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Biomedical subjects

T Ihara

Publications and source records attributed to T Ihara.

At least 109 records · Page 6Linked to original sources
PubMed1994

[Pharmacokinetic and clinical studies of cefozopran in the field of pediatrics].

Cefozopran (CZOP) was administered intravenously to 22 infants (aged 3 months to 15 years) with infections excluding suppurative meningitis in doses of 10 to 40 mg/kg 3 to 4 times daily for periods of 3 to 16 days and its efficacy and safety in infantile infections as well as pharmacokinetic parameters were determined. The half-lives of CZOP after intravenous administration at doses of 10, 20 and 40 mg/kg were 2.84, 2.36 +/- 0.67, and 2.48 hours, respectively. The rates of recovery in the urine within 6 hours of administration were 83.6%, 62.9 +/- 23.1%, and 77.3%, respectively. The subjects for whom drug responses were evaluable consisted of 1 case of suppurative meningitis, 8 cases of respiratory tract infection, 2 cases of urinary tract infection, 2 cases of oral infection, 2 cases of pharyngotonsillitis, 1 case of skin soft tissue infection, and 1 case of external otitis, totaling 17 cases. The efficacy rate was 88.2%. The drug proved so effective on suppurative meningitis in particular that the patient was healed without leaving any sequela behind. Seven strains were identified as causative pathogens (5 strains of Haemophilus influenzae, 1 strain of Staphylococcus aureus, 1 strain of group B Streptococcus) isolated from 6 patients. All but 1 strain were eradicated (the rate of eradication 83.3%). In the patients with suppurative meningitis the bacterial count of spinal fluid was markedly decreased 6 hours after drug administration and the organism was eradicated in 45 hours. Eruption was noted in 1 patient as a side effect of CZOP, but disappeared soon after discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Experience of fluconazole granules and injection in pediatric patients].

Fluconazole (FLCZ) is an antifungal agent of triazole class and has been proven to be effective against deep-seated mycosis caused by Candida spp., Aspergillus spp. and Cryptococcus spp. This time, as we had an opportunity to use fluconazole granules, a new dosage form of the agent, we investigated its efficacy and safety in children with deep-seated mycosis together with the efficacy of the injectable form of the agent. FLCZ was administered to 6 patients with fungal infections for treatment and 5 compromised hosts with a high risk of fungal infections for evaluation of its prophylactic effect. The patients enrolled in the study were 11 in total, of whom 6 patients were evaluated for efficacy: fungal phlegmon in 2, esophageal candidiasis in 2, fungal bronchitis in 1 and oral mycosis in 1. Causative fungi for those infections were Candida albicans in 4 patients, Aspergillus, fumigatus in 1 and Aspergillus flavus in 1. The clinical efficacies were excellent in 3 patients and good in 3. The mycological efficacies were rated as eradicated in 5 patients and reduced in 1. In 5 patients to whom FLCZ was given prophylactically, development of neither fungal infection nor unknown fever was noted. No side effects nor clinical laboratory abnormalities were observed during treatment with either granules or injection, indicative of its safety in children.

Administration, Oral↗
PubMed1993

Ten-year survey of the intellectual deficits in children with acute lymphoblastic leukemia receiving chemoimmunotherapy.

Effects of chemoimmunotherapy, including cranial irradiation for central nervous system (CNS)-directed therapy, on children with acute lymphoblastic leukemia (ALL) were investigated. Fifty-five children with ALL in continuous complete remission (> 5 yr) and without evidence of current or past CNS diseases were evaluated in this retrospective study. Using standard measures of intelligence (IQ), we repeatedly (1-4 times/person; mean 2.1 times) evaluated IQ in the cohort of patients for the mean follow-up time of 9.7 yr, ranging from 5.4 to 15.8 yr. Fifty-five patients received the total number of 118 IQ testings and 40 patients received them more than twice. Patients were examined periodically at intervals of 1.4 to 10.0 yr (mean 4.8 yr) following diagnosis. Most of the published studies dealt with single IQ testing, and long-term follow-ups were not enough to assess the consequent IQ change. This report confirms and extends the previous findings: decreased IQ was related to age at diagnosis and irradiation (< 5 yr of age at diagnosis), irradiation-examination interval, and female sex. Further long-term follow-up study will be needed in these groups, since their IQs are still on the decline even after 10 yr of diagnosis.

Adolescent↗
PubMed1993

Increase of interleukin 2 receptor and CD45RO antigen on lymphocytes cultured with human cytomegalovirus.

