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Biomedical subjects

K Kuno

Publications and source records attributed to K Kuno.

At least 73 records · Page 4Linked to original sources

[Pharmacokinetic and clinical studies with cefluprenam in the pediatric field. Pediatric Study Group of Gefluprenam].

Evaluation of efficacy and safety of cefluprenam (code number: E1077, abbreviation: CFLP), a newly developed injectable cephem antibiotics was conducted on adult patients with various infections, and followed by the study group organized from 39 institutions in pediatric field, as the drug showed no toxicity problems in suckling animals. Informed consents from legal representatives were obtained prior to the study. 1. Clinical efficacy. Two-hundred eighty one cases were included for analysis of clinical efficacy after 40 cases of exclusion or drop-out were subtracted from a total of 321 cases. However, the cumulative number of cases evaluable for analysis was considered to be 289, because 8 cases that had 2 different diseases at the same time were counted in each category of disease. In the cases in which causative organisms were identified (group A), 148 of 154 cases were rated as good or excellent, with an efficacy rate of 96.1%. As for clinical efficacies by disease, efficacy rates were 6/6 for purulent meningitis, 4/5 for sepsis, 95.7% (62/65) for pneumonia, 100.0% (29/29) for urinary tract infections, and 94.1% (16/17) for skin and soft tissue infections. The rate of excellent responses among excellent and good responses was 73.6% (109/148), showing a higher value than any of recent injectable beta-lactams. On 32 cases with S. pneumoniae infection, the efficacy rate of CFLP was 100.0%. In the cases where causative organisms were not identified (group B), 128 of 135 cases were rated as good or excellent, with an efficacy rate of 94.8%. In the all cases including both the group A and the group B, the efficacy rate was 95.2% (276/289) and the rate of excellent responses among excellent and good response was 70.7% (195/276). Against severe infections, CFLP exhibited excellent clinical efficacy, showing an efficacy rate of 8/8 for meningitis, 3/5 for sepsis and 100.0% (22/22) for severe pneumonia. As for bacteriological responses, eradication rates were 95.2% (177/186) in total. Against Gram-positive cocci, the eradication rate was 92.7% (76/82), with eradication rates of 94.3% (33/35) for Staphylococcus aureus, and 93.3% (28/30) for Streptococcus pneumoniae. Against Gram-negative rods, the eradication rate was 97.1% (101/104), and eradication rates were 100.0% (22/22) for Escherichia coli, 97.5% (39/40) for Haemophilus influenzae and 100.0% (19/19) for Molaxella catarrhalis. In cases in which more than 3 days of treatment with previous chemotherapy resulted in no response, the efficacy rate of CFLP was 94.2% (98/104), rated excellent in 68 cases and good in 30 cases. In these cases, the eradication rate was 98.1% (52/53). 2. Pharmacokinetics. CFLP was intravenously administerrd to 12 subjects at doses of 20 to 40 mg (potency)/kg. In 9 subjects aged more than 12 months, maximum serum levels (Cmax), T 1/2 beta and AUC of CFLP were 155.3 +/- 9.8 micrograms/ml, 1.43 +/- 0.18 hours and 111.7 +/- 15.0 micrograms.hr/ml, respectively, when a dose of 20 mg (potency)/kg was used. In 2 subjects aged not more than 12 months, the mean Cmax, T 1/2 beta and AUC were 153 micrograms/ml, 1.6 hour and 81 micrograms.hr/ml, respectively, at a dose of 20 mg(potency)/kg. The mean Cmax, T 1/2 beta and AUC were 332 micrograms/ml, 0.93 hours and 157.3 micrograms.hr/ml, respectively, in 1 subject at a dose of 40 mg (potency)/kg. In 10 subjects dosed 20 mg (potency)/kg, urinary levels were 2413 +/- 512, 1471 +/- 524, and 470 +/- 115 micrograms/ml in 0-2, 2-4, and 4-6 hours after dosing, respectively, showing a cumulative urinary excretion rate of 61.4 +/- 6.3%. In 1 subject dosed 40 mg (potency)/kg, urinary levels were 5700 and 4770 micrograms/ml in 0-2 p3d 2-4 hours after dosing, respectively, showing a cumulative urinary excretion rate of 42.1%. Cerebrospinal fluid concentrations of CFLP, on 10 subjects with purulent meningitis dosed 40-103 mg (potency)/kg were 3.2-32.9 micrograms/ml at 0.5-2 hours after administration within 4 days after the onset of

Bacteria↗

Involvement of transcription factors TCF-1 and GATA-3 in the initiation of the earliest step of T cell development in the thymus.

