Fluorometholone Reference Standard (control 011) of National Institute of Health Sciences

The raw material of fluorometholone was examined for the preparation of the "Fluorometholone Reference Standard (Control 011)". The analytical data obtained were: optical rotation, [alpha]20D = .5 degrees; UV spectrum, lambda max of 240 nm and specific absorbance in methanol at 240 nm = 350.7; IR spectrum, same as that of the Fluorometholone Reference Standard (Control 864); high-performance liquid chromatography (HPLC), total amount of impurities estimated to be less than 0.5%; loss on drying, 0.01%. Based on the above results, the raw material was authorized as the Fluorometholone Reference Standard (Control 011) of the National Institute of Health Sciences.     

Tandem high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation for recurrent soft tissue sarcoma

BACKGROUND: Patients with recurrent soft tissue sarcoma (STS) are seldom curable, with 5-year survival rates of less than 10% in all large series. The role of high-dose chemotherapy (HDC) with hematopoietic stem cell support in this disease has not been established. CASE REPORT: We report on two patients with recurrent STS who were treated with tandem HDC supported by autologous peripheral blood stem cell transplantation (PBSCT). One patient with malignant fibrous histiocytoma recurred with multiple lung metastases. This patient achieved a partial response after two cycles of induction chemotherapy consisting of ifosfamide and epirubicin. During four cycles of induction chemotherapy, peripheral blood stem cells (PBSCs) were harvested. Tandem high-dose ICE regimen (ifosfamide 3 g/m2 on days-7 to -3, carboplatin 400 mg/m2 on days-7, -5 and 3, etoposide 500 mg/m2 on days-7, -5 and 3) supported by autologous PBSCT gave rise to further regression of the tumors. Another patient with malignant hemangiopericytoma was treated by tandem high-dose ICE regimen supported by autologous PBSCT after the 3rd removal of abdominal tumors. Relapse-free intervals until the 1st, 2nd and 3rd relapses were 40, 19 and 22 months, respectively. Tandem high-dose ICE regimen might delay the relapse. CONCLUSION: These observations suggest that a tandem high-dose ICE regimen with autologous PBSCT is feasible with some clinical efficacy in the control of refractory STS.     

Combination chemotherapy with carboplatin and etoposide for elderly patients aged 76 years or older with small cell lung cancer

Eighteen elderly patients aged 76 years or older with small cell lung cancer were treated with carboplatin (AUC = 4 mg/ml.min, i.v. day 1) and etoposide (70 mg/m2 i.v. day 1-3) and 17 patients were evaluable. The median age of the study population was 77 years (range: 76-81). Eight patients had limited disease (LD) and nine did extensive disease (ED). The overall response rate was 88% for LD patients and 67% for ED patients. Median survival time was 219 days for LD patients and 158 days for ED patients. Grade 3 and 4 leukopenia, neutropenia, thrombocytopenia and anemia occurred in 41%, 76%, 24% and 6% of patients, respectively. There was one treatment-related death due to pneumonitis.     

Induction of different types of uterine adenocarcinomas in Donryu rats due to neonatal exposure to high-dose p-t-octylphenol for different periods

Inappropriate exposure to estrogens in the fetal and/or newborn period can exert irreversible influence, including carcinogenesis on the reproductive system in mammals. The present study was conducted to investigate uterine carcinogenesis in Donryu rats treated neonatally with a high-dose estrogenic compound, p-t-octylphenol (OP) for different exposure periods. Female Donryu rats were subcutaneously administered 100 mg/kg/day OP every other day for the first 5 postnatal days (PNDs 1-5) or the first 2 weeks (PNDs 1-15). They received a single injection of 20 mg/kg N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) into a uterine horn at 11 weeks of age and were examined until 15 months of age. PNDs 1-5 OP-treated rats showed normal development of the female reproductive system, including uterine gland genesis and normal estrous cycling after vaginal opening. The treatment, however, accelerated an earlier occurrence of persistent estrus and increased the number of well differentiated uterine adenocarcinomas as compared with controls. This indicated that PNDs 1-5 OP treatment acts as a delayed modulator of the hypothalamus-pituitary-ovarian hormonal control system and the modulation increased the serum estrogen:progesterone ratio, resulting in induction of uterine tumors. On the contrary, PNDs 1-15 OP treatment demonstrated immediate and irreversible influences on the control system, called 'androgenization', and induced abnormal uterine development manifested by prolonged persistent estrus immediately after vaginal opening and also suppression of uterine gland genesis. In addition, uterine tumor malignancy in morphological and biological property clearly increased in this group although the total number of adenocarcinomas was not increased. The present study provides evidence that neonatal exposure to a high-dose OP enhances uterine carcinogenesis in rats, and the type of uterine tumors is changed by the periods of neonatal exposure to OP, suggesting that the mechanism of uterine tumor development is dependent upon neonatal exposure periods.     

Association of Lewy bodies and glial cytoplasmic inclusions in the brain of Parkinson's disease

We report the histopathological and immunohistochemical findings from the brain of an elderly patient diagnosed with Parkinson's disease (PD). Neuropathological examination revealed moderate neuronal cell loss and astrocytosis in the substantia nigra. Lewy bodies were found in many sites characteristic for PD, including the substantia nigra, locus coeruleus, hypothalamus, substantia innominata, pontine raphe nucleus, and dorsal motor vagal nucleus, cingulate and insular cortices. Furthermore, argyrophilic glial intracytoplasmic inclusions were found predominantly in the ventral pons, cerebellar white matter, precentral and frontal white matter, internal and external capsule, claustrum, and putamen. Inclusions were triangular in shape, and immunopositive for ubiquitin and alpha-synuclein. In view of these histopathological and immunohistochemical findings and patterns of distribution, the inclusions were suggested to be glial cytoplasmic inclusions (GCIs) in multiple system atrophy (MSA). These findings suggested that our case might have experienced two pathological processes; PD and the early stage of MSA (striatonigral degeneration) that had not progressed to striatal involvement. Alternatively a common pathological background including abnormal processing of alpha-synuclein could contribute to widespread accumulation of Lewy bodies and GCIs in a single condition accompanied by nigral degeneration.