Prevalence of Salmonella spp., Campylobacter spp. and Listeria spp. in ring-billed gulls (Larus delawarensis). Cloacal swabs collected from 264 ring-billed gulls (Larus delawarensis) at four sites near Montréal, Canada were cultured for the presence of Salmonella spp., Campylobacter spp. and Listeria spp. All birds were apparently healthy when captured or killed. Of all birds examined, 8.7%, 15.9% and 9.5%, respectively, were infected with Salmonella spp., Campylobacter spp. and Listeria monocytogenes. Overall, 29.9% of gulls sampled harbored one or more of these bacteria. Gulls probably play only a minor role in the epizootiology of these bacteria.


Mass mortality in cultured coho salmon (Oncorhynchus kisutch) due to Saprolegnia parasitica coker. Epizootics of saprolegniasis occurred in 20 to 60 g freshwater-cultured coho salmon (Oncorhynchus kisutch) in Miyagi Prefecture, Japan. Cotton-like mycelia occurred on the body surface of infected fish, especially around the head, the adipose fin and the caudal fin, and aseptate hyphae occurred in the lesions. The hyphae also penetrated into the muscle and blood vessels. The isolated fungus was identified by asexual morphological characteristics as Saprolegnia parasitica (syn. S. diclina Type 1), a known salmonid fish pathogen.


Ectoparasite-induced lesions in mite pockets of the Yarrow's spiny lizard, Sceloporus jarrovii (Phrynosomatidae). Histopathological effects of the chigger, Eutrombicula lipovskyana, on the mite pockets of neonatal, juvenile and adult Yarrow's spiny lizard, Sceloporus jarrovii, were investigated. Focal ulcerative dermatitis was noted in all age classes. This reaction was more diffuse in older animals in which penetration as deep as the panniculus occurred. Based on the occurrence of inflammatory reactions in neonatal lizards, S. jarrovii appears capable of recognizing foreign antigens shortly after birth. There was an increased inflammatory response in older lizards that may have been an augmented host sensitivity following repeated exposure to chiggers. Granulomas, which were interpreted as an attempt to isolate the effects of chigger bites, were noted in juveniles and adults. We propose that S. jarrovii does not develop resistance after repeated exposures to E. lipovskyana.


Exposure to Psoroptes sp. mites is common among bighorn sheep (Ovis canadensis) populations in California. Sera (n = 806) from 50 populations of bighorn sheep (Ovis canadensis) in California (USA) were evaluated for antibodies to Psoroptes sp. mites using a kinetic enzyme-linked immunosorbent assay (ELISA). Test values for each sample were determined to be either positive or negative at each of two ELISA cutoff values that provided either 100% sensitivity (low cutoff) or 100% specificity (high cutoff), respectively. One hundred sixty-eight (20.8%) sera were seropositive at the low cutoff value, and 87 (10.8%) of these sera also were seropositive at the high cutoff value. Eleven populations were designated as scabies-suspect and 25 populations were designated as scabies-positive because they had at least one seropositive animal at the low and the high cutoff values, respectively. Based on these results, exposure to Psoroptes sp. mites appeared to be widely distributed among bighorn sheep populations from 1980 to 1990 and infested animals may have been present prior to 1980.


Carcass disappearance and estimation of mortality in a simulated die-off of small birds. Carcasses of day-old chicks were placed randomly in grazed, mixed-grass pasture at a density of 50/ha each day for 5 days. Randomly chosen circular plots with a combined area equal to 10% of the total were searched each day for 10 days. The search method detected 95.2% of carcasses placed the day of the search but remains were found of only 20.8% of chicks placed 24 hr prior to searches. Seventy-six percent of carcasses that were observed daily disappeared completely within 24 hr. Although 250 carcasses were placed over a 5-day period, only two intact carcasses that had been in place for > or = 24 hr were found during searches. Estimates derived by extrapolation from the sampled area underestimated cumulative "mortality" on the entire area and did not reflect the course of the simulated outbreak well. There was a low degree of precision among repeated samples from the same area.


Lead exposure and recovery rates of black ducks banded in Tennessee. American black ducks (Anas rubripes) wintering in Tennessee during 1986 to 1988 were tested for exposure to lead. Twelve percent of the birds had blood lead concentrations exceeding 0.2 ppm. Significant differences in the prevalence of lead exposure were found for adults (14.4%) and juveniles (8.2%). Exposed birds had higher blood lead concentrations at one study site, corresponding with a lower survival index.


Trap-vaccinate-release and oral vaccination for rabies control in urban skunks, raccoons and foxes. Two rabies control tactics, trap-vaccinate-release (T-V-R) and oral vaccination were used for the control of rabies in skunks (Mephitis mephitis), raccoons (Procyon lotor), and foxes (Vulpes vulpes) in metropolitan Toronto, Canada. Using T-V-R, a mean of 45% to 72% (95% confidence limits of 40% to 81%) of the skunks and a mean of 17% to 68% (95% confidence limits of 14% to 76%) of the raccoons in a 60 km2 area of Toronto were vaccinated against rabies between 1987 and 1991. The area has been free of skunk rabies from May 1989 to April 1992. Forty-five rabies cases were diagnosed during 1980 to 1986. In contrast, only three skunk cases have been reported since the vaccination program began in July 1987. The T-V-R area also remained rabies free during an epizootic of skunk rabies in metropolitan Toronto during 1991. Following distribution of rabies vaccine-baits throughout the ravines of metropolitan Toronto, June 1989 to December 1991, 46% to 80% of the Toronto fox population was immunized during 1989, 1990 and 1991. Only one case of fox rabies was reported in metropolitan Toronto since vaccination began, compared to 80 cases reported between 1982 and 1988. The area has been free of reported fox rabies from October 1990 to April 1992.


Diseases, parasites and survival of coyotes in south-central Georgia. Serologic testing, radio-telemetry and post-mortem diagnostic evaluations were used to investigate survival and causes of mortality among 17 coyotes (Canis latrans) in south-central Georgia (USA). Prevalence of canine heartworm (Dirofilaria immitis) microfilariae was lower (P = 0.057) among fall-captured (22%) than among winter-captured (75%) coyotes. Prevalence of heartworm was higher among adults than juveniles in the fall, but no significant difference was detected between animals captured in winter. Antibodies were found against canine parvovirus (65%), canine parainfluenza virus (59%), infectious canine hepatitis virus (41%), and Toxoplasma gondii (18%). Antibodies were not found to Brucella canis, canine coronavirus, five serovars of Leptospira interrogans, or canine distemper virus. Seroprevalence of canine parvovirus was lower (P = 0.009) among fall-captured animals (33%) than winter-captured animals (100%). The Kaplan-Meier estimate of annual survival was 0.500 for all animals. Juvenile survival did not differ (P = 0.79) from adult survival, but male survival (S = 0.217) was lower (P = 0.11) than female survival (S = 0.804). Two of nine (22%) mortalities were human-caused, one was due to concurrent canine parvovirus and canine distemper virus infections, one animal died of trauma, two were considered natural mortalities of unknown cause, and no cause of death could be determined for the remaining three animals. Natural mortality may be significant for coyotes in south-central Georgia, although there was no apparent link between exposure to pathogens and the animals' subsequent fate in our small sample.


Diseases and parasites of red foxes, gray foxes, and coyotes from commercial sources selling to fox-chasing enclosures. Fifty-six red foxes (Vulpes vulpes), 18 gray foxes (Urocyon cinereoargenteus), and 13 coyotes (Canis latrans) obtained by the South Carolina Wildlife and Marine Resources Department during an investigation of suspected illegal wildlife translocation were examined for diseases and parasites. Red foxes and coyotes were confiscated from an animal dealer based in Ohio (USA), and gray foxes were purchased from an animal dealer in Indiana (USA). Emphasis was placed on detection of pathogens representing potential health risks to native wildlife, domestic animals, or humans. All animals were negative for rabies; however, 15 gray foxes were incubating canine distemper at necropsy. Serologic tests disclosed antibodies to canine parvovirus, canine distemper virus, canine adenovirus, canine coronavirus, canine herpesvirus, and canine parainfluenza virus in one or more host species. Twenty-three species of parasites (two protozoans, three trematodes, four cestodes, eleven nematodes, and three arthropods) were found, including species with substantial pathogenic capabilities. Echinococcus multilocularis, a recognized human pathogen not enzootic in the southeastern United States, was found in red foxes. Based on this information, we conclude that the increasingly common practice of wild canid translocation for stocking fox-chasing enclosures poses potential health risks to indigenous wildlife, domestic animals, and humans and, therefore, is biologically hazardous.


Pregnancy and ovulation detection in bison (Bison bison) assessed by means of urinary and fecal steroids. Sexually mature bison (Bison bison) cows were tested for both pregnancy and ovulation by means of urinary steroid metabolites and fecal steroids. The accuracy of pregnancy diagnosis was determined among 18 bison cows, in approximately the third month of gestation, by means of urinary pregnanediol-3 delta-glucuronide (PdG), urinary estrone conjugates (E1C), and fecal total estrogens (TE). Urinary PdG was 100% accurate, urinary E1C was 89% accurate, and fecal TE was 100% accurate in predicting pregnancy. Fecal progesterone (P4) and TE, as well as urinary E1C and PdG concentrations all increased from conception (August) through January, but significant differences were not apparent until November. During the rutting season ovulation was detected by increases in either urinary PdG or fecal P4 concentrations. Both pregnancy and ovulation were detected in uncaptured bison with reasonable accuracy by means of urinary and fecal steroids or their metabolites.


Necrotizing lesions in the intestine, gizzard, and liver in captive capercaillies (Tetrao urogallus) associated with Clostridium perfringens. During the period from 1982 to 1991, 863 captive and 32 wild capercaillies (Tetrao urogallus) were necropsied. The most common cause of death in captive capercaillies was necrotizing enteritis, diagnosed in 110 (13%) birds. Of these, 31 (28%) birds also had necrotizing lesions in the liver. Necrotizing gastritis occurred in 29 birds, two of which had concurrent necrotizing enteritis. In the capercaillies with necrotizing enteritis, Clostridium perfringens type A was isolated more frequently and in larger numbers than in birds which died from other causes. Thus, Clostridium perfringens type A may be of etiological importance in necrotizing enteritis. Necrotizing enteritis was not diagnosed in wild capercaillies.


Histomorphometric studies of dermal bone in the desert tortoise, Gopherus agassizii. Dermal bone biopsies were collected from the periphery of the carapaces of adult desert tortoises (Gopherus agassizii) from grazed and ungrazed habitats near the Arizona/Utah border (USA). Quantitative bone histomorphometry was performed on these biopsies as well as on dermal bone biopsies collected from captive juvenile desert tortoises. Except for mild osteomalacia, carapaces of adult desert tortoises from the grazed habitat were relatively normal. No signs of osteopenia were observed. Based on the low numbers of osteoblasts and osteoclasts in dermal bone of both populations of adult desert tortoises, it appears that the peripheral carapace is relatively inert with very low levels of dermal bone turnover. Bone cells and osteoid were more common in dermal bone biopsies from the carapace and plastron of captive juvenile desert tortoises than in adult desert tortoises. However, the great variability in the incidence of bone cells among individuals and the difficulty in collecting juvenile desert tortoises in the field limit the usefulness of dermal bone biopsies from animals of this age group. Based on these results, we propose that dermal bone of the peripheral carapace is a poor sample site for evaluating the effects of dietary or environmental conditions on calcified tissues in desert tortoises.


