UMLS:C0001430 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0001430 (adenoma)
21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parathyroid tumors can be divided in adenomas and carcinomas, usually detected by hypercalcemia. We report a case of parathyroid adenoma in a young man, who complained of a pressure in the left neck region. Physical examination revealed a firm mass in the neck, without lymphnodes. Although Ca (9.7 mg/dl), phosphorus (3.3 mg/dl) and intact-PTH (49 pg/ml) were normal, imaging techniques (computed tomography scan and sestamibi substraction scan) suggested that the mass could arise from the parathyroid gland. Histology and immune staining for chromogranin and parathyroid hormone confirmed the parathyroid nature of the mass. Histological criteria defined the lesion as an atypical parathyroid adenoma. We review the pathology, diagnosis and treatment of parathyroid adenomas in its non-secreting atypical form.
...
PMID:Non-secreting atypical parathyroid adenoma. 1126 67

The authors report three cases of primary hyperparathyroidism (HPT) in patients with differentiated thyroid carcinoma (DTC) developed a few years after initial surgical and radiometabolic treatment of DTC. The early diagnosis of HPT in these patients was made possible because of laboratory tests performed during follow-up, including the assay of serum calcium and serum phosphorus levels. Scinti-graphy using 99mTc-MIBI enabled the correct preoperative localisation of a single parathyroid adenoma in two of these patients and multiglandular pathology in the third.
...
PMID:[Primary hyperparathyroidism in patients treated for non-medullary thyroid carcinoma]. 1132 65

In this paper we describe a patient with polycythemia vera (PV), who presented with hypercalcemia due to a parathyroid adenoma. In November 1999, the patient was admitted to our hospital with meteorism and constipation. Her physical examination revealed plethora and hepatosplenomegaly. Laboratory data revealed hyperparathyroidism in addition to PV: Rbc 8 x 10(6)/mm3, Hct 63.7%, serum calcium 13.4 mg/dl, serum phosphorus 1.2 mg/dl, albumin 4.25 mg/dl, and alkaline phophatase activity 433 U/l. Intact Parathyroid Hormone level (iPTH) was 376 pg/ml (n.v.12-72 pg/ml). Twenty-four hour urinary calcium excretion was higher than normal (900 mg). A parathyroid adenoma was detected with Tc-99m sesta-MIBI scanning under the left lobe of the thyroid gland and an ultrasonographic examination of the neck also supported the diagnosis. The patient was recommended for surgery. The histopathological examination confirmed the diagnosis. Postoperatively, iPTH dropped to 53.4 pg/ml at the 15 th minute and to 33.5 pg/ml at the first hour. The calcium level was 7.5 mg/dl one hour after the operation. Five days later, Hct was 40.8%. This case represents a rare association between PV and primary hyperparathyroidism, and may provide evidence for a causal link between PTH and polycythemia vera in our patient. In conclusion, this case indicates that the differential diagnosis of hypercalcemia and polycythemia vera should also include the possibility of a parathyroid tumor in addition to malignancy.
...
PMID:An unusual cause of hypercalcemia in polycythemia vera: parathyroid adenoma. 1210 88

We report the case of a 30-year-old eastern European female who presented with right upper quadrant pain. Clinical examination was unremarkable and liver function tests were normal. CT identified a 5 cm lesion in segment V of the liver, which was of homogeneous low density with no calcification or significant enhancement. MRI showed the lesion to be hypointense to liver on T(1) weighted sequences and isointense on T(2) weighted sequences. Rapid arterial enhancement with gadolinium-DTPA faded without leaving a definite central scar. Ultrasound showed the lesion to be echogenic with minimal vascularity. Administration of a liver-specific microbubble contrast agent showed low uptake relative to the surrounding liver. Phosphorus-31 MR spectroscopy, localized to the lesion itself, revealed a markedly increased phosphomonoester resonance with a decreased phosphodiester resonance, compatible with increased cell turnover. Biopsy confirmed the lesion to be a hepatocellular adenoma. The diagnosis of a hepatic adenoma is difficult with tissue diagnosis the gold standard, but it may be suggested by a combination of imaging modalities. We have described two new imaging techniques not previously described in characterization of hepatic adenomata, namely ultrasound with contrast agent and MR spectroscopy.
...
PMID:Hepatocellular adenoma: diagnostic difficulties and novel imaging techniques. 1215 46

Parathyroidectomy is effective in avoiding complications of primary hyperparathyroidism (pHPT) during pregnancy, because in about 90% of cases, it is caused by parathyroid adenomas. We present a case of severe pHPT during pregnancy of unknown etiology and without detectable parathyroid adenoma so that surgery was not a therapeutic option. The patient was a 29-year-old gravida 1 who presented with pHPT at 11 weeks of gestation. Although her serum calcium levels were elevated throughout pregnancy (>3.05 mmol/l; reference range: 2.05-2.65), a vigorous premature infant was delivered at 35 weeks of gestation. The infant received calcium intravenously, vitamin D(3) orally and was fed with raw human milk (low phosphorus) to prevent hypocalcemia. The baby did not develop clinical signs of hypocalcemia. Her initial parathyroid hormone level was suppressed (1.1 pg/ml; reference range: 15-65) and was normal at the age of 8 weeks. She was discharged from hospital at 14 days of life. Her physical, cognitive and motor development was normal through infancy and early childhood. In conclusion, pHPT during pregnancy does not necessarily lead to fetal or neonatal morbidity or mortality.
