A Report on the Positive Response to an Outdoor Nature Challenge of a Snow Camp for Young Liver Transplant Patients.

OBJECTIVES: More than two decades have passed since the first living donor liver transplantation was performed in Japan in 1989. There are many reports about problems in adherence to taking medication and medical follow-ups in children who received liver transplants, because there is no transition strategy for those children and parents or guardians. The objective of this study is to measure the effect of nature and outdoor activity to improve children's medical adherence. METHODS: We recruited participants from 9-year-old children who are attending the outpatient liver transplant clinic in a stable condition (no event such as rejection or surgical procedure within 6 months). We took participants to a snow camp and measured its effect by using the IKIRU CHIKARA (IKR) tool, which contain 28 items divided into 3 categories: psychosocial ability, moral fitness, and physical ability. Children were tested on three occasions, before, just after, and 1 month after the camp. RESULTS: Eight patients participated in the snow camp and 7 patients were eligible for the study. The average age was 12.6 with a range 10 to 17 years. There were 3 girls and 4 boys. The average IKR scores before, just after, and 1 month after the camp were 127.9, 131.5, and 126.6, respectively. CONCLUSION: An outdoor activity such as a snow camp can be safely conducted, and it is an acceptable option to incorporate within a pediatric liver transplant program. There were no significant changes in IKR scores during this short observation. Longer observation is needed to measure the effect of nature and outdoor activities.

Left-side hepatectomy in living donors: through a reduced upper-midline incision for liver transplantation.

BACKGROUND: We present our attempts at reducing the length of incision in living donor left-side hepatectomy without laparoscopic approach. METHODS: The chief surgeon initially made a 10-cm upper midline incision and performed all procedures through a minilaparotomy without abdominal wall lifting or pneumoperitoneum. For the procedures in the lateral and deep areas, we effectively applied traction to the wound in multiple directions using a wound retraction system so that the chief surgeon could obtain a good direct view. We also placed a fiberscope on the minilaparotomy so that the assistant surgeons could obtain an additional video view via a monitor. Surgeons lengthened the incision at their own discretion if the initial length was thought to be too short for the donor's safety. Since February 2009, we have employed this operation for 19 living donors (12 lateral segmentectomies and 7 left hepatectomies) and compared parameters between the 19 donors and 34 previous donors who underwent the procedure with standard incision (11 lateral segmentectomies and 23 left hepatectomies). RESULTS: The resultant length of incision was significantly reduced in operations with reduced incision length as compared with standard incision. Clinical outcomes such as operation time and length of hospital stay were comparable or significantly reduced with the reduced incision. The resultant incision length remained within 10 and 12 cm in lateral segmentectomy and left hepatectomy cases, respectively, whose body mass index was less than 22. CONCLUSION: It appears to be feasible to reduce the incision length for living donor left-side hepatectomy, especially in nonobese cases.

Treatment for hypergranulation at gastrostomy sites with sprinkling salt in paediatric patients.

OBJECTIVE: To estimate the efficacy of sprinkling salt treatment (SS) of hypergranulation at gastrostomy sites in paediatric patients. METHOD: A prospective case-series study of paediatric patients with hypergranulation at gastrostomy sites. About one-third of a 5ml-teaspoon of table salt was sprinkled over the tissue once a day, either by the doctors/nurses in the wards or doctors in the outpatient setting. Treatment was continued by the patients or carers in the home, until the hypergranulation was seen to flatten. The patients were followed up by health professionals once a month. RESULTS: Eight paediatric patients (seven females and one male) were included in the study. The hypergranulation decreased in size and became almost flat in all patients within 3 days to 2 months (median 7 days). Five patients had a recurrence of hypergranulation, but were treated successfully by repeated SS. Skin erosion was observed in one patient when SS was continued too long; therefore, the treatment protocol was altered so that the salt was irrigated 10 minutes after SS. A biopsy of the hypergranulation tissue was taken from a patient and salt was sprinkled on the tissue in a dish to simulate SS for histopathological examination. Histopathologically, hypergranulation treated by SS exhibited reduced interstitial oedema. CONCLUSION: The results of this study suggest that hypertonic environment induced by SS effectively reduced the oedematous hypergranulation tissue. SS is advantageous over traditional treatment such as silver nitrate in that SS is inexpensive and can be continued by the parents and repeated if necessary at home.

