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Summary Aim Lateral internal sphincterotomy (LIS) remains a standard for chronic anal fissure even though other surgical techniques have shown high efficacy. Faecal incontinence is a well-documented complication of LIS. We devised modified open posterior internal sphincterotomy (m-OPIS) with sliding skin graft (SSG), which is a combined procedure of OPIS and anal advancement flap. The aim of this study is to evaluate m-OPIS + SSG. Methods This was a retrospective, observational, single-arm study. m-OPIS + SSG was performed for chronic anal fissure and anal stenosis. m-OPIS involved incision of the internal sphincter muscle at the posterior midline until four fingers could be passed. The incision wound was closed by anastomosis of the anoderm and skin. Then, an arcuate skin incision was created and the skin graft was advanced into the anal canal. Follow-up was conducted by clinical consultation and telephone interview. Faecal continence was assessed by Cleveland Clinic Faecal Incontinence (CCFI) score. Results m-OPIS + SSG was performed in 143 patients. The mean patient age was 50 ± 16 years. The success and overall recurrence rates after m-OPIS + SSG were 99% and 0.7%, respectively, with a median follow-up period of 16.3 years. One patient developed incontinence with liquid stools once during the 6-month period. None of the other patients suffered permanent faecal incontinence postoperatively. The postoperative CCFI score was 0.5 ± 0.9. Conclusions We consider m-OPIS + SSG as one of the efficacious options of procedure for chronic anal fissure and anal stenosis, owing to its high success rate, low recurrence rate and no postoperative complication of serious faecal incontinence.

Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P = 9.93 × 10-8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10-9; OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). Conclusions: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease marked by frequent recurrence and metastasis and stagnant survival rates. To enhance molecular knowledge of HNSCC and define a non-coding RNA (ncRNA) landscape of the disease, we profiled the transcriptome-wide dysregulation of long non-coding RNA (lncRNA), microRNA (miRNA), and PIWI-interacting RNA (piRNA) using RNA-sequencing data from 422 HNSCC patients in The Cancer Genome Atlas (TCGA). 307 non-coding transcripts differentially expressed in HNSCC were significantly correlated with patient survival, and associated with mutations in TP53, CDKN2A, CASP8, PRDM9, and FBXW7 and copy number variations in chromosomes 3, 5, 7, and 18. We also observed widespread ncRNA correlation to concurrent TP53 and chromosome 3p loss, a compelling predictor of poor prognosis in HNSCCs. Three selected ncRNAs were additionally associated with tumor stage, HPV status, and other clinical characteristics, and modulation of their expression in vitro reveals differential regulation of genes involved in epithelial-mesenchymal transition and apoptotic response. This comprehensive characterization of the HNSCC non-coding transcriptome introduces new layers of understanding for the disease, and nominates a novel panel of transcripts with potential utility as prognostic markers or therapeutic targets.

Objective We report a case of the clinical course and pathologic findings for a kidney transplant recipient with plasma cell–rich rejection (PCRR) accompanied by antibody-mediated rejection (ABMR). Methods A 29-year-old man with end-stage renal disease caused by lupus nephritis received an ABO-compatible living kidney transplant. Results Eighteen months after transplantation, the patient presented with proteinuria and increased serum creatinine. An episode biopsy revealed severe tubulointerstitial infiltration with plasma cells accompanied by peritubular capillaritis and positive findings on immunofluorescent C4d staining. Donor-specific antibodies were positive for DR52, and the patient was subsequently diagnosed with PCRR accompanied by ABMR. Treatment was initiated with high-dose steroids, intravenous immunoglobulin, gusperimus hydrochloride, muronmonab antibody CD3, and rituximab. However, ABMR persisted and allograft failure developed 20 months after onset. Conclusions We argue that PCRR accompanied by ABMR is a subtype of PCRR that can progress to allograft failure owing to persistent ABMR.

Aim Rectal prolapse (RP) is usually associated with elderly women and is well recognized as having a detrimental effect on quality of life. A number of surgical procedures for RP are available, but morbidity and mortality are substantial. The Gant-Miwa-Thiersch procedure (GMT) has been frequently used for RP in Japan. However, as GMT has a high recurrence rate it is not widely used elsewhere. The aim of this study was to evaluate a modified version of GMT (mGMT) in comparison with other procedures. Method mGMT was performed under spinal or local anaesthesia in 187 patients with RP. No normal mucosa was left between the tags and lateral wounds were created in the Thiersch procedure. Morbidity, mortality and recurrence rates were recorded. Results No serious postoperative complications and no operative deaths occurred after mGMT. Eight per cent of patients suffered from infection of the strings. The overall recurrence rate after mGMT was 7.5% with a median follow-up period of 13.8 years. Conclusion On the basis of these results, we consider that mGMT has a number of advantages: it is minimally invasive, does not require general anaesthesia, is technically simple to perform and is associated with satisfactory outcomes and low morbidity. mGMT should be considered an option for the treatment of RP in elderly patients.

Objective: This study aimed to compare thin-section CT images from sarcoidosis patients who had either normal or elevated serum KL-6 levels. Methods: 101 patients with sarcoidosis who underwent thin-section CT examinations of the chest and serum KL-6 measurements between December 2003 and November 2008 were retrospectively identified. The study group comprised 75 sarcoidosis patients (23 male, 52 female; aged 19–82 years, mean 54.1 years) with normal KL-6 levels (152–499 Uml –1 , mean 305.7 Uml –1 ) and 26 sarcoidosis patients (7 male, 19 female; aged 19–75 years, mean 54.3 years) with elevated KL-6 levels (541–2940 Uml –1 , mean 802.4 Uml –1 ). Two chest radiologists, unaware of KL-6 levels, retrospectively and independently interpreted CT images for parenchymal abnormalities, enlarged lymph nodes and pleural effusion. Results: CT findings in sarcoidosis patients consisted mainly of lymph node enlargement (70/75 with normal KL-6 levels and 21/26 with elevated KL-6 levels), followed by nodules (50 and 25 with normal and elevated levels, respectively) and bronchial wall thickening (25 and 21 with normal and elevated levels, respectively). Ground-glass opacity, nodules, interlobular septal thickening, traction bronchiectasis, architectural distortion and bronchial wall thickening were significantly more frequent in patients with elevated KL-6 levels than those with normal levels (p,0.001, p,0.005, p,0.001, p,0.001, p,0.001 and p,0.001, respectively). By comparison, there was no significant difference in frequency of lymph node enlargement between the two groups. Conclusion: These results suggest that serum KL-6 levels may be a useful marker for indicating the severity of parenchymal sarcoidosis.