Flow cytometric and immunocytochemical analyses of murine fetal thymus (FT) cells with antibodies to various surface markers and transcription factors reveal that the synthesis of TCF-1 and GATA-3 protein begins simultaneously in a fraction of the most immature population of FT cells, which have the phenotype of CD4-CD8-CD44+CD25-. No TCF-1-producing cells is found in the fetal liver (FL). In CD44+CD25- FT cells, the production of TCF-1 is immediately followed by intracellular expression of CD3 epsilon. It is also found that the T cell development from FL, but not FT, progenitors in the FT organ culture system is severely inhibited by the addition of antisense oligonucleotides for either TCF-1 or GATA-3. These results strongly suggest that TCF-1 and GATA-3 play essential roles in the initiation of the earliest steps of T cell development in the thymus.

3T3 Cells↗

Novel insight into molecular mechanism of endotoxin shock: biochemical analysis of LPS receptor signaling in a cell-free system targeting NF-kappaB and regulation of cytokine production/action through beta2 integrin in vivo.

Lipopolysaccharide (LPS), a constituent of gram-negative bacteria cell wall, plays an essential role in the pathogenesis of septic shock by generating endogenous mediators such as cytokines, nitrous oxide, superoxide anions, and lipid mediators. In vitro, LPS induces the transcription of a set of genes involved in inflammatory reactions by activating several types of transcription factors, particularly nuclear factor-kappaB (NF-kappaB). An analysis of NF-kappaB activation using a cell-free system demonstated that two pathways converge to activate NF-kappaB; one is staurosporine-sensitive, the other is staurosporine-insensitive and tyrosine kinase-dependent. Furthermore, the latter pathway culminates in IkappaBalpha phosphorylation at serine/threonine residues in its carboxyl-terminal acidic region with dissociation of IkappaBalpha from NF-kappaB, thereby activating NF-kappaB. The requirement for the phosphorylation at this site was confirmed by the specific inhibition of NF-kappaB activation in a cell-free system by the synthetic peptide corresponding to this site. The in vivo administration of an anti-CD18 antibody prevented elevation of plasma tumor necrosis factor (TNF) levels and acute lethality induced by injection of a low dose of LPS into Propionibacterium acnes-primed rabbits or by the administration of a single high dose of LPS into animals. Anti-CD18 also prevented acute lethality induced by one of the main mediators of endotoxin shock, TNF-alpha. Furthermore, an antibody to a ligand for CD18, intercellular adhesion molecule-1, also prevented TNF-induced shock as well as endotoxin shock in rabbits. These observations suggest that the interaction between leukoytes and endothelium through beta2- integrin adhesion molecules may be of primary importance in mediating LPS signals in vivo.

Animals↗

A candidate for cancer gene therapy: MIP-1 alpha gene transfer to an adenocarcinoma cell line reduced tumorigenicity and induced protective immunity in immunocompetent mice.

PURPOSE: To evaluate the possibility of cancer gene therapy by the gene delivery of chemokine, the effects of human macrophage inflammatory protein 1 alpha (hu-MIP-1 alpha), murine-macrophage inflammatory protein 1 alpha (mu-MIP-1 alpha), and human-interleukin 8 (hu-IL-8) on tumor progression and immunization were studied. METHODS: Cachexia-inducing and highly tumorigenic adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid, hu-MIP-1 alpha, mu-MIP-1 alpha, or hu-IL-8 expression vector. The production of hu-MIP-1 alpha reached > 1.5 ng/ml in vitro when transfectant cells were cultured at a cell density of 2 x 10(5) cells in 7 ml for 3 days. Immunocompetent BALB/c mice were inoculated into the footpad with the tumor cells, and then primary tumor growth, morphological analyses, and tumor immunogenicity were studied. RESULTS: The secretion of hu-MIP-1 alpha, mu-MIP-1 alpha, and hu-IL-8 did not affect the growth rate in vitro. Reduced tumorigenicities in vivo were observed in transfected cells with hu-MIP-1 alpha and mu-MIP-1 alpha. Morphologic observation of the site of inoculation of cells transfected with hu-MIP-1 alpha showed infiltration of macrophages and neutrophils on the 5th day after the inoculation. Mice that had rejected cells transfected with hu-MIP-1 alpha gene were immune to a subsequent challenge with the parental cells. CONCLUSIONS: The rejection of the cells depends on cytolysis and generates potent and long lasting antitumor immunity. These data suggest that tumor cells transfected with the MIP-1 alpha gene might be useful as an effective therapy for the treatment of certain tumors.

