of the motoneurons. Therefore, it is demonstrated that a thorough examination of blink reflexes provides a useful method for examination of a state of the underlying neural activity.

Blinking↗
PubMed1990

Prediction of skin permeability of drugs. I. Comparison with artificial membrane.

In order to measure the contribution of lipid and pore (aqueous) pathways to the total skin permeation of drugs, and to establish a predictive method for the steady state permeation rate of drugs, the relationship between permeability through excised hairless rat skin and some physicochemical properties of several drugs were compared with those through polydimethylsiloxane (silicone) and poly(2-hydroxyethyl methacrylate) (pHEMA) membranes, as typical solution-diffusion and porous membranes, respectively. A linear relationship was found between the permeability coefficients of drugs for the silicone membrane and their octanol/water partition coefficients. For the pHEMA membrane, the permeability coefficients were almost constant independent of the partition coefficient. On the other hand, the skin permeation properties could be classified into two types: one involves the case of lipophilic drugs, where the permeability coefficient is correlated to the partition coefficient, similar to the silicone membrane; and the other involves hydrophilic drugs, where the permeability coefficients were almost constant, similar to pHEMA membrane. From the above results, the stratum corneum, the main barrier in skin, could be described as a membrane having two parallel permeation pathways: lipid and pore pathways. An equation for predicting the steady state permeation rate of drugs was derived based on this skin permeation model.

Animals↗
PubMed1989

[Carcinoma of male breast--with special reference to noninvasive carcinoma].

Seven cases of carcinoma of male breast were reported. The mean age of them was about 65 years, 17 years older than that of female breast cancer. Six tumors out of 7 were located under the areola. By histological examination, 4 of 7 cases were proved to be noninvasive ductal carcinoma, and the others are invasive ductal carcinoma (2 : scirrhous, 1 : solid-tubular). We focused on clinicopathological features of noninvasive carcinoma. There were two points to be mentioned. One is the nipple discharge as a chief complaint, and the other is cyst formation as a macroscopic observation. These features are characteristic to noninvasive carcinoma and contribute to diagnosis. Therefore, for screening the mass of male breast, ultrasonography (U.S.) is most useful. For preoperative final diagnosis, aspiration or smear cytology is essential. In regard to postoperative survival, all of the 3 invasive cases were dead but all of the 4 noninvasive cases are alive. So the prognosis of noninvasive carcinoma of male breast does not appear to be worse than the female one. These observations indicate that the prognosis of carcinoma of male breast can be improved by early diagnosis and appropriate surgical therapy.

Aged↗
PubMed1989

Electroencephalographic changes during interferon therapy in a case of subacute sclerosing panencephalitis.

We treated a case of subacute sclerosing panencephalitis (SSPE) with interferon and observed electroencephalographic (EEG) changes and the clinical condition during the treatment period. EEG studies were carried out more than 30 times over the period of 1 year. It was observed that, especially after the first intravenous injection of interferon, periodic synchronous discharges on EEG completely disappeared and the clinical condition improved, although transiently. We found that interferon has some temporary influence on the course of SSPE.

Adolescent↗
PubMed1989

[A newly devised continuous catheter flush system for arterial pressure monitoring].

Since Gardner et al. demonstrated a useful continuous catheter flush system in 1970, various systems for blood pressure monitoring have been commercialized. However, some problems have not been solved yet, such as hazard of embolism, infarction, unexpected infusion of large amount of fluid etc.. We have introduced a new type of flush system. which consists of disposable plastic unit with a one-way valve newly developed by us (SAT-route) and a syringe pump (Terumo STC-521). Using this system, only 0.5 ml.hr-1 infusion of heparinized saline was sufficient to prevent the formation of thrombus. Flushing was easily achieved by only pushing the purge button of the pump. As a result, simple, safe and high fidelity pressure monitoring was achieved without much altering the waveform of arterial pressure during flushing. The dynamic frequency response obtained from a square wave test was excellent, with natural frequency of about 40 Hz and damping coefficient of about 0.3. This system is useful especially for perioperative management of small children undergoing cardiac surgery, who require an exquisite infusion therapy and fluid restriction.

Blood Pressure Monitors↗
PubMed1988

Auditory brainstem response in neonates--an attempt to reduce the number of stimuli.

We tried to shorten the ABR testing time by reducing the number of stimuli. There was no difference in both the wave form and latency of each wave between 256 times-averaged ABR and 1,024 times-averaged ABR. The total testing time, using 256 stimuli, was about 20 minutes shorter than the testing time using 1,024 stimuli.

Audiometry, Evoked Response↗
PubMed1988

Effect of chlorpromazine on the pharmacokinetics and pharmacodynamics of pentobarbital in rats.