The aim of this study was to retrospectively compare high-resolution CT findings among cryptogenic organizing pneumonia (COP) patients with normal and elevated serum KL-6 levels. Chest CT scans performed between April 1999 and April 2007 in 20 COP patients with a normal KL-6 level and 17 COP patients with an elevated KL-6 level were evaluated retrospectively by two chest radiologists. The CT findings in the COP patients with either a normal or an elevated KL-6 level mainly consisted of consolidation (n = 17 and n = 13, respectively) followed by ground-glass opacity (n = 11 and n = 13, respectively). Traction bronchiectasis and architectural distortion were significantly more frequent in patients with an elevated KL-6 level than in those with normal levels (n = 7 and n = 1, and n = 13 and n = 3, respectively) (p = 0.0077 and p = 0.00017, respectively). In follow-up CT scans, a relapse within 1 year after initial treatment with steroids, performed in 16 patients with a normal KL-6 level and 16 with an elevated KL-6 level, occurred in 2 (12.5%) patients with a normal KL-6 level and in 6 (37.5%) with an elevated KL-6 level. The frequency of relapse in patients with an elevated KL-6 level was higher than in those with a normal KL-6 level; however, no significant difference between the two groups was observed (p = 0.103). In conclusion, CT findings of traction bronchiectasis and architectural distortion in COP patients are associated with increased serum KL-6 levels, which might be related to a relapse after treatment.

Head and neck squamous cell carcinoma persists as one of the most common and deadly malignancies, with early detection and effective treatment still posing formidable challenges. To expand our currently sparse knowledge of the noncoding alterations involved in the disease and identify potential biomarkers and therapeutic targets, we globally profiled the dysregulation of small nucleolar and long noncoding RNAs in head and neck tumors. Using next-generation RNA-sequencing data from 40 pairs of tumor and matched normal tissues, we found 2808 long noncoding RNA (lncRNA) transcripts significantly differentially expressed by a fold change magnitude ≥2. Meanwhile, RNA-sequencing analysis of 31 tumor-normal pairs yielded 33 significantly dysregulated small nucleolar RNAs (snoRNA). In particular, we identified two dramatically down-regulated lncRNAs and one down-regulated snoRNA whose expression levels correlated significantly with overall patient survival, suggesting their functional significance and clinical relevance in head and neck cancer pathogenesis. We confirmed the dysregulation of these noncoding RNAs in head and neck cancer cell lines derived from different anatomic sites, and determined that ectopic expression of the two lncRNAs inhibited key EMT and stem cell genes and reduced cellular proliferation and migration. As a whole, noncoding RNAs are pervasively dysregulated in head and squamous cell carcinoma. The precise molecular roles of the three transcripts identified warrants further characterization, but our data suggest that they are likely to play substantial roles in head and neck cancer pathogenesis and are significantly associated with patient survival.

We demonstrate the rare disorder of triple H syndrome in a 25-year-old man. He was pointed out as having short stature, at -5.9 s.d., and diagnosed as GH deficient at 6 years old. Approximately a year ago, he noticed systematic hair loss. He lost body weight by 7 kg during the last half year. He was admitted to Jichi Medical School Hospital because of unconsciousness. Physical findings showed disturbance of consciousness with Japan Coma Scale I-3. He had emaciation and alopecia universalis. Laboratory findings showed plasma glucose was as low as 1.11 mmol/l. GH and ACTH deficiency with hypoadrenocorticism were clarified. His intelligence was in the low normal range with a WAIS IQ of 70, and anterograde amnesia was suggested in the presence of a little, but not significant, morphological change in the hippocampus on a magnetic resonance imaging scan. Replacement by a physiological dose of hydrocortisone normalized plasma glucose, and restored body weight and growth of hair during the 7 month therapeutic period. The present finding strongly supports a clinical entity of triple H syndrome, including ACTH deficiency, alopecia universalis and anterograde amnesia, and that there may be some variation of the triad among the subjects.

Summary The aim of this study was to investigate effects of interocclusal distance (IOD) on bite force and masseter electromyographic (EMG) activity during different isometric contraction tasks. Thirty-one healthy participants (14 women and 17 men, 21·2 ± 1·8 years) were recruited. Maximal Voluntary Occlusal Bite Force (MVOBF) between the first molars and masseter EMG activity during all the isometric-biting tasks were measured. The participants were asked to bite at submaximal levels of 20%, 40%, 60% and 80% MVOBF with the use of visual feedback. The thickness of the force transducer was set at 8, 12, 16 and 20 mm (= IOD), and sides were tested in random sequence. MVOBF was significantly higher at 8 mm compared with all other IODs (P

Short-term intensive insulin therapy (IIT) in patients with Type 2 diabetes mellitus (T2DM) has beneficial effects on insulin secretion. However, IIT effect on glucagon and glucagon-like peptide-1 (GLP-1) secretion is unknown.We evaluated short-term intensive glycemic control effects on insulin, glucagon, and GLP-1 secretory dynamics in T2DM.Twenty-six patients with T2DM were hospitalized and treated with IIT for 10-14 days. A meal tolerance test was performed before and after IIT and the differences in serum immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) as well as plasma glucagon and active GLP-1 levels were evaluated.Glycoalbumin levels decreased significantly from 23.0% before to 19.6% after IIT (p0.001). However, pre- and post-IIT, IRI and CPR levels were not significantly different; post-IIT glucose levels were significantly decreased. The post-IIT glucagon levels at 0 and 60 min were lower than pre-IIT levels. Moreover, post- IIT area under the curve (AUC) of glucagon significantly reduced from 6755 ± 996 pg/dl · 60 min to 5796 ± 1074 pg/dl · 60 min (p0.001). Furthermore, post-IIT GLP-1 levels and AUC were significantly higher than pre-IIT values.Our results suggest that patients with T2DM who received shortterm IIT demonstrated decreased postprandial glucagon levels and increased GLP-1 levels following a meal tolerance test.

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of the lysosomal hydrolase, α-galactosidase A (α-Gal A). We report a case of a renal transplant recipient with unrecognized Fabry disease who received the allograft from a sibling donor with unrecognized Fabry disease. The recipient began to show a gradual increase of the serum creatinine with mild proteinuria at 3 years after transplantation. Histopathologic examination revealed finely vacuolated podocytes, demonstrated by ultrastructural examination to contain osmophilic myelin bodies. Furthermore, the recipient showed reduced circulating levels of α-Gal A and elevated urinary levels of globotriaosylceramide. These findings indicated that both the recipient and the donor suffered from Fabry disease of the renal variant phenotype. Enzyme replacement therapy (ERT) was initiated in the recipient, which resulted in a slight decrease of serum creatinine. Although mild proteinuria persisted, initiation of ERT in the recipient led to improvement of the renal function.

