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Biomedical subjects

M Kino

Publications and source records attributed to M Kino.

At least 37 records · Page 2Linked to original sources

[Clinical evaluation of a new oral penem, SY5555, in infants and children].

A clinical study was performed on SY5555, a newly developed penem antibiotic, in children. SY5555 was given orally to 14 patients at 19-29 mg/kg/day in 3 doses for 4 to 12 days. Clinical evaluations were made on the 14 patients including 4 with pharyngitis, 7 with tonsillitis, one with urinary tract infection, and 2 with impetigo. Overall clinical effects were excellent in 2, good in 12, with an efficacy rate of 100%. Causative organisms (Staphylococcus aureus and Streptococcus pyogenes) were all eradicated. As to adverse reactions, mild diarrhea was observed in 4 patients. These data suggest that SY5555 is a useful oral antibiotic for the treatment of bacterial infections in children.

Administration, Oral↗

Thiamine disulfide as a potent inhibitor of human immunodeficiency virus (type-1) production.

Thiol and disulfide compounds were tested as an anti-HIV drug against transactivator (Tat)-mediated transactivation of HIV-1. Of all the compounds tested, thiamine disulfide, alpha-lipoic acid, and N-acetycysteine significantly depressed HIV-1 Tat activity. Thiamine disulfide alone in these compounds possessing anti-HIV-Tat activity markedly inhibited production of progeny HIV-1 in acute and chronic HIV-1-infected CEM at nontoxic concentrations of 500-1000 microM. Thiamine disulfide (500 microM) blocked 99.7% of HIV-1 production after 96 hr culture in acute HIV-1 (LAV-1) infection (m.o.i. = 0.002), whereas it inhibited 90-98% of HIV-1 production in chronic-infected cells (CEM/LAV-1, H9/MN, and Molt-4/IIIB). The results suggest that thiamine disulfide may be important for AIDS chemotherapy.

Acetylcysteine↗

[Clinical evaluation of a new parenteral cephem, cefozopran, in children].

Cefozopran (CZOP, SCE-2787), a new parenteral cephem, was evaluated for its antibacterial activity and clinical efficacy. CZOP, 24.0-78.0 mg/kg/day, was given to 11 pediatric patients in 3 dose a day via 30-minute drip infusion. Clinically evaluated were nine patients including 4 with acute pneumonia, 2 with urinary tract infections, 2 with lymphadenitis and 1 with sepsis. Two patients were excluded because of possible non-bacterial infections. Clinical efficacies were excellent in 5, good in 3 and fair in 1. Bacteriological responses were confirmed for 5 strains in 5 patients. Four strains were eradicated, but one strain was not. MICs of CZOP were equal to those of ceftazidime. Side effects or abnormal laboratory test results were observed in 3 patients; diarrhea in 1, elevated GPT in 1 and thrombocytosis in 1, but none of them was significant.

Bacteria↗

Allyl compounds selectively killed human immunodeficiency virus (type 1)-infected cells.

Various allyl compounds were tested as anti-HIV reagents. Of all the allyl compounds tested, allyl disulfide (CH2 = CH-CH2-S-S-CH2-CH = CH2), allyl alcohol (CH2 = CH-CH2-OH), and its ester strongly depressed cell proliferation of HIV-1-infected cells. KC50 (50% killing concentration) of the allyl disulfide and the allyl alcohol were 34 microM and 10 microM, respectively. The allyl alcohol, in particular, completely inhibited cell growth of HIV-1-infected cells by a single injection at a concentration of 40 microM, ultimately killing the viable CEM/LAV-1 cells within 96 hr cultivation. No effect of the allyl alcohol and its esters on cell proliferation of CEM cells, which are a HIV-1 noninfected human T-cell cell line, was observed at the concentration range of 20 to 200 microM under the same experimental conditions. The results suggest that the effect of the allyl alcohol and its esters resulted in remarkable promotion of the cytopathic effect induced by HIV-1 virus.

1-Propanol↗

[Clinical evaluation of a new cephem S-1108 in infants and children].

A clinical study in children has been performed on S-1108, a newly developed cephem antibiotic. S-1108 was given orally to 30 patients, at doses between 8 and 12 mg/kg/day in 3 divided doses for 2 to 10 days. Clinical evaluations were made on 26 patients consisting of 12 patients of pharyngitis, 5 of tonsillitis and of impetigo, one each of bronchitis, cystitis, lymphadenitis and cellulitis. Overall clinical effects were excellent in 10, good in 15, fair in 1 with an efficacy rate of 96%. As to adverse reactions, mild diarrhea (2 patients) and transients elevation of transaminases (one patient) were observed. These data suggest that S-1108 is a useful oral antibiotic for the treatment of bacterial infections in children.