Interactive Radiology teaching file system: the development of a MIRC-compliant and user-centered e-learning resource.

Radiology teaching usually employs a systematic and comprehensive set of medical images and related information. Databases with representative radiological images and documents are highly desirable and widely used in Radiology teaching programs. Currently, computer-based teaching file systems are widely used in Medicine and Radiology teaching as an educational resource. This work addresses a user-centered radiology electronic teaching file system as an instance of MIRC compliant medical image database. Such as a digital library, the clinical cases are available to access by using a web browser. The system has offered great opportunities to some Radiology residents interact with experts. This has been done by applying user-centered techniques and creating usage context-based tools in order to make available an interactive system.

Positive association of genetic variants in the upstream region of NKX2-3 with Crohn's disease in Japanese patients.

BACKGROUND AND AIMS: A number of genome-wide association studies have been performed as a robust means of identifying susceptibility loci for Crohn's disease (CD). The loci detected after the completion of the HapMap project are quite concordant among these studies, suggesting that the results are reliable. Recently, the Wellcome Trust Case Control Consortium (WTCCC) reported the primary scanning of 17,000 individuals for seven diseases, including CD, and a subsequent study has validated these susceptible genetic variants in independent UK sample sets. The purpose of this study was to study the possible association of the variants reported by the WTCCC with CD in a Japanese population. PATIENTS AND METHODS: A total of 484 patients with CD and 470 healthy controls were examined. Seventeen genetic variants at eight newly identified loci, including IRGM, NKX2-3 and PTPN2, were genotyped using the TaqMan assay or the invader assay. RESULTS: A positive association signal presumably common to different ethnic groups for rs10883365 was detected in the upstream region of NKX2-3 (p = 0.019 under the genotypic model, p = 0.0065 under the allelic model, p = 0.019 under the recessive model, p = 0.036 under the dominant model). In addition to rs10883365, marginal associations for two single nucleotide polymorphisms (SNPs) were detected in the Japanese population; rs6887695 near IL12B and rs10761659 on 10q21. Further genotype-phenotype analysis found a significant association between rs6887695 and patients with pure ileal CD. CONCLUSIONS: The results indicate that the three loci are possible candidates for conferring susceptibility to CD in people of different ethnicities.

5-Methoxy-N,N-diisopropyltryptamine (Foxy), a selective and high affinity inhibitor of serotonin transporter.

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is a synthetic orally active hallucinogenic tryptamine derivative, known also as Foxy or Foxy methoxy. However, few studies have examined its effects in vitro. In the present study, we investigated the actions of 5-MeO-DIPT against monoamine neurotransmitter transporters, including the transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT), using COS-7 cells heterologously expressing these transporters and rat brain synaptosomes. 5-MeO-DIPT specifically inhibited the uptake of [3H]serotonin (5-HT) by the SERT-expressing COS-7 cells and rat striatal synaptosomes in a high affinity manner at concentrations similar to those for cocaine. The effect was reversible and competitive. 5-MeO-DIPT failed to stimulate reverse transport of [3H]5-HT through SERT, while it prevented the releasing action of methamphetamine. 5-MeO-DIPT induced cell toxicity at high concentrations in COS-7 cells, and it was not influenced by the expression of SERT. These results demonstrated that 5-MeO-DIPT acts as a competitive SERT inhibitor and has an inability to cause reverse transport, underlying its serotonergic actions.

In vitro metabolism of the glycosidic sweeteners, stevia mixture and enzymatically modified stevia in human intestinal microflora.

