Protective effect of hypotaurine against oxidative stress-induced cytotoxicity in rat placental trophoblasts.

INTRODUCTION: Hypotaurine is a precursor of taurine and an antioxidant, and is concentrated in fetal plasma compared to maternal plasma. Hypotaurine is significantly decreased in fetal plasma of ezrin (Vil2) knock-out mice, and fetuses show intrauterine growth retardation. The aim of this study was to characterize the mechanism through which cellular hypotaurine level is maintained in placental trophoblasts, and the effect of hypotaurine on oxidative stress induced by hydrogen peroxide (H2O2). METHODS: Hypotaurine transfer from extracellular fluid and antioxidant effect of hypotaurine were analyzed in rat placental trophoblast TR-TBT 18d-1 cells. RESULTS: We found that hypotaurine is concentrated into rat placental trophoblast TR-TBT 18d-1 cells, and the level of hypotaurine was markedly reduced by culture in medium supplemented with dialyzed fetal bovine serum (FBS) instead of normal FBS. The hypotaurine level recovered almost completely when hypotaurine was added to the culture medium, indicating that intracellular hypotaurine is predominantly supplied by transport across the plasma membrane from extracellular fluid rather than by biosynthesis. Hypotaurine showed a cytoprotective effect against H2O2-induced oxidative damage in TR-TBT 18d-1 cells. Hypotaurine treatment of TR-TBT 18d-1 cells increased antioxidant capacity against hydroxyl radical and peroxyl radical. The concentration of intracellular hydroxyl radical induced by H2O2 in TR-TBT 18d-1 cells was significantly reduced by hypotaurine treatment. DISCUSSION: These results indicate that intracellular hypotaurine is mainly supplied to placental trophoblasts by transfer from extracellular fluid across the plasma membrane, and may play a role in cell protection by scavenging reactive oxygen species.

Dental hygiene residential care in a 3-year dental hygiene education programme in Japan: towards dysphagia management based on the dental hygiene process of care.

This paper reports an evaluation of a residential care practice, which was part of a 'Dysphagia Management' course introduced into a 3-year dental hygiene curriculum in Japan. The clinical practice was performed at a care facility for the elderly people. Dental hygiene interventions, which consisted mainly of professional oral care, were implemented on a client who was bed-bound after suffering from a stroke. As the client had severe tension in muscles around oral cavity, it was difficult for the facility care workers to provide daily oral hygiene care. The goals of the dental hygiene care plan included decreasing tension of oral muscles and reducing periodontal inflammation and halitosis. The dental hygiene interventions were given once a month for 5 months. Evaluation in the fifth month demonstrated relaxation of oral muscles, decrease in plaque accumulation, and improvements in levels of gingival inflammation, indicating the partial achievements of the initial goals. Possibilities for revision of the care plan could call for more active involvement of the facility care workers and client-centered goal setting. This learning experience provided an opportunity for continuing intervention and evaluation of dental hygiene care for the same client. The positive results of our limited interventions further confirmed the importance of professional oral care in organic and functional improvements in oral health for the elderly people.

Bleeding tendency as a first symptom in children with congenital biliary dilatation.

AIM OF THE STUDY: Although a bleeding tendency as a first symptom is a critical condition in congenital biliary dilatation (CBD), the clinical details of this symptom remain unclear. We assessed this condition in children with CBD in this paper. MATERIALS AND METHODS: Sixty-five children with CBD were treated at our institute between 1983 and 2004. The children, initially presenting with bleeding manifestations such as intracranial hemorrhage and bloody stools, were defined as the bleeding group, and the remaining children with digestive symptoms such as abdominal pain and vomiting were defined as the digestive group. The clinical features were compared between these two groups. RESULTS: In 6 of the 65 cases, bleeding manifestations were noted (9.2 %). All six had cystic-type choledochal dilatation. The mean age of the bleeding group was significantly younger than that of the digestive group, and bleeding was more frequent, especially in infants less than 12 months of age. In a laboratory study, the bleeding group showed a more prolonged blood coagulation time than the digestive group did. Serum amylase and lipase levels in the bleeding group were almost normal, while those in the digestive group were significantly higher. The direct bilirubin level in the bleeding group was significantly higher than that in the digestive group. CONCLUSIONS: Disturbed blood coagulation due to vitamin K deficiency related to cholestasis results in a bleeding tendency in children with CBD. Therefore, pediatric surgeons should be aware of this rare but critical condition which can be prevented by rapid and precise treatment with vitamin K supplementation.

