Effect of chlorhexidine mouth rinse on Streptococci counts of tooth-tissue-borne palatal expander biofilm.

OBJECTIVES: To assess total Streptococci (TS) counts and biofilm mass over tooth-tissue-borne palatal expander (TTBPE), as well as the effect of chlorhexidine (CHX) mouth rinse on these variables. DESIGN: A cross-sectional study design employed clinical procedures and laboratorial techniques. SETTING AND SAMPLE POPULATION: Patients who had TTBPE removal indicated were divided into two groups: a CHX group (n = 26) in which three times a day of 0.2% CHX digluconate mouth rinses were prescribed 7 days before TTBPE removal; and a control (CON) group (n = 25) in which no antimicrobial treatment was applied. EXPERIMENTAL VARIABLE: 'Gender', 'Age', and 'TTBPE wear time' were recorded. After TTBPE removal, biofilm mass was determined by the difference between (TTBPE + biofilm) and (TTBPE only) masses. TS counts were determined by biofilm suspension followed by progressive dilutions and culture on Mitis Salivarius agar with incubation at 37 degrees C for 72 h. OUTCOME MEASURE: Biofilm mass (mg) and Colony Forming Units of TS / mg of biofilm (CFU-TS / mg) were calculated. Results - Total Streptococci mean values in CHX (6.77 x 10(6)CFU-TS / mg) were statistically lower (p < 0.01) than those in CON (3.82 x 10(7)CFU-TS / mg), but there was no statistical difference (p > 0.05) between CHX (168.88 mg) and CON (182.04 mg) masses nor statistical correlation (p > 0.05) between biofilm mass and CFU-TS / mg in the two groups. CONCLUSION: Chlorhexidine reduces the TS counts in TTBPE, but has no effect on biofilm mass.

Hepatitis C virus (HCV) genotype 1b sequences from fifteen patients with hepatocellular carcinoma: the 'progression score' revisited.

The genome of hepatitis C virus (HCV) associated with hepatocellular carcinoma (HCC) may have some characteristics which would barely be found in those of HCV from asymptomatic carriers (ASC). We analyzed 15 HCC patients who were infected with HCV genotype 1b (HCV-1b) for complete nucleotide sequences of the viral genomes. Of the 15 isolates, three were sequenced up to the first nucleotide of the 5'UTR, and six were sequenced to encompass the X-tail at the 3' end: sequencing of at least three-quarters of the 5'UTR and entire polyprotein-ORF was accomplished in all 15 isolates. Analyses of these sequences together with those reported previously by Nagayama et al. [Hepatology; 31 (2000) 745] suggested that nine residues (nt 119 of 5'UTR and aa 90, 434, 938, 962, 1176, 1412, 2143, and 2774 of polyprotein) might be useful to discriminate HCC-type sequences from ASC-type ones. The 'progression score' was 1.4+/-0.9 in ASC versus 3.7+/-1.5 in HCC (P=3.87E-07) when calculated with the Nagayama et al.'s seven residues, but was 1.4+/-0.6 versus 4.6+/-1.9 (P=1.33E-09) with our nine residues: a greater difference between HCC and ASC was achieved in the latter system. Further analyses, by increasing the sample size and/or by extending the comparison to include entire 5'UTR and 3'UTR/X-tail, may thus contribute to define the 'progression score' more appropriately.

Role of prostaglandin E2 and leukotriene B4 in skin reaction induced by transdermal application of propranolol.

Dermal application of propranolol (PRL) induced formation of erythema and edema, and pseudoeosinophil infiltration in epidermis and dermis at the application site in guinea pigs. We investigated the production of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) at the application site of PRL and the role of these inflammatory chemical mediators in the occurrence of the skin reactions. PGE2 was found to be produced at the application site slightly after the accumulation of PRL released from the adhesive bandage in the patch test, and the amount of PGE2 increased continuously, with a peak value obtained at 24 h after application. The time-course changes resembled those of delta a* value, the index of erythema formation determined by colorimetric measurement, and edema formation. The production of PGE2 by dermal application of PRL was suppressed by local pretreatment with dexamethasone or indomethacin. However, no notable production of LTB4 was observed at the application site of PRL.

