Search

Objectives: To determine the optimal management for early-onset thrombophilia (EOT), the genetic and clinical features of protein C (PC)-, protein S (PS)-, or antithrombin (AT)-deficient patients of ≤20 years of age were studied in Japan., Methods/results: Clinical and genetic information of all genetically diagnosed cases was collected through the prospective, retrospective study, and literature review. One-hundred-one patients had PC (n = 55), PS (n = 29), or AT deficiency (n = 18). One overlapping case had PC- and PS-monoallelic variant. Fifty-five PC-deficient patients (54%) had 26 monoallelic or 29 biallelic variant(s), and 29 (29%) PS-deficient patients had 20 monoallelic or nine biallelic variant(s). None of the patients had AT-biallelic variants. The frequent low-risk allele p.K193del (PC-Tottori) was found in five patients with monoallelic (19%) but not 29 with biallelic variant(s). The most common low-risk allele p.K196E (PS-Tokushima) was found in five with monoallelic (25%) and six with biallelic variant(s) (67%). One exceptional de novo PC variant was found in 32 families with EOT. Only five parents had a history of thromboembolism. Thrombosis concurrently developed in three mother-newborn pairs (two PC deficiency and one AT deficiency). The prospective cohort revealed the outcomes of 35 patients: three deaths with PC deficiency and 20 complication-free survivors. Neurological complications were more frequently found in patients with PC-biallelic variants than those with PC-, PS-, or AT-monoallelic variants (73% vs. 24%, p = .019)., Conclusions: We demonstrate the need for elective screening for EOT targeting PC deficiency in Japan. Early prenatal diagnosis of PC deficiency in mother-infant pairs may prevent perinatal thrombosis in them., (© 2023 Wiley Periodicals LLC.)

Objective: To clarify the incidence and genetic risk of neonatal-thromboembolism, we conducted a nationwide study exploring the impact of thrombophilia on neonatal-thromboembolism in Japan., Study Design: A questionnaire survey was conducted for perinatal centers in Japan, focusing on the clinical expression, genotype, treatment, and outcome of patients who developed thromboembolism within 28 days of birth from 2014 to 2018., Results: The estimated incidence of neonatal-thromboembolism was 0.39 cases per 10 000 live births. Intracranial lesions and purpura fulminans occurred in 66 and 5 of 77 patients, respectively. Fifty-eight (75.3%) infants presented within 3 days after birth. Four (5.2%) died, and 14 (18.2%) survived with disability. At the diagnosis, <20% plasma activity of protein C was noted in 16 infants, protein S (in 2), and antithrombin (in 1). Thirteen genetic tests identified 4 biallelic and 5 monoallelic protein C-variants but no protein S- or antithrombin-variants. Protein C-variants had purpura fulminans (P < .01), ocular bleeding (P < .01), positive-family history (P = .01), and death or disability (P = .03) more frequently than others. Protein C-variants were independently associated with disability (OR 5.74, 95% CI 1.16-28.4, P = .03) but not death. Four biallelic variants had serious thrombotic complications of neurologic disability, blindness, and/or amputation. Three monoallelic variants survived without complications. The only protein C-variant death was an extremely preterm heterozygote infant., Conclusions: Monoallelic protein C-variants had a higher incidence of neonatal-thromboembolism than biallelic variants. Thrombophilia genetic testing should be performed in the setting of neonatal-thromboembolism and low protein C to identify the underlying genetic defect., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: This study aimed to investigate the utility of transcutaneous (tc) measurements of partial pressure of oxygen (tcPO 2 ) and carbon dioxide (tcPCO 2 ) monitoring in neonatal intensive care units (NICUs) in Japan., Methods: At the end of 2016,we sent a survey questionnaire on tc monitoring to all 106 NICUs registered with the Japanese Neonatologist Association. The questions included usage, subjects, methods, management, and the practical usefulness of tc monitoring., Results: The questionnaire was returned by 69 NICUs (65.1% of response rate). Seventeen institutions (24.6%) measured both tcPCO 2 and tcPO 2 , and 42 (60.9%) measured tcPCO 2 alone. Transcutaneous PCO 2 or tcPO 2 monitoring was applied for "pre-viable" infants born at 22-23 weeks' gestational age (18.6% vs 23.5%), and infants of <500 g birthweight (30.5% vs 17.6%). The tcPCO 2 and tcPO 2 monitoring was started at birth in 49.2% and 70.6% of the newborn infants, respectively. The temperature of the sensor was set at <38°C for tcPCO 2 in 54.3% and >42°C for tcPO 2 in 58.9% of NICUs. The accuracy for tcPO 2 was rated as good in 35.3% or moderate in 64.7%, of institutions but or for tcPCO 2 as 1.7% or 93.2%of institutions , respectively., Conclusion: Transcutaneous monitoring was widely, but limitedly, used for preterm infants. The lower temperature of the tcPCO 2 sensor compared to that reported in other developed countries might compromise the accuracy but increase the feasibility of tc monitoring in Japan., (© 2019 Japan Pediatric Society.)