To determine the expression of interleukin 2 receptor (IL-2R) and the change of CD45RA and CD45RO antigen on lymphocytes in response to human cytomegalovirus (HCMV), peripheral blood mononuclear cells (PBMC) were cultured with HCMV antigen, and the expression of IL-2R and of CD45RA and CD45RO antigens on lymphocytes was analyzed by flow cytometry. The expression of IL-2R alpha (p55) and -beta (p75) was significantly increased on T cells obtained from CMV-seropositive donors following culture with the CMV antigen. An increased expression of IL-2R alpha and -beta was observed on both CD4+ and CD8+ cells, but the percentage of cells that expressed IL-2R was higher in CD4+ cells. The percentage of CD45RA+ cells was decreased and the percentage of CD45RO+ cells, especially of CD4+CD45RO+ cells, was increased when cultured with the CMV antigen. These observations suggest that switching of CD45RA+ cells to CD45RO+ cells occurred following stimulation with the CMV antigen. The expression of IL-2R and the activation of memory T cells are important to the recovery from and the protection against CMV infection.

Adult↗
PubMed1993

Role of pseudorabies virus glycoprotein II in protection from lethal infection.

A monoclonal antibody (mAb), named 1.21, with complement-dependent neutralizing activity was produced against glycoprotein II (gII) of pseudorabies virus (PRV). By immunoaffinity chromatography using a mAB 1.21 column, gII was purified from Nonidet P40-lysates of PRV infected BHK21/13 cells. When mice and pigs were immunized with purified gII, complement-dependent virus-neutralizing antibodies were produced. The immunized animals survived potentially lethal challenge with PRV. These results indicate that an immunological response against gII plays an important role in the protection from PRV infection.

Animals↗
PubMed1993

Inhibition of varicella-zoster virus (VZV) glycoprotein expression by a human monoclonal antibody against VZV glycoprotein III.

Effects of human monoclonal antibodies (MAbs) against varicella-zoster virus (VZV) glycoproteins (gp) on VZV glycoprotein expression were analyzed by flow cytometry. Human embryonic fibroblast (HEF) cells were inoculated with cell-free VZV and cultured in the presence of human MAbs. While human MAbs directed against gpI (V2) and -II (V1) did not affect VZV expression, a human MAb against gpIII (V3) inhibited expression of VZV gpI, -II, -III, and -IV. V3 also inhibited spread of VZV from infected to uninfected cells. Interferon-alpha, -beta, and -gamma and tumor necrosis factor-alpha were able to synergize with V3 and inhibit VZV gp expression. These results suggest that human MAb V3 may be useful for passive prophylaxis against VZV infection and for treatment of severe VZV infection.

Antibodies, Monoclonal↗
PubMed1993

Exhaustion of Frank-Starling mechanism in conscious dogs with heart failure.

The goal of this study was to elucidate the ability of the left ventricle to accommodate an increase in preload (Frank-Starling mechanism) in the presence of congestive heart failure (CHF) but in the absence of the complicating effects of hypertrophy and fibrosis. To accomplish this, the effects of volume loading were examined in eight conscious dogs during the control state and after 3 wk of right ventricular pacing (240 beats/min). CHF increased heart rate (by 16 +/- 5 from 92 +/- 5 beats/min), left ventricular (LV) end-diastolic pressure (by 17 +/- 2 from 10 +/- 1 mmHg), and LV end-diastolic volume (EDV; by 23 +/- 4 from 57 +/- 3 ml). Despite reduced LV ejection fraction (from 54 +/- 3 to 31 +/- 3%), there was no significant change in cardiac output (2.5 +/- 0.3 l/min) compared with control (2.7 +/- 0.2 l/min). Stroke volume was preserved (control 19 +/- 2 ml; CHF 18 +/- 2 ml) at a constant heart rate by a shift to the right in the relationship between LV stroke volume and EDV, indicating the importance of chronic ventricular dilatation in maintaining pump performance. In the control state, acute volume load increased LV EDV (by 17 +/- 2 ml) and stroke volume (by 11 +/- 2 ml), whereas in CHF it did not increase LV EDV or stroke volume. Scanning electron microscopy revealed areas of reduced collagen weave pattern surrounding myofibers. Myocyte cross-sectional area by transmission electron microscopy was significantly reduced, and there were multiple electron-dense expansions of the Z lines with disruption of the normal lateral sarcomere alignment. These morphological findings suggest that chronic ventricular dilatation utilized in CHF results from myocyte stretch and morphological intracellular rearrangement. Furthermore, the failing heart cannot further augment stroke volume by acutely increasing EDV in CHF, suggesting that the Frank-Starling reserve is essentially exhausted.

Animals↗
PubMed1993

Cholinergic modulation of the coronary vasoconstriction induced by cocaine in conscious dogs.