A 33-year-old man was referred by a local dentist for autotransplantation of the right mandibular third molar to the site of the left mandibular first molar. Before the operation, dental-cone-beam computed tomography was performed to measure the dimensions of the graft tooth and the bone volume of the socket. The three-dimensional (3D) structure of the graft tooth was created from the 3D imaging data. A replica of the graft tooth was produced using a stereolithographic CAD/CAM system before autotransplantation. A socket of the appropriate size and structure was created and the graft tooth was extracted immediately before grafting. This procedure shortened the time needed to fit the graft tooth into the socket and reduced injury to the periodontal membrane. The postoperative outcomes of autotransplantation of the tooth were good.

A group of 22 patients (27 nostrils) with nasal allergies was treated with 80 w/v trichloroacetic acid applied to the inferior turbinates. Patients were then evaluated prospectively based on both subjective responses and clinical examinations. Allergic symptoms were reduced significantly, especially those involving nasal obstruction and watery rhinorrhea. Nasal airflow resistance also improved after treatment (P < 0.001). Nasal provocation testing revealed a significant decrease in post-treatment responses (P < 0.001). No severe side effects were noted after treatment. Findings demonstrated that local application of trichloroacetic acid is a safe, effective and simple treatment for outpatients with symptomatic nasal allergies.

To elucidate the role of osteopontin (OPN) in monocyte recruitment in crescentic glomerulonephritis, we investigated immunohistochemical localization of OPN in the kidney and its correlation with clinical and histopathologic parameters in biopsy specimens of patients with myeloperoxidase antineutrophil cytoplasmic autoantibody- (MPO-ANCA) associated glomerulonephritis.Twelve patients with MPO-ANCA-associated glomerulonephritis were enrolled in this study. Clinical parameters such as creatinine clearance and urinary protein excretion of each patient were obtained at the time of biopsy. Paraffin-embedded sections were used for immunohistochemical staining using the LSAB method. Five cortical interstitial fields randomly selected at original magnification x 200 were assessed using a computer-assisted color image analyzer. Tubular OPN expression was assessed as the percentage of positive area in the tubulointerstitium. Double immunofluorescent staining using antibodies against OPN and alpha(v)beta3 was performed.In all of the cases studied, OPN was occasionally localized within the glomeruli, and expressed slightly in proximal tubular epithelium and significantly in distal tubular epithelium. Tubular OPN expression tended to be promoted in the interstitium infiltrating by numerous monocytes/macrophages. The extent of tubular OPN expression was positively correlated with serum ANCA titers and urinary OPN concentrations. Enhanced alpha(v)beta3 expression appeared in the distal tubular epithelium expressing OPN.These results suggest that inducible expression of OPN and alpha(v)beta3 in the tubular epithelium seems to be associated with interstitial moncyte infiltration and subsequent tubulointerstitial changes in human MPO-ANCA-associated glomerulonephritis.

Estrogen receptor (ER) and p53 are important transcription factors in the growth regulation of tumor cells in breast cancer. We reported previously that thioredoxin (TRX) regulates the DNA binding activities of ER and p53 in vitro. The expression of pS-2, a trefoil factor, is also correlated with that of ER. To clarify the regulation mechanism of tumor growth in breast cancer, here we investigated the expression of TRX, ER, pS-2, and p53 and the mitotic index (MI) in 147 breast cancer tissues using immunohistochemical analysis. Of 123 TRX+ cases, ER+ cases (n = 62) showed a higher pS-2 score and lower MI than did ER- cases (n = 61). Furthermore, p53- cases (no mutation in p53; n = 76) also showed a lower MI than did p53+ cases (n = 47). There was no significant correlation between pS-2 and ER, MI and ER, or p53 and MI in the TRX- group. Among the ER+ and p53- cases (ER+/p53- group; n = 61), MI was lower in the TRX+ group (n = 46) than in the TRX- group (n = 15). However, in all other groups (n = 86) with abnormalities in the immunohistochemical expression of either p53 or ER, there was no significant correlation between MI and TRX expression. In the TRX+ and ER +/p53- group (n = 46), histological grading was lower than that in all other groups (n = 101). These findings suggest that TRX expression is linked to the ER- and p53-dependent regulation of tumor growth in breast cancer. In addition, TRX expression in ER+ and p53 intact (wild-type p53+) groups may mean better prognosis than in other conditions.

By considering three kinds of music and noise, this research investigates the influence of music on the living body by comparing the difference of influence on heart rate variability and comfort when subjects listen to music and are exposed to noise. We used two pieces of classical music, rock music, and noise recorded by a tape recorder. The following conclusions were made from the findings of the research: 1) Hearing classical music results in a small variance of Mayer Wave related Sinus Arrhythmia (MWSA) component and Respiratory Sinus Arrhythmia (RSA) component compared with a body being at rest. This is because the sympathetic nerve is suppressed by the sound of classical music. With rock music and noise, however, the MWSA component increases and the RSA component decreases. 2) From a psychological evaluation, we found that classical music tends to cause comfort and rock music and noise tend to cause discomfort. 3) A correlation was found between the balance of the MWSA component and the RSA component and the psychological evaluation. As the comfort increases, the variance of MWSA decreases; as discomfort increases, the variance of MWSA increases.

To identify prognostic factors for myeloperoxidase anti-neutrophil cytoplasmic antibody- (MPO-ANCA) associated glomerulonephritis.We analyzed the relations between the clinical and histological features of MPO-ANCA-associated glomerulonephritis and clinical outcome in 14 patients with the disease. The patients were divided into two groups: group 1 consisted of 5 patients with progressive deterioration of renal function leading to end-stage renal disease or chronic dialysis, group 2 consisted of 9 patients in whom the initial deterioration of renal function had improved by the time of the final examination.Creatinine clearance at the time of biopsy was significantly lower in group 1 than in group 2, and urinary protein was higher. The mean interval between onset of symptoms and biopsy in both groups was almost the same. Recovery of renal function was correlated with the percentage of global sclerosis, but patients who had severe crescent formation did not always have a poor response to steroid therapy. There was no statistical difference between the two groups in treatment regimens. Four patients required hemodialysis at the time of biopsy (3 in group 1 and 1 in group 2). Plasmapheresis was performed in 5 patients (1 in group 1 and 4 in group 2).Degree of proteinuria and renal dysfunction are indicators of a poor prognosis in MPO-ANCA-associated glomerulonephritis. Global sclerosis is a histological feature that is an indicator of a poor prognosis, whereas cellular crescent formation is a predictor of a good response to steroid therapy.

