A case of a bacterial brain abscess presenting as symptoms of 'sudden stroke-like' onset

We report a case of a bacterial brain abscess presenting symptoms of 'sudden stroke-like' onset, associated with infective endocarditis. A 59-year-old woman experienced a sudden stroke-like onset of left hemiplegia. Computed tomography (CT) and magnetic resonance imaging (MRI) were performed on the day of ictus. No lesion responsible for the symptom was seen on either CT or a T2 weighted image (T2WI), but a diffusion-weighted image (DWI) revealed focal increased signal intensity in the right frontal lobe. An initial diagnosis of acute embolic infarction associated with infective endocarditis was made. Although the patient's neurological state had been stable, motor paresis of her left extremities became worse starting one month after her admission. MRI with gadolinium-diethylenetriaminepenta-acid (Gd-DTPA) at 37 days after admission showed an irregular-shaped ring-enhancement lesion located at the same place as the initial infarction, and in the left frontal lobe. Surgical drainage of the lesion in the right frontal lobe was performed, and diagnosed as a bacterial abscess. The exact mechanism of a bacterial brain abscess presenting with 'sudden stroke-like' onset is unknown, but various hypotheses have been proposed. One is that paroxysmal septic emboli lead to abscess formation within or near the area of embolic infarction. Our case showed that the creation of a brain abscess followed embolic strokes, and that this hypothesis was demonstrated by MRI carried out on the day of ictus.     

A case of thoracic disc herniation with sudden onset paraplegia on toilet straining: case report

Thoracic disc herniation is less common rather than cervical or lumbar herniation. Cases of sudden onset without trauma are especially rare. Generally, the neurological onset of disc herniation is caused by mechanical cord compression due to a protruded disc, and its onset is usually gradual. Ischemia is also considered as a factor of neurological onset. We report a case of a 78-year-old male with sudden paraplegia while straining at the toilet. T2 weighted MR image on admission showed mild disc protrusion at the level of Th8-9 and intramedullary high signal intensity below the Th8-9 level. We speculate that Valsalva-like maneuver had led to the congestion of vertebral venous plexus or compression of the anterior spinal artery, and spinal ischemia occurred.     

Ionic interaction of [<Superscript>11</Superscript>C]-<Emphasis Type="Italic">N</Emphasis>, α-dimethylbenzylamine (DMBA) in rodent brain

The [S] enantiomer of [11C]-N,alpha-dimethylbenzylamine (DMBA) was synthesized by N-methylation of [S]-alpha-methylbenzylamine, and its biodistribution in mice was measured. [11C]-[S]-DMBA was rapidly distributed into the brain, heart and lungs, and considerable long-term retention in the brain was observed. The radioactive metabolites in the plasma were analyzed by liquid chromatography. Kinetic analysis using unmetabolized [11C]DMBA in the plasma as the input function was performed employing a simplified two-compartment model. The estimated distribution volumes (DV) of [11C]DMBA in the brain and heart were 6.05 and 3.95, respectively. The right striatum of the rat brain was lesioned with ibotenic acid 2 weeks before the tracer experiment. Both in vitro and in vivo autoragiographic studies were performed, and revealed significant reduction of the radioactivity levels in the lesioned striatum. On the other hand, the regional cerebral blood flow, as measured by [14C]iodoantipyrine, was not significantly altered in the lesioned striatum. These results indicate that the ionic binding component for DMBA exists mainly in neural cells rather than in glial cells. [11C]DMBA might be a useful radiotracer for detection of neural cell loss in the brain.     

A phase I study of gemcitabine and irinotecan as second line treatment for advanced non-small cell lung cancer

A phase I study was conducted to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of gemcitabine and irinotecan combination therapy as second line treatment in patients with advanced non-small cell lung cancer (NSCLC). Twelve patients with measurable NSCLC (age range 46-74 years; 7 males, 5 females; performance status 0 = 4, 1 = 8) who progressed or failed first-line chemotherapy were enrolled. Prior chemotherapy was platinum-based without gemcitabine or irinotecan. Gemcitabine was administered at a fixed dose of 1,000 mg/m2 after irinotecan administration, and irinotecan was administered at doses from 50 to 125 mg/m2 with an increment of 25 mg/m2, both on day 1 and 8. Chemotherapy was repeated every 3 weeks. Grade 3/4 leukopenia occurred in three patients (25%), neutropenia in four (33%), anemia in one (8%), and thrombocytopenia in one (8%). Grade 3 nausea and vomiting was observed in three (25%), grade 2 diarrhea in one (8%), and liver dysfunction in one (8%). Other toxicities were mild. Two of the three patients at level 4 (irinotecan 125 mg/m2) experienced dose limiting toxicity: one patient experienced grade 4 leukopenia and neutropenia, and the other experienced treatment delay of more than 2 weeks. The objective response rate was 16.6% (2/12). The maximum tolerated dose in this combination therapy was gemcitabine 1,000 mg/m2 and irinotecan 125 mg/m2. The dose level of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 on day 1 and 8 of a 3-week cycle is recommended for a phase II study.     