Plague surveillance by serological testing of coyotes (Canis latrans) in Los Angeles County, California. Sera from 19 (5.6%) of 338 coyotes (Canis latrans) collected in Los Angeles County, California between 1986 and 1990 had antibodies against Yersinia pestis using the passive hemagglutination test. Coyotes were excellent sentinels of plague activity in Los Angeles County. Enzootic plague declined dramatically in the county during the 5-yr period.


Possible vaccine-induced canine distemper in a South American bush dog (Speothos venaticus). Suspected vaccine-induced canine distemper was diagnosed in a captive female bush dog (Speothos venaticus). Macroscopic lesions included mild congestion of the gastric mucosa and focal consolidation of the lung. Histopathological lesions included status spongiosis, gliosis, widespread eosinophilic, intranuclear and intracytoplasmic inclusion bodies in neurons, astrocytes and gitter cells of the cerebral, cerebellar and spinal white matter.


Consideration of inactivated rabies vaccines as oral immunogens of wild carnivores. An experimental beta-propiolactone (BPL)-inactivated rabies virus vaccine was evaluated for the oral immunization of captive raccoons (Procyon lotor) and red foxes (Vulpes vulpes). None of 10 red foxes administered a single 1.0 ml dose of BPL-inactivated rabies virus vaccine (PM strain; 100 or 500 micrograms protein) per os developed detectable anti-rabies virus-neutralizing antibodies (VNA) at any time over 8 wk of observation. Foxes were excluded from further study. In two different groups of five to six raccoons, each administered a single 1.0 ml dose of BPL-inactivated rabies virus vaccine (ERA strain) per os, at concentrations of 100 or 400 micrograms protein, only a single animal in each group demonstrated evidence of seroconversion within 4 wk. In contrast, instillation of a single dose (500 micrograms protein) of BPL-inactivated rabies virus vaccine (ERA strain), directly into the small intestine via fiberoptic endoscope, or ERA vaccine (800 micrograms protein) instillation to the buccal cavity by needle-less syringe, resulted in the production of rabies-specific VNA and protection against lethal rabies infection in three of six, and in four of six raccoons, respectively; all seven control raccoons succumbed to street virus challenge. These preliminary challenge studies, while somewhat encouraging, demonstrate that considerable quantities of purified viral antigen are required for even minimal oral efficacy against lethal rabies infection. At the present time, therefore, potent, self-replicating, attenuated, or recombinant viruses offer the most versatile, economic, efficacious, and safe solutions to terrestrial rabies control of free-ranging carnivores.


Sparganosis in the monotremes Tachyglossus aculeatus and Ornithorhynchus anatinus in Australia. Sparganosis in the echidna, Tachyglossus aculeatus, is characterized by large subcutaneous masses that may be confused with neoplasms. Plerocercoids, believed to be Spirometra erinacei, were found in the ventral or lateral subcutaneous tissues of three echidnas. In each case there was a prominent fibrous mass < or = 12 cm in diameter enclosing plerocercoids, which were surrounded by an intense inflammatory infiltrate dominated by plasma cells and lymphocytes, with focal suppuration. Multiple, small (< or = 2 mm) plerocercoids were present in the lungs and pleural cavity of a fourth echidna that died due to severe pneumonitis. Several plerocercoids also were found in the lung of a platypus (Ornithorhynchus anatinus) associated with parenchymal compression and focal pneumonia.


Verminous bronchitis and bronchiolitis in potoroid marsupials associated with a new Capillaria sp. We describe verminous bronchitis and bronchiolitis in potoroid marsupials associated with a new species of Capillaria resident in the epithelial lining of bronchi and bronchioles. The parasites was associated with alveolar oedema and emphysema, and a mixed inflammatory cell exudate within and surrounding the airways.


Cuterebrid parasitism (Rogenhofera bonaerensis) on the shrubland mouse (Akodon molinae), in Argentina. We evaluated the influence of temperature, rainfall, and host relative abundance on Rogenhofera bonaerensis (Diptera, Cuterebridae) parasitism prevalence in shrubland mouse (Akodon molinae) populations in central Argentina, from February 1983 to December 1987. Parasitism did not vary significantly with host age: juvenile-subadults (32%), adults (26%), and old adults (29%). Females were more frequently parasitized (36%) than were males (20%). There was no correlation between parasitism and reproductive activity. Infested hosts were recorded most commonly in summer (January to March, 19%), and in fall (April to June, 30%). During the dry season, July through November, cuterebrid parasitism averaged only 3%. The monthly prevalence of parasitism throughout the year was not associated either with monthly precipitation nor with mean monthly temperature at the time of sampling. But a 2 to 3 month time-lag effect of both climatic variables on parasitism was recorded. Bot fly prevalence was correlated to an index of host density. We propose climate and host availability as important factors affecting bot fly parasitism in the semiarid shrubland of central Argentina.


Mass stranding of striped dolphin, Stenella coeruleoalba, at Augusta, Western Australia: notes on clinical pathology and general observations. Seventeen striped dolphins, Stenella coeruleoalba, were found stranded on a West Australian beach. Three animals died before a rescue attempt was made and a further three died during the rescue. The remaining dolphins were released 24 km offshore and were not seen again. One dolphin was noted to have a broken mandible. Evidence of physical trauma to the other dolphins was minimal; one adult female was observed with some peeling skin. Blood was collected for analysis. All dolphins were slightly dehydrated and had a leukogram typical of a stressed animal. Plasma biochemistry reflected primary muscle trauma. There were no clues to the cause of the stranding; observed pathology reflected damage that occurred as a direct consequence of stranding.


Histopathology of eighth cranial nerve of mass stranded dolphins at Goto Islands, Japan. We examined four dolphins (Grampus griseus) of 582 mass-stranded. Almost no contents were found in the alimentary canal. Nasitrema gondo and Crassicauda grampicola were found in the tympanic cavity. Severe degeneration of the eighth cranial nerve was observed microscopically in all animals and an egg of Nasitrema was found in a tissue crevice of the nerve. We propose that the nerves were damaged directly by Nasitrema.


Field immobilization of American martens (Martes americana) and short-tailed weasels (Mustela erminea). Ketamine hydrochloride (KH) and a 5:1 combination of KH and xylazine hydrochloride (XH) were used successfully to immobilize short-tailed weasels (Mustela erminea) and American martens (Martes americana), respectively. Four adult male martens were intramuscularly injected with 30 to 82 mg/kg KH and 8.0 to 16.4 mg/kg XH. Three adult male short-tailed weasels were intramuscularly injected with 20.8 to 42.1 mg/kg KH. Mean (+/- SE) induction times for martens and short-tailed weasels were 1.8 +/- 0.2 min and 46 +/- 4.1 sec, respectively; recovery times were 100.4 +/- 19.3 min and 97.9 +/- 6.3 min, respectively. Heart rate was relatively constant among martens; however, respiration varied widely (21 to 122 breaths per minute). Marten body temperature decreased between 0 and 20 min post-recumbency. Short-tailed weasel heart rate and respiration decreased in response to sedation until slightly before arousal. Body temperature stabilized by 20 min post-recumbency. Two short-tailed weasels tremored slightly within 10 min of arousal. I conclude that KH and KH/XH are safe immobilizing agents for martens and short-tailed weasels, respectively.


Prevalence of spindle cell sarcomas among wild Canada geese from southern Illinois. Over a 6-yr period, two cases of neoplastic disease were diagnosed among 1,272 wild Canada geese (Branta canadensis interior) collected in Illinois (USA), Wisconsin (USA), and Ontario, Canada. One juvenile goose of each sex was involved. In both cases > 35 discrete masses were observed subdermally, intramuscularly, and within the body cavity. The tumors, diagnosed as spindle cell sarcomas, are among the most commonly observed neoplasms in free-living North American waterfowl. Based on our data, we suggest that these neoplasms occur with extremely low prevalence (0.002%) in free-living Canada geese.


White phosphorus poisoning of waterfowl in an Alaskan salt marsh. The cause of the yearly death of an estimated 1,000 to 2,000 migrating dabbling ducks (Anas spp.) and 10 to 50 swans (Cygnus buccinator and C. columbianus) has remained a mystery for the last ten years in Eagle River Flats (ERF), a 1,000 ha estuarine salt marsh near Anchorage, Alaska, used for artillery training by the U.S. Army. We have gathered evidence that the cause of this mortality is the highly toxic, incendiary munition white phosphorus (P4). The symptoms of poisoning we observed in wild ducks included lethargy, repeated drinking, and head shaking and rolling. Death was preceded by convulsions. Farm-reared mallards dosed with white phosphorus showed nearly identical behavioral symptoms to those of wild ducks that became sick in ERF. White phosphorus does not occur in nature but was found in both the sediments where dabbling ducks and swans feed and in the gizzards of all carcasses collected in ERF. We hypothesize that feeding waterfowl are ingesting small particles of the highly toxic, incendiary munition P4 stored in the bottom anoxic sediments of shallow salt marsh ponds.


Somatic afferent regulation of plasma luteinizing hormone and testosterone in anesthetized rats. The effects of cutaneous stimulation on plasma luteinizing hormone (LH) and testosterone were examined in adult male Wistar rats anesthetized with pentobarbital. Under the resting condition without somatic sensory stimulation, plasma LH and testosterone measured every 30 min between 1400 and 1730 h revealed no significant fluctuations. Nociceptive mechanical stimulation of bilateral hindpaws by pinching for 10 min significantly increased plasma LH and testosterone. Plasma LH was increased 30 and 60 min after stimulation, while plasma testosterone was increased 60-150 min after stimulation. However, innocuous mechanical stimulation of bilateral hindlimbs by brushing for 10 min did not significantly change either plasma LH or testosterone. These results indicate that, when emotional factors were eliminated by anesthetization, cutaneous nociceptive information led to the increased secretion of LH from the anterior pituitary, resulting in an increase in testosterone secretion from the testes into the plasma.


Responses of sympathetic nerves innervating blood vessels in interscapular, brown adipose tissue and skin during cold stimulation in anesthetized C57BL/6J mice. The effect of cold stimulation on the activity of sympathetic nerves running along blood vessels in interscapular, brown adipose tissues (IBAT) and skin overlying IBAT was examined in 15, urethane-anesthetized, artificially ventilated, C57BL/6J mice. Cold stimulation was applied caudal to the pelvic area using a plastic bag containing iced water. The stimulation of 14-16 min duration reduced core temperature measured at the esophagus or muscle near the esophagus by approximately 4 degrees C from a control temperature of about 38 degrees C. The stimulation decreased the activity of the nerve branches to IBAT, while it increased the activity of the nerve branches to skin. Blood flow in the IBAT increased significantly following the stimulation; however, this effect was abolished by the denervation. These findings suggest that the sympathetic innervation of the blood vessels in the IBAT plays a major role in thermoregulation against cold by decreasing the vascular tone and thus increasing the IBAT blood flow. An increase in the IBAT blood flow would facilitate the dissipation of heat from the IBAT to various organs as well as the supply of energy stuffs to the IBAT.