To evaluate the thickness of the roof of the glenoid fossa of the temporomandibular joint (TMJ) in relationship to the stage of internal derangement from autopsy material.The minimum thickness of the roof of the glenoid fossa was measured with a caliper in 61 TMJ autopsy specimens. Based on macroscopic examination the joints were categorized as normal (30 joints), disk displacement (eight joints), disk displacement with osteoarthritis (12 joints) and osteoarthritis with perforation of the disk or posterior attachment (11 joints). The relationship between thickness of roof of the glenoid fossa and status of the joint was analysed.The roof of the glenoid fossa was on the average 0.6 mm in normal joints, 1.1 mm in joints both with disk displacement and disk displacement with osteoarthritis and 2.6 mm in joints with osteoarthritis and perforation. The difference between the normal joints and those with perforation was significant (P0.01).Progressive remodeling with thickening of the roof of the glenoid fossa seems to be associated with perforation of the disk or posterior attachment.

Inactivation of the tumour suppressor gene, p53, is the commonest genetic abnormality in human cancer. The study of the type of p53 mutation in a given tumour may provide prognostic information, clues to aetiology and become useful for therapeutics.The molecular characterisation of p53 was performed by restriction analysis, denaturing gradient gel electrophoresis, and gene sequencing for exons 5-9.We report, p53 mutational analysis in exons 5-9 in 29 European patients with hilar cholangiocarcinoma who underwent attempted resection. Four patients (14%) showed somatic single nucleotide substitutions with amino acid changes (146, 163, 175, 158, and 175) with one showing mutations in two different positions involving a loss of two CfoI sites. All the mutations occurred in exon 5. Three patients had a germline polymorphism (10%) with a silent substitution in codon 213 (exon 6).The systematic screening for p53 mutations in European patients with hilar cholangiocarcinoma has shown that the type of mutation (except 175) is different and its incidence is much lower when compared to the pattern previously reported for intrahepatic cholangiocarcinoma in East Asian patients. A probable explanation is that the presence and type of p53 mutation is dependent on geographic and environmental factors which vary in different populations.

CTLA-4, expressed on activated T cells, is thought to be a negative regulator of T cell function. Its gene (2q33) may confer genetic susceptibility to type 1 diabetes mellitus (IDDM12). The present study was undertaken to clarify the role of CTLA-4 gene polymorphism in Japanese subjects with type 1 diabetes and its effect on their clinical features.In 117 Japanese subjects with type 1 diabetes, the CTLA-4 exon 1 polymorphism (49 A/G) was defined by PCR-RFLP analysis. Anti-GAD antibodies (GAD-Ab) and fasting serum C-peptide were also determined. 141 healthy age- and sex-matched subjects served as controls.The frequency of each polymorphism was not different between the type 1 diabetic subjects and the controls; AA 21, AG 42 and GG 54 for the diabetic subjects, and AA 22, AG 47 and GG 72 for the controls. The frequency of the GG genotype was higher in the diabetic subjects with positive GAD-Ab (greater than 8 U/ml) (67%) than in the GAD-Ab negative subjects (39%) (P0.05). The prevalence of positive GAD-Ab declined with the duration of diabetes. In the diabetic subjects with disease duration of less than 5 years (n = 40), the frequency of the GG genotype was also higher in the GAD-Ab positive subjects (71%) (P0.05). In the analysis of all the diabetic subjects, there was a strong association between positive GAD-Ab and beta cell function (P0.0001).There was no evidence that the CTLA-4 exon 1 polymorphism (49 A/G) confers genetic susceptibility to type 1 diabetes mellitus in our case-control study in Japanese subjects. However, the frequency of positive GAD-Ab was higher in the GG subjects. CTLA-4 polymorphism might contribute to the clinical heterogeneity of type 1 diabetes mellitus in Japanese subjects.

To investigate the serum levels of vascular endothelial growth factor (VEGF) in human crescentic glomerulonephritis (CRGN).The serum VEGF levels in CRGN patients were compared with those in healthy subjects and in various types of glomerulonephritis. In addition, we investigated the relationship between serum VEGF levels and creatinine levels (Scr) and pathological parameters.The serum VEGF levels of the CRGN patients were significantly higher than in the healthy subjects and patients with MCNS, IgAN, and FGS. No correlation was found between serum VEGF levels and Scr in the RPGN patients. The serum VEGF levels in 6 CRGN patients had significantly decreased after 6 months of corticosteroid therapy. Moreover, there was a significant correlation between the serum VEGF levels and the crescent frequency or the grade of interstitial injury, and the rates of glomerular infiltration by macrophages.In the CRGN patients, severe glomerular and interstitial damages would result in increased serum VEGF levels and corticosteroid therapy may exert its efficacy through reduction of serum VEGF levels.

High dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) is safe and useful for the treatment of refractory or relapsed testicular tumors, but is sometimes accompanied by serious complications. We report a case of relapsed testicular tumor complicated by neutropenic enterocolitis during high dose chemotherapy with PBSCT.

The present study was designed to elucidate whether glomerular epithelial cell (GEC) injury is associated with the mechanism of proteinuria in biopsy-proven IgA nephropathy (IgAN). Twenty-four IgAN patients were divided into 4 groups based on their grade of proteinuria. Light microscopic examination revealed that GEC injury appeared prior to glomerular lesions such as sclerosis, crescent and adhesion. Reduced glomerular expression of C3b receptor (CR1), an indicator of GEC injury, was detected initially at the portion of damaged GEC and around the lesions of sclerosis, crescent and adhesion. CR1 expression eventually disappeared in the group IV patients who had nephrotic range proteinuria. Moreover, the grade of proteinuria in IgAN patients was associated with GEC injury and reduced glomerular expression of CR1. Taken together, GEC injury might be an important pathological finding which appears initially in the glomeruli, suggesting that GEC injury is a predictor of proteinuria in IgAN patients.

Factor VIII (IX) inhibitors represent one of the most serious problems for the treatment of patients with hemophilia. The Blood Products Research Organization (Japan) has supported a study group for treatment of hemophiliacs with inhibitors. In 1995 the study group started a prospective matched control study of hemophiliacs with and without inhibitors and compared such factors as quality of life and economic cost. Each inhibitor patient was matched with a control patient in terms of age, type of hemophilia, and severity of hemophilia. A total of 136 patient-pairs were enrolled. Bleeding episodes were more frequent in the control group than in the inhibitor group. Days of hospitalization, days in wheelchairs, and the number of impaired joints were significantly higher for the inhibitor group. Number of blood-product infusions, days of bed rest at home, and days of brace use were the same for both groups. Blood-product expenditures were significantly higher for the inhibitor group than for the control group (yen 10,872,283/patient/year vs. yen 4,327,542/patient/year). Our study highlighted the higher cost of treatment and lower quality of life for hemophiliaes with Factor VII inhibitors.

