In vivo release of cisplatin from a needle-type copolymer formulation implanted in rat kidney

Cisplatin, cis-dichlorodiamine platinum (II), was incorporated in a needle-type copolymer formulation (0.8 mm diameter, 6 mm long) by radiation-induced polymerization. The copolymer used was copoly(diethylene glycol dimethacrylate/polyethylene glycol #600 dimethacrylate, 80/20 vol%). This copolymer, containing 6 mg of cisplatin, was implanted into the kidney of adult male Wistar rats (420 +/- 20 g). A total of 70 d was required for 100% release of cisplatin in vivo. The kidney tissue surrounding the formulation was strongly necrotized by the action of cisplatin. Two layers of necrosis could be distinguished: necrotic tissue surrounding the formulation and necrobiotic tissue surrounding the necrotic tissue. The amount of necrotic tissue changed markedly over time, but no change was apparent in the amount of necrobiotic tissue. The maximal amounts of necrotized tissue were observed 14 d after implantation: 3100 microns and 600 microns thick for the necrotic and necrobiotic tissues, respectively.     

Effect of anti-androgen (TZP-4238) on steroid-induced canine prostatic hyperplasia. Light and electron microscopic investigations.

The effect of a synthetic steroidal anti-androgen, TZP-4238, on steroid-induced canine prostatic hyperplasia was studied by light and electron microscopy. Male beagle dogs (1-2 years old) were divided into four experimental groups. Group 1 consisted of intact controls. The other animals were castrated. The castrated animals were treated for 25 weeks with 1) 5 alpha-androstane-3 alpha, 17 beta-diol (A-diol) plus 17 beta-estradiol (E2) (Group 2), 2) A-diol plus E2 + TZP-4238 0.5 mg/kg (Group 3) and 3) A-diol plus E2 + chlormadinone acetate (CMA) 2.5 mg/kg (Group 4). TZP-4238 and CMA were administered orally for 21 weeks after 4 weeks treatment with A-diol plus E2. In group 2, glandular hyperplasia of the prostate was clearly noted. In contrast, combined treatment with TZP-4238 (Group 3) or CMA (Group 4) produced marked atrophy of the glandular epithelium. Loss of secretory and metabolic activities was confirmed by ultrastructural investigations. Our data indicate that TZP-4238 is a potent anti-androgen for the prevention of canine prostatic hyperplasia in the steroid-induced benign prostatic hyperplasia (BPH) model.     

EXPERIMENTAL MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS IN RATS INDUCED BY INTRAVENOUS ADMINISTRATION OF ANTI-THYMOCYTE SERUM

Focal glomerulonephritis was induced in rats, by a single intravenous injection of anti-Thy-1.1 antibody (ATS). One hour after the administration, the glomeruli of affected rats developed necrotic changes of the mesangial cells while after two hours, mesangiolytic changes appeared. From six days onwards, focal segmental mesangial proliferation which persisted until 30 days, occurred. This is thought to be the first report of experimental nephritis induced by pure anti-mesangial antibody.     

QT interval and QT dispersion in eating disorders

BACKGROUND: Eating disorders are thought to be risk factors for cardiac sudden death secondary to arrhythmia. Results in previous studies on QT interval and QT dispersion, markers of fatal arrhythmia, have been inconsistent. METHODS: We prospectively examined 179 female eating disorder patients, being over 18 years old and diagnosed according to the DSM-IV criteria between January 1995 and December 2002, and 52 healthy women. Patients with abnormal plasma electrolytes or taking medications that might influence the electrocardiogram (ECG) were excluded from the study. QT intervals were corrected for heart rate using Bazett's formula and the nomogram method, which is more reliable at extremely low heart rates than Bazett's formula. QT dispersion was measured as the difference between the longest and shortest QT intervals. QT intervals and QT dispersion in each patient group were compared with those in the control group. RESULTS: The 164 eligible patients consisted of 43 patients with anorexia nervosa restricting type, 35 with anorexia nervosa binge eating/purging type, 63 with bulimia nervosa purging type, and 23 with bulimia nervosa non-purging type. There was no significant difference in age between eating disorder patients and controls. QT interval and QT dispersion were significantly longer in all eating disorder subtypes than in the control group. QT interval and QT dispersion were significantly correlated with the rate of body weight loss in bulimia nervosa. CONCLUSIONS: QT interval and QT dispersion were prolonged in both anorexia nervosa and bulimia nervosa. Examination of ECG in eating disorder patients without extremely low body weight also appears to be clinically important.     

Skull base metastasis of prostatic cancer presenting as exophthalmos--a case report

A 72-year-old man was admitted to our hospital complaining of diplopia and right exophthalmos. Craniography and CT scan showed thickening of the right orbital roof and no intracranial lesion. Total acid phosphatase and prostatic acid phosphatase were high. Bone scintigraphy revealed high uptake at that lesion and the right pelvis. Unroofing of the right orbit and opening of the optic canal were performed in order to reduce intraorbital pressure. Microscopic examination revealed a metastatic lesion of prostatic cancer. Postoperatively, the patient was treated with "Honvan" and the course has been good.