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.

Quantification of hepatitis C virus in patients treated with peginterferon-alfa 2a plus ribavirin treatment by COBAS TaqMan HCV test.

Extremely low levels of serum hepatitis C virus (HCV) RNA can be detected by COBAS TaqMan HCV test. To investigate whether the COBAS TaqMan HCV test is useful for measuring rapid virological response (RVR) and early virological response (EVR) to predict sustained virological response (SVR), we compared the virological response to PEG-IFN-alfa 2a plus RBV in 76 patients infected with HCV genotype 1 when undetectable HCV RNA by the COBAS TaqMan HCV test was used, with those when below 1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test was used, which corresponded to the use of traditional methods. Among the 76 patients, 28 (36.8%) had SVR, 13 (17.1%) relapsed, 19 (25.0%) did not respond, and 16 (21.0%) discontinued the treatment due to side effects. The positive predictive values for SVR based on undetectable HCV RNA by COBAS TaqMan HCV test at 24 weeks after the end of treatment [10/10 (100%) at week 4, 21/23 (91.3%) at week 8 and 26/33 (78.7%) at week 12] were superior to those based on <1.7 log IU/mL HCV RNA [17/19 (89.4%) at week 4, 27/38 (71.0%) at week 8, and 27/43 (62.7%) at week 12]. The negative predictive values for SVR based on <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test [46/57 (80.7%) at week 4, 37/38 (97.3%) at week 8, and 32/33 (96.9%) at week 12] were superior to those based on undetectable HCV RNA [48/66 (72.7%) at week 4, 46/53 (86.7%) at week 8, and 41/43 (95.3%) at week 12]. The utilization of both undetectable RNA and <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test is useful and could predict SVR and non-SVR patients with greater accuracy.

Comparative analysis of putative periodontopathic bacteria by multiplex polymerase chain reaction.

BACKGROUND AND OBJECTIVE: The polymerase chain reaction (PCR) has been applied for the rapid and specific detection of periodontopathic bacteria in subgingival plaque and is potentially of clinical benefit in the diagnosis and treatment of periodontitis subjects. However, several technical points need to be modified before the conventional PCR detection system can be used by clinicians. MATERIAL AND METHODS: To develop a PCR-based technique more applicable for clinical use than conventional PCR, we established a multiplex PCR for five putative periodontopathic (Treponema denticola, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Tannerella forsythia) and two nonperiodontopathic (Streptococcus sanguinis and Streptococcus salivarius) species of bacteria using whole-plaque suspension as templates, and detected bacteria in subgingival plaque taken from 85 subjects at the supportive periodontal therapy stage after active periodontal treatments. RESULTS: Among putative periodontopathic bacteria, the detection frequency of T. denticola and P. gingivalis was elevated in parallel with higher probing pocket depth and clinical attachment loss, and had 4.2-14.1 times increasing odds of the clinical parameters tested. Detection of any of the five species of putative periodontopathic bacteria markedly increased the odds ratio of a higher probing pocket depth, clinical attachment loss and bleeding on probing. CONCLUSION: The multiplex PCR system developed in this study enabled the detection of all the bacteria under investigation in one reaction tube in a less time- and labor-intensive manner than conventional PCR. These results support the potential clinical use of multiplex PCR for detecting periodontopathic bacteria and for evaluating therapeutic strategies and predicting the prognosis for each subject.

Amino acid residues complexed with eosin 5-isothiocyanate in band 3 protein of the human erythrocyte.

The amino-acid residues of band 3 protein taking part in the ionic interaction with an anion-transport inhibitor, eosin 5-isothiocyanate (EITC), were determined by pH titration. The plots of the absorbance of EITC-ghost system against pH reveal five equilibria, at pH 3.7, 6.4, 8.0, 11.0 and 13.1. Since the three equilibria, 3.7, 8.0 and 11.0, are representative of the EITC molecule, the others, 6.4 and 13.1, may be due to the interaction of EITC molecules with histidine and arginine residues, respectively. The same experiment using a reconstituted system of band 3-lipid vesicles gave results in good agreement with the EITC-ghost system. The intensity of the induced CD band at 530 nm of EITC molecules bound to ghosts was decreased by preincubation with arginine-specific reagents, phenylglyoxal and 1,2-cyclohexanedione, or histidine-specific reagents, diethylpyrocarbonate (DEPC) and p-diazobenzene sulfonate. The repression effects by these chemical modifiers were evaluated by measuring the concentrations which elicit 50% reduction. The histidine-specific reagents repressed the CD of EITC more effectively than the arginine-specific reagents. Furthermore, it was found that DEPC effectively inhibited the sulfate efflux from intact erythrocytes. These results suggest that the histidine residues participate in the anion-transport system of human red cells.

A new technique of thoracoscopic pleurodesis for refractory hepatic hydrothorax.