Administration, Oral↗

[Clinical evaluation of a new oral cephalosporin, cefprozil, in pediatrics].

Cefprozil (CFPZ, BMY-28100), a new oral cephalosporin, was evaluated for its antibacterial activity and clinical efficacy. Thirty-four patients were treated with 7.7-36.2 mg/kg per day of CFPZ divided into 3 times. A total of 33 patients including 3 with acute pneumonia, 2 with acute bronchitis, 17 with acute upper respiratory tract infections, 4 with urinary tract infections, 1 with suppurative lymphadenitis and 6 with other soft tissue infections were evaluated for clinical efficacy except for 1 patient whose general conditions were too serious to continue to be treated with orally medication. Clinical effects were excellent in 8 patients and good in 23 but 2 cases were excluded because they were suspected for viral infections, hence the overall efficacy rate was 100%. Bacteriological responses were confirmed on 6 (66.7%) strains which were eradicated by the treatment out of 9 strains identified. CFPZ showed stronger antibacterial activities than those of cefaclor. Side effects or abnormal laboratory test results were observed in 2 patients; nausea and pallor of face in 1 patient and an increase of eosinophil in 1. The above findings suggest that CFPZ is a safe and useful antibiotics for the treatment of bacterial infections in pediatric patients.

Age Factors↗

Platelet-activating factor detected in bronchoalveolar lavage fluids from an asthmatic patient.

It recently has been recognized that platelet-activating factor (PAF) may be a mediator of asthma exacerbation. We had the opportunity to analyze bronchoalveolar lavage fluids from an asthmatic infant, which were characterized by neutrophil infiltration. The patient's lungs were washed on three occasions with saline during asthmatic attacks. PAF was found in each case on the basis of its ability to cause the immediate aggregation of washed rabbit platelets. The PAF detected was equivalent to 1-1.4 pmol of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine, three quarters of which were recovered in cell-associated form. By contrast, we did not detect PAF in bronchoalveolar exudates from patients with laryngeal stenosis or with respiratory distress syndrome. LysoPAF, the direct precursor as well as initial metabolite of PAF, was also analyzed after being converted to PAF by acetylation. There was a wide variation in the amount of lysoPAF present in individual patients, suggesting that lysoPAF levels cannot be taken as an indicator for the presence of PAF.

Asthma↗

[Pharmacokinetic and clinical study of cefpirome in children].

Pharmacokinetic and clinical studies of cefpirome (CPR) in children were carried out, and the following results were obtained. 1. Peak serum levels were obtained at the end of drip infusion of 20.0, 17.5 and 6.8 mg/kg for 30 minutes and the half-lives were 1.93, 1.91 and 0.48 hours, respectively. 2. Urinary excretion rates in 6 hours were 40.0-96.2%. 3. Thirty-two patients including 17 with respiratory infections, 7 with urinary tract infections and 8 with skin and soft tissue infections were treated with CPR at 52.2-92 mg/kg per day by intravenous administration. Clinical effects were excellent in 12 cases, good in 13 cases, fair in 3 cases and unknown in 4 cases, and the overall efficacy rate was 89.3% (25 cases/28 cases). 4. Bacterial eradication rate was 93.8% (15 strains/16 strains). 5. Rash and diarrhea were found in 1 case each, and abnormal laboratory test values were found in 7 cases.

Adolescent↗

Cardiorenal effects of an orally active dopamine prodrug (TA-870) in patients with congestive heart failure.

The effects of TA-870, a newly synthesized orally active dopamine prodrug, on the cardiorenal functions were investigated in 12 patients with severe chronic congestive heart failure. A single oral dose of TA-870 (1,200 mg) improved left ventricular fractional shortening and mean circumferential velocity on M-mode echocardiography (p less than 0.01 for both). Renal plasma flow and glomerular filtration rate improved with TA-870 (p less than 0.01 and p less than 0.05, respectively); urine volume and sodium excretion increased (p less than 0.01 for both). Blood pressure and heart rate did not change during the 4-h experimental period. Mean plasma free dopamine levels peaked 1 h after dosing. These data suggest that the cardiorenal effects of oral TA-870 are comparable with those of continuous intravenous injections of dopamine. Thus, TA-870 appears to be a useful alternative drug to intravenous dopamine.

Adult↗

Recurrent bacterial meningitis. Secondary to malformation of the inner ear.

