[Spontaneous cerebrospinal fluid otorrhea in association with an aqueductal stenosis. Case report].
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Biomedical subjects
Publications and source records attributed to M Takase.
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Movement of fluorescein and fluorescein glucuronide, a fluorescent metabolite of fluorescein, across the isolated iris-ciliary body of the albino rabbit was determined under short-circuit conditions using a modified Ussing's chamber. The permeabilities of this tissue to these dyes were calculated. The outward permeability (from the aqueous to the stromal side) of the iris-ciliary body preparation averaged 6.63 +/- 0.86 for fluorescein and 1.51 +/- 0.47 X 10(-6) cm/sec for fluorescein glucuronide, and the inward permeability (from the stromal to the aqueous side) was 1.68 +/- 0.41 for fluorescein and 1.37 +/- 0.77 X 10(-6) cm/sec for fluorescein glucuronide, respectively. Application of probenecid or ouabain decreased the outward permeability of fluorescein, but it had no significant effect on the fluorescein glucuronide movement. Application of 10(-5) M 2,4-dinitrophenol showed no significant effect on the fluorescein or fluorescein glucuronide movement, but application of 5 X 10(-4) M 2,4-dinitrophenol decreased the outward fluorescein transfer, which was also markedly suppressed by incubation at 0 degrees C. It is possible that an active transport mechanism is involved in the outward fluorescein movement across the iris-ciliary body, while the inward movement of fluorescein and also the fluorescein glucuronide movement across this tissue is mainly by passive diffusion.
In an experiment on skin rash caused by diapers, adult skin was used to compare the effects of disposable diapers (A; Pampers), conventional disposable diapers (B), and cotton diapers. Pieces of each type of diaper measuring 2 X 2 cm and containing 0.2 ml saline solution were pasted on forearm skin for 5 h. Water content of the corneum was measured with an impedance meter 1 h after the pieces were removed. Results were excellent for diapers A and B: there were no significant differences observed in water content of the corneum when A and B were compared with conventional cotton diapers. The advantages of disposable diapers were confirmed in infants.
The corneal endothelial permeability coefficient (Pac) for fluorescein and fluorescein glucuronide was determined in ten normal young volunteers. After oral administration of fluorescein, the apparent concentrations of both dyes in the corneal stroma and the anterior chamber were measured by differential fluorometry. The apparent dye levels calculated directly from the in vivo fluorometric measurements were converted to the true ones, based on the result of a normalization experiment performed in rabbit eyes. The value of Pac averaged 5.44 +/- 1.77 X 10(-4) cm/min for fluorescein and 3.77 +/- 1.10 X 10(-4) cm/min for fluorescein glucuronide (mean +/- SD, N = 20); the former was significantly greater than the latter (paired t-test, P less than 0.001). The aqueous-cornea distribution ratio was 0.50 +/- 0.14 for fluorescein and 0.66 +/- 0.16 for fluorescein glucuronide; the latter was significantly greater than the former (paired t-test, P less than 0.001). It was suggested that the previously reported values of Pac for fluorescein in the human eye were underestimates.
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Comparative studies of fluorescein and fluorescein glucuronide were carried out. Binding to human serum protein was studied using an Amicon MPS-3 ultrafiltration unit; it averaged 63% for fluorescein glucuronide and 85% for fluorescein. Intracameral penetration of both compounds was studied in the human eye, and the concentration changes of both compounds in the plasma ultrafiltrate and in the anterior chamber were analyzed, based on Davson's equation. The coefficient of entry into the anterior chamber (ki) was 0.018 +/- 0.007 h-1 (mean +/- SD, n = 10) for fluorescein glucuronide and 0.054 +/- 0.033 h-1 for fluorescein, and the former was significantly lower than the latter (P less than 0.005). The rate of loss from the vitreous (kv) was studied by injecting each compound into the vitreous of the pigmented rabbit and following the fluorescein intensity changes in it. It was 0.042 +/- 0.008 h-1 (mean +/- SD, n = 8) for fluorescein glucuronide and 0.17 +/- 0.01 h-1 for fluorescein, and the former was significantly smaller than the latter (P less than 0.001). Intraperitoneal injection of probenecid significantly decreased the kv of fluorescein but had little effection that of fluorescein glucuronide. It was suggested that fluorescein glucuronide is lost from the vitreous mainly by a passive mechanism.
