Antiphospholipid syndrome and multiple ischemic strokes in a patient with myasthenia gravis

Little is known about ischemic stroke occurrence in patients with myasthenia gravis (MG), although antiphospholipid antibodies are detectable in many MG patients. A 47-year-old woman with a 20-year history of generalized MG had an acute onset of right hemiparesis. She had undergone thymectomy 10 years previously and was treated for phlebothrombosis of the lower extremity 3 years previously. Computed tomography (CT) demonstrated an old infarct in the left frontal lobe and a new lesion in the right parietal lobe. Multiple small cortical and subcortical infarcts were demonstrated on fluid attenuated inversion recovery (FLAIR) images. Thrombocytopenia (5.9 x 10(4)/microL), a prolonged activated partial thromboplastin time (aPTT; 50.2 sec), and an elevation of beta 2-IgG-glycoprotein I anticardiolipin antibodies (beta 2-GPIaCL; 55.7 U/mL) were observed. Neurological defects improved significantly over 2 weeks. She then was treated with oral prednisolone (30 mg/day) for 18 months, with resolution of laboratory abnormalities and no new cerebrovascular events or findings on imaging. We believe that our patient's multiple infarcts are caused by antiphospholipid antibodies and recommend glucocorticoid therapy to prevent recurrent of ischemic stroke in similar case.     

Efficient drug delivery to atherosclerotic lesions and the antiatherosclerotic effect by dexamethasone incorporated into liposomes in atherogenic mice

In order to confirm the efficacy of dexamethasone (DXM) incorporated into liposomes (DXM-liposomes) on atherosclerosis, drug delivery to atherosclerotic lesions and the antiatherosclerotic effect by DXM-liposomes were investigated in atherogenic mice. DXM-liposomes were prepared with egg yolk phosphatidylcholine, cholesterol and dicetylphosphate in a lipid molar ratio of 7/2/1 by the hydration method and then adjusted to three different particle sizes to clarify the influence of particle size on the drug delivery to atherosclerotic lesions and the effect on atherosclerosis. The particle sizes of DXM-liposomes were 519 nm (L500), 202 nm (L200) and 68.6 nm (L70), respectively. In both size, DXM concentration and DXM/lipid molar ratio in DXM-liposomes suspension were 1 mg DXM/ml and 0.134 mol DXM/mol total lipids, respectively. Atherogenic mice used as an experimental model develop an atherosclerotic lesion in the aorta and they were prepared by feeding an atherogenic diet for 14 weeks. The aortic pharmacokinetics of DXM-liposomes was examined by intravenous administration to atherogenic mice. The aortic uptake clearance of DXM in atherogenic mice treated with L200 was 2.6--3.2 fold greater than that in animals treated with L500, L70 or free DXM (f-DXM). Furthermore, the effects of DXM-liposomes on atherosclerosis were examined by intravenous administration to atherogenic mice once a week from 8 to 14 weeks. The antiatherosclerotic effects of DXM-liposomes were evaluated by determination of the aortic cholesterol ester (CE) level. The aortic CE level in atherogenic mice treated with L200 (55 microg DXM/kg) was significantly lower than that in animals treated with PBS. The antiatherosclerotic effect of L200 (55 microg DXM/kg) was significantly more potent than that of f-DXM (550 microg DXM/kg). These findings suggest that efficient delivery of DXM to the atherosclerotic lesions by L200 induces an excellent antiatherosclerotic effect at a lower dose. Therefore, L200 may be useful in the development of drug delivery systems for atherosclerotic therapy.     

The increase of female breast cancer incidence in Japan: emergence of birth cohort effect

During recent decades, breast cancer incidence has been increasing in Japan. According to the latest reports from several cancer registries in Japan, the breast has become the leading cancer site in female cancer incidence. To analyze the trend of breast cancer incidence in detail, we summarized female breast cancer incidence in Miyagi Prefecture, Japan during 1959-1997, and evaluated the period and cohort effect on breast cancer incidence using the age-period-cohort model. Age-specific and age-standardized rates have increased over successive calendar periods. Around 1980, an accelerated increase in these incidence rates took place. A full model including age, period and cohort was best fitted to the trend of incidence. In the model, the effects of period and cohort were statistically significant. The nonlinear effect for cohort indicates an increasing trend, beginning with the cohort in 1888-1897, and the nonlinear effect for period showed a clear increase in risk with calendar period. Furthermore, the full model including a linear component showed a steadily upward trend in the cohort effect. Based on our own epidemiologic studies previously conducted in Miyagi Prefecture, and other published reports, the cohort effect is likely to be related to the change in prevalence of women with risk factors such as low parity and insufficient breastfeeding. We believe that the emergence of the cohort effect is an important finding, although the period effect may also persist. The significant cohort effect may give a caution for continuous increase of breast cancer incidence in Japan.     

