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Biomedical subjects

Y Shin

Publications and source records attributed to Y Shin.

108 records · Page 6Linked to original sources
PubMed1993

Long-term outcome in 134 patients with galactosaemia.

In a retrospective study 134 galactosaemic patients, born between 1955 and 1989 in the Federal Republic of Germany were traced and their long-term outcome evaluated. We investigated 83 galactosaemic patients (78 homozygotes, 5 compound heterozygotes) by clinical, psychometric and laboratory testing; 31 patients were evaluated by medical history, the remaining 20 patients had died due to sequelae of the underlying disease. In 48 out of 78 classical galactosaemia patients galactose-free therapy had been started before the 15th day, in 19 between days 15 and 56 and in 11 patients after the 56th day. Physical findings revealed that puberty was delayed in 1 out of 18 males and 6 out of 11 females. Neurological abnormalities included ataxia (n = 6), intention tremor (n = 11) and microcephaly (n = 10). Speech abnormalities were found in 43 out of 66 patients over 3 years of age and disturbance of visual perception and/or arithmetic deficits in 29. Intelligence declined with age, i.e., a DQ or IQ less than 85 was found in 4 out of 34 patients less than 6 years of age (12%), in 10 out of 18 between 7 and 12 years (56%) and in 20 out of 24 older than 12 years (83%). Metabolite patterns (RBC galactose-1-phosphate and UDP-galactose, plasma and urinary galactitol) did not correlate with DQ or IQ. Dietary compliance was good in almost all patients. Compound heterozygotes (n = 5) had normal mental and growth development and all laboratory parameters were in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Interactions of nonprostanoid trimetoquinol analogs with thromboxane A2/prostaglandin H2 receptors in human platelets, rat vascular endothelial cells and rat vascular smooth muscle cells.

Trimetoquinol (TMQ), a nonprostanoid compound, inhibits thromboxane A2 agonist-induced responses in platelets and vascular smooth muscle. Sixteen TMQ analogs were used to examine the stereochemical requirements of the interaction with thromboxane A2/prostaglandin H2 (TP) receptor sites in human platelets (HP), and cultured rat vascular endothelial (RVEC) and smooth muscle (RVSMC) cells. [3H]SQ 29548 was used as the ligand for TP receptors. The receptor binding affinities of these TMQ analogs for TP receptors in HP, RVEC and RVSMC were highly correlated with each other, and to their reported inhibitory potency values against U46619-induced HP aggregation and serotonin secretion, and contraction of rat aorta. TP receptor binding affinities of TMQ and 8-fluoro TMQ isomers were highly stereoselective (R-isomer > S-isomer), and only the 8-fluoro TMQ isomers gave qualitatively different functional responses in rat aorta. The affinity of TMQ for TP receptors was increased by addition of iodine and fluorine atoms at the 5- and 8-positions of the catechol ring or by replacement of the methoxy groups with iodine atoms on the 1-benzyl ring system. The results indicate that: 1) the stereochemical requirements of TMQ analogs for interaction with TP receptors in these cell systems are the same; 2) although TMQ analogs act as TP receptor antagonists, differences in functional responses by 8-fluoro TMQ isomers in platelets and aorta are not explained by their relative binding affinities to TP receptors; and 3) asymmetric halogenated TMQ analogs should be useful as affinity probes for further characterization of TP receptors.

Adrenergic beta-Agonists↗
PubMed1992

Synthesis of halogenated trimetoquinol derivatives and evaluation of their beta-agonist and thromboxane A2 (TXA2) antagonist activities.

The 5,8-difluoro (4), 5-iodo (5), 8-iodo (6), and 5-trifluoromethyl (7) derivatives of trimetoquinol (TMQ, 1) have been synthesized and evaluated for their ability to stimulate beta 1 (guinea pig atria) and beta 2 (guinea pig trachea) adrenoceptors as well as for their inhibitory activity against U46619 [a thromboxane A2 (TXA2) mimetic]-mediated contraction of rat thoracic aorta and human platelet aggregation. Both 5 and 6 were considerably less active than TMQ on both beta-adrenergic systems and gave a rank order of stimulatory potency of 1 much greater than 6 greater than or equal to 5. Similarly, iodine substitution at either position also caused a reduction in TXA2 antagonist activity with a rank order potency of 1 greater than 6 much greater than 5. Compared to 1, however, 5-iodo-TMQ (5) showed a marked selectivity for blockade of U46619 responses in rat aorta over human platelets. On beta-systems, 4 had reduced potency compared to TMQ and was similarly nonselective. Introduction of a trifluoromethyl group at the 5-position of TMQ completely abolished both beta 1- and beta 2-adrenergic agonist activities while imparting weak antagonist activity on beta 1 receptors. On TXA2 systems, both 4 and 7 possessed significantly decreased inhibitory activity compared to TMQ. The synthetic approaches to the synthesis of 8-(trifluoromethyl)-TMQ (8) are also described. The enantiomers of the 8-fluoro derivative (3) of TMQ were separated on a preparative Chiralcel OD column and evaluated on beta-adrenergic systems and TXA2 systems. On beta-adrenergic systems, (S)-(+)-8-fluoro-TMQ was at least 10-fold more potent than (R)-(-)-8-fluoro-TMQ. Conversely, (R)-(-)-8-fluoro-TMQ was approximately 14-fold more potent as an antagonist of TXA2-mediated aggregation in human platelets than (S)-(+)-8-fluoro-TMQ. In contrast to platelets, (S)-(+)-8-fluoro-TMQ was an agonist in rat aorta whereas (R)-(-)-8-fluoro-TMQ was an antagonist.

