Study of pyogenic granuloma of the oral cavity]

Pyogenic granuloma is one of the diseases sometimes seen in otorhinolaryngology clinics. The clinical features of this disease are understood to be that the lesion is located in the oral cavity in the majority of cases that its causative agent is usually discovered and that it most likely grows as a malignant tumor. However, the entity of pathological diagnosis has not been established. Thirty-one cases of oral pyogenic granuloma, including 16 males and 15 females, are reported in this paper. The granuloma was located most frequently at the tongue, followed, in order, by the gingiva, buccal mucosa, hard palate, lip and oral floor. The period between the patient's first visit to our clinic and the onset of his/her complaint was variable. It was relatively shorter in those cases with the lesion at the gingiva or tongue as compared to other locations. The size of the lesion was smaller than 10 x 10 mm. We classified the pathological features into three patterns; granuloma type, hemangioma type, and intermediate type. Many cases of lesions located at the back of the tongue, buccal mucosa, or hard palate were of the hemangioma type, while many cases of lesions located at the top of the tongue, gingiva, or oral floor were of the granuloma type. We have the impression that pyogenic granuloma could be one of the purulent changes associated with benign oral tumors.     

Kaposi's sarcoma-associated herpesvirus (KSHV) sequences in premalignant and malignant skin tumors

Summary The novel herpesvirus-like DNA sequences, which were identified in AIDS-related Kaposi's sarcoma (KS) and designated KS associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8), have been reported to be associated with various forms of KS. Here, we searched for the presence of KSHV sequences in various other skin lesions including premalignant or malignant skin tumors of a total of 69 clinical cases without immunodeficiency due to AIDS or following organ transplantation. Strikingly high rates of detection were obtained for premalignant Bowen's disease and malignant squamous cell carcinoma, accounting for 71.4% and 50%, respectively. A less frequent but as yet high incidence (33.3%) was scored for actinic keratosis, a premalignant epidermal disorder. In contrast, the frequency remained low (16.7%) for another type of proliferative skin lesions of extramammary Paget's disease and non-proliferative skin lesions (dermatitis, morphea, epidermal cyst and scar). These results suggest a close association of KSHV with at least some non-KS malignant and premalignant skin lesions in non-immunocompromised patients.     

Mechanism of the inhibitory effect of OPB-9195 [(+/-)-2-isopropylidenehydrazono-4-oxo-thiazolidin-5-yla cetanilide] on advanced glycation end product and advanced lipoxidation end product formation

The accumulation in uremic plasma of reactive carbonyl compounds (RCO) derived from both carbohydrates and lipids ("carbonyl stress") contributes to uremic toxicity by accelerating the advanced glycation and lipoxidation of proteins. It was previously demonstrated that OPB-9195 [(+/-)-2-isopropylidenehydrazono-4-oxo- thiazolidin-5-ylacetanilide] inhibited the in vitro formation of advanced glycation end products (AGE) in uremic plasma. This study was designed to elucidate the mechanism of action of OPB-9195 by further delineating the AGE and advanced lipoxidation end product (ALE) precursors targeted by this drug. The inhibitory effects of OPB-9195 on the formation of two AGE (N:epsilon-carboxymethyllysine and pentosidine) on bovine serum albumin incubated with various AGE precursors were examined. Inhibition of N:epsilon-carboxymethyllysine and pentosidine formation with OPB-9195 was more efficient than with aminoguanidine. OPB-9195 also proved effective in blocking the carbonyl amine chemical processes involved in the formation of two ALE (malondialdehyde-lysine and 4-hydroxynonenal-protein adduct). The efficiency of OPB-9195 was similar to that of aminoguanidine. When glucose-based peritoneal dialysis fluid was incubated in the presence of OPB-9195, a similar inhibition of AGE formation was observed. The direct effect of OPB-9195 on major glucose-derived RCO in peritoneal dialysis fluids was then evaluated. The effects of OPB-9195 could be accounted for by its ability to trap RCO. The concentrations of three major glucose-derived RCO (glyoxal, methylglyoxal, and 3-deoxy-glucosone) were significantly lower in the presence of OPB-9195 than in its absence. Aminoguanidine had a similar effect. In conclusion, OPB-9195 inhibits both AGE and ALE formation, probably through its ability to trap RCO. OPB-9195 might prove to be a useful tool to inhibit some of the effects of RCO-related uremic toxicity.     

Renoprotective properties of angiotensin receptor blockers beyond blood pressure lowering

Clinical studies have demonstrated that some antihypertensive agents provide renoprotection independent of BP lowering. Recent in vitro and in vivo studies evaluated the mechanisms involved in this protection. First, the in vitro effects of several angiotensin II type 1 receptor blockers (ARB), calcium channel blockers (CCB), and beta blockers (BB) on various mediators were compared: Formation of pentosidine (an advanced glycation end product), hydroxyl radical-induced formation of o-tyrosine, and transition metals-induced oxidation of ascorbic acid (the Fenton reaction). All of the six tested ARB but neither the six CCB nor the nine BB inhibited pentosidine formation. ARB, as well as BB but not CCB, inhibited hydroxyl radicals-mediated o-tyrosine formation. ARB but neither BB nor CCB inhibited efficiently transition metals-catalyzed oxidation of ascorbic acid. Second, the in vivo consequences for the kidney of these various in vitro effects were evaluated. Hypertensive, type 2 diabetic rats with nephropathy, SHR/NDmcr-cp, were given for 20 wk either olmesartan (ARB) or nifedipine (CCB), or atenolol (BB). Despite similar BP reduction, only ARB significantly reduced proteinuria and prevented glomerular and tubulointerstitial damage (mesangial activation, podocyte injury, tubulointerstitial injury, and inflammatory cell infiltration). It is interesting that only ARB prevented abnormal iron deposition in the interstitium, corrected chronic hypoxia, reduced expressions of heme oxygenase and p47phox (a subunit of NADPHoxidase), and inhibited pentosidine formation (which correlates well with proteinuria). These observations confirm unique renoprotective properties of ARB, independent of BP lowering but related to decreased oxidative stress (hydroxyl radicals scavenging and inhibition of the Fenton reaction), correction of chronic hypoxia, and inhibition of advanced glycation end product formation and of abnormal iron deposition. These benefits of ARB may contribute to the renoprotection observed beyond BP lowering.     

