[The way of living in our age. Provision of quality care based on respect of patient's individuality].
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Biomedical subjects
Publications and source records attributed to Y Kuroda.
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The effects of S-1108, an orally active cephem antibiotic newly synthesized by Shionogi Res. Lab., on pediatric bacterial infections was studied. S-1108 was administered orally at a daily dose between 9.3 and 12.4 mg/kg in three divided doses (after each meal) for 5 to 11 days to patients with pharyngitis (2), tonsillitis (1), bronchitis (3), pneumonia (1), lymphadenitis (1), enteritis (1) and cystitis (1). The clinical efficacy rate was 100% with excellent responses in 3, good in 6 and undetermined in 1. Bacteriological effects observed indicated that one strain each of Streptococcus pneumoniae, Streptococcus pyogenes, Klebsiella pneumoniae and two strains of Haemophilus influenzae were eradicated by the treatment. No clinical side effects and laboratory test abnormalities were observed at all in this study. These results suggested that S-1108 would be a useful antibiotic for the treatment of bacterial infections in the pediatric field.
The two-layer cold storage method using the University of Wisconsin solution (UW) allows continuous tissue adenosine triphosphate (ATP) production during the preservation period. UW contains 5mM of adenosine which has several mechanisms of action, however, its efficacy is controversial. In this study, at first, we investigated the metabolism of exogenous adenosine during preservation by the two-layer method in the canine pancreas graft subjected to 60 min warm ischemia. High concentration (> 5 mM) of adenosine in Euro-Collins' solution (EC) remarkably increased ATP and total adenine nucleotide (TAN) levels during 24 hr preservation by the two-layer method using EC. Furthermore, experiments with 5 mM of [2-3H] adenosine demonstrated that adenosine was metabolized and incorporated into adenine nucleotides (ANs). However, neither 5 mM of inosine, hypoxanthine nor adenine substituted for adenosine. It was clear that adenosine was directly phosphorylated and converted into ANs. Secondly, the effect of adenosine on the viability of the ischemically damaged pancreas graft was evaluated by graft survival following autotransplantation. The ischemically damaged pancreas grafts were preserved for 24 hours by simple cold storage in EC (group 1), EC with 5 mM of adenosine (group 2), the two-layer method using EC (group 3), EC with 5 mM of adenosine (group 4). Graft survival rates were 0/5 (0%), 1/5 (20%), 0/3 (0%) and 4/5 (80%) in groups 1, 2, 3 and 4 respectively. Adenosine was clearly effective on graft survival via recovering high tissue ATP and TAN levels only in case of the preservation by the two-layer method. We conclude that exogenous adenosine works as a substrate for ANs synthesis and is directly phosphorylated to ANs during preservation by the two-layer method. This is essential to repair damaged cells and maintain cellular integrity, making it possible to preserve ischemically damaged pancreas.
Malignant rhabdoid tumor is initially differentiated from renal tumors and characterized by extremely rapid growth. We report a newborn case of extrarenal malignant rhabdoid tumor and review the literature.
A newborn with isolated atrial discordance complicated by primary atrial situs inversus and dextrocardia is reported. She received a Mustard's corrective procedure with a good clinical outcome. To our knowledge, this is the third report of a patient with isolated atrial discordance and viscero-atrial discordance or ambiguus.
Dipyridamole enhanced the anti-cancer activity of VCR toward both wild type HL-60 and VCR-resistant subline, HL-60/R, which had a 15 fold greater resistance to VCR as compared with the wild type cell line. The resistance to VCR of HL-60/R cells was associated with a marked decrease in the intracellular VCR accumulation. After incubation with VCR for 24 hrs, 0.61 and 0.24 pmol VCR per one million cells were accumulated in the wild and the resistant cells, respectively. Dipyridamole dose-dependently increased the intracellular VCR accumulation in the wild type cells and also it restored the intracellular VCR accumulation in the VCR-resistant cells. Addition of 10 microM dipyridamole to the culture medium enhanced the intracellular accumulation of VCR during 24 hr incubation by 2.6 fold and 6.0 fold in HL-60 and HL-60/R cells, respectively. The VCR-resistance in HL-60/R cells was able to be overcome by the addition of 2.5 microM dipyridamole to the culture medium. This concentration of dipyridamole could be obtained by the intravenous administration without severe adverse effects. These results indicate that dipyridamole should be effective in the treatment of patients with hematologic malignancy resistant to VCR.
