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PubMed1992

[A 13-week subcutaneous toxicity study of prednisolone farnesylate (PNF) in rats].

The toxicity of Prednisolone farnesylate (PNF), a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF was injected subcutaneously at doses of 0.03, 0.3, 3 and 30 mg/kg/day for 13 weeks. In addition, 18.7 mg/kg/day prednisolone (PN), which is approximate to 30 mg/kg/day PNF in prednisolone molarity, was also administered to the rat for comparison. The results are summarized as follows: 1. All animals from the PN 18.7 mg/kg/day group, and four(4) out of ten(10) males and three(3) out of ten(10) females from the PNF 30 mg/kg/day group died having shown weakened condition such as unkempt fur and emaciation. Histopathologically, systemic suppurative inflammation, as shown by pyeronephritis and abscess formation in many organs and tissues, was observed and it was considered that the administration of steroid induced weakened condition and systemic suppuration which resulted in death. In addition, atrophy was noted in the adrenal glands, lymphatic organs and skin, and histopathological lesions were also observed in the lungs, liver, pancreatic islets, bone, bone marrow and mammary glands. 2. Surviving animals in the PNF 30 mg/kg/day group showed almost the same changes as those observed in the dead animals that died. Hematological examination revealed an anemic change and a decrease in lymphocytes with an increase in segmented neutrophils and eosinophils. In the urinalysis and blood chemistry, the changes suggesting damages to the liver and kidneys were mainly observed. 3. In the PNF 3 and 0.3 mg/kg/day groups, several changes such as atrophy of the adrenal glands, lymphatic organs and skin were noted in a dose dependent manner. 4. In the PNF 0.03 mg/kg/day group, ther were no toxic signs. 5. Based on these results, it was concluded that the overt toxic dose of PNF was 0.3 mg/kg/day and the non-toxic dose was 0.03 mg/kg/day in the present study.

Animals↗
PubMed1996

[Single dose toxicity studies of calcipotriol (MC903) in rats and dogs].

A single dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, administered subcutaneously (s.c.) and percutaneously (p.c.) was studied in Slc:SD rats (s.c. and p.c.) and beagle dogs (s.c.). The LD50 values of MC903 were as follows: rats, 2.19 mg/kg in males and 2.51 mg/kg in females by s.c., and more than 15 mg/kg in both sexes by p.c.; dogs, more than 1.5 mg/kg in males by p.c. No sexual difference was noted in LD50 values of rats. Death of rats was observed from 1 to 3 days after administration by both routes. Dead animals showed decreases in body weight and locomotor activity, reddish tear, abnormal gait and dirty hair by both routes. Furthermore, dead animals administered by s.c. showed salivation, nasal discharge, piloerection, ptosis, diarrhea, urorrhea, nasal and vaginal bleeding, subnormal temperature, loose stool, cyanosis, irregular and deep respirations, clonic and tonic convulsions. Survival of rats showed similar signs to those of dead animals except for nasal discharge, nasal and vaginal bleeding, cyanosis, agonal respiration and convulsion. Discoloration of the kidney, white patch of the heart and a dilatation of the stomach wall were observed on macroscopic examinations. No mortalities were observed in dogs which showed vomiting, conjunctival congestion, circumoral and auricular reddenings, periblepharal purplish reddening, decreases in locomotor activity and defecation, emaciation, eye discharge, skin desquamation of treated area and an increase in respiration. On macroscopic examination, desquamation of the skin, reddening of the circumoral mucosa, pale gray yellow striations in renal tubules of the cortex and discoloration of the thyroid were observed. Histopathological findings revealed epidermal thickening with parakeratosis, fibrocytes, hypertrophy and hypersecretion of the sebaceous and sweat glands, formation of epitheloid glanulomas and infiltration of neutrophils in the subcutaneous tissues. Furthermore, moderate calcium deposits in the renal tubules, fatty cells and slight calcium deposits in interstitial tissues of the thyroid, and a cystic nest of an ectopic intestinal epithelium between muscle layers of the duodenum were observed at the highest dose. On the basis of results obtained in the present study, rats administered MC903 by s.c. or p.c. died probably due to the circulatory and renal disturbance resulted from effects of this drug on the heart and kidney.

