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Biomedical subjects

B K Kim

Publications and source records attributed to B K Kim.

At least 163 records · Page 9Linked to original sources

Procoagulant activity and thrombelastography in Korean hemorrhagic fever.

Twenty male patients with Korean hemorrhagic fever were evaluated with thrombelastography (TEG) to assess the changes in coagulation system, and the results were compared with those of conventional coagulation tests. Procoagulant activity in the plasma was determined by comparing the reaction time "r" of the normal plasma and that of the mixture of equal parts of the normal plasma and the patient's plasma. The TEG was found to be a useful measure of the changes in the coagulation profile, and provided instant accurate assessment of the patient's hemostatic function. Presence of the procoagulant activity was demonstrated in the plasma of the patients and indicated occurrence of active intravascular coagulation during the early stage of the disease.

Adult↗

Seroepidemiology of human T-cell leukemia virus type-I in the Republic of Korea.

We investigated the prevalence of antibodies to human T-cell leukemia virus type I (HTLV-I) associated antigens in various patients and healthy individuals in the Republic of Korea. Seventeen out of 6,255 individuals (0.27%) were seropositive. The positive rate in males was 0.21% and that in females was 0.36%, the sex difference being similar to that in endemic areas in Japan. HTLV-I carriers were found in Seoul and neighboring areas, but not in Busan city or Jeju Island, which are adjacent to Kyushu, Japan. The prevalence of sera with definite anti HTLV-I antibodies seems to be very low in the Republic of Korea.

Adolescent↗

A novel therapeutic approach for reversal of left ventricular hypertrophy and blood pressure control in hypertensive patients treated with alpha-methyldopa or propranolol.

A recently added goal in the control of primary hypertension is the reversal of left ventricular hypertrophy which may occur early in the disease and which can have serious consequences. We have attempted to define the hemodynamic parameters which distinguish most sensitively between the long-term effects of two antihypertensive drugs, alpha-methyldopa and propranolol, with a view to determining the optimal conditions under which each of the drugs may be used therapeutically. Twenty matched hypertensive patients, all with established left ventricular hypertrophy, were divided at random into two groups who received either alpha-methyldopa or propranolol as monotherapy. Dosage was titrated until blood pressures were normalized (diastolic blood pressure (DBP) less than or equal to 95 mmHg) (1 mmHg = 133.322 Pa); then therapy was maintained for 48-52 weeks. Supine and erect blood pressures, heart rates, and eight echocardiographic indices were recorded before commencement of therapy and at the 48- to 52-week period. Stepwise discriminant analysis identified erect DBP, erect heart rate, and posterior wall thickness of the left ventricle as being the parameters which distinguished most clearly the therapeutic effects of the chosen drugs. Using these three parameters, all 20 patients were correctly classified into their respective drug groups. We propose that these results may form the basis of a more rational choice of antihypertensive therapy with alpha-methyldopa or propranolol for hypertensive patients based on the initial determination of these three parameters.

Adult↗

Modulation of right and left ventricular wall thicknesses in experimental hypertension.

Enalapril maleate and hydrochlorothiazide were administered over an 8-week period to groups of Dahl salt-sensitive and Dahl salt-resistant rats receiving either a high (8%) or low (0.4%) salt diet. Regional differences of interventricular septal thickness, left ventricular free wall thickness, right ventricular free wall thickness, right ventricular weight/body weight ratio, left ventricular weight/body ratio, and heart weights were determined. For salt-sensitive rats of both diet groups, lowering of blood pressure induced by either drug was associated with a reduction in cardiac weight which was localized to the left ventricle. For salt-resistant rats, irrespective of diet, the associated reduction of cardiac mass induced by enalapril maleate was largely confined to the right ventricle. Regional changes in tissue thickness were, however, not always associated with corresponding changes in tissue mass or blood pressure. These regional modulations appeared to be quite dependent on salt intake and the nature of the antihypertensive drug, for a given animal type, suggesting that pressure afterload is not the only factor in the pathogenesis of left and right ventricular hypertrophy. The responses of the right ventricle were not necessarily the same as those of the left ventricle to identical dietary and drug regimens. In all animal groups, ventricular mass and tissue thickness did not always change in the same sense, suggesting that alterations in the nature and packaging of the cellular constituents may be induced by the combined actions of the dietary salt and antihypertensive medications.

