Incidence and prognostic factors of Japanese breast cancer patients with bone metastasis

Background Few previous studies have analyzed the incidence of bone metastases in a defined population of Japanese breast cancer patients and their prognosis after chemotherapy. Methods This is a retrospective cohort study. We investigated 695 patients who underwent surgery for breast cancer. The strategy of adjuvant therapy was as follows. Patients with both estrogen receptors (ERs) and progesterone receptors (PgRs) had endocrine therapy as initial adjuvant therapy (n = 239). Patients with neither ERs nor PgRs had chemotherapy. When metastasis to other organs, including bone, was identified, patients received chemotherapy. The survival rates after surgery and after the onset of bone metastasis, as well as the incidence of bone metastasis, were calculated. We also evaluated the prognostic and predictive factors. Results Bone metastases developed in 148 of 695 patients. All 148 received chemotherapy, and 121 of them developed spinal metastases. The 5-year survival rate after bone metastases was 26.1%. Prognostic factors for bone metastases were visceral metastases and PgR status. Cord compression was observed in 17 of the 148 patients, with the thoracic spine being the most common. The 1-year survival rate for patients with bone metastases who received chemotherapy was 66.3%, whereas that of patients with paralysis after spinal metastases was 17.6%. Within 6 months of the development of spinal cord compression, 70.6% of the patients died. Conclusions We reported the incidence and prognostic factors for a defined population of Japanese breast cancer patients with bone and spinal metastases. Our results suggest that the expected survival time for patients with paralysis who received adequate endocrine therapy or chemotherapy is generally poor. However, to detect a predictive factor of long survival after paralysis and establish the indications for surgery, a comparative study among large groups of patients with paralysis and with different backgrounds is necessary.     

Investigation of where schizophrenic patients receive treatment

Schizophrenic patients receiving treatment in Kagawa Prefecture were studied as to where treatment was obtained. Analysis showed that there was a tendency by schizophrenic patients to seek treatment in institutions distant from their place of residence. The direction in which a patient proceeded to seek treatment varied and showed no pattern. Analysis by age groups showed that patients in the 15 to 39 years age group were most likely to seek treatment in locations other than where they lived and traveled the longest distance. The tendency to seek treatment away from their place of residence decreased with increasing age. However even among the elderly there were patients who traveled long distances for treatment. Factors associated with geographical or social relationships between the cities/towns could not explain the tendency observed. Neither was there a relationship to specialized medical care. Factors such as the related to the mental health care system, including prejudice and lack of societal understanding were inferred to be associated to this problem. Results of this study indicate a need to organize the community mental health system to serve districts with wider areas than that established for other diseases. However in the future there should be a gradual narrowing of the district area, a broadening of services offered, and a removal of societal prejudice against psychiatric patients.     

Effects of iomeprol,a new nonionic contrast medium,vis a vis iopamidol and nitroglycerin,on coronary diameter and blood flow in chronically instrumented dogs

The effects of an intracoronary administration of iomeprol, a new nonionic tri-iodinated water-soluble contrast medium, on coronary circulation were compared to those of iopamidol and those of nitroglycerin in 6 chronically instrumented conscious dogs. A pair of 10 MHz piezoelectric crystals and an electromagnetic flow probe were placed on the left circumflex coronary artery (LCCA) to measure the epicardial coronary diameter (CD) and coronary blood flow (CBF). Polyethylene tubing for drug administration was inserted into the LCCA proximal to the sonomicrometers. Iomeprol at the dose of 1 ml and 3 ml/min for 1 min significantly increased CD by 0.6±0.1% and 1.4±0.3%, respectively and CBF by 44.5±9% and 70±10%, respectively. Iopamidol at the same rates also significantly increased CD by 0.8±0.1% and 1.5±0.3% and CBF by 50±11% and 82±14%, respectively. There was no statistically significant difference between iomeprol-and iopamidol-induced increases in CD and CBF. However, the duration of the increase in CD was significantly shorter (p<0.05) after iomeprol than after iopamidol. Nitroglycerin (10 μg/kg) significantly increased CD by 4.5±1% and CBF by 105±10%. The increases in CD and CBF in response to iopamidol and iomeprol were significantly smaller (p<0.01) than to nitroglycerin. We conclude that vasodilating effects of iomeprol and iopamidol on the large epicardial coronary artery and coronary blood flow are comparable in conscious dogs and significantly lower than after nitroglycerin in the doses used by us. This study was supported by a grant from the EI-ZA1 Pharmaceutical Co., Tokyo, Japan.     