...
PMID:[Primary hyperparathyroidism with persistent hypercalcemia in pregnancy]. 1249 56

Phenolphthalein is used as a laboratory reagent and acid-base indicator and in over-the-counter laxative preparations. The National Cancer Institute nominated phenolphthalein for study because of its widespread use as a component in numerous laxative preparations and the lack of adequate testing for carcinogenicity in experimental animals. Male and female F344/N rats and B6C3F1 mice were exposed to phenolphthalein (98% to 99% pure) in feed for 14 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood. 14-DAY STUDY IN RATS: Groups of five male and five female F344/N rats were given 0, 6,250, 12,500, 25,000, 50,000, or 100,000 ppm phenolphthalein in feed for 14 days. All rats survived to the end of the study. The final mean body weights of all exposed groups of rats were similar to those of the controls. No chemical-related gross or microscopic lesions were observed. 14-DAY STUDY IN MICE: Groups of five male and five female B6C3F1 mice were given 0, 6,250, 12,500, 25,000, 50,000, or 100,000 ppm phenolphthalein in feed for 14 days. All mice survived to the end of the study. The final mean body weights of all exposed groups of mice were similar to those of the controls. No chemical-related gross or microscopic lesions were observed. 13-WEEK STUDY IN RATS: Groups of 10 male and 9 or 10 female F344/N rats were given 0, 3,000, 6,000, 12,000, 25,000, or 50,000 ppm phenolphthalein (equivalent to average daily doses of approximately 200, 400, 800, 1,600, or 3,500 mg phenolphthalein/kg body weight to males and 200, 400, 800, 1,700, or 3,600 mg/kg to females) in feed for 13 weeks. Additional groups of 10 male and 10 female rats designated for clinical pathology evaluations were also given 0, 3,000, 6,000, 12,000, 25,000, or 50,000 ppm phenolphthalein in feed until day 21. All core study rats survived to the end of the study. The final mean body weight of the 50,000 ppm females and the body weight gains of the 25,000 and 50,000 ppm females were significantly lower than those of the controls. The final mean body weights and mean body weight gains of all other exposed groups were similar to those of the controls. There was no cathartic action or any other clinical finding attributed to exposure to phenolphthalein. The few differences in the hematology and clinical chemistry parameters were sporadic and were not considered to be chemical related. The percentage of motile sperm in the 12,000 ppm males was significantly greater than that in the controls, but no other significant differences in sperm morphology or vaginal cytology between exposed and control groups were observed. Absolute and relative liver weights of 25,000 and 50,000 ppm males were significantly greater than those of the controls. No chemical-related gross or microscopic lesions were observed. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were given 0, 3,000, 6,000, 12,000, 25,000, or 50,000 ppm phenolphthalein (equivalent to average daily doses of approximately 500, 1,000, 2,000, 4,100, or 9,000 mg phenolphthalein/kg body weight to males and 600, 1,200, 2,400, 5,000, or 10,500 mg/kg to females) in feed for 13 weeks. All mice survived until the end of the study. The final mean body weights and mean body weight gains of all exposed groups were similar to those of the controls. There was no cathartic action or any other clinical finding attributed to exposure to phenolphthalein. The absolute right cauda weight of the 12,000 ppm males and the absolute right epididymis weights of 12,000, 25,000, and 50,000 ppm males were significantly less than those of the controls. The percentages of abnormal sperm in 12,000, 25,000, and 50,000 ppm males were significantly greater than that in the control group, and the sperm concentrations in 12,000 and 50,000 ppm males were significantly less than that of the control group. The absolute and relative right testis weights of males exposed to 6,000 ppm or greater and the absolute right testis weight of 3,000 ppm mof 3,000 ppm males were significantly less than those of the controls. The incidences of hypoplasia of the bone marrow in males and females exposed to 12,000 ppm or greater were significantly greater than those in the controls. The incidences of hematopoiesis of the spleen in 25,000 and 50,000 ppm males were significantly greater than that in the controls. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female F344/N rats were given 0, 12,000, 25,000, or 50,000 ppm phenolphthalein (equivalent to average daily doses of approximately 500, 1,000, or 2,000 mg phenolphthalein/kg body weight to males and 500, 1,000, or 2,500 mg/kg to females) in feed for 2 years. Survival, Body Weights, and Clinical Findings: Survival of exposed males and females was similar to that of the controls. The mean body weights of exposed males were less than those of the controls through most of the second year of the study, and the mean body weights of exposed females were less than those of the controls from about week 16 until the end of the study. Clinical findings attributed to phenolphthalein exposure included thin appearance and ruffled fur in all exposed groups of males. Determinations of Total Phenolphthalein in Plasma: The mean plasma concentrations of total phenolphthalein (free and conjugated) after 2 years of exposure varied little with time of day. Plasma concentrations of total phenolphthalein were