Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038379 (strabismus)
 9,317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Squamous cell carcinoma was the most common neoplasm found in a review of case records of 21 cats with histopathologically confirmed orbital neoplasms. Other neoplasms found were lymphosarcoma, undifferentiated carcinoma, malignant melanoma, adenocarcinoma, fibrosarcoma, chondroma, and hemangiosarcoma. Three (14%) neoplasms were primary, 15 (71%) were secondary, invading the orbit from adjacent tissues, and 3 (14%) were a manifestation of multicentric disease. The most common clinical sign was exophthalmia, followed by chronic epiphora, enophthalmia, and strabismus. Mean survival time after diagnosis was 1.9 months. Ten cats were euthanatized at the time of diagnosis because of extensive disease. Mean survival time of the other 11 cats was 4.3 months. Skull radiography was helpful in diagnosing orbital neoplasms in 8 of 11 cats that had invasion of the orbit by adjacent neoplasms.
 ...
PMID:Orbital neoplasms in cats: 21 cases (1974-1990). 142 40

Over a six-year period, between 1984 and 1990, 622 patients with basal cell and squamous cell carcinoma of the eyelids were examined at our institution. Thirteen patients had orbital invasion at initial examination. The average age of patients at orbital invasion was 75.8 years. Ten patients were men, eight of whom had basal cell carcinoma and two of whom had squamous cell carcinoma. Most patients had an orbital mass and incomitant strabismus at initial examination. Invasive basal cell carcinoma developed in 11 patients, and squamous cell carcinoma developed in two patients. Ten patients were treated for cutaneous carcinoma at the site of invasion before examination at our institution. The average duration between onset of a cutaneous lesion and our examination for orbital invasion was 9.8 years for basal cell carcinoma and one year for squamous cell carcinoma. Radiologic and histopathologic features were reviewed. The clinical characteristics of these patients were reviewed and orbital exenteration was recommended to all 13 patients. Nine patients underwent exenteration and four refused the operation.
 ...
PMID:Clinical characteristics associated with orbital invasion of cutaneous basal cell and squamous cell tumors of the eyelid. 155 Jan 79

A 10-year-old boy was followed up from the stage of biopsy-proven dysplastic conjunctival mass to carcinoma in situ. This carcinoma was managed by radical excision and lamellar sclerokeratoplasty. To our knowledge, this case represents the first reported successful management of conjunctival carcinoma in xeroderma pigmentosum.
J Pediatr Ophthalmol Strabismus
PMID:Lamellar sclerokeratoplasty of epibulbar tumor in xeroderma pigmentosum. 234 14

A patient with rapidly progressive metastatic gastric carcinoma developed diplopia and diminished adduction of the right eye. The right medial rectus muscle belly was enlarged, as shown by computed tomography. This case is unusual, because gastric carcinoma comprises only 1% of orbital metastases and less than 5% of all orbital metastases localize to extraocular muscle.
J Pediatr Ophthalmol Strabismus
PMID:Acquired divergent strabismus: presumed metastatic gastric carcinoma to the medial rectus muscle. 291 14

A 15-month-old boy with rapidly progressive proptosis had an unusual malignant germ-cell tumor of the orbit and nasopharynx identified as an endodermal sinus tumor (yolk-sac carcinoma). Endodermal sinus tumors arising in extra gonadal locations are highly malignant and generally lethal. The boy was treated with radiation and three-drug chemotherapy and has survived more than eight years.