[The relapse rate in patients with bronchial asthma remission and the risk factors of relapse].

To investigate the relapse rate in patients with bronchial asthma remission, a questionnaire study was performed. The answer sheets from 450 of 865 patients who first visited Saitama Medical School Hospital before the age of 16 were obtained. 281 patients had been in asthma remission more than one year after the last their attack. Among them, 31 patients (14 males and 17 females) relapsed. Their average age of last attack was 15.1 +/- 3.6 years old. While the average age of the last attack in patients who did not relapse was 12.9 +/- 4.1. The average age of relapse was 20.8 +/- 4.2 and their duration of remission was 5.8 +/- 2.9 years. No relapse was observed after 14 years of remission. The most of the patients relapsed within 10 years. The relapse rate calculated by life table method was 13.5%. Relapse retes were calculated in various characteristics: females; 24.9%, patients who had severe symptoms at the first visit and moderately severe; 22.4%, 23.1%, respectively, positive history of steroid therapy; 25.1%, IgE level of more than 500 IU/ml; 19.7%, patients whose last attack was after the age of 13; 21.2%. Those figures are significantly higher than the opposite characteristics. The environmental factors significantly contribute to the relapse of remitted asthmatics. They are apartment house, ferroconcrete and aluminum-framed house, carpet in bedroom, pets, maternal or self-smoking. The asthmatic children who have those risk factors should be followed to prevent relapse and their environment controls should be adequately stressed even in asthma remission.

Skin toxicity of propranolol in guinea pigs.

The skin toxicities of propranolol were studied in guinea pigs. In the primary and cumulative skin irritation studies, the skin reactions and the histopathological changes were observed in all animals treated with propranolol, and those tended to increase with the increase of propranolol dosage. The skin reactions increased with the application times of propranolol up to 7 days in the cumulative skin irritation study. In the skin sensitization, the phototoxicity and the skin photosensitization studies, no skin reactions were observed in any animals used in the studies. These results indicate that propranolol caused skin irritation, but was negative for skin sensitization, phototoxicity and skin photosensitization in guinea pigs.

Relationship between the skin permeation movement of propranolol and skin inflammatory reactions.

We studied inflammatory reactions induced by dermal application of the beta-blocker propranolol (PRL) in ethanol to guinea pigs in order to elucidate the relation of the reactions with the cumulative PRL permeating amount through the stratum corneum or the PRL content in the stripped skin, and to investigate the chemical mediators responsible for the reactions. The cumulative PRL permeating amount through the stratum corneum increased rapidly up to 2 h after dermal application, then increased linearly with time up to 24 h after application. Visual observation revealed formation of erythema and edema at the applied site of PRL, and histopathological examination revealed infiltration of pseudoeosinophiles of dermis and epidermis and degeneration/necrosis of epidermis. In general, it was considered that the duration and the extent of these reactions were dependent on the PRL dosage and application time. It was expected that the cumulative PRL permeating amount through the stratum corneum could be used to predict possible inflammatory reactions during development of transdermal drug delivery systems. On the other hand, contact of PRL with guinea pig skin tissues released histamine, and intradermal injection of PRL caused an increase of capillary permeability at the site of application. Also, the inhibitory effects of anti-inflammatory agents (diphenhydramine, dexamethasone, indomethacin, cyproheptadine hydrochloride, CV3988 and AA-861) to PRL-induced erythema formation demonstrated that histamine and prostaglandins were responsible for the inflammatory reactions induced by PRL.

[Appearance of extrahepatic lesions in the superior lip and orbit of a patient with liver metastases of gastric cancer following partial response by hepatic arterial infusion chemotherapy].