Stevia mixture, sweeteners extracted from the leaves of Stevia rebaudiana Bertoni, consists mainly of stevioside and rebaudioside A (glycosides of the diterpene derivative steviol). The aim of this study was to investigate human intestinal metabolism of stevia mixture and its alpha-glucose derivative (known in Japan as enzymatically modified stevia) by LC/MS/ESI analysis. Degradation was examined by incubating stevia mixture, enzymatically modified stevia, stevioside, rebaudioside A, alpha-monoglucosylstevioside, alpha-monoglucosylrebaudioside A and the aglycone, steviol with pooled human faecal homogenates (obtained from five healthy volunteers) for 0, 8 and 24 h under anaerobic conditions. Stevia mixture, enzymatically modified stevia, stevioside and rebaudioside A (0.2 mg/ml) were completely eliminated within 24 h, whereas no degradation of steviol (0.08 and 0.2 mg/ml) appeared to be found during the incubation period. Stevia mixture, stevioside and rebaudioside A appeared to be hydrolyzed to steviol by human intestinal microflora: this observation is consistent with previous rat metabolism studies. Similarly, enzymatically modified stevia appeared to be metabolized via stevia components and, finally, to steviol. This study suggests that there are apparently no species differences in intestinal metabolism of stevia mixture between rats and humans.

[Relationship between fatty liver and coronary risk factors].

Fatty liver is a common finding in abdominal ultrasonographic examination in health check-ups, but the relationship between fatty liver and so-called coronary risk factors has rarely been investigated from the viewpoint of prevention of coronary heart disease. The purpose of the present study was to elucidate such a relationship by comparing the coronary risk factors with and without fatty liver by using data from health check-ups for the mid-management and management staff of a manufacturing company. The majority (77.1%) of those with fatty liver in the present study were categorized as "normal" or "marginally obese" and only a small portion (22.9%) were categorized as "obese" according to the classification of the body mass index. The group of subjects with fatty liver had significantly lower mean HDL-cholesterol and higher levels of fasting blood sugar, HDL/total cholesterol ratio, triglyceride, uric acid and transaminases, than those parameters in subjects without fatty liver, even after adjustment for age and body-mass index. The blood pressure (both systolic and diastolic) and total cholesterol level did not show any significant difference after controlling the covariates. Our results indicated that fatty liver has a close correlation with the majority of coronary risk factors causing atheroscleotic diseases, and most of these relationships are independent of total body mass. Our results regarding fatty liver are a help to occupational health personnel when advising workers to reduce their own risk of atherogeic diseases.

Lipoprotein(a) is a potential coronary risk factor.

Lipoprotein(a) (Lp(a)) is recognized as a new coronary risk factor, but few studies have quantitatively assessed the relationship of serum Lp(a) levels with other coronary risk factors in many patients undergoing coronary cineangiography. Seventeen coronary risk factors were quantified (i.e., age, gender, hypertension, impaired glucose tolerance, cerebrovascular accident, hyperuricemia, smoking, family history of ischemic heart disease (IHD), history of hyperlipidemia, Lp(a), total cholesterol, high density lipoprotein (HDL)-cholesterol, triglyceride, low density lipoprotein-cholesterol, apolipoproteins(apo)A-I,B, E) to determine their relationship with the numbers of involved coronary vessels using multiple regression test in 1,006 patients who underwent coronary cineangiogram (280 non-IHD patients: 144 men, 136 women; 726 IHD patients: 460 men, 266 women; age 16-84 years, mean 60.5+/-0.3). Multiple regression test indicated R = 0.506 and items that showed high beta weight and significant p level were age, Lp(a), impaired glucose tolerance, total cholesterol, cerebrovascular accidents, HDL-cholesterol, smoking, gender, family history of IHD, and apo-A-I (0.221, p<0.001; 0.174, p<0.001; 0.616, p<0.001; 0.138, p<0.001; 0.122, p<0.001; -0.12, p<0.001; 0.092, p<0.01; 0.091, p<0.01; 0.067, p<0.05; -0.065, p<0.05; respectively). It was concluded that Lp(a) is an independent, potential, and modifiable coronary risk factor, and that reduction of serum Lp(a) is important in the clinical management of patients with IHD.

