Perilymph Fistula as a Complication of Eustachian Tube Dilation and Tympanoplasty.

Eustachian tube dilation (ETD) is an established, minimally invasive therapeutic approach for chronic eustachian tube dysfunction. The complications associated with performing a ETD are rare. A 22-year-old female patient presented with chronic otitis media on the right side and chronic obstructive tube dilation disorder on both sides. A type I tympanoplasty was performed on the right side because of a tympanic membrane perforation after a ETD on both sides without apparent complications. On the 5th postoperative day, she presented with headache, dizziness and hearing loss on the right side. There was a decrease of hearing threshold on the right side in the pure-tone audiogram and vHIT, cVEMP, and SVV were irregular. The ß-2-transferrin test was positive. Since a right-sided perilymph fistula was suspected, an emergency tympanotomy was performed with a round window membrane cover with fascia on the right side. Intraoperatively, a regular, intact ossicular chain was found with a slightly moist middle ear mucosa. The round window membrane was covered by the promontorial lip. Under these measures, the patient's dizziness regressed. The right ear pure-tone threshold vHIT, cVEMP, and SVV normalized.

Spontaneous regressive epitheliomas in the Japanese newt, Cynops pyrrhogaster.

Spontaneous tumors in urodele amphibians have been considered uncommon, and this resistance has sometimes been associated with the natural regenerative capacity of tissues in such species. This report describes spontaneous, nonpigmented, benign epitheliomas which were found in 44 of 1586 (2.8%) adult newts, Cynops pyrrhogaster, captured in central Japan. Both sexes were affected equally, usually with single tumors occurring at any epidermal site. Under laboratory conditions, these large tumors rapidly regressed or disappeared. Lesions were histologically noninvasive, hyperplastic epidermal reactions accompanied by loss of basal, subdermal melanocytes. Ultrastructurally, enlargement of intercellular spaces between tumor cells, increased pigment granules and membrane-bound cytoplasmic aggregates within the spaces, swollen rough endoplasmic reticula, degenerating pigment granules, and altered corneal cells were noted. Virus-like particles were observed in one tumor cell. Prelminary attempts failed to demonstrate transmissibility of the tumor, and no new cases arose under laboratory conditions. The cause of these tumors in the Japanese newt remains unknown, and it is suggested that if a viral agent is involved then other environmental cofactors (diet, temperature, or water constituents) are required for its expression.

Susceptibility of healed gastric ulcers to chemical carcinogenesis in rats and implications of cellular kinetic changes.

The susceptibility of healed, experimental gastric ulcers to chemical carcinogenesis was investigated. Slowly healing gastric ulcers were induced by the acetic acid method in the fundic and pyloric gastric mucosae of inbred male Wistar rats. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered in drinking water at a concentration of 50 mg/liter for 360 days after ulcer induction. Twenty-eight adenomatous hyperplasias and six-adenocarcinomas developed in the pyloric mucosae of rats, including five cases of adenomatous hyperplasia which developed in the periphery of the healed ulcer. In contrast, only one adenomatous lesion was found in the regenerated mucosa of the healed pyloric ulcer. No neoplasm was observed in the healed fundic ulcer area. The results demonstrated an increased incidence of neoplasms in the peripheral area of the healed pyloric ulcer and a decreased incidence of neoplasms in the regenerated mucosa within the healed pyloric ulcer scar, although these differences were not statistically significant in comparison with the intact pyloric mucosae of the MNNG-treated rats. Histoautoradiographs of the gastric mucosae demonstrated increased labeling indices in the healed ulcer periphery of the pyloric mucosa and decreased labeling indices in the regenerated mucosa within the healed pyloric ulcer scar of MNNG-treated rats, which might be related to the differential susceptibility of the two regions to gastric carcinogenesis. Intestinal metaplasia preferentially developed near the pyloroduodenal junction in MNNG-treated rats but was not localized in control rats. In the fundic ulcer scar area, an unusual squamous cell metaplasia was observed in one rat.

Inhibition by zinc of hepatic lysosomal release of beta-glucuronidase induced by phorbol-12-myristate-13-acetate (PMA).

The tumor promoter, phorbol-12-myristate-13-acetate (PMA), elicited a significant increase in lysosomal membrane permeability, as measured by release of free beta-glucurnidase, in guinea pig and hamster isolated hepatic lysosomes in vitro. This response was antagonized by zinc sulfate; zinc compounds having previously been shown to inhibit tumor growth at multiple sites in several species. Since phorbol ester tumor promotion is likely associated in part with actions on cellular membrane systems, its inhibition by zinc may relate to the membrane stabilizing activity of zinc compounds.

