A suspicious case of central neurosarcoidosis, manifesting as a progressive gait disturbance with a lesion in the central gray matter of the midbrain, accompanying an elevated level of angiotensin converting enzyme in the cerebrospinal fluid]

We present a suspicious case of central neurosarcoidosis that presented with progressive gait disturbance probably caused by central vestibular dysfunction. And this case showed elevated level of angiotensin converting enzyme (ACE) in the cerebrospinal fluid, compared with the average level of two cases with acute inflammatory demyelinating neuropathy syndrome and four cases of multiple sclerosis. A 33-year-old man was admitted to our hospital with chief complaint of a gait disturbance that had appeared 3 years prior to the admission. And the symptom had exacerbated in these 3 months. Except for the gait disturbance and positive Romberg's sign, no neurological abnormality was detected. The findings of the cerebrospinal fluid test supported the diagnosis of meningitis. An increased level of angiotensine converting enzyme was detected when compared with our previous samplings from two cases of Guillain Barré syndrome and four cases of multiple sclerosis. With T1 weighted imaging of brain MRI, a high intensity lesion with gadolinium enhancement was identified in the central gray matter of the midbrain. Scan of the chest confirmed bilateral hilar lymphadenopathy. Based on these findings and the patient's clinical course, central neurosarcoidosis was suspected. The patient's symptoms improved dramatically after the administration of corticosteroid. The enhancement of the central gray matter ameliorated, and the ACE level of the CSF was decreased to the level of the demyelinating disorders.     

Enhanced expression of the sis and c-myc oncogenes in human meningiomas

In 19 human meningiomas (14 primary and four recurrent tumors and one tumor transplanted into athymic nude mice), oncogene expression, amplification, and rearrangement, and loss of heterozygosity on chromosome 22 were examined. Compared to nontumor brain tissue, there was greater than a fivefold expression of the sis oncogene in six (40%) of 15 tumors studied and of the c-myc oncogene in 12 (63%) of the total 19 tumors. Expression of the sis gene was lower in the recurrent tumors than in the primary cases, and there was no detectable expression in anaplastic meningioma cells. Rearrangement of the sis gene was found in one meningioma. Loss of heterozygosity on chromosome 22 was detected in two of the five informative heterozygous cases. Expression of the c-myc gene was higher in cases with a loss of heterozygosity than in those without. These results suggest that the sis and c-myc oncogenes are associated with tumorigenicity and that c-myc may induce meningiomas through loss of the putative tumor suppressor gene.     

A case of diphenylhydantoin-induced pneumonitis]

A 60-year-old man had been administered diphenylhydantoin (DPH) for prevention of convulsive seizures following clipping of an aneurysm of the middle cerebral artery. About one month after the commencement of DPH administration, he developed cough and low grade fever. He was treated with various antibiotics, but his condition increasingly worsened. Chest X-ray film revealed bilateral interstitial processes throughout the entire lung fields. Transbronchial lung biopsy was performed and the obtained specimen showed histological findings compatible with drug-induced pneumonitis. Administration of DPH was stopped immediately and 50 mg/day of prednisolone was started. The patient's condition rapidly improved, and the abnormal shadows on chest X-ray film gradually diminished. The lymphocyte stimulation test by DPH was positive with a stimulation index of 282%.     

Ammonia: a possible promotor in Helicobacter pylori-related gastric carcinogenesis.

Helicobacter pylori (HP) has been shown to possibly be a pathogen of gastric carcinoma. HP has urease activity and produces ammonia in the stomach. In this study, the role of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in rats. After 24 weeks pretreatment with MNNG (83 mg/l), 0.01% ammonia or tap water as a drinking water was administered for 24 weeks. The ammonia-treated rats showed a significantly higher incidence of gastric cancer (percent of animals with tumors and number of tumors per rat). Ammonia would thus appear to have an important role in HP-related human gastric carcinogenesis.     