The effects of chlorpromazine (4 mg/kg i.v.) on the disposition and duration of loss of the righting reflex (LRR, sleeping time) produced by intravenous pentobarbital (5 to 50 mg/kg) were studied in rats. The plasma concentration time profile following i.v. administration of pentobarbital alone was reasonably well described by a three compartment open model with Michaelis-Menten type elimination kinetics. The brain to plasma concentration ratio of pentobarbital was 1.5 and was almost constant during the experiment. Coadministration of chlorpromazine significantly reduced the systemic clearance of pentobarbital. Since pentobarbital is eliminated from the body mainly by hepatic metabolism, reduction of systemic clearance reflects the reduction of hepatic metabolism of pentobarbital. The hepatic intrinsic clearance of pentobarbital was decreased from 0.438 to 0.331 l/h by chlorpromazine coadministration. Hepatic blood flow was also decreased significantly, whereas the plasma protein binding and the distribution to the red blood cell were not appreciably altered. The profile of duration of LRR versus the logarithm of the dose of pentobarbital was linear over a 20 to 70 mg/kg dose range irrespective of chlorpromazine coadministration. The awakening plasma and brain concentrations of pentobarbital without chlorpromazine were estimated as 12.4 micrograms/ml and 17.8 micrograms/g, respectively. The sleeping time versus the logarithm of pentobarbital dose under chlorpromazine coadministration was shifted to the left and the slope of the linear portion was also decreased. There was no single value of awakening plasma or brain concentration. Plasma concentration at the end of the action decreased with decreasing dose. These facts indicated that the sensitivity of the central nervous system to pentobarbital might be increased by chlorpromazine. In conclusion, chlorpromazine inhibited the hepatic metabolism of pentobarbital, resulting in significant increases in plasma and brain concentrations. However, this pharmacokinetic change could not fully explain the pharmacodynamic alternation.

Animals↗
PubMed1988

The pharmacodynamic and pharmacokinetic interaction of pentobarbital and chlorpromazine in rats.

The effect of chlorpromazine on the duration of loss of righting reflex (LRR, sleeping time) of pentobarbital and vice versa in a various dosage ranges were studied in rats. The logarithm of the dose versus sleeping time profile of pentobarbital was shifted to the left and the slope of the profile was decreased as the dose of chlorpromazine was increased. The logarithm of chlorpromazine dose versus duration of LRR during pentobarbital coadministration also showed a distinct dose-dependent profile. However, chlorpromazine itself showed ambiguous duration of LRR because the terminal point of the pharmacologic effect, i.e., the recovery of the righting reflex (RRR, the awakening time), was often difficult to determine clearly. The isobolographic method was introduced to describe the drug interaction of pentobarbital and chlorpromazine quantitatively. Assuming that the sites of action of chlorpromazine and pentobarbital were in the brain, the brain concentrations of pentobarbital at RRR were plotted against the brain concentration of chlorpromazine at RRR. The plots showed a hyperbola-like curve, indicating that there was a supra-additive interaction. In order to clarify the relationship between brain concentrations of the two drugs at RRR, a theoretical consideration was made under the following assumptions: (1) chlorpromazine and pentobarbital have a common central depressant effect, (2) the concentration-effect relationship is described by Hill's equation and (3) the mode of interaction of these drugs is simple additive. The results indicated that the isobolographic plot of pentobarbital and chlorpromazine was reasonably described by the theory and that chlorpromazine enhanced the effect of pentobarbital at least in an additive manner.

Animals↗
PubMed1988

A kinetic study of chlorpromazine on the hyperglycemic response in rats. I. Effect of chlorpromazine on plasma catecholamines.

The effect of chlorpromazine (0.5 and 4 mg/kg) on plasma catecholamines (adrenaline and noradrenaline) concentrations was investigated in rats. After an i.v. bolus administration of chlorpromazine, plasma adrenaline and noradrenaline concentrations showed a dose dependent increase. In order to clarify the pharmacokinetics of catecholamines in plasma, i.v. infusion of adrenaline or noradrenaline was also carried out. Plasma catecholamines after i.v. infusion showed typical characteristics of a one compartment model with a zero order production rate of endogenous catecholamines. From the data observed, a mathematical model was constructed to elucidate the relationship between the pharmacokinetics (brain concentrations) and the pharmacologic effect (plasma catecholamines concentrations) of chlorpromazine in rats. The results indicated that the time courses of plasma adrenaline and noradrenaline concentrations after an i.v. administration of chlorpromazine were described reasonably well by a simple pharmacokinetic-pharmacodynamic model.

Animals↗
PubMed1988

Myocardial mechanical and myosin isoenzyme alterations in streptozotocin-diabetic rats.

Fifteen week old male Wistar rats (n = 7) were made diabetic by intravenous injection of streptozotocin (50 mg/kg). Age-matched, untreated male Wistar rats (n = 9) served as controls. Hearts were removed after 5-6 weeks of diabetes, and the isometric developed tension (T) of isolated left ventricular papillary muscles and its first derivative (dT/dt) were measured at a frequency of 0.2 Hz. During testing, the muscles were perfused with Tyrode's solution (Ca2+ concentration was half of normal Tyrode's solution, pH 7.4, 32 degrees C, bubbled with 95% O2 and 5% CO2). In addition, the left ventricular isoenzyme pattern, which is related to myocardial energetics, was determined by pyrophosphate gel electrophoresis. There was no significant difference in isometric developed tension between diabetic and control rats (DM: 2.90 +/- 0.89 vs controls: 2.87 +/- 0.85 g/mm2, mean +/- SD), but in diabetic rats, dT/dtmax decreased significantly as compared with controls (DM: 23.5 +/- 4.2 vs controls: 31.9 +/- 7.9 g/mm2.s, p less than 0.05). Myocardial mechanical responses to isoproterenol (10(-7)M) and dibutyryl cyclic AMP (10(-5)M) also decreased in diabetic rats. The left ventricular myosin isoenzyme pattern shifted toward VM-3 in diabetic rats (VM-3: DM: 74.9 +/- 10.7 vs controls: 9.5 +/- 4.1%, p less than 0.001). These results indicate that diabetes influences myocardial contractility and changes cardiac energetics. Post-receptor processes may play a role in myocardial mechanical responses to catecholamines in streptozotocin-diabetic rats.

Animals↗