Diagnostic imaging of spinal cord lesions

Magnetic resonance imaging (MRI) has greatly facilitated morphologic evaluation of spinal cord lesions. Eleven cases representative of inflammatory, demyelinating, neoplastic and vascular diseases, are presented which illustrate and summarize important abnormal features in spinal cord imaging, particularly MR findings. Recently, specialised techniques such as MR angiography, fat-inhibiting methods, dynamic MRI and functional imaging have been developed. These methods have facilitated not only lesion diagnosis but also qualitative assessment, and are being used to analyze pathophysiology. Comprehensive diagnoses based on such modalities may be important in determining indications for surgery or defining the extent of surgery or the intensity of other treatments.     

The efficacy of fluconazole in treating prosthetic valve endocarditis caused byCandida glabrata: Report of a case

A case of active prosthetic valve infective endocarditis (PVE) due toCandida glabrata was successfully treated by the systemic administration of fluconazole. A 66-year-old Japanese man with infective endocarditis of unknown etiology underwent aortic and mitral valve replacement to treat severe aortic and mitral regurgitation associated with multiple organ failure. Postsurgical cultures of arterial blood were repeatedly positive forC. glabrata, and therefore fluconazole was administered either intravenously or orally at a dose of 400 mg/day for 46 days. During that time the signs of inflammation including fever such as an elevated white blood cell count and the presence of C-reactive protein (CRP) all improved while the blood cultures became negative. Fluconazole is thus considered to be effective in treating PVE caused byC. glabrata. When administering this treatment, it is also important to monitor the patient's renal and liver function.     

The effect of adjuvant therapy with or without tamoxifen on the endocrine function of patients with breast cancer

The ovarian and pituitary functions of 64 operable breast cancer patients undergoing adjuvant therapy with cytotoxic chemotherapy and/or tamoxifen were investigated. The post menopausal patients, divided into 3 treatment groups, one with tamoxifen alone, one with tamoxifen and chemotherapy and the other with chemotherapy alone had serum estradiol 17-β (E2) and progesterone levels lower than the evaluable limits. Although there was no significant difference in the level of estrone sulfate (E1-S) between these three groups, the level of lutainizing hormone (LH) and follicle stimulating hormone (FSH) in the patients treated with tamoxifen alone and tamoxifen and chemotherapy were significantly lower than those treated with chemotherapy alone. The decrease in gonadotropin levels induced by tamoxifen treatment was reversible as it appeared after the initiation of tamoxifen and recovered after its cessation. In the premenopausal patients, a group treated with tamoxifen and chemotherapy had significantly higher E1-S, E2 and progesterone levels and significantly lower gonadotropin levels than a group treated with chemotherapy alone or one treated with a cyclophosphamide regimen. These increases in the levels of estrogen and progesterone were also reversible, and induced by tamoxifen. Thus, adjuvant endocrinochemotherapy causes profound alteration in the hypothalamo-pituitary-ovarian axis and therefore, monitoring a variety of hormonal levels is thought to be necessary for assessing the consequences of adjuvant therapy in breast cancer patients, especially in premenopausal patients using tamoxifen.     

A common FGFR3 mutation functions as a diagnostic marker for achondroplasia-group disorders in the Japanese population

Recent DNA studies performed by several groups have detected mutations of the gene encoding fibroblast growth factor receptor 3 (FGFR3) in patients with achondroplasia-group disorders, including achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia (TD). For this study, we analyzed theFGFR3 gene in 31 Japanese patients with typical ACH, four with HCH, three with a condition intermediate between ACH and HCH (ACH/HCH-intermediate), and one with TD. Of the 31 typical ACH patients, 29 showed a G1138 to A transition and the other two a G1138 to C transversion, both resulting in a common Gly380Arg substitution in the transmembrane domain of FGFR3. The one TD and the four HCH patients did not display any mutations in the transmembrane domain of FGFR3. Of the three ACH/HCH-intermediate cases, one patient showed the Gly380Arg substitution and one did not, and further analysis of the second patient revealed the presence of Asn540Lys substitution. The first patient was, therefore, genotypically diagnosed as ACH and the second as HCH. Peripheral blood leukocyte DNA analysis in the remaining ACH/HCH-intermediate patient indicated an unequal ratio of mutant to normal PCR products, possibly representing a somatic mosaic for the Gly380Arg mutation. Analysis of the common FGFR3 mutation thus appears to help in the molecular diagnosis of patients with achondroplasia-group disorders.     

Reversal of multidrug resistance by new dihydropyridines with lower calcium antagonistic activity

Summary BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1–2 M, whereas they showed hardly any synergistic effect in the parental cell line (P388/S) at the same concentration. They inhibited the active drug efflux in P388/ADR cells as well as the binding of [G-³H]-vinblastine to membrane vesicles from P388/ADR, which was increased in resistant P388 cells as compared with parental cells. Besides, unlike the activity of clinically used calcium antagonists, the calcium antagonistic activity associated with BS compounds was very weak: their arterial relaxation activity was <21% of that of verapamil. These data suggest that BS compounds specifically overcome multidrug resistance without the serious hypotensive side effects that accompany the use of verapamil orother calcium antagonists.