J Pediatr Ophthalmol Strabismus
PMID:Endodermal sinus tumor (yolk-sac carcinoma) of the orbit. 717 25

Fourteen patients with tuberculosis of the orbit and lacrimal gland seen over a period of 20 years have been presented. The majority of them were between the ages of 4 to 15 years. Males were affected twice as frequently as females. Left side was affected four times as frequently as the right side. There were eight patients of periostitis of orbital margin, one patient of dacryoadenitis, three patients of tuberculoma of orbital tissues, and two patients of tuberculoma of maxillary sinus. One patient with periostitis had involvement of the greater and lesser wings of sphenoid in addition to the involvement of upper-outer orbital margin. Two periostitis patients had prolapse of the palpebral portion of the lacrimal gland. The clinical presentation and gross appearance of the tuberculoma of the lacrimal gland was similar to those found in benign mixed tumor. The patients with tuberculoma of orbital tissues presented as pseudotumors. The mimicry of tuberculoma of maxillary sinus to carcinoma has been mentioned. Associated tuberculous lesions were pulmonary in eight patients, cervical lymphadenitis in ten patients, intestinal in one patient, and caries spine in one patient. In two patients the disease developed in the absence of any other tuberculous lesion discovered in the body. The cases were cured by wide surgical removal of all the diseased tissues combined with antituberculous chemotherapy.
J Pediatr Ophthalmol Strabismus
PMID:Tuberculosis of the orbit and lacrimal gland: a clinical study of 14 cases. 741 35

Metastatic carcinoma to the extraocular muscles is extremely rare; it is reported to occur from breast, lung, and gastric carcinoma as well as skin melanoma. (1-3) Overall, intraocular metastases occur much more frequently than orbital metastases.(4) The most common primary tumors causing orbital metastases are breast and lung carcinomas.(5) Strabismus due to orbital metastases from breast carcinoma usually results from fibrosis of the muscle, which often causes painful ophthalmoplegia and enophthalmos. (6,7) We report a case of presumed metastatic carcinoma to the medial rectus muscle causing restrictive strabismus in which surgery was complicated by the "pulled in two syndrome," or PITS.
 ...
PMID:Strabismus surgery complicated by "pulled in two syndrome" in a case of breast carcinoma metastatic to the medial rectus muscle. 1077 11

Theophylline is an alkaloid found in tea (Thea sinensis) and chocolate and is structurally related to caffeine and theobromine. Theophylline is used as a pharmaceutical agent. It stimulates the heart and central nervous system, relaxes the smooth muscles of the bronchi and blood vessels, and causes diuresis. The drug is used mainly as a bronchodilator in obstructive airway diseases, such as bronchial asthma, and for myocardial stimulation. Theophylline was nominated for toxicologic and carcinogenicity testing as a representative of the purine structural subclass, particularly because of its relationship to purines such as caffeine, 1-methyl-3-hydroxyguanine, and 3-hydroxy-1-methylxanthine, the latter two compounds having been shown to induce sarcomas in rats. Additional reasons for testing theophylline included its widespread use in humans as a pharmaceutical agent, its possible genotoxicity in vitro, and the lack of information on its potential toxicity and/or carcinogenicity under conditions of chronic oral usage. Based on reported teratogenicity and testicular toxicity, it was also recommended that reproductive studies be included in the evaluation of theophylline. The oral route of administration was selected because it is the primary route of human exposure, and the gavage route was selected because it mimics the pharmaceutical use of theophylline in humans. Male and female F344/N rats and B6C3F1 mice were given theophylline (greater than 99% pure) in feed or in corn oil by gavage for 16 days or 14 weeks or in corn oil by gavage for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, mouse bone marrow, and mouse peripheral blood. 16-DAY FEED STUDY IN RATS: Groups of five male and five female F344/N rats were given 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm theophylline in feed for 16 days, which resulted in approximate daily doses of 50, 100, 250, 450, or 1,000 mg theophylline/kg body weight to males and 75, 150, 250, 450, or 1,100 mg/kg to females. All rats survived until the end of the study. The final mean body weights and body weight gains of 8,000 ppm males and females were significantly less than those of the controls. The absolute and relative testis weights of 4,000 ppm males were significantly greater than those of the controls. Increased incidences of uterine hypoplasia were observed microscopically in exposed groups of females. 