Clinical impact of using chemoradiotherapy as a primary treatment for hypopharyngeal cancer

Eighty-eight patients with hypopharyngeal cancer who received chemoradiotherapy as the primary treatment between 1979 and 1997 were investigated. Forty-six patients who received surgery as the primary treatment were analyzed as a control group. There were no statistically significant differences regarding TN classification, tumor stage, tumor site, age or sex between the radiation and surgery groups. The 5-year cumulative survival rate of primary chemoradiotherapy was 47% and this did not differ significantly from that for the primary surgery group. The larynx was preserved in 74% of cases in the primary chemoradiotherapy group, a far better preservation rate than that in the surgery group. After primary chemoradiotherapy, complete remission (CR) was observed in 59% of cases and the average period of CR was 38 months. Among patients with residual tumor, a salvage operation was employed in 31 cases, 13 patients refused to receive surgery and 8 were inoperable. A salvage operation was performed in 35% of all cases and the 5-year cumulative survival rate was 50%. Based on the 5-year survival, primary CR, salvage and laryngeal preservation rates, we conclude that chemoradiotherapy is a good primary treatment for hypopharyngeal cancer.     

Treatment of maxillary sinus carcinoma: clinical results using the Kitasato modality

The conventional therapeutic regimen for maxillary sinus carcinoma consists of dissection of the maxilla, full-dose irradiation and extensive chemotherapy. However, the results obtained with this treatment are often poor. Even when patients recover, their quality of life is significantly reduced as a result of deformity of facial structures and swallowing and articulation dysfunctions. A retrospective analysis of 68 patients with maxillary sinus carcinoma treated with the Kitasato modality between 1975 and 1999 was conducted. All patients underwent pergingival maxillary sinus surgery combined with pre- and postoperative irradiation therapy with standardized total doses of 16 Gy; the postoperative irradiation was given in combination with regional intra-arterial infusion chemotherapy administered via the superficial temporal artery. All visible tumor lesions were removed where possible in order to preserve or facilitate cellular immunity after surgery. The cumulative 5-year survival rates were 85.7% for Stage II patients, 88.1% for Stage III, 76.6% for Stage IVA and 75.% for Stage IVB.     

Carcinoma of the nasopharynx: analysis of treatment results in 91 patients

The outcome of 91 patients (69 males, 22 females; age range 16-82 years) with nasopharyngeal carcinoma treated in our hospital between 1971 and 1999 was evaluated. Factors that appeared to influence prognosis were assessed using the Kaplan-Meier method. The cause-specific cumulative 5-year survival rate for the entire study population was 61.2%. The 1997 International Union Against Cancer classification was used for disease staging. The 5-year survival rates were as follows: 66.7% (n = 3) for Stage I; 100% (n = 2) for Stage IIA; 90.9% (n = 11) for Stage IIB; 78.8% (n = 25) for Stage III; 53.0% (n = 29) for Stage IVA; 37.5% (n = 16) for Stage IVB; and 20.0% (n = 5) for Stage IVC. The disease-free cumulative 3-year survival rates of the patients classified based on initial therapy were as follows: radiation alone, 50.0% (n = 28); combined radiotherapy and chemotherapy that included an undefined anti-cancer drug, 67.2% (n = 39); combined radiotherapy and chemotherapy that included carboplatin (CBDCA), 92.3% (n = 19). These results showed a statistically significant difference (p = 0.043; log-rank test). Stage IVC patients were excluded from the analysis. We conclude that combined therapy, including chemotherapy with CBDCA, is necessary for the treatment of nasopharyngeal carcinoma. In terms of radiation therapy, a field covering the bilateral cervical regions seemed to produce favorable results, even if cervical node metastasis was not confirmed by palpation at the first hospital visit. Key words: carboplatin, chemotherapy,     

Evaluation of skin barrier function using direct current III: effects of electrode distance,boundary length and shape

The objective of this study was to propose a suitable electrode disposition and shape for iontophoretic drug delivery systems in consideration of a reduction in skin barrier function and a distribution of current density. The reduction in barrier function was evaluated with our proposed method, which measured the resistance in the short term. The distribution was estimated using an electromagnetic waves analysis program. Using rectangular electrodes, effects of distance between electrodes and boundary length of the electrode on the barrier function were examined. A distance of 2 mm decreased the barrier function effectively. The barrier function was reduced with increasing electrode boundary length. Furthermore, a surrounded square type electrode was more effective in the reduction of barrier function than a paired square type. With respect to the surrounded type electrodes, both square and circle types decreased the barrier function. However, percutaneous absorption using the circle type electrode was greater than with the square type. These phenomena are attributed to not only the electrode boundary length but also the homogeneous distribution of current density. Therefore, the surrounded circle type electrode was suitable for iontophoretic transdermal drug delivery systems.