Objective: To determine clinical features of very low birth weight infants (VLBWIs) who had developed epilepsy by age 3 years., Study Design: Multicenter cohort study using the Neonatal Research Network of Japan database. We analyzed clinical variables of 8431 VLBWIs who had recorded data of neurological sequelae at age 3 years. Logistic regression identified the association between variables and development of epilepsy., Result: One hundred and forty-three (1.7%) infants developed epilepsy, 683 (8.1%) showed cerebral palsy (CP), and 1114 (13.2%) had psychomotor delay. Epilepsy was associated with history of sepsis [adjusted odds ratio (AOR) 3.23], severe intraventricular hemorrhage (IVH; AOR 5.13), and cystic periventricular leukomalacia (PVL; AOR 12.7). Severe IVH and cystic PVL were also frequently associated with CP and psychomotor delay., Conclusion: Severe IVH and cystic PVL are strongly associated with development of epilepsy, as well as other neurological sequelae, and are potential critical therapeutic targets.

Background: To investigate the hematological features of infants with bronchopulmonary dysplasia (BPD) and their relationships with clinical severity., Methods: This prospective observational study enrolled 73 BPD patients from a total of 331 infants with a birth weight of <1500 g from 2005 to 2013. The clinical severity of BPD was defined by the duration of oxygen supplementation and positive pressure ventilation (PPV) in line with the diagnostic criteria of BPD. The hematological status and cytokine levels were surveyed from blood samples at birth and at 2 and 4 weeks of life., Results: Thirty-four (46.6%) cases were classified as "moderate-to-severe" BPD. Small-for-gestational-age (SGA) was associated with the severity of BPD (OR: 5.05; 95% CI: 1.45 to 17.2). The CRP level at 2 weeks (partial regression coefficient [rc]: 21.8; 4.01 to 39.7) and the neutrophil count at 4 weeks (0.005; 0.001 to 0.007) were positively correlated with the oxygenation period. The PPV period was found to be correlated with the CRP level at 2 weeks (27.2; 14.9 to 39.5), and the neutrophil count (0.003; 0.001 to 0.004) at 4 weeks., Conclusion: The aggravation of BPD was associated with both SGA at birth and inflammation during neonatal period., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To investigate whether the development of postnatal, late-onset refractory hypotension, referred to as late-onset circulatory collapse, was associated with an increased risk of developing cerebral palsy (CP) at 3 years of age in extremely preterm infants., Methods: In this historical cohort study, infants who were born at 22-27 weeks of gestation from 2008 to 2012 in the Neonatal Research Network of Japan were eligible. The study sample consisted of 3474 infants (45.6% of 7613 potentially eligible infants) who were evaluated at 36-42 months of age. Late-onset circulatory collapse was defined as a clinical diagnosis of late-onset circulatory collapse requiring treatment with corticosteroids. We compared the neurodevelopmental outcomes between infants with and without late-onset circulatory collapse., Results: Late-onset circulatory collapse was diagnosed in 666 of the infants studied. Infants with late-onset circulatory collapse had a higher incidence of CP than those without late-onset circulatory collapse (18.0% vs 9.8%; P < .01). In multivariable logistic analysis, late-onset circulatory collapse was independently associated with CP (aOR, 1.52; 95% CI, 1.13-2.04) and developmental quotient score of <50 (OR, 1.83; 95% CI, 1.23-2.72)., Conclusions: Late-onset circulatory collapse may be a relatively common event occurring in extremely preterm infants and an independent risk factor for CP at 3 years of age., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Abstarct: OBJECTIVE: The diagnosis of neonatal-onset protein C (PC) deficiency is challenging. This study aimed to establish the neonatal screening of heritable PC deficiency in Japan., Study Design: We determined the changes in plasma activity levels of PC and protein S (PS) in healthy neonates, and studied newborn patients with PROC mutation in the Japanese registry., Result: Physiological PC and PS levels increased with wide range. The PC/PS-activity ratios converged after birth. The PC/PS-activity ratios of 19 patients with biallelic mutations, but not, 9 with monoallelic mutation, were lower than those of 13 without mutation. The logistic regression analyses established a formula including two significant variables of PC activity (cut-off < 10%, odds ratio = 30.0) and PC/PS-activity ratio (cut-off < 0.35, odds ratio = 22.7), with 93% sensitivity and 44% specificity for determining patients with mutation(s)., Conclusion: The PC/PS-activity ratio is an effective parameter for the genetic screening of neonatal-onset PC-deficiency in Japanese population.