Older pediatric patients with cyanotic congenital heart disease (CCHD) often develop nephropathy. Although felt to be secondary to glomerular dysfunction, there have been only a few papers examining renal tubular abnormalities in such patients. We therefore evaluated renal function in 16 patients with CCHD aged 3 to 28 years. The six oldest patients (aged 15 to 28 years), had documented proteinuria and low creatinine clearance levels. The urinary concentration of microalbumin was increased when compared to control values in 7 of the 16 patients; six of the patients had proteinuria while one did not. Urinary levels of N-acetyl-beta-D-glucosaminidase (NAG) were elevated in 14 patients including those without proteinuria. Concentrations of blood urea nitrogen and creatinine as well as serum and urinary concentrations of beta 2-microglobulin levels were elevated in certain patients. The serum concentration of uric acid was notably greater in all CCHD patients relative to controls. Furthermore, serum uric acid concentrations and urinary microalbumin levels correlated with patient age. In conclusion, renal tubular dysfunction as well as glomerular dysfunction occur in patients with CCHD. Urinary NAG may be useful as an early marker for the early detection of tubular dysfunction, while urinary microalbumin levels are useful in assessing glomerular dysfunction in these patients.
Electrocardiographic changes were evaluated in 20 patients with a diagnosis of Duchenne's muscular dystrophy (DMD) for a period of 4 to 9 years preceding their death. Certain common electrocardiographic findings were noted in patients during the terminal stage of their disease, and may have prognostic significance. These included: an R wave in lead V1 of less than 0.6 mV, in lead V5 of less than 1.1 mV, and in lead V6 of less than 1.0 mV; abnormal T waves in leads II, III, a VF, V5 and V6; cardiac conduction disturbances; premature ventricular contractions; and sinus tachycardia. A predictive scoring system was proposed based on these findings. The predictive scores for patients who died primarily from cardiac failure were significantly higher than for patients who died primarily from respiratory failure. This score increased to over 10 points as the patient's clinical condition deteriorated. In conclusion, a predictive score is useful in managing patients with DMD, particularly when evaluating for possible cardiac failure.
We investigated the effect of hypothermic aerobic perfusion of the rat liver using perfluoro-N-methyl-decahydroisoquinoline (FMIQ) on the cell viabilities of hepatic parenchyma and nonparenchyma in comparison with University of Wisconsin (UW) solution. Rat liver were perfused at 4 degrees C up to 24hr at a flow rate of 0.2 ml/g liver tissue/min with either UW or a perfusate (m-FMIQ) containing 20% FMIQ with or without oxygen saturation. After storage, livers were perfused with Krebs-Henseleit buffer containing trypan blue (200 microM). Nuclear dye uptake was measured as an indicator of cell death. Dye uptake of parenchymal cells remained less than 2% for up to 24hr, regardless of perfusate or O2-saturation. In UW perfused livers, nonparenchymal cells showed time related increases of dye positive nuclei, which were not affected by O2-saturation (39.9 +/- 4.7% and 36.5 +/- 4.2% at 24hr in O2-saturated and nonsaturated groups, respectively). In contrast, we found excellent protective effects of oxygen supply with m-EMIQ on the nonparenchymal cell viability, the dye uptake values being 16.9 +/- 5.7% and 39.4 +/- 9.1% at 24hr in O2-saturated and nonsaturated groups, respectively (p < 0.001). In conclusion, oxygen supply during hypothermic perfusion may be useful in preventing nonparenchymal cell injury of the liver, thereby leading to dramatic improvement of the hepatic microcirculation.
