Effect of maintenance therapy with low-dose peginterferon for recurrent hepatitis C after living donor liver transplantation.

Approximately 30% of patients who have recurrent hepatitis C after liver transplantation achieve sustained virological response (SVR) by taking a combination therapy of pegylated interferon and ribavirin. For the remaining non-SVR patients, an effective management treatment has not yet been established. In this study, efficacy of long-term peginterferon maintenance therapy for non-SVR patients was evaluated. Forty patients who had previously received the combination therapy for hepatitis C after living donor liver transplantation were classified into one of the following three groups: the SVR group (n = 11); the non-SVR-IFN group (n =17), which received low-dose peginterferon maintenance therapy for non-SVR patients; and the non-SVR-Withdrawal group (n = 12), which discontinued the interferon treatment. We then compared histological changes among these three groups after 2 or more years follow-up. Activity grade of liver histology improved or remained stable in patients in the SVR and non-SVR-IFN groups, but deteriorated in half of the patients in the non-SVR-Withdrawal group. Fibrosis improved or remained stable in 10 of 11 SVR patients and in 13 of 17 non-SVR-IFN patients, but deteriorated in all non-SVR-Withdrawal patients. Mean changes in fibrosis stage between pretreatment and final liver biopsy were -0.18, +0.06 and +2.2 in the SVR, non-SVR-IFN and non-SVR-Withdrawal groups, respectively. Fibrosis stage deteriorated to F3 or F4 significantly more rapidly in the non-SVR-Withdrawal group than in the other two groups. In conclusion, continuing long-term maintenance therapy with peginterferon prevented histological progression of hepatitis C in patients who had undergone living donor liver transplantation.

Hashimoto's encephalopathy after interferon therapy for hepatitis C virus in adult liver transplant recipient accompanied by post-transplant lymphoproliferative disorder related to Epstein-Barr virus infection.

A 55-year-old woman underwent living-donor liver transplantation (LDLT). She had no history of autoimmune diseases. Spleen was preserved. Steroids were withdrawn at 3 months after LDLT. Epstein-Barr virus (EBV) infection occurred at 3.5 years after LDLT. Recurrent hepatitis C virus infection was confirmed at 4.5 years after LDLT, and pegylated interferon was introduced. Diagnosis of EBV-positive post-transplant lymphoproliferative disorder (PTLD) was made at 4.8 years after LDLT, and tacrolimus (Tac) was stopped completely. Then, unconsciousness, convulsion, and cervical stiffness appeared suddenly. Electroencephalography, cerebrospinal fluid analysis, and image studies revealed normal or only nonspecific findings. The patient was in a state of exhaustion; therefore, steroid pulse therapy (SPT) was attempted. Surprisingly, her general condition, including consciousness disturbance, was improved markedly, and Hashimoto's encephalopathy (HE) was suspected, based on this reaction to SPT. Elevations of anti-thyroglobulin antibody and anti-thyroid peroxidase antibody were confirmed. After withdrawal of Tac, and treatment with acyclovir and steroids, EBV-positive PTLD and HE improved, although they recurred at 5.1 years after LDLT. SPT improved only neurological symptoms. Molecular-targeted therapy was given for recurrent PTLD, based on analysis of sampling specimens. This therapy was effective, but tumor lysis syndrome occurred, and the patient died at 5.3 years after LDLT.

Chemical mapping of tulobuterol in transdermal tapes using microscopic laser Raman spectroscopy.