Occlusive arterial diseases of the upper and lower extremities found in workers occupationally exposed to vibrating tools.

Hand-arm vibration syndrome (HAVS) is primarily a disorder of the fingers and hands. However, in some cases, vibration-exposed workers are observed to have also episodic blanching of the hands and feet. In latter cases, arteriographies of both the upper and lower extremities are necessary to diagnose the background arterial disorders. In this study, eight HAVS subjects with such disorders were examined by arteriography for differential diagnosis in cases of workers' accident compensation. In three HAVS cases with thromboangiitis obliterans, the arteriographic examination revealed obstructive changes in the palm and forearm as well as three below-knee lesions in the lower extremities. In five HAVS cases with arteriosclerosis obliterans, obstruction kinking or coiling, stenosis and/or tapering-off of the proper digital arteries were observed together with two below-knee lesions and three high lesions in the lower extremities. From the viewpoint of occupational health, palpation of superficial arteries of both the upper and lower extremities should be routinely performed during both pre-placement and periodic medical examinations for workers exposed to vibrating tools for early detection and/or prevention of any worsening of the background disorders.

Exposure of macrophage-like cells to titanium particles does not affect bone resorption, but inhibits bone formation.

We examined the capacity of culture supernatants of macrophage-like cells exposed to titanium particles to influence bone formation and bone resorption, our aim being to elucidate the mechanism of implant loosening. A mouse macrophage-like cell line, J774, was exposed to titanium particles and the concentrations of prostaglandin E2, tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-6 in the supernatants were measured. Titanium particles stimulated the J774 cells to release tumor necrosis factor-alpha, whereas prostaglandin E2, interleukin-1alpha and interleukin-6 concentrations remained low. The bone resorptive activity of the supernatants was measured by determining 45Ca release from cultured pre-labeled newborn mouse calvariae. The culture supernatants of J774 cells exposed to titanium particles showed no significant difference in bone resorptive activity in mouse calvariae from that of culture supernatants of J774 cells not exposed to titanium particles. The bone-forming activity of the supernatant was evaluated by determining bone nodule formation and alkaline phosphatase activity in cultured mouse calvaria cells. The bone-forming activity of the supernatants exposed to titanium particles was significantly decreased compared with the supernatants of unexposed J774 cells. This inhibition was reversed by the addition of anti-tumor necrosis factor-alpha neutralizing antibody. We conclude that tumor necrosis factor-alpha released from J774 cells exposed to titanium particles played an important role in the inhibition of bone formation rather than in the stimulation of bone resorption.

[A case of prostatic ductal adenocarcinoma with endometrioid features, associated with rectal invasion and multiple liver metastases].

In a case histologically proven prostatic ductal adenocarcinoma with endometrioid features associated with rectal invasion and multiple liver metastases the expression of prostate specific antigen (PSA) and carcinoembryonic antigen (CEA) was studied immunohistochemically on paraffin sections to clarify markedly elevated PSA and relatively elevated CEA in sera. All of prostatic ductal adenocarcinoma with endometrioid features, rectal invasion and liver metastases gave positive staining for PSA. Although rectal invasion and liver metastases gave positive staining for CEA, the primary tumor was never stained for CEA. Further study is necessary to clarify any significance of CEA within the cancer cell.

High catalytic activity of human cytochrome P450 co-expressed with human NADPH-cytochrome P450 reductase in Escherichia coli.

Forms of human cytochrome P450 (P450 or CYP), such as CYP1A1, CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4, were expressed or co-expressed together with human NADPH-P450 reductase in Escherichia coli. When P450 was expressed alone in E. coli, the expression level of holo-P450 ranged from 310 to 1620 nmol/L of culture. The expression level of holo-P450 decreased by co-expression with the reductase, and the level ranged from 66 to 381 nmol/L of culture. The expression level of the reductase varied depending on the forms of P450 co-expressed, and ranged from 204 to 937 U/L of culture. We assayed the catalytic activity of P450 using E. coli cells disrupted by freeze-thaw. When co-expressed with the reductase, human P450 catalyzed the oxidation of representative substrates at efficient rates. The rates appeared comparable to the reported activities of P450 in a reconstituted system containing purified preparations of P450 and the reductase.