Animals↗

Storage iron exchange in the rat as affected by deferoxamine.

The initial tissue localization and redistribution of radioactive iron injected intravenously into the rat as ferritin, chondroitin sulfate, and nonviable red cells was determined. Ferritin iron, initially localized in the hepatocyte, showed minimal redistribution over 24 hours in the normal animal. This may be compared with the active release of iron from the reticuloendothelial cell after the intravenous injection of nonviable red cells and chondroitin sulfate iron. All forms of iron were actively mobilized in iron-deficient animals. The effect of chelation of iron by deferoxamine (DFO) on the redistribution pattern over 4 to 6 hours was determined in iron-deficient, normal, iron-loaded, and phenylhydrazine-treated rats to evaluate the effect of iron stores and erythropoiesis. Use of DFO resulted in extensive chelation of radioactive iron within the hepatocyte and greatly reduced the amount of hepatocyte iron available for erythropoiesis. Very little chelation of reticuloendothelial cell-processed iron occurred, and there was little decrease in its utilization for red cell production. Total urinary chelate iron was independent of erythropoiesis but varied in parallel with the iron load of the animal. These studies suggest that DFO does not act on the reticuloendothelial cell but does have at least two sites of action, both of which relate to total storage iron. One involves hepatocyte stores with excretion into the intestinal tract. The other, possibly located at the hepatocyte membrane, results in urinary iron excretion.

Anemia, Hemolytic↗

Diadenosine 5',5'''-p1,p4-tetraphosphate deficiency in blood platelets of the Chédiak-Higashi syndrome.

Diadenosine tetraphosphate (AP4A) is an unusual nucleotide found in a variety of cells, including platelets. It has been suggested that platelet AP4A is stored in the dense granules and is metabolically inactive. We have studied the AP4A content of blood platelets in two patients and three cattle with Chédiak-Higashi syndrome (CHS), a hereditary platelet defect with dense granule deficiency. Acid-soluble extractions of whole blood and platelets were neutralized. The adenosine triphosphate (ATP) level was measured by luminescence technique. To measure the AP4A content, the neutralized extract was treated with phosphomonoesterase for removal of ATP. The AP4A content was then measured by coupling the phosphodiesterase and luciferase reaction. The AP4A content was 0.43 nmol/mg protein for normal human platelets and 0.004 nmol/mg protein for CHS platelets. The ATP/AP4A ratio was 67 for normal and 3,023 for CHS platelets. The whole blood AP4A was reduced by 89% in CHS patients who had only a slight decrease in ATP level (26% reduction). Similarly, bovine platelets with CHS showed a marked decrease of AP4A content and a moderate reduction of the ATP level. The platelet ATP/AP4A ratio was 351 and 3,133 for normal and CHS cattle, respectively. Results demonstrate a marked reduction of AP4A in CHS platelets and suggest that AP4A may be a useful marker for the measurement of dense granule content in platelets.

Adenine Nucleotides↗

Systolic blood pressure responses to enalapril maleate (MK 421, an angiotensin converting enzyme inhibitor) and hydrochlorothiazide in conscious Dahl salt-sensitive and salt-resistant rats.

Systolic blood pressure responses to enalapril maleate (MK 421, a new angiotensin converting enzyme inhibitor (CEI] and hydrochlorothiazide (HTZ) were studied in conscious Dahl salt-sensitive (DS) and salt-resistant (DR) rats maintained on a high salt (8.0% NaCl) and a normal salt (0.4% NaCl) diet. The DS rats were severely hypertensive after 3 weeks on the high salt diet whereas the systolic blood pressure (SBP) of the DR rats were normotensive. Oral treatment with enalapril (15-100 mg X kg-1 X day-1) and HTZ (60-400 mg X kg-1 X day-1) caused a significant reduction of SBP in the DS rats with the high salt diet (P less than 0.001); however, this was not observed until after 4 weeks of treatment when the dosage was 30 and 150 mg X kg-1 X day-1, respectively. Furthermore, enalapril therapy alone significantly reduced the SBP of all groups of rats regardless of diet or Dahl strain (P less than 0.001), but this was not observed until the end of the 7th week of therapy in DR rats on 8.0% NaCl and the end of the 3rd week of therapy for DR and DS rats on 0.4% NaCl. These results suggest that enalapril may lower SBP by mechanisms other than those related to an action as a CEI.