Administration, Cutaneous↗
PubMed1996

[A 4-week repeated percutaneous dose toxicity study of calcipotriol (MC903) followed by a 4-week recovery test in rats].

A 4-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a recovery for 4 weeks was studied in Slc:SD rats at doses of 4, 20 and 100 micrograms/kg/day as low, mid and high dose levels. 1. One male and female at high dose died probably due to stress and circulatory failure. One female at mid dose died with clonic convulsion considered to be results in attached error of a neck collar. Survival of rats showed reddish tear, reddening and desquamation of the skin at application site, and vocalization at all groups including control. Furthermore, abnormal gait, dirty hair, emaciation and opacity of the eyeball surface in both sexes were observed at high dose. 2. A decreased body weight and a slight increased water consumption in both sexes, and a decreased food consumption in males were observed at high dose. 3. An increased incidence of corneal opacity was noted significantly in both sexes as compared with control at high dose. Urinalysis revealed an increased Ca excretion in both sexes at more than mid dose, and lower pH in females at mid dose and in both sexes at high dose, and a decreased urinary volume in males at high dose. The increases of neutrophil and serum beta-globulin ratios in females, and serum Ca level in both sexes were observed at high dose. The increased mineralization of the cornea in males at mid dose and in both sexes at high dose, and of the Kidney in males at high dose were observed. At the skin of application site, cellular infiltration in the epidermis and dermis in both sexes at more than mid dose was observed. Furthermore, hyperplasia of the squamous cell in females, and hyperkeratosis in the epidermis and hypertrophy of the sebaceous gland in both sexes were observed at high dose. 4. After a 4-week recovery period, the changes related with application disappeared except for opacity of the eyeball surface and cornea, and mineralization of organs. 5. On the basis of results obtained in the present study, it is considered that 4 micrograms/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of rats.

Administration, Cutaneous↗
PubMed1996

[Oral single-dose toxicity study of a new antineoplastic agent S-1, and its components, CDHP, and Oxo].

S-1, an antineoplastic formulation of a fluorinated pyrimidine derivative containing tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1, was recently developed by Taiho Pharmaceutical Co., Ltd., with the aim of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) over that produced by FT alone and reducing its dose-limiting gastrointestinal toxicity. As a part of the S-1 toxicity study, the single-dose toxicity of S-1 as well as that of its components, CDHP and Oxo, was investigated in mice, rats, and dogs. The following results were obtained. 1. In mice and rats, excretion of diarrheal stools, salivation, and alopecia were observed after S-1 administration. In severe cases, the animals subsequently showed emaciation due to weight loss or suppressed weight gain, decreased spontaneous motor activity, an anemic appearance, bradypnea, prone position, and death. In the CDHP and Oxo treatment groups of rats, the only toxic signs were soft or diarrheal stools on the dosing day. 2. In dogs, vomiting and excretion of diarrheal, mucous, or soft stools was observed after S-1 administration. In the CDHP and Oxo treatment groups, excretion of soft and diarrheal stools and vomiting were observed relatively frequently from the dosing day until day 1. 3. In the pathological examination of the animals given S-1, mice and rats showed pulmonary congestion/edema, dark red discoloration of the mesenteric lymph nodes, atrophy of lymphatic tissues such as the thymus and lymph nodes, decreases of lymphocytes in the splenic white pulp and mesenteric lymph nodes, a decrease in bone marrow cells, congestion of the glandular stomach, and aggregates of bacteria in the lung, liver, or spleen. In dogs, abnormal changes were observed mainly in the lymphatic organs such as the thymus and lymph nodes. 4. The LD50 values of S-1 in terms of the amount FT they contained were estimated to be 549 mg/kg for mice(male), 441-551 mg/kg for rats (both sexes) and about 53 mg/kg for dogs (male). The LD50 values of CDHP and Oxo were 2000 mg/kg or higher for both rats (both sexes) and dogs (male). 5. Hematopoietic and lymphatic impairments, immunosuppression associated with respiratory were considered to be the cause of death from S-1. The toxicity of S-1 reflects the toxicity of 5-FU and was not found the different toxicity by the addition of CDHP and Oxo.