A 76-year-old man was totally gastrectomized in June, 1996 for advanced gastric cancer. In February, 1997, multiple liver metastases were found by abdominal CT scan, and hepatic arterial infusion chemotherapy was started with 5-FU, EPI and MMC by an implantable reservoir indwelled via the left subclavian artery. This treatment was judged to have led to a partial response because reduced focus size of the liver metastasis was revealed by CT scan and levels of tumor markers decreased significantly. However, metastatic foci were found in the skin of the superior lip and the orbit in December 1997. He was treated with a variety of therapies, but died in January, 1998. Many cases with metastatic hepatic cancer have a poor prognosis because of the appearance of extrahepatic lesions in spite of the fact that a partial response can be obtained by hepatic arterial infusion chemotherapy. The present case was unique since extrahepatic lesions appeared at very rare sites such as the superior lip and the orbit.

Relationship between amount of beta-blockers permeating through the stratum corneum and skin irritation after application of beta-blocker adhesive patches to guinea pig skin.

We evaluated the relationship between the cumulative amounts of 5 kinds of beta-blockers (alprenolol, oxprenolol, timolol, acebutolol and atenolol) permeating through the stratum corneum and a* values obtained by measuring the formation of erythema, a skin irritation reaction, with a chromameter after transdermal application of adhesive patches containing 2 beta-blocker to the skin of guinea pigs. The cumulative amount of beta-blocker released from each adhesive patch to the skin increased with the increase in application time. The contents of alprenolol, oxprenolol and timolol in the stratum corneum and in the stripped skin increased markedly up to 4 h after application and thereafter were maintained at high levels up to 24 h. The contents of acebutolol and atenolol, on the other hand, increased up to 24 h, but these values were low. a* values of all adhesive patches 24 h after application were higher than those before application. The correlation coefficients between the cumulative amounts of alprenolol, oxprenolol, timolol, acebutolol or atenolol permeating through the stratum corneum and (delta a* -delta a*Placebo) values were 0.739, 0.717, 0.722, 0.551 and 0.633, respectively. The correlation coefficient calculated by averaging the cumulative amounts of 6 kinds of beta-blockers permeating through the stratum corneum [including propranolol which was reported previously (Kobayashi I., et al., Biol. Pharm. Bull., 19, 839-844 (1996))] was 0.731, higher than the correlation coefficient between contents of these beta-blockers in the stripped skin and (delta a* -delta a*Placebo) values (r = 0.552). This suggests that there was a high correlation between the cumulative amounts of beta-blockers permeating through the stratum corneum and (delta a* -delta a*Placebo) values.

[An unusual case of pyogenic hepatic abscess rupturing into the pericardial cavity].

A rare case of pyogenic hepatic abscess that ruptured into the pericardial cavity is reported. A 50-year-old female who had been admitted for cholangitis associated with bi-lateral stricture of bile duct and intrahepatic stones, presented a pyogenic hepatic abscess in the left lobe on an abdominal computed tomography (CT). Percutaneous transhepatic abscess drainage (PTAD) was performed. But during PTAD-graphy five days later, cardiac tamponade developed secondarily to rapid accumulation of contrast medium in the pericardial cavity flowing from liver abscess. An emergency subxiphoid pericardectomy was performed and she made a good recovery. Unfortunately seven months later, she died of septicemia caused by a newly developed abscess in the right lobe of the liver.

[Clinical evaluation of urinary leukotriene E4 levels in asymptomatic bronchial asthma].

To evaluate the significance of peptide leukotrienes (LTC4, D4, E4) in asymptomatic asthmatic patients, we measured urinary LTE4 levels which is thought to reflect in vivo production of peptide LTs. Urinary LTE4, was extracted using C18 solid phase column and measured by radioimmunoassay. There was no significant difference in urinary LTE4 levels among asthmatics with different severity or between atopic and non-atopic asthmatics. Urinary LTE4 levels were significantly elevated in asthmatics compared with normal controls (p < 0.05). When compared with normal controls, urinary LTE4 levels were significantly elevated in moderate to severe asthma (p < 0.05), and non-atopic asthmatics (p < 0.001). Urinary LTE4 levels were significantly elevated in aspirin-sensitive asthmatics compared with aspirin-tolerant asthmatics (p < 0.05). There was no significant difference in urinary LTE4 levels among aspirin-sensitive asthmatics with different severity. These results suggest that increased production of peptide LTs is a characteristic in aspirin-sensitive asthma, and that the severity and type of asthma and the presence of aspirin-sensitive asthma should be taken into consideration in the analysis of urinary LTE4 levels.