Microscopic Laser Raman Spectroscopy and Mapping (MLRSM) technique was used to investigate the distribution of tulobuterol (TBR) crystals in transdermal tapes. TBR is one of suitable compounds for the transdermal pharmaceuticals because it has high permeability into skin. In case of TBR transdermal tapes, some commercial products also contain TBR crystals in order to control a release rate from a matrix. Therefore, the presence of TBR crystals in the matrix is a critical factor for quality assurance of this type of TDDS tapes. The model tapes prepared here employed two kinds of matrices, i.e., rubber or acrylic, which are generally used for transdermal pharmaceuticals. TBR crystals in the matrix were observed by MLRSM. Accurate observation of the distribution of TBR in the tapes was achieved by creating a Raman chemical map based on detecting unique TBR peak in each pixel. Moreover, differences in the growth of TBR crystals in the two kinds of matrices were detected by microscopic observation. MLRSM also enabled the detection of TBR crystals in commercial products. The present findings suggest that Raman micro-spectroscopic analysis would be very useful for verifying and/or assessing the quality of transdermal pharmaceuticals in development, as well as for manufacturing process control.

Experience with FK506 in living-related liver transplantation.

The new immunosuppressive agent FK506 was used with steroids to treat 22 pediatric patients who received living-related partial liver transplantation. Seventeen recipients survived and 5 died between one and 16 months after transplantation. Three of the 5 patients who died had required intensive care preoperatively. Autopsy findings showed no evidence of rejection. There was no episode of rejection that required retransplantation in any of the patients. Liver allograft dysfunction, which was suspected to be a rejection response, was encountered in 2 recipients with ABO-nonidentical but compatible grafts. However, their clinical and biochemical findings were ameliorated upon steroid pulse therapy or upon augmented FK506 administration without additional potent immunosuppressive agents. Steroid treatment has been discontinued in all surviving patients at 1-9 months after transplantation. Infectious complications encountered in 9 patients included 2 bacterial, 5 viral, and 2 fungal infections. One recipient died of fungal pneumonia. Abnormal increase of serum creatinine level was confined to the complicated patients. Hypertension was a temporary adverse reaction in the early postoperative period, and only one patient needed an antihypertensive drug at 2 months after transplantation. Acute pancreatitis with hyperamylasemia was observed in one patient who was treated successfully with reduction of FK506 administration. Tremor was observed in 8 patients, itching in 4, insomnia in 2, and vomiting in one. Hirsutism, gingival hypertrophy, and lymphoma were not observed. FK506 was highly effective in living-related partial liver transplantation not only in terms of immunosuppressive potential but also because it produced fewer adverse effects.

Casting behavior of titanium alloys in a centrifugal casting machine.

Since dental casting requires replication of complex shapes with great accuracy, this study examined how well some commercial titanium alloys and experimental titanium-copper alloys filled a mold cavity. The metals examined were three types of commercial dental titanium [commercially pure titanium (hereinafter noted as CP-Ti), Ti-6Al-4V (T64) and Ti-6Al-7Nb (T67)], and experimental titanium-copper alloys [3%, 5% and 10% Cu (mass %)]. The volume percentage filling the cavity was evaluated in castings prepared in a very thin perforated sheet pattern and cast in a centrifugal casting machine. The flow behavior of the molten metal was also examined using a so-called "tracer element technique." The amounts of CP-Ti and all the Ti-Cu alloys filling the cavity were similar; less T64 and T67 filled the cavity. However, the Ti-Cu alloys failed to reach the end of the cavities due to a lower fluidity compared to the other metals. A mold prepared with specially designed perforated sheets was effective at differentiating the flow behavior of the metals tested. The present technique also revealed that the more viscous Ti-Cu alloys with a wide freezing range failed to sequentially flow to the end of the cavity.

Bond strength of binary titanium alloys to porcelain.

The purpose of this study was to investigate the bond strength between porcelain and experimental cast titanium alloys. Eleven binary titanium alloys were examined: Ti-Cr (15, 20, 25 wt%), Ti-Pd (15, 20, 25 wt%), Ti-Ag (10, 15, 20 wt%), and Ti-Cu (5, 10 wt%). As controls, the bond strengths for commercially pure titanium (KS-50, Kobelco, Japan) and a high noble gold alloy (KIK, Ishifuku, Japan) were also examined. Castings were made using a centrifugal casting unit (Ticast Super R, Selec Co., Japan). Commercial porcelain for titanium (TITAN, Noritake, Japan) was applied to cast specimens. The bond strengths were evaluated using a three-point bend test according to ISO 9693. Since the elastic modulus value is needed to evaluate the bond strength, the modulus was measured for each alloy using a three-point bend test. Results were analyzed using one-way ANOVA/S-N-K test (alpha = 0.05). Although the elastic moduli of the Ti-Pd alloys were significantly lower than those of other alloys (p = 0.0001), there was a significant difference in bond strength only between the Ti-25Pd and Ti-15Ag alloys (p = 0.009). The strengths determined for all the experimental alloys ranged from 29.4 to 37.2MPa, which are above the minimum value required by the ISO specification (25 MPa).