A new anti-ulcer agent, ecabet sodium, is active against Helicobacter pylori.To assess the efficacy of ecabet sodium for the eradication of H. pylori in patients with gastroduodenal diseases.In a prospective, randomized and controlled study, patients infected with H. pylori were assigned to one of the following two groups: group LA, who received lansoprazole 30 mg o.d. + amoxycillin 500 mg q.d.s. after meals for 2 weeks, and group LAE, who received lansoprazole 30 mg o.d. + amoxycillin 500 mg q.d.s. + ecabet sodium 1000 mg b.d. after meals for 2 weeks. H. pylori status was determined before and at least 4 weeks after the therapy by rapid urease test, histology and a urea breath test.Of 101 patients (mean age 53 years, range 17-77 years, M/F: 68/33) enrolled in the study, 97 patients completed the protocol. Four patients were withdrawn because of diarrhoea (three from group LA) and skin rash (one from group LAE). The eradication of H. pylori was achieved in 28/48 (58%) patients in group LA and 38/49 (78%) patients in group LAE. The rate of eradication of H. pylori produced by the LAE treatment was significantly higher than that produced by the LA treatment. Side-effects appeared in two patients (malaise 1, skin rash 1) in group LAE and in seven patients (diarrhoea 6, dizziness 1) in group LA. These side effects disappeared spontaneously with cessation of the treatment.Ecabet sodium in combination with lansoprazole and amoxycillin increased the rate of eradication of H. pylori. Ecabet sodium appeared to reduce the incidence of diarrhoea as a side-effect of the dual LA therapy.

We performed esophageal endoscopy with concurrent chemo-radiotherapy for lung cancer in 19 patients. Endoscopical examination proved that seven patients (36.8%) had esophageal erosion or coating (grade 2), four patients (21.1%) had ulcer or bleeding (grade 3) confined to the radiation field, and only one patient (5.3%) had severe symptoms (WHO grade 3). There was a discrepancy between patients' symptoms and endoscopical findings. Endoscopically proven esophagitis, that is, erosion or coating (grade 2), and ulcer or bleeding (grade 3), was more frequent in the daily low-dose chemotherapy group (5/5) than in the full dose chemotherapy group (5/14) (p0.05). One patient with grade 3 endoscopial damage showed less recovery in spite of three months medication. In concurrent radiochemotherapy in which the radiation field includes the esophagus, careful attention should be given to radiation esophagitis, which may be underestimated when assessed on the basis of subjective symptoms alone. Therefore, endoscopy is recommended even if patients have few complaints, and once the esophageal ulcer is proven (grade 3), it should be closely followed up using endoscopy.

A 44-year-old male, engaged in the transportation of dry ice, was found dead on the floor of the freezer of his refrigerator car which was parked in front of the place where he was scheduled to make a delivery. Autopsy was performed to investigate the cause of death. Apart from the signs of acute death, no other significant findings were obtained, either macro or microscopically; carbon dioxide poisoning was thus strongly suspected. We created a simulation experiment by using the refrigerator car to reproduce the events of the accident. The oxygen concentration in the freezer was 21.0% as indicated by oxygen sensors, but decreased to 17.1-17.4% when the engine was stopped. This decrease in oxygen concentration supposedly results from the production of carbon dioxide by the vaporization of dry ice. Carbon dioxide concentration in the air could be calculated from the change in the oxygen concentration in the closed space of the freezer. The concentration was assessed at 17.1-18.6%. An oxygen concentration of 17.1-17.4% does not of itself cause serious hypoxia, but a carbon dioxide concentration of 17.1-18.6% probably causes serious intoxication, because this value is beyond that of intoxication levels published in references. Therefore, we concluded that the cause of death in this case was carbon dioxide intoxication.

13C-urea breath test (UBT), available for diagnosis of Helicobacter pylori (HP) in the stomach, measures the 13CO in the breath in which 13C urea is resolved in the stomach by urease derived from HP. Accordingly UBT is useful for a test of HP infection. This study is aimed at clarifying the relationship between the UBT and gastric histological findings. For this study we selected 63 patients with HP infection who showed both positive UBT and positive histological diagnosis. Briefly in the UBT procedure, the patients were given 13C-urea (100 mg dissolved 100 ml water) in a fasting state and kept in the left decubitus position for 5 minutes, and then the patients were asked to expire into testing bags before and 20 minutes after administration of the urea. Biopsy specimens were taken endscopically from the gastric antrum and the body. The specimens of all patients showed positive CLO test. HP organisms, inflammation, activity, and atrophy of the gastric specimens, were expressed in score from 0 to 3 according to the Update Sydney system. The UBT values were high correlated with the increase of HP organisms. The UBT was 11.8, 26.3, and 37/1000 in the groups with the scores of 0.1, and 2 in the number of HP organisms from the gastric body, respectively. The UBT was 19.2, 22.2, 36.1, 26.7/1000 in the groups with scores of 0, 1, 2, and 3 for the specimens from the antrum, respectively. The results show that there is a positive correlation between the UBT values and HP organisms. As a result, the UBT correlated with the activity score. Grade of gastric mucosal atrophy was expressed histologically in scores of 0,1,2, and 3. The UBT was 29.4, 19.1, 17.5, and 9.3/1000 in the groups with scores 0,1,2, and 3 in the grades of gastric atrophy from the gastric body, respectively. There was a negative correlation between the UBT values and the grade of gastric atrophy. We conclude that the UBT values which indicate the number of HP organisms can be used not only for diagnosis of HP infection but also the quantitative index of HP load.