approximately the same between exposure groups and between males and females. Pathology Findings: The incidences of benign pheochromocytoma of the adrenal medulla in all exposed groups of males were significantly greater than those in the controls and occurred with a significant positive trend. The incidences of benign pheochromocytoma in 12,000 ppm females and of benign or malignant pheochromocytoma (combined) in 12,000 and 25,000 ppm females were significantly greater than those in the controls. The numbers of exposed males with bilateral benign pheochromocytomas exceeded the number of controls with these neoplasms. The incidences of malignant pheochromocytomas in exposed rats were similar to those in the controls. The incidences of focal hyperplasia of the adrenal medulla in the 12,000 and 50,000 ppm males were significantly greater than in the controls. The incidences of renal tubule adenoma in 50,000 ppm male rats and of renal tubule adenoma or carcinoma (combined) in 12,000 and 50,000 ppm male rats were significantly greater than those in the controls. Although the increased incidences were predominantly of renal tubule adenoma, four carcinomas were observed in exposed males (0 ppm, 0/50; 12,000 ppm, 1/50; 25,000 ppm, 1/50; 50,000 ppm, 2/50). The incidences of renal tubule neoplasms in exposed groups of females were similar to those in the controls. The findings from an extended evaluation (step section) of the kidneys of female rats were similar to those from the standard evaluation. The incidences of nephropathy in all exposed groups of females were significantly greater than in the controls, and the severity of nephropathy in all exposed groups of males and in 25,000 and 50,000 ppm females was significantly greater than in the controls. The incidences of diffuse hyperplasia of the parathyroid gland (0/41, 16/48, 14/49, 14/46), fibrous osteodystrophy of the bone (0/50, 17/50, 14/50, 12/50), and mineralization (0/50, 11/50, 5/50, 5/49) and degeneration (0/50, 11/50, 5/50, 4/49) of the glandular stomach in exposed groups of males were generally significantly greater than those in the controls. The incidences of hyperplasia of the thyroid gland C-cells (13/50, 3/50, 9/49, 4/49) in 12,000 and 50,000 ppm males were significantly less than in the controls. These lesions are commonly observed in male rats with more advanced nephropathy and are considered to be associated with a calcium/phosphorus imbalance created by compromised functional capacity of the kidney. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female B6C3F1 mice were given 0, 3,000, 6,000, or 12,000 ppm phenolphthalein (equivalent to average daily doses of approximately 300, 600, or 1,200 mg phenolphthalein/kg body weight to males and 400, 800, or 1,500 mg/kg to females) in feed for 2 years. Survival, Body Weights, and Clinical Findings: Survival of the 12,000 ppm females was significantly lower than that of the controls; survival of all other exposed groups of mice was similar to that of the controls. The mean body weights of 12,000 ppm males were slightly less than those of the controls beginning at week 93 of the study, and the mean body weights of the 3,000, 6,000, and 12,000 ppm females were less than those of the controls during most of the second year of the study. In exposed mice, there were no clinical findings related to phenolphthalein exposure. Determinations of Total Phenolphthalein in Plasma: The mean plasma concentrations of total phenolphthalein (free and conjugated) after 2 years of exposure varied little with time of day. Plasma concentrations of total phenolphthalein were approximately the same between exposure groups and between males and females. Pathology Findings: The incidences of histiocytic sarcoma in 6,000 and 12,000 ppm males and females were significantly greater than those in the controls and occurred with a significant positive trend. In this study, histiocytic sarcoma was consistently observed in the liver with several other sites (e.g., spleen, lung, bone marrow, and various lymph nodes) involved less frequently. The incidences of all types of malignant lymphoma and of lymphoma of thymic origin in all exposed groups of females were significantly greater than those in the controls and occurred with significant positive trends, while the incidences of all types of malignant lymphoma in all exposed groups of males were similar to that in the controls. The incidences of lymphoma of thymic origin were increased in exposed groups of males, but were significantly increased only in the 6,000 ppm group. The incidences of atypical hyperplasia of the thymus in 6,000 and 12,000 ppm males and in all exposed groups of females were significantly greater than those in the controls. The incidences of benign sex-cord stromal tumors of the ovary in all exposed groups of females were significantly greater than in the controls. The incidences of hyperplasia of the ovary in 3,000 and 12,000 ppm females were significantly greater than in the controls. The incidences of germinal epithelial degeneration of the testis in all exposed groups of males were significantly greater than that in the controls. There were increased incidences of myelofibrosis of the bone marrow in 12,000 ppm males (0 ppm, 3/50; 3,000 ppm, 8/50; 6,000 ppm, 8/50; 12,000 ppm, 19/49) and an increased severity but not incidence of this lesion in exposed females. There were also increased incidences of pigmentation of minimal to mild