Viruses: causative agents of cancer.

Evidence accumulated over a period of 60 years has clearly established that a number of different viruses cause neoplasia (of a broad spectrum) amongst a variety of animals. Although it is known that viruses do produce self-limiting proliferative human diseases, complete verification of a human viral carcinogen remains to be provided. This paper presents an overview of the conceptual and practical tools for the detection of tumor viruses, which have derived from experimental model systems. It indicates how these are being applied to studies of human malignant disease, with special reference to assessing a possible viral etiology for laryngeal cancer.     

The effect of sedative agents in psychotropic drugs on acoustically evoked responses

Summary All of the drugs used (Atosil, Nembutal, Mandrax, and Valium) tend to attenuate the acoutically-evoked responses. As was observed in monkeys at an earlier occasion, there are large fluctuations in response magnitude under the affect of Nembutal. It appears therefore that Nembutal is not a suitable sedating agent for the present purposes. Whereas Mandrax attenuates the response potentials strongly for period of up to 4 h, they begin to recover already about 3 h after the administration of Valium. (For details on the effects of these drugs upon the response latencies, cf. the paper by Karnahl and Benning in the same issue.) The situation was best when Atosil was being used-which is known Phenergan in English-speaking countries. In that case, response amplitudes were reduced by a mere 20-300/0 during the first 90–120 min after medication; otherwise, thresholds and ERA characteristics were registered in a normal manner. If registrations were continued for longer periods of time, the depressing effect of Atosil became more marked, although responses remain generally superior to those obtainable under the effects of Valium or Mandrax. The combination of electronic rejection of response artifacts and slight sedation by means of Atosil appears to be quite promising at the present time, especially with respect to evoked-response audiometry in children.

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Zusammenfassung Alle untersuchten Medikamento (Atosil, Nembutal, Mandrax, Valium) haben einen dämpfenden Einfluß auf die gemittelten akustischen langsamen Rindenpotentiale. Schon früher wurde von uns beobachtet, daß bei Affen unter dem Einfluß von Nembutal ein ständiger, starker Wechsel der Amplitudenhöhe eintritt. Dieses Medikament scheint sehr wenig geeignet zu sein für these Untersuchungen. Mandrax und Valium erlauben beim Menschen eine Registrierung zentraler akustischer Reizantworten, deren Ergebnisse sind aber in ihrer Beurteilung äußerst kritisch zu betrachten. Die Amplituden sinken his zur Schwellennähe sehr rasch ab. Nach einem Einfluß von 1/12–2/12 Std ist eindeutig eine Schwellenverschiebung um etwa 20 dB SPL eingetreten. Während Mandrax nun these Potentiale bis zu 4 Std weiterhin stark dämpft, sind ab der 3. Std Einwirkungszeit die Potentiale unter Valium wieder wesentlich besser zu registrieren. Am giinstigsten sind die Ergebnisse unter der Einwirkung von Atosil, das im englischen Sprachraum als Phenergen bekannt ist. Hier wird deutlich, daß bis zu einer Einwirkungszeit von

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With financial assistance of SFB 70 (Sonderforschungsbereich für Hirnforschung and Sinnesphysiologie der Deutschen Forschungsgemeinschaft) and Stiftung Volkswagenwerk.

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Paper presented at the IInd International Symposion of the International Electric Response Study Group in Vienna, Austria, on September 3, 1971.     

The effect of alpha receptor-blocking agents on inner ear function (author's transl)

Nicergolin is used in the treatment of tinnitus, cerebral insufficiency, and sensorineural hearing loss. An increase of cerebral blood flow was observed after i.v. injection of Nicergolin (0.1 mg/kg). The effect of this drug on the inner ear was studied by measuring the DC potential and K+ activity in the endolymph. A rapid fall of the DC potential and hypocapnea were observed after the injection of Nicergolin (0.2 mg/kg). An increase of expiratory PCO2 (10-20 mm Hg) was also observed. Arteficial respiration with pure oxygen prevented the fall of the DC potential. The present investigation demonstrates that this drug primarily acts on the respiratory center with secondary PCO2 increase in the blood which then causes the dilatation of cerebral vessels. The fall of the DC potential after the injection of Nicergolin appears to be caused by hypoxia and not by direct effect on the inner ear.     