Administration, Oral↗
PubMed1996

[A 13-week oral repeated dose toxicity study of a new antineoplastic agent S-1 in rats].

S-1, an antineoplastic formulation of a fluorinated pyrimidine derivative containing tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1, was recently developed by Taiho Pharmaceutical Co., Ltd., with the aim of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) over that produced by FT alone and reducing its dose-limiting gastrointestinal toxicity. As a part of the S-1 toxicity study, a 13-week oral repeated dose toxicity study and a recovery study using male and female rats was conducted. Doses of S-1 were adjusted to deliver 1.5, 5, and 15 mg/kg/day as doses of FT, and FT was given at 15 mg/kg/day. The following results were obtained. 1. In clinical observation, edema of the limbs and face or swelling of the auricle of the ear and an anemic appearance were observed in both sexes in the 15 mg/kg/day group as dose of FT. Subsequently, males in this group developed severe anemia, decreased spontaneous motor activity, emaciation, and subnormal skin temperature, and many males died. In the survivors, keratosis of the palm, sole, or tail was observed, with necrosis and loss of the tail tip in the severe cases. 2. Body weight gain was suppressed from about week 2 of treatment in both sexes in the 15 mg/kg/day group as dose of FT, and there was almost no weight gain after week 4-5. Food consumption was consistently less than the control value for males in the 15 mg/kg/day group as dose of FT throughout the treatment period. 3. No marked changes were observed in water intake and on opthalmologic examination. 4. In the fecal test for occult blood, a positive tendency was observed in both sexes in the 15 mg/kg/day group as dose of FT. 5. Urinalysis disclosed a slight increase in protein and decrease in sodium, potassium, and chloride in males, and an increase in protein in females in the 15 mg/kg/day group as dose of FT. 6. Hematologically, both sexes in the 15 mg/kg/day group as dose of FT showed decreases in red blood cell count, hemoglobin, and hematocrit, and increases in platelet count and fibrinogen, with a slight decrease in white blood cell count in males. 7. In the blood biochemical test, abnormal findings included increases in total cholesterol and free cholesterol, and decreases in non-esterified fatty acid and albumin in both sexes in the 15 mg/kg/day group as dose of FT. 8. In organ weight measurement, abnormal changes included a decrease in thymus weight in both sexes in the 5 mg/kg/day or higher dosage groups and a decrease in the testis weight in males and an increase in the liver weight in females in the 15 mg/kg/day group as dose of FT. 9. Histopathologically, both sexes in the 15 mg/kg/day group as dose of FT showed a decrease in the red pulp of the bone marrow, atrophy of the thymus, white pulp of the spleen, and testes. degeneration of the renal tubules, and ulcerative changes of the skin or oral mucosa. 10. The findings were unremarkable in the FT group. 11. During the recovery study, all the toxic effects tended to reverse. 12. The NOAEL of S-1 was estimated to be 1.5 mg/kg/day as dose of FT for both sexes.

Administration, Oral↗
PubMed1997

Long-term, low-dose, cadmium-induced nephropathy with renal osteopathy in ovariectomized rats.

To establish an animal model of chronic cadmium nephropathy and osteopathy, we intraperitoneally administered 0.228 mg CdCl2 (Cd) or normal saline (NS) to 52 female Sprague-Dawley (S.D.) rats 3 times a week for 16 months following ovariectomy (OV) or sham surgery (Sham), dividing the animals into three experimental groups (OV-Cd, Sham-Cd and OV-NS). Two groups of male S.D. rats were also administered Cd or NS (22 animals; Male-Cd and Male-NS). Cd-administered rats gained significantly less body weight than NS rats after 16 months of experiments with no signs of emaciation. Serum creatinine levels and Cd contents in the kidney had significantly increased in the Cd-administered rats. OV-Cd rats showed significant decreases in PTH levels and increases in calcium contents in the kidney and other organs. Kidneys of Cd-administered rats showed atrophy, dilatation, and interstitial fibrosis of tubules. Sclerosis and collapse of the glomeruli were observed in the Cd groups with no proliferation in mesangial cells or matrix. The Haversian canal system of the Cd-administered rats disappeared and was replaced by a large quantity of degenerated, necrotic, and restorative tissues. Bone histomorphometric parameters showed that osteoid volume and osteoid surface had significantly increased in the Male-Cd group. In contrast, decreases in bone mass and increases in fibrous tissue were found to be more prominent in the OV-Cd group. Our results have demonstrated for the first time that long-term, low-dose CdCl2 administration to ovariectomized S.D. rats is capable of inducing irreversible nephropathy with osteopathy exhibiting pathological and bone histomorphometric characteristics that are very similar to those of Itai-Itai disease.