Adenocarcinoma↗

Periventricular leukomalacia and West syndrome.

The authors studied the clinical course and electroencephalograms (EEGs) of 27 patients with periventricular leukomalacia (PVL), to investigate the relation between PVL and West syndrome. Seven of the 27 patients with PVL developed WS; in all seven the PVL was severe. Bilateral parieto-occipital dominant irregular polyspike-and-wave (PO-polySpW) bursts were seen in eight of the 21 patients whose EEGs were recorded within the age of one year (corrected for preterm birth). All eight had severe PVL, and in six, bilateral PO-polySpW bursts were followed by hypsarrhythmia and spasms. None of the 12 patients without polyspike-and-wave bursts developed West syndrome, the study shows that West syndrome is a common complication of severe PVL and that it correlates strongly with the occurrence of bilateral PO-polySpW bursts on follow-up EEGs.

Birth Weight↗

Benign partial epilepsy in infancy.

The aim was to examine the occurrence of benign partial epilepsy in infancy (BPEI). BPEI was defined as epilepsies with complex partial seizures (CPS) or secondary generalised seizures (SGS), or both, compatible with the following characteristics: normal development before and after onset, no underlying disorders, normal interictal electroencephalograms (EEGs), and good response to treatment. All 75 patients who developed epilepsy within the first 2 years of age between 1987 and 1993 were evaluated: 22 patients fulfilled the definition completely; eight had CPS only, four SGS only, and 10 had both CPS and SGS; 17 had clusters of seizures. Eight patients had a positive family history. The average age of onset of seizures was 5.9 months. Interictal EEGs were all normal. Response to treatment was excellent and the average period of seizure persistence was 3.0 months. All had normal psychomotor development. Patients with BPEI were more common in this study than previously reported.

Anticonvulsants↗

Hypoxic contraction of contractile interstitial cells isolated from bovine lung.

Although contractile interstitial cells (CIC) in the alveolar septum have been suggested to be involved in hypoxic pulmonary vasoconstriction (HPV), direct demonstration of cellular contraction under hypoxia has been lacking. To achieve this, we purified CIC from collagenase-dissociated bovine lung cells and examined the response of these cells to hypoxia. Prostaglandin (PG) F synthase served as a marker of CIC, and the isolated PGF synthase-positive cells were shown to preserve the ultrastructural features characteristic of CIC, most notably bundles of microfilaments. Isolated CIC seeded onto collagen gel disks became embedded and formed a lattice network with collagen fibrils. Exposure of these CIC-bearing gels to hypoxia (PO2 = 20-40 Torr) evoked a reversible reduction in gel volume, as assessed by measuring the surface area of the gel disks photographically. Thus CIC were shown to contract under hypoxia, providing the supportive evidence for the involvement of CIC in HPV.

Animals↗

Inhibitory effect of an intellectual task on breathing after voluntary hyperventilation.

We investigated the effects of an intellectual task on posthyperventilation (PHV) breathing by using a video game. Eight normal subjects were placed in a supine positions. The game task by itself led to increase ventilation compared with the control tasks via an increase in the average inspiratory flow rate (P < 0.01) and the respiratory frequency (P < 0.001). After hypocapnic voluntary hyperventilation (VHV), the task led to a decrease in the 1-min PHV breathing level compared with the control tasks after VHV [after VHV, first 60 s average minute ventilation while watching television and while playing a video game are 5.54 +/- 2.91 (SD) and 2.05 +/- 1.40 l/min, respectively; P < 0.01]. Only one subject showed PHV apnea for at least 10 s during the control protocol, whereas seven of the same eight subjects showed PHV apnea while performing the task. After isocapnic VHV, the task still led to a decrease in PHV breathing compared with the control tasks. However, this decrease was smaller than in the hypocapnic studies and was only significant during the first 15 s of recovery. These results suggest that increased activity in the higher centers of the central nervous system has an inhibitory effect on PHV breathing at a time when the effects of short-term potentiation after VHV, hypocapnia, and perhaps other mechanisms would be expected to be acting on breathing.