Adrenergic beta-Agonists↗
PubMed1991

Pharmacologic antagonism of thromboxane A2 receptors by trimetoquinol analogs in vitro and in vivo.

Although (-)-(S)-trimetoquinol [1-(3,4,5-trimethoxy-benzyl)- 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; TMQ] is recognized as a potent bronchodilator, (+)-(R)-TMQ is a selective antagonist of human platelet aggregation and serotonin secretion induced by thromboxane A2 (TXA2) agonists. To confirm the pharmacological actions of TMQ analogs, the interaction of the drugs with TXA2 receptors was examined in human platelets and in a mouse sudden death model. The inhibitory potencies of TMQ analogs (pIC50 values) for displacement of [3H]SQ 29,548 binding to platelets showed excellent correlation with the respective pIC50 (-log IC50) values for U46619-induced aggregation (r = 0.99, P less than 0.01) and serotonin secretion (r = 0.99, P less than 0.01) in human platelet-rich plasma and for whole blood aggregation (r = 0.99, P less than 0.01). In each system, the rank order of inhibitory potencies was rac-iodoTMQ greater than or equal to (+)-(R)-TMQ greater than rac-TMQ much greater than (-)-(S)-TMQ. Antithrombotic effects of TMQ analogs were evaluated in a mouse sudden death model. In vivo antithrombotic potencies of these compounds were consistent with the in vitro potencies as TXA2 receptor antagonists in platelet systems. Administration of rac-iodoTMQ, (+)-(R)-TMQ and rac-TMQ 15 min before the injection of U46619 (800 micrograms/kg, iv) protected mice against U46619-induced sudden death. On the other hand, (-)-(S)-TMQ did not protect animals against death. Protection of U46619-induced cardiopulmonary thrombosis by TMQ analogs was seen at doses of 3-100 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

Hormonal and circulatory responses to chronically controlled increments in right atrial pressure.

To study the time-dependent changes in the secretion of atrial natriuretic peptide (ANP) in response to chronic stimulation by controlled increments in atrial pressure, we developed methodology for precise control of right atrial pressure (RAP) in dogs by employing an externally adjustable occluder around the pulmonary artery and a servo-control system. During 7 days of servo-control of RAP at 6.3 +/- 0.1 mmHg above control levels (1.3 +/- 0.1 mmHg), the 24-h coefficient of variation in RAP was 1/45 the variation that occurred under control conditions. After 30 min of increased RAP, mean arterial pressure (MAP) was reduced from 101 +/- 4 to 84 +/- 3 mmHg in association with increments in plasma renin activity (PRA) from 0.6 +/- 0.1 to 2.5 +/- 0.9 ng angiotensin I (ANG I).ml-1.h-1 and in the plasma concentrations of ANP, arginine vasopressin (AVP), and epinephrine from 93 +/- 18 to 484 +/- 61 pg/ml, from 0.5 +/- 0.1 to 9.2 +/- 2.4 pg/ml, and from 82 +/- 27 to 585 +/- 133 pg/ml, respectively. In comparison, on day 7 of servo-control of RAP, sodium balance was achieved and MAP remained depressed (82 +/- 4 mmHg) along with sustained increments in both plasma ANP concentration (482 +/- 67 pg/ml) and PRA (1.7 +/- 0.6 ng ANG I.ml-1.h-1); on the other hand, the plasma concentrations of AVP and epinephrine returned to control levels. This quantitative study indicates that ANP secretion does not chronically adapt to stimulation by increased atrial pressure and suggests that the plasma levels of ANP achieved in heart failure markedly increase renal excretory capability and allow fluid balance to be achieved at a substantial fall in renal perfusion pressure.

Angiotensin I↗
PubMed1991

The mechanical properties and solubility of strontium-substituted hydroxyapatite.

The mechanical properties and solubility of sintered Sr-substituted hydroxyapatites were examined in order to investigate the influences of Sr incorporation into hydroxyapatite in bones and teeth on them. Hydroxyapatite (HAp), Sr-substituted hydroxyapatite (Ca.SrAp), and strontium-hydroxyapatite (SrAp) were synthesized and sintered. The bending strength and Young's modulus were measured. Also, solubility in isotonic NaCl solution was examined. The Young's modulus of Sr-substituted hydroxyapatite (Sr wt% = 1.0) and hydroxyapatite surface treated with Sr ion were greater than that of hydroxyapatite. The bending strengths of Sr-substituted hydroxyapatites (Sr/Ca = 4/6 and less) were reduced slightly compared to that of hydroxyapatite. The bending strength of hydroxyapatite surface treated with Sr ion was increased compared to that of hydroxyapatite. The solubility in isotonic NaCl solution at 37 degrees C was increased with an increase in Sr content. The effects of Sr on the mechanical properties and solubility of bones and/or teeth are discussed.