Catheter-tip fixation of a percutaneously implanted port-catheter system to prevent dislocation.

The aim of this study was to evaluate the incidence of catheter tip dislocation in patients with percutaneously implanted port-catheters for hepatic arterial chemotherapy with catheter tip fixation. Forty-seven patients (31 men and 16 women; mean age 66 years) with unresectable advanced liver cancers (primary liver cancer, n=19; metastatic liver cancer, n=28) underwent percutaneously implantable port-catheter system placement with the tip fixed at the gastroduodenal artery with coils and side hole opened at the common hepatic artery. In 39 patients, n-butyl cyanoacrylate (NBCA) mixed with Lipiodol was added for fixation. The position of the side hole after the indwelling port-catheter system was investigated, and the correction method in cases with catheter dislocation was determined. In 2 (25%) of the 8 patients without NBCA fixation, dislocation of the catheter was noted, in contrast to none (0%) of 37 patients with NBCA fixation. Two patients in whom NBCA was used could not undergo long-term intra-arterial chemotherapy because of hepatic arterial thrombotic occlusion which occurred after placement of the indwelling catheter, and were excluded from the evaluation. Fixation of the catheter tip with combined use of coils and NBCA--Lipiodol mixture to the gastroduodenal artery is important to prevent dislocation of the port-catheter system.

Triptolide attenuates pulmonary arterial hypertension and neointimal formation in rats.

This paper reports the effect of triptolide (a diterpenoid triepoxide) on the development of monocrotaline (MCT)-induced pulmonary hypertension in pneumonectomized rats. Male Sprague- Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Rats received therapy from Day 5 to 35 with triptolide (0.25 mg/kg intraperitoneally, every other day, n = 10), or vehicle (0.1 ml of ethanol/cremophor intraperitoneally, every other day, n = 10). By Day 35, triptolide-treated rats demonstrated lower mean pulmonary arterial pressure (mPAP) than vehicle-treated rats (mPAP 21 +/- 3 versus 42 +/- 5 mm Hg, p < 0.001). Triptolide-treated rats also had significantly less right ventricular hypertrophy (RVH) and pulmonary arterial neointimal formation. In a rescue experiment, rats initiated therapy on Day 21. At Day 35, vehicle-treated rats (n = 4) had higher mPAP (40 +/- 9 mm Hg), greater RVH, and more severe pulmonary arterial neointimal formation than rats that received triptolide (0.25 mg/kg every other day, n = 7, mPAP 30 +/- 4 mm Hg) and rats that received triptolide (0.2 mg/kg daily, n = 7, mPAP 25 +/- 5 mm Hg, p < 0.01). In pneumonectomized rats that receive MCT, triptolide attenuates the development of pulmonary hypertension and RVH, and promotes regression of pulmonary arterial neointimal formation.

Early and delayed Tc-99m ECD brain SPECT in SLE patients with CNS involvement.

We compared early and delayed Tc-99m ECD SPECT scans in 32 SLE patients (Group 1, definite neuropsychiatric disorders; Group 2, minor neurologic symptoms or normal) with those of normal controls by visual inspection and semi-quantitative evaluation. With visual interpretation, 13 out of 14 patients in Group 1 (93%) and 7 out of 18 patients in Group 2 (39%) had diffuse uneven decrease in early scans. Seven patients in Group 2 (39%) who had normal early scans demonstrated focal decrease in the medial frontal lobe in delayed scans. With cerebral region to cerebellar ratios, in early scans, the medial frontal lobe in Group 1 and Group 2 was significantly lower than in normal controls, and lateral frontal lobe and occipital lobes in Group 1 were significantly lower than in normal controls. Nevertheless, in delayed scans, every cortical region except for the parietal lobe in Groups 1 and 2 was significantly lower than in normal controls. The retention rates in all regions in SLE patients were significantly lower than in normal controls. No case showed SPECT improvement on follow-up studies in either group in spite of clinical improvement. Delayed Tc-99m ECD brain SPECT of high sensitivity might be useful in detecting CNS involvement. Although the SPECT findings did not correlate with the neuropsychiatric symptoms, early and delayed Tc-99m ECD SPECT seems to provide useful objective diagnostic information in SLE patients.

Functional brain areas used for the lifting of objects using a precision grip: a PET study.

