Basic and clinical studies on norfloxacin in the pediatric field

Pharmacokinetic , bacteriological and clinical studies on norfloxacin (NFLX), a quinolone-carboxylic acid antibacterial agent, were conducted in the pediatric field. 1. Serum concentrations and urinary excretion of NFLX after single dose of 2.2 approximately 5.6 mg/kg (mean 4.4 +/- 1.2 mg/kg) were determined in 13 children with ages between 6 and 11 years. The mean peak serum concentration of the drug was 0.37 +/- 0.20 micrograms/ml at 2 hours after administration. The mean half-life of the drug in serum was 2.8 +/- 0.4 hours and the serum concentration at 8 hours was 0.11 +/- 0.06 micrograms/ml. The mean urinary concentration reached a maximum of 125.2 +2- 166.2 micrograms/ml in pooled urine from 0 to 2 hours and the mean urinary recovery rate in the first 8 hours after administration was 22.1 +/- 6.0%. A dose-response relationship was observed between doses/body weight and peak serum concentrations. 2. The clinical efficacy, bacteriological efficacy and the safety of NFLX were evaluated in 65 pediatric patients with ages between 2 years 10 months and 15 years 7 months with infections. In 62 assessable cases (acute purulent tonsillitis 9 cases, acute pneumonia 3 cases, chronic rhinitis 1 case, urinary tract infections 15 cases, and acute colitis 34 cases), clinical efficacies were excellent in 48 cases, good in 13 cases, and fair in 1 case with an overall efficacy rate of 98.4%. Staphylococcus aureus 1 strain, Staphylococcus epidermidis 1 strain, Escherichia coli 10 strains, Salmonella sp. 5 strains, Morganella morganii 1 strain, Pseudomonas aeruginosa 3 strains, Haemophilus parainfluenzae 1 strain and Campylobacter jejuni 12 strains were isolated from the patients as pathogens. Bacteriologically, all of these strains were eradicated except that 3 strains of C. jejuni only decreased. With regard to side effects, dizziness and nausea were observed in 1 case each but they were slight and the continuation of the treatment was possible. No abnormal laboratory test data were observed. From the above results, NFLX was considered to be a useful drug for the treatment of pediatric infections.     

Anti-Oxidative Therapy with Oral Dapsone Improved HCV Antibody Positive Annular Elastolytic Giant Cell Granuloma

A 72-year-old fisherman who was positive for the HCV antibody developed an annular, erythematous, infiltrated lesions on sun-exposed areas. The lesions were diagnosed as annular elastolytic giant cell granuloma both clinically and histologically. Topical corticosteroid and cryotherapy with liquid nitrogen for several months failed to improve the lesions. We then started dapsone, a known anti-oxidant, at 50 mg/day. A month later, the margins of the erythematous lesions faded, and the infiltration gradually decreased. No recurrence has been observed for one year after the start of the therapy. Anti-oxidative therapy appears to be effective for annular elastolytic giant cell granuloma and could be an alternate therapy for refractory granulomatous disease.     

Squamous cell carcinoma of the thyroid--a report of three cases

Three cases of squamous cell carcinoma of the thyroid are reported herein. In all cases, the carcinoma occurred in old age and was characterized by a rapidly growing tumor, usually associated with dyspnea and dysphagia. The prognosis of all 3 cases was poor, with a mean survival of only 6.3 months. Although squamous metaplasia is an accepted etiology of this disease, clinical investigation of the cases presented here does not favor it in consideration of the clinical features of papillary carcinoma of the thyroid with squamous metaplasia. The histological findings of our cases revealed areas of cystic formation, suggesting that some of these carcinomas may be derived from remnants of embryonic origin.     

A case of lymphocytic adenohypophysitis associated with sarcoidosis of the lung and eye

Lymphocytic adenohypophysitis is considered to be an inflammatory disease of the adenohypophysis that is commonly present with visual disturbance and hypopituitarism. Its etiology remains unclear but it is often related to an autoimmune disorder involving other organs, such as the thyroid, parathyroid, or adrenal glands. We encountered a rare case of lymphocytic adenohypophysitis associated with sarcoidosis of the lung and eye during the follow-up period. A 23-year-old woman was hospitalized in July 1986, with a one-month history of headache and visual disturbances which began three days after her second normal delivery. On admission, she showed slight visual impairment and had a left temporal superior quadrantanopia. Endocrinological evaluation revealed thyroid and adrenal hypofunction, and low response of human growth hormone to the loading test. A skull X-ray showed normal shaped sella with some erosion of the dorsum. CT scan showed a rounded contrast-enhanced intrasellar mass extending into the suprasellar cistern. MRI (SR: 500/30) showed a homogeneous low intensity mass which contained a small high intensity area on the relative T2-weighted image (2000/50). A biopsy was performed via right frontotemporal craniotomy. The consistency of the resected tissue was firmer than that of pituitary adenoma. Histologically, the tissue showed diffuse lymphocytic infiltration with some normal adenohypophysis. Her postoperative course was uneventful and the visual impairment improved two months later after the operation. Six months after the operation, she was readmitted with complaints of general fatigue and breathlessness. Chest X-ray showed diffuse infiltration throughout both lung fields, but there was no bilateral hilar lymphadenopathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium urolithiasis and bone change