Mold filling of titanium alloys in two different wedge-shaped molds.

Pure titanium and titanium alloys are potential materials for the fabrication of cast dental appliances. One important factor in producing sound castings is the capacity of the metal to fill the mold. This study used a wedge-shaped mold to compare the mold filling of titanium with that of conventional dental casting alloys. The metals used were CP Ti, Ti-6Al-7Nb, Ti-6Al-4V, Ti with 1 and 4wt% Cu and ADA Type III gold alloy and an Ni-Cr alloy. The castings were cut into four pieces parallel to the triangular surface. Mold filling was evaluated as the distance between the tip of the cast wedge and theoretical tip of the triangle. The mold filling of the gold alloy was superior compared to all the metals tested, while the mold filling of the Ni-Cr alloy was the worst. There were no statistical differences at the 30 degrees marginal angle for all the cast titanium metals. At the sharper 15 degrees angle, CP Ti and Ti-6Al-7Nb was superior to both the Ti-Cu alloys. Although the mold filling of titanium was inferior compared to the gold alloy, the data justify the use of titanium for the production of dental appliances.

Localization of human seminal plasma No. 7 antigen (Ferrisplan) in accessory glands of male genital tract and spermatozoa.

The establishment of a hybridoma (1C4) producing sperm immobilizing monoclonal antibody to human seminal plasma No. 7 antigen (HSP No. 7 Ag.) and the isolation of the pure antigen by immunoaffinity chromatography bound monoclonal antibodies have been reported previously. In the present investigation, HSP No. 7 Ag. has been termed 'Ferrisplan' and its distribution in male genital organs, spermatozoa and body fluids has been studied. The amount of Ferrisplan in the body fluids was determined by radioimmunoassay. Large amounts were detected in seminal plasma and milk, trace amounts in saliva, and none in the serum and urine. The concentration of Ferrisplan was highest in the seminal plasma of azoospermic patients and gradually decreased from oligospermia to normospermia. Using an immunofluorescent method with anti-Ferrisplan monoclonal antibody, strong staining was observed on the epithelial layers of human seminal vesicles, no staining on testes and bright staining on the post-nuclear cap and mid-piece segment of spermatozoa. These results indicate that Ferrisplan is excreted mainly from the seminal vesicle and adheres to the post-nuclear cap and mid-piece of the spermatozoa as a sperm-coating antigen.

Microstructure and corrosion behavior of binary titanium alloys with beta-stabilizing elements.

Binary titanium alloys with the beta-stabilizing elements of Co, Cr, Cu, Fe, Mn and Pd (up to 30%) and Ag (up to 45%) were examined through metallographic observation and X-ray diffractometry to determine whether beta phases that are advantageous for dental use could be retained. Corrosion behavior was also investigated electrochemically and discussed thermodynamically. Some cast alloys with Co, Cr, Fe, Mn, and Pd retained the beta phase, whereas those with Ag and Cu had no beta phase. In some alloys, an intermetallic compound formed, based on information from the phase diagram. The corrosion resistance deteriorated in the TiAg alloys because Ti2Ag and/or TiAg intermetallic compounds preferentially dissolved in 0.9% NaCl solution. On the other hand, the remaining titanium alloys became easily passive and revealed good corrosion resistance similar to pure titanium since their matrices seemed to thermodynamically form titanium oxides as did pure titanium.