Animals↗
PubMed1997

[Oral single-dose and 13-week repeat-dose toxicity studies of RCC-36, the active metabolite of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence, in rats].

Oral single-dose and 13-week repeat-dose toxicity studies of (+/-)-4-ethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride (RCC-36), an active metabolite of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, were conducted in male and female Sprague-Dawley rats. In the single-dose toxicity study, rats were given the drug at doses of 0 (control), 400, 600, 900, 1350 and 2030 mg/kg. In the 13-week repeat-dose toxicity study, rats were given the drug for 13 weeks at doses of 0 (control), 3, 30 and 300 mg/kg. After discontinuation of the treatment, a 5-week recovery test was also conducted. In the single-dose toxicity study, death occurred in the 600 mg/kg group and over, and LD50 values were 735 mg/kg in both sexes. The major clinical signs observed following the administration of this drug were mydriasis, salivation, decreased spontaneous locomotor activity, ataxic gait, lacrimation and urorrhea in the 400 mg/kg group and over, hypopnea and soft feces in the 600 mg/kg group and over. In addition, prone or lateral position and tonic or clonic convulsion were observed in the dead animals. Rats showed a decrease in body weight or a suppression of its weight gain in the 400 mg/kg group and over. Macroscopic findings in the dead animals were congestion in lung and retention of foamy mucinous fluid in trachea. The animals alive showed no abnormalities attributable to the treatment. In the 13-week repeat-dose toxicity study, 13 cases of death occurred in the 300 mg/kg group. Main pathological findings in these cases were congestion and edema in lung. Mydriasis was seen in the 30 mg/kg group and over. Lacrimation, salivation, wheezing, emaciation [corrected] wasting and unkempt fur were seen in the 300 mg/kg. A suppression of body weight gain and a decrease in food consumption were observed in the 300 mg/kg group. An increase in water consumption was seen in the 30 and 300 mg/kg groups. Ophthalmologic examination confirmed the mydriasis in the 30 mg/kg group and over. Urinalysis showed an increase in urine volume and a decrease in Na+ excretion in the 30 and 300 mg/kg groups and decreases in K+ and Cl- excretions in the 300 mg/kg group. Hematological examination showed decreases in hemoglobin, hematocrit, MCV and MCH, and an increase in MCHC in the 300 mg/kg group. Blood chemical examination showed decreases in triglyceride and glucose, and an increase in total protein in the 300 mg/kg group. Pathological examination disclosed hepatocellular hypertrophy associated with hyperplasia of smooth-ER, a decrease in number of glycogen granules and an increase in number of lipofuscin in the 300 mg/kg group. Stimulated thyroid follicles were seen in the 300 mg/kg/group. In kidney, an increase in number of hyaline droplets in the proximal tubular epithelium, in which lysosomes and dense bodies were increased, was observed in the 300 mg/kg group. Dense bodies were increased also in the glomerular epithelium. In this dose group, adrenocortical hypertrophy was also observed. The recovery test showed that the above-mentioned changes were satisfactorily reversible or the degree and frequency of these changes were lowered. No treatment-related effects were seen in the 3 mg/kg group. These results show that the NOAEL (no observed adverse effect level) of RCC-36 is 3 mg/kg for 13-week oral toxicity in rats.

Administration, Oral↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 18). Comparative 4 and 2 weeks oral repeated dosing studies on male reproductive organs in rats treated with 5-fluorouracil.