Objectives: Tracheostomy is indicated for very-low-birth-weight infants (VLBWIs) with prolonged respiratory problems during the perinatal period. The objective of this study is to clarify the epidemiology and risk factors in VLBWIs with tracheostomy after birth in Japan., Methods: A total of 40 806 VLBWIs were registered in the Neonatal Research Network of Japan database from 2003 to 2012. Among them, 34 674 infants (85%) survived over 28 days after birth and were subjected to this study. The clinical variables at birth, outcomes at hospital discharge and associated factors for tracheostomy were examined., Results: The proportion of VLBWIs with tracheostomy did not increase during the study period (mean 36 cases per year, 0.93%). The rate of in-hospital death over 28 days after birth did not differ between tracheostomized and non-tracheostomized infants (2/324, 0.6% vs 314/34 350, 0.9%). Tracheostomized infants more frequently had severe or moderate bronchopulmonary dysplasia (BPD) (75.5% vs 26.0%, P < 0.01) and longer hospitalization (229 days vs 83 days, P < 0.01) than non-tracheostomized infants. Tracheostomized patients showed higher comorbidities with hypoxic ischemic encephalopathy (odds ratio [OR] 10.98, P < 0.01), muscular disease (OR 10.95, P < 0.01), severe or moderate BPD (OR 7.79, P < 0.01), chromosomal abnormality (OR 4.43, P < 0.01) or sepsis (OR 1.78, P < 0.05) at hospital discharge than non-tracheostomized patients., Conclusion: We demonstrated the non-increasing rate in tracheostomy for VLBWIs and such cases were associated with an excellent survival in Japan. These data provide evidence that more attentive care must be practiced in order to reduce the pulmonary and neuromuscular burdens of VLBWIs at birth., (© 2018 Wiley Periodicals, Inc.)

Objectives: To determine neurodevelopmental outcomes at 3 years of age in children born with a birth weight (BW) of ≤500 g., Methods: Infants who were born with a BW of ≤500 g from 2003 to 2012 in the Neonatal Research Network of Japan and survived to discharge from the NICU were eligible in this study. The study population consisted of 460 children (56.7% of 811 surviving infants) who were evaluated at 36 to 42 months of age. Neurodevelopmental impairment (NDI) was defined as having cerebral palsy, visual impairment, hearing impairment, or a developmental quotient score of <70., Results: The overall proportion of NDI was 59.1% (95% confidence interval [CI]: 54.6%-63.5%). The trend revealed no significant change during the study period. In a multivariate modified Poisson regression analysis, NDI was associated with severe intraventricular hemorrhage (adjusted risk ratio [RR]: 1.42; 95% CI: 1.19-1.68; P < .01), cystic periventricular leukomalacia (adjusted RR: 1.40; 95% CI: 1.13-1.73; P < .01), severe necrotizing enterocolitis (adjusted RR: 1.31; 95% CI: 1.07-1.60; P < .01), surgical ligation for patent ductus arteriosus (adjusted RR: 1.29; 95% CI: 1.09-1.54; P < .01), and male sex (adjusted RR: 1.19; 95% CI: 1.01-2.40; P = .04)., Conclusions: This cohort showed that neurodevelopmental outcomes of infants with a BW of ≤500 g have not improved from 2003 to 2012. Multivariate analysis revealed that severe intracranial hemorrhage and cystic periventricular leukomalacia were the strongest risk factors for NDIs. Our data suggested that measures aimed at reducing neurologic morbidities will be important for improving outcomes of infants with a BW of ≤500 g., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Background: Lipomyelomeningocele (LMMC) is defined by a low-lying tethered spinal cord protruding posteriorly from the spinal canal and terminating in a lipomatous mass in the subcutaneous meningeal sac. The coexistence of LMMC with split cord malformation (SCM) is rare., Clinical Presentation: We report on a patient with laterally protruded LMMC arising from the hemicord of SCM type I. Direct coronal and axial views (instead of sagittal views) of 3D heavily T2-weighted MR imaging (3D-hT2WI) clearly demonstrated the topographical relationship between both of the hemicords, the bony septum, and nerve roots in the right subcutaneous meningeal sac., Conclusion: Combined use of axial and coronal images of 3D-hT2W is useful for visualization and surgery of such a complicated anomaly.