Angiotensin-Converting Enzyme Inhibitors↗

Left ventricular changes after chronic therapy with enalapril maleate in moderate to severe hypertensive patients.

A randomized double-blind trial was carried out to determine the relationship of the changes in blood pressure and heart rate with changes in echocardiographic left ventricular indices in moderate to severe hypertensive patients with established left ventricular hypertrophy who were being treated chronically with enalapril or hydrochlorothiazide plus propranolol for 26 weeks. After a 2-week period on placebo, drug dosages in the two groups were adjusted to individual needs until blood pressure was normalized (diastolic less than 90 mmHg). Patients in Group I received 10 to 40 mg enalapril/day; those in Group II received 50 mg hydrochlorothiazide plus 80 to 240 mg propranolol/day. Echocardiographic measurements were made at the end of the placebo and 26-week active treatment periods. Significant correlations were observed between the changes in four pairs of variables in each group. In the 8 patients receiving enalapril, there were negative correlations between interventricular septal thickness and supine systolic blood pressure, erect and supine heart rates, and a positive correlation between relative wall thickness and erect diastolic blood pressure. In the 7 patients on hydrochlorothiazide plus propranolol, there were negative correlations between relative wall thickness and erect and supine heart rate, and positive correlations between left ventricular mass and erect diastolic blood pressure, and the percentage change in internal diameter of the left ventricle and supine systolic blood pressure. Possible explanations for and implications of these regional changes are discussed.

Adult↗

The correlation of changes in systolic blood pressure with regional anatomical regression of hypertensive left ventricular hypertrophy in patients on chronic antihypertensive therapy (greater than 1 year): alpha-methyldopa compared to propranolol.

Twenty patients with mild to moderate hypertension and evidence of left ventricular hypertrophy (relative wall thickness greater than or equal to 0.45), who previously had not received either alpha-methyldopa or propranolol, were allocated at random to treatment with one or other of these drugs as monotherapy after a 2-week baseline period on no medication. Dosage was titrated until normotension was attained and patients were then maintained on this treatment for a year. Analysis of blood pressure measurements and echocardiograms taken before and during maintenance therapy showed that there were significantly correlated changes in systolic blood pressure and heart rate with left ventricular cavity and regional wall changes during chronic drug administration. In the alpha-methyldopa group there were significant correlations between changes in erect and supine systolic blood pressure and the posterior wall index, and in erect systolic blood pressure and left ventricular mass. In the propranolol group, there were significant correlations between changes in supine systolic blood pressure and interventricular septal thickness, and in erect heart rate and supine systolic blood pressure with the percentage change in internal diameter of the left ventricle. It is suggested that these observations may have important therapeutic implications for hypertensive patients with documented left ventricular hypertrophy.

Adult↗

The reversal of left ventricular hypertrophy with control of blood pressure in experimental hypertension.

The precise mechanisms of hypertensive left ventricular hypertrophy and reversal with antihypertensive drugs are unclear and complex. Enalapril maleate (MK421) and hydrochlorothiazide (HTZ) were used to assess the control of hypertension, and reversal of left ventricular hypertrophy in Dahl sensitive (DS) and Dahl resistant (DR) rats given either a high (8% NaCl), or a low (0.4% NaCl) salt diet. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), left ventricular weight/body weight (LVwt/Bwt) ratio were determined. Both drugs were effective in reducing blood pressure and left ventricular mass in DS rats placed on a high salt diet. For DR rats under the same conditions, only MK421 induced significant lowering of blood pressure. Neither drug caused significant change in ventricular mass. Both DS and DR rats on a low salt diet underwent significant blood pressure reduction with MK421 but not HTZ. Significant regression of the left ventricle was observed only in DS rats treated with MK421. Regression was not observed in DR rats even though MK421 reduced blood pressure to distinctly hypotensive levels. The dissociation of left ventricular mass and blood pressure control observed with both MK421 and HTZ suggests that pressure afterload is not the only factor involved in the pathophysiology of hypertensive cardiac hypertrophy. The mechanisms of anti-hypertensive drug action and salt intake both appear to play a significant if unexplained role.