Oral repeated toxicity studies were conducted to compare the effects of 5-fluorouracil (5-FU) administered for 4 or 2 weeks on male reproductive organs of Sprague-Dawley (SD) rats. In both studies, decrease of feces, abnormal fur and emaciation were observed. On gross autopsy examination, softening/atrophy of the testis as well as atrophy of accessory reproductive organs were noted, and absolute organ weights of male reproductive organs were almost all reduced in both studies. Histopathologically, degeneration of the seminiferous epithelium in the testis and desquamated cell debris in the epididymal ducts were apparent after both time periods. In the 2-week study, furthermore, exfoliation of the seminiferous epithelium, formation of multinucleated giant cells and vacuolation of Sertoli cells in the seminiferous tubules in the testis, and decrease of sperms in the epididymal ducts were observed. The present results indicated that a 2-week study is sufficient to detect effects on the male reproductive organs of 5-FU treatment. In our study, however, changes in associated parameters after 2-week treatment of 8-week-old rats were greater than those after 4 weeks in 6-week-old rats. Thus, for detection of 5-FU-induced male reproductive toxicity, we can evaluate more accurately by using maturated rats of the same age.

Animals↗
PubMed1980

[Studies on toxicity of clobetasone-17-butyrate (II)--chronic toxicity in rats (author's transl)].

Chronic toxicity of clobetasone-17-butyrate, an anti-inflammatory corticosteroid, was investigated in rats. Subcutaneous administration with the drug at dose of 0.003, 0.01 and 0.03 mg/kg/day for three and six months induced no significant changes in the rats. At 0.1 and 0.3 mg/kg/day, however, some dose-dependent symptoms such as suppression of body weight gain, emaciation, regressive changes in adrenals, lymphatic and hematopoietic tissues, decrease in circulating white blood cell and lymphocyte counts, which have been known as toxic effects of synthetic corticosteroids, were induced. The results indicates that the maximum no-toxic dose of clobetasone-17 butyrate was 0.03 mg/kg/day on this experimental condition. In the recovery test for two months no significant differences in the treated rats from controls were found, suggesting that the toxic effects were reversible in the animals treated at 0.3 mg/kg/day and lower than that.

Adrenal Glands↗
PubMed1981

[Studies on toxicity of hydrocortisone 17-butyrate 21-propionate -3. Subacute toxicity in rats by percutaneous administration (author's transl)].

Subacute toxicity of hydrocortisone 17-butyrate 21-propionate (HBP) was studied in rats. HBP was percutaneously given to rats with 0.1% and 0.5% creame (0.1% HBP-C, 0.5% HBP-C) and ointment (0.1% HBP-O, 0.5% HBP-O) at the daily dose level of 150 mg per 100 g body weight for 1 month. Rats receiving HBP-C and HBP-O showed some dose-dependent symptoms such as the suppression of body weight gain, emaciation, decrease in the number of white blood cells, hemoglobin, hematocrit, and serum total cholesterol level, regressive changes in adrenals, skin, lymphatic and hematopoietic tissues, which are known as toxic effects of synthetic corticosteroids. These symptoms were comparatively high toxic in male rats and in cream groups, and almost disappeared in rats elapsed recovery time of 1 month after withdrawal of HBP.

Administration, Topical↗
PubMed1981

[Studies of toxicity of hydrocortisone 17-butyrate 21-propionate -5. Chronic toxicity in rats by percutaneous administration (author's transl)].

Chronic toxicity of a new synthetic corticosteroid, hydrocortisone 17-butyrate 21-propionate (HBP), was investigated in rats of both sexes. HBP was percutaneously given to rats with 0.1%, 0.5% cream and ointment at the daily dose level of 150 mg per 100 g body weight for 6 months. For the comparison, the percutaneous toxicity with 0.12% betamethasone 17-valerate (BV) cream and ointment, and 0.1% hydrocortisone 17-butyrate (HB) cream and ointment at the daily dose level of 150 mg per 100 g body weight were studied. Rats receiving HBP showed the dose-dependent changes such as the suppression of body weight gain and food intake, emaciation, decrease in the number of white blood cells and lymphocytes, total protein, increase in the number of red cells, hematocrit, hemoglobin, blood sugar and total cholesterol, regressive changes in adrenal cortex, lymphatic and hematopoietic tissues and skin, and gastric erosion, which have been well known as toxic effects of synthetic corticosteroids. These findings were comparatively high toxic in male, and almost disappeared in rats elapsed recovery time of month after withdrawal of HBP. The toxicities of HBP, BV and HB were qualitatively same. However, the grade of effects of HBP toxicity was similar to that of HB, weaker than of BV.