Adult↗

Prevalence of severity of hypoxemia following clinical voluntary hyperventilation.

The voluntary hyperventilation (VHV) test is used in many clinical examinations. However, arterial hypoxemia following a clinical VHV test is not a well-studied phenomenon. We analyzed the arterial blood gases (ABGs) of 61 patients during a VHV test. The ABG were taken prior to (PaO2-Prior), immediately following (PaO2-Immediate), and 5 min after (PaO2-After) the VHV test. The patients' average PaO2 rose significantly (p < 0.0001) from the PaO2-Prior (88 +/- 8 mm Hg; mean +/- SD) to the PaO2-Immediate (118 +/- 13 mm Hg) and then dropped significantly (p < 0.0001) to the PaO2-After (74 +/- 16 mm Hg). Two of the 20 patients who experienced an angina pectoris attack (AP(+)) following the VHV test showed severe arterial hypoxemia (PaO2-After < 60 mm Hg), whereas 9 of the 41 patients who did not experience an angina pectoris attack (AP(-)) showed a PaO2-After < 60 mm Hg. The PaO2-After did not correlate with the PaO2-Prior. The decrease in the PaO2-Prior to After did not correlate significantly with the left ventricular ejection fraction rate (n = 58, r = 0.18, not significant). However, the decrease in the PaO2-Prior to After correlated well with the degree of recovery of the PaCO2 following the VHV test (r = -0.69, p < 0.0001). The age, gender ratio, changes in arterial blood gases, number of patients who experienced PaO2-After < 60 mm Hg, and left-ventricular ejection fraction rate were not significantly different between the AP(-) and AP(+) groups. Posthyperventilation hypoxemia developed frequently following the VHV test during coronary angiography. Although this arterial hypoxemia was not directly correlated with the occurrence of AP attacks following VHV in this study, continuous SaO2 monitoring is recommended whenever a VHV test is used as a diagnostic technique to avoid the potentially deleterious effects of arterial hypoxemia.

Arteries↗

Effects of NCPAP therapy on fibrinogen levels in obstructive sleep apnea syndrome.

In patients with obstructive sleep apnea syndrome (OSAS), the blood coagulation system may contribute to an increased risk of cardiovascular events, which occur most frequently in the morning. Nasal continuous positive airway pressure (NCPAP) treatment can improve the mortality of patients with OSAS. We measured the plasma fibrinogen concentration, which is an independent risk factor for cardiovascular events, in the afternoon (3:30 P.M.) and the next morning upon awakening (8:30 A.M.) in 11 patients with OSAS (apnea and hypopnea index > 20) before and after NCPAP therapy. We also measured the hematocrit, the C-reactive protein, and the total plasma protein at the same time. The plasma fibrinogen and hematocrit levels in the morning (298 +/- 16 mg/dl and 48.5 +/- 1.5%, mean +/- SEM) were significantly higher than on the previous afternoon (275 +/- 14 mg/dl and 46.6 +/- 1.3%) (fibrinogen, p < 0.02; hematocrit, p < 0.005). The whole blood viscosity (WBV) at a shear rate of 208 inverse seconds, which can be predicted based on the hematocrit and total plasma protein, was also significantly higher in the morning (4.98 +/- 0.20/s) than in the afternoon (4.73 +/- 0.17/s) (p < 0.005). These increases in the plasma fibrinogen concentration and the WBV in the morning disappeared after NCPAP treatment. The attenuation of morning increases in the plasma fibrinogen concentration and WBV induced by NCPAP treatment may contribute to an overall improvement in the mortality from cardiovascular events in patients with OSAS.

Adult↗

Prostaglandin F synthase is localized to contractile interstitial cells in bovine lung.