Animals↗

An appraisal of antihypertensive efficacy and adverse reactions with two drug regimens: enalapril maleate as part of triple therapy compared to conventional triple therapy in moderate to severe hypertension.

A randomized, double-blind, parallel treatment trial was carried out in 24 patients with moderate to severe hypertension to compare the effectiveness and tolerance of two treatment regimens in reducing and maintaining supine diastolic blood pressure below 90 mmHg. Patients in Group I received 10 to 40 mg enalapril maleate per day with the addition of 50 mg hydrochlorothiazide per day and then 250 to 1000 mg alpha-methyldopa per day, if necessary. Patients in Group II received 50 mg hydrochlorothiazide per day with the addition of 80 to 240 mg propranolol and then 100 to 200 mg hydralazine per day, if necessary. Apart from the hydrochlorothiazide dosage which was fixed, the dosage of the other active drugs was titrated incrementally until the target blood pressure level was achieved. Blood pressures, heart rate and body weight were monitored at 2-weekly intervals during 26 weeks of active therapy. In Group I, blood pressure control was achieved and maintained with enalapril alone in 9 patients, 2 patients required double therapy and 1 patient triple therapy. In Group II, 9 patients required double therapy, 2 triple therapy, and only 1 patient received monotherapy. Supine and erect blood pressure control was comparable in both groups. There was, however, a significant decrease in supine heart rate in patients in Group II. More importantly, 8 of the 12 patients in Group II experienced non-life threatening adverse reactions (4 were hypokalaemic and required supplementary potassium, 2 had cold hands and feet, 1 man had sexual dysfunction and 1 acute gout) and no adverse reactions were reported by Group I patients.

Adult↗

Specific HPLC assay for serum nifedipine.

A method has been devised for the sensitive, specific and reproducible estimation of nifedipine in human serum. The assay is based on reverse-phase HPLC of an ether extract of serum at pH 9 using nisoldipine as internal standard. The two compounds are detected and quantitated by spectrophotometry at 350 nm. The mean recovery of nifedipine added to blank serum (60-250 ng/ml) was 70%, with a minimum detectable level of 10 ng/ml. Replicate determinations of patients' serum nifedipine (90-150 ng/ml) yielded coefficients of variation of 3.3%. Twelve drugs and non-prescription medicaments which could be ingested at the same time as nifedipine were assessed for interference with the assay but none were found to do so. The rates of absorption and peak serum levels of nifedipine were compared in normo- and hypertensive subjects who received sublingually a single 10 mg dose of the drug. Half the subjects displayed mean maximum serum levels of 148 +/- 34 ng/ml while the other half achieved only 48 +/- 15 ng/ml. The times required to reach those peak levels varied from 30 min to greater than 60 min. These results suggest that the rate of absorption of this drug varies widely among individuals. No significant differences were observed between the normo- and hypertensive groups.

Chromatography, High Pressure Liquid↗

Cardiac regression and blood pressure control in the Dahl rat treated with either enalapril maleate (MK 421, an angiotensin converting enzyme inhibitor) or hydrochlorothiazide.