Ventilatory response to the onset of passive and active exercise in human subjects. Ventilatory responses at the onset of passive and active exercise with different amount of exercising muscle mass were studied in 10 healthy male subjects. Four exercise tests were performed for each subject with appropriate intervals on the same day, i.e., two voluntary exercises of one leg or both legs and two passive exercises of one leg or both legs. Inspiratory minute volume (VI), end-tidal CO2 and O2 partial pressures (PETCO2, PETO2) were measured breath-by-breath using a hot-wire flowmeter, infrared CO2 analyzer, and a rapid O2 analyzer. Average values of VI were obtained from 5 breaths at rest preceding exercise and the first and second breaths after the onset of exercise. The ventilatory response to exercise was calculated as the difference (delta) between the mean of exercise VI and mean of resting VI. In this study, the PETCO2 decreased by about 0.5 Torr in four exercise tests, though the decrement of PETCO2 was not statistically significant. The average values and standard deviation of delta VI were 4.22 +/- 1.63 l/min for the one leg and 6.46 +/- 1.80 l/min for the two legs in the active exercise, and were 2.46 +/- 1.12 l/min for the one leg and 3.44 +/- 1.55 l/min for the two legs in the passive exercise, respectively. These results suggest that in awake conditions, the ventilatory response at the onset of passive or active exercise does not increase additively with the increasing amount of muscle mass being exercised.


Properties of active magnesium flux across the small intestine of the guinea pig. Steady-state net flux of Mg2+ was measured in everted preparations of guinea pig jejunum and ileum, and effects of anoxia, Na+ and Ca2+ concentration, ouabain, and Ca2+ channel blockers were examined. Uphill Mg2+ flux in the mucosal-to-serosal direction was seen in both intestinal segments, with the flux value being 1.5 times greater in the ileum than in the jejenum. The Mg2+ flux was 1.7 times greater than the net Ca2+ flux under the same experimental conditions. The Mg2+ flux was strongly dependent on oxygen and the presence of Na+ in the medium; both anoxia and total replacement of Na+ inhibited the flux by 90-100%. Also, ouabain added to the serosal side, and verapamil or D600 added to the mucosal side, inhibited the flux by about 90%. Inhibitory effects of both ouabain and Na(+)-free conditions were much greater for the Mg2+ flux than for the Ca2+ flux. A stepwise increase in Mg2+ concentration in a Na(+)-free mucosal solution caused a stepwise elevation of the mucosal negativity. The relative elevation of the evoked potential in response to Mg2+ concentration possessed saturable and linearly increasing components. Only the saturable component was found to be dependent on oxygen and sensitive to ouabain. Under the influence of ouabain and verapamil, the generation of the Mg(2+)-evoked potential was greatly inhibited. These findings suggest that Mg2+ is actively absorbed by the jejunum and ileum of the guinea pig, and that active transcellular transport involves a verapamil-sensitive entry step and Na(+)-dependent or ouabain-sensitive exit process which differs from Ca2+ extrusion mechanisms.


Dependence of endocochlear potential on basolateral Na+ and Cl- concentration: a study using vascular and perilymph perfusion. Inside-positive endocochlear potential (EP) and high potassium concentration in the endocochlear duct are generated by transepithelial K+ transport in marginal cells of the stria vascularis. In order to estimate the degree of involvement of Na+ and Cl- in K+ transport in marginal cells, EP in guinea pigs was measured under artificial vascular and perilymphatic perfusion in situ. Na+ depletion due to both vascular and perilymphatic perfusion decreased EP by -10.0 +/- 4.1 mV (delta EP = -86 +/- 5.2 mV, n = 5) from the control value of 78 +/- 4.3 mV (p < 0.01). Cl- depletion due to vascular and perilymphatic perfusion also decreased EP by -10.0 +/- 4.9 mV (delta EP = 8.5 +/- 4.8 mV, n = 6) from the control value of 77 +/- 5.1 mV (p < 0.01). However, under either vascular or perilymphatic perfusion, even lowering of Na+ or Cl- concentration in the perfusate decreased EP only slightly compared to the results under both vascular and perilymphatic perfusion. Furosemide, a blocker of Na+/K+/2Cl- symport, decreased EP under vascular perfusion. This dependency of EP on basolateral Na+ and Cl- concentration strongly suggests that K+ transport by the marginal cell is dependent on the basolateral Na+ and Cl- concentration, and that Na+/K+/2Cl- symport is raised as a possible mechanism for Na+ and Cl- dependency of EP.


Blood flow dependence of local capillary permeability of Cr-EDTA in the rabbit skeletal muscle. To examine direct influences of capillary blood flow on its permeability of water-soluble substances, we measured the local capillary permeability in the rabbit tenuissimus muscle at various capillary blood flow levels by the use of microscopic tissue clearance method. After staining the muscle with Cr-EDTA (M.W.: 341) as the test tracer by suffusing its solution around the tissue, subsequent concentration change in the tissue due to the tracer washout by capillary blood flow was measured from the intensity change on the TV monitor through the vital-microscope. The decay constant of obtained tissue clearance curve has been theoretically predicted to be equal to the local capillary permeability surface area product (PS) per unit tissue volume (Vt). The local capillary permeability (P) could be quantified by calculating the capillary surface area (S) from the perfused capillary density in the visualized microscopic field. The calculated values of P and PS/Vt in the high flow state were 6.00 +/- 0.70 (X 10(-6) cm/s) and 5.85 +/- 0.77 (X 10(-4)/s), respectively, which were significantly larger than those in the low flow state (p < 0.01). It was suggested that there was a mechanism in the red cell passage through the capillary which facilitated the substance exchange across the capillary wall.


Effect of vagotomy on cardiovascular adjustment to hyperthermia in rats. To elucidate the contribution of cardiopulmonary baroreflexes on the control of total peripheral vascular conductance (TVC) during hyperthermia, alpha-chloralose-anesthetized rats with (VX-groups) or without (C-groups) vagotomy were subjected to body heating raising arterial blood temperature (Tb) at a rate of 0.1 degree C/min. In both the C- and VX-groups, rats were divided into normovolemia (C-NBV and VX-NBV) and furosemide-induced hypovolemia (C-LBV and VX-LBV) and cardiovascular responses to hyperthermia were compared between the four groups. Central venous pressure (CVP) decreased as Tb rose to 43 degrees C by 1.92 +/- 0.24, 1.36 +/- 0.28, 0.62 +/- 0.14, and 0.35 +/- 0.23 mmHg in the C-NBV, VX-NBV, C-LBV, and VX-LBV groups, respectively. Mean arterial pressure increased by 35-45 mmHg in the C-groups and by 25-35 mmHg in the VX-groups at Tb of 42-43 degrees C in the C-groups and 42 degrees C in the VX-groups. Heart rate response to increased Tb was not affected by vagotomy or LBV. Stroke volume correlated with CVP (r = 0.769) and this relationship did not differ among the four groups. TVC was more highly correlated with CVP in the C-groups (r = 0.925) than in the VX-groups (r = 0.757). The slope of TVC vs. CVP (TVC/CVP) for the VX-groups lowered by about 40% from that for the C-groups. These results suggest that during hyperthermia, cardiopulmonary baroreflexes may partly contribute to the control of TVC, and other mechanisms related to decreased BV and increased Tb play some roles in the control of TVC.


Importance of sympathetic nerves for the stimulatory effect of cold exposure on glucose utilization in brown adipose tissue. The effects of cold exposure on glucose transport system in brown adipose tissue (BAT) and the role of sympathetic nerves in this response were studied in rats. The rate constant of glucose uptake in BAT increased 10-, 13-, and 14-fold after 6 h, 1 d, and 2 d of cold exposure, respectively, as compared with controls. After 2 d of cold exposure, the number of glucose transporters in the plasma membranes increased from 10.2 +/- 1.1 to 16.7 +/- 1.4 pmol/mg protein and the transporter number in the microsomal membranes decreased from 15.1 +/- 1.0 to 9.0 +/- 1.1 pmol/mg protein, as measured by cytochalasin B binding. However, the increase in glucose utilization in BAT preceded the recruitment of glucose transporters to the plasma membranes. Thus, the glucose utilization markedly increased 6 h after cold exposure without significant increase in the glucose transporter number. The apparent dissociation constant (Kd) for cytochalasin B was unchanged. The stimulatory effect of cold exposure on glucose utilization in BAT was prevented by sympathetic denervation. In denervated BAT, cold exposure conversely decreased the number of glucose transporters in the plasma membranes. These results indicate that: (1) cold exposure increases glucose utilization in BAT and promotes translocation of glucose transporters from the microsomes to plasma membranes; (2) the effects of cold exposure depend entirely upon sympathetic innervation of BAT; (3) the recruitment or redistribution of glucose transporters accounts only partly for the large increase in glucose utilization in BAT after acute cold exposure.


Does Ca2+ release by acetylcholine enhance the synthesis of inositol 1,4,5-trisphosphate in smooth muscle of the porcine coronary artery? A possible role was investigated of the Ca2+ released by acetylcholine (ACh) in the ACh-induced synthesis of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) in smooth muscle of the porcine coronary artery. In Ca(2+)-free solution, 10 microM ACh transiently increased the cellular concentration of Ca2+ ([Ca2+]i) and Ins(1,4,5)P3. Divalent cation ionophores abolished the increase in [Ca2+]i but not the synthesis of Ins(1,4,5)P3 induced by subsequent application of 10 microM ACh in Ca(2+)-free solution, suggesting that the Ca2+ released by Ins(1,4,5)P3 following application of ACh does not act to accelerate the ACh-induced synthesis of Ins(1,4,5)P3 in smooth muscle of the porcine coronary artery.


Brown adipose tissue thermogenesis and metabolic rate contribute to the variation in obesity among rats fed a high fat diet. A high fat (HF) diet is known to induce obesity, but susceptibility to obesity induced by a HF diet differs not only among different strains of rats but also within the same strain. The present study revealed that the Lee index (an index of obesity) positively correlated with insulin, and inversely correlated with both the mitochondrial oxygen consumption in interscapular brown adipose tissue (BAT) and the resting metabolic rate (RMR) in Sprague-Dawley rats. This suggests the contribution of BAT thermogenesis and RMR, in addition to hyperphagia, to the intrastrain variation in susceptibility to HF diet-induced obesity.