Administration, Topical↗
PubMed1981

[One month studies on the subacute toxicity of captopril in rats].

Subacute toxicity of captopril by daily oral administration at dose levels of 10 mg/kg, 30 mg/kg, 100 mg/kg, 300 mg/kg, 900 mg/kg and 2700 mg/kg for one month was studied in Sprague-Dawley rats. In the 2700 mg/kg group, 13 of 18 males and 17 of 18 females died with marked emaciation and abdominal distension. In the 900 mg/kg group, 1 of 18 males and 3 of 18 females died also during the administration period. In dead animals, a marked dilatation of gastrointestinal tract was noted showing multiple hemorrhagic erosions and/or ulcers in the glandular stomach. The remainder of these groups exhibited polydipsia and polyuria during the dosage period. In the 300 mg/kg and 100 mg/kg groups, all animals survived throughout the entire experimental period showing polydipsia and polyuria. In the 30 mg/kg and 10 mg/kg groups, all animals survived also throughout the entire dosage period without showing any toxic sign. Regarding plasma analysis, the BUN and creatinine concentration was significantly elevated in the group of 100 mg/kg or more. In the hematological examination, there was a decrease of erythrocyte counts, hemoglobin contents and hematocrit values in the group of 300 mg/kg or more. Pathological examinations revealed a marked thickening of the wall in afferent arterioles and interlobular arteries of the kidney in association with hypertrophy and hyperplasia of juxtaglomerular cells in 100 mg/kg, 300 mg/kg, 900 mg/kg and 2700 mg/kg groups. In these groups, multiple hemorrhagic erosions with or without ulcer were also noted in the glandular stomach. In the spleen, a slight increase of extramedullary hematopoiesis and hemosiderosis was noted in the 100 mg/kg, 300 mg/kg, 900 mg/kg and 2700 mg/kg groups, in which an increase of erythropoietic elements was also noted in the bone marrow. From these results, the maximum nontoxic dose was estimated as about 30 mg/kg/day by oral administration of captopril in the rats.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Bence-Jones myeloma with pleural effusion: response to alpha-interferon and combined chemotherapy.

A 73-year-old female patient with myelomatous pleural effusions is described. She was admitted to our hospital with lumbago and emaciation. Laboratory findings revealed cytopenia and hypogammaglobulinemia. Immunoelectrophoresis demonstrated Bence-Jones monoclonal protein in the serum, but not in the urine. Bence-Jones myeloma was diagnosed by the bone marrow aspiration. Chest X-ray film, however, showed bilateral pleural effusions. Fluid cytology revealed numerous immature plasma cells, indicating pleural involvement. Intrapleural administration of alpha-interferon combined with systemic chemotherapy (oral melphalan-prednisolone with alpha-interferon im.) was successful in maintaining the resolution of pleural effusions. Intrapleural alpha-interferon administration seems to be effective in the management of myelomatous pleural effusions.

Aged↗
PubMed2004

Two young female patients with anorexia nervosa complicated by Mycobacterium tuberculosis infection.

Patients with anorexia nervosa (AN) seldom present with infectious illness, despite malnutrition-induced immunodeficiency. We described two young women who had a long-standing history of severe emaciation and pulmonary or lymph node tuberculosis discovered during the treatment of AN. Both patients reported a positive history of BCG vaccination. Contact tracing failed to reveal sources of infection, although the tuberculosis was considered transferred. Since the decline of notification rates for tuberculosis have been stagnant and outbreaks in schools or hospitals have been increasing in Japan, special attention must be given to the possibility of opportunistic infections in AN patients.