We determined whether alteration in urinary excretion of aquaporin-2 (UAQP-2) is of value to diagnose central diabetes insipidus (CDI). First, UAQP-2 was determined in 16 normal subjects under ad libitum water drinking (n = 6) and after an overnight dehydration (n = 10). UAQP-2 has a positive correlation with plasma arginine vasopressin (AVP) levels (r = 0.61, P0.05) but not with urinary osmolality (Uosm). Second, a hypertonic saline (5% NaCl)-infusion test was studied in 5 normal subjects (21 to 25 yr old) and 10 patients with CDI (22-68 yr). After drinking water ad libitum, they were given 20 mL/kg water orally and then given 5% NaCl (0.05 mL/kg x min) i.v. for 120 min. Finally, 0.1 U of AVP was administered i.v. During the period, 30-min urine collections were made. In the normal subjects, after the infusion of 5% NaCl, plasma AVP levels and Uosm markedly increased in parallel with an increase in plasma osmolality (Posm, 294-320 mOsm/kg H2O; Uosm, 102-737 mOsm/kg H2O; AVP, 0.4-2.6 pg/mL, P0.001). In the CDI patients, plasma AVP and Uosm failed to increase, despite an increase in Posm (Posm, 306-332; Uosm, 102-164; AVP, 0.9-1.2). UAQP-2 was markedly greater in the normal subjects than the CDI patients (7.2 vs. 0.9 pmol/L/mg creatinine, P0.05) under water intake ad libitum. UAQP-2 was changeable in the wide range in physiological condition. After the 5%-NaCl infusion, UAQP-2 elevated to 12.5 from 0.9 pmol/L x mg creatinine in the normal subjects. In contrast, UAQP-2 remained low during the 5%-NaCl infusion in the CDI patients. Exogenous AVP promptly increased UAQP-2 to a similar extent in two groups of the normal subjects and the CDI patients. These results indicate that measurement of UAQP-2 is of value to diagnose CDI in the 5%-NaCl infusion test.

Twelve women (13 pregnancies) with antiphospholipid antibodies (APA) who had suffered from two or more recurrent spontaneous abortions or fetal deaths and had successful pregnancy outcomes after immunosuppressive therapy were studied. APA titers were determined by enzyme-linked immunosorbent assay against cardiolipin, phosphatidyl serine and phosphatidyl inositol. Plasma levels of 6ketoprostaglandin F1 alpha (6ketoPGF1 alpha) and thromboxane B2 (TXB2) were determined by radioimmunoassay. All of the 13 pregnancies resulted in term delivery. None of the 13 patients suffered from pregnancy-induced hypertension, and only one showed intrauterine growth retardation. A significant decrease of APA titer was observed after immunosuppressive therapy. The 6ketoPGF1 alpha/TXB2 ratios before the therapy, after it and at the 1st, 2nd and 3rd trimesters of pregnancy were 0.62 +/- 0.398, 0.88 +/- 0.106, 0.84 +/- 0.550, 1.25 +/- 0.834 and 0.67 +/- 0.413, respectively. The ratio at the 2nd trimester was significantly higher than that before the therapy (P0.05, paired t-test, n = 9). The results indicate that the immunosuppressive therapy affected the physiological balance between thromboxane A2 and prostacyclin, and improved clinical symptoms such as recurrent fetal wastage.

From January 1984 to December 1993, 184 patients with previously untreated T1 and T2 (UICC 1987) laryngeal glottic cancer underwent radiotherapy at Hyogo Medical Center for Adults. The prognostic variables analyzed included sex, age, smoking index, T stage, tumor size, tumor type, gross anterior commissure involvement (gross ACI), histological differentiation, administered dose, TDF, overall treatment time, chemotherapy, initial response, and the dose required to achieve CR. Both univariate and multivariate analyses were performed. The T stage, tumor size, and gross ACI were significant variables in univariate analysis, while the tumor type and gross ACI were significant on multivariate analysis. The 5-year recurrence-free survival of patients with gross ACI was significantly worse than that of those without ACI (57.6% vs. 89.9%). Among gross ACI patients, the recurrence-free survival of those treated with 70-72 Gy was superior to that of those receiving 60-62 Gy, suggesting that at least 70 Gy was necessary to control such diseases.

Cord blood stem cell transplantation (CBSCT) was performed on a patient with acute promyelocytic leukemia. The patient was a boy 3 years and 8 months old, who had shown complete remission following treatment with intensive chemotherapy. However, after the final course of consolidation chemotherapy, chromosome analysis of his bone marrow aspirates revealed 46XY, t(15,17)(q22;q21), and a PML-RAR alpha fusion gene was detected by the reverse transcriptase-polymerase chain reaction test. All-trans retinoic acid diminished the chromosomal abnormality, but the PML-RAR alpha fusion gene remained. The patient was then treated with CBSCT from an HLA-matched sibling donor. The number of nucleated cells in the cord blood was 2.2 x 10(7)/kg of body weight, and that of granulocyte-macrophage colony-forming units 0.6 x 10(4)/kg. Methotrexate was given, on days 3 and 6, as prophylaxis against graft-versus-host disease (GVHD). The neutrophil count rose to above 500/microliters on day 22. The platelet count exceeded 50,000/microliters on day 48. Platelet transfusions were given 12 times after CBSCT, the last one on day 36. Grade I acute GVHD was treated with steroids. The patient was well and discharged on day 103, without symptoms or laboratory data suggestive of relapse. Following this experience we instituted a project of the Kanagawa Cord Blood Bank, which is scheduled for expansion nationwide.

In this study, we investigate simple breath test for detection of Helicobacter pylori (HP) infection using 13C-urea. Thirty-nine patients (30 were HP positive, 9 were HP negative) were given three different doses (50, 100 and 150 mg) of 13C-urea at fasting, and keep sitting after mouth washing with water. Breath samples were taken before and 10, 20, 30, 45, and 60 minutes after urea administration. More than 100mg of 13C-urea was necessary for correct diagnosis of HP infection, because 2 HP positive cases were not detected by 50mg 13C-urea administration. In cases with patchy distribution of HP in the stomach, it may be necessary to change the posture to distribute urea within the whole stomach. In most of HP positive cases, peak delta 13CO2 were obtained within 30 minutes, but one HP negative case showed high delta 13CO2 at 10 minutes, which was probably caused by urease activity in the mouth. So it is appropriate to take breath sample at 20 minutes after urea administration. In this study, cut-off value for a positive test can be setted between 4 to 7 delta/1000, it is necessary to investigate much more cases to set exact cut-off value.

This is a case report of a 23 year old female involved in a car accident that caused blunt trauma to the patient. First of all, she was found to have cardiac tamponade when the abdomen was explored to suture and to put the gaze compression on for hemostasis of the ruptured liver. Then, she was brought to our institution by the ambulance. Upon the exploration of the heart under standby of extracorporal circulation (ECC), small multiple lacerations were found at the junction of the right atrium and superior vena cava. These were sutured directly to close without ECC. On the 2nd postoperative day, she was bought to the OR again to removal of the gaze tamponade from the ruptured liver and to complete hemostasis. The patient was discarded 35 days after admission.