[Concomitant graft replacement of the total aortic root and the transverse aortic arch for type A aortic dissection associated with annuloaortic ectasia]. Between April 1988 and February 1992, eight patients with type A aortic dissection associated with annuloaortic ectasia (AAE) underwent the concomitant graft replacement of the total aortic root and the transverse aortic arch at our institution. The acuity of the aortic dissection was acute stage in 3 patients and chronic stage in 5 including 3 cases of re-do operation. All operations were performed with an aid of extracorporeal circulation, blood cardioplegia, selective cerebral perfusion and open distal anastomosis. The operative techniques employed in this series consisted of total aortic root replacement using a composite graft (Bentall, Cabrol or Piehler's technique), and total arch replacement using en bloc arch reconstruction or three vessels graft replacement. One patients underwent re-do operation for coronary anastomotic false aneurysm following Bentall operation and aneurysmal dilatation of the false lumen at the aortic arch, and died of LOS because of the prolonged myocardial ischemia. Other seven patients survived the operation, and lead the normal life at the present time. The present data suggests that type A aortic dissection associated with AAE involving aortic arch could be treated by concomitant graft replacement of the total aortic root and the transverse aortic arch.


[Changes of plombage-operations in respiratory surgery]. The first plombage-operation for pulmonary tuberculosis was by Dr. Nagaishi (1947) and Dr. Wilson, who developed the plombage method employing hollow polymethylmethacrylate spheres. Although the method presented a relatively effective option at a time when no effective drugs were available, its use was discontinued because of such complications as lung injury, cavity-perforation, and empyema. Therefore, soft elastic resin materials, such as those used in sponge-plombage and air-plombage, replaced the hard resin materials. Each plombage method is associated with a certain medical historical period, in Japan. Still the "Kinchyu" method was used. However, the complication of chronic empyema with bronchopleural fistula was difficult to treat. A notable recent method is the pedicled omentum plombage method, which is effective in the treatment of patients who have not responded to standard operations. Finally there was surely a clinical significance in each medical historical period.


[Surgical treatments of nonconfluent pulmonary arteries with congenital cardiac defects]. Pulmonary artery angioplasty or reconstruction was performed in seven patients with nonconfluent pulmonary arteries and congenital cardiac defects. Age of these patients were ranged from 6 months to 41 years old. Five of them had pulmonary truncal atresia and complex cardiac anomalies. Two of these five patients demonstrated nonconfluent pulmonary arteries due to deformities at ductal insertion of pulmonary arteries. Three patients had had previous systemic to pulmonary artery shunt operations which caused pulmonary artery distortions. Other two patients had intrapulmonary arterial obstructions due to pulmonary artery thrombosis. Patch pulmonary artery plasty was carried out in three patients, dilatation of severe stenotic pulmonary artery was done in one patient simultaneously with pulmonary valvotomy. Central shunt operation was added in one patient with the pulmonary artery which was unable to be reconstructed. Last two patients underwent intrapulmonary artery reconstruction with the rolled pericardial graft. Hospital death occurred in one patient with unproperly increased pulmonary blood flow by central shunt. Average follow-up period of these six survivors after operation was 1.4 +/- 0.8 years. As definite repairs, two patients had Fontan operation, two patients had right ventricle to pulmonary artery reconstruction. And remaining two patients are still to be followed until sufficient growth of pulmonary artery suitable for Fontan operation.


[Studies on acute surgical therapy for DeBakey III aortic dissection: especially on the CT images and the operative indication]. Nine patients with DeBakey type III aortic dissection (type III a; 6, type III b; 3) that underwent acute surgical therapy were studied with particular emphasis on the preoperative CT images and operative indication. It took 6 approximately 192 hours (mean 40.6 +/- 56.0) from onset of the disease to the operation. The reasons why operations were required in acute phase were prolonged pain; 2, fluid retensionin in thoracic cavity; 3, increasing fluid retension; 3, shock state; 1, anuria; 1.6 (75%) of 8 thoracic aortic dissection cases showed intra-thoracic fluid retension in chest roentogenogram or CT image. We performed prosthetic interposition of descending thoracic aorta in 8 patients and Y-graft interposition of abdominal aorta in a patient. During the operations, we found fluid retension in the thoracic and pericardial cavity in 83% (5 cases) of 6 non-ruptured cases. To diagnose ruptured aneurysm, CT image played very important role. But we could not discriminate between ruptured aneurysm and intrapleural serous fluid retension on the CT image. Puncture of intra-thoracic fluid is effective procedure to diagnose rupture of the aneurysms but it is impossible in some cases and traumatic tap may lead misdiagnosis. Therefore we think moderate or increasing fluid retension in the thoracic cavity should be added to the operative indication of acute DeBakey type III aortic dissection and that the early operation will make mortality rate lower.


[Differential diagnosis between acute rejection and infection after lung transplantation in rats]. Infiltration of mononuclear cell subpopulations was analyzed immunohistochemically in acute lung allograft rejection (BN/LEW) and mycoplasma pulmonis bronchopneumonia in inbred rats. In lung allograft rejection, marked infiltration of activated macrophages, moderate infiltration of helper and suppressor T lymphocytes, and slight or moderate infiltration of B lymphocytes were observed around bronchioles and vessels, as a thick layer of cells like concentric circles, forming a dense cuff. In acute and chronic mycoplasma infection, focal inflammatory reactions were observed with various degrees of infiltration of mononuclear cell subpopulations around bronchioles and vessels, ranging from very mild to severe infiltration, even in the same section or even around the same bronchiole. This difference in the infiltration pattern between the focal, unequal and dappled infiltration in lung infection and the homogeneous and even cuff infiltration in acute rejection may be useful in differential diagnosis between acute rejection and infection following lung transplantation.


[Combined superior-transseptal approach to the mitral valve]. We report a technique to improve exposure of the mitral valve apparatus. This technique that combines superior left atriotomy and interatrial septotomy can be helpful in patients with a small left atrium and reoperation. It has been used effectively in five patients and potential complication with this procedure has not occurred. The operative technique and indication are discussed in this paper.


[Combined resection of the aorta in a T4 lung cancer under nonheparinized temporary bypass using Anthron tube]. A 63-year-old male had squamous cell carcinoma in the left upper lobe. CT scan suggested the invasion of the tumor into the vertebral body and the descending aorta. Left pneumonectomy and combined aortic resection under the temporary bypass using Anthron tube was performed. The bypass using Anthron tube provides us no systemic heparinization and the procedure is easy. So the danger of massive bleeding during and after the operation can be decreased and the operative time can also be shortened. This procedure may be a great help for carrying out the operation with combined aortic resection more safely and speedily.


[A case of Marfan's syndrome that required emergency Bentall's operation due to acute dissecting aortic aneurysm (DeBakey type II) following surgery of abdominal aortic aneurysm]. Graft replacement was performed in a 29-year-old man for an abdominal aortic aneurysm associated with Marfan's syndrome. Since the dissecting aortic aneurysm (DeBakey type II) accompanied by disruption of the right coronary artery developed 74 days after operation, the emergency Bentall's operation was successfully carried out with bypassing of the right coronary artery using a saphenous vein graft. Fifteen Japanese cases operated on for abdominal aortic aneurysm associated with Marfan's syndrome are reviewed, and the problems concerning surgery of abdominal aortic aneurysm and Bentall's operation are discussed.


[Invasive thymoma involving the liver: a case report of transdiaphragmatic extension]. A 38-year-old woman had an invasive thymoma which disseminated into the thoracic cavity and infiltrated the lateral liver surface. Such transdiaphragmatic extension by an invasive thymoma is rare, however, routine abdominal CT should be performed in invasive thymoma cases to avoid underestimating the extent of disease.


[A case report of primary rhabdomyosarcoma of the heart treated with mitral valve replacement]. We report a case of rhabdomyosarcoma involving the mitral valve of a 57-year-old female. She was referred to our hospital for progressive orthopnea and edema. Chest X-ray showed marked cardiomegaly and pulmonary congestion. Echocardiogram revealed solid mass in left atrium involving the mitral valve. Emergency operation was required because of acute heart failure. At the operation, the mitral orifice was obstructed by the tumor arising from the left atrium. After partial resection of the left atrium, mitral valve replacement with a Carpentier-Edward prosthesis was performed. Subsequently microscopic examination diagnosed as rhabdomyosarcoma. She died three months after the operation of heart failure probably due to progression of the remnant of the tumor. This, to our knowledge, is the first case of mitral valve replacement for a primary rhabdomyosarcoma of the heart in Japan.


[Left ventricular-right atrial communication with a residual ventricular septal defect: a case report of successful VSD patch closure with tricuspid valvuloplasty using folded patch]. A 18-year-old woman with combination of left ventricular right atrial communication (LV-RA communication) and residual ventricular septal defect (VSD) was presented. She underwent the radical operation of atrial septal defect, VSD and infundibular pulmonary stenosis at the age 11 years. Surgery was performed under the diagnosis of LV-RA communication and residual VSD. Two small defect were existed at the septal leaflet of the tricuspid valve, which communicated to left ventricle. The part of patch being used as closure of VSD at the previous operation, including perforated part of the septal leaflet was resected. A folded patch was used to reinforce the residual VSD and valvuloplasty was made using the remaining intact tricuspid tissues. Post-operative clinical course was uneventful. Shunt flow from LV to RA was not demonstrated in the postoperative left ventricular angiocardiography.


[A case report of oozing type cardiac rupture following acute myocardial infarction: hemostasis with fibrin glue and oxycellulose]. A 65-year-old man was admitted due to acute anterior myocardial infarction. After admission, he fell into cardiac shock. Echocardiogram showed cardiac tamponade due to cardiac rupture. He was immediately transferred to the operating room. After opening the pericardium, 300 ml of bloody pericardial fluid containing coagula was excluded. Hematoma-like infarcted lesion was found on the surface of the left ventricular apex. Because there was no bleeding point, fibrin glue and oxycellulose was fixed on this lesion for pressure hemostasis without any suture. The postoperative course was uneventful.


[A case report of ruptured aneurysm of the sinus Valsalva resulted in tricuspid valve endocarditis]. A case of a 42-year-old man with ruptured aneurysm of the sinus Valsalva resulted in tricuspid valve endocarditis was reported. The aneurysm originating from the right sinus Valsalva ruptured into the right atrium, which caused tricuspid valve endocarditis. The aneurysm was closed through right atrial approach. A part of the septal leaflet of tricuspid valve including vegetation was resected and repaired.


[Aortic root reconstruction in the patient with aortic root dissection and aortic valve regurgitation: a case report]. The reported patient was a 60-year-old man with congestive heart failure and recurrent inferior myocardial infarction. The aortogram revealed severe aortic regurgitation, aortic root dilatation and dissection with involvement of the right coronary ostium. Aortic root reconstruction using the valved conduit was performed. The left coronary ostium was reimplanted with Carrel patch method and the right coronary artery was bypassed with the saphenous vein graft. Postoperative course was uneventful and he is asymptomatic in one year after operation. Although aortic root reconstruction with Carrel patch procedure is not widely adopted in Japan, we recommend this procedure because the anastomosis between the coronary ostium and the graft is tight.