It was recently found that certain cells in the alveolar septum of the bovine lung are enriched in prostaglandin F (PGF) synthase. In this study we used immunohistochemical techniques at both light and electron microscopic levels to further characterize the PGF synthase-positive cells. By double immunofluorescence staining of bovine lung cryostat sections, the alveolar septal cells labeled by anti-PGF synthase antibody were also intensely labeled for cytoplasmic actin but not for alpha-smooth muscle actin. This labeling pattern suggests that the PGF synthase-positive cells in the septum are "contractile interstitial cells," which resemble conventional fibroblasts but characteristically contain prominent bundles of actin filaments. Immunogold electron microscopy of ultra-thin frozen sections of bovine lung showed that alveolar interstitial cells extending long cytoplasmic processes and closely associated with alveolar capillaries were intensely labeled for PGF synthase. Capillary endothelial cells, alveolar epithelial cells, and some fibroblastic cells were devoid of labeling. On the basis of these findings, we conclude that PGF synthase is specifically expressed in contractile interstitial cells within the alveolar septum. The protein may be a useful marker for contractile interstitial cells, whose physiological function and role in various pathological conditions have not been characterized in detail.

Animals↗

Relationship between dyspnea in daily life and psycho-physiologic state in patients with chronic obstructive pulmonary disease during long-term domiciliary oxygen therapy.

We examined the relationships among dyspnea ratings in daily life, the physiologic state, and anxiety and depression of fifty-two patients with chronic obstructive disease (COPD) during long-term domiciliary oxygen therapy (LTOT). Clinical ratings of dyspnea were assessed by the visual-analog scale (VAS) during eight types of basic behavior in indoor daily life. Analysis of the physiologic state included forced expiratory volume in 1 second (FEV1.0), and arterial blood gas (PaO2, PaCO2) at rest while breathing room air. The hospital anxiety and depression (HAD) scale, which consists of 14 questions, was used to assess the degree of anxiety (HAD-A) and depression (HAD-D). The mean age of the patients was 69.5 +/- 10.8 year (SD), and the duration of LTOT was 944 +/- 739 days. The mean values were 0.77 +/- 0.45 L for FEV1.0, 57.7 +/- 7.4 Torr for PaO2, and 47.4 +/- 8.1 Torr for PaCO2. FEV1.0 was correlated with PaCO2(r = -0.548, p < 0.0001), but it was not correlated with PaO2. High correlation was noted between HAD-A and HAD-D (r = 0.693, P < 0.0001), whereas correlation was not noted between HAD and the physiologic state. VAS was significantly correlated with FEV1.0 (r = 0.320, p < 0.05), as well as with HAD-A (r = 0.358, p < 0.01) and HAD-D (r = 0.444, p < 0.01). Dyspnea ratings were found to be influenced by anxiety and the depression state, and also by the degree of flow limitation in patients with COPD during LTOT. In contrast, the physiologic state scarcely influenced the anxiety and depression state. Thus, psychotherapy may play an important role in the reduction of dyspnea sensation, which is an important determinant of quality of life.

Activities of Daily Living↗

[Oligohidrosis caused by zonisamide].

We studied 70 patients who took zonisamide (ZNS) in August 1994, to clarify the relation between ZNS and oligohidrosis. Twelve of the 70 patients were revealed to have oligohidrosis by the interview with patients' mothers. Six of these 12 patients were evaluated by heat loading test, which showed a decreased sweat response in all patients. Five of the 12 oligohidrotic patients were evaluated by acetylcholine (Ach) loading test and all of them showed a decreased sweat response. On two patients poor sweat responses to heat loading and Ach loading recovered after discontinuation of ZNS. These results suggest that ZNS causes dysfunction of sweat glands.

Acetylcholine↗

[Perinatal brain injury in infants with depressed EEG activities immediately after birth].

We investigated the developmental outcome and features of brain imaging in 33 infants with moderate or severe depression of background EEG activities immediately after birth. Lesions due to perinatal injury were observed in 25 infants on neonatal ultrasonography and/or childhood MRI. These findings strongly correlated with their gestational age. Periventricular leukomalacia and posthermorrhagic porencephaly were observed in preterm infants. On the other hand, perinatal injury of mature brain type, such as multicystic encephalomalacia, parasagittal infarct, bilateral basal ganglia/thalamic lesion, and subcortical leukomalacia, were observed in full-term infants. Periventricular leukomalacia rather correlated with moderate depression of EEG activities than severe depression like observed in full-term neonates who have brain lesions due to perinatal asphyxia.