severity in the bone marrow of 6,000 and 12,000 ppm males (0/50, 2/50, 5/50, 16/49) and females (2/50, 3/50, 11/50, 11/50). Also, the incidences of hematopoietic cell proliferation in the red pulp of the spleen (10/50, 22/50, 28/50, 21/49) in all exposed groups of males were significantly greater than that in the controls, and the severity of this lesion increased with increasing exposure concentration. The incidences of hepatocellular adenoma in all exposed groups of males and females and of hepatocellular adenoma or carcinoma (combined) in 6,000 and 12,000 ppm males and all exposed groups of females were significantly less than those in the controls, and these lesions occurred with significant negative trends. Multiple hepatocellular adenomas were observed more frequently in the control groups than in the exposed groups. The incidences of clear cell and eosinophilic foci in all exposed groups of males and of mixed cell foci in 12,000 ppm males were significantly less than those in the controls. The incidences of eosinophilic foci in exposed groups of females were significantly less than that in the controls. GENETIC TOXICOLOGY: Phenolphthalein, tested in two laboratories, was not mutagenic in any of four strains of Salmonella typhimurium with or without S9 metabolic activation enzymes, and no induction of sister chromatid exchanges was observed in cultured Chinese hamster ovary cells treated with phenolphthalein with or without S9. However, significant increases in chromosomal aberrations were observed after treatment of cultured Chinese hamster ovary cells with phenolphthalein in the presence of S9, and the frequencies of micronucleated erythrocytes were increased in peripheral blood samples from male and female mice administered phenolphthalein in feed for 13 weeks. CONCLUSIONS: Under the conditions of these 2-year feed studies, there was clear evidence of carcinogenic activity of phenolphthalein in male F344/N rats based on markedly increased incidences of benign pheochromocytomas of the adrenal medulla and of renal tubule adenomas and adenomas or carcinomas (combined). There was some evidence of carcinogenic activity of phenolphthalein in female F344/N rats based on the increased incidences of benign pheochromocytomas of the adrenal medulla in the 12,000 ppm group and of benign or malignant pheochromocytomas (combined) in the 12,000 and 25,000 ppm groups. There was clear evidence of carcinogenic activity of phenolphthalein in male B6C3F1 mice based on increased incidences of histiocytic sarcomas and of malignant lymphomas of thymic origin. There was clear evidence of carcinogenic activity of phenolphthalein in female B6C3F1 mice based on increased incidences of histiocytic sarcomas, malignant lymphomas of all types, lymphomas of thymic origin, and benign sex-cord stromal tumors of the ovary. Exposure of rats to phenolphthalein in feed for 2 years resulted in increased incidences of focal hyperplasia of the adrenal medulla in males and in increased incidences and/or severity of nephropathy of the kidney in males and females. Exposure of mice to phenolphthalein in feed for 2 years resulted in increased incidences of atypical hyperplasia of the thymus in males and females, degeneration of the germinal epithelium of the testis in males, and ovarian hyperplasia in females. Exposure of mice to phenolphthalein in feed for 2 years resulted in decreased incidences of hepatocellular neoplasms and nonneoplastic lesions in males and females. Synonyms: 3,3-Bis(4-hydroxyphenyl)-1(3H)-isobenzofuranone; 3,3-bis( p-hydroxyphenyl)phthalide; a-p -hydroxyphenyl)-a- (4-oxo-2,5-cyclohexadien-1-ylidene)- o-toluic acid Trade names: Agoral®, Alophen®, Colax®, Correctol®, Dialose®, Doxidan®, Espotabs®, Evac-U-Gen®, Evac-U-Lax®, Ex-Lax®, Feen-A-Mint®, FemiLax®, Kondremul®, LaxCaps®, Lax-Pills®, Medilax®, Modane®, Phenolax®, Prulet®
...
PMID:NTP Toxicology and Carcinogenesis Studies of Phenolphthalein (CAS No. 77-09-8) in F344/N Rats and B6C3F1 Mice (Feed Studies). 1257 99

Some pituitary adenomas seem to be related to bone loss. It is unknown what kinds of pituitary adenomas affect bone mass. We attempted to determine what kinds of pituitary adenomas caused osteoporosis, and whether hormonal disturbance in pituitary adenoma patients affected bone mass. This study included 53 surgical patients (39 women of premenopausal age and 14 men) aged 21 to 62 years. We measured vertebral bone mineral density (BMD); various bone metabolic parameters, such as serum calcium, phosphorus, alkaline phosphatase, and blood urea nitrogen, parathormone, vitamin D, vitamin K, and hormonal activity in the anterior lobe of the pituitary gland. Comparisons were made of the mean Z scores (the ratio to the mean BMD of age-matched healthy Japanese women and men) among patient groups and controls. Compared with the female controls, the mean Z score was significantly higher in the women with acromegalic adenoma and significantly lower in those with adrenocorticotrophic hormone (ACTH)-secreting adenoma. In male patients, the mean Z scores were significantly decreased in prolactin-secreting adenoma and nonfunctioning adenoma, compared with that in normal controls. Acromegalic adenoma contributes significantly to vertebral bone mass acquisition, although ACTH adenoma may carry a significant risk of osteoporosis in female patients. Male patients with prolactin-secreting and nonfunctioning adenoma have a significant risk of bone decrease.