A high incidence of vaginal adenosis-like lesions (ADL, 67%) was found in 30-day-old offspring of ICR/JCL mice given 4 daily subcutaneous injections of 2,000 micrograms diethylstilbestrol (DES) on days 15-18 of gestation. The prenatally DES-exposed mice and the controls ovariectomized at 10 days of age were given 5 daily subcutaneous injections of 10(-4), 10(-3), 10(-2), 10(-1), or 1 micrograms 17 beta-estradiol (E2), respectively, starting at 25 days of age. ADL was never observed in the age-matched controls given prepubertal injections of any E2 dose. In contrast, high incidences of ADL (63-100%) were found in the vaginal fornix and upper vagina of 30-day-old DES mice receiving prepubertal injections of 10(-3)-1 micrograms E2/day, whereas in DES mice given prepubertal injections of the vehicle alone and a lower daily dose of 10(-4) micrograms E2, incidences were nil and 25%, respectively. Mitotic figures were found in the columnar epithelium with ADL, although the rate was lower than in the ADL-freed stratified epithelium. It is suggested, therefore, that an ovarian hormone (probably estrogen) participates in the prepubertal induction of ADL in DES mice.
Pregnant ICR/JCL mice were given either four daily subcutaneous injections of 20-2000 micrograms diethylstilbestrol (DES)/day or a 4-day intravenous infusion of 20-200 micrograms DES/day starting on Day 15 of gestation. Female mice were injected with 0.01-50 micrograms DES/day for 5 days starting on the day of birth. Females given oil injections during the neonatal period and offspring of mothers given injections of an infusion of respective vehicles alone served as controls when corresponding ages were attained. Incidence of adenosis-like lesions (ADL) in the vaginal epithelium and stratification of the uterine epithelium (UST) were determined in both offspring and neonatally exposed mice at 30 days of age. Injections of 0.1-50 micrograms DES/day during the neonatal period induced ADL in the fornical epithelium of vagina (36-70%), but not UST. A high incidence of ADL (80-88%) was found in the fornical and upper-vaginal epithelia in offspring of mothers given injections of 200-2000 micrograms DES/day, and UST was encountered in 38-70% of these mice. Offspring of mothers given an infusion of 20 micrograms DES/day had low incidences of ADL (11%) and UST (22%), whereas offspring of mothers infused with 200 micrograms DES/day exhibited high incidences of ADL (71%) and UST (86%). In offspring of mothers given injections of 2000 micrograms DES/day, ADL appeared in the fornical and upper-vaginal epithelial as early as 15 days of age. Thus, the present study revealed that ADL and UST occur at a high incidence in infantile mice exposed prenatally to high doses of DES. Previous studies failed to detect such effects perhaps due to the strain of mice, methods, duration, and/or dose of DES used.
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Transport of timolol and befunolol in the anterior uvea of the albino rabbit was studied in vitro. Also, the mode of timolol elimination from the living eye was investigated. The isolated iris-ciliary body incubated at 37 degrees C accumulated 14C-timolol and 14C-befunolol against the concentration gradient, and the tissue-to-medium ratio was 5.45 +/- 0.29 and 5.46 +/- 0.44, respectively. The accumulation of both drugs was significantly suppressed by incubation at 0 degrees C and also by pretreatment with ouabain or cyanine but not with probenecid. The relationship between the initial velocities of accumulation and medium drug concentrations conformed with saturation kinetics, indicating the presence of mediated transport of these drugs. The apparent Km was 1.08 X 10(-6) mole per liter for timolol and 8.00 X 10(-7) for befunolol, and the Vmax was 5.46 X 10(-9) mole per g per hour for timolol and 1.52 X 10(-8) for befunolol. A mixture of 14C-timolol and 3H-sucrose was injected into the center of the vitreous cavity of the living rabbit. Timolol was lost from the vitreous at a rapid rate of about 36% per hour, while sucrose was lost very slowly, at about 5% per hour. Thus it was thought that an energy-requiring carrier-mediated transport system is operative in the anterior uvea of the albino rabbit, and that this would account for the rapid removal of the beta-blockers out of the eye.
Previous reports concerning the acute effects of topical forskolin on the intraocular pressure (IOP) and the aqueous humor dynamics in human eyes gave conflicting results, and this led us to reevaluate the effects of this drug in a total of 20 young normal Japanese volunteers. Fifty microliter of 1% forskolin was instilled in one eye, and the vehicle to the fellow control eye. After two instillations of the drug at an interval of 5 minutes, the maximum IOP fall of 2.4 +/- 1.3 mmHg occurred after 1 hour; a single instillation had no significant effect. The effects on the aqueous flow rate and iris permeability factor were determined by the oral fluorescein method. Two instillations of the drug reduced the aqueous flow rate to 87 +/- 7% of the control, while the iris permeability factor was increased to 114 +/- 11% (mean +/- SD, N = 10, P less than 0.005). Pretreatment with topical 0.25% 1-timolol in both eyes 1 hour prior to the drug administration did not significantly alter the forskolin effects.