Positron emission tomography (PET) was performed in 10 normal volunteers to investigate regional cortical and subcortical activation induced by the lifting of an object repetitively using a precision grip between the index finger and thumb. Data were obtained for three object weights (4, 200 and 600 g) and a resting condition. Grip and lift forces on a similar object and the activity of selected muscles in the hand, arm and shoulder were also recorded in separate lifting trials. A comparison between all movement conditions and the resting condition revealed significant activation of the primary motor (M1), primary sensory (S1), dorso-caudal premotor (PM), caudal supplementary motor (SMA) and cingulate motor (CMA) cortices contralateral to the hand used. On the ipsilateral side, activation of the M1, caudal SMA and inferior parietal cortex (BA 40) was also found. In the subcortical areas, the bilateral hemispheres and right vermis of the cerebellum, left basal ganglia and thalamus were activated. Behavioral adaptation to a heavier object weight was revealed in a nearly proportional increase of both grip and lift forces, prolonged force application period and a higher level of hand and arm muscle activities. An increase in the rCBF associated with these changes was noted in several cortical and subcortical areas. However, consistent object weight-dependent activation was observed only in the M1/S1 contralateral to the hand used.

Lumped constant for deoxyglucose is decreased when myocardial glucose uptake is enhanced.

Quantification of myocardial glucose uptake by positron emission tomography with [18F]fluorodeoxyglucose (FDG) requires the "lumped constant" (LC), which corrects the difference of affinity between glucose and FDG to glucose transporters and phosphorylating system. Since LC was introduced, it has been considered to be constant. However, this has recently been questioned. To elucidate the constancy of LC by other than radioisotope techniques, the accumulation rate of sugar phosphates (d[SP]/dt) was measured in isolated, perfused rat hearts by 31P NMR spectroscopy with 2-deoxyglucose (DG). We postulate alpha as the affinity of DG to transporters and the phosphorylating system relative to that of glucose. Theoretically, alpha is equivalent to LC. We determined alpha by measuring d[SP]/dt at DG concentration ([DG]) = 10, 7, 5, and 3 mmol/l, keeping the total of glucose concentration ([glucose]) and [DG] to 10 mmol/l. When the glucose uptake was enhanced by insulin (10 mU/ml) or stunning, calculated alpha was reduced (insulin stimulated, 0.15; stunning, 0.19) compared with the control (0.59). These results indicate that LC can be evaluated by methods without radiolabeled tracers and is smaller when glucose uptake is augmented.

NMDA receptors in the inferior colliculus are critically involved in audiogenic seizures in the adult rats with neonatal hypothyroidism.

The effects of N-methyl-d-aspartate (NMDA) and non-NMDA receptor antagonists were compared on audiogenic seizures in the rats neonatally exposed to propylthiouracil (PTU). The rats treated with 0.02% PTU through mother's milk during days 0-19 after delivery showed a high incidence of audiogenic seizures consisting of running fit (RF) followed by generalized tonic-clonic seizure (GTCS) after matured. The systemic administration with MK-801, a NMDA receptor antagonist dose-dependently inhibited both RF and GTCS. NBQX (6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione), a non-NMDA receptor antagonist, when systemically administered, failed to block audiogenic seizures. Audiogenic seizures caused a marked induction of c-fos messenger RNA (mRNA) in septal nucleus, bed nucleus of stria terminalis, amygdaloid nuclei, peripeduncular nucleus, and inferior colliculus, which was almost completely blocked by the pretreatment with MK-801. Bilateral microinjection of MK-801 into the inferior colliculus showed a tendency for inhibiting GTCS, but not RF, whereas CPP (3-(R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid), a competitive NMDA receptor antagonist produced a significant inhibition against both RF and GTCS. These NMDA receptor antagonists administered into cisterna ambience, the floor of which is composed of inferior colliculus and neighboring structures, have shown potent blocking effects on both RF and GTCS. The present results suggest that NMDA receptors in the inferior colliculus, presumably in the subnucleus of external cortex may play the critical role in the initiation of audiogenic seizures in PTU-treated rats.

Immunosuppressive effects of gallic acid and chebulagic acid on CTL-mediated cytotoxicity.

Gallic acid (GA) and chebulagic acid (CA) were isolated from the extract of a herbal medicine, kashi (myrobalans: the fruit of Terminalia chebula) as active principles that blocked the cytotoxic T lymphocyte (CTL)-mediated cytotoxicity. GA and CA inhibited the killing activity of CD8+ CTL clone at IC50 values of 30 microM and 50 microM, respectively. Granule exocytosis in response to anti-CD3 stimulation was also blocked by GA and CA at the equivalent concentrations.