Adult↗
PubMed1983

Hypopituitarism who had undergone prolonged treatment with thyroid hormones alone for primary hypothyroidism.

A patient with hypopituitarism which is believed to have developed immediately after birth had been treated with thyroid hormones alone for a prolonged year of seven years until the time of the initial examination by the author. The subject has severe emaciation and lack of secondary sexual characteristics, but no past history of adrenocortical crisis was present, and, in fact, she manifested hyperthyroidism. It is questionable whether the preceding administration of thyroid hormones on the case with hypopituitarism should have been contraindicated. The two major complaints were improved through proper supplementary hormone treatment.

Adolescent↗
PubMed1984

Isolated ACTH deficiency associated with Hashimoto's thyroiditis: report of a case.

A 65-year-old female with general malaise, anorexia and marked emaciation was studied by secretion stimulation tests on 6 anterior pituitary hormones. Only ACTH showed no response and the other 5 hormones responded normally. The basal value of antidiuretic hormone was normal. She was found to be suffered from primary hypothyroidism. Though neither antithyroid antibodies nor other autoantibodies were found, Hashimoto's thyroiditis was confirmed by a thyroid open biopsy. Neoplastic lesions of the hypophysis were ruled out by various X-ray and CT examinations of the sella turcica as well as the brain. The case was concluded to be isolated ACTH deficiency associated with Hashimoto's thyroiditis. The substitution therapy using small doses of adrenocortical hormone and thyroid hormone has kept her well and she has been living normally for these five years.

Adrenocorticotropic Hormone↗
PubMed1996

Distribution of serouslike bone marrow changes in the lower limbs of patients with anorexia nervosa: predominant involvement of the distal extremities.

OBJECTIVE: To assess the distribution of marrow changes in the bones of the lower limbs of patients with anorexia nervosa (AN) and to correlate the importance of the extent of marrow changes with clinical and hematologic data. MATERIALS AND METHODS: The frequency of serouslike marrow (low signal intensity on T1-weighted images and very high signal intensity on T2-weighted images) was determined with MR imaging in the bones of the feet, distal tibias, and proximal femurs in 19 patients with AN. RESULTS: Serouslike marrow was found with an increasing frequency from proximal to distal in the lower-limb bones (femur, 31%; distal phalanx of the first toe, 79%). The patients with abnormal femoral marrow (n = 6) were more severely emaciated and had lower leukocyte and neutrophil counts than the patients with normal femoral marrow (n = 13). Among these patients, the six patients with at least two involved bones in the feet had lower blood cell counts than the seven patients with fewer than two involved bones. CONCLUSION: In the lower limbs of patients with AN, marrow changes predominate in the distal aspects. This distribution pattern is the reverse of that seen in most bone marrow disorders but is similar to the normal conversion of hematopoietic to fatty marrow. The importance of the blood cell count changes is correlated with the extent of marrow changes in the limbs.

Adolescent↗
PubMed1989

A study on the toxicity of antineoplastic drugs (bleomycin, peplomycin and cis-diamminedichloroplatinum) by simultaneous administration (Part 1).

In order to clarify the toxicity of the antineoplastic drugs, bleomycin (BLM), peplomycin (PEP) and cis-diamminedichloroplatinum (CDDP), which are commonly used to treat head and neck cancer by simultaneous administration, the semiacute toxicity of each of these drugs in rats was studied as an initial step. Body-weight change, general behavior, red blood cell count (RBC), white blood cell count (WBC), serum biochemistry (s-GOT, s-GPT, BUN, GLU, ALB, TP), A/G ratio, relative organ weight and histopathological features were determined. BLM and PEP given by ip administration once a week produced severe diarrhea, decreased diet consumption, emaciation, piloerection and loss of hair, enhancements of RBC and WBC, several changes in serum biochemistry, proliferation and mitosis of epithelial cells in the forestomach and occasional granular and vacuolar degeneration in the liver. CDDP administered in the same manner produced a significant decrease of WBC, several changes in serum biochemistry parameters especially BUN, an increased focal-segmental mesangial matrix in the glomeruli and vacuolar degeneration of epithelial cells of the convoluted tubule of the kidney.

Animals↗