Development of inactivated vaccine against virus causing haemorrhagic fever with renal syndrome

B-1 virus belonging to the hantavirus group was serially passaged in the brains of newborn mice. Inactivated vaccine was prepared from the brains after inactivation with formalin and then purification by ultracentrifugation. The antigenic potency of this vaccine in vitro was determined by antibody-bound enzyme-linked immunosorbent assay (ELISA) and serial diluted vaccine bound to an aluminium hydroxide gel was inoculated into Balb/c mice to test immunogenicity. After two injections of this vaccine preparation, antibodies were detected in the mice by immunofluorescent, neutralizing and haemagglutination inhibition antibody tests. When mice immunized with this vaccine were challenged with B-1 virus and Hantaan virus (KHF-83-61BL strain), the virus titres in their lungs and spleens were significantly less than those in non-immunized mice. These results suggest that inactivated B-1 virus vaccine is effective against virus challenge by homotypic (B-1 virus) and heterotypic (Hantaan virus) viruses.     

Olopatadine hydrochloride suppresses the rebound phenomenon after discontinuation of treatment with a topical steroid in mice with chronic contact hypersensitivity

BACKGROUND: Olopatadine hydrochloride (olopatadine; Allelock) is one of the second-generation antihistamines that are treated for allergic disorders such as rhinitis, urticaria and eczema dermatitis. Olopatadine has recently been shown to have inhibitory effects on the chronic contact hypersensitivity induced by repeated application of oxazolone in mice. Although topical steroids have widely been prescribed for atopic dermatitis, a relapse often occurs within several days after discontinuation of their prolonged use. OBJECTIVES: We investigated the possible efficacy of olopatadine against the relapse after discontinuation of prolonged use of topical prednisolone in the Balb/c mice with oxazolone-induced chronic contact hypersensitivity. METHODS: Mice with the chronic contact hypersensitivity induced by repeated application of oxazolone were treated with olopatadine as a sequential therapeutic agent. The effects of olopatadine were quantified by measurements of ear-swelling, and levels of cytokines and histamine in the lesioned ear. Results Topical prednisolone (0.05 mg/ear/day) significantly inhibited the increases in ear swelling and production of IL-1beta, IL-4, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF) and histamine. However, after discontinuation of the treatment with topical prednisolone, the inflammation relapsed and the IL-4 level exceeded the control one. The sequential treatment with olopatadine (10 mg/kg/day) after discontinuation of the treatment with topical prednisolone alone, or topical prednisolone with olopatadine, significantly inhibited the increases in ear swelling and levels of IL-1beta, IL-4, IL-18, GM-CSF, nerve growth factor and histamine. CONCLUSIONS: These results indicate that olopatadine is an antihistamine agent having inhibitory activities against the rebound phenomenon following the discontinuation of topical steroid therapy. Olopatadine is thus expected to be a sequential therapeutic agent after discontinuation of the chronic treatment with a topical steroid.     

Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer.

Between April 1985 and May 1988, we conducted a randomized study comparing two standard chemotherapy regimens with the same regimens given on an alternating basis in patients with small-cell lung cancer. The patients were randomly assigned to receive cyclophosphamide at a dose of 800 mg/m2 intravenously (IV) on day 1, doxorubicin at 50 mg/m2 IV on day 1, and vincristine at 1.4 mg/m2 IV on day 1 (CAV); cisplatin at 80 mg/m2 IV on day 1 and etoposide at 100 mg/m2 IV on days 1, 3, and 5 (PE); or CAV alternating with PE (CAV/PE). Each regimen was repeated every 3-4 weeks. Three hundred patients were entered in the study, and 288 of them were eligible for analysis (97 for CAV, 97 for PE, and 94 for CAV/PE). The response rates for PE (78%) and CAV/PE (76%) were significantly higher than the rate for CAV (55%), while the complete response rates were similar (14%, 16%, and 15%, respectively). Nine (23%) of 39 patients who failed to respond to the initial CAV regimen responded to PE when they were crossed over. In contrast, only one (8%) of 13 patients responded to CAV after failing to respond to the PE regimen, suggesting that these two regimens were partially non-cross-resistant. The response duration on CAV/PE was significantly longer than that with CAV (P = .004). The survival time with CAV/PE (11.8 months) was superior to that with CAV (9.9 months) (P = .027) or that with PE (9.9 months) (P = .056). In patients with limited disease, the survival in the alternating arm was significantly superior to the survival in the CAV arm (P = .014) or the survival in the PE arm (P = .023). The toxic effects were acceptable in all three chemotherapy regimens. These results favor the alternating chemotherapy over either standard chemotherapy, such as CAV and PE, although the differences are not dramatic.