Intra-individual differences between technetium-99m-HMPAO and technetium-99m-ECD in the normal medial temporal lobe.

UNLABELLED: Regional distributions of 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO) and 99mTc-ethyl cysteinate dimer (99mTc-ECD) were compared in the normal brain. METHODS: Six paid, healthy volunteers (mean age 26 yr) had high-resolution neuroperfusion SPECT using both 99mTc-HMPAO and 99mTc-ECD on separate days. RESULTS: Regional distribution of the two tracers differed. Technetium-99m-HMPAO accumulated more in the thalamus, frontal lobe, temporal lobe and cerebellum than 99mTc-ECD, which accumulated more in the occipital and parietal lobes. There was a considerable difference in the accumulation of the two tracers in the medial temporal lobe. The percent accumulations of 99mTc-HMPAO and 99mTc-ECD in the medial temporal lobe compared with the mean global cerebral cortical accumulation were 93.9% +/- 2.4% and 83.1% +/- 4.1% (mean +/- s.d.), respectively. CONCLUSION: The results suggest that 99mTc-HMPAO and 99mTc-ECD require specific and separate criteria for diagnosing temporal lobe pathologies, such as dementia and temporal lobe epilepsy.

Enhancement of [123I]beta-CIT binding in the striatum with clomipramine: is there a serotonin-dopamine interaction?

Many reports support the concept of serotonergic-dopaminergic interaction in the brain. However, at present, there are few methods to study this relationship in vivo. The purpose of this study was to investigate the effect of serotonin (5-HT) uptake inhibitor, clomipramine, on a dopamine (DA) transporter ligand, [123I]beta-CIT (RTI-55), in rat brain. Dose-dependent changes in [123I]beta-CIT specific binding induced by clomipramine were studied in the striatum (rich in DA transporter) and the hypothalamus (rich in 5-HT transporter). The changes in the time-activity curves of [123I]beta-CIT specific binding after clomipramine injection were also examined in these two regions. Using the cerebellum as the reference region, k3 and k4 values with and without clomipramine administration were estimated by a two-compartment kinetic analysis. Clomipramine inhibited [123I]beta-CIT specific binding in the hypothalamus, but enhanced its specific binding in the striatum in a dose-dependent manner. Kinetic analysis showed that k3 in the striatum was increased by 55%. In conclusion, enhancement of [123I]beta-CIT binding in the striatum after clomipramine administration indicated the possibility of 5-HT-DA interaction.

Enhancement of glucose uptake in stunned myocardium: role of glucose transporter.

This study quantifies the myocardial glucose uptake and clarifies the pathway of augmented glucose uptake in myocardium reperfused after a brief period of ischemia (stunned myocardium). The glucose uptake rate was determined from the time course of the sugar phosphate (SP) resonance in rat myocardium (d[SP]/dt) with 31P nuclear magnetic resonance after the substitution of glucose with its analog 2-deoxyglucose. The d[SP]/dt in stunned myocardium [1.03 +/- 0.05 (SE) micromol x g wet wt(-1) x min(-1); n = 8] increased significantly compared with nonischemic control myocardium (0.18 +/- 0.03 micromol x g wet wt(-1) x min(-1); n = 8; P < 0.0001), reaching the maximal stimulatory uptake rate during exposure to insulin (1.05 +/- 0.04 micromol x g wet wt(-1) x min(-1); n = 8). Twenty minutes after reperfusion, the d[SP]/dt was still augmented (0.41 +/- 0.05 micromol x g wet wt(-1) x min(-1); n = 5; P < 0.05 vs. control myocardium). To elucidate further the mechanism of augmented glucose uptake, N6-(L-2-phenylisopropyl)-adenosine (PIA; 100 micromol/l), a potent blocker of the glucose transporter, was administered to stunned hearts and, as a control, to insulin-stimulated hearts. PIA significantly and comparably inhibited the increase in d[SP]/dt in stunned myocardium (0.36 +/- 0.07 micromol x g wet wt(-1) x min(-1); n = 4; P < 0.0001 vs. without PIA) and in insulin-stimulated myocardium (0.38 +/- 0.02 micromol x g wet wt(-1) x min(-1); n = 4; P < 0.0001 vs. without PIA). These results indicate that the augmented glucose uptake in stunned myocardium is maintained by the glucose transporter, the amount of which is almost equal to that which can be maximally recruited by insulin.