BACKGROUND: Hepatic hydrothorax is defined as a pleural effusion that arises in patients with cirrhosis of the liver and no cardiopulmonary disease; it is believed to result from peritoneopleural communication through a defect in the diaphragm. METHODS: Nine patients underwent thoracoscopic pleurodesis. The diaphragmatic defect was detected and corrected in two cases. In all patients, an argon beam coagulator was applied to the diaphragm surface, which was then completely covered with bioabsorbable prostheses. We then spread 3 ml of fibrin glue on the covered diaphragm and sprinkled 5 KE of OK-432 and 100 mg of minocycline hydrochloride in the thoracic cavity. RESULTS: All patients showed clinical improvement. The pleural effusion and breathlessness resolved immediately after pleurodesis. There were two recurrences after 1 and 4 months, respectively. One of these patients improved after repeat pleurodesis; the other was treated conservatively. CONCLUSION: Our new technique of thoracoscopic pleurodesis is an effective and minimally invasive treatment for patients with refractory hepatic hydrothorax.

Adjunct antibiotic combination therapy for steroid-refractory or -dependent ulcerative colitis: an open-label multicentre study.

BACKGROUND: We previously demonstrated that antibiotic combination therapy is effective for induction and maintenance of ulcerative colitis (UC) remission. AIM: To assess whether antibiotic combination therapy is effective for active UC refractory to or dependent on steroids in a multicentre, open-label trial. METHODS: We enrolled 30 patients with steroid-refractory and 64 with steroid-dependent active UC. These patients received three-times-daily by mouth amoxicillin 500 mg, tetracycline 500 mg and metronidazole 250 mg, for two weeks, as well as conventional treatment. Symptom assessment and colonoscopic evaluation were performed before enrolment and at 3 and 12 months after treatment completion. Clinical response was defined as a Lichtiger symptom score decrease in ≥3 points and clinical remission as a score ≤4. RESULTS: Nineteen of the 30 steroid-refractory (63.3%) and 47 of the 64 steroid-dependent (73.4%) patients showed a clinical response within 2 weeks. At 3 and 12 months, 60% and 66.6% of steroid-refractory patients, and 56.3% and 51.6% of steroid-dependent patients, respectively, achieved clinical remission. In the steroid-dependent group, 39 of the 64 patients (60.9%) were able to stop steroid therapy and remained in remission for 3 months. Three (10%) steroid-refractory and four (6.3%) steroid-dependent patients underwent colectomy. CONCLUSIONS: This multicentre, long-term follow-up study suggests 2 week antibiotic combination therapy to be effective and safe in patients with active UC refractory to or dependent on steroids.

Congenital epulis of the newborn: report of a case with a review of the Japanese literature.

Congenital granular cell tumor is a rare tumor which arises from alveolus. We describe a case diagnosed and treated in a neonate. Twenty-eight cases have been reported in Japan, with a male:female ratio of 1:6.3. The location of the tumor was the mandible in 13, the maxilla in 15 and multiple in 1. The left side incisor region was the most common site.

[Drug information in recent 5 volumes of the Year Book of Dentistry].

The Year Book of Dentistry appears annually, providing a review of dental articles. We surveyed the abstracts of the recent 5 volumes of the Year Book of Dentistry, from 1985 to 1989. Two hundred and eighty articles were abstracted in each volume, divided into about 13 categories. The proportion of abstracts concerned with drugs and drug therapies (here termed drug information) was almost 20% in all volumes. Most of the drug information appeared under the heading "Oral Medicine and Oral Pathology" (63%). The original articles for the abstracts were from many journals, but 70% of the drug information articles were from JADA, Oral Surgery, and 10 other journals. The classification of the drugs in the drug information were: drugs for dental treatment, antibacterials, antiinflammatories, hemostatics, anesthetics, and others. Oral manifestations of systemic diseases or side effects of drugs used for these diseases were also abstracted. There were numerous articles of systemic diseases, due to dental treatments, including infective, hematologic diseases.

Homologous desensitization of histamine H2 receptors in the human gastric carcinoma cell line MKN-45.

The poorly differentiated human gastric carcinoma cell line MKN-45 possesses histamine H2 receptors, which are linked to stimulation of adenosine 3',5'-cyclic monophosphate (cAMP) production. Pretreatment of MKN-45 cells with histamine elicited a rapid and dose-dependent inhibition of cAMP production in response to subsequent administration of histamine, whereas pretreatment with prostaglandin E2 (PGE2) or forskolin, both of which stimulate cAMP formation in these cells, had no effect on the histamine-induced cAMP production. Neither NaF- nor forskolin-induced cAMP production was affected by histamine pretreatment. Scatchard analysis of data obtained for [3H]-tiotidine binding showed that histamine pretreatment affected neither the number of histamine H2 receptors nor the binding affinity of the ligand for the receptors. Finally, histamine pretreatment had no effect on cAMP response to subsequent addition of PGE2, which was reduced by PGE2 pretreatment. These results suggest that histamine induces homologous desensitization of H2 receptors on MKN-45 cells by a mechanism that does not involve stimulation of cAMP production.

Improvement of in vivo stability of alginate-polylysine capsules.