A 59-year-old man, under treatment for osteoarthritis of the right hip joint, was admitted to the Department of Orthopedic Surgery of Health Insurance Nankai Hospital with complaints of high fever and severe right hip joint pain. Since he developed shock, he was transferred to the Department of Internal Medicine. The laboratory data showed marked increase of acute phase reactants, and Staphylococcus aureus was cultured from the abscess in the right hip joint. The chest X-ray film the next day showed diffuse pulmonary edema of both lungs. The diagnosis of adult respiratory distress syndrome (ARDS) due to sepsis caused by S. aureus was made. Septic ARDS due to S. aureus is rare. The patient was cured by mechanical ventilation and administration of antibiotics, methyl-prednisolone and Urinastatin, along with drainage of the abscess in the right hip joint.
We investigated the optimal condition to detect abnormalities on the fast-Fourier transformation of the signal-averaged electrocardiogram (SA-ECG) by studying the effects of analyzed signal duration, attenuation of low frequency components by using filtering processing and the criteria for abnormal SA-ECG. Subjects were 23 patients with Duchenne's muscular dystrophy (DMD) and were divided into two groups by the presence of ventricular tachycardia (VT). Age-matched healthy volunteers were obtained as controls. Abnormal SA-ECG was identified from the data in the controls as over 97 percentile of H/L ratio. Frequency domain analysis from last 40 ms of QRS wave to 80 ms of ST segment was most capable to distinguish the DMD patients with VT from the patients without VT, compared to analysis from last 20 ms. Whereas, analysis from QRS onset failed to detect VT patients. Although filter processing reduce the power of low frequency and increase the H/L ratio, sensitivity for predicting VT was not enhanced significantly. In conclusion, the frequency-domain analysis during the terminal 40 ms of the QRS complex and 80 ms of ST segment was most optimal condition to distinguish the DMD patients with VT.
Neuroradiological and neurophysiological studies were done in two male siblings with carbohydrate-deficient glycoprotein syndrome (CDGS) (case 1 and 2) and one male second cousin presumed with CDGS (case 3). Case 1 and 2 had abnormality of epileptic discharge in EEG. Case 1 had MCV in the lowest normal range, giant SEP was observed in SSEP in case 1 and low voltage of P 14 in case 3. Case 1 had low voltage of wave V in ABR and case 3 had low voltage of wave V on one side and no response on the other side. The all cases showed the normal pattern for VEP and MEP. All showed cerebellar hypoplasia and various degree of pontine hypoplasia on MRI. SPECT showed hypoperfusion in cerebellum, brainstem and left centroparietal region in case 1. In CDGS we found the hypoplasia of cerebellum and pons in common, but it was suggested that CDGS might have the heterogeneity of pathophysiology on the basis of various neurological abnormalities.
The origin of the 0.1 Hz bursting of cultured rat cortical neurons in zero Mg2+ was studied by whole-cell recording, fluo-3 Ca2+ imaging, and multi-unit electrode array recording. A model is proposed in which spontaneous synaptic currents act as a random pacemaker.
A 26-year-old woman had the right shoulder pain, weakness in her right arm, and noticed coldness in her right arm when it is down. On examination, she had droopy shoulder dominantly in right side, weakness and paresthesia in her right upper limb in the distribution of C8-Th1. The thoracic outlet compression tests were positive in her right side. Angiography of the right subclavian artery and brachial plexography under Allen's position revealed compression at the thoracic outlet. A cervical MRI revealed localized atrophy of the spinal cord (right side dominant) at the level of C5-6 vertebral body. Her spinal cord and dural sac moved anteriorly in cervical flexion. Droopy shoulder may be a risk factor of thoracic outlet syndrome and also flexion myelopathy. Double crush nerve compression of lower motor neuron at anterior horn of the cord and at the thoracic outlet may have accelerated the symptoms.