Relationship between the amount of propranolol permeating through the stratum corneum of guinea pig skin after application of propranolol adhesive patches and skin irritation.

In the present study we evaluated the relationship between the cumulative amount of propranolol permeating through the stratum corneum and the formation of erythema, a skin irritation reaction, after transdermal application of adhesive patches containing propranolol to the skin of guinea pigs. The intensity of erythema was expressed in terms of a* values measured with a chromameter. The a* values increased in guinea pigs after application of the adhesive patches containing 0.4 mg/cm2 of propranolol to the skin. Since the adhesive patches showed good adhesion to the skin (propranolol content is less than the saturated concentration in the adhesive base) and the cumulative amount of propranolol permeating through the stratum corneum is small, the development of erythema was considered to be mainly due to physical factors such as peeling. Even in adhesive patches containing 0.8 mg/cm2 or 1.2 mg/cm2 of propranolol, a* values increased, although adhesion to the skin is low because of crystallization of propranolol in the adhesive base. On the other hand, in these two adhesive patches, the cumulative amount of propranolol permeating through the stratum corneum increased up to 24 h after application. These findings suggest that the skin irritation reaction is due to propranolol mainly absorbed transdermally, because there is a high correlation between the cumulative amount of propranolol permeating through the stratum corneum and the a* values (r = 0.928).

[Outcomes of effective treatment of cases of metastatic liver tumors by intra-arterial infusion chemotherapy].

We studied the prognoses of unresectable liver tumors, including 31 colorectal cancers and 10 gastric cancers treated by intra-arterial infusion chemotherapy using an implantable reservoir. Adriamycin, epirubicin, or cisplatin were administered intermittently early on. Cisplatin and 5-FU combined therapy were given later. In nine with colorectal metastases and six with gastric metastases, metastatic lesions decreased, and in 4 patients with metastatic lesions could be resected. But in many patients, hepatic and other organ recurrences were observed. We need to try many other treatments.

[Evaluation of cases of metastatic liver tumors resected following intra-arterial infusion chemotherapy].

We encountered four cases whose unresectable metastatic liver tumors could be resected by operation after intra-arterial infusion chemotherapy using an implantable reservoir. Metastatic lesions were thus markedly reduced and localized. Three cases were metastases of colorectal cancer and one of gastric cancer. All cases of liver metastases were synchronous and more than H2 stage. In these cases, metastatic lesions were reduced at an early stage of this chemotherapy after resection of the primary lesions. Resection of metastases was carried out from 4 to 14 months after the first operation. Effects of this chemotherapy were also observed histologically; necrosis and fibrosis were found in the cancer nest, which paralleled the reduction in tumor size. Our results indicate that this chemotherapy could be a neoadjuvant chemotherapy for unresectable metastatic liver tumors which may become resectable after this chemotherapy as seen in our cases. However, lung metastases and peritoneal dissemination influenced the prognosis of our cases. Treatment of extra-hepatic recurrence seemed important to improve the prognosis of these patients.

[Reservoir system implantation technique via the inferior epigastric artery for local recurrence of rectal cancer].

A reservoir system was implanted via the inferior epigastric artery into the internal iliac artery for local recurrence of rectal cancer under lumbar anesthesia. At the same time, the internal iliac artery on the opposite side of the tumor and the superior and inferior gluteal artery on the tumor side were embolized by gelform and coil. Five-hour continuous intraarterial infusion of 1,000 mg/m2 of 5-FU with intravenous drip infusion of 20 mg/m2 of leucovorin and one shot intraarterial infusion of 50 mg/m2 of cisplatin were performed as the treatment. This technique allows easier insertion of the catheter than by the conventional method, elevates the anticancer drug levels in the pelvic cavity and prevents ulcer of the buttocks and perineum. The technique is considered an effective form of treatment for local recurrence of rectal cancer.