Non-invasive pulmonary aspergillosis is frequently seen in cases with cavity as sequela of tuberculosis. Diagnosis of non-invasive pulmonary aspergillosis is not easy except for cases whose chest X-ray findings show a typical fungus ball. How to diagnose pulmonary aspergillosis was studied in 21 patients who showed changes in the radiological findings of cavity as sequela of tuberculosis. We made sputum culture of Aspergillus, measurement of precipitin antibody titer to Aspergillus fumigatus and measurement of PASTOREX ASPERGILLUS in serum and sputum on the 21 patients (group A). PASTOREX ASPERGILLUS in sputum was evaluated in three grades: 1+ approximately 3+. We diagnosed 14 patients as pulmonary aspergillosis (PA group) among the 21 patients taking into account the chest X-ray findings and the results of the above-stated investigations. The types of chest X-ray findings of these 14 patients were fungus ball type (FB) in 2 patients, productive aspergilloma on the inner wall of a cavity (PAIC) in 8, mixed type with FB and PAIC in 2 and non-specific change in 2. However, there were 3 patients with the chest X-ray findings suggestive of PAIC in 7 patients (non-PA group) who were not diagnosed as pulmonary aspergillosis. Sputum culture were positive in 11 patients of PA group (79%) and negative in all patients of non-PA group. Precipitin antibody were positive in 8 patients of PA group (67%) and negative in all patients of non-PA group. PASTOREX ASPERGILLUS in serum were negative in all 21 patients. PASTOREX ASPERGILLUS in sputum were 3+ (+3) in all 14 patients of PA group and in 2 patients of non-PA group and 2+ (+2) in 2 patients of non-PA group. 12 patients of PA group were treated by antifungal agents and 11 patients responded well to the treatment. We also made sputum culture of Aspergillus and measurement of PASTOREX ASPERGILLUS in sputum on 14 patients (group B) who had respiratory diseases with stable cavities and 17 patients (group C) who had respiratory diseases without a cavity. In group B, sputum culture were positive in 1 patient and PASTOREX ASPERGILLUS in sputum were 3+ (+3) in 2 patients, 2+ (+2) in 1 and 1+ (+) in 2. In group C, sputum culture were negative in all patients and PASTOREX ASPERGILLUS in sputum were 3+ (+3) in 1 patient, 2+ (+2) in 3 and 1+ (+) in 2. Measurement of PASTOREX in sputum was a useful tool to diagnose non-invasive aspergillosis in addition to sputum culture and measurement of precipitin antibody titer. The sensitivity of PASTOREX in sputum was high but its specificity was low, however, its specificity could be raised by applying semi-quantitative analysis of PASTOREX in sputum.

A pilot study, to assess the therapeutic potential of percutaneous injection of wild-type p53 (wt-p53) in five patients with primary hepatocellular carcinoma is reported. Three of the five patients showed objective tumor response with reduction of the tumor volume on computed tomographic (CT) scan measurements as well as a significant fall of serum alphafetoprotein. Much further work will be needed to elucidate the mechanism of action.

This study clarifies the characteristics of the time keys that are taken to enter Roman letters for Japanese sentences. First, test the appearance frequency of two consecutive characters of the alphabet in the input of English sentences and in the input of the Roman characters of Japanese sentences. Based on these results, we analyzed the features of stroke frequency of the keys in the Roman character input. Based on the result of the analysis, we clarified the features of the keystroke interval time for two consecutive characters in the Roman character input. Then, keys were struck to enter Japanese sentences for a fixed period of time and a test was made for the characteristics. As a result, the following points were clarified: 1) The time keys struck were divided into two large groups. One for two consecutive alphabet letters that corresponded to Kana, or the Japanese syllabary, and the other with no correspondence. The former had smaller values for the mean time and deviations, and the latter had larger values for them. 2) The subjects who struck a larger number of keys per unit time took less time in typing two consecutive letters which did not correspond to Kana.

The aim of the present study was to assess immunological aspects in patients on continuous ambulatory peritoneal dialysis (CAPD). The CAPD patients were divided into two groups. Group A consisted of patients in which high-somolar dialysate was used infrequently, and group B consisted of patients in which high-osmolar dialysate was used frequently. We characterized cell populations in the peritoneal effluent (PE) of CAPD patients. Analysis of the nucleated cell composition revealed that one-third of the PE cells were lymphocytes. Flow cytometric analysis of the surface antigen expression on lymphocytes revealed that the proportion of helper/inducer T-cells was lower in PE than in peripheral blood (PB). By contrast, the rates of DR antigen expression on T-cells and CD45RO antigen expression on helper/inducer T-cells (memory T-cells) were higher in PE than in PB. However, there were no statistically significant differences between the rates of expression of any lymphocyte surface antigens in the two groups. Expression of intercellular adhesion molecules, such as ICAM-1 and LFA-1, was higher in PE than in PB. It is of interest that the expression of ICAM-1 and LFA-1 on T-cells in PB was significantly higher in group B than in group A. In summary, there is an increase in memory T-cells in the PE and up-regulation of intercellular adhesion molecules of PE lymphocytes of CAPD patients. The up-regulation of intercellular adhesion molecules is also observed in PB lymphocytes in whom high-osmolar dialysate is used frequently.

Functional abnormalities of the liver uncovered during preoperative routine evaluation were analyzed in 109 donor candidates for 100 cases of living-related liver transplantation (LRLT) performed during the period from June, 1990 to May, 1994 at the Second Department of Surgery, Kyoto University Hospital. High serum transaminase (GOT, GPT) levels were noted in 10 (9.2%) cases among 109 candidates, high alkaline phosphatase in 4 (3.7%), hyperbilirubinemia in 3 (2.8%), anemia in 3 and high choline esterase in 3 cases. Positive hepatitis C antibody (HCV) was also noted in 1 case. Fatty liver was detected in 10 (9.2%) cases, cholecystitis in 2 cases, 1 case each of cyst and calcification in the liver by diagnostic imaging (ultra sonograph and/or computed tomography). These abnormalities of the liver necessitated replacing the initial candidate with the other parent in 9 cases, including 1 case without any functional abnormality whose graft liver was too large to fit the recipient abdominal cavity. There were 14 cases of ABO blood type incompatible combination. Switching the initial candidate due to these abnormalities mentioned above resulted in incompatible combinations in 4 of these 14 cases. Although the advantages of the LRLT are the superior viability of the donor graft and the genetic histocompatibility between recipient and donor, to optimize the advantage of LRLT, all donor candidates should be strongly advised to make every effort preoperatively to improve their physical condition in preparation for the LRLT protocol, since many of these abnormalities are typically reversible.