An in vitro model for studying growth and effect of trauma and external agents on the cricoid at the cellular level.

Over the past several years it has become evident that expansion laryngotracheal surgery is effective in the treatment of laryngotracheal stenosis. Several clinical and animal studies have been performed to study the process of laryngotracheal stenosis and its treatment. However, there are still many questions that cannot be addressed by currently used clinical and animal research. Further indepth study of the behavior of the subglottis at the cellular level is necessary. We present an in vitro model for studying chondrocyte metabolism of the bovine cricoid. Cartilage was successfully grown in an explant culture system, and it was shown that the chondrocytes were metabolically active and responded to external agents. This model will serve to study the mechanism of growth and effects of trauma and external agents on the cricoid at the cellular level.     

不同栓塞剂治疗头面部肿瘤和血管性病变

为评价不同栓塞剂用于头面部肿瘤和血和性病变栓塞治疗的疗效，将２１例患者分为３组进行治疗。结果发现，明胶涨绵组８例术前栓塞达到预期目的。术中分离容易，出血减少，有１例术后１个月血管再通，３例效果好；白芨组均达到预期效果；弹簧钢圈组３例栓塞术后发现侧支供血动脉，２例达到预期目的。认为，头面部肿瘤和血管性病主一适宜栓塞治疗。栓塞剂和选用在术前栓塞是以明胶海绵为佳，如有必要可加用弹簧钢圈，姑息性栓塞治疗技     

The evaluation of pharmacologic agents on composite graft survival.

This study assessed the efficacy of various pharmacologic agents in improving composite graft viability in 60 New Zealand white rabbits given bilateral auricular composite grafts. Treatments included methylprednisolone preoperatively and for 3 days postoperatively or for 7 days postoperatively only; chlorpromazine, dimethylsulfoxide, or superoxide dismutase preoperatively; or indomethacin preoperatively and for either 3 or 7 days postoperatively. Four treatment modalities yielded a statistically significant decrease in percentage of necrosis. Methylprednisolone, when given preoperatively and continued postoperatively, produced the greatest increase (77%) in composite graft tissue survival. Dimethylsulfoxide, chlorpromazine, and indomethacin for 3 days were also effective, but to a much lesser extent. It is speculated that these agents may help stabilize cell membranes during the anoxic phase of plasmic imbibition and minimize cellular edema until revascularization can occur.     

Cochlear blood flow in response to dilating agents.

Reduced cochlear blood flow (CBF) has been implicated in various pathologies of the inner ear, including sudden deafness, noise-induced hearing loss and Meniere's disease. Thus the aim of some current therapeutic regimens to treat these conditions is to increase CBF and thereby improve oxygenation of the inner ear tissues. Most of the vasodilating agents in clinical use, however, do not have specific experimental evidence to support their effects on CBF. The hypotension which can follow systemic administration may limit their local effectiveness and general utility, just as it complicates the interpretation of the data in animal experiments. In the current study we investigated the effect of six agents, known for their systemic cardiovascular actions, on CBF: hydralazine, sodium nitroprusside, papaverine, nicotinic acid, verapamil and histamine. The effect of these drugs was studied after topical applications on the round window membrane (RWM) and systemic intravenous administrations. CBF was monitored with a laser Doppler flowmeter (LDF). Topical administration of sodium nitroprusside was the most effective in increasing CBF, followed, in order, by hydralazine and histamine. No change in CBF was observed for papaverine, verapamil or nicotinic acid. Systemic administrations of all the agents caused a marked decrease in blood pressure and variable effects on CBF. We discuss the CBF changes in relation to the different pharmacological mechanisms of action of each drug. The study demonstrates the effectiveness of topical application of vasodilating agents in increasing CBF.     

Tumor necrosis factor and chemotherapeutic agents. Potentiation of cytotoxicity with interferon gamma.