A 5-year-old girl with congenital sensorial deafness experienced four episodes of bacterial meningitis in a 13-month period. On the fourth episode, an extensive search for the cause of recurrent meningitis was conducted. Complete immunologic studies, humoral, cellular, and phagocytic, yielded negative results. Precise otological examination, i.e., skull roentgenograms, an inner ear target CT scan, and puncture of the eardrum, was attempted, which disclosed the inner ear malformation (Mondini's anomaly) and a cerebrospinal fluid (CSF) fistula. CSF discharge from the oval window was repaired surgically. Extensive otologic evaluation should be conducted in patients with recurrent bacterial meningitis.

Cerebrospinal Fluid Otorrhea↗

[Clinical and pharmacokinetic evaluation of cefodizime in children].

Cefodizime (CDZM, THR-221), a new cephem antibiotic, was investigated for its clinical efficacy and pharmacokinetics in children. The results obtained are summarized as follows. 1. Antimicrobial activities Antimicrobial activities of CDZM against clinically isolated organisms were determined. MICs of CDZM against 1 strain each of Streptococcus pneumoniae, Escherichia coli and Klebsiella pneumoniae were 0.05 micrograms/ml to 0.10 micrograms/ml. Especially, MIC against all 6 strains of Haemophilus influenzae was less than or equal to 0.024 micrograms/ml. This MIC value was lower than those of other antibiotics such as cefotaxime, cefotiam, cefazolin, piperacillin. 2. Pharmacokinetics CDZM was given to 1 case at a dose of 20 mg/kg by a 60-minute intravenous drip infusion. The peak value of serum concentration of CDZM was 207.80 micrograms/ml at the end of the infusion. The half-life was 2.15 hours. The mean urinary excretion rate was 68.5% in the first 4 hours, 79.2% in 6 hours and 76.5% in 8 hours after the 30-minute drip infusion. 3. Clinical efficacy CDZM was given to a total of 27 patients, 13 with pneumonia, 1 with bronchitis, 2 with acute pharyngitis, 1 with purulent tonsillitis, 5 with urinary tract infection, 1 each with retrograde cholangitis, acute enteritis, pericementitis, phlegmon and inguinal lymphadenitis. Overall clinical efficacies were excellent in 5 cases, good in 17 and the efficacy rate was 81%. Bacteriological effects were investigated in 13 cases and the eradication rate was 85%. No adverse reactions were observed in any case. As abnormal laboratory findings, elevated GOT, GPT, A1-P, LAP and gamma-GTP, were noted in 1 out of the 28 cases examined.

Adolescent↗

Refined evaluation of the exponential curve parameters and initial exchange rate constant for 22Na+ washout in cultured human skin fibroblasts.

A technique is proposed to evaluate the exponential curve parameters and the initial exchange rate constant (kie) for 22Na+ washout from cultured human skin fibroblasts. After loading with the isotope, the cells were subjected to cold washing and warming steps. A desaturation curve for 22Na+ washout was developed including the activity in the warming medium that corresponded to t = 0 min. Using nonlinear regression analysis, a general three exponential function adequately described the 22Na+ washout in the time interval of 0-70 min. A back extrapolation was performed to estimate the initial time (ti; a negative number) when the total activity was present in the cells. The ti was substituted into the first derivative function of the three exponents to yield the kie. Calculated from the equilibrium distribution of 22Na+ and the specific activity of the medium, the concentration of Na+ (in mM; mean +/- SD) for fibroblasts of two individuals were 13.3 +/- 2.3, n = 3, and 19.0 +/- 5.2, n = 4. This indicates that the washout originated mainly or exclusively from the cellular milieu. Therefore, the kie represents the equilibrium exchange rate constant for Na+ washout from an inhomogeneous cell-related space. Multiple experiments demonstrated that the kie value for the two subjects were significantly higher than the initial slopes of the washout curves (kA), a commonly used parameter to characterize Na+ washout, and significantly lower than the slopes of the fastest exponential components (k3): kie = 0.531 +/- 0.017, kA = 0.502 +/- 0.019, and k3 = 0.557 +/- 0.017 min-1 (n = 3) for one subject, and kie = 0.567 +/- 0.065, kA = 0.479 +/- 0.031, and k3 = 0.667 +/- 0.094 min-1 (n = 6) for the other subject. The respective equilibrium exchange rates for these cells, namely the products of kie and cellular Na+ contents, were 1.10 +/- 0.16 and 1.19 +/- 0.24 nmole/10(5) cells. Using the exponential curve parameters, analytical solutions of a serial model and a parallel model with three compartments were performed. According to these analyses the major portion of the cellular Na+ comprises a fast exchangeable cellular compartment. The relative size of this compartment (expressed as a fraction of total cellular Na+ content) for fibroblasts of the two subjects was 96.2 and 89.2% for the serial model and 96.1 and 89.3% according to the parallel model.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Angiotensin II effect on 22Na+ transport in vascular smooth muscle cells.

