Based on careful and extensive review of the data, we have concluded that IHCC is well tolerated as a grafting material in rhinoplasty and yields superb functional, structural, and cosmetic results in the most complex and challenging operative cases necessitated by previous unsuccessful nasal surgery, septal perforations, and even in autoimmune diseases that led to nasal deformity. Not only did very few complications occur following the use of 1025 IHCC grafts in 357 patients after 386 rhinoplasties over 24 years (rate, 3.25%), but the rate of complications was no greater than rhinoplasty complication rates when AC grafts are used. The results indicate safety and reliability and justify the convenient use of IHCC grafts for primary and revision rhinoplasty without creating donor site morbidity. Irradiated homograft cartilage grafts are quite stable in the nose and maintain structural contour and support in most cases. Irradiated homograft cartilage grafts should be considered as an alternative or even a primary grafting material when the patient does not have adequate quantities of septal or auricular cartilage remaining to provide the correction or when the shape or quality of such an AC does not adequately provide the structure required. Autogenous rib cartilage is also an alternative material but also increases operative and anesthesia time and adds potential morbidity. The use of IHCC is both cost- and time-effective.

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SUMMARY1. The effects of removal and readmission of substrates on the K contracture were investigated in the guinea-pig taenia coli. When, after exposure to excess K in Ca-free and glucose-free medium, the readmission and removal of 2-4 mM-Ca were repeated at regular intervals, the Ca-induced contractions decreased progressively. The decrease was more marked in the late than in the early part of the tension response.2. The rate of 02 consumption decreased when the normal medium was replaced by glucose-free, Ca-free, excess-K solution, but substantially recovered following Ca readmission. ATP and creatine phosphate contents decreased during the Ca-induced contraction, but recovered partially during the subsequent relaxation in Ca-free solution.3. The effects of glucose removal were rapidly reversed when glucose or ,ihydroxybutyrate (fl-HB) were readmitted to the bathing solution. In the absence of Ca, readmission and removal of the substrates produced an insignificant change in 02 consumption, but the next Ca contraction was potentiated, the effect being stronger with glucose than f-HB.4. When the tonic contraction evoked by 2-4 mM-Ca readmission had been abolished in glucose-free, high-K solution, a rise of the external Ca concentration to 10 mM, or 5 ,SM-carbachol, still produced a transient contraction. This suggests that the tonic contraction has disappeared partially because of diminished Ca influx.5. In glycogen-depleted preparations, the depolarization caused by carbachol, or by 20 mM-K, was increased and spike discharge initiated when glucose was readmitted. Verapamil, which scarcely affected the depolarization by carbachol

SUMMARY1. Mechanical responses to noradrenaline (NA) were investigated in the rat vas deferens exposed to Ca-free solution containing 0.5 mM-EGTA. A tonic response was produced in Ca-free solution at the epididymal portion, while almost no response could be observed at the prostatic portion.2. In most experiments NA (10-4 M) was applied for 4 min, every 20 min. The absolute tension development in Ca-free solution was usually 60-80 %0 of the control tonic response in the presence of 2-4 mM-Ca. The response could be produced repeatedly, even after exposure to Ca-free solution for more than 20 hr, without a significant decrease. During the first hour of exposure to Ca-free solution, the rate of rise and the magnitude of the NA contraction increased and then remained constant, though the relaxation became slow. 3. Transient treatment with 2-4 mM-Ca slightly suppressed the subsequent NA response in Ca-free solution. Similarly, the NA response was smaller during readmission of 0-2-0{5 mM-Ca than that obtained before Ca readmission.4. A high concentration of verapamil (2 x 10-4 M) reversibly reduced the NA response by about 700 after 30 min. Theophylline (10 mM) and dibutyryl cyclic AMP (10-4 M) also reversibly suppressed the NA response, the suppression being about 800%. None of these substances produced a tension change by themselves. The suppressing effect may be mediated via an increase of intracellular cyclic AMP which reduces phosphorylation of myosin. Caffeine (10 mM) and dibutyryl cyclic GMP (10-4 M) had similar but much weaker effects than theophylline and dibutyryl cyclic AMP.5. A calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1 -naphthalene sulphonamide (W-7) slowly reduced the NA response. The block was nearly complete after 30 min treatment with 3 x 10-4 M-W-7, and the recovery was very poor after prolonged exposure. This effect of W-7, which is the same in the presence and absence of Ca, suggests that a Ca-calmodulin reaction is involved in the NA response in Ca-free solution.6. Fluoride at a concentration higher than 3 mm increased the muscle tone in the absence of external Ca, and transiently potentiated the NA response. In the presence of F-, the relaxation of the NA response was incomplete and the muscle tone increased stepwise after each NA application. When the muscle tone became higher than the F. ASHOORI AND T. TOMITA NA response in the absence of F-, the NA response was abolished. The action of several metabolic inhibitors (2,4-dinitrophenol carbonylcyanide chlorophenyl hydrazone, NaCN, monoiodoacetate) was similar to that of F-, suggesting that they release Ca from mitochondria, causing tension development.7. The observations are consistent with the hypothesis that the contraction of the vas deferens caused by NA in the absence of external Ca depends on the availability of intracellular Ca, stored in mitochondria and released by NA.

There is a need to improve the treatment of superficial bladder cancer. One area which holds promise is intravesical gene therapy. Recently, studies undertaken by us have shown that marked tumor regression of bladder cancers occurred after two daily intravesical administrations of an adenovirus encoding human interferon a (Ad-IFNa) using a mouse superficial bladder cancer model in which human bladder tumors are growing. A dose of 1 Â 10 11 particles/ml (P/ml) was used along with 1 mg/ml of Syn3, a gene transfer-enhancing agent. Since clinical studies are being planned using this approach, it became critical to determine if one exposure and lower particle number could be equally effective. We report that indeed a single dose of Ad-IFNa in Syn3 at doses of 1 Â 10 10 -1 Â 10 11 P/ml is highly effective in reducing the size of the tumors, whereas 1 Â 10 9 P/ml was not. Efficacy was also correlated with the level of IFN produced in the urine after treatment. Based on the results of the present studies, a Phase I trial is being planned for superficial bladder cancer, which will involve a single initial treatment with Ad-IFNa/Syn3 and measurement of IFN in the urine over time as an indicator of adequate gene transfer and expression.