BACKGROUND: The effects of cocaine on the coronary circulation were examined in conscious dogs chronically instrumented to measure arterial and left ventricular pressures, coronary blood flow, and arterial and coronary sinus oxygen content. METHODS AND RESULTS: With heart rate held constant, the peak effects of cocaine (1 mg/kg i.v.) occurred within 2 minutes, when mean arterial pressure increased by 42 +/- 5 mm Hg, coronary blood flow increased by 13 +/- 3%, and coronary vascular resistance increased by 24 +/- 3%. The arterial oxygen content increased significantly (by 2.8 +/- 0.3 vol%), the arterial-coronary sinus oxygen difference increased by 2.5 +/- 0.6 vol%, and myocardial oxygen consumption increased by 41 +/- 9%. The increase in coronary vascular resistance induced by cocaine was attenuated (p < 0.05) in the presence of cholinergic blockade (12 +/- 3%) despite a similar increase in MVO2 (49 +/- 8%). The increase in coronary vascular resistance was enhanced (p < 0.05) in the presence of beta-adrenergic receptor blockade (46 +/- 8%), whereas the MVO2 response was less (28 +/- 3%). Again, the addition of cholinergic blockade to beta-blockade attenuated the increase in coronary vascular resistance (23 +/- 6%) without affecting the increase in MVO2 (25 +/- 4%). Combined alpha-, beta-, and cholinergic blockades abolished the systemic hemodynamic and coronary vasoconstrictor response to cocaine. CONCLUSIONS: In conscious dogs, cocaine induces coronary vasoconstriction, which competes with coronary vasodilator responses to increases in myocardial oxygen consumption. The mechanisms of cocaine's coronary vascular effects are mediated via adrenergic stimulation, and the intensity of the vasoconstrictor effects was reduced significantly by cholinergic blockade, in both the presence and absence of beta-adrenergic receptor blockade.

Animals↗
PubMed1993

Acute intravenous cocaine causes transient depression followed by enhanced left ventricular function in conscious dogs.

BACKGROUND: Prior studies in experimental canine models have demonstrated that intravenous cocaine administration causes myocardial depression. The purpose of the present study was to establish the mechanisms of cocaine's actions on myocardial and left ventricular performance after single intravenous bolus doses in conscious, chronically instrumented dogs, in which the full autonomic influences of cocaine would be manifest. METHODS AND RESULTS: In the intact state, cocaine (1 mg/kg) caused a transient decrease in left ventricular dP/dt (baseline; 3,086 +/- 107 mm Hg/sec; 2.5 minutes, 2,649 +/- 114 mm Hg; p < 0.05) followed by a 25 +/- 4% increase in left ventricular dP/dt that peaked at 15 minutes (left ventricular dP/dt, 3,751 +/- 127 mm Hg/sec, p < 0.01) and remained elevated during the 30-minute period of observation. Both the initial depression and the sustained increase in left ventricular contractile response were dose related. The increase in left ventricular dP/dt persisted under circumstances in which the responses were normalized for changes in heart rate and preload that accompanied cocaine administration. The positive inotropic effects were abolished by full autonomic or selective beta-adrenergic blockades. Finally, both cardiac output (baseline, 2,461 +/- 142 min/mL; peak [5 minutes], 3,434 +/- 218 mL/min; p < 0.05) and left ventricular stroke work (baseline, 39 +/- 5 g.m; peak, 49 +/- 6 g.m; p < 0.05) were increased at all times after cocaine administration, suggesting that pump performance was enhanced, despite early reductions in myocardial contractility. Similarly, indexes of early diastolic filling were enhanced despite transient early prolongation in isovolumic relaxation. CONCLUSIONS: Acute intravenous cocaine administration (0.1-2 mg/kg) has a biphasic effect on myocardial and left ventricular function with a transient depression followed by significant sustained increases in left ventricular contractility. The results are in keeping with an early local effect followed by significant adrenergic stimulation, which may be obscured by anesthesia or masked by changes in loading conditions.

Animals↗
PubMed1993

[Clinical evaluation of S-1108 in children].

We administered S-1108 to 16 children with ages ranging from 7 month to 15 years at doses between 1.8 and 6.0 mg/kg x 3/day for 3 to 13 days. We evaluated the efficacy and safety of S-1108 in 11 children with respiratory tract infections, 3 urinary tract infections, and 2 skin infections. The efficacy rate of S-1108 was 100% and bacteriological eradication rate was 83.3%. No adverse effects were observed. These results suggested that S-1108 could be used safely in children.

Adolescent↗
PubMed1992

Flow cytometric analysis of effects of cytokines on the expression of varicella-zoster virus glycoproteins.