Corrosion resistance of the Pt-Fe-Nb magnets for dental-casting.

Magnetic attachments have been used in clinical dental practice, but there is some difficulties associated with removable bridges. One possible solution is to make whole bridges of Pt-Fe magnet alloys and its abutment out of magnetic stainless steel by casting. In terms of castability and magnetic properties, the promising composition of the Pt-Fe-Nb magnet alloy is Pt-30.0 mass% Fe-0.6 mass% Nb and Pt-30.0 mass% Fe-0.5 mass% Nb-0.03 mass% Si. In the present study, the corrosion resistance of these alloys was investigated based on the elusion test, electrochemical behavior and surface characterization by EPMA analysis. The released elements from the Pt-Fe-Nb magnets were mainly Fe ions in quantities similar to that of stainless steel for biomedical use, and the Pt-Fe-Nb magnet alloy, the Pt-Fe-Nb-Si magnet alloy and platinum resembled each other in electrochemical behavior. The present findings suggest, that the Pt-Fe-Nb magnet alloy provides excellent corrosion resistance and has important clinical dental applications.

Isothermal age-hardening behaviour in a Au-1.6 wt% Ti alloy.

This study describes research with a view to developing a new age-hardenable, high-carat dental gold alloy with better biocompatibility by addition of a small quantity of titanium to gold. The relationship between isothermal age-hardening and phase transformation of the Au-1.6 wt% Ti alloy was investigated by means of hardness testing, X-ray diffraction study, scanning electron microscopic observation and energy dispersive spectroscopy. The hardening in the initial stage of ageing seemed to be attributable to the continuous precipitation of the Au4Ti ordered phase in the supersaturated alpha solid solution matrix. The overaging with softening was attributed mainly to the formation of precipitates at the grain boundaries, which grew to bright lamellae and seemed to be composed of the Au4Ti phase.

Fluid-path in the mandible and maxilla.

We examined fluid-paths in the maxilla and mandible of the dog, and compared them with Kihara's extravascular fluid-path-system. Areolar tissue is formed in the walls of the Volkmann's and Haversian canals. This tissue is composed of collagenous and reticular fibers. Kihara confirmed the collagenous fibers were encircled, however we could not ascertain whether they were encircled or not. We have compared the paths in the walls of the Volkmann's and Haversian canals with Kihara's fluid paths, and found the paths in the bone do not belong to the category of Kihara's paths. Namely, the term "extravascular fluid path" should not be applied to the areolar tissue in the bone. We suggest the term "fluid path" for this tissue in the bone. The areolar tissue in the walls of the Volkmann's and Haversian canals and endosteum communicate with one another. We call them collectively endosteum. Yoshikawa called the areolar tissue in the Volkmann's and Haversian canals perivasculäre lymsphräume. However, this designation is inadequate considering the actual characteristics of this tissue.

[Case-control study of moyamoya disease].

The cause of Moyamoya disease is still unknown. We made a research about the factors closely related to Moyamoya disease through a case-control study. The number of cases studied was 66. Controls were selected from among patients' friends, matched as to sex, age and residential area. Questionnaires were sent to the cases and the respective controls by mail. The questions were about past history, developmental history, school records, habitual factors, dietary habits and pets. The first symptoms and age at onset were also surveyed in the cases. The response rate was 84.8% (56 cases) of the cases and 76.5% (101 cases) out of the 132 controls. There was no significant difference in the prevalence of tonsillitis, conjunctivitis, otitis media, and bronchitis. Odds ratio of fever of unknown origin is 2.793 and X2 is 7.213. Diseases whose odds ratio was over 1 were herpes, appendicitis, bronchitis, asthma, anemia, dental caries, head injury and drug allergy. But all of them were not significantly prevalent. Odds ratios of school records were 4-9 and X2 were 4-17 from elementary to junior high school. Odds ratio of western dishes was 2.709 and X2 was 5.189. There was no significant difference as to pets kept. We could not find overt relationships between Moyamoya disease and diseases of head and neck like tonsillitis.