To investigate if ipragliflozin, a novel sodium-glucose co-transporter 2 inhibitor, alters body composition and to identify variables associated with reductions in visceral adipose tissue in Japanese patients with type 2 diabetes mellitus. This prospective observational study enrolled Japanese participants with type 2 diabetes mellitus. Subjects were administered ipragliflozin (50 mg/day) once daily for 16 weeks. Body composition, visceral adipose tissue volume and plasma variables were measured at 0, 8, and 16-weeks. The subjects' lifestyle habits including diet and exercise were evaluated at baseline and 16 weeks. The primary endpoint was defined as the decrease of visceral adipose tissue mass. Twenty-four of 26 enrolled participants completed the study. The visceral adipose tissue decreased significantly (110 ± 33 to 101 ± 36 cm(2), p = 0.005) as well as other parameters for metabolic insufficiency including hemoglobin A1c. Seventy-one % of the total body weight reduction (-2.49 kg) was estimated by a decrease in fat mass (-1.77 kg), and the remaining reduction (22%) by water volume (-0.55 kg). A minor but significant reduction in the skeletal muscle index was also observed. Correlation analyses were performed to identify variables associated with changes in visceral adipose tissue and the only significant variable identified was diet therapy (Spearman's r = -0.416, p = 0.043). Ipragliflozin significantly decreased visceral adipose tissue, and improved parametres for metabolic dysfunction. Adequate diet therapy would be necessary to induce and enhance the therapeutic merit.

Severe protein C-deficiency is a rare heritable thrombophilia of the newborn. Infants with biallelic PROC mutations present purpura fulminans and intracranial thromboembolism, while the prenatal onset of mutated heterozygotes remains unclear. We herewith present the first case of fetal ventriculomegaly and neonatal stroke associated with heterozygous PROC mutation. The infant was born to a healthy mother at 38 gestational weeks. The fetal growth had been normal, but the routine ultrasound screening had indicated mild hydrocephalus at 28 weeks of gestation. He developed convulsions two days after birth. Computed tomography of the brain revealed multiple hemorrhagic infarctions and ventriculomegaly. Dissociated levels of the plasma activity between protein C (21%) and protein S (42%) reached to determine the heterozygote of PROC c.574&#95;576delAAG, a common thrombophilic predisposition in Asian ancestries. PC-mutant heterozygotes may have a limited high risk of cerebral thromboembolism during the perinatal course., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

To investigate the differences in glycemic variability between the long-acting insulins glargine and degludec using continuous glucose monitoring, we conducted an open-label, multicenter, prospective, observational study that enrolled 21 participants with type 1 diabetes mellitus currently receiving basal-bolus insulin therapy with glargine. To avoid the potential influence of diet and exercise on glycemic control, all participants were housed and monitored within the hospital for the duration of the study. Once glycemic control was achieved with glargine, glycemic variability was evaluated using continuous glucose monitoring for 3 days. Glargine was then replaced by degludec and glycemic variability again assessed via continuous glucose monitoring. The primary outcome measure of mean amplitude of glycemic excursions was significantly reduced with degludec (p = 0.028), as was area under the curve for daily blood glucose level <70 mg/dL (p = 0.046). The required insulin dose was reduced up to 25% in the degludec group, although 24-h mean glucose concentrations were not different between groups. In conclusion, once or twice daily glargine was successfully replaced by a daily injection of degludec. When replacing glargine with degludec, a lower dose should be utilized to avoid hypoglycemia. Degludec is an effective and promising long-acting insulin that reduced hypoglycemia and daily blood glucose variability in participants with type 1 diabetes.

Background: The early diagnosis of inherited thrombophilia in children is challenging because of the rarity and hemostatic maturation., Methods: We explored protein C (PC), protein S (PS), and antithrombin (AT) deficiencies in 306 thromboembolic patients aged ≤20 y using the screening of plasma activity and genetic analysis., Results: Reduced activities were determined in 122 patients (40%). Low PC patients were most frequently found in the lowest age group (0-2 y, 45%), while low PS or low AT patients were found in the highest age group (16-20 y; PS: 30% and AT: 20%). Genetic study was completed in 62 patients having no other causes of thromboembolism. Mutations were determined in 18 patients (8 PC, 8 PS, and 2 AT genes). Six of eight patients with PC gene mutation were found in age 0-2 y (75%), while six of eight patients with PS gene mutation were in 7-20 y. Two AT gene-mutated patients were older than 4 y. Four PC-deficient and two PS-deficient patients carried compound heterozygous mutations. All but one PC gene-mutated patient suffered from intracranial thromboembolism, while PS/AT gene-mutated patients mostly developed extracranial venous thromboembolism., Conclusion: Stroke in low PC infants and deep vein thrombosis in low PS/AT school age children could be targeted for genetic screening of pediatric thrombophilias.