[A case report of pulmonary embolectomy for acute pulmonary embolism]. In recent years, case reports of the pulmonary thromboembolism which had been comparatively less in our country, have been gradually increasing. However, this disease is more often reported in the chronic stage, and case reports of severe cases in the acute stage are still less. The case reported here was admitted to our hospital by emergency ambulation with severe chest pain. On the second day after the admission, respiratory standstill developed suddenly following recurrent chest pain, which necessitated cardiopulmonary resuscitation. The patient was intubated and the IABP was instituted because of hemodynamic instability. An emergent cardiac catheterization under the mechanical ventilation and the IABP supported displayed massive shadow defect on the pulmonary arteriogram, which was indicating acute pulmonary embolism. The pulmonary pressure was 58/18 mmHg despite of the shock state (the aortic pressure: 60/28 mmHg). Subsequently, a pulmonary thrombectomy was carried out under the emergency cardiopulmonary bypass. The cardiac catheterization performed two weeks after the operation. Revealed that the pulmonary pressure returned to the almost normal volume (38/18 mmHg) in association with the aortic pressure of 113/72 mmHg. The venogram of lower extremities revealed thrombi in the deep veins, suggesting the cause of the thromboembolism in the pulmonary arteries. The Bird's nest filter was inserted for the prevention of recurrence of pulmonary embolism. This patient is doing well 10 months postoperatively.


[Benefit of the autoperfusion balloon catheter for emergency coronary artery grafting after failed percutaneous transluminal coronary angioplasty]. A 61-year-old man was operated on an emergent basis because of abrupt closure of left anterior descending coronary artery (LAD) following failed coronary angioplasty. At once abrupt closure occurred, Stack autoperfusion balloon catheter was placed across the coronary lesion to reestablish blood flow to the ischemic myocardial area with intraaortic balloon counterpulsation. Despite a longtime of 12 hours to cardiopulmonary bypass, the patient had been managed with excellent resolution of symptoms and ST elevation. Under a stable hemodynamic state, saphenous vein grafting to LAD was performed with minimal myocardial infarction. Stack catheter made it possible to perform the subsequent coronary bypass operation as a controlled, optimal revascularization procedure because of its passive autoperfusion effect.


[Surgical treatment of acute aortic dissection in the aged: a case report]. A 77-year-old woman with Stanford type A acute aortic dissecting aneurysm was successfully treated by the sutureless technique using arringed intraluminal graft. A month after the operation, re-dissection to the distal abdominal aorta occurred. Because of the poor condition of the patient and her great age, we chose an antihypertensive therapy instead of a reoperation. Two years after the operation this patient leads a sound life without any symptoms. In a case of acute aortic dissection of the aged, special consideration may be allowed to a surgical method and a decision-making for a reoperation.


[A case of mediastinal seminoma which penetrated pericardium and invaded left upper lobe]. A 35-year-old man admitted at our hospital, with a complaint of anterior chest pain. Chest x-ray film and CT showed an anterior mediastinal tumor. An invasive thymoma was suspected by the biopsy specimen, invading left upper lobe of the lung. Resections of the tumor, thymus, invasion to the part of the left upper lobe and the pericardium were performed. The pathology showed pure seminoma penetrating the pericardium. As testis and the retroperitoneum were normal, the tumor was diagnosed as mediastinal origin. Adjuvant chemotherapy (CDDP, BLM and etoposide) and irradiation were performed. The patient is alive and well for 7 months postoperatively.


[Investigation on unsuccessful endoscopic operation for cases with vesicoureteral reflux]. Endoscopic operation of vesicoureteral reflux (VUR) has several advantages such as less invasiveness and technical ease with the procedure and shorter hospitalization for the operation in comparison with coeliotomy, but the cure rate achieved by endoscopic operation compares unfavorably with that by coeliotomy. The unsuccessful cases of VUR by endoscopic operation were investigated to promote the success rate by endoscopic operation. Of 66 ureters in 55 patients 50 were successfully treated with the first operation, and 4 of 8 ureters with the second one. All 15 infants were cured, but the cure rate in females between 17 and 45 year old was significantly low (57%). An equally high cure rate was obtained by the endoscopic operation even in patients who had a high grade VUR, patulous ureteral orifices, an underlying neurogenic bladder, or episodes of urinary tract infection. All ureters were cured just after operation. The recurrence of VUR occurred in 19 ureters (29%) and 16 ureters were discovered at one month examination after operation, which indicates that olive oil dissolving teflon paste was partly absorbed to bladder tissue. Teflon paste shifted to internal urethral orifice in 4 unsuccessful ureters. Based on these findings, the endoscopic operation should be considered to be the preferred treatment among others in the management of VUR and the injection of sufficient volume of teflon paste into submucosal and muscular space of the bladder trigone could promote the cure rate.


[Study of 54 renal allograft recipients in the cyclosporin A era. What influences acute rejection episode and long-term graft survival?]. During the past 5-year period from 1986 to 1991, a total of 54 patients received living-related renal allograft and has been managed with vagaries of cyclosporin A (CYA) immunosuppressive regimen. In order to determine the ideal form of induction regimen, combination drugs with CYA, the initial dosage of CYA and its blood trough level were retrospectively analyzed with particular reference to the possible factors relevant to the occurrence of acute rejection episode in the first three post-transplant months and graft survival. The combination drugs with CYA were prednisolone (PRD) in 10 patients, PRD + azathioprine (AZA) in 19 and PRD+mizoribine (MIZ) in 25. The initial dosage of CYA was 6 mg/kg B.W. in 6 patients, 8 mg/kg in 17, 10 mg/kg in 15 and > or = 12 mg/kg in 16. Blood trough level of CYA measured principally by high performance liquid chromatography was arbitrarily divided into < 100, 100-150, 150-200, > or = 200 mg/kg ranges for the analysis. By arbitrarily dividing the post-transplant period into four (period I: 0-15th day, period II: 16-30th, period III: 31-60th and period IV: 61-90th), the correlation of the incidence of acute rejection episode and aforementioned factors was studied. Relevance of these factors to the graft survival was also studied. The administration of AZA to MIZ to CYA + PRD had no suppressive effect upon the occurrence of acute rejection during the first three months and similarly it had no effect upon graft survival. Rejection episodes, however, occurred more frequently in the recipients with less than 150 ng/ml of CYA trough level in the period I and less than 100 ng/ml in the period III (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


[Adherence of E. coli to bladder epithelia in compromised mice and plasma endotoxin level]. The role of bacterial adherence in association with complicated urinary tract infections (UTI) and the correlation between bacterial adherence and plasma endotoxin (ET) levels were experimentally investigated by using mouse UTI models. Mice with foreign bodies induced in the bladder or voiding dysfunction were more susceptible to UTI than untreated mice. But diabetic or granulocytopenic mice were little susceptible to UTI in comparison with other two models. Adherence activities of 6 strains of E. coli to mice bladder epithelia in the 4 compromised models showed no difference when compared with those in normal control. Binding patterns of 8 kinds of lectins and mouse uromucoid polyclonal antibody to the mice bladder epithelia in compromised models appeared to be almost the same as those in the normal bladder epithelia. These results suggested that the reason for the susceptibility to UTI in the compromised mice was not necessarily explained based on the increased adherence of E. coli due to qualitative or quantitative changes in receptors on the bladder mucosa. Impairment of other host defense mechanisms may be considered in this regard. Three strains of E. coli expressing type 1 pili adhered to the bladder epithelia in greater numbers in vivo than non piliated strains. E. coli No. 113 strain expressing both type 1 and p pili appeared to be the most virulent in vivo among all 6 strains. Plasma ET levels increased 6 to 24 hours after inoculation of 2 strains of E. coli expressing only type 1 pili or p pili, while a little increase in the levels was observed in mice inoculated with non piliated E. coli. Bacterial adherence to the bladder epithelia may play an important role for the increase in ET levels.


[Radiopacity of the cystine calculi on KUB]. To study the radiopacity of cystine calculi. We have compared them with oxalate and/or phosphate calculi on plain X-ray films (KUB). Eleven pure cystine calculi from 5 people in 4 families, and 8 oxalate and/or phosphate calculi as controls were obtained from patients by lithotomy or spontaneous discharge in Dokkyo University School of Medicine and affiliated hospitals, since 1978. The radiopacity of cystine calculi was measured by a densitometer PDA-60 (Konika Co.), comparing the density of the calculus with that of the area surrounding the calculus on KUB. All cystine calculi were easily recognized on KUB, and their densities were fairly identical with those of oxalate and/or phosphate calculi.


[Trial of in vitro fertilization via epididymal duct aspirated sperm]. We made a trial of our method by which sperm are collected directly from epididymal duct, then subjected to in vitro fertilization. The subjects were a total of 22 cases comprising 14 of obstructed azoospermia and 8 of severe oligoasthenozoospermia, on which the surgery was performed 26 times. Using the microscope, an epididymal duct was directly punctured to make a suction of the fluid or was slightly incised to make a suction of the outflow. Sperms thus collected were preincubated for 4 to 6 hours, then subjected to in vitro fertilization. Condition of collected sperms; 32 x 10(4)-15300 x 10(4) sperms were obtained in real number. Sperm motility rate was 0-82%, averaging 25.0%. Sperm forward motility were fairly good in 18 of 26 test cases. Sperm condition was so poor as to make the insemination impossible in 4 test cases (16%). Fertility rate for cases of obstructed azoospermia was 53% (8/15 test cases) and 63% (55/87 eggs) in the test cases and the number of eggs, respectively, compared with 33% (2/6 test cases) and 5.4% (2/37 eggs), respectively for cases of oligo-asthenozoospermia. Pregnancy; Successful pregnancy was obtained in 2 of the cases of obstructed azoospermia, in each of which sperms were collected from the head of the epididymis, then passed into the maternal body by zygote intra fallopian tubal transfer (ZIFT); with the one case resulting in uneventful delivery in November 1991 and the other in a miscarriage. The above results suggested the present method would become an epoch-making approach in the treatment of severe male infertility.


[Effects of afferent vagal stimulation and distention of the upper digestive tract on the micturition reflex and activity of the pontine micturition center in dogs]. (1) The study was performed to elucidate the effects of afferent vagal stimulation and distension of the digestive tract on the micturition reflex in 21 acute decerebrate dogs immobilized with gallamine. Electrical stimulation of the central cut end of the cervical vagus nerve with high voltage (17.5-25 V) and moderate frequency (10-50 Hz) elicited in most cases inhibition of the periodic bladder contractions and of outflows of the pelvic vesical branch which were induced by a sustained intravesical pressure of 10-15 cmH2O. Distension of the thoracic esophagus, the stomach, and the duodenum also induced inhibition of the bladder contractions and of the pelvic outflow to the bladder. Such inhibitions were abolished after bilateral cervical vagotomies except a few cases of distension of the duodenum. (2) Another series of experiments were undertaken to clear the effect of afferent vagal stimulation on the electrical activity of the pontine micturition center in 10 acute decerebrate dogs. By means of an extracellular glass microelectrode method, unitary discharges synchronized with the grouping discharges in the pelvic vesical branch with a rhythm of 2.2-2.5 Hz were recorded from the pontine micturition center in the dorsolateral pontine tegmentum. Such a type of discharges was detected in 6 of 59 units which discharged by afferent stimulation of the pelvic vesical branch. This type of discharges was inhibited by afferent vagal stimulation at the supradiaphragmatic level. From these results, it may be concluded that the afferent pathway of the bladder relaxation reflex induced by distension of the upper digestive tract is mainly involved in the vagal nerves, but in some cases of the strong distension of the duodenum, the pathway is in splanchnic nerves, and that inhibition of the bladder contraction after stimulation of vagal nerve is induced by suppression of the pontine micturition centers.