Functional morphology of the equine pelvic flexure and its role in disease. A review.

The hindgut is the major site in the horse for nutrient digestion and absorption. Most of this activity occurs in the large intestinal compartments, i.e., cecum, right and left ventral colon and left and right dorsal colon. The colonic pelvic flexure is a short and narrow loop connecting the left ventral and left dorsal colon. It is not significant directly in digestive and absorptive processes but plays an important functional role in regulating colonic aboral and retropropulsive transit of digesta through its motility pacemaker activity. The pelvic flexure also contributes to the pathophysiology of colic, the leading cause of death in horses. Its narrow lumen may contribute to colonic impaction, and malfunctions of the pacemaker may contribute to volvuli and colonic displacements. Neuronal and ganglion density of the myenteric plexus is increased at the pelvic flexure and adjacent left dorsal colon pacemaker region. Contractile activity, vasoactive intestinal peptide (VIP) and neurokinins-1 and -3 are all enhanced in the pelvic flexure. The mucosa histologically resembles that of the ventral and dorsal colon, with apically-granulated principal cells and goblet cells lining the luminal surface. Clustered intranuclear inclusions resembling the cytoplasmic granules are also observed by electron microscopy in the principal cells as elsewhere in the horse colon. Further neuroendocrine and morphologic investigation of the pelvic flexure is warranted due to the great importance of this localized region for normal function and pathophysiology.

Electron microscopic perspectives of gill pathology induced by 1-naphthyl-N-methylcarbamate in the goldfish (Carassius auratus Linnaeus).

This experiment has clarified the ultrastructural pathology, by scanning (SEM) and transmission electron microscopy (TEM), induced by 1-naphthyl-N- methylcarbamate (carbaryl) in the gills of juvenile goldfish (Carassius auratus Linneaus). Carbaryl is a low toxicity pesticide commonly used in forestry and agriculture and for controlling aquatic weeds and crustacean predators of shellfish, and has been known to cause gill damage in fish and clams. A variety of cellular changes were observed after exposure of goldfish for 96 h to a sublethal dose of 10 mg carbaryl/l of water. SEM revealed secondary lamellar fusion, distortion, thinning, and mucus release. TEM responses included enlargement of subepithelial lymphatic spaces and mitochondrial disruption and distortion of the lamellar covering epithelium. Pillar cells became detached and chloride cells were vacuolated. Fish were able to withstand these changes in subacute experiments due to redundancy in gill surface area.

Neural and muscular control functions of the gut in odontocetes: morphologic evidence in beaked whales and beluga whales.

The present data provide some new and unique, gastrointestinal morphologic findings in two species of toothed whales, the Cuvier's beaked whale (Ziphius cavirostris) and the beluga or white whale (Delphinapterus leucas), which are discussed relative to their atypical feeding behavior and alimentary tract functions. Specifically, the findings show myenteric neural modifications and muscularis externa structural specializations which may support voluntary and involuntary fore- and hindgut behavior. Histologic evidence of intercalation-like striations in the gastric and colonic musculature was discovered, as well as an unusual massive size of the colonic myenteric plexuses. These observations, which are not evident in terrestrial mammalian gastrointestinal tracts, may help explain the unusual upper gastrointestinal tract motility such as ingestion-by-sucking in the absence of prehensile teeth and processing of ingesta in a multi-compartmentalized pyloric stomach. Further, the hindgut modifications may help explain the animal's acute, rectal discharge escape mechanism, likened to squid inking, which seems to be an evolved function of some cetaceans.

Reduction of colonic mucus by repeated short-term stress enhances experimental colitis in rats.

The role of stress in inflammatory bowel disease remains debated and few studies have tested the role of stress in conjunction with experimental animal models of colitis. In this investigation we tested the hypothesis that cold-restraint stress would adversely effect the severity of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, and examined mechanisms for the response. Results indicated that increasing intermittent prior exposures to stress significantly enhanced TNBS-induced colitis severity. An associated stress-induced decrease in colonic mucin glycoprotein content, reduction in goblet cells, and histochemical mucin suggested reduced mucin was a pathogenetic factor. Myeloperoxidase content increased and mast cell counts in the colon decreased but colonic permeability only temporarily increased with increasing stress exposure. Prior adrenalectomy or administration of an adrenergic blocking agent did not prevent the colonic changes to stress, but mast cell stabilization or inhibition of cholinergic pathways reduced the stress-induced colonic changes.

Reserpine-induced gastric ulcers: protection by lysosomal stabilization due to zinc.