Varicella-zoster virus (VZV)-infected human embryonic fibroblast (HEF) cells were stained with monoclonal antibodies directed against VZV glycoprotein I, II and IV, and then labeled with fluorescein isothiocyanate (FITC)-conjugated goat anti-mouse IgG. The cells were analyzed by flow cytometry. VZV-infected cells expressing VZV glycoproteins were clearly distinguished from uninfected cells. This method was useful for analyzing expression of VZV glycoproteins in different experimental conditions. Interferon alpha, beta, and gamma and tumor necrosis factor (TNF)-alpha reduced the percentage of positive cells and the mean fluorescence intensity of the cells expressing VZV glycoproteins. Interleukin(IL)-1 beta, IL-6 and TNF-beta had little effect on the expression of VZV glycoproteins.

Cells, Cultured↗
PubMed1992

Activation of lymphocytes by varicella-zoster virus (VZV): expression of interleukin-2 receptors on lymphocytes cultured with VZV antigen.

The expression of human leukocyte antigen (HLA-DR) and interleukin-2 receptor (IL-2R; alpha and beta subunits) was significantly increased in peripheral blood mononuclear cells (PBMC) from varicella-zoster virus (VZV)-seropositive donors when PBMC were cultured with VZV antigen for 6 days. The increased expression of HLA-DR and IL-2R was observed in both CD4+ and CD8+ lymphocytes, which suggests that both types of lymphocytes from VZV-seropositive donors were activated when PBMC were cultured with VZV antigen. Adding anti-IL-2R alpha did not inhibit lymphocyte proliferation in response to VZV antigen, although marked inhibition was obtained by adding anti-IL-2R beta. No IL-2 was detected in the supernatant of PBMC cultured with VZV antigen; however, antibody to IL-2 inhibited lymphocyte proliferation on exposure to VZV antigen. These results indicate that IL-2 and expression of IL-2R beta are essential to lymphocyte activation by VZV antigen.

Adult↗
PubMed1992

Mechanisms of subendocardial dysfunction in response to exercise in dogs with severe left ventricular hypertrophy.

The effects of exercise on regional myocardial blood flow and function were examined in the presence and absence of beta-adrenergic receptor blockade in 10 adult conscious dogs with severe left ventricular (LV) hypertrophy induced by aortic banding in puppies, which increased the LV weight/body weight ratio by 87%. Exercise at the most intense level studied increased LV systolic (+87 +/- 8 mm Hg) and end-diastolic (+28 +/- 5 mm Hg) pressures, systolic (+85 +/- 12 g/cm2) and diastolic (+49 +/- 11 g/cm2) wall stresses, and subepicardial wall thickening (+0.18 +/- 0.05 mm) but reduced subendocardial wall thickening (-0.45 +/- 0.12 mm) and full wall thickening (-0.42 +/- 0.13 mm). This was associated with a fall in the subendocardial/subepicardial (endo/epi) blood flow ratio to 0.87 +/- 0.06 from 1.24 +/- 0.08. Subendocardial dysfunction persisted during recovery, at a time when transmural blood flow distribution returned to baseline, suggesting myocardial stunning. At the least intense level of exercise studied, the endo/epi blood flow ratio did not fall (1.27 +/- 0.14), but increases in heart rate (+73 +/- 8 beats per minute) and LV systolic (+35 +/- 8 g/cm2) and diastolic (+27 +/- 3 g/cm2) wall stresses were observed, and subendocardial wall thickening fell significantly (-0.21 +/- 0.08 mm, p less than 0.05). With anticipation of exercise, subendocardial wall thickening was not changed. However, subendocardial dysfunction was even evident after 10 beats, i.e., the first 3 seconds of exercise, at a time when LV pressures and stresses had not increased. After beta-adrenergic receptor blockade with propranolol, the most intense level of exercise was associated with lesser increases in systolic and diastolic LV wall stresses, heart rate, and LV dP/dt, and the endo/epi blood flow ratio was no longer reduced below unity (1.17 +/- 0.09). In addition, there were no decreases in subendocardial or full wall thickening, and myocardial stunning was no longer observed. Thus, the subendocardial hypoperfusion and depression in subendocardial wall thickening observed during exercise in dogs with LV hypertrophy was prevented by pretreatment with beta-adrenergic receptor blockade. Furthermore, the subendocardial dysfunction occurred rapidly, before alterations in LV systolic or diastolic wall stress or an alteration in the endo/epi blood flow ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗
PubMed1992

Alterations in left ventricular diastolic function in conscious dogs with pacing-induced heart failure.

We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327 +/- 105 mmHg/s and ejection fraction by -22 +/- 2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., tau increased by +14.0 +/- 2.8 ms and the myocardial stiffness constant by +6.5 +/- 1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV end-systolic (+28.6 +/- 5.7 g/cm2) and LV end-diastolic stresses (+40.4 +/- 5.3 g/cm2). When stresses and heart rate were matched at the same levels in the control and failure states, the increases in tau and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition.

Animals↗