Detuning of cochlear action potential tuning curves at high sound pressure levels: influence of temporal, spectral and intensity variables

Action potential (AP) tuning curves (TCs), generated by probe stimuli of 60-65 dB SPL with short rise and decay (r&d) times, are less sensitive (have elevated tip thresholds) and are detuned (the frequency is shifted away from that of the probe stimulus, towards a middle frequency of the audiogram). These effects are more pronounced with forward than with simultaneous masking. TCs generated by masking tonal and narrow band noise stimuli are nearly identical, even though the spectrum is much wider for the noise stimulus. Decreasing r&d time has the same effect on TCs generated from both noise and tonal stimuli, even when it only measurably increases the acoustic splatter of the latter. Detuning appears to be related to a temporal-intensity interaction.     

Clinical aspects, diagnosis and therapy of cancer of Vater's ampulla

The carcinoma of the papilla occupies a special position among the periampullary carcinomas by its favourable prognosis. Responsible for this are the early appearance of symptoms due to the close neighbourhood to the common bile duct and the restriction of the metastasation to the first stage of lymphatic nodes in the majority of cases. Symptoms are jaundice, epigastric pain and decrease of weight. In the carcinoma of the papilla the duodenoscopy with biopsy and ERCP is the method of choice. The reliability of the biopsy is larger, when it is performed after an endoscopic sphincterotomy. For the delimitation of the carcinoma of the papilla against other causes can further be used the hypotensive duodenography, the abdominal computerd tomography, the sonography and the PTC. A curative treatment is possible only surgically. On account of the better long-term results the partial duodenopancreatectomy is to be preferred to the local exstirpation of the papilla. Endoscopic drainages of the biliary tract carried out preoperatively may reduce the lethality of operations. A palliative drainage of the biliary tract on the endoscopic or percutaneous transhepatic way as well as the endoscopic sphincterotomy may improve the patients' quality of life and prolong the survival time, when there are non-resectable tumours or a general inoperability.     

Effect of arachidonic acid metabolites on bone resorption by isolated rat osteoclasts

Arachidonic acid metabolites (eicosanoids) have major effects on bone but their role is unclear. Many are known to stimulate bone resorption in organ culture, but paradoxically, previous work has suggested that at least some of them act as direct inhibitors of osteoclastic function. In an attempt to clarify the role of eicosanoids in bone physiology, we have defined the duration of action and relative potencies of prostaglandin (PG) E1 and E2 and have extended the range of eicosanoids tested on isolated osteoclasts. We have found that PGE1 and PGE2 inhibited bone resorption by isolated osteoclasts for at least 6 h. Inhibition was followed by recovery to control, not supranormal levels. Bone resorption was inhibited in the range 10(-5)-10(-9) M for PGE1 and PGE2, and the rank order as resorption inhibitors was PGE1 greater than 6-keto PGE1 greater than PGE2 greater than PGA2 greater than PGB2. None of the products of lipoxygenase metabolism showed a significant direct effect. The effects of PGE1 and PGE2 were not antagonistic. Prostaglandin production does not seem to be implicated as a second messenger for the action of calcitonin. Although inhibition of osteoclasts by PGs was less prolonged than that observed in the presence of calcitonin, the sensitivity of osteoclasts to inhibition by PGs, and the duration of the effect without subsequent direct stimulation, suggests that inhibition of osteoclastic resorption is a major physiological role of PG production in bone.     

Localization of 3H-proline, 35S-sulfate and 3H-glucosamine in rat cornea following epithelial removal: epithelio-stromal interaction

Localization of 3H-proline, 35S-sulfate and 3H-glucosamine was studied by autoradiography in the rat cornea following the removal of the epithelium. The three labeling chemicals were injected into the anterior chamber of rats, one chemical in each rat, 24 hours after the removal of the epithelium. Animals were sacrificed at various intervals up to 7 days after the injection. The silver grains of 35S-sulfate incorporated into the re-covered epithelium gradually shifted into the stroma. On the other hand, the 3H-glucosamine tended to move toward the epithelial cell membrane and the superficial layer of the epithelium. The 3H-proline incorporated in the epithelium remained in the cells without movement. These results suggest that the 35S-sulfate in the epithelium shifted into the stroma as 35S-phosphoadenosine-phosphosulfate [35S-PAPS] before sulfation of glycoconjugates occurred in the epithelium. A large amount of 3H-glucosamine was utilized as a component of low-sulfated glycoconjugates in the epithelial cell membrane and other cell-coating substances.     

Zinc, calcium, and magnesium metabolism: effects on plasmacytomas in Balb/c mice

The effects of different amounts of dietary zinc on the Zn absorption rate and on Zn, calcium and magnesium concentrations in tissues of MOPC 104E tumor-bearing Balb/c mice were determined. The Zn absorption rate was inversely related to the amounts of Zn in their diets and was lower than that of nontumor-bearing control mice fed a laboratory mice chow. Zn concentrations of tumor-bearing mice were also low compared with control mice but tumor Zn concentrations, regardless of the concentrations of Zn in the diets, were higher than those of normal tissues of the host other than the pancreas. Ca concentrations in tumor and tissues of tumor-bearing mice were higher than in control animals but Mg concentrations in tissues of tumor-bearing mice appeared to be similar to those of control mice. Results suggest that tumor-bearing mice have a lower intestinal Zn absorption capacity and a higher Zn uptake rate causing other tissues to become hypozincemic and hypercalcemic.     

Protection of photosensitized rats against long ultraviolet radiation by topical application of compounds with structures similar to that of dihydroxyacetone

Dihydroxyacetone (DHA), a browning agent, protects photosensitive rats and humans against long ultraviolet radiation (UVA, 320-400 nm) and visible (blue) light. The photoprotective efficacy of DHA and structurally similar compounds was assessed as prevention of edema in the paws of psoralen-sensitized rats, after exposure to blacklight fluorescent lamps. Methylglyoxal produced a yellow-brown color and provided nearly the same protection as DHA, whereas monohydroxyacetone did not color the skin and afforded little or no protection. Glyceraldehyde provided a moderate amount of protection, which was enhanced by prior exposure of the agent to alkaline pH. A solution of 5-hydroxymethylfurfuraldehyde was yellow and provided minimal protection by staining the skin rather than browning it. We conclude that the ability to produce a brown color in skin is a useful criterion for screening compounds for photoprotective efficacy against UVA radiation.     

Clinical phase I study of T-2588

A clinical phase I study for T-2588 was carried out in 25 healthy male volunteers. Each volunteer received T-2588 in one of the following doses: 100 mg capsule or tablet as a single oral administration in fasting or non-fasting state, 200 or 400 mg capsule as a single oral administration in non-fasting state or 300 or 600 mg daily for 14 approximately 15 days as a repeated administration in non-fasting state. The results are summarized below. No subjective or objective adverse effects were noted after a single oral administration. But repeated dose of 300 mg daily for 15 days and 600 mg daily for 14 days brought about abdominal distension in 1 case and soft stool in 1 case, respectively. As an abnormal change in clinical laboratory findings, 1 case with slight increase in transaminase after a single administration and 3 cases with slight increases in transaminase after repeated doses were observed. Time to reach a maximum concentration of T-2525 in blood (Tmax) was longer in subjects at non-fasting states than subjects in fasting states. Maximum blood concentration was lower in the latter than in the former. Urinary excretion rate in 8 hours after an oral administration was 19 approximately 28% and it was higher in non-fasting subject than in fasting subject. No accumulation of T-2588 was noted after repeated doses.     

Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182