Background: Increasing attention has been given to neuro-developmental problems of very low birth weight infants (VLBWIs) at school age. However, it remains unknown whether their neuro-cognitive function and psychiatric symptoms are mutually associated., Aim: The aim of this study was to investigate the characteristics of neuro-cognitive functions in VLBWIs and their relationship with psychiatric symptoms., Methods: A total of 160 VLBWIs who were born at our institute between 2001 and 2005 were recruited consecutively and followed up until nine years of age. The developmental profiles were obtained from 77 children (45 males and 32 females) at six to nine years of age using the ADHD Rating Scale-Fourth edition (ADHD-RS), Autism Screening Questionnaire-Japanese version (ASQ-J) and the Wechsler Intelligence Scale for Children-Third edition (WISC-III)., Results: The full-scale intelligence quotient did not significantly differ between the male and female VLBWIs (median: 91 vs. 99, p=0.17). The males had higher total scores (median: 13 vs. 4, p<0.01) and higher scores on the subscales of Inattention (8 vs. 2, p<0.01) and Hyperactivity-Impulsivity (5 vs. 1, p<0.01) of the ADHD-RS compared with the females. The Verbal Comprehension Index (VCI) of the WISC-III was inversely correlated with the total scores of the ASQ-J for all VLBWIs (n=77, rc: -0.32, 95% CI: -0.19 to -0.01, p=0.04). We also observed that the Freedom from Distractibility Index (FDI) of the WISC-III was significantly correlated with the Inattentive scores of the ADHD-RS (n=45, rc: -0.18, 95% CI: -0.35 to -0.02, p=0.03) in male, but not female VLBWIs., Conclusions: We herein report that the VCI and FDI of the WISC-III were correlated with the autism spectrum disorder and attention deficit hyperactivity disorder symptoms, respectively, in male VLBWIs., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

A 12-year-old Japanese boy suffered from severe acute hepatitis and pancytopenia. The patient underwent successful bone marrow transplantation from an HLA-identical sister. Torque teno virus (TTV) DNA of genotype 1a and IgM-class antibody against the virus were detected in sera at the onset of hepatitis. TTV/1a DNA and anti-TTV/1a IgM antibody levels were undetectable on the 16th and 46th days after the onset of illness, respectively. Anti-TTV/1a IgG antibody was positive throughout the observation period. Sequential viral load and anti-TTV/1a IgM antibody suggested a primary infection of TTV/1a. Genomic sequence of the virus coincided with that of the original strain first isolated from human. TTV DNA was quantified at 130 copies in 10(5) bone marrow mononuclear cells, which suggested that infection of hematopoietic cells might be the cause of aplasia. This is the first report of TTV hepatitis-associated aplastic anemia assessed by the anti-TTV antibodies and viral load in peripheral blood and bone marrow.

We reported two cases of massive bleeding due to critical hyperfibrinolysis during living-related liver transplantation (LRLT) for end stage liver cirrhosis. The total volume of bleeding amounted to 57930 ml with the case 1, and amounted to 55980 ml with the case 2. TEG was useful for diagnosis of the hyperfibrinolysis. We administrated large amounts of FFPs, MAPs, PLTs, and gabexate mesilate. By rapid transfusion, we could manage to finish the procedures without hypotension, and complications were not observed at the early postoperative stage. We thought that the cause of the hyperfibrinolysis is the increasing blood tissue plasminogen activator (t-PA) due to long-anhepatic stage and small graft size. During anesthesia, since the functional start of a transplant liver is indispensable to it, in order to support a transplant liver for an improvement of hyperfibrinolysis, it is important to keep the homeostasis, such as body temperature, blood pressure.