16-DAY GAVAGE STUDY IN RATS: Groups of five male and five female F344/N rats were given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), or 400 (once daily) mg theophylline/kg body weight in corn oil by gavage. All rats receiving 400 mg/kg once daily and all but one female receiving 200 mg/kg twice daily died during the study. In groups dosed once daily, final mean body weights and body weight gains of males receiving 100 or 200 mg/kg and mean body weight gains of females receiving 50, 100, or 200 mg/kg were less than those of controls. The final mean body weights and body weight gains of groups receiving theophylline twice daily were generally similar to those of groups receiving the same daily dosages once daily. Clinical findings included rapid or labored respiration, hunched posture, and squinting. In groups dosed once daily, absolute and relative uterus weights of females receiving 100 or 200 mg/kg once daily were significantly less than those of the controls, and the absolute and relative uterus weights of females receiving 100 mg/kg once daily were significantly less than those of females receiving 50 mg/kg twice daily. Uterine atrophy was observed in three females receiving 200 mg/kg twice daily. Periarteritis of the mesenteric arteries was observed in two males and two females receiving 400 mg/kg once daily. 16-DAY FEED STUDY IN MICE: Groups of five male and five female B6C3F1 mice were given 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm theophylline in feed for 16 days, resulting in approximate daily doses of 250, 475, 950, 1,800, or800, or 2,000 mg theophylline/kg body weight to males and 300, 450, 1,225, 2,000, or 4,375 mg/kg to females. All mice survived until the end of the study. Final mean body weights of 4,000 and 8,000 ppm females and mean body weight gains of 2,000, 4,000, and 8,000 ppm females were significantly greater than those of the controls. Feed consumption by exposed groups was similar to that by the controls, except that by the 8,000 ppm males, which was approximately 40% the amount of feed consumed by the control group. Histopathologic examinations were not performed due to the absence of mortality and significant exposure-related lesions. 16-DAY GAVAGE STUDY IN MICE: Groups of five male and five female B6C3F1 mice were given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), or 400 (once daily) mg theophylline/kg body weight in corn oil by gavage. Three males and all females receiving 400 mg/kg once daily died on day 1. There were no significant differences in final mean body weights or body weight gains. There were no histopathologic findings attributed directly to theophylline. 14-WEEK FEED STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were given 0, 1,000, 2,000, or 4,000 ppm theophylline in feed for 14 weeks, which resulted in approximate daily doses of 75, 125, or 250 mg theophylline/kg body weight to males and 75, 125, or 275 mg/kg to females. The final mean body weight of 1,000 ppm females was significantly greater than that of the control group. Feed consumption by exposed groups was similar to that by the controls. Mean cell volume and mean cell hemoglobin were significantly greater in males exposed to 2,000 or 4,000 ppm than those in the control group. Segmented neutrophil counts of all groups of exposed females were significantly greater than that of the control group. The absolute and relative kidney weights of 4,000 ppm males were significantly greater than those of the controls, and there was an exposure-related increase in the severity of nephropathy in males. Exposure-related increases in the incidences of mesenteric and/or pancreatic periarteritis were observed in males and females. 14-WEEK GAVAGE STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were given 0, 37.5, 75, or 150 mg theophylline/kg body weight in corn oil by gavage for 14 weeks. One male and one female receiving 150 mg/kg died before the end of the study. The mean body weight gain of 150 mg/kg females was significantly greater than that of the controls. Mean cell volume of 150 mg/kg males and mean cell hemoglobin of all groups of dosed males were significantly greater than those of the control group. There were slight dose-dependent increases in the incidences of mesenteric periarteritis in dosed males and females. 14-WEEK FEED STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were given 0, 1,000, 2,000, or 4,000 ppm theophylline in feed for 14 weeks, resulting in approximate daily doses of 175, 400, or 800 mg theophylline/kg body weight to males and 225, 425, or 850 mg/kg to females. All mice survived until the end of the study. The final mean body weights and body weight gains of all exposed groups of males and females were significantly less than those of the controls. Feed consumption by exposed groups was similar to that by the controls. Leukocyte, segmented neutrophil, and lymphocyte counts of 4,000 ppm males were significantly greater than those of the controls. Leukocyte and segmented neutrophil counts of 2,000 or 4,000 ppm females were significantly greater than those of the controls. There were no histopathologic findings attributed directly to theophylline exposure. 14-WEEK GAVAGE STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were given 0, 75, 150, or 300 mg theophylline/kg body weight in corn oil by gavage for 14 weeks. Three males and all females receiving 300 mg/kg, one 75 mg/kg male, and one control female died before the end of the study. Final mean body weights and body weight gains of 150 and 300 mg/kg males were significantly less than those of the controls. Mean cell volume and mean cell hemoglobin of 300 mg/kg males were significantly greater than those of the controls. There were no histopathologic findings attributed directly to theophylline treatment. 