Asphyxia Neonatorum↗

[Optimum dose study of cefozopran in the pediatric field].

Cefozopran (SCE-2787, CZOP) was administered to patients with pediatric infections three to four times daily by intravenous injection or 30-minute intravenous drip infusion, and investigations were made in individual cases, on relationships among doses, pharmacokinetics, effects on pathogenic bacteria and MIC against them, and clinical effects. The following results on optimal doses of CZOP were obtained. 1. Clinical cases in which CZOP was administered at a dose of 10 mg (potency)/kg The subjects were 7 patients including 4 patients with pneumonia. Severities of the diseases were severe in one of the patients with pneumonia, and moderate in the other patients. The MIC against pathogenic bacteria (4 strains) isolated from these cases ranged from 0.2 to 1.56 micrograms/ml. The serum concentrations were in a range between 1.4 and 7.6 micrograms/ml at 4 hours after administration. In some cases, the serum concentrations were lower than the MICs, though slightly. In the clinical evaluation, CZOP was excellent in 3 cases, good in 2 cases and fair in 1 case. The evaluation was impossible in 1 case. The efficacy rate was 83.3% (5/6). In bacteriological evaluation, 3 out of the 4 strains disappeared. Adverse reactions and abnormal laboratory test values were not observed. 2. Cases in which CZOP was administered at a dose of 20 mg (potency)/kg The subjects were 5 patients including 2 with pneumonia, and severities were severe in one of the patients with pneumonia, and moderate in the other patients. The MICs against the pathogenic bacteria (3 strains) isolated from these cases ranged from 0.1 to 1.56 micrograms/ml. While, serum concentrations at 4 hours after administration were in a range between 3.0 and 7.7 micrograms/ml sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 1 case and good in four cases, with an efficacy rate of 100% (5/5). In the bacteriological evaluation, all the 3 strains disappeared. No adverse reactions were observed, but an abnormal laboratory test value showing eosinophilia was noted in one case. 3. Cases in which CZOP was administered at a dose of 40 mg (potency)/kg The subjects were 5 patients including 3 with pneumonia. The severity was moderate in 2 of the pneumonia patients, and severe in the other three cases. The MICs against the pathogenic bacteria (4 strains) isolated from these cases were in a range between 0.1 and 0.78 micrograms/ml. The serum concentrations at 4 hours after administration ranged from 6.5 to 21.9 micrograms/ml, sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 4 cases and good in 1 case, with an efficacy rate of 100% (5/5). The efficacy rate in the bacteriological evaluation was also 100%. As adverse reaction, red urine was observed in one case. Eosinophlia was noted in one case in the laboratory tests. When CZOP was administered to patients with pediatric infections at a dose of 10 mg (potency)/kg, the clinical effect of the drug was insufficient in a case in which serum concentration of CZOP at 4 hours after administration was lower than the MICs against the pathogenic bacteria. When CZOP was administered at a dose of 20 mg (potency)/kg, sufficient concentrations were obtained, and the drug efficacies were found to be excellent or good in all cases. Therefore, the effective dose normally used is considered to be 20 mg (potency)/kg. When CZOP was administered at a dose of 40 mg (potency)/kg, the drug was found to be excellent or good in all of the cases although the severities were high in more than half of the cases tested. In addition, the rate of excellent efficacies was 80% (4/5). Furthermore, no severe adverse reactions were observed. It was, therefore, confirmed that CZOP should be administered at a dose of 40 mg (potency)/kg in severe or intractable cases.

Bacterial Infections↗

[A case of pachygyria with cystic changes in the periventricular white matter and putamen].