Comparison of the qualified occupational physician systems in the United Kingdom and Japan.

The British educational system of occupational medicine was compared to the Japanese system. Furthermore, a comparison was carried out between the certified occupational physician (COP) recognized by the Japan Society for Occupational Health in Japan and the Associateship of the Faculty of Occupational Medicine (AFOM) by the Faculty of Occupational Medicine (FOM) which is a part of the Royal College of Physicians in the United Kingdom. Judging from the comparison of the minimum total training period, the clinical training period, the occupational health training period, the method of examination and the success rate between COP and AFOM, it is suggested that the British system of occupational physicians may be better as a training system for occupational medicine and may regard occupational clinical training as more important than the Japanese system does. A comparison of a Diploma in Occupational Medicine (Dip Occ Med) approved by the FOM and the certification of occupational physicians by the Japan Medical Association has shown that the former has an examination but there is no test system in the latter. It should be discussed whether an examination system for the certification of occupational physicians should be introduced into the Japanese system in the near future.

Determination of carcinogenic potential of mineral fibers by 8-hydroxydeoxyguanosine as a marker of oxidative DNA damage in mammalian cells.

8-Hydroxydeoxyguanosine (8-OH-dG) is a typical form of oxidative DNA damage, which causes mutations in vitro and in vivo. To develop a simple method of testing the carcinogenicity of fibrous materials, the formation of 8-OH-dG was determined in the DNA of J774 cells, an established reticulum cell sarcoma line, after treatment with various natural and man-made mineral fibers. The amount of 8-OH-dG was determined using high-pressure liquid chromatography (HPLC) equipped with an electrochemical detector (ECD). We tested three natural mineral fibers (crocidolite, amosite, and chrysotile) and three man-made mineral fibers (ceramic, glass, and potassium octatitanate). Among them, a significant increase in 8-OH-dG formation was observed in the crocidolite- and amosite-treated cells. We also measured the amount of tumor necrosis factor (TNF) produced by J774 cells incubated with the fibrous materials. Cellular TNF production increased after treatment with all the fibers tested, but it was not statistically significant except in the case of chrysotile. Therefore, these results indicate that the mechanism of TNF production is different from that of 8-OH-dG formation, and that the carcinogenicity of various fibrous materials can be better evaluated by measuring the 8-OH-dG level in J774 cellular DNA after treatment with these fibers.

Basophilic deposits on the cupula: preliminary findings describing the problems involved in studies regarding the incidence of basophilic deposits on the cupula.

In this study, the possibility of whether basophilic deposits adhered to the cupulas in the semicircular canals was investigated histologically. Results indicated that basophilic deposits were present in all three cupulas of the semicircular canals. The overall incidence of basophilic deposits in the superior, lateral and posterior semicircular canal cupulas was 26%, 41% and 37%, respectively. The incidence of basophilic deposits bound to the cupulas increased with age. The possible origin of these basophilic deposits on the cupulas and the increased incidence of basophilic deposits with increasing age are discussed.

Influence of vestibular organ stimulation on stomach movement and respiration.

Some previous investigators have reported controversial results in the stomach movement in response to labyrinthine stimulation (1). The purpose of the present study was to investigate the influence of vestibular stimulation on the stomach movement and respiration in anesthetized cats, and to investigate the differences between increased and decreased responses of the stomach movement. This study used an electrophysiological technique: a bipolar stainless-steel stimulating electrode with a tip diameter of 20 microns introduced chronically into the anterior and/or lateral semicircular canal (2). The intragastric pressure was recorded by using a balloon-transducer system. Respiration was recorded by measurement of the thorax. When the peripheral labyrinth was stimulated, we found conflicting results in that the pressure in the stomach increased several times and sometimes decreased. Respiration usually became irregular or intensified. It seems that forced respiration may be involved in vestibular vomiting but we were unable to induce vomiting.