2-YEAR GAVAGE STUDY IN RATS: Groups of 50 male and 50 female rats were given 7.5, 25, or 75 mg theophylline/kg body weight in corn oil by gavage for 2 years. Survival and Body Weights: There were no significant differences in survival between dosed and control groups. Final mean body weights of all groups of dosed males and females were significantly less than those of the controls. Pathology Findings: There were no significantly increased incidences of neoplasms in dosed rats. The incidence of chronic inflammation of the mesenteric arteries was significantly increased in males receiving 75 mg/kg compared to the controls. There were doserelated negative trends in the incidences of mammary gland fibroadenoma and fibroadenoma or carcinoma (combined) in females; these differences correlated with decreased body weights. 2-YEAR GAVAGE STUDY IN MICE: Groups of 50 male B6C3F1 mice were given 0, 15, 50, or 150 mg theophylline/kg body weight and groups of 50 female B6C3F1 mice were given 0, 7.5, 25, or 75 mg/kg in corn oil by gavage for 2 years. Survival and Body Weights: Survival of 150 mg/kg males was significantly less than that of the controls. The final mean body weights of 150 mg/kg males, 25 mg/kg females, and 75 mg/kg females were significantly less than those of the control groups. Pathology Findings: There were no treatment-related increases in incidences of nonneoplastic lesions or neoplasms. In males and females, there were decreased incidences of hepatocellular adenoma and of the combined incidences of hepatocellular adenoma or carcinoma compared to the controls. Male mice had a pattern of nonneoplastic liver lesions along with silver-staining helical organisms in the liver consistent with Helicobacter hepaticus infection. The incidences of these liver lesions in 150 mg/kg males were significantly lower than those in control males. Increases in the incidences of hepatocellular neoplasms in male mice have been shown to be associated with H. hepaticus infection when hepatitis is also present. Because of this association, interpretation of the decreased incidence of liver neoplasms in male mice was more difficult. Incidences of lesions at other sites in this study were not considered to have been significantly impacted by H. hepaticus infection or its associated hepatitis. GENETIC TOXICOLOGY: Theophylline was not mutagenic in Salmonella typhimurium, with or without metabolic activation (S9). It induced sister chromatid exchanges but not chromosomal aberrations in cultured Chinese hamster ovary cells. The positive sister chromatid exchange response was noted only in the absence of S9. In vivo, a mouse bone marrow sister chromatid exchange test showed positive results at a standard 23-hour harvest time; however, this test was not repeated and the response is unconfirmed. An in vivo mouse bone marrow chromosomal aberrations test, that employed both standard and extended exposure protocols, gave negative results. The frequency of micronucleated erythrocytes was determined in peripheral blood of male and female mice exposed to theophylline in dosed feed or in corn oil by gavage for 14 weeks. No significant increases in the frequencies of micronucleated cells were seen in male or female mice in either of the studies. CONCLUSIONS: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of theophylline in male or female F344/N rats administered 7.5, 25, or 75 mg/kg. There was no evidence of carcinogenic activity of theophylline in male B6C3F1 mice administered 15, 50, or 150 mg/kg or female B6C3F1 mice administered 7.5, 25, or 75 mg/kg. Gavage administration of theophylline caused chronic inflammation of the mesenteric arteries in dosed male rats. Decreased incidences of mammary neoplasms in female rats were likely associated with lower body weights. There were dose-related decreases in the incidences of hepatocellular adenoma and hepatocellular carcinoma in male and female mice. Synonyms: 3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione; 1,3-dimethylxanthine; 1H-purine-2,6-dione; NSC 2066; pseusdotheophylline; theocin; theophyllin; theophylline, anhydrous Trade names: Accurbron; Aerobin; Aerolate III; Afonilum; Aminophylline; Aquaphyllin; Armophylline; Asmalix; Bilordyl; Bronchoretard; Bronkodyl; Cetraphylline; Constant-T; Diffumal; Duraphyl; Duraphyllin; Elixicon; Elixophyllin; Euphylline L.A.; Euphylong; LaBID; Labophylline; Lanophyllin; Lasma; Liquophylline; Optiphyllin; Parkophyllin; Phylocontin; Physpan; Pro-Vent; PulmiDur; Pulmo-Timelets; Quibron; Respbid; Rona-Phyllin; Sabidal; Slo-bid; Slo-Phyllin; Solosin; Sustaire; Tefamin; Teobid; Teofyllamin; Tesona; Theal tablets; Theo-24; Theobid; Theocap; Theochron; Theoclear; Theocontin; Theo-Dur; Theofol; Theograd; Theolair; Theolan; Theolix; Theophyl; Theoplus; Theo-Sav; Theosol; Theospan; Theostat; Theovent; TheoX; T-Phyl; Truphylline; Uni-Dur; Unifyl; Uniphyl; Uniphyllin; Xanthium
 ...