[Effect of unilateral hydronephrosis upon contralateral renal growth]. To evaluate the effect of hydronephrosis on the growth of contralateral normal kidney, following experiment was designed and performed. Three to four weeks old S-D rats weighing 80-90 g were used. The kidney development of these rats is considered to be roughly equivalent to that of a one year old child. Those rats were divided into three groups: (1) left nephrectomy (group N), (2) left ureteral ligation (group H), and (3) sham operation (group S). Bromodeoxy uridine (BrdU) was administered intraperitoneally on the 1st, 3rd, 5th, 7th and 14th days after operations. One hour after injection of BrdU, right kidneys were removed and wet weight and labelling index (LI) of BrdU were calculated. Compensatory renal growth of right kidneys was observed in both group H and group N on and after 1st or 3rd day. In group N, the growth was accompanied by cellular proliferation, while in group H, hypertrophy was the major finding for up to 5th day. From 7th day on, when significant disorders became histologically evident in the left hydronephrotic kidneys, cell proliferation was also observed in the group H. The above results indicate that compensatory renal growth occurred in the contralateral normal kidney after unilateral ureteral ligation. Although proliferation of right renal tubular cells were recognized when significant tubular and interstitial damage of the left hydronephrotic kidneys were observed, hypertrophy was a major finding in an early stage. We suggest that these results were attributed to (1) reduction of nephron triggered to proliferate tubular cells and (2) the existence of hydronephrotic kidney inhibited tubular cell proliferation.


[Study on chemosensitivity test of urogenital tumors by ATP assay]. In order to improve the efficacy of chemotherapy against urogenital cancers, we developed a chemosensitivity test by measuring intracellular ATP in cancer cells. In the fundamental experiments using HeLa cells, a significant correlation was observed between intracellular ATP levels and numbers of viable cells. We employed 8 drugs, ADM, VCR, VLB, MTX, 5-FU, PEP, MMC, and CDDP for the assay Thirty-four renal tumors, 68 urothelial tumors and 19 testicular tumors were tested, and evaluable results were obtained in 25 specimens of renal tumors (76%) 55 specimens of urothelial tumors (80%) and 17 specimens of testicular tumors (98%). According to the ATP assay, renal tumors were sensitive to ADM and MMC, urothelial tumors to ADM, MMC and CDDP and testicular tumors to ADM and MMC. The ATP assay to determine the chemosensitivity to clinical specimens was sensitive and efficient. Thus the ATP assay could be applied for selection of anticancer drugs in the chemotherapy of urogenital cancers.


[Urinary managements of 332 stroke patients in the chronic phase]. Urinary managements of 332 stroke patients in the chronic phase were performed at Bobath hospital. Cerebrovascular accidents (CVA) were caused by cerebral infarction in 178 (53.6%), intracerebral hemorrhage in 123 (37.1%) and subarachnoid hemorrhage in 31 (9.3%). Voluntary urination appeared in 124 patients before treatment, however in 29 of them occasional incontinence were observed. One hundred forty-three patients used diapers and 64 were controlled by indwelling catheters. The remaining one patient was treated by intermittent catheterization. Sixty-two patients who seemed to have communicative abilities in daily living were assessed with regard to their cerebrovascular dementia by Hasegawa's Dementia Rating Scale. After treatment 235 patients (70.8%) were able to urinate voluntarily, and only 15 of them remained incontinent and could use small pads successfully. TURP was effective for the stroke patients with benign prostatic hypertrophy (BPH) or bladder neck sclerosis (BNS). Fifty-three patients (16.0%) with persistent urinary incontinence were managed by diapers or a system of condom drainage. Thirty-nine patients (11.7%) were kept dry with intermittent catheterization at home, and long-standing use of indwelling catheters were required in the remaining 5 patients (1.5%). These results indicate that the lower level of activity, mobility and mental state tended to prevent the stroke patients from improvement of urinary disorders.


[A clinico-pathological study of inverted papilloma of the urinary bladder. Analysis of histogenesis]. A clinico-pathological study was conducted on 9 cases with inverted papilloma of the urinary bladder. 1. Clinical study: The incidence of inverted papillomas, when compared with transitional cell carcinoma of the urinary bladder, was much higher in men than in women in our study and in the literature dealing with this subject as well. Eight of 9 inverted papillomas were localized in the bladder neck. Cystoscopic examination revealed that all tumors were pedunculated and 8 of the 9 tumors had non-papillary surfaces. These clinical findings suggest that inverted papillomas localized in the bladder neck are very similar to posterior urethral polyps with prostatic type epithelium. Transurethral resection (TUR) was performed in all cases. Recurrence was not observed. 2. Pathological study: Inverted papillomas were classified into two types according to their histological patterns, determined by Hematoxylin-Eosin (H-E) staining. One pattern was glandular and the another was trabecular. Of the 9 cases, 2 were glandular, 5 were trabecular and the remaining 2 were a mixed type. Immunohistochemical staining with anti-prostate specific antigen antibody revealed 3 of the 9 tumors were stained positively, and these tumors were classified a glandular type. Inverted papilloma were classified into two patterns according to their histological patterns, determined by immunohistochemical staining with anti-keratin antibody, namely a bladder tumor pattern and a urethral tumor pattern. Inverted papillomas with a urethral tumor pattern were of the glandular type and included anti-PSA antibody positive staining tumors. These findings suggest that a portion of inverted papillomas may have arisen from neoplastic transformation of prostatic tissue.


[Results of total prostatectomy for treatment of prostatic cancer]. Between 1970 and 1989, total prostatectomy was performed in 31 patients with prostatic cancer at the Department of Urology, Tokyo Metropolitan Fuchu Hospital. These cases were composed of 4 cases of stage A, 8 cases of stage B and 19 cases of stage C. The surgical procedures were perineal prostatectomy in 25 cases, combined method of perineal and retropubic prostatectomy in 5 cases and transsacral prostatectomy in one case. Blood loss was 762 ml on the average. Blood transfusion was unnecessary in 15 cases all of whom underwent perineal prostatectomy. Endocrine or radiation therapy were administered after total prostatectomy to 23 or 13 cases, respectively. Postoperative complications included early postoperative death due to apoplexy in 1 cases, recto-vesical fistula in 1, bladder neck or urethral stricture in 9 (mild 7, severe 2) and urinary incontinence in 20 (mild 13, moderate 4, severe 3). Frequency and grade of urinary incontinence tended to become higher as the pathological stage progressed. The 5-year survival rates for clinical stage A and B, and C were 83% and 63%, respectively. We conclude that total perineal prostatectomy was less traumatic operation for prostatic cancer, and would be indicated in clinical stage A and B for radical operation and in stage C for one of the combination therapy.


[Flow cytometric analysis of the DNA content in the urinary bladder cancers treated by radical cystectomy and pre-operative irradiation]. The DNA ploidy of bladder cancers treated by radical cystectomy following pre-operative irradiation was analyzed by flow cytometry using paraffin embedded samples. The DNA ploidy and its changes by irradiation were studied. We used flow cytometry in 30 patients with transitional cell carcinoma of the bladder who received pre-operative irradiation (40 Gy in 24 patients, 20 Gy in 5 patients and 60 Gy in one) with follow-up for at least 3 years. Total 140 paraffin embedded samples (4.6 samples per one patient) were available. The effects of therapy were related to the DNA patterns before irradiation and to the DNA ploidy changes after irradiation. 1. Eight DNA diploid tumors and twenty-two DNA aneuploid ones were detected before irradiation. Although diploid group didn't change its DNA ploidy after irradiation, of 22 aneuploid tumors 18 were changed to DNA diploid and 4 were not changed in their ploidy. 2. The tumor eradicating effect of irradiation was shown to be higher (p < 0.05) in the diploid group (5 of 8, 63%) than in the aneuploid group (5 of 22, 23%). 3. Overall survival rates were discussed in 3 groups (A, B and C), the group A was 10 of tumor free and 3 diploid tumors after irradiation, the group B was 13 of aneuploid tumors which changed to diploid ones and the group C was 4 of persistent aneuploid tumors. Each of 5 year survival rate was 100% (A), 58% (B) and 0% (C). Overall survival for C group was significantly shorter than for other groups (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


[Urinary disturbance due to HTLV-1 associated myelopathy]. Patients with human T-cell lymphotropic virus type 1 associated myelopathy (HAM) have complaints of urinary disturbance frequently. Symptoms and urodynamic examinations were evaluated in untreated twenty-one patients with HAM. Although two cases (11%) had no urinary symptom, nineteen cases (89%) suffered from dysuria, pollakisuria, incontinence or urgency. The combination of irritative and obstructive urinary disturbance was a characteristic symptom in the HAM patients. In three cases the urinary symptoms preceded the gait disturbance which is a main symptom of HAM. In urodynamic study overactive bladder was found in fourteen cases (66%), although three cases (15%) showed underactive or acontractile bladder with disturbance of urinary sensation. There was no abnormal finding by urethral pressure profile (UPP), but detrusor sphincter dyssynergia (DSD) was revealed frequently by EMG. This typical dysfunction of the HAM patients was thought to be caused by destruction of the lateral column of the spinal cord.