For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we have directed our attention to superantigens (SAgs), the most potent known activators of T lymphocytes. In our previous study, staphylococcal enterotoxin A (SEA) was conjugated chemically with MUSE11 mAb, which recognizes the MUC1 cancer-associated antigen, and shown to enhance the specific cytotoxic activity of T-LAK cells against MUC1-expressing BDC cells (TFK-1) in vitro and in vivo. However, it is probable that SEA might cause side-effects because of nonspecific binding to class II positive cells. In order to overcome these, we generated mutated SEA (mSEA) by changing Asp at position 227 of native SEA to Ala, which has reduced affinity to MHC class II molecules, but retains the potential for T cell activation. When mSEA-D227A was administered to rabbits to examine effects on blood pressure, 500 times more mSEA-D227A was tolerated than native SEA. This prompted us to construct a mSEA-D227A-conjugated mAb, reactive with MUC1. It augmented the antitumor activity of T-LAK cells significantly, and furthermore, mSEA-D227A could be conjugated to two bispecific antibodies, BsAb (anti-MUC1 x anti-CD3) and BsAb (anti-MUC1 x anti-CD28), which in combination had greater enhancing effects than mSEA-D227A-conjugated anti-MUC1 mAb, and combination of unconjugated BsAbs. These findings indicate a utility of mSEA-D227A-conjugated antibodies for targeted cancer immunotherapy.

In order to enhance cell mediated cytotoxicity, bispecific antibodies (BsAbs), molecules combining two or more antibodies with different antigenic specificities, have been developed as new agents for immunotherapy. Our recent studies revealed that simultaneous administration of two kinds of BsAbs (anti-tumor x anti-CD3 plus anti-tumor x anti-CD28) together with lymphokine activated killer cells with a T cell phenotype (T-LAK cells) inhibited growth of human xenotransplanted tumors in severe combined immunodeficient (SCID) mice, while single BsAb was without effect. Three kinds of BsAbs (anti-tumor x anti-CD3, anti-tumor x anti-CD28, anti-tumor x anti-CD2) showed the highest cytotoxicity against tumor cells when given simultaneously with T-LAK cells or peripheral blood mononuclear cells in vitro and in vivo. BsAbs can be preserved for immediate application, while cytotoxic T lymphocytes (CTLs) must be made-to-order, and are time-consuming to prepare. Tumor associated antigens, such as MAGE antigens, SART antigens, MUC1 antigen, c-erbB 2 antigen or cancer/testis antigens can be served to target antigens for BsAb production. By conjugation with antibodies to effector cells (anti-CD3, anti-CD28, anti-CD16, anti-CD64, anti-CD89 or anti-CD2), many kinds of BsAbs can be produced to cover most types of cancers from different organs. Therefore this strategy might be ubiquitously applicable to most malignancies.

Wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) injection into the facial nerve of the cat resulted in retrograde labeling in the geniculate and jugular ganglia ipsilaterally. Labeled fibers were found to enter into the brain stem through the intermediate and vagal nerves. These fibers ascended or descended into the dorsal portion of the spinal trigeminal tract and were distributed to the principal sensory nucleus of the trigeminal nerve, marginal layer of the interpolar part of the spinal trigeminal nucleus, nucleus of the solitary tract and ventrolateral portion of the cuneate nucleus. It was of particular interest in the present study that the intensive labeling was present in the medial portion of laminae I-IV of the upper cervical spinal cord. The immunohistochemical study revealed a lot of substance P-immunoreactive neurons in the geniculate and jugular ganglia, and heavy accumulation of immunoreactive fibers in laminae I-II of the upper cervical spinal cord.

L. Benjamin's (1984) structural analysis of social behavior (SASB) system was used as the organizing framework within which to characterize the phenomenology of self and other relationship experience among subtypes of alcoholic men. Within the context of a community-based study of psychopathology, groups of antisocial alcoholic (AAL), nonantisocial alcoholic (NAAL), and nonalcoholic (control) men completed ratings of their introject (self-concept) and spousal experience. Group differences in demography and psychopathology provided strong support for subtype variations among alcoholic men that could not be attributed to global differences in adaptive functioning. SASB data showed consistency in circumplex ordering across the groups in ratings of self-experience and in ratings of the spousal relationship. AAL men were the most self-neglecting, blaming, and least trusting, and control men were the most relationally connected, with NAAL men falling in between. Despite the importance of the subtyping distinction, in some areas, alcoholism, regardless of subtype, was the core differentiating factor.

Coronary artery bypass surgery in a 67-year-old male with severe calcified ascending aorta was performed without cardiopulmonary bypass under beating heart, utilizing the left internal thoracic artery graft. No neurological complication was observed and postoperative angiogram showed good graft patency. We think coronary revascularization without cardiopulmonary bypass can be one of the safe and reliable methods to avoid complications associated with aortic cross clamping and aortic cannulation with severely calcified aorta.