It is well established that angiotensin II (AII) rapidly increases free cytosolic Ca2+ in vascular smooth muscle cells (VSMCs). Several studies have indicated that the hormone also plays a role in Na+-K+ regulation of these cells. In this study, we explored the mechanism of AII effect on 22Na+ transport in cultured rat VSMCs. The 22Na+ washout from these cells was described by three exponents with exponential factors k1 greater than k2 greater than k3. In 1.8 mM Ca2+ medium, AII (10(-9)-10(-6) M) increased (in a dose response manner) the k1 value, and consequently the initial washout rate constant (kei) for the isotope. AII had no effect on kei in Ca2+-deficient medium or in the presence of ouabain. Amiloride (10(-3) M) and verapamil (10(-5) M) abolished the AII induced increase in kei. These findings are consistent with angiotensin II stimulation of an amiloride-sensitive Na+ transport, which is likely to represent the Na+/H+ antiport. In cultured VSMCs, the sustained stimulation by AII of this transport system requires the presence of extracellular Ca2+ and its influx into these cells.

Amiloride↗

Effect of acute serum depletion on Na+-K+ homeostasis in cultured human skin fibroblasts.

In order to elucidate changes in cell transport behavior of cultured human skin fibroblasts in response to acute serum depletion, we performed uptake and washout of 22Na+ and 86Rb+ as well as measurements of the intracellular Na+ and K+ levels in the presence and absence of ouabain. Pronounced and lasting increase in cellular Na+ and decrease in K+ were observed after removal of fetal bovine serum (FBS) from the medium. The sum of the Na+ and K+ contents (nEq/10(5) cells) was lower in FBS-free medium (mean +/- SD; 17.3 +/- 2.2) than in FBS-containing medium (26.2 +/- 3.8; P less than .02). Simultaneously, a decrease in cellular water volume was detected in the FBS-free medium. The cation uptake and washout data suggest that FBS removal primarily renders the cells more permeable to Na+ and K+ with a secondary stimulation of the ouabain-sensitive Na+ extrusion mechanism. FBS at a concentration of 0.2% prevented approximately 50% of the maximal increase in the 86Rb+ washout rate constant associated with FBS depletion. Ouabain (2 microM) produced an increase in the 86Rb+ washout rate constant. This effect was substantially larger in cells subjected to medium without FBS (from 0.0303 to 0.2500 min-1) than in fibroblasts incubated in medium with FBS (from 0.0107 to 0.0487 min-1). The cellular K+ content was drastically reduced by ouabain to a level not different in medium with or without FBS (33.9 +/- 4.5 to 1.75 +/- 0.38 and 16.7 +/- 1.4 to 1.4 +/- 0.13 nEq/10(5) cells, respectively). The 22Na+ washout data exhibited a three-exponential pattern. Analytical solutions of the washout data by means of two models (serial and parallel) with three compartments showed that FBS depletion resulted in increase of the size of all three compartments. It is concluded that in cultured human skin fibroblasts, FBS is essential to the maintenance of a normal Na+ and K+ homeostasis. The removal of FBS results in dramatic permutation of this homeostasis that develops within minutes and lasts for hours.

Adult↗

Functional and histopathologic correlation in patients with dilated cardiomyopathy: an integrated evaluation by multivariate analysis.

To correlate left ventricular function and histologic features in patients with dilated cardiomyopathy, precise indexes of hemodynamics and semiquantitative histologic data were combined for multivariate analysis. Right endomyocardial biopsy was performed at the time of cardiac catheterization. Five hemodynamic indexes were used for functional assessment: ejection fraction, ratio of end-systolic stress to volume index, end-diastolic stress, time constant (T) of left ventricular pressure fall, and end-systolic stress. Six histologic findings (disarray of myofibers, hypertrophy of myofibers, scarcity of myofibrils, nuclear changes of myofibers, vacuolization of myofibers and proliferation of collagen fibers) were graded from (-) to (4+). Each finding was assigned to category (-) or (+) according to the absence or presence of significant abnormality. Ordinary statistical analysis revealed that, although ejection fraction was lower in category (+) for proliferation of collagen fibers, ratio of end-systolic to volume index was reduced for category (+) of hypertrophy of myofibers. A significant correlation was present between hypertrophy of myofibers and proliferation of collagen fibers by Spearman rank correlation. When principal component analysis was applied to the hemodynamic data, two principal components could be extracted. Fisher's discriminant analysis could clearly differentiate two categories (-) and (+) in the semiquantitative histologic finding of proliferation of collagen fibers. The analysis indicated that contractility was reduced with elevated afterload in that category (+). Thus, proliferation of collagen fibers may play a pivotal role in deteriorating contractility in patients with dilated cardiomyopathy.