[Clinical study of total parathyroidectomy and autotransplantation for secondary hyperparathyroidism]. From April 1983 to September 1991 total parathyroidectomy (PTX) and parathyroid autotransplantation were carried out in 27 patients for secondary hyperparathyroidism. Of these patients, 13 were males and 14 were females. Their average age was 43 years old and their mean duration of dialysis was 126.4 months. As preoperative clinical symptoms, bone pain was observed in 19 cases, joint pain in 18, decrease of height in 7, pruritus in 3, muscle pain in 2, red eyes in 2 and others in 2. As roentgenographic findings, subperiosteal bone resorption and skull-salt and pepper were demonstrated in 26 cases, rugger jersey spine in 15, soft tissue calcification in 11, and pathological fractures in 4. Four parathyroid glands were removed in 23 cases, three glands in 4. Serum calcium level decreased remarkably within 24 hours after parathyroidectomy in all cases. The average total weight of parathyroid glands was 4.48 g. The preoperative diagnostic accuracy of echogram was 94% and that of CT scan was 90%. The clinical improvement after PTX was excellent in 12 cases and good in 11. The roentgenographic improvement of skull and/or finger bone more than one year after PTX was excellent in 11 cases and good in 11. Judging from histopathological findings of the bone, the clinical and roentgenographic improvement was observed better in the osteitis fibrosa group than in mild group. A significant correlation was found between the level of preoperative c-PTH and the weight of resected parathyroid glands. The level of preoperative ALP correlated with intact-PTH and was higher in the osteitis fibrosa group than in the mild group.(ABSTRACT TRUNCATED AT 250 WORDS)


[Diagnosis of gonococcal urethritis and chlamydial urethritis by polymerase chain reaction]. A polymerase chain reaction (PCR) method was compared to standard methods (cultures for Neisseria gonorrhoeae and Chlamydia trachomatis and an enzyme-immunoassay for C. trachomatis) in diagnosis of gonococcal and chlamydial urethritis in 40 male patients with urethritis. Gonococcal urethritis was diagnosed by detection of a 206 bp DNA fragment amplified by PCR with N. gonorrhoeae-specific primers. Chlamydial urethritis was diagnosed by detection of a 242 bp DNA fragment amplified by PCR with C. trachomatis-specific primers. Gonococcal and chlamydial urethritis, gonococcal and non-chlamydial urethritis, non-gonococcal and chlamydial urethritis, and non-gonococcal and non-chlamydial urethritis were diagnosed in 8, 10, 14 and 8 patients, respectively, by the PCR method. In 9 patients with gonococcal and chlamydial urethritis, 10 with gonococcal and non-chlamydial urethritis, 12 with non-gonococcal and chlamydial urethritis, and 9 with non-gonococcal and non-chlamydial urethritis, diagnosed by the standard methods, the coincidence rates of the PCR to the standard methods were 78% (7/9), 90% (9/10), 100% (12/12), and 89% (8/9), respectively. The overall coincidence rate between the PCR and the standard methods in diagnosis of urethritis were high (90%). In addition, N.gonorrhoeae and C.trachomatis could be simultaneously detected from one urethral sample in approximately 6 hours by means of the PCR. Thus, the PCR method could clinically be applied and would offer several advantages to diagnosis of urethritis, compared to the standard methods.


[Localization of androgen receptor in male sex organ, accessory sex organs and external genital skin]. Previously, we established an anti-androgen receptor (AR) monoclonal antibody. Using the antibody, we investigated immunohistological AR localization in human testes, epididymides, seminal vesicles and scrotal skins. The testes, epididymides and scrotal skins were obtained from a prostate cancer patient without pre-hormonal therapy undergoing bilateral orchiectomy. The seminal vesicles were obtained from a bladder cancer patient undergoing radical cystectomy. The tissues were immediately frozen in liquid nitrogen and kept at -80 degrees C until used. Cryostat-frozen sections were cut at 5 microns and stained by an indirect method. We obtained the following results. 1) In the testes, nuclei of Leydig cells were stained though Sertoli cells were not stained. AR localization in Leydig cells which produce testosterone suggests autocrine or intracrine mechanism in the testis. 2) In the epididymides, nuclei of epithelial cells of epididymal ducts were stained, while muscles and connective tissues were not stained. In the seminal vesicles, nuclei of glandular epithelial cells were stained. 3) In the scrotal skins, the cells of squamous cell layer have positive stainings. The cells in the upper portion of squamous cell layer were stained more intensely than the cells in the lower portion. The basal layer was not stained. The cells of the outer root sheath of hair follicles in the scrotal skins were also stained. 4) In androgen target organs, AR-positive cells and AR-negative cells were mixed in the epithelium of a glandular duct, which suggests heterogeneity of AR localization in the androgen target organs.


[A study on urinary free gamma-carboxyglutamic acid in patients with idiopathic urinary calcium stone]. Currently, urinary excretion of free gamma-carboxyglutamic acid (gamma-gla.), a terminal amino acid degraded from gamma-gla. containing protein including bone Gla. Estimated to be a more specific marker for bone metabolism and useful clinically rather than urinary excretion of hydroxyproline. In addition, serum levels of BGP have proved to be a significantly valuable indicator for bone metabolism, especially for process of bone formation, in recent studies. Therefore, we measured these parameters in 40 patients with idiopathic urinary calcium (Ca) stone and investigated bone metabolism in those patients. However, in majority of cases studied, urinary levels of gamma-gla. as well as that of hydroxyproline proved to be definite difference from that in healthy subjects (n = 12) and failed to suggest the presence of abnormality in bone turnover in the background of stone formation. Urinary excretion of hydroxyproline were 6.68 +/- 3.89 micrograms/mg.Cr in the patients and 6.95 +/- 3.08 micrograms/mg.Cr in healthy subjects. Urinary excretion of gamma-gla were 55.0 +/- 15.8 nmol/mg.Cr in the patients and 47.2 +/- 7.3 nmol/mg.Cr in healthy subjects.


[A case of renal hemangiopericytoma].

[A case of renal hemangiopericytoma]. A 27-year-old female was referred with an abdominal mass. Examination revealed a non tender firm mass in the right flank and hypertension (200/100 mmHg). An angiomyolipoma was suspected on computed tomography and arteriography and a radical nephrectomy was performed. On cut section, the kidney was occupied by a well-capsulated, grayish tumor measuring 10 x 9 cm. Pathological diagnosis was a renal hemangiopericytoma without involvement of the capsule. Her blood pressure has normalized after the operation. She has no evidence of recurrence after 18 months' follow-up.


Cardiopulmonary bypass in the successful resuscitation of a 28-year-old woman with cardiac arrest. This patient remained hospitalized for several weeks, and her stay was relatively uneventful. She extubated herself 2 days after admission, after an operative procedure to remove the cannulas and repair the right femoral cutdown site. A fasciotomy of her right calf was done for compartment syndrome. The patient had minor neurologic deficits of short-term memory loss and spatial depth perception loss. These deficits, attributed to postresuscitative hypoxia, eventually resolved. Extensive cardiac testing performed to pinpoint the underlying cause of her cardiac dysfunction were inconclusive. Because no cause was found, an automatic implantable cardiodefribrillator was recommended to prevent future cardiac events. The patient agreed and the device was implanted before her discharge. With expert occupational therapy, physical rehabilitation, nursing care, and medical treatment the patient regained her previous level of functioning. Her October wedding was postponed to December, but she was able to return to work in November 1990.


The problems of intrahospital transfer of patients with trauma and one solution: the "Trauma Transfer Backpack". With long stays for computed tomographic scans and x-ray exams and long trips to ICUs, patients with trauma may need extra fluids, drugs, or equipment outside the emergency department. Putting everything in a backpack saves time, leaves the nurse's hands free, and does not take up room on the stretcher.


A successful prehospital quality assurance program in compliance with New York State regulations. Reviews provide valuable information and insight about the overall status of community-wide emergency medical services. Specific areas of concern are readily identified and can be addressed within a reasonable time by the group responsible for instituting corrective actions.


Treating cancer-related pain in the emergency department: the emergency nurse's role. Ask for and believe the patient's report of pain, use a preventive approach, combine opioids and nonopioids when possible, and consider adjuvant drugs for neuropathic pain not relieved by an adequate trial of opioids and NSAID. Remain a patient advocate through careful assessment and reassessment of the patient and informative collaboration with the physician and other colleagues. Anticipate and treat side effects, and identify and address pain myths held by patients and families that interfere with sound pain management practices. Establish mutually set goals and direct the patient to necessary follow up. Emergency nurses can do much to alleviate unnecessary suffering and improve quality of life for patients with cancer who come to the emergency department for help.


The Glasgow Coma Scale: do it and do it right. Monitoring of GCS parameters is an essential part of the initial and ongoing assessment of patients with trauma. It is important that health care professionals recognize the limitations of the GCS and consistently and correctly apply the scoring criteria when assessing patients.


The Oregon Health Plan.

The Oregon Health Plan. The Oregon Health Plan is an innovative approach to providing a basic level of health care coverage for all citizens. A major component of the plan provides for prevention of illness. True, there is rationing of health care in the plan, but without such a plan the uninsured are currently limited in access to care. The plan may be flawed, but this cannot be known until it has been tried and monitored. The reality is that health care dollars are diminishing, and alternative approaches to health care are going to have to be investigated. This plan is truly a starting point for the development of a national health care policy. Let us hope that the federal government will allow Oregon to begin this bold experiment, and perhaps benefit the disenfranchised in this country.


When is cortisol a mineralocorticoid?

When is cortisol a mineralocorticoid? (1) Decreased 11 beta-OHSD activity permits binding of cortisol to the Type I (mineralocorticoid) receptor in humans, thereby producing spironolactone-inhibitable Na+ retention, hypokalemia and hypertension, the syndrome of apparent mineralocorticoid excess (AME). (2) Blockade of either the Type I receptor with spironolactone or the Type II (glucocorticoid) receptor with RU-486 does not consistently abolish the effects of stress level cortisol on Na+ retention and hypertension in acute studies in normal humans, suggesting the existence of an additional glucocorticoid receptor. (3) Enhanced glucocorticoid 6 beta-hydroxylation could play an etiologic role in certain hypertensive syndromes. (4) Both decreased 11 beta-OHSD and increased 6 beta-OHase are candidates as intermediate phenotypes for the remote phenotype essential hypertension.


Autocrine secretion of transforming growth factor-beta in cultured rat mesangial cells. Transforming growth factor-beta (TGF-beta) recently has been shown to modulate mesangial cell growth and to stimulate mesangial matrix synthesis by mesangial cells. Here we examined whether mesangial cells expressed TGF-beta mRNA and secreted mature TGF-beta, and we investigated the role of TGF-beta in mesangial cell growth. Cultured rat mesangial cells expressed 2.5 kb TGF-beta mRNA, and removal of fetal calf serum (FCS) for two days decreased the TGF-beta mRNA level, which was then stimulated by re-addition of 17% FCS reaching the maximum at nine hours. 12-O-tetradecanoyl phorbol-13-acetate (TPA), one of the phorbol esters, markedly increased the mRNA level and reached the maximum at six or nine hours. Immunoblot analysis of the conditioned media using specific anti-TGF-beta 1 antibodies revealed single 12.5 kDa proteins, the size compatible with mature TGF-beta subunits. By means of bioassay using CCL-64 cell line, TGF-beta production rate by mesangial cells was estimated to be 22.1 +/- 6.5 (mean +/- SD) ng/10(6) cells/24 hours, 96% of which was in latent forms. Exogenously added TGF-beta inhibited mesangial cell growth at 10 pM or higher. Moreover, addition of anti-TGF-beta neutralizing antibodies augmented mesangial cell growth, indicating that the secreted TGF-beta actually exerted a growth-inhibitory action. In summary, mesangial cells produce and secrete substantial amounts of TGF-beta but mostly in latent forms, and the secreted TGF-beta may regulate mesangial cell growth and differentiation. We conclude that TGF-beta may function as an autocrine factor in mesangial cells.