Serial 30 microns-thick sections through the midbrain tegmentum were stained with cresyl violet. The PL was found to be situated along the medial edge of the lateral lemniscus. The PL consisted of small- (10-15 microns) and medium-sized neurons (25-35 microns), and was the most prominent at the caudal level of the superior colliculus. In order to confirm the existence of the inhibitory paralemniscal-facial pathway, a combined HRP and immunohistochemical technique was use in the rat. This experiment revealed that 10.9% of the total number of GABA immunoreactive PL neurons also labeled with HRP after HRP injection was made in the medial part of the facial nucleus (FN). Electron microscopic observations were carried out on the medial part of the facial nucleus (FN) after kainic acid injection was made into the contralateral PL in the cat. The majority of degenerating PL fibers were ranged from 0.5 to 3.1 microns in diameter and made synaptic contacts with somata, proximal dendrites and dendritic profiles. These fibers, containing either round or pleomorphic vesicles, formed asymmetrical or symmetrical synapses. It was of particular interest in the present study that 40.7% of the total number of degenerating fibers make synaptic contacts with large dendrites more than 3.0 microns in diameter.

Two cases of vein patch angioplasty for ischemic heart disease were presented. The first case (59-year-old female) admitted to our hospital because of posterolateral infarction. Preoperative coronary angiogram (CAG) showed stenosis of 4-PD of RCA, proximal LAD and distal LCX. The second case (62-year-old male) admitted for operation of abdominal aortic aneurysm. Preoperative CAG showed stenosis of proximal RCA and mid LAD. Stenosis of 4-PD and proximal RCA was relieved by patch angioplasty using saphenous vein graft and coronary artery bypass to LAD was performed by left internal thoracic artery graft. Both cases showed successful enlargement of RCA stenosis and good graft patency at the postoperative CAG. Vein patch angioplasty is thought to be an alternative method for coronary revascularization to ischemic heart disease.

Objective: To evaluate the tumor extension of extrahepatic bile duct cancer by means of intraductal ultrasonography (IDUS)., Methods: IDUS preoperatively assessed the tumor extensions in 25 patients with extrahepatic bile duct cancer. The diagnostic accuracy of IDUS was investigated by comparison with other diagnostic imaging modalities in all cases and with histopathological findings of resected specimens in 18 cases., Results: IDUS proved useful in assessing the extension of cancer invasion to the pancreas parenchyma, portal vein, and right hepatic artery. The limitation of the degree of accuracy, based on the group staging criteria, was 68%. IDUS could not assess tumor invasion to the perimuscular loose connective tissue. Therefore, it could not distinguish stage II from stage I. IDUS could not sufficiently assess epicholedochal lymph node metastases (differential diagnosis between stages II and III) and could not demonstrate distant metastases (differential diagnosis between stages IVA and IVB) because of the inevitable attenuation of the echo itself. IDUS could assess cases of stage IVA correctly in 8/8 (100%) cases. The combination of PTC/ERC and IDUS could assess the horizontal extension correctly in 13/18 (72%) cases. The combination of PTC/ERC, percutaneous transhepatic cholangioscopy (PTCS), and IDUS assessed the horizontal extension in 14/15 (93%) cases., Conclusion: 1) IDUS, with a high-frequency probe, was very useful for assessing tumor infiltration in the hepatoduodenal ligament. 2) IDUS could not assess tumor extension outside of the hepatoduodenal ligament, but conventional ultrasonography and angiography could compensate for it. 3) The combination of PTC/ERC, PTCS, and IDUS could assess horizontal extension correctly.

We report a case of chronic pancreatitis with pseudocysts complicated by infection and obstructive jaundice. A 49-yr-old male was admitted with the complaints of fever and jaundice. Laboratory findings included high biliary tract enzyme values and normal serum amylase value. Ultrasonography and computed tomographic scan demonstrated a cyst, 4 cm in diameter, in the pancreas head. Cholangiography revealed a long, tapered obstruction of the common bile duct which was apparently compressed by the cyst. Although the jaundice improved after percutaneous transhepatic biliary drainage, fever continued, and the cyst was aspirated. Bacteriological examination of the contents revealed infection. The symptoms disappeared rapidly and the cyst decreased in size soon after aspiration. The stenosis of the common bile duct showed improvement for several weeks but then regressed. In a patient with secondary pancreatic infection or obstructive jaundice following pancreatic disease, distinguishing the condition is an important aspect of accurate diagnosis and therapy.