Bone mineral contents of calcium urolithiasis patients (105 males and 52 females) were measured by the microdensitometry (MD) method, and the patients were divided into the MD normal group and the MD abnormal group. The patients were also divided into the group (21 males and 3 females) treated with thiazides for 1 year or more and the nontreated group to examine various factors in blood and urine. [Nontreated group] The rate of MD abnormality was higher in younger males. The rate tended to increase with age in females. Alkaline phosphatase values were significantly higher in MD abnormal group males than in MD normal group males. Urinary calcium excretion and PTH values were significantly higher in MD abnormal group females than in MD normal group females. Comparison of hypercalciuria and normocalciuria revealed no significant difference between the MD normal rate and the MD abnormal rate. Comparison of single of stone formers and recurrent stone formers also revealed no significant difference between the MD normal rate and the MD abnormal rate. [Treated group] PTH and alkaline phosphatase values were significantly higher in the treated group than in the nontreated group. Alkaline phosphatase values were significantly higher in the MD abnormal group. From the viewpoint of stone recurrence prevention, the monitoring of bones where the majority of calcium in the body is present is considered important besides behavior of calcium in blood and urine.     

Relationship of plasma and urine composition to recurrence of calcium urinary stones in patients on drug therapy

Factors relating alterations in plasma and urine composition to recurrence of urinary stones during drug therapy were investigated by using a multiple regression analysis technique. These factors were influenced not only by the efficacy of the drugs but also by other factors (plasma or urinary constituents and overall health of the patients, etc.). In order to study the effect of drug therapy or other treatment on the alteration of plasma and urine constituents, multiple regression analysis is more appropriate than Student's pairedt-test which has been used by some workers. These two analytical methods yield different results even if used on the same data.     

Effects of activin A on anterior pituitary cells fractionated by centrifugal elutriation.

We have shown previously that activin A increases the number of immunoreactive follicle-stimulating hormone (FSH) cells. To further investigate the action of activin A, we examined its effects on anterior pituitary cells fractionated by centrifugal elutriation. Before activin A treatment, FSH cells were widely distributed among various fractions; a higher proportion of FSH cells was found in larger cell fractions (fractions 5-9), and a lower proportion in smaller cell fractions (fractions 2-4). After culture of the cells in each fraction with activin A (10 ng/ml) for 72 h, the number of FSH cells in fraction 4 only was significantly (P less than 0.05) higher by 225% than that in cells cultured without activin A. The amount of FSH secreted into the medium was minimal or undetectable in fractions 1-4. However, FSH secretion tended to be, or was significantly (P less than 0.01 in fraction 9), stimulated by activin A in fractions 5-9, in which the numbers of FSH cells were not significantly affected. These results suggest a dual mode of action of activin A on FSH: activin A increases the number of FSH cells in a specific type(s) of middle-sized cell fraction, and stimulates FSH secretion at least from larger cells without affecting the number of FSH cells.     

Ethylnitrosourea-induced apoptosis in primordial germ cells of the rat fetus.

Ethylnitrosourea (ENU) is a simple alkylating agent. It induces gene mutations in fetal primordial germ cells (PGCs), and a high incidence of congenital malformations is also found in the offspring of male mice treated with ENU at the embryonic stage. It is also reported that decreases in the fertility rate and weights of the testis and ovary were found in the offspring from dams treated with ENU. In this study, we analyzed the occurrence of apoptotic cell death and the expression of p53 protein which is thought to play an important role in the DNA damage-induced apoptosis after administration of ENU to pregnant rats on day 13 of gestation to obtain a clue for clarifying the toxic effect of ENU on PGCs. Apoptotic cells increased in PGCs in fetal gonads from 3 h after treatment. The number of apoptotic PGCs peaked at 6 h and gradually decreased towards 24 h after treatment. On the other hand, p53-positive PGCs increased from I h after treatment, prior to the induction of apoptosis. The number of p53-positive PGCs peaked at 3 h and returned to the control level at 24 h after treatment. These results suggest that ENU induces apoptosis in rat fetal PGCs immediately after its administration to dams and excess cell death by apoptosis may have a close relation to the later occurrence of decreases in the fertility rate and gonadal weight. Moreover, a possible involvement of p53 is suggested in the ENU-induced apoptosis in PGCs.