Enalapril maleate (MK 421), and hydrochlorothiazide were used to evaluate the control of hypertension and reversal of myocardial hypertrophy in Dahl sensitive (DS) and Dahl resistant (DR) rats given either a high (8% NaCl) or a low salt (0.4% NaCl) diet. Groups of six-week-old male DS and DR rats were treated with enalapril (15-100 mg/kg/day) in drinking water for eight weeks. Additional comparable groups of DS and DR were also treated with hydrochlorothiazide (60-400 mg/kg/day). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and heart weight/body weight (Hwt/Bwt) ratio were determined. We observed significant reduction in Hwt/Bwt ratio (P less than 0.001) along with control of SBP and DBP in the DS given a high salt diet treated with either enalapril or hydrochlorothiazide. However, in the DR given a high salt diet, cardiac regression (Hwt/Bwt ratio, P less than 0.05), SBP and DBP (P less than 0.01) reduction were seen only with enalapril. Similarly, cardiac regression (Hwt/Bwt ratio, P less than 0.05) was observed along with reduction of SBP and DBP (P less than 0.001) in the DS given a low salt diet and DR given enalapril. These data indicate that enalapril reduced SBP and DBP in association with cardiac regression in hypertensive and normotensive rats. In contrast, hydrochlorothiazide only reduced SBP, DBP and caused cardiac reversal (Hwt/Bwt ratio) in DS placed on a high salt diet.

Animals↗

Normal ventilatory movement of the right hemidiaphragm studied by ultrasonography and pneumotachography.

The ventilatory movement of the right dome of the diaphragm was studied over the range of the inspiratory capacity in 50 healthy adults in the supine position using simultaneous ultrasonography and pneumotachography. Regional differences were found in movement of the hemidiaphragm; there was greater movement of the middle and posterior thirds of the diaphragm than of the anterior third. A significant positive correlation was found between body weight and amount of diaphragm movement. An apparently greater degree of movement of the diaphragm was found in males than females; this may be related to weight. About 64% of diaphragm movement has occurred by the time midinspiratory capacity is reached. These data may help to define normal movement and also to differentiate abnormal from normal diaphragm movement.

Adult↗

Disseminated intravascular coagulation in Korean hemorrhagic fever.

To investigate the nature and role of coagulation and complement alterations in the pathogenesis of Korean hemorrhagic fever (KHF), the profiles from the early stages in 27 male patients were serially evaluated. Evidence of disseminated intravascular coagulation (DIC) was observed in 14 of the 27 patients (51.8%) sometime during the course of the disease. The earlier the coagulation tests were performed, the more frequently the evidence of DIC was found. The mean serum C3 concentration was significantly decreased during the early stages, while serum C4 concentrations revealed no significant variation. A significant decrease of the serum C3 concentration, however, was found only in the group with DIC. Korean hemorrhagic fever (KHF) is an acute, systemic disease characterized by fever, hemorrhagic manifestations, and renal failure. This disease has been known to occur from the Pacific Ocean to the Baltic Sea under various synonyms and toponyms including epidemic hemorrhagic fever, hemorrhagic nephrosonephritis and hemorrhagic fever with renal syndrome. Recent investigations demonstrated the identity of these conditions described from Korea, the Soviet Union, Japan, and China. Nephropathia epidemica of Scandinavia was also revealed to have a close serological relation to this disease, but with antigenic differences. The etiologic agent was identified in 1978 by Lee et al., who isolated a viral antigen from a field mouse, Apodemus agrarius coreae, which is the natural reservoir of this disease in Korea. The KHF or Hantaan virus has been propagated in cell cultures and observed electronmicroscopically. In thin sections, the virus was detected within the cytoplasmic granular matrices (viroplasms) of the infected cells. Virus particles were spherical and had an extremely electron-dense core. Negative-contrast staining showed that the virus had an icosahedral structure and annular surface capsomeres. The morphology and morphogenesis of the virus were similar to those of the orbiviruses. The characteristic pathologic findings observed in fatal cases of KHF are congestion and hemorrhage of the renal medulla, hemorrhage in the right atrial wall of the heart, and hemorrhage and necrosis in the anterior lobe of the pituitary gland. The microscopic characteristics of these lesions consist of hemorrhage, coagulation necrosis, and mononuclear cell infiltration. The clinical course of typical KHF may be divided into five phases, each designated for a characteristic physiologic aberration; febrile, hypotensive, oliguric, diuretic, and convalescent.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