A novel procedure combining transoral resection and set-back tongue flap for oropharyngeal cancer

Seven patients with advanced lateral oropharyngeal cancer (T3N2bM0, or T4N2bM0) underwent transoral lateral oropharyngectomy (TLO) with reconstruction performed through set-back tongue flap and polyglycolic acid (PGA) sheet. TLO was performed following en bloc resection of tumors using endoscopy. To cover the resulting defect in the lateral oropharyngeal wall, the set-back tongue flap was moved posteriorly and laterally to the area of the tongue base and lateral pharyngeal wall. The tip of the set-back tongue flap was sutured to the lateral pharynx to reconstruct the elevated tongue base and altered anterior pillar. The defect on the floor of the mouth was reconstructed using a PGA sheet. Following surgery, the mean observation period was 24 months. The mean operating time was 4 h and 2 min, with an average blood loss of 68.1 ml. All oral intake resumed on the first postoperative day via gastric tube. The mean gastric tube removal time was 1.6 postoperative days as a result of sufficient oral intake. None of the patients received postoperative radiotherapy or displayed evidence of tumor recurrence. We conclude that this novel procedure is highly effective for treating advanced oropharyngeal cancer as it demonstrates good prognostic and functional outcomes.     

Antitumor effect of KT6124, a novel derivative of protein kinase inhibitor K-252a and its mechanism of action

Summary Novel derivatives of K-252a, (8R*,9S*,11S*)-(–)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8, 11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo [a,g]-cycloocta[cde]trinden-1-one, an inhibitor of protein kinases and calmodulin-dependent phosphodiesterase, were synthesized and evaluated for their antitumor activity in vitro and in vivo. Of ten derivatives tested, four were active against the P388 murine leukemia i. p.-i. p. system, although K-252a was inactive. Among these derivatives, KT6124 was selected for further biological evaluation studies because its efficacy was the highest. KT6124 was also active against sarcoma 180 and B16 melanoma. It exerted a relatively broad spectrum of antiproliferative activity against 20 human tumor cell lines in vitro. To determine the mechanism(s) of action underlying the antitumor activity of KT6124, we tested the drug for inhibition of protein kinases, including Ca²⁺-and phospholipid-dependent protein kinase (PKC), in intact A431 human epidermoid carcinoma cells in comparison with the PKC-inhibitory activity of K-252a. KT6124 did not antagonize the action of phorbol 12-myristate 13-acetate (PMA) in A431 cells, whereas K-252a did, suggesting that KT6124 may not act on protein kinases in the cells. The interaction of KT6124 with DNA in living cells was examined by the alkaline elution method. KT6124 apparantly exhibited DNA scission both dose-and time-dependently in the target cells. The DNA breakage was dependent on proteinase K treatment, suggesting its possible interaction with DNA-related enzyme(s). These results indicate that KT6124 exerts antitumor activity by acting on DNA or on DNA-related enzyme(s) in tumor cells rather than via the inhibition of protein kinases.     

CROSSOVER COMPARISON BETWEEN THE DEPRESSOR EFFECTS OF LOW AND HIGH WORK-RATE EXERCISE IN MILD HYPERTENSION

1. The relationship between work-rate and the antihypertensive effect of exercise in hypertensives, and the mechanism of that effect, were investigated by a crossover clinical trial. 2. Ten mild hypertensives were randomly divided into two groups. One group performed low work-rate exercise (LWE) on a cycle ergometer for 10 weeks (blood lactate threshold; ～50% of maximum oxygen consumption [V?_O2max]). After a 10 week interval without exercise training, these subjects were then switched to a high work-rate exercise (HWE) regimen (4 mmol/ L of blood lactate; ～75% of V?_O2max) for another 10 weeks. In the other group, the order of exercise training was reversed. Since two patients withdrew from the protocol during HWE periods, statistical analysis was performed on the data from the remaining eight patients. There were no order effects observed in any of the data from the two groups. 3. During both LWE and HWE, resting blood pressure (BP) fell significantly after the initiation of exercise therapy (P<0.05). Furthermore, the overall effects of 10 weeks of LWE and HWE on BP were not significantly different. 4. The work-rate at the lactate threshold, which reflects physical fitness, had increased significantly by 16 W (P<0.01) after the LWE period and by 11 W (P<0.01) after the HWE. 5. During the LWE period, changes in haemodynamic and humoral variables were not significant, except for a reduction in plasma norepinephrine at week 10 (P<0.05). In the HWE period, changes in haemodynamic and humoral variables were not significant. 6. Based on these findings, LWE is recommended for mild hypertensives because of its safety.     

Skeletal myoclonus in olivopontocerebellar atrophy: treatment with trihexyphenidyl

We studied two patients with nonfamilial olivopontocerebellar atrophy with skeletal myoclonus. Palatal or skeletal myoclonus is probably not a coincidental finding but another manifestation of the underlying disease. In both cases, the myoclonus was suppressed by administration of trihexyphenidyl, indicating a cholinergic disorder.     

Classification of Diabetes Mellitus by Studies of C-Peptide Secretory Capacity

Residual pancreatic B-cell function was investigated in children with diabetes mellitus in whom classification of the type of disease was difficult at the first visit. Intravenous glucagon tests were performed at the first visit and subsequently, the C-peptide responses compared. Based on our data on a limited number of patients, we propose C-peptide concentrations of 3.0 to 3.5 ng/ml at the peak or at 6 min after injection of glucagon, as the critical level which distinguishes non-insulin dependent from insulin-dependent diabetes mellitus. However, the degree of obesity, clinical stage and other factors also need to be considered in the classification of diabetes mellitus.     

Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal.

Recently an essential role of interstitial cells of Cajal (ICC) within myenteric plexus (ICC-MY) was suggested in ascending contraction and descending relaxation in the mouse ileum. The role of ICC in these neural reflexes was examined in the distal colonic segments prepared from the wild type and c-kit mutant, W/W(V) mice, in the present study. Localized distension of the segments from the wild type mice by using a small balloon resulted in ascending contraction and descending relaxation. In the segments from the mutant mice, localized distension also induced these neural reflexes similar to those observed in the wild type mice. Immunohistochemical examination demonstrated that ICC-MY and ICC present in muscle layers (ICC-IM) were severely disrupted in the mutant mouse, but only ICC, present within submucosal plexus (ICC-SMP), remained unchanged. In the small strips with ICC-SMP absent prepared from the mutant mouse, electrical field stimulation induced contraction or relaxation in the absence or presence of atropine, respectively. It was suggested that ICC have no important role in the ascending and descending neural reflexes in the mouse distal colon, this is in direct contrast to the role of ICC-MY in the ileum.