...
PMID:Various risks of osteoporosis in patients with pituitary adenomas. 1260 73

Barium chloride dihydrate, a white crystalline granule or powder, is used in pigments, aluminum refining, leather tanning and coloring, the manufacture of magnesium metal, ceramics, glass, and paper products, as a pesticide, and in medicine as a cardiac stimulant. Toxicology and carcinogenicity studies were conducted by administering barium chloride dihydrate (99% pure) in drinking water to F344/N rats and B6C3F1 mice for 15 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse lymphoma cells. 15-DAY STUDY IN RATS: Groups of five males and five females received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 250, 500, 1,000, or 2,000 ppm for 15 days, corresponding to average daily doses of 10, 15, 35, 60, or 110 mg barium/kg body weight to males and females. No chemical-related deaths, differences in final mean body weights, or clinical findings of toxicity were observed. Water consumption by male and female rats exposed to 2,000 ppm was slightly less (S16%) than controls during week 2. There were no significant differences in absolute or relative organ weights between exposed and control rats. No biologically significant differences in hematology, clinical chemistry, or neurobehavioral parameters occurred in rats. 15-DAY STUDY IN MICE: Groups of five males and five females received barium chloride dihydrate in the drinking water at concentrations of 0, 40, 80,173, 346, or 692 ppm for 15 days, corresponding to average daily doses of 5,10, 20, 40, or 70 mg barium/kg body weight to males and 5, 10, 15, 40, or 85 mg barium/kg body weight to females. No chemical-related deaths, differences in mean body weights or in water consumption, or clinical findings of toxicity were observed in mice. The relative liver weight of males receiving 692 ppm was significantly greater than that of the controls. The absolute and relative liver weights of females that received 692 ppm were significantly greater than those of the controls. No histopathologic evidence of toxicity was observed in mice. 13-WEEK STUDY IN RATS: Groups of 10 males and 10 females received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 500, 1,000, 2,000, or 4,000 ppm for 13 weeks, corresponding to average daily doses of 10, 30, 65, 110, or 200 mg barium/kg body weight to males and 10, 35, 65, 115, or 180 mg barium/kg body weight to females. Three males and one female in the 4,000 ppm groups died during the last week of the study. The final mean body weights of male and female rats receiving 4,000 ppm were significantly lower (13% and 8%) than those of the controls. Water consumption by male and female rats in the 4,000 ppm groups was approximately 30% lower than that by the controls. No clearly chemical-related clinical findings of toxicity or neurobehavioral or cardiovascular effects were noted. Serum phosphorus levels in 2,000 and 4,000 ppm male and female rats were significantly higher than those in controls, but there were no biologically significant differences in hematology parameters or in serum sodium, potassium, or calcium levels. Renal tubule dilatation in the outer stripe of the outer medulla and cortex occurred in male and female rats receiving 4,000 ppm. 13-WEEK STUDY IN MICE: Groups of 10 males and 10 females received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 500, 1,000, 2,000, or 4,000 ppm for 13 weeks, corresponding to average daily doses of 15, 55, 100, 205, or 450 mg barium/kg body weight to males and 15, 60, 110, 200, or 495 mg barium/kg body weight to females. Six males and seven females that received 4,000 ppm and one male that received 125 ppm died during the study. Final mean body weights of male and female mice receiving 4,000 ppm were significantly lower (>30%) than those of controls. Water consumption by male mice in the 4,000 ppm group was 18% lower than that by the controls; water consumption by other exposed groups of male and female mice was similar to thatd groups of male and female mice was similar to that by the controls. Clinical findings of toxicity were limited to debilitation in the surviving male and female mice receiving 4,000 ppm. The absolute and/or relative liver weights of mice receiving 1,000, 2,000, and 4,000 ppm were significantly lower than those of the controls. Multifocal to diffuse nephropathy characterized by tubule dilatation, regeneration, and atrophy occurred in 4,000 ppm male and female mice. 2-YEAR STUDY IN RATS: Groups of 60 males and 60 females received barium chloride