Biomechanical Phenomena↗
PubMed1990

Chronic effects of a physiological dose of ANP on arterial pressure and renin release.

To determine the long-term effects of a physiological dose of atrial natriuretic peptide (ANP) on renin release, the renin response to reductions in renal arterial pressure (RAP) was studied during 1) control conditions and 2) acute and 3) chronic (5 days) intravenous infusion (5 ng.kg-1.min-1) of alpha-human ANP in conscious dogs maintained on a normal sodium intake. Renal perfusion pressure was servo controlled at reduced levels with an inflatable occluder placed around the abdominal aorta just above the renal arteries. Under control conditions, reducing RAP by 30 and 40 mmHg increased plasma renin activity (PRA) 4- to 5- and 9- to 10-fold, respectively. Acute ANP infusion had no significant effect on either basal levels of PRA or the PRA response to reduced RAP. During chronic ANP infusion there was a two- to threefold increment in plasma ANP concentration and approximately a twofold increase in urinary sodium excretion on day 1; however, there were no significant long-term changes in mean arterial pressure, basal PRA, or the levels of PRA achieved during reductions in RAP. These findings indicate that the changes in plasma ANP concentration that occur under normal physiological conditions do not appreciably alter either basal PRA or renin release in response to renal hypotension in conscious sodium-replete dogs studied under resting conditions.

Animals↗
PubMed1987

Sintered hydroxyapatite for a percutaneous device and its clinical application.

The sintered hydroxyapatite was designed to be utilized as a percutaneous device. The device was percutaneously fixed through the back skin of mongrel dogs. The tissue reaction around the implants was examined histologically. At 1 month the sintered hydroxyapatite was closely contacted with the skin tissue and downgrowth of epidermis was not observed. The long-term implantation ranging from 3 to 17 months showed that the depth of epidermis downgrowth was limited to only 1 mm. The amino acid composition of fibrous capsule formed around the hydroxyapatite showed close resemblance to vertebrate periosteum. It was confirmed that the sintered hydroxyapatite had good compatibility and long-term stability with skin tissue.

Amino Acids↗
PubMed1986

Studies on alterations in blood coagulative and fibrinolytic activities after single and multiple administrations of carbon tetrachloride in mice.

The time course of alterations in coagulative and fiblinolytic activities was studied in CCl4-induced liver disease in mice. Liver disease was induced by administration of 20% CCl4 in olive oil (p.o.). After single administration of CCl4, significant prolongation of r and k values and decrease in the ma value of thromboelastogram and apparent prolongation of PT and PTT were seen at 24 hr. Fibrinogen content decreased from 12 to 72 hr after single administration, while a mild but significant decrease in fibrinogen was observed after multiple administrations. The activity of factor XIII increased from 5 to 12 hr and then decreased from 24 to 168 hr after single administration. The activity of the hepaplastintest and Antithrombin III decreased apparently after single and multiple administrations. The plasminogen content and the activity of alpha 2-plasmin inhibitor decreased severely after single and multiple administrations. These results indicate that the coagulative and fibrinolytic activities were decreased to the most lowest value at 24 or 48 hr after single administration of CCl4, and the severe suppression of fibrinolysis and the mild decrease in coagulative activity were observed after multiple administrations of CCl4. The reason for the different effects between single and multiple administrations on coagulative and fibrinolytic systems was discussed.

Acute Disease↗
PubMed1978

One strategy for controlling costs in university teaching hospitals.

Major teaching hospitals, because they treat a more complex mix of patients than do nonteaching hospitals, usually show higher costs per patient day or per case. As a result, teaching hospitals are particularly vulnerable to the decisions of those cost control and planning agencies that are unable or unwilling to treat the problem of case mix. Research at Yale University reported here demonstrates the effect of case mix on costs. A methodology is outlined that can be used by teaching hospitals in determining their costs of treating patients with a complex mix of diagnoses. It is not held that case mix alone explains all of the cost differences between teaching and nonteaching hospitals; but until that factor is isolated and identified, the other contributors to cost variation cannot be examined.

Costs and Cost Analysis↗
PubMedDate not supplied

Probable amniotic fluid embolism during curettage for a missed abortion: a case report.

Diagnosis of amniotic fluid embolism is difficult in a patient under general anesthesia and may initially resemble several other conditions. Successful treatment requires maintenance of adequate cardiac output and oxygenation and prompt heparin treatment of the disseminated intravascular coagulation. The presented case exemplifies another group of patients who are ar risk for amniotic fluid embolism.

Abortion, Missed↗