Mitochondrial abnormalities in a murine model of primary carnitine deficiency. Systemic pathology and trial of replacement therapy.

Mitochondrial abnormalities and effectiveness of replacement therapy were examined in a murine model of systemic carnitine deficiency, namely the juvenile visceral steatosis (JVS) mouse. Homozygous JVS mice revealed severe lipid deposition and abnormal mitochondria in liver, heart, skeletal muscle, and kidney, but there was no pathological change in the nervous system, though they showed cerebral signs. There were numerous ragged-red fibers in muscles, but enzyme activities of the respiratory chain were intact. Histograms of oxidative and nonoxidative muscle fibers showed an increase in small and oxidative muscle fibers in 4-week-old JVS mice, but this difference no longer existed in 8-week- or 1-year-old JVS mice. On the contrary, Mn-superoxide dismutase immunostaining of muscle showed a focal increase in every age of JVS mice. With L-carnitine treatment, JVS mice could survive for a year, but to some extent, there were the same pathological changes as those seen in untreated mice.

Super-early iodine-123-iodoamphetamine SPECT imaging of human primary motor cortex.

UNLABELLED: This study was designed to visualize the motor function area related to finger movements in normal human brain using super-early (first 640 sec of acquisition) [123l]iodoamphetamine ([123I]IMP) SPECT. METHODS: Seven healthy male volunteers performed paired, isolated baseline and task sessions. The task was a right thumb-to-fingers opposition task, which was loaded for the initial 11 min of the session. A high-performance, four-head SPECT camera was used. At each session, administration of 222 MBq [123I]IMP was followed by 16 serial 160-sec dynamic SPECT acquisitions. To obtain matched brain anatomical images, MRI was also performed using the same slice formation as in the SPECT study. After image reconstruction, ROIs were set on bilateral sensorimotor hand areas (SMHA), the supplementary motor area (SMA), the frontal, temporal and occipital lobes and the cerebellar hemispheres. The percent increase of ROI activity (%INC) in the task session compared with that in the baseline session was calculated in each ROI after normalization to the global brain radioactivity. RESULTS: There was significant activation of the left SMHA by the task, the amplitude of which was maximal in the initial phase of dynamic images (the super-early phase). This area was located in the left peri-central area identified on the analogous slice in the MR image. The left SMHA showed gradual and statistically significant decrease of %INC during the three phases. CONCLUSION: Super-early [123I]IMP may be used to identify the primary motor cortex and to evaluate its function in some pathological conditions.

Effect of etodolac on prostaglandin E2 biosynthesis, active oxygen generation and bradykinin formation.

The inhibitory actions of etodolac on prostaglandin (PG) E2 biosynthesis, active oxygen generation and bradykinin formation were compared with those of indomethacin, diclofenac Na, piroxicam, naproxen, ketoprofen and aspirin. The inhibitory action (IC50 5.35 x 10(-8) M) of etodolac on PGE2 biosynthesis in rabbit articular chondrocytes stimulated by interleukin-1 (IL-1) beta was about 1/5 that of indomethacin. The inhibitory action of etodolac on spontaneous PGE2 biosynthesis in rabbit gastric epithelial cells (RGEs) (IC50 2.27 x 10(-5) M) and Madin-Darby canine kidney cells (MDCKs) (IC50 4.54 x 10(-7) M) was much less than that in rabbit articular chondrocytes stimulated by IL-1 beta and about 1/19 and 1/9 that of indomethacin in rabbit gastric epithelial cells (RGEs) and Madin-Darby canine kidney cells (MDCKs), respectively. The inhibitory action of etodolac on active oxygen generation was similar to that of indomethacin and piroxicam, and more potent than that of naproxen, ketoprofen and aspirin. The inhibitory action of etodolac on bradykinin formation was the most potent among the seven anti-inflammatory drugs tested. Both etodolac and bromelain inhibited the inflammatory pain in concanavalin A-treated paws of rats in a dose-dependent manner, but indomethacin did not. These results indicate that etodolac is an anti-inflammatory drug which suppress IL-1 beta-stimulated PGE2 biosynthesis in rabbit articular chondrocytes, active oxygen generation and bradykinin formation. It has less suppressive action against spontaneous PGE2 biosynthesis in RGEs and MDCKs. Thus, etodolac is considered to be a safe anti-inflammatory drug for clinical use.