The effects of graded doses of zinc sulfate pretreatment on reserpine-induced gastric ulceration and on lysosomal fragility both in vivo and in vitro, were studied in rats. Reserpine treatment (5 mg/kg, i.p., 18 h before sacrifice) induced marked gastric glandular ulceration and elicited the release of free beta-glucuronidase from lysosomes in the gastric mucosa. A similar effect on release of this enzyme from isolated rat hepatic lysosomes was observed after in vitro incubation with reserpine. Zinc sulfate (22, 44 or 88 mg/kg, i.p., 30 h before reserpinization, or 10(-3) M in vitro) inhibited the reserpine-induced response, and zinc sulfate alone (10(-11)--10(-3) M) also stabilized lysosomal membrane permeability to beta-glucuronidase. No direct effect of zinc or reserpine on purified beta-glucuronidase activity was observed. In conclusion, it is postulated that the stabilizing effect of zinc on lysosomal membranes, as manifest by reduced release of beta-glucuronidase from isolated lysosomes, is one of the protective mechanisms of zinc against reserpine-induced ulceration.

Epidermal lipid in several cetacean species: ultrastructural observations.

The ultrastructure of the skin of four cetacean species, bottlenose dolphin (Tursiops truncatus) long-finned pilot whale (Globicephala melaena), humpback whale (Megaptera novaeangliae), and fin whale (Balaenoptera physalus) was investigated with particular reference to epidermal lipid. It has already been established that massive lipid reservoirs exist in whales, that the biochemical structures of cetacean lipids are unique, and that unusual intracellular lipid droplets appear in the epidermis. We report here some novel findings on scanning electron microscopic morphology of epidermal lipid, and on its ultrastructural morphology in general and specialized integumentary sites, including species not previously investigated. The intracellular epidermal lipid droplets were more extensive than lamellar body-derived intercellular lipid which is within the interstices of stratum externum cells. The intracellular droplets were spherical, highly variable in size ranging from 0.24 micron to 3.0 microns in diameter, appeared singly or were aggregated in cytoplasmic cavitations, and often were closely associated with epidermal cell nuclei. Evidence for exocytosis of the intracellular droplets was not observed. Significant numbers of intracellular lipid droplets are not observed in the epidermis of terrestrial mammals, so their presence is one of several aquatic specializations of the cetacean integument. Its full significance remains obscure, but it is more probably associated with epidermal cell metabolism than with secretion of lipid.

Studies of zinc and histamine on lysosomal fragility: possible role in stress ulceration.

A combined in vivo and in vitro study was undertaken with rats to test the hypothesis that zinc would protect against cold water immersion--restraint gastric ulcers, and that this phenomenon was mediated in part by stabilization of lysosomal membranes. This postulate was confirmed by observed activity changes in released beta-glucuronidase in mucosal tissue, as well as by dose-response in vitro data on isolated hepatic lysosomes exposed to zinc. Histamine, a known ulcer-enhancing agent, induced the opposite effect and increased the lysosomal release of this marker acid hydrolase.

Effects of chronic nitric oxide synthase inhibition on TNB-induced colitis in rats.

Nitric oxide (NO) synthesis is increased in ulcerative colitis, but the role of NO in colitis is poorly understood. The present study employed Nw-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, in rats to evaluate the effect of NO on 2,4,6-trinitrobenzenesulphonic acid (TNB)-induced colitis. L-NAME solutions were placed in subcutaneous, osmotic mini-pumps which continuously released L-NAME at 0.042, 0.208, 0.417, or 1.667 mg kg-1 h-1. L-NAME dose-dependently enhanced lesions in TNB-induced colitis. The two higher doses of L-NAME significantly increased colonic mucosal damage, although there was slight, nonsignificant reduced lesion formation with the lowest dose of L-NAME. 0.042 mg kg-1 h-1. A single dose of L-NAME at 100 mg kg-1 subcutaneously injected daily in TNB-treated rats also increased lesions, and these ulcerogenic actions of L-NAME were reversed by L-arginine but not by D-arginine (both at 500 mg kg-1, s.c.). Only the highest dose of L-NAME (mini-pump) significantly depressed myeloperoxidase (MPO) activity. Faecal occult bleeding showed a close relationship with severity of colitis. These findings suggest that there may exist a balance between NO protective and aggressive effects. In TNB-induced colitis, antagonism of endogenous NO generation was intensified, whereas slight inhibition of NO synthesis reduced lesions. Variations in responses, related to timing or dose changes in L-NAME, may reflect the differences in inducible vs constitutive NO synthase isoforms.

Ulcerogenic mechanism of ethanol and the action of sulphanilyl fluoride on the rat stomach in-vivo.