Dextran (MW 70,000) and rat islets were encapsulated in alginate-polylysine membrane. The capsules were further coated with tolylene 2,4-diisocyanate. Both of positive and negative charges were detected on the surface of alginate-polylysine capsules, which were absent after coating the capsules with tolylene 2,4-diisocyanate. In the peritoneal cavity, alginate-polylysine capsules were entrapped by the peritoneum, and 89% of dextran was leaked out of the capsules. Alginate-polylysine capsules coated with tolylene 2,4-diisocyanate were present freely in the peritoneal cavity and no leakage of dextran from the capsules were detected. Insulin release from the encapsulated islets was almost the same in both of tolylene 2,4-diisocyanate-coated and uncoated capsules. This study demonstrates that in vivo stability of capsules is dependent on the charge on the surface and can be improved by coating with tolylene 2,4-diisocyanate.

Activation of PKC inhibits NaF-induced inositol phospholipid turnover in rat insulinoma cells.

An investigation was done to elucidate the regulatory role of protein kinase C (PKC) in insulin release and also the effects of PKC activation on NaF-induced inositol phospholipid (PI) turnover in and insulin release from rat insulinoma cells (RINr). NaF stimulated insulin secretion in association with an increase in [3H]inositol phosphate formation in RINr cells. Furthermore, NaF induced a rapid decrease in 32P-labeling of phosphatidylinositol-4,5-diphosphate (PIP2) with a concomitant increase of [32P]phosphatidic acid in prelabeled cells. In contrast, NaF had no effect on cyclic AMP production. Although phorbol 12,13-dibutyrate (PDBu) also stimulated insulin release, on concomitant administration of NaF and PDBu, insulin secretion was clearly less than that expected on the basis of an additive action. Moreover, PDBu significantly inhibited NaF-enhanced PI turnover. However, this inhibition was abolished after downregulating PKC by pretreating RINr cells with PDBu. Thus NaF-induced insulin release from RINr cells appears to involve enhancement of PI turnover. Moreover, because NaF is known to activate guanine nucleotide binding proteins (G proteins) directly, PKC activation appears to induce a mechanism that inhibits stimulus-secretion coupling at a level between G protein and phospholipase C-induced PIP2 hydrolysis.

[Radiation-induced malignant skin tumors in the hands of five doctors].

Radiation-induced malignant skin tumors in the hands in 3 surgeons, one physician, and one dentist are reported. The latent period of the irradiation ranged between 16 years and 34 years. Clinically, small keratotic lesions were seen in 4 doctors and a large tumor the remaining doctor. On histological examination, one of the tumors was a squamous cell carcinoma, 3 were carcinomas in situ, and the fifth was a basal cell carcinoma with a squamous cell carcinoma. While the occupational hazard of developing malignant skin tumors following irradiation have decreased recently, this paper emphasizes precautions should be taken when diagnosing and caring for cancer patients.

Gastroesophageal reflux after endoscopic injection sclerotherapy.

The effect of sclerotherapy of esophageal varices on the gastroesophageal reflux was studied. Gastroesophageal reflux was monitored by a 24-h pH-monitoring catheter introduced into the distal esophagus. The results of pH monitoring of 16 patients who underwent sclerotherapy were compared with those of 21 patients with untreated varices. Seven of the 16 treated patients showed high occurrence rates of gastroesophageal reflux comparable to those observed in cases with severe reflux esophagitis. In the untreated group, only one patient showed pathological reflux (there was a significant difference between treated and untreated groups; p less than 0.01). When the level of reflux was compared with factors that might influence sclerotherapy-induced gastroesophageal reflux, there was a positive correlation between the magnitude of reflux and amount of sclerosant injected paravariceally in the submucosal tissue (p less than 0.05). The results indicate that the paravariceal injection of sclerosant for the treatment of esophageal varix may cause pathological gastroesophageal reflux after sclerotherapy is completed.

Development of an oral drug delivery system targeting immune-regulating cells in experimental inflammatory bowel disease: a new therapeutic strategy.

Several studies have indicated the involvement of macrophages and dendritic cells in active inflammatory bowel disease (IBD). Manipulation of these cells is considered a very important therapeutic strategy for patients with IBD. We evaluated the effect of a new drug delivery system targeting microfold cells and macrophages with poly(DL-lactic acid) microspheres containing dexamethasone (Dx). Colitis was induced in BALB/c mice by 5% dextran sodium sulfate. Dx microspheres (n = 10) and only Dx (n = 10) were orally administered to dextran sodium sulfate-treated mice. Thereafter, serum levels and tissue distributions of Dx were investigated. To estimate the efficacy of this drug delivery system, we measured the histological score, myeloperoxidase activity and nitric oxide production, and gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma in the colonic tissue. Serum Dx levels were not increased after oral administration of Dx microspheres. The tissue distribution of microspheres containing (125)I-labeled Dx in inflamed colon was significantly higher than in other organs. The histological score, myeloperoxidase activity, and nitric oxide production of the group treated with Dx microspheres were significantly lower than of those treated with Dx alone. Gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma were down-regulated in mice treated with Dx microspheres. Microspheres containing glucocorticoids such as Dx, which target microfold cells and macrophages, can facilitate mucosal repair in experimental colitis and could be an ideal agent for treatment of human IBD.