Twenty patients with essential hypertension were given 400 mg acebutolol once daily for 24 weeks. In order to study if side effects resembling the "Practolol syndrome" developed, ocular effects were sought and antinuclear antibody (ANA) in blood was assessed before and after treatment. ANA was negative both before and after the study in 17 patients; in one patient ANA was positive, but the titre (1:10) was low and did not change during the study. Acebutolol produced no undesirable effects on cornea, conjunctiva or lens. During acebutolol treatment, tear secretion was reduced but tear lysozyme concentration was not significantly altered. Overall, acebutolol had no undesirable action similar to the practolol-induced syndrome, nor did it cause such common clinical ocular symptoms such as dry or gritty eyes.
The effects of S-596 and coarteolol, new beta-adrenergic blockers, were studied by means of the oral fluorescein method. Transfer coefficients by diffusion, kd.pa, and by flow, kfa, were estimated in a total of 11 normal young volunteers, in whom the drug was instilled in one eye and the placebo in the fellow eye. With 0.5% dl-S-596, kd.pa increased to 124 +/- 9% (mean +/- SD) and kfa decreased to 67 +/- 10% of the control eye. With 1% dl-carteolol, kd.pa increased to 121 +/- 4%, and kfa decreased to 84 +/- 11% of the control eye. Both S-596 and carteolol increased iris permeability and decreased the aqueous flow rate significantly. In a group of 13 cases, intracapsular extraction of senile cataract was carried out with postoperative routine instillations, and in another group of 7 cases, it was carried out with additional topical flurbiprofen, a new nonsteroidal anti-inflammatory drug. Flurbiprofen ophthalmic solution (0.1%) was instilled 3, 2, 1, and 0.5 h before the surgery and 4 times a day postoperatively. On the 6th postoperative day, a fluorophotometric study was carried out using oral fluorescein, and a coefficient that reflects the permeability of the blood-aqueous barrier after the cataract surgery was calculated. It was found that additional topical flurbiprofen considerably suppresses the disruption of the blood-aqueous barrier.
Two neonates with tuberous sclerosis are reported. The patients presented convulsive seizures 30 mins or 5 days after birth. Computer-assisted cranial tomography (CT) on admission showed typical paraventricular calcifications in Case 1 and a calcified mass in Case 2. In addition to the CT findings, the diagnosis was made on the basis of the depigmented skin, and the mother with tuberous sclerosis in Case 1 and the pathological findings after surgery in Case 2. The importance of CT as a diagnostic procedure for this disease within 1 wk after birth is emphasized.
In male offspring of mice given a continuous intravenous infusion of 24 IU/day hCG from days 15 to 19 of gestation (hCG-primed mice), the number of Leydig cells/testis at 15 days of age was similar to the value at 10 days, whereas the cells were decreased in number in the controls at 15 days. Mitotic rate of the interstitial tissue in 30-day-old, hCG-primed mice was lower than in the controls. In seminiferous tubules of hCG-primed mice, intratubular spaces were formed at 15 days, while the spaces in the controls were observed at 30 days. Various disorganization of the germinal epithelium occurred in some tubules of hCG-primed mice at 30-90 days. Spermatogenesis was impaired in the damaged tubules. Female hCG-primed mice showed a slightly longer estrus (24 IU/day), a higher frequency of estrus and larger number of total estrus days (120 IU/day) than those in the controls. Ovaries of 160-day-old, hCG-primed mice (24 IU/day) contained normal follicles more than those in the controls. Corpora lutea decreased in number in both groups of hCG-primed mice, showing a lower corpus-luteum occupancy. These findings suggest the occurrence of a slight degree of persistent-estrus syndrome in hCG-primed female mice.
Subconjunctival injection of 0.2 ml of the following solutions was carried out once a day for two weeks in the albino and pigmented rabbit: commercial 0.5% timolol or 1% befunolol ophthalmic solutions, both containing benzalkonium chloride, and also these drug solutions containing no preservative, ophthalmic base solutions containing benzalkonium chloride, physiological saline solution or phosphate buffer solution. One week after daily injections of the commercial drug solutions or base solutions with benzalkonium chloride, the electroretinogram (ERG) showed a marked reduction in the a- and b-wave amplitudes in the pigmented rabbit, but the ERG changes were slight in the albino rabbit. After two weeks of injections, histological studies of the pigmented rabbit eyes revealed retinal detachment, visual cell loss and atrophy of the retinal pigment epithelium and choroid; the changes in the albino rabbit eyes were minimal. Injections of the beta-blockers containing no benzalkonium resulted in no significant changes in the ERG or in the tissue structures of all rabbits. Injections of only physiological saline or phosphate buffer had no deleterious effects. Therefore, the ocular toxicity of the beta-blockers was thought to be minor and the toxic effects seen in this study were thought to be due to benzalkonium chloride, which possibly accumulates in the ocular pigments.
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