Datura stramonium agglutinin released histamine from rat peritoneal mast cells that was inhibited by pertussis toxin, haptenic sugar and N-acetylglucosamine-specific lectins: involvement of glycoproteins with N-acetylglucosamine residues.

The N-acetyl glucosamine (GlcNAc)-specific lectin Datura stramonium agglutinin (DSA) rapidly and sugar-specifically released histamine from rat peritoneal mast cells, and pertussis toxin (IAP) inhibited it, suggesting that DSA activated mast cells via an IAP-sensitive G protein pathway. The additive effects of DSA and basic secretagogues such as compound 48/80 that activate IAP-sensitive G protein directly suggest that they shared the same mechanism of action including involvement of the IAP-sensitive G protein. Using lectin-blotting, blots of the corresponding glycoproteins detected by DSA diminished by haptenic sugar or pretreatment of the cells with N-glycosidase F, suggesting that the binding of DSA was responsible for the mast cell activation. The other GlcNAc-specific lectins such as Phytolacca americana mitogen, Solanum tuberosum agglutinin and wheat germ agglutinin (WGA) inhibited the histamine release induced by DSA, suggesting that these lectins were antagonists, but DSA was an agonist. Sialic acid-specific Macckia amurensis mitogen (MAM) inhibited the histamine release, and neuraminidase-treatment decreased mast cell activation induced by DSA. At least four mast cell glycoproteins that have affinity to DSA, WGA and MAM and are sensitive to neuraminidase-treatment were detected by lectin-blotting. Some of them may be binding sites coupled to histamine release including the IAP-sensitive G protein pathway. DSA is a useful tool for studying signal transduction of mast cells including the involvement of the IAP-sensitive G protein.

An initial signal of activation of rat peritoneal mast cells stimulated by Datura stramonium agglutinin: a confocal fluorescence microscopic analysis of intracellular calcium ion and cytoskeletal assembly.

A confocal fluorescence microscope using fluo-3 and 9-(dicyanovinyl)- julolidine (DCVJ) was used to study the mast cell activation by the N-acetyl glucosamine oligomer specific lectin Datura stramonium agglutinin (DSA) and inhibition by antagonist lectins having affinity to N-acetyl glucosamine (GlcNAc). DSA induced a transient increase in intracellular free calcium concentration ([Ca2+]i) followed by cytoskeletal disassembly and reassembly in rat peritoneal mast cells. These changes induced by DSA resulted in histamine release. The time course of fluorescence intensity in mast cells loaded with fluo-3- or DCVJ and activated by DSA resembled those activated by the basic polymer compound 48/80. Inhibition of [Ca2+]i rise by antagonist lectins was responsible for the inhibition of cytoskeletal assembly and the consequent histamine release induced by DSA. At the level of the individual cell, a mast cell stimulated by DSA responds in an all-or-none fashion. DSA possible induced intracellular calcium mobilization and cytoskeletal change by recognizing the GlcNAc-oligomer residues of specific glycoproteins of mast cells.

[A comparative clinical study on the treatment of head and neck tumors by adjuvant chemotherapy with HCFU--Second Study by Kinki Head and Neck Tumor Study Group].

In the first study by the "Kinki Head and Neck Tumor Study Group," we performed a comparative study to investigate intergroup difference between a control group consisting of patients given radical treatment only, and a HCFU group consisting of patients receiving long-term administration of HCFU after radical treatment. We earlier reported that subsequent observations by stratification revealed a favorable tendency in the cumulative disease-free rate in Stage II and Stage III patients in the HCFU group. In the second study, the same methods of treatment as in the first study were compared in a prospective control study. No differences were found between the two groups in Stage II patients. In Stage III patients, however, the disease-free rate tended to increase significantly in the HCFU group as in the first study.

[Clinical evaluation of S-1108 in pediatric field].

Nine pediatric patients with bacterial infections (5 cases of tonsillitis, 3 cases of impetigo and 1 case of UTI) were treated with S-1108, and the efficacy and the safety were evaluated. The clinical responses to S-1108 treatment were excellent in 7 cases and good in 2. The efficacy rate was 100%. Bacteriologically, the causative organisms (Streptococcus pyogenes, Staphylococcus aureus, Haemophilus parainfluenzae and Escherichia coli) were eradicated. No clinical side effects were observed. Elevation of CK in 2 cases and eosinophilia in 1 case were noted.