PMID:NTP Toxicology and Carcinogenesis Studies of Theophylline (CAS No. 58-55-9) in F344/N Rats and B6C3F1 Mice (Feed and Gavage Studies). 1257 77

Scopolamine hydrobromide trihydrate is used in ophthalmic preparations and as a preanesthetic sedative. Its major use is in transdermal patches for the treatment of motion sickness. Scopolamine hydrobromide trihydrate was selected for study because of considerable human exposure resulting from its use in prescription and over-the-counter preparations. Scopolamine was a suspect carcinogen because it contains an aliphatic epoxide moiety which may act as a biological alkylating agent. Male and female F344/N rats and B6C3F1 mice received scopolamine hydrobromide trihydrate (89% pure) in distilled water by gavage for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. 16-DAY STUDY IN RATS: Groups of five male and five female rats were administered 0, 75, 150, 300, 600, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 16 days. All rats survived to the end of the study. The final mean body weights and body weight gains of males receiving 600 and 1,200 mg/kg and the mean body weight gain of males receiving 300 mg/kg were significantly lower than those of the control group. Clinical findings included bilateral pupillary dilation in all dosed animals and red eyelids in males and females receiving 1,200 mg/kg. There were no significant treatment-related gross or microscopic lesions. 16-DAY STUDY IN MICE: Groups of five male and five female mice were administered 0, 150, 250, 450, 900, or 1,800 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 16 days. One male and two females receiving 1,800 mg/kg and one female receiving 150 mg/kg died during the study. The final mean body weights and body weight gains of dosed mice were similar to those of the control groups. Clinical findings related to scopolamine hydrobromide trihydrate administration included bilateral pupillary dilation and squinting in all dosed males and females. The relative liver weights of males receiving 1,800 mg/kg and of females in all dosed groups were significantly greater than those of the control groups. There were no significant treatment-related gross or microscopic lesions. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were administered 0, 15, 45, 135, 400, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 14 weeks. One female receiving 45 mg/kg, one male and one female receiving 135 mg/kg, six males and one female receiving 400 mg/kg, and eight males and seven females receiving 1,200 mg/kg died during the study. The final mean body weights and mean body weight gains of all dosed males and females were significantly lower than those of the control groups. Clinical findings included bilateral pupillary dilation in all dosed males and females and reddening of the eyes in 15 mg/kg males and 135, 400, and 1,200 mg/kg males and females. Hematocrit, hemoglobin concentration, and/or erythrocyte count in male and female rats receiving 45 mg/kg or greater were slightly higher than those of the control groups. In general, these changes were most prominent in rats in the 400 and 1,200 mg/kg groups. Higher hematocrit, hemoglobin concentration, and erythrocyte count were likely due to hemoconcentration from dehydration (relative erythrocytosis). A minimal to mild mature neutrophilia, evidenced by higher segmented neutrophil numbers than in the control group, occurred in all dosed male rats. Sperm morphology and vaginal cytology parameters in dosed rats were similar to those in the control groups. Nine male and five female dosed rats died from esophageal obstructions consisting of feed and bedding material in the posterior pharynx. Tracheal obstruction occurred concurrently with esophageal obstruction as a result of food build-up in the oropharyngeal region. This condition is considered to be secondary to the inhibitory effects of scopolamine hydrobromide trihydrate on salivary gland secretions and on esopon esophageal smooth muscle involved in swallowing. There were no other significant treatment-related gross or microscopic findings. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were administered 0, 15, 45, 135, 400, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 14 weeks. One male receiving 135 mg/kg and two males and one female receiving 1,200 mg/kg died during the study. The final mean body weights and mean body weight gains of all dosed male groups and females receiving 45 mg/kg and above were significantly lower than those of the control groups. Clinical observations included bilateral pupillary dilation, hyperactivity, and hypoactivity. A minimal to mild mature neutrophilia, similar to that which occurred in the 14-week rat study, occurred in male mice receiving 45 mg/kg or greater. As in the rat study, there was no microscopic evidence of inflammation that could account for the neutrophilia. The estrous cycle length of 1,200 mg/kg females was significantly greater than that in the control group. There were no significant treatment-related gross or microscopic lesions. 2-YEAR STUDY IN RATS: Groups of 60 male and 60 female rats were administered 0, 1, 5, or 25 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 104 weeks. Ten males and ten females from each dose group, excluding the 1 mg/kg female group, were evaluated at 15 months. Survival, Body Weights, Clinical Findings, and Ophthalmic Examination Findings: The survival rates of female rats receiving 1 and 25 mg/kg were significantly lower than that of the control group. Mean body weights of 1 and 5 mg/kg males and females were similar to those of the controls throughout the study. However, mean body weights of 25 mg/kg males and females were generally lower than those of the control groups after about week 25. Clinical findings included bilateral pupillary dilation in all dosed males and females. Ophthalmic examination revealed no significant findings. Hematology: Compared to controls, hematocrit was slightly higher in the 25 mg/kg male rats, similar to the effects observed in the 14-week study; this is consistent with dehydration resulting in hemoconcentration. Reticulocyte numbers in the 25 mg/kg female rats were slightly lower than those in the controls. This result is consistent with the lower body weights, and thus a decreased nutritional status, exhibited by these animals. Plasma Scopolamine Determinations: The serum scopolamine concentrations were 6 ng scopolamine/mL serum for the 5 mg/kg female sample and 12 and 28 ng/mL for the 25 mg/kg male and female samples, respectively. The amounts of scopolamine in the other serum samples were below the minimum detection limit (4 ng/mL) of the analysis method. Neurobehavioral Findings: Horizontal motor activity of 25 mg/kg females was significantly greater than that of the control group on days 90, 180, and 360. Startle response of 5 and 25 mg/kg females was significantly lower than that of the control group on day 90. On day 180, passive avoidance of 25 mg/kg males was significantly lower than that of the control group. Pathology Findings: The incidences of adenoma of the pituitary gland pars distalis decreased with increasing dose in both male and female rats; however, this trend was only significant in males (males: vehicle control, 19/49; 1 mg/kg, 17/49; 5 mg/kg, 13/50; 25 mg/kg, 10/50; females: 20/50, 13/60, 14/50, 10/50). The incidences of adenoma of the pituitary gland pars distalis in 25 mg/kg males and all groups of dosed females were below the NTP historical control range. The incidences of hyperplasia were not significantly different from those in the control groups. The incidences of mononuclear cell leukemia in 25 mg/kg males and females were significantly lower than those of the control groups (males: 33/50, 21/50, 26/50, 24/50; females: 20/50, 6/60, 13/50, 4/50). The incidence of mononuclear cell leukemia in females receiving 25 mg/kg was well below the NTP historical range. 