Impact of walking upon medical care expenditure in Japan: the Ohsaki Cohort Study

BACKGROUND: Physical activity is expected to reduce medical costs by lowering the risk for a variety of chronic diseases. However, little is known about the actual magnitude of medical cost saved by physical activity. We attempted to quantify the association between time spent walking and medical care costs, based on a 4-year prospective observation of National Health Insurance (NHI) beneficiaries in rural Japan. METHODS: In 27 431 Japanese men and women, aged 40-79 years, who had no functional limitation or conditions interfering with physical activity at the baseline survey in 1994, we ascertained all hospitalizations, outpatient visits, and the costs through computerized linkage with NHI claims history files between January 1995 and December 1998. RESULTS: Medical costs significantly reduced with longer time spent walking. Per capita medical cost was pound 111.80 per month (95% CI: 109.3, 114.2) in those who walked for < or =30 minutes/day, pound 108.10 (95% CI: 105.7, 110.5) in those who walked for 30 minutes-1 hour, and pound 97.30 (95% CI: 95.5, 99.0) in those who walked for > or =1 hour, after multivariate adjustment of potential confounders. CONCLUSIONS: This prospective study in Japan indicated that time spent walking was significantly associated with lower medical costs.     

Visualization of pulmonary arteriovenous malformation by three dimensional computed tomography: a case report

Pulmonary arteriovenous malformation (PAVM) is an anomaly condition characterized by abnormal vascular communications between arteries and veins in the lungs. Hereby we describe a 60-year-old female with PAVM. Although the patient was asymptomatic, an abnormal round opacity was found on a chest X-ray film. Computed tomography (CT) of the lung disclosed nodules connected with enlarged vessels. Because PAVM was suspected, the patient was further evaluated by spiral CT coupled with three dimensional reconstruction of the images (3D-CT). As a result, PAVM was clearly visualized and invasive procedures such as angiography was not performed. The present case illustrates that 3D-CT is a diagnostic procedure of choice when PAVM is suspected.     

Combination chemotherapy with irinotecan and ifosfamide as second-line treatment of refractory or sensitive relapsed small cell lung cancer: a phase II study

This phase II study was conducted to investigate the efficacy and safety of irinotecan (CPT-11) and ifosfamide as second-line chemotherapy for relapsed small cell lung cancer (SCLC). Eligibility criteria included histologically or cytologically confirmed SCLC, prior chemotherapy including platinum + etoposide, and measurable or evaluable disease. CPT-11 (80 mg/m(2)) was administered intravenously on days 1, 8 and 15, while ifosfamide (1.5 g/m(2)) was given on days 1 through 3 every 4 weeks. Thirty-four patients (29 men) with a median age of 69 years (range 42-77) and a median Eastern Cooperative Oncology Group (ECOG) performance status of 1 (range 0-2) were enrolled. The response rate was 52.9% (95% confidence interval: 29.8-64.9%) with 2 complete responses and 16 partial responses. Our analyses of prognostic factors showed risk factors assessed before receiving second-line chemotherapy, which were the number of metastatic sites, performance status and the type of relapse. WHO grade 3-4 neutropenia was recorded in 52.9% of the patients, grade 3 diarrhea in 5.9%. The combination of CPT-11 and ifosfamide demonstrated clinical efficacy in relapsed SCLC with a favorable toxicity profile, particularly for performance status 0-1 and sensitive cases with only one metastatic site.     

Mutations of a novel human RAD54 homologue, RAD54B, in primary cancer.

Association of breast tumor susceptibility gene products BRCA1 and BRCA2 with the RAD51 recombination protein suggested that cancer could arise through defects in recombination. The identification of NBS1, responsible for Nijmegen breakage syndrome, from the MRE11/RAD50 recombination protein complex also supports this hypothesis. However, our mutation analysis revealed that known members of the RAD52 epistasis group are rarely mutated in human primary cancer. Here we describe the isolation of a novel member of the SNF2 superfamily, characterized with sequence motifs similar to those in DNA and RNA helicases. The gene, designated RAD54B, is significantly homologous to the RAD54 recombination gene. The expression of RAD54B was high in testis and spleen, which are active in meiotic and mitotic recombination. These findings suggest that RAD54B may play an active role in recombination processes in concert with other members of the RAD52 epistasis group. RAD54B maps to human chromosome 8q21.3-q22 in a region associated with cancer-related chromosomal abnormalities. Homozygous mutations at highly conserved positions of RAD54B were observed in human primary lymphoma and colon cancer. These findings suggest that some cancers arise through alterations of the RAD54B function.