Deletions of the COL4A5 gene in patients with Alport syndrome. Mutations in the COL4A5 gene encoding the alpha 5 chain of type IV collagen have been found in linkage with X-chromosomal Alport syndrome (AS). To identify COL4A5 mutations in patients from Germany with clinically defined AS, DNA from 20 unrelated patients was analyzed by conventional Southern blotting. By using full length alpha 5(IV) cDNA probes, large COL4A5 deletions could be detected in two patients. In one case, a 34 kb deletion affecting the 14 most 3' exons of the gene was observed. The second patient harbored a complete COL4A5 deletion. In both cases, functional alpha 5(IV) mRNA was unlikely to be present. Clinically, both patients developed end-stage renal failure before age 30. Furthermore, they had characteristic retinal flecks, and sensorineural hearing loss with typical changes on the audiogram. The patient with the complete deletion of COL4A5 lost the renal allograft due to an anti-GBM mediated glomerulonephritis.


Prostaglandins protect kidneys against ischemic and toxic injury by a cellular effect. The ability of prostaglandins to protect the kidney against ischemic and toxic renal injury was evaluated by in vivo and in vitro models of renal ischemia. The prostaglandin E1 analogue, misoprostol, was found to provide significant protection against ischemia-induced renal dysfunction in rats subjected to 40 minutes of renal artery occlusion. Misoprostol-treated rats had glomerular filtration rates almost threefold greater than control animals, although renal blood flow and renal vascular resistance were not significantly different. Improved tubular function was reflected in a lower fractional excretion of sodium and a higher urine-to-plasma creatinine ratio. Misoprostol also provided similar protection in a model of toxic renal injury produced by mercuric chloride. In an in vitro model employing primary cultures of proximal tubule epithelial cells subjected to hypoxia and reoxygenation, misoprostol limited cell death. Posthypoxic cells had apical membrane disruption and loss of microvilli when examined by transmission electron microscopy. These changes were not seen in misoprostol-treated cells. The "cytoprotective" effect was also produced by prostaglandin E2 and prostacyclin. The ability of prostaglandin E to protect against toxic and ischemic renal injury did not appear to be due to an antioxidant effect because misoprostol did not limit lipid peroxidation in vivo and did not protect against oxidant injury by tert-butyl hydroperoxide in vitro. Although the exact mechanism of prostaglandin protection was not revealed, these studies demonstrate that prostaglandins protect renal tubule epithelial cells from hypoxic injury at the cellular level independent of hemodynamic factors or inflammatory responses. Such a "cytoprotective" effect of prostaglandins may be a generalized phenomenon since it has also been demonstrated in gastrointestinal epithelium.


Anti-DNA antibodies can bind to the glomerulus via two distinct mechanisms. It is generally assumed that antibodies to double stranded DNA (anti-DNA) play a pivotal role in the pathogenesis of SLE nephritis. Recently, we reported that anti-DNA antibodies can bind to heparan sulphate proteoglycan (HSPG), a constituent of the glomerular basement membrane (GBM), via histones and DNA. We postulated that these histone/DNA/anti-DNA complexes can bind via their histone part to the glomerulus in vivo. To test this hypothesis we performed in vitro binding studies with isolated GBM loops and renal perfusion studies in the rat using histones, DNA and an anti-DNA monoclonal antibody (mAb) with high avidity for dsDNA. A strong granular binding of anti-DNA mAb to isolated GBM loops occurred via histones and DNA and a moderate granular binding was found via DNA alone. Anti-DNA mAb alone did not bind to the GBM loops. After perfusion of histones, DNA and immediately thereafter anti-DNA, we found with immunoelectron microscopy (IEM) a strong binding to endothelial cells in the glomerulus and to a lesser extent in the GBM. When the anti-DNA mAb was injected i.v. one hour after perfusion of histones and DNA, we observed a strong fine granular binding to the capillary wall by immunofluorescence (IF) in a membranous pattern along with some minor mesangial deposits. After perfusion of DNA alone followed by anti-DNA mAb, binding in the glomerulus was less than with histones and DNA, and was more restricted to the mesangium. No direct binding to the glomerulus was observed after perfusion with anti-DNA mAb alone, histones and anti-DNA mAb, or histones, DNA and a control mAb.(ABSTRACT TRUNCATED AT 250 WORDS)


High resolution localization of angiotensin II receptors in rat renal medulla. The cellular localization of angiotensin II (Ang II) receptors in the inner stripe of the outer medulla of the rat kidney was investigated by using high resolution light and electron microscopic autoradiography. Fresh tissue blocks from the inner stripe of the outer medulla were incubated with 125I-[Sar1, Ile8] Ang II and prepared for microscopic autoradiography. At the light microscopic level, 125I-[Sar1, Ile8] Ang II was found to penetrate into the tissue and to bind specifically to sites outlining renal tubules and vasa recta bundles. Electron microscopic autoradiography revealed that silver grains were detected over interstitial cells located between the tubules and components of the vasa recta bundles, but no silver grains were detected overlying the cells of the thin descending or thick ascending limbs of the loop of Henle, the collecting ducts, the vasa recta, or other blood vessels. These interstitial cells contained abundant endoplasmic reticulum, microfilaments, occasional lipid droplets and extensive cytoplasmic processes which closely related to the basement membranes of the vasa recta and loops of Henle. The cells therefore closely resemble type 1 interstitial cells. Since Ang II binding sites are absent in the inner medulla, the cells labelled by this technique must be a subset of type 1 interstitial cells, distinct from the typical lipid-laden interstitial cells most abundant in the inner medulla. These findings demonstrate that type 1 interstitial cells are the primary sites for a high density of Ang II receptors located in the inner stripe of the outer medulla.


Dyslipoproteinemia in diabetic renal failure. Plasma concentrations of lipids and apolipoproteins (Apo) were determined in 34 patients with long-standing type I (insulin-dependent) diabetes mellitus. Twenty-four patients had renal insufficiency (GFR 4 to 55 ml/min) due to diabetic nephropathy, while 10 patients had no clinical signs of nephropathy. Results were compared with those in 42 non-diabetic patients with comparable degree of renal insufficiency and with asymptomatic control subjects. Diabetic patients without nephropathy had plasma lipid and apolipoprotein concentrations similar to those of the control subjects. Diabetic patients with renal insufficiency had a significant increase in triglycerides (TG) and, to a lesser extent, in total cholesterol (TC). The patients also had reduced levels of ApoA-I and ApoA-II, increased levels of ApoC-II and ApoC-III, while increases in levels of ApoB and ApoE were statistically significant in patients with GFR < 20 ml/min. These lipids and apolipoprotein abnormalities were accentuated with decreasing renal function. The reduction in the ApoA-I/ApoC-III ratio characteristic of renal insufficiency was found in normo- and hyper-TG diabetic patients with nephropathy; this ratio was correlated with the GFR levels. Patients with higher HbA1C values had higher levels of ApoC-II and ApoC-III. The findings in the diabetic patients corresponded with those in non-diabetic patients with renal insufficiency. However, diabetic patients had higher ApoC-III and ApoE levels. The abnormalities of lipid metabolism in diabetic renal insufficiency seem to reflect primarily metabolic impairments characteristic of renal insufficiency, but may be further accentuated by the diabetic state and the metabolic control.


Percutaneous transvenous angioplasty in the treatment of vascular access stenosis. This study was undertaken to evaluate percutaneous transvenous angioplasty (PTVA) for the treatment of all types of vascular access stenosis in a large population of dialysis patients. Stenoses were identified by venography in patients who met a set of clinical criteria indicating the need for evaluation. The lesions were classified by location and type. Data were collected prospectively and analyzed separately for each lesion type. A total of 536 PTVA procedures was performed in 285 patients. This included 107 cases of long venous stenosis (> 6 cm) and 149 cases of mid-graft stenosis. In the total group, an initial success rate of 94% was obtained (80% or greater dilatation). A decrease in VPm (venous pressure measured on dialysis) of 35.9%, 32.4%, and 22.6% was seen at one week, one month, and three months, respectively. At 90 days, 180 days, and 360 days 90.6%, 61.3%, and 38.2%, respectively, of the treated grafts were continuing to be patent and functional with no need for repeat PTVA treatment. Repeat treatments for recurrent lesions were as successful as the initial treatment. It is concluded that vascular access stenosis can be easily diagnosed and that all categories of stenotic lesion can be effectively treated with PTVA.


Effect of intraperitoneal neostigmine on peritoneal transport characteristics in CAPD. Lymphatics have been suggested to play a major role in the absorption of dialysate, which consequently affects the adequacy of peritoneal dialysis. Neostigmine has been found to decrease lymphatic absorption in rats, presumably by causing constriction of the lymphatic stomata. We investigated the effect of neostigmine on seven continuous ambulatory peritoneal dialysis (CAPD) patients in a prospective study. We performed modified peritoneal equilibration tests both with and without intraperitoneal neostigmine in a random order. Radiolabeled albumin (0.8 mg) was added to 2 liters of dialysate +/- 2.0 mg neostigmine. We evaluated ultrafiltration and creatinine, phosphate, and urea clearances. The dialysate bag and the peritoneum were scanned at the initiation and conclusion of the four-hour dwell period. We found no change in ultrafiltration, residual volumes, creatinine, phosphate and urea clearances, or albumin recovered. Of the seven patients exposed to neostigmine, four had diarrhea, abdominal cramps, nausea, and vomiting. In conclusion, we found that 2 mg i.p. neostigmine did cause significant side-effects and did not alter transport characteristics in CAPD patients.


Clinical and pathologic features of fibrillary glomerulonephritis. A diagnosis of fibrillary glomerulonephritis was made in 31 renal biopsies from 28 patients on the basis of the electron microscopic identification of glomerular deposits of randomly arranged fibrils that resembled amyloidosis but were larger. This accounted for approximately 1% of all nontransplant renal biopsy diagnoses. Renal biopsy specimens with parallel arrays of 30 nm to 50 nm microtubules (that is, immunotactoid glomerulopathy) were not included in the study. The patients had a mean age of 49 years with a range of 21 to 75. The male to female ratio was 1:1.8 and the ratio of Whites to Blacks was 8.3:1, which differs from the 3:1 ratio in our overall biopsy population. All patients had proteinuria (mean 6.0 g/day), and most had hematuria and renal insufficiency. After a mean follow-up of 24 months, there was 48% renal survival. The light microscopic appearance of the fibrillary glomerulonephritis was quite varied. Capillary wall thickening and matrix expansion were the most frequent alterations. Nineteen percent of specimens had crescents. Morphometric ultrastructural analysis demonstrated a mean fibril diameter of 22.4 +/- 7.4 nm. Immunofluorescence microscopy revealed that IgG was the dominant and often the only immunoglobulin class in immune deposits, and subclass analysis revealed that IgG4 was the dominant or exclusive subclass in all specimens tested. We hypothesize that the relatively homogeneous nature of the immunoglobulin in the immune deposits is the basis for the fibril formation.