dihydrate in the drinking water at concentrations of 0, 500, 1,250, or 2,500 ppm for 104 (males) or 105 weeks (females), corresponding to average daily doses of 15, 30, or 60 mg barium/kg body weight for males and 15, 45, or 75 mg barium/kg body weight for females. The high dose of 2,500 ppm was selected based on decreased final mean body weights, mortality, decreased water consumption, and chemical-related kidney lesions observed in the 4,000 ppm groups in the 13-week study. Survival, Body Weights, Water Consumption, and Clinical Findings: Two-year survival of exposed male and female rats was similar to that of the controls. The final mean body weights of male and female rats that received 2,500 ppm were (5&percnt; and 11&percnt;) lower than those of controls. Beginning as early as week 5, water consumption by male and female rats receiving 2,500 ppm was substantially lower than that by controls (male: 11&percnt; to 30&percnt;; female: 19&percnt; to 33&percnt;). There were no chemical-related clinical findings. Hematology and Clinical Chemistry: There were no chemical-related differences in hematology or clinical chemistry parameters in male or female rats. Special Studies: At the 15-month interim evaluation, the plasma barium concentrations (mg/ml) were significantly increased in males receiving 1,250 and 2,500 ppm and in all exposed groups of females (male: 0 ppm, 0.98; 500 ppm, 1.00; 1,250 ppm, 1.23; 2,500 ppm, 1.68; female: 0 ppm, 0.74; 500 ppm, 0.99; 1,250 ppm, 0.97; 2,500 ppm, 1.43). Barium levels in bone in rats from the 2,500 ppm groups were about 400 times greater than those in the controls. Pathology Findings: At the end of 2 years, there were no increased incidences of neoplasms or nonneoplastic lesions that could be attributed to barium chloride dihydrate. However, there were dose-related decreased incidences of adrenal medulla pheochromocytomas and mononuclear cell leukemia in male rats. 2-YEAR STUDY IN MICE: Groups of 60 males and 60 females received barium chloride dihydrate in the drinking water at concentrations of 0, 500, 1,250, or 2,500 ppm for 103 (males) or 104 weeks (females), corresponding to average daily doses of 30, 75, or 160 mg barium/kg body weight for males and 40, 90, or 200 mg barium/kg body weight for females. The high dose of 2,500 ppm was selected based on decreased final mean body weights, mortality, decreased water consumption, and chemical-related kidney lesions observed in the 4,000 ppm groups in the 13-week study. Survival, Body Weights, Water Consumption, and Clinical Findings: Two-year survival of male and female mice receiving 2,500 ppm was significantly lower than that of the controls due to renal toxicity. Final mean body weights of 2,500 ppm males and females were 9% and 12% lower than those of controls. Water consumption by male and female mice receiving barium chloride was similar to that by the controls. There were no chemical-related clinical findings. Hematology and Clinical Chemistry: There were no differences in hematology or clinical chemistry parameters measured at the 15-month interim evaluation. Special Studies: At the 15-month interim evaluation, plasma barium concentrations (mg/mL) were significantly increased in all exposed groups of mice (male: 0 ppm, 0.62; 500 ppm, 0.77; 1,250 ppm, 0.89; 2,500 ppm, 1.49; female: 0 ppm, 0.52; 500 ppm, 0.74; 1,250 ppm, 1.01; 2,500 ppm, 1.35). Pathology Findings: At the end of the 2-year study, there were increased incidences of nephropathy in male and female mice (male: 1/50, 0/50, 2/48, 19/50; female: 0/50, 2/53, 1/50, 37/54). There were no chemical-related increased incidences of neoplasms in male or female mice. The incidence of hepatocellular adenoma was significantly decreased in male mice receiving 2,500 ppm. GENETIC TOXICOLOGY: Barium chloride dihydrate was not mutagenic in Salmonella typhimurium strains TA97, TA98, TA100, TA1535, or TA1537, with or without exogenous metabolic activation (S9). It was mutagenic in L5178Y mouse lymphoma cells in the presence of S9, but it did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9. CONCLUSIONS: Under the conditions of these 2-year drinking water studies, there was no evidence of carcinogenic activity of barium chloride dihydrate in male or female F344/N rats that received 500, 1,250, or 2,500 ppm. There was no evidence of carcinogenic activity of barium chloride dihydrate in male or female B6C3F1 mice that received 500, 1,250, or 2,500 ppm. There were chemical-related increased incidences of nephropathy in male and female mice.
...