We reported a case of type I lissencephaly/pachygyria which had cystic changes in the periventricular white matter and lentiform nuclei. The patient developed neonatal seizures and was referred to Anjo Kosei Hospital His seizures were frequent and refractory to anticonvulsants. His development was severely retarded. CT and MRI revealed cystic changes in the periventricular white matter and lentiform nuclei as well as bilateral diffuse pachygyria and agenesis of corpus callosum. He died of unknown cause at 5 months of age and postmortem examination was performed. Type I lissencephaly/pachygyria, almost complete agenesis of corpus callosum, leptomeningeal glioneuronal heterotopia and hypoplasia of corticospinal tract were seen pathologically. Marked gliosis and CD 68 positive macrophages were found around the cystic lesions in the periventricular white matter and lentiform nuclei, which suggests that these lesions were the secondarily destructive lesion. We considered that these secondary lesions were due to frequent seizures which could cause insufficient supply of blood and glucose in those areas.

Brain↗

Validity of a random noise oscillation and body box system for the measurement of the respiratory impedance of small animals.

The accuracy and validity of a body box system which was developed for the measurement of airway and chest wall impedance in small animals such as canines was evaluated. Input impedance was calibrated using a resistance tube and the mouth flow sensing system was designed to be as symmetrical as possible such that the minimal common mode rejection ratio (CMRR) from 10 to 40 Hz was greater than 60 dB. The validity of this system using the resistance tube and inertant models indicated that the average error ratio for the input impedance and for the flow transfer function between the mouth and chest flow was within 3 and 0.5%, respectively. The location of the box pressure port near to the oscillatory flow inlet was shown to potentially give rise to errors in the measurement of the flow transfer factor due to the direct effects of the inflow. A distance of 60 cm was adopted in the present system, which proved to be sufficient to avoid this effect. It was concluded that the body box system which is described for small animals in the present study is appropriate for obtaining separate and accurate airway and tissue impedance data.

Airway Resistance↗

Chest flow during the initial inspiratory phase (V0.1) in pulmonary diseased patients.

We measured the chest flow 0.1 s after the onset of the inspiratory phase (V0.1) in patients with chronic pulmonary emphysema (CPE: n = 5), interstitial pneumonitis (IP: n = 5) and normal subjects (Nor: n = 5). The subjects sat in a body box and breathed air from outside of the body box. V0.1 was measured during rest and during maximal breathing (V0.1-rest, V0.1-max) and then these results were compared with P0.1 (P0.1 rest, P0.1-max) values. V0.1-rest was not significantly different between the three groups (Nor: 0.25 +/- 0.10, CPE: 0.27 +/- 0.06, IP: 0.26 +/- 0.06, l/s), whereas the P0.1-rest in IP patients was significantly greater than in normal subjects (Nor: 1.98 +/- 0.61, CPE: 3.00 +/- 0.80, IP: 3.60 +/- 0.68 hPa; P < 0.05 compared with normal). The V0.1-max in CPE and IP patients was significantly lower than in normal subjects (Nor: 3.66 +/- 1.16, CPE: 0.82 +/- 0.25, IP: 1.02 +/- 0.21 l/s, P < 0.05 compared with normal subjects (Nor: 3.66 +/- 1.16, CPE: 0.82 +/- 0.25, IP: 1.02 +/- 0.21 l/s, P < 0.05 compared with normal), whereas P0.1-max in IP patients was not significantly different with in normal subjects (Nor: 33.2 +/- 10.2, CPE: 9.8 +/- 3.7, IP: 19.5 +/- 3.4 hPa, P < 0.05 compared with normal, P < 0.05 compared with CPE). A simulation of the influence of the mechanical properties of the respiratory system on V0.1 and P0.1 using the Runge-Kutta method suggested that V0.1 was negatively affected by airway resistance but positively affected by chest wall and lung compliance. In contrast, the influence of respiratory mechanics on P0.1 was much less than on the V0.1, except for highly decreased lung compliance. In CPE patients, it was suspected that mechanical disorders might not simply be the determining factors of V0.1-max, but that limitations of the neuro-muscular drive due to chest wall deformity may also play a definitive role in the smaller V0.1-max. In contrast, it may be inferred that IP patients had to exert greater inspiratory effort as compared with the other two groups in order to maintain a similar V0.1-rest because of the increased airway resistance and decreased tissue compliance; thus these abnormal mechanical properties suppress the increase in the V0.1-max. It may be concluded that V0.1 is a good index of chest wall acceleration, which is determined by both the neuro-muscular drive and the mechanics of the respiratory system.

Aged↗