A 26-year-old man was admitted to our hospital with a 10-day history of sore throat, high fever, and right knee joint pain. On physical examination, the pharynx was considerably inflamed, and the right knee joint was swollen and extremely tender. Chest radiography showed multiple, bilateral nodules and masses with pleural effusions. Fusobacterium necorforum grew from samples of blood, pleural effusion, and pus taken from the knee joint. The patient was treated with intravenous clindamycin, ventilatory support, and continuous chest and knee joint drainage. His condition progressively improved and he was discharged on the 66th hospital day. A disease caused by an oropharyngeal infection with secondary suppurative thrombophlebitis of the internal jugular vein, and complicated by multiple metastatic infections is called postanginal septicemia, or Lemierre syndrome. Before the discovery of antibiotics, this disease usually was fatal. The widespread use of antibiotics for treat oropharyngeal infections may have caused a number of reported cases. Lemierre syndrome is an uncommon complication of oropharyngeal infection, and it may be fatal if diagnosis is delayed. Careful attention must be directed to patients with oropharyngeal infection who have signs and symptoms that suggest metastatic infection.

We analyzed the DNA in the remains of three skeletons affected by severe post-mortem modification to identify the sex of the cases. We analyzed DNA extracted from bone, bone marrow and a tooth by Southern blot hybridization with Y chromosome specific probe and PCR to amplify the sex chromosome specific sequence. The first case had been preserved underground in a deep grave for two months, the second case was found in a forest after more than five years, and the last case had been kept in a styrofoam box for few years. The detective sensitivity of Southern hybridization improved to nearly the same level as PCR with the aid of computed image processing. Although PCR was of obvious benefit when analyzing small amounts of biological evidence, amplification was impossible in case the target sequence became lost or changed. As a result, we identify the sexes of the three cases by Southern blot hybridization or PCR using bone, bone marrow and tooth DNA. The old skeletal remains were suitable for sex identification in spite of severe post-mortem change, due to preservation in a condition protected from external influences.

The purpose of this case study was specifically to reinforce the necessity for proper positioning in a wheelchair for an adult athetoid cerebral palsy patient. A 36-year old female with cerebral palsy sat in the wheelchair with pelvic sliding, uneven weight distribution on the hips, hip adduction, and right lateral trunk tilt and rotation. The abnormal posture observed was first corrected by seating the patient well back in the wheelchair with the patient's weight evenly distributed between both hips. A seat belt, abduction pommel, trunk belt, seat cushion, and foot pad were inserted to help the patient maintain the corrected posture. Points to consider when ordering a wheelchair and adaptive equipment are reviewed. The optimal sitting position and positioning objectives and considerations, as well as the selection process are also presented. Participation of the patient and the caregivers in the selection and decision-making processes helps lead to successful results. A thorough assessment of the patient's prognosis and environment is important to prevent harmful, expensive, and disappointing results. On-going reviews of the patient and use of the equipment are helpful in preventing deformities and other problems. As we already know, increasing the patient's function and ability to move around and explore the environment can affect his/her attitude toward daily living as well as quality of life.

This study was designed to evaluate effects of fentanyl (F) on heart rate (HR), systemic blood pressure (SBP) and renal sympathetic nerve activity (RNA) in urethane- or halothane-anesthetized rabbits. Twenty three urethane-anesthetized rabbits were divided into the following four groups: animals with neuraxis intact (Intact group, N = 8), cervical vagotomized animals (Vagotomy group, N = 5), animals treated with sino-aortic denervation (SAD group, N = 5), and those with sino-aortic denervation with vagotomy (SADV group, N = 5). In the intact group, administration of F (20 micrograms.kg-1, i.v.) caused a significant decrease in HR, but not in SBP, even in the presence of increase in RNA. In the Vagotomy group, no significant alterations in HR and SBP occurred despite activation of RNA. In the SAD group, F caused a significant decrease in HR and an increase in both SBP and RNA. In the SADV group, a decrease in HR disappeared but a significant increase in both SBP and RNA developed. In halothane-anesthetized rabbits having intact baroreceptors (N = 5), similar hemodynamic and sympathetic responses to F were observed. In human (N = 5), F (6 micrograms.kg-1, i.v.) caused a decrease in HR but the effect was not significant on SBP. Thus similar hemodynamic changes occurred in both human and in the animals. These results suggest that F may cause a simultaneous activation of vagal nerve and sympathetic nervous system, which might contribute to the hemodynamic stability when F is administered in human.

The IgE response to Cryptomeria japonica pollen antigen (CPAg) in vivo was determined by radioimmunoassay of the plasma of 525 members from 98 families with known nasal allergies. Based on responses, patients were classified into a non-responder or low-responder group (non/low) and a high-responder group. Segregation analysis revealed that the IgE non/low responsiveness to CPAg involved a single dominant trait. The gene frequency was calculated to be 0.44-0.60. The IgE non/low response to CPAg was found to be mediated by CPAg-specific suppressor T cells. These findings demonstrated that the phenotypic variation of IgE responsiveness to CPAg is not due the immune response gene, but rather is mediated by the immune suppression gene for CPAg, via CPAg-specific suppressor T cells.

We conducted in-depth case studies of traffic accidents involving 118 pedestrians, who were struck by the fronts of bonnet-type cars. The data were reviewed in order to correlate injury severity with pedestrian age, and area of body contact, contact surface of vehicle or the local environment, and impact speed. It was found that head injuries caused by impacts against the top surface of car bonnets and leg injuries caused by front bumpers both showed high incidence rates. Both head and leg injuries caused by striking the vehicle were more severe than those caused by striking the road surface. In cases of impact between the head and the solid portion of the vehicle, such as the A-pillar, or in cases of secondary impact between the head and underhood solid structures such as shock tower, injuries tended to be more severe. The location of head impact varied according to the stature of the pedestrians.

Plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) was measured in 19 patients with acute schizophrenia before and after neuroleptic therapy. Plasma antinoradrenergic activity (pANA) of the neuroleptics used was measured after treatment. Before treatment, pMHPG was higher in the patients than in 20 normal controls. There was a positive correlation between pMHPG level and the global severity of positive symptoms. After neuroleptic therapy, pMHPG was reduced, and there was a significant correlation between the decline in pMHPG and the improvement in positive symptom score. The decline in pMHPG was also correlated with pANA. These results suggest that there is a dysfunction of the noradrenergic system in the brains of some acute schizophrenics with mainly positive symptoms, and that this dysfunction may be improved, along with positive symptom score, after neuroleptic therapy.