PMID:NTP Toxicology and Carcinogenesis Studies of Barium Chloride Dihydrate (CAS No. 10326-27-9) in F344/N Rats and B6C3F1 Mice (Drinking Water Studies). 1261 99

Furan serves as an intermediate in the synthesis and preparation of numerous linear polymers used to prepare temperature-resistant structural laminates and to prepare copolymers used in machine dishwashing products as alternatives to phosphorus- and nitrogen-containing detergents. Toxicology and carcinogenesis studies were conducted by administering furan (purity > 99%) in corn oil by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 16 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Drosophila melanogaster, mouse bone marrow cells, mouse L5178Y lymphoma cells, and Chinese hamster ovary cells. 16-Day Studies: Groups of five male rats received doses of 0, 5, 10, 20, 40, or 80 mg of furan per kg of body weight and groups of five female rats and five mice of each sex received doses of 0, 10, 20, 40, 80, and 160 mg/kg in corn oil by gavage. All male and female mice and female rats that received 160 mg/kg, all male and female rats and all male and four female mice that received 80 mg/kg, and three male mice that received 40 mg/kg died by day 8. Final mean body weights of male rats that received 20 mg/kg and of male and female rats that received 40 mg/kg were significantly lower than controls. Final mean body weights of male mice that received 10 or 20 mg/kg were significantly greater than controls. Mottled and enlarged livers were observed at necropsy in male rats that received 20, 40, or 80 mg/kg and in females that received 40, 80, or 160 mg/kg. No lesions were observed at necropsy that were considered related to furan administration in mice. 13-Week Studies: Groups of 10 rats of each sex and groups of 10 female mice received doses of 0, 4, 8, 15, 30, or 60 mg of furan per kg of body weight, and groups of 10 male mice received doses of 0, 2, 4, 8, 15, or 30 mg/kg in corn oil by gavage. Nine male and four female rats that received 60 mg/kg died before the end of the studies. There were no chemical-related deaths in mice. Final mean body weights of male rats that received 15 or 30 mg/kg and female rats that received 60 mg/kg were significantly lower than controls. Final mean body weights of male mice that received 60 mg/kg were significantly lower than controls. Relative and absolute liver weights in both sexes of rats and mice were increased in groups that received furan, as were relative and absolute kidney weights in female rats that received furan. Thymus weights were decreased in all groups of rats that received furan. Toxic lesions of the liver (bile duct hyperplasia, cholangiofibrosis, cytomegaly and degeneration of hepatocytes, and nodular hyperplasia of hepatocytes) were associated with furan administration in all dose groups of rats; the severity of the lesions increased with dose. Kidney lesions (tubule dilatation and necrosis of tubule epithelium) were present in rats that received 30 or 60 mg/kg. Thymic atrophy and testicular or ovarian atrophy were also observed in rats exposed to 60 mg/kg furan. Toxic liver lesions (cytomegaly, degeneration, and necrosis of hepatocytes) were also present in all groups of furan-exposed mice. Bile duct hyperplasia and cholangiofibrosis were observed in groups of mice receiving 30 or 60 mg/kg. Doses selected for the 2-year studies of rats and mice were based on the hepatotoxicity associated with exposure to furan. 2-Year Studies: Groups of 70 rats of each sex were administered 2, 4, or 8 mg furan per kg body weight in corn oil by gavage 5 days per week for 2 years. After 9 and 15 months of chemical exposure, 10 rats per group were evaluated for the presence of treatment-associated lesions. Groups of 50 mice of each sex received doses of 8 or 15 mg/kg furan 5 days per week for 2 years. Body Weight and Survival: Mean body weights of male rats that received 8 mg/kg furan were lower than controls from approximately week 73 to the end of the study. Survival of male and female rats that received 8 mg/kg was lower than controls from approximately week 85 to the end of the studies as a result of moribund condition associatedassociated with liver and biliary tract neoplasms and mononuclear cell leukemia. Mean body weights of male and female mice that received 15 mg/kg furan were lower than controls during the studies. Survival of low- and high-dose male and high-dose female mice was lower than controls from approximately week 80 to the end of the studies as a result of moribund condition associated with liver neoplasms. Neoplastic and Nonneoplastic Lesions: Cholangiocarcinoma of the liver occurred in all groups of dosed rats (males: control, 0/50; low dose, 43/50; mid dose, 48/50; high dose, 49/50; females: 0/50; 49/50; 50/50; 48/50) and was present in many rats of each sex at the 9- and 15-month interim evaluations (9-month: males - 0/10, 5/10, 7/10, 10/10; females - 0/10, 4/10, 9/10, 10/10; 15-month: males - 0/10, 7/10, 9/10, 6/10; females - 0/10, 9/10, 9/10, 7/10). Hepatocellular adenomas or carcinomas (combined) were significantly increased in male rats after 2 years of chemical administration (1/50, 5/50, 22/50, 35/50) and hepatocellular adenomas were significantly increased in female rats (0/50, 2/50, 4/50, 7/50); hepatocellular neoplasms were not observed at the 9- or 15-month interim evaluations. Increased incidences of numerous nonneoplastic liver lesions were present in rats administered furan. These lesions included biliary tract fibrosis, hyperplasia, chronic inflammation, and proliferation and hepatocyte cytomegaly, cytoplasmic vacuolization, degeneration, nodular hyperplasia, and necrosis. The incidence of mononuclear cell leukemia was increased in male and female rats that received 4 or 8 mg/kg furan (males: 8/50, 11/50, 17/50, 25/50; females: 8/50, 9/50, 17/50, 21/50); the incidence in the 8 mg/kg groups of each sex exceeded the historical control ranges for corn oil gavage studies. The severity of nephropathy increased with dose and the incidence was