[Facilitation of tibialis anterior H reflex and depression of reciprocal Ia inhibition on soleus motoneurons during teeth-clenching in man].

Modulation of the tibialis anterior (T.A.) H reflex and the reciprocal Ia inhibition from the ankle flexor to the extensor were studied during voluntary teeth-clenching in 7 healthy adult volunteers to investigate the correlation between the oral motor activity and the somatic motor function. The T.A. H reflex was significantly facilitated during voluntary teeth-clenching, and the amount of this facilitation increased with the level of masseter EMG activity. Furthermore, the reciprocal Ia inhibition of the soleus H reflex, induced by stimulation of the common peroneal nerve at a subthreshold intensity for evoking the T.A. M wave, was significantly depressed during voluntary teeth-clenching. It was concluded that 1) the T.A. H reflex is facilitated during voluntary teeth-clenching, 2) there is a positive correlation between the amount of facilitation of the T.A. H reflex and the level of teeth-clenching force, and 3) the reciprocal Ia inhibition of the crural muscle is reduced during voluntary teeth-clenching. It was suggested that teeth-clenching contributes to stability of body stance by increasing the stiffness of the ankle joint.

Milk basic protein increases alveolar bone formation in rat experimental periodontitis.

BACKGROUND AND OBJECTIVE: It is conceivable that the active components extracted from milk whey protein (i.e. milk basic protein, MBP) stimulate bone formation and suppress bone resorption. Periodontitis is characterized by excessive alveolar bone resorption. We examined whether milk basic protein could recover alveolar bone loss in rat experimental periodontitis. MATERIAL AND METHODS: A nylon ligature was placed around the cervix of molars in 8-wk-old male Fischer rats for 20 d. Then, the ligature was removed and a powder diet containing 0.2 or 1.0% milk basic protein was provided daily for another 45-90 d. On days 45 and 90, the maxillae were extracted and analyzed using microcomputerized tomography (micro-CT), followed by histological analysis. RESULTS: Micro-CT images showed that alveolar bone resorption was severely induced around the molar by the 20-d ligature procedure. Treatment with high-dose milk basic protein (1.0%) clearly recovered ligature-induced alveolar bone resorption on days 45 and 90, whereas low-dose milk basic protein (0.2%) did not show such a clear effect. Histological examination clarified that the osteoid thickness of alveolar bone was dose dependently increased by milk basic protein treatment for 90 d. CONCLUSION: These findings suggest that a systemic administration of milk basic protein may be effective for the recovery of alveolar bone loss in periodontitis.

A survey of the appropriate use of antiseptic agents in the operating room of several key health care facilities. A comparison between surveys in 2000 and 2004.

Since 2000, new hand and environmental hygiene guidelines have been published by the Center for Disease Control and Prevention (CDC) based on scientific evidence. Accordingly, we expected that the use of disinfectants in clinical settings had been changed. To compare the use and amount of disinfectants before and after the publication of these guidelines, we conducted a questionnaire-based survey on the use of antiseptic agents in operating rooms (ORs) in 6 key hospitals over a period of a month in 2000 and 2004. As a result, the amount of disinfectants used in ORs was reduced in all hospitals in 2004. Especially, amphoteric detergents and glutaral products showed significant reductions in the total amount used in the 6 hospitals, by 94.8 and 96.8%, respectively. The use of povidone-iodine (PVP-I) was decreased by 23.4% overall, although it was increased in 3 hospitals by 11.0-58.6%. The number of applications of PVP-I on the surgical site did not change; however, the site was left to dry without wiping after PVP-I application more frequently in 2004 than in 2000. The time for surgical scrubbing was shortened in 2004, but brush scrubbing was still used as often as in 2000. Many of the hospitals used brush scrubbing in conjunction with alcohol-based rubs. These results indicated changes in infection control measures in hospital settings after publication of the new CDC guidelines; environmental disinfection had been limited and excessive use of disinfectants reevaluated.