2-YEAR STUDY IN MICE: Groups of 70 male and 70 female mice were administered 0, 1, 5, or 25 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 104 to 105 weeks. Ten control animals and ten animals from each dose level were evaluated at 15 months. Survival, Body Weights, Clinical Findings, and Ophthalmic Examination Findings Survival of dosed males and females was similar to that of the controls. The mean body weights of males and females receiving 1 mg/kg were similar to those of the control groups throughout the majority of the study. The mean body weights of 5 mg/kg males and females were slightly lower than those of the controls. The mean body weights of males and females receiving 25 mg/kg were lower than those of the control groups after week 13. Clinical findings included bilateral pupillary dilation in all dosed male and female groups. Ophthalmic examination revealed no significant findings. Hematology: Hematocrit, hemoglobin concentration, and erythrocyte count in 25 mg/kg female mice were slightly lower than those in the control group. These results are consistent with development of a minimal normocytic, normochromic nonresponsive anemia. The anemia may be related to the lower body weights exhibited by these animals and are presumed to be due to a decreased nutritional status. Pathology Findings: The combined incidences of hepatocellular neoplasms (adenoma or carcinoma) occurred with a significant negative trend in males and females (males: vehicle control, 30/50; 1 mg/kg, 33/50; 5 mg/kg, 14/50; 25 mg/kg, 15/50; females: 22/51, 21/50, 16/50, 9/51). The combined incidences of hepatocellular neoplasms in 5 and 25 mg/kg males were within the NTP historical control range. The incidences of clear cell foci and eosinophilic foci in dosed male groups, and eosinophilic foci in 25 mg/kg females, were significantly lower than those of the control groups. The incidences of many spontaneously occurring nonneoplastic lesions were significantly lower in dosed mice than in the control groups and usually decreased with increasing dose. These included kidney nephropathy, alveolar epithelial hyperplasia, hyperplasia of the pancreatic islets, bone marrow myelofibrosis, hyperplasia of the pituitary gland pars distalis, cystic hyperplasia of the uterus, and hematopoietic cell proliferation of the spleen. The decreased incidences of these spontaneous lesions were most likely a result of lower body weights in dosed animals. GENETIC TOXICOLOGY: Scopolamine hydrobromide trihydrate did not induce mutations in any of five strains of Salmonella typhi murium, with or without S9 metabolic activation enzymes, nor did it induce sister chromatid exchanges in cultured Chinese hamster ovary cells, with or without S9. A weakly positive response was obtained, however, in a chromosomal aberrations test conducted in cultured Chinese hamster ovary cells with very high doses of scopolamine hydrobromide trihydrate in the presence of S9; without S9, no increase in aberrations was noted. Despite the evidence for chromosomal damage observed in vitro, no increase in the frequencies of micronucleated normochromatic erythrocytes was observed in peripheral blood samples of male or female mice exposed to scopolamine hydrobromide trihydrate for 14 weeks by gavage. CONCLUSIONS: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of scopolamine hydrobromide trihydrate in male or female F344/N rats or B6C3F1 mice administered 1, 5, or 25 mg/kg. Synonyms: Scopolamine hydrobromide, 6,7-epoxytropan-3-yl, euscopol, hydroscine hydrobromide, hyoscine bromide, (-)-hyoscine hydrobromide, hysco, isoscopil, scopolammonium bromide, (s)-tropate hydrobromide trihydrate, lα-tropyl-a-scopine
 ...
PMID:NTP Toxicology and Carcinogenesis Studies of Scopolamine Hydrobromide Trihydrate (CAS No. 6533-68-2) in F344 Rats and B6C3F1 Mice (Gavage Studies). 1259 30

Anterior segment ischemia after strabismus surgery is a rare occurrence. Risk factors include single-stage surgery of three or more muscles in one eye, dysthyroid eye disease, and advanced age. The authors report a case of anterior segment ischemia after single-stage surgery of two horizontal muscles without previous reported risk factors. However, the patient had received radiotherapy for nasopharyngeal carcinoma more than 20 years ago. The case was successfully treated with systemic steroids but with reduced best-corrected visual acuity. Previous radiotherapy in the related orbital field may be a new risk factor for this condition.
J Pediatr Ophthalmol Strabismus
PMID:Anterior segment ischemia after two-muscle surgery in a patient with radiation-treated nasopharyngeal carcinoma. 1828 62


1 2 Next >>