Frequency domain analysis of signal-averaged electrocardiograms (SAECGs) were investigated in 24 patients with right bundle branch block (RBBB) following repair of congenital heart disease, in order to determine the block site of RBBB using a SAECG. The block site of RBBB was first identified by a body surface map; 10 patients had proximal RBBB, 14 had distal RBBB. The peak amplitude, the amplitudes on 20 Hz, 40 Hz, 50 Hz, and 100 Hz in the proximal RBBB patients were significantly (p < 0.01) smaller than in the distal RBBB patients. The areas between 0 to 20 Hz, between 0 to 40 Hz, between 20 to 50 Hz, between 40 to 100 Hz in the proximal RBBB patients were significantly (p < 0.01) smaller than in the distal RBBB patients. In conclusion, frequency domain analysis of SAECG was useful for determining the block site of RBBB following surgical correction.
A 34-year-old woman was admitted to our hospital in 1991, because of progressive headache, nausea and generalized edema. She was diagnosed as Crow-Fukase syndrome associated with plasma cell dyscrasia (IgA lambda type) in 1987, presenting with polyneuropathy, edema, and dermatologic changes. Those manifestations were improved with irradiation and corticosteroids, but headache, nausea and generalized edema gradually developed after the discontinuation of corticosteroid therapy in 1991. On admission, marked bilateral papilledema was noted but fever and meningeal irritation signs were absent. A spinal tap showed a clear cerebrospinal fluid (CSF) with an open pressure of more than 400 mmH2O, normal cell count, total protein level of 87 mg/dl, and IgG level of 12.3 mg/dl. The CSF culture for microorganisms was negative and the cytological study of CSF also was normal. De novo synthesis rate of CSF IgG was markedly elevated (35.3 mg/day). MRI of the head using Gd-DTPA revealed diffuse hypertrophic dura mater, which made the diagnosis of chronic pachymeningitis. Cerebral angiographies were normal. An RI cisternography demonstrated delayed absorption of the CSF without ventricular reflux. Gallium and bone scintigrams did not show any pathological accumulation of the isotopes in the head. The lack of abnormalities causing chronic pachymeningitis in this case suggests that the chronic pachymeningitis might be associated with Crow-Fukase syndrome. The development of increased intracranial pressure is not rare in Crow-Fukase syndrome but the etiology remained unknown in most cases. We therefore suggest that MRI study with contrast enhancement should be performed in cases of this condition with increased intracranial pressure.
We followed up the clinical course and changes of brain magnetic resonance imaging (MRI) findings in a case of neuro-Behçet's disease, and performed serial immunological examinations of the cerebrospinal fluid (CSF). On the two episodes of acute exacerbation, gadolinium (Gd)-enhancement effects on brain MRIs were observed in the brain stem and the deep white matter of cerebral hemispheres. The CSF abnormality of this period was characterized by increases in proportions of polymorphonuclear leukocytes and intrathecal IgG synthesis in addition to the findings suggesting breakdown of the blood brain barrier (BBB). These findings disappeared in parallel with clinical improvement by corticosteroid therapy. In contrast, during a subsequent chronic progressive stage, steroid-resistant neuropsychiatric symptoms and an absence of Gd-enhancement effects on brain MRIs were observed despite progressive breakdown of BBB. These findings suggest that neuro-Behçet's disease should comprise two distinct immunopathogenetic stages, that is, a relatively early steroid-responsive stage with a relapsing-remitting clinical course and a late steroid-nonresponsive stage with a chronic progressive course.
A 67-year-old man with an extensive hepatocellular carcinoma (HCC) was treated successfully with intraarterial infusion of high-dose adriamycin (ADR), 150 mg/m2, five minutes continuous infusion using an extra-corporeal system consisting of direct hemoperfusion (DHP) under hepatic venous isolation (HVI). During drug infusion, hepatic effluent was isolated and adsorbed by the DHP for 30 mins. Plasma ADR levels in the radial artery reached a peak of 2.00 micrograms/ml at five mins after the initiation of drug infusion. Peak values at the inlet and outlet of the DHP were 19.71 micrograms/ml and 1.75 micrograms/ml, respectively, indicating substantial drug adsorption by the DHP. The estimated drug removal rate was 31.1%. This treatment led to a marked regression of tumors with tolerable systemic toxicities. Although the patient subsequently died 9 months after treatment of progression of disease, this treatment resulted in a remission of significant duration.