Relationship of periodontal bacteria and Porphyromonas gingivalis fimA variations with phenytoin-induced gingival overgrowth.

OBJECTIVES: We investigated the relationship between phenytoin-induced gingival overgrowth (GO) and the harboring of periodontal bacteria. MATERIALS AND METHODS: Periodontal conditions and subgingival bacterial profiles were examined in 450 sites of 75 subjects. A polymerase chain reaction method was used to detect six bacterial species; Porphyromonas gingivalis (Pg), Actinobacillus actinomycetemcomitans (Aa), Tannerella forsythia, Treponema denticola (Td), Prevotella intermedia (Pi), and Prevotella nigrescens (Pn). Genetic variations of the Pg fimA gene were also examined. Bacterial occurrence was compared with the severity of GO, and alterations in the bacterial occurrence rate and quantities were monitored following periodontal treatment. RESULTS: The occurrences of Aa, Td, Pi, Pn, and Pg with type II fimA (type II Pg) were significantly associated with the severity of GO. Td occurrence was reduced in association with gingival improvement following ultrasonic scaling, however, no such relationship was observed with Aa, Pi, Pn, and Pg. In addition, Pg and Pi markedly persisted after treatment. Clinical improvement of the sites, following an Er:YAG laser treatment, significantly associated with quantitative reduction of Pg in improved sites, however, not that of Pi. CONCLUSION: Type II Pg and Td were each found to have a significant relationship with the development and deterioration of GO.

Reexamination of the extent of the activation of Lys78 plasminogen by tissue plasminogen activator in the presence of polymerized fibrin.

The rate of the conversion of Lys78 plasminogen (Lys78-plg) to Lys78 plasmin by tissue plasminogen activator (tPA) was directly quantitated by SDS-PAGE. The apparent second-order rate constant (Kapp) was (0.27 +/- 0.07) x 10(3)/M/s for single-chain tPA and Lys78-plg, and was enhanced approximately 5-fold by fibrinogen and 17-fold by polymerized fibrin. Kapp was (1.57 +/- 0.46) x 10(3)/M/s for two-chain tPA and Lys78-plg, and was enhanced approximately 2.6-fold by fibrinogen and 3.6-fold by fibrin. The factor of the enhancement by polymerized fibrin was far less than in previous reports in which chromogenic substrate was commonly employed.

Golden proportion for maxillofacial surgery in Orientals.

The facial position and balance of eyes, nose, and mouth in typical Japanese individuals were investigated, based on the golden proportion for each of these relationships. We found that Japanese tend to have a longer upper lip and shorter chin length compared with Caucasians. We believe that this tendency represents a general facial characteristic of the Oriental population. Each ratio obtained from determinations by our method was used for preoperative and postoperative aesthetic analysis in maxillofacial surgery. This method is considered useful because it permitted us to understand quantitatively the positional relationship and the balance of eyes, nose, and mouth in the face and to make comparisons with typical subjects.

Inhibition of eukaryotic dna polymerase alpha by persimmon (Diospyros kaki) extract and related polyphenols.

The effects of persimmon extract (Diospyros kaki) and related polyphenols on eukaryotic DNA polymerase alpha were examined. It was found that persimmon extract, epigallocatechin gallate, and epicatechin gallate strongly inhibited the activity of DNA polymerase alpha purified from calf thymus. Among these polyphenols, persimmon extract had the most potent effect on DNA polymerase alpha activity and the concentration of persimmon extract producing 50% inhibition of the activity was 0.191 microM. Persimmon extract showed a weaker effect on DNA polymerase beta and slightly inhibited primase and DNA polymerase I. The inhibition of DNA polymerase alpha by persimmon extract was competitive with the template-primer and noncompetitive with dTTP substrate. The Ki value of DNA polymerase alpha for persimmon extract was estimated to be 70 nM. Moreover, persimmon extract inhibited [3H]thymidine incorporation of human peripheral lymphocyte cells stimulated by PHA.