significantly increased in all groups of dosed rats; this increased severity was accompanied by an associated increased incidence of parathyroid hyperplasia (renal secondary hyperparathyroidism). The incidence of forestomach hyperplasia was increased in male and female rats (males: 1/50, 4/49, 7/50, 6/50; females: 0/50, 2/50, 5/50, 5/50) and the incidence of subacute inflammation of the forestomach was increased in female rats (0/50, 1/50, 5/50, 6/50). No forestomach neoplasms were observed in males; a squamous papilloma was present in one low-dose female. The incidences of hepatocellular adenomas and carcinomas were significantly increased in mice receiving furan (males: adenoma - 20/50, 33/50, 42/50; carcinoma - 7/50, 32/50, 34/50; females: adenoma - 5/50, 31/50, 48/50; carcinoma - 2/50, 7/50, 27/50). The incidences of numerous nonneoplastic hepatocellular lesions were increased in dosed mice. These lesions included hepatocyte cytomegaly, degeneration, necrosis, multifocal hyperplasia, and cytoplasmic vacuolization and biliary tract dilatation, fibrosis, hyperplasia, and inflammation. The incidences of benign pheochromocytoma and focal hyperplasia of the adrenal medulla were increased in low- and high-dose male and in high-dose female mice (benign pheochromocytoma: males - 1/49, 6/50, 10/50; females - 2/50, 1/50, 6/50). The incidences of squamous papilloma, focal inflammation, and papillary hyperplasia of the forestomach were increased in male mice (squamous papilloma: 0/49, 1/50, 3/50; focal inflammation: 9/49, 13/50, 21/50; papillary hyperplasia: 7/49, 14/50, 22/50). Stop-Exposure Study: A separate 2-year study was conducted in which 50 male rats were administered 30 mg/kg furan in corn oil by gavage 5 days per week for 13 weeks and then maintained for the remainder of the 2 years without additional furan administration. Groups of 10 animals were evaluated for the presence of treatment-related lesions at the end of the 13-week period of furan administration and at 9 and 15 months. Neoplastic and Nonneoplastic Lesions: Cholangiocarcinoma of the liver occurred with an overall incidence of 100&percnt; (40/40) and hepatocellular carcinoma occurred with an overall incidence of 15&percnt; (6/40) in stop-exposure male rats that survived at least 9 months. Cholangiocarcinoma was observed in all 10 males at both the 9-month and 15-month interim evaluations. Hepatocellular carcinoma was first observed in 2 males at the 15-month interim evaluation. Genetic Toxicology: Furan was negative for induction of gene mutations in Salmonella typhimurium strains TA100, TA1535, TA1537, and TA98 in the presence and the absence of exogenous metabolic activation (S9). Furan was negative for the induction of sex-linked recessive lethal mutations in germ cells of male Drosophila melanogaster when administered either by feeding or by injection. In vitro tests for genotoxicity in mammalian cells, however, were positive. Furan induced trifluorothymidine resistance in mouse L5178Y lymphoma cells in the absence of S9, and sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells, with and without S9. Furan administered to male B6C3F1 mice by intraperitoneal injection induced chromosomal aberrations but not sister chromatid exchanges in bone marrow cells. Conclusions: Under the conditions of these 2-year gavage studies there was clear evidence of carcinogenic activity of furan in male and female F344/N rats based on increased incidences of cholangiocarcinoma and hepatocellular neoplasms of the liver and on increased incidences of mononuclear cell leukemia. There was clear evidence of carcinogenic activity of furan in male and female B6C3F1 mice based on increased incidences of hepatocellular neoplasms of the liver and benign pheochromocytomas of the adrenal gland. Nonneoplastic liver lesions associated with furan administration in rats and mice included biliary tract fibrosis, hyperplasia, inflammation, and proliferation, as well as hepatocellular cytomegaly, degeneration, hyperplasia, necrosis, and vacuolization. In rats, increased severity of nephropathy with an associated increased incidence of parathyroid hyperplasia was associated with exposure to furan. Synonyms: Divinylene oxide, tetrole, furfuran, oxole, 1,4-epoxy-1,3-butadiene, axole, oxacyclopentadiene
...
PMID:Toxicology and Carcinogenesis Studies of Furan (CAS No. 110-00-9) in F344 Rats and B6C3F1 Mice(Gavage Studies). 1262 16

Extracapsular parathyroid haemorrhage is a rare but ominous occurrence, which may cause cervico-mediastinal haematoma and a severe calcaemia imbalance. We identified only 23 cases reported in the literature and these were always secondary to adenoma, hyperplasia or cysts, and never to carcinoma. We describe a case of a 56-year-old man who was admitted to our Institute because of the sudden development of an anterior neck swelling, together with dysphagia, dyspnoea and hoarseness. Physical examination revealed a large ecchymosis extending from the anterior neck to the upper chest, while the early symptoms had disappeared. Laboratory studies, ultrasonography and 99mtTC-Sestamibi scintiscan demonstrated the presence of primary parathyroidism due to a right inferior parathyroid neoplasm. At operation, the parathyroid was excised en bloc with the right thyroid lobe because they were joined together by an extensive fibrous reaction. Histological examination showed a well-differentiated parathyroid carcinoma with evidence of recent haemorrhage. To the best of our knowledge this is the first case of extracapsular haemorrhage due to a parathyroid carcinoma. In summary, although parathyroid haemorrhage is a rare condition, it should always be suspected when a painful mass or diffuse swelling suddenly occurs in the anterior neck, with or without ecchymosis, especially when serum calcium and phosphorus are abnormal.
...
PMID:[Cervico-mediastinal hematoma secondary to extracapsular hemorrhage of parathyroid carcinoma. Clinical case and review of the literature]. 1287 80

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>