[Study of intra-arterial infusion chemotherapy for hepatocellular carcinoma using an implantable reservoir].

Twenty-two patients with unresectable hepatocellular carcinoma were treated by intra-arterial infusion chemotherapy using an implantable reservoir. The catheter was placed in the hepatic artery via the left subclavian artery. Adriamycin or epirubicin were administered intermittently. From the result, the response rate in all cases was 22.7%, and no difference in the response rate by Stage was observed. However, the less the hepatic disturbance, the greater the effect was: 75% in clinical stage I, 18.2% in II and 0% in III. Significant differences of ICG R15, doses and frequency of intra-arterial infusion were observed between PR, NC and PD cases. The usefulness of this chemotherapy was suggested in highly advanced hepatocellular carcinoma, especially in Vp3.

[The analysis of factors contributing to the safety and efficacy of rush immunotherapy in bronchial asthma].

In order to establish guidelines for the optimal use of rush immunotherapy (RI) in mite-sensitive adult bronchial asthmatics, we clinically analyzed 38 cases treated with RI. In all cases, it was possible to reach a maintenance dose greater than 0.10 ml of 1/10 solution of house dust (HD) within 10 days. Most of the systemic reactions occurred after doses greater than 0.15 ml of 1/10 solution. The patients who showed the maximum size of skin reaction > or = 8 cm were susceptible to systemic reactions. Prior to the occurrence of asthma, most cases complained of some prodrome of airway irritation. The clinical efficacy of RI was significantly lower in patients whose FEV1% was < 70%, and no difference was observed between patients whose maintenance dose was 0.10 ml and those whose maintenance dose was greater than 0.20 ml. These results suggest: 1) RI should be performed on patients whose FEV1% is > or = 70%, 2) 0.10 ml of 1/10 solution is an optimal dose, 3) when a local skin reaction is > or = 8 cm in diameter and/or a prodrome of airway irritation occurs, one should be careful when increasing the dosage.

[Postoperative hypophosphatemia in patients with cancer of the thoracic esophagus].

Postoperative phosphate dynamics were studied in 30 patients who underwent radical surgery for thoracic esophageal cancer and who were postoperatively nourished by total parenteral nutrition. There was a significant fall in the serum phosphate level on the 2nd and 3rd postoperative days in all patients. Postoperative hypophosphatemia was due to an increase in urinary phosphate excretion which was indicated by the fall in TRP% and TmPO4/GFR. A highly significant positive correlation was observed between the increase in urinary phosphate loss and the enhanced secretion of parathyroid hormone which was possibly triggered by surgical stress, a decrease in the serum level of calcium, the action of phosphate buffer or diuretics. All the patients except for those with postoperative pulmonary complications responded to the drop in serum phosphate by renal conservation of phosphate. A slight decrease in the serum level of phosphate was also found on the 6th postoperative day in most patients who were receiving parenteral hyperalimentation. The second fall in phosphate was due to transcellular shifts of phosphate. It is concluded that patients with postoperative pulmonary complications develop severe hypophosphatemia which should be prevented by replacement therapy with phosphate in the immediate postoperative period.

[A case of liver metastasis from retroperitoneal leiomyosarcoma successfully treated by intra-arterial infusion chemotherapy of adriamycin or epirubicin using an implantable reservoir].

A 59-year-old woman was diagnosed as having liver metastasis (H3) 38 months after undergoing resection for retroperitoneal leiomyosarcoma. A catheter was placed in the hepatic artery and intra-arterial infusion chemotherapy using an implantable reservoir was performed with 30 mg of adriamycin or epirubicin at each treatment every 2-4 weeks. Imaging revealed that the tumor had been markedly reduced, and a partial response was obtained for 18 months. The patient has survived for 33 months since liver metastasis was detected. Although effective chemotherapy for metastatic leiomyosarcoma in the liver has been poorly documented, intra-arterial infusion chemotherapy proved highly effective in this case, suggesting that it effectively improved the prognosis.