This study examined combinations of the recombinant human cytokines, tumor necrosis factor alpha and interferon gamma, with doxorubicin and dactinomycin as well as other drugs on six squamous cell carcinoma cell lines of head and neck origin using the 3(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide proliferation assay. Interferon gamma significantly enhanced the cytotoxicity of tumor necrosis factor alpha with dactinomycin on all six cell lines investigated, while in four of six cell lines the cytotoxicity of tumor necrosis factor alpha with doxorubicin was significantly augmented by interferon gamma. Additional experiments showed no effect with either cytokine in combination with cisplatin, fluorouracil, methotrexate, or etoposide. These data demonstrate that human recombinant cytokines in concert with certain drugs improve in vitro cytotoxicity and may have a potential for improving in vivo therapy.     

The effects of three nebulized osmotic agents in the dry larynx.

PURPOSE: This investigation examined the effects of nebulized hypertonic saline, isotonic saline (IS), and sterile (hypotonic) water on phonation threshold pressure (PTP) and self-perceived phonatory effort (PPE) following a surface laryngeal dehydration challenge. METHOD: In a double-blind, randomized experimental trial, 60 vocally healthy women (n = 15 per group) underwent a laryngeal desiccation challenge involving oral breathing for 15 min using medical-grade dry air (RH<1%). Three of the four groups then received nebulized isotonic saline (0.9% NaCl), hypertonic saline (7% NaCl), or sterile (hypotonic) water, respectively; the 4th group served as a nontreatment control. PTP and PPE were estimated for high-pitched productions at baseline, immediately postdesiccation, and at 5, 20, 35, and 50 min postnebulization. RESULTS: PTP increased significantly for all groups following the desiccation challenge. PTP values were, on average, 0.5 cm H(2)O greater immediately postdesiccation versus baseline. In contrast, PTP values did not change significantly following the administration of nebulized treatments, although a temporary trend toward a reduction in PTP was observed for the IS group. Unexpectedly, PPE ratings decreased significantly after the desiccation challenge. In general, PPE ratings were poorly correlated with PTP measures. CONCLUSION: A laryngeal desiccation challenge (i.e., temporary exposure to extremely low relative humidity while breathing transorally) significantly increased PTP. Although interesting trends emerged, none of the nebulized treatments significantly enhanced recovery from the negative effects of desiccation on PTP. In light of very low correlations between PTP and PPE, serious questions are raised regarding presumed associations between these measures.     

Tumor necrosis factor and cytotoxic agents. Effect on squamous carcinoma lines

The cytotoxicity of dactinomycin (actinomycin D), doxorubicin hydrochloride (Adriamycin), cisplatin, fluorouracil, and methotrexate alone and in combination with recombinant human tumor necrosis factor (rHuTNF) on human squamous cell carcinoma lines was studied by an MTT proliferation assay. The rHuTNF alone caused no inhibition after 24 to 72 hours. All lines investigated showed a dose-dependent response to dactinomycin and doxorubicin. Potentiation of dactinomycin and doxorubicin cytotoxicity occurred with four of six cell lines following incubation of rHuTNF and the drug. No synergistic effect on cytotoxicity was seen with rHuTNF and any chemotherapeutic agent on two cell lines. The addition of rHuTNF did not augment the cytotoxic effect seen with cisplatin, methotrexate, or fluorouracil on any cell line. These results show that rHuTNF can enhance the cytotoxic effect of certain chemotherapeutic agents on squamous cell lines in vitro.     

苯丁酸钠对喉癌Hep-2细胞株诱导化疗的影响

目的:研究苯丁酸钠(PB)与诱导化疗药物对体外喉癌Hep2细胞株的联合作用,探讨PB对喉癌诱导化疗的影响。方法:采用四甲基偶氮唑蓝法(MTT)检测PB分别与5氟脲嘧啶(5FU)和顺铂(CDDP)联合作用时对喉癌细胞的生长抑制作用。结果:5FU和CDDP分别与PB联合应用时,两药各个剂量组与对照组比较及各个剂量组之间比较,差异均有统计学意义(均P<0.05);当5FU和CDDP的浓度一定时,PB的各个剂量组之间比较差异均有统计学意义(均P<0.05)。结论:PB能增强诱导化疗药物对体外喉癌细胞的细胞毒作用,为临床增强喉癌诱导化疗的疗效,减少并发症和毒性反应的发生提供了新的思路。