Cardiomyopathy, Dilated↗

Multifactorial evaluation of blood pressure fall upon hospitalization in essential hypertensive patients.

1. Studies were prospectively performed on 72 hospitalized patients with essential hypertension. Blood pressure was normalized within 1 week of admission in 33 patients (group I), but did not decrease in 39 patients (group II). To determine the factors that differentiate group I from group II, cardio-renal haemodynamic and endocrinological indices were evaluated using multivariate analysis. 2. Systolic, diastolic and mean blood pressures on admission were higher in group II (P less than 0.001), whose optic fundi showed more severe changes (P less than 0.001). Although group II had greater left ventricular posterior wall thickness (P less than 0.02), left ventricular mass index (P less than 0.05) and systemic vascular resistance (P less than 0.01) on echocardiography, their cardiac index and ejection fraction were comparable with those of group I. 3. Renal blood flow (P less than 0.05) and glomerular filtration rate (P less than 0.01) were lower in group II than in group I. Renal vascular resistance was more elevated (P less than 0.01) in group II than in group I. 4. After severe sodium depletion and ambulation, group I showed a greater increase in plasma noradrenaline and adrenaline (P less than 0.05). On multivariate analysis, those with lower systolic blood pressure, better renal function and more reactive sympathetic nervous system were discriminated as group I. 5. These data suggest that group I patients have lower systolic blood pressure on admission, greater sympathetic reactivity and better renal function, all of which contribute to their spontaneous blood pressure fall after admission.

Adult↗

Intravenous isosorbide dinitrate infusion in the management of unstable angina pectoris refractory to conventional medical therapy.

During the past 2 years, 102 patients were treated for unstable angina pectoris (AP) in our department. Fifteen of them had recurrent chest pain at rest despite treatment with various anti-anginal agents, or prolonged chest pain unresponsive to sublingual nitroglycerin; they received intravenous isosorbide dinitrate (ISDN) infusion. A rapid bolus injection of 2 to 6 mg followed by an infusion of 2 to 5 mg/hr was given to 10 patients with acute chest pain, and 5 patients, who were free of chest pain at the time, but had repeated episodes of angina in the past 24 hours, were given ISDN infusion without a bolus injection. Chest pain disappeared completely in 13 patients, but recurred in 2 of them when the dose was tapered. Two other patients experienced recurrent chest pain during ISDN infusion, and additional boluses were given. The hospital course was uneventful in 11 patients. Four patients who had recurrent anginal attacks underwent emergency coronary cineangiography under intraaortic ballon counterpulsation and aorto-coronary bypass surgery. There were no hospital deaths, no one had subsequent acute myocardial infarctions, and only 2 patients had mild to moderate headache as a side effect. Although the patient population is small, intravenous ISDN infusion is useful in the management of severe unstable AP.

Acute Disease↗

[Noninvasive estimation of left ventricular end-systolic pressure].

A method for noninvasively determining left ventricular (LV) end-systolic pressure (ESP) using carotid pulse tracings and cuff-measured blood pressure was re-evaluated. It was validated during diagnostic cardiac catheterization in 60 patients with cardiovascular diseases. LVESP calculated by this method and systolic blood pressure measured by the cuff were compared with aortic dicrotic notch pressures obtained by a catheter-tip manometer system as true LVESP. The calculated ESP was measured by the following formula; [the ratio of the excursion of dicrotic notch (b) to the peak (a) in carotid pulse tracings: (b/a) x pulse pressure] + diastolic blood pressure. This calculated ESP had a high correlation coefficient with true ESP invasively measured (r = 0.96), but was estimated to be 5.3 +/- 5.0 mmHg less than true ESP. Systolic blood pressure, used as a noninvasive index of ESP, accurately estimated ESP, but it was higher by 14.8 +/- 11.2 mmHg (r = 0.84). Calculated ESP measured by the present method was not affected by age or systemic vascular resistance. This is a reliable noninvasive means of estimating LV end-systolic pressure. Compared with the peak arterial pressure, this is a better parameter for the analysis of LV contractility, such as stress-shortening, and end-systolic pressure-volume relations.

Adolescent↗