A 55-yr-old female was hospitalized with epigastric pain. Conventional ultrasonography revealed marked dilation of the common bile duct (CBD). Endoscopic retrograde cholangiopancreatography showed fusiform dilation of the CBD. The common channel of the pancreatic duct and choledochus was 20 mm long. A diagnosis of congenital choledochal dilation accompanied by anomalous arrangement of the pancreaticobiliary ductal system (AAPBDS) was made. Intraductal ultrasonography (IDUS) was performed. IDUS demonstrated the union of the pancreatic duct and choledochus within the pancreatic parenchyma. This meant that the union existed outside the duodenal wall, confirming the diagnosis of AAPBDS. Although endoscopic retrograde cholangiopancreatography alone could show the maljunction in this case, simultaneous IDUS will be useful in making an accurate diagnosis of AAPBDS.

Intraductal ultrasonography (IDUS) were performed in patients with extrahepatic bile duct cancer and compared to other diagnostic modalities and to resected specimens. Endoscopic ultrasonography (EUS) is a non-invasive diagnostic method useful for screening patients with bile duct cancers and determining whether they are resectable or not. While, EUS was not useful for the differential diagnosis of advanced and early tumors, and less useful in case of bile duct tumors located at the hilus hepatitis. IDUS proved useful without blind spot even in case of bile duct cancers at the hilus hepatis. IDUS was especially useful for the differential diagnosis of advanced and early tumors. IDUS is the very accurate diagnostic modality which make up for EUS and essential to determine the appropriate operation plan.

We have performed percutaneous transhepatic cholecystoscopic lithotomy (PTCCSL) in 37 cases of cholecystolithiasis and have succeeded in the removal of the stones in all cases without any serious complications. The average period from gallbladder puncture until the completion of lithotomy was 11.8 days and PTCCSL was performed an average of 2.1 times. The follow-up period after lithotomy ranged from one to 60 months, with an average of 24.7 months. Gallbladder function returned to the pretreatment level. However, gallstones recurred in 7 cases (18.9%). In comparison with both cholecystectomy by laparotomy and laparoscopic cholecystectomy, PTCCSL is less invasive, but recurrence may occur in a relatively short period with PTCCSL. Therefore PTCCSL is particularly indicated for high-risk patients who cannot undergo general anesthesia.

A three-dimensional model of adult dreaming styles shows a close correspondence with other models representing frameworks of waking experience and interpersonal behavior. These close parallels support the ubiquity of the factors identified by Robert F. Bales in his integrative new field theory and may help to bring the study of dream function more clearly into the realm of personality and social psychology.

1. The effects of 14 lignocaine homologues on the maximum upstroke velocity (Vmax) of the action potentials (AP) were studied in guinea-pig papillary muscles. These drugs possess one, two or three methyl groups in different positions: an ortho-chloro, -carbomethoxy or -ethyl group instead of an ortho-methyl group; or an N-butyl group instead of an N-diethyl group in lignocaine molecules. 2. At 50-100 mumol/L, six drugs possessing two ortho substituents (but not the other eight) reduced Vmax more prominently at 2-4 Hz than at 1 Hz, and slowed the time courses of recovery of the premature responses. None of the drugs affected resting potential. 3. Besides the two-state piecewise exponential model (models I and II) frequently used, a time-dependent and time-independent, two-state model (model III) was formulated and applied to these experimental data. The above two groups were effectively distinguished by the difference of the estimated association and dissociation rate constants (model II) and equilibrium constants for phasic state (model III) and for resting (model II) or tonic (model III) states. 4. The equilibrium constants for resting or tonic state correlated well with log P (where P = the n-octanol: water partition coefficients), but correlated better with an indicator variable that denotes the existence of two ortho substituents, suggesting the importance of the contribution of steric factors to the activity.

Amygdaloid projections to the superior salivatory nucleus (SSN) were investigated in the cat by using the anterograde and retrograde tracing techniques of horseradish peroxidase (HRP). After HRP injections were made into the lingual nerve, retrogradely labeled SSN neurons were located in the lateral tegmental field medial to the spinal trigeminal nucleus from the middle level of the superior olivary nucleus to the caudal level of the facial nucleus. These labeled neurons, triangular, oval or polygonal in shape, were small to medium-sized (12-29 microns) and formed loosely packed clusters. In further HRP studies, HRP injections were made into the amygdala and in the reticular formation containing the SSN neurons. The results suggested that the SSN receives direct afferents from the central nucleus of the amygdala with ipsilateral predominance. Final proof of such direct connections from amygdala to the SSN can be obtained only by electron microscopic study. Therefore, HRP injections were made into the lingual nerve and in the amygdala in the same animal and electron microscopic observations were carried out on the SSN. It appeared that anterogradely labeled amygdalo-tegmental fibers formed axosomatic and axodendritic synaptic contacts with retrogradely labeled SSN neurons.