Vestibular training for acute unilateral vestibular disturbances: its efficacy in comparison with antivertigo drug.

We carried out a clinical trial on the treatment of acute unilateral vestibular disturbances (AUVD) without typical Meniere's disease and benign paroxysmal positional vertigo. Two therapy groups were selected: vestibular training (VT) with drug therapy and drug administration alone. After the experimental period of 8 weeks, all patients were classified into two groups depending on the methods of treatment, and the clinical courses of the patients were compared statistically. It was confirmed statistically by global judgments of symptoms and signs that improvement rates were higher in the group treated by VT with medication than the improvement rate in the group with medication alone. It is concluded that VT is effective for early relief from vestibular ataxia.

Initial symptoms and retrospective evaluation of prognosis in Menière's disease.

Clinical studies on an initial symptom and a long-term course of vertigo and hearing impairment and retrospective evaluation of the prognosis were performed in Menière's disease. One hundred and fifty-one patients (67 males and 84 females) with Meniere's disease were treated in the Neuro-otological clinic, Kitasato University Hospital from 1990 to 1995. Ages ranged from 17 to 77 years (mean 47.3 years) at the onset of the disease when the first vertigo attack occurred. There were 106 (70.1%) in their 30s, 40s and 50s, and 28 (18.5%) aged 60 years or over. Seventy-eight patients visited the clinic within one year of the onset of the disease, but the mean interval was 4 years and 5 months (the longest was 25 years). The mean duration time for the follow-up studies from the time of their first visit to the hospital was 2 years and 5 months. The bilateral ears were invaded in 19 patients (12.6%) and the mean length of their time course was 9 years and 10 months which is longer than the length in unilateral cases. Several important key points for diagnosis of Menière's disease were investigated in 28 of the 151 cases who had been followed up successfully over a relatively long time course (the mean follow-up time was 7 years and 3 months). Fluctuated or stational cochlear signs, such as tinnitus, hearing impairment and/or fullness in the ear, had started prior to the onset of the first vertigo attack in 17 (61%) of 28 cases. Vertigo without cochlear sign appearing at the onset and cochlear signs were combined later in six (21%) of the 28 cases. Only five (18%) of the 28 cases had vertigo combined with a cochlear sign simultaneously at the onset of the disease. The affected ear was on the left in 15 cases and on the right in seven of 22 unilateral cases. In six bilateral cases the left ear was the first to be invaded in four out of six cases. The interval between the first and second attacks was over 1 year in six of the 28 cases and over 6 months in 10 of the 28 cases. Nine out of the 28 patients had recurrence of vertigo attacks during the first month and five of the nine had a cluster of attacks in the first month. Our study of 28 patients over a long time course revealed eight patients (28.6%) free from the disease. These patients had no recurrence of vertigo for more than 2 years after their last attack, and sixteen (57.1%) of the 28 patients had no recurrence of vertigo for more than 1 year. However, a long period of relief time of more than 2 years in 11 of the 28 patients and a period of more than 1 year was noticed in 16 of the 28 patients. Hearing levels at the middle and low frequencies in the first hearing test were compared with the last test. The mean of hearing levels changed from 38.1 to 36.2 dB after 2 years and 1 month in six cases with the right ear affected and from 34.1 to 45.3 dB after 5 years and 3 months in 15 cases with the left ear affected, but in seven cases with bilateral diseased ears the hearing in both ears became worse, from 25.5 to 57.1 dB in the right ear and from 30.5 to 53.6 dB in the left ear during a period of more than 10 years. These clinical findings should be utilized for diagnosis at the onset of Menière's disease to determine the interval for observation in order to evaluate the efficacy of treatment.

Effectiveness of fibronectin in myringoplasty using temporal fascia.

A study of myringoplasty with temporal fascia homograft employing fibronectin was conducted in 14 ears in which the same myringoplasty procedure without fibronectin (1-5 times) had failed to afford closure of tympanic membrane perforation. Closure was obtained in eight ears. These results suggest that fibronectin is effective in myringoplasty using treated temporal fascia homograft.