The effects of ethanol alone and in combination with sulphanilyl fluoride on some of the antioxidant defences in the stomach of rats have been examined. These effects were correlated with lesion formation in the gastric mucosa. Oral administration of ethanol induced gastric lesions which were prevented by sulphanilyl fluoride pre-treatment. N-Ethylmaleimide antagonized the anti-lesion action of sulphanilyl fluoride. Ethanol administration lowered the glucose-6-phosphate dehydrogenase activity in the gastric mucosa, an effect potentiated by N-ethylmaleimide pre-treatment. The total superoxide dismutase activity was unaffected by the drugs used in the present study. Ethanol, however, markedly increased mucosal catalase activity which was reduced by sulphanilyl fluoride pretreatment and reversed by N-ethylmaleimide. It is concluded that the ulcerogenic mechanism of ethanol is mediated at least in part by the depression of the hexose monophosphate shunt and the production of active oxygen species, whereas the anti-lesion action of sulphanilyl fluoride is probably not mediated through these mechanisms.

Gastric leiomyomas in the Japanese newt, Cynops pyrrhogaster; ultrastructural observations.

Nineteen of 700 outwardly healthy captive adult Japanese newts, Cynops pyrrhogaster, had nodular neoplasms protruding on the gastric serosal surface. These tumours were characterized as sharply circumscribed leiomyomas of the muscularis externa with occasional submucosal involvement. Ultrastructural analysis of tumour myocytes revealed irregular-shaped, well-differentiated cells with cytoplasmic processes, and reduced quantities of intracellular myofibrils. They were surrounded by enlarged intercellular spaces filled with disorganized and increased amounts of collagen. Vacuolation was seen both in tumour myocytes and in mucous epithelial cells. Virus-like particles were observed in nuclei of some tumour myocytes. Interstitial cells with laminated-type granules were seen amongst tumour cells. These relatively benign leiomyomas shared some morphologic features with human gastric leiomyomas. Their cause and prognosis remain unknown.

Reduction of papilloma size by ultraviolet irradiation in the Japanese newt, Cynops pyrrhogaster.

Experiments were conducted on 44 captive Japanese newts (Cynops pyrrhogaster) to test the hypothesis that ultraviolet (UV) irradiation might inhibit growth or induce regression of spontaneous skin papillomas of probable viral origin. An empirically derived exposure to UV irradiation (42 microW per cm2 per day) induced reduction of papilloma size which began approximately 4 weeks after irradiation was initiated. This regression included histological evidence of tissue vacuolization and cellular necrosis of papillomatous epithelium. These findings, taken together with previous data on seasonal, temperature and geographical influences on papilloma prevalence, lend support to the notion that solar UV radiation may modulate papilloma prevalence in the natural environment, possibly by direct effects on viral infection.

Spontaneous thyroid-containing teratoma associated with impaired development in the African clawed frog, Xenopus laevis.

Teratomas are rare in amphibians and the neoplasm described here, which had a significant thyroid carcinoma component, is the first tumour of this type to be reported in Xenopus laevis. The thyroid component contained moderately to well-differentiated acinar glands showing much hyperplasia, dysplasia, and reduced and distorted colloid reservoirs. Cartilaginous, neural, muscular, mesenchymal and gut-like epithelial components were also observed in this ventral mediastinal neoplasm, indicating aberrant proliferation from all three germ layers. This teratoma was only one abnormality in a complex of developmental changes, followed for 28 months, which appeared in a single generation of sibling 2-week-old Xenopus larvae. Two hundred larvae produced by an apparently normal adult pair initially showed ocular defects, including microphthalmia, anophthalmia and tumours projecting near the eyes. During further development up to 28 months, mediastinal tumours developed in nine frogs; these tumours were associated with reduced growth, the frogs reaching only 13-20% of normal weight, and greatly enhanced ventral pigmentation.

Ultrastructure of the olfactory organ of the newt, Cynops pyrrhogaster.

The ultrastructure of the nasal sacs of the Japanese newt, Cynops pyrrhogaster, was studied by scanning and transmission electron microscopy. The paired nasal sacs of the newt are dorsoventrally flattened with a lateral nasal sinus off the main cavity of each sac. Throughout each sac is a series of ridges and grooves. In the main cavity, sensory epithelium with ciliated and microvillous receptor cells lines the grooves, and a thin, ciliated non-sensory epithelium lines the ridges. Secretory glands are present in the lamina propria. In the lateral nasal sinus, the ridges are lined with a thick, non-ciliated sensory epithelium that lacks glands. This region resembles and may function as a primitive vomeronasal organ.

Topographic localization of gastric lesions and key role of plasma bicarbonate concentration in dogs with experimentally induced gastric dilatation.

The canine gastric response to acute dilatation, its correlation with selected systemic cardiovascular changes, and preliminary study of its modulation by membrane-stabilizing agents were studied in 21 Beagle dogs. Gastric mucosal damage and adverse cardiovascular sequelae were induced by inflation of an intragastric balloon to 60 mm of Hg in each anesthetized dog for 2.5 hours. At this time, dogs were given 1 of 4 treatments: control; lidocaine HCl, 2.2 mg bolus + 66 micrograms/min, IV; prednisolone succinate, 6.6 mg, IV; and zinc sulfate, 2.2 mg bolus + 66 micrograms/min, IV. After treatments were given, there was a 4-hour deflation period. Throughout the 6.5 hours, continuous measurements were made of stroke volume, arterial blood pressure, PaO2, PaCO2, and plasma HCO3- concentration. Gastric lesions, assessed by planimetric analysis of ulcer indices, were limited to the fundus and corpus and were significantly decreased by lidocaine administration. As seen by histopathologic examination, a sharply delineated transverse area bordering the corporeal-antral junction near the lesser curvature demonstrated minimal resistance to ulceration and showed mucus depletion. Plasma HCO3- concentration, base excess, and CO2 values were negatively correlated with development of gastric damage, indicating that plasma HCO3- concentration has a key role in mucosal resistance to ulcerogenesis.

Comparative effects of cholera toxin, Salmonella typhimurium culture lysate, and viable Salmonella typhimurium in isolated colon segments in ponies.

Isolated segments of left dorsal colon and a side-to-side colocolostomy (between the left ventral colon and left dorsal colon) were surgically created in 6 adult ponies. Four segments, each separated by an empty segment, were inoculated (20 ml) with 1 of the following 4 solutions: phosphate buffered saline solution (PBSS)/1% polyethylene glycol (PEG); purified cholera toxin in PBSS/1% PEG (5 micrograms cholera toxin/ml of PBSS/1% PEG); lyophilized Salmonella typhimurium UCD 1755 culture lysate, reconstituted in PBSS/1% PEG; and viable S typhimurium UCD 1755 (10(8) organisms/ml of PBSS/1% PEG). Twenty hours following inoculation of the treatment solutions into the isolated colon segments, the ponies were reanesthetized. Fluid accumulation in the isolated segments was measured, and tissue samples from isolated segments were taken for examination by light microscopy and electron microscopy, and for measurement of mucosal cyclic adenosine monophosphate levels. There was fluid accumulation in segments inoculated with cholera toxin in 4 ponies (29.5 +/- 12.7 ml), and in segments inoculated with S typhimurium UCD 1755 culture lysate in 3 ponies (14.0 +/- 8.7 ml). There was no fluid accumulation in segments inoculated with either the control solution (PBSS/1% PEG) or viable S typhimurium UCD 1755. There was significantly (P less than 0.05) less cyclic adenosine monophosphate in segments inoculated with cholera toxin, Salmonella lysate, and viable Salmonella, compared with control segments. Histologically, there were minimal changes in control segments, consisting of mild to moderate submucosal edema and capillary congestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidermal ultrastructure of the southern right whale calf (Eubalaena australis).

An ultrastructural analysis by transmission and scanning electron microscopy was carried out on normal epidermis of six southern right whale (Eubalaena australis) calves which stranded over a period of several months at Peninsula Valdes, Argentina. This was undertaken to 1) provide the first normal skin ultrastructural data on this highly endangered species which is known to display skin pathology in some instances, and 2) to elucidate further the integumentary specializations which have developed in diving marine mammals. Southern right whale lipokeratinocytes demonstrated parakeratosis and numerous intracellular lipid bodies, keratin and melanosomes, as reported for other cetacean species, but showed several unique ultrastructural features as well. These included a high prevalence of intranuclear inclusion bodies resembling small fragments of cytoplasmic keratin, and close structural relationship between cytoplasmic lipid droplets and the nucleus. The subcellular morphology supported the concept of possible nuclear import of cytoplasmic keratin and lipid metabolites through enlargements of the nuclear pore complex or other disruptions of the nuclear envelope. The light microscopy and scanning electron microscopy also revealed an irregular contour of the lipokeratinocytes which comprised the thick stratum externum, and surface flaking of the outermost cells which were covered by stubby microvillous-like remnants of intercellular junctions. These results thus suggest that the long-tem aquatic evolution of this cetacean species has resulted in a number of integumentary specializations and that investigation of their submicroscopic cytology may help elucidate the general cell biology of nuclear-cytoplasmic interactions.