Effects of hot deep seawater bathing on the immune cell distribution in peripheral blood from healthy young men

Objectives Deep seawater (DSW) utilization technology has been developed for the fields of medicine and health, among others. To clarify the health effects of DSW as compared with surface seawater (SSW) or tap water (TW), we investigated the changes of immune cell distribution of the peripheral blood, or subjective judgment scores, after hot water bathing. Methods Ten healthy young men were immersed for 10 min in DSW, SSW and TW heated to 42°C. Blood samples were collected before bathing, immediately after bathing and 60 min after bathing. Total and differential numbers of leucocytes and lymphocyte subsets (CD3, CD4, CD8, CD19, CD16, and CD56) were examined using an automated hematology analyzer and a flow cytometer, respectively. The subjective judgment scores were obtained by an oral comprehension test. Results Since the pre-bathing leukocyte count in the TW group was significantly different from those in the DSW and SSW groups, we excluded the findings of TW bathing from consideration. In hot DSW bathing, CD8-lymphocytes increased significantly immediately after bathing (p<0.05), in contrast to hot SSW bathing, in which no significant changes were detected in the lymphocyte subsets. Additionally, there were no significant changes between repeated measurements in the subjective judgment scores, though the score of thermal sensation in SSW bathing showed a significantly higher value immediately after bathing than before bathing (p<0.01). Conclusions Our findings suggest that increased CD8-lymphocytes in hot DSW bathing may improve human immune function as well as hot springs do, as compared with SSW bathing. Although hot DSW bathing may have the ability to change human immune cell distribution, well-designed studies are needed to clarify the health effects including not only DSW and SSW but also TW.     

Oral-Antigen Delivery via a Water-in-Oil Emulsion System Modulates the Balance of the Th1/Th2 Type Response in Oral Tolerance

Purpose. To evaluate the ability of a water-in-oil (W/O) emulsion containing ovalbumin (OVA), a model antigen, to induce oral tolerance and to elucidate the mechanism for the induction of oral tolerance by the emulsion system. Methods. A W/O emulsion containing OVA was prepared and evaluated its ability to induce oral tolerance in mice. Also, the Th1/Th2 balance in the mice tolerized was investigated in terms of the ratios of anti-OVA IgG2a titer to anti-OVA IgG1 titer (IgG2a/IgG1 ratios) and cytokine profiles. Results. Anti-OVA total IgG antibody titer of mice administered OVA in saline was approximately 3.5-fold higher than that of the mice administered OVA in W/O emulsion at a dose of 0.1 mg/mouse/day. Similar total IgG responses were observed between the above two at a dose of 1 mg/mouse/day. The IgG2a/IgG1 ratios decreased as the dose of OVA in W/O emulsion, but not in saline, increased at doses of 0, 0.1, and 1 mg/mouse/day. Interferon- secretion of PLN cells from the mice administered OVA in W/O emulsion decreased, whereas their interleukin-4 secretion remained high. Although interferon- secretion for the mice administered OVA in saline decreased, interleukin-4 secretion did not change. Conclusions. The present study suggests that oral delivery of OVA via the W/O emulsion system may more efficiently enhance the induction of Th2-dominated imbalance than that of OVA in saline.     

Effect of pravastatin on coronary plaque volume

A volumetric analysis by 3-dimensional intravascular ultrasound revealed that lipid-lowering therapy with pravastatin significantly reduced coronary plaque volume. The changes in plaque volume were inversely correlated with the changes in plasma levels of high-density lipoprotein cholesterol but not with changes in levels of total cholesterol or low-density lipoprotein cholesterol.     

Evaluation of Carboxymethylpullulan as a Novel Carrier for Targeting Immune Tissues

Purpose. To demonstrate the potential of carboxymethylpullulan (CMPul) as a carrier for targeting immune tissues, and to find whether immune tissues could be set as the target of an immunosuppressant to treat autoimmune diseases. Methods. The biodistribution of CMPul was investigated to evaluate its potency as a carrier for targeting immune tissues. Furthermore, an immunosuppressant-CMPul conjugate was prepared and its suppressive effect on rat adjuvant arthritis was examined. Results. The disappearance rate of ³H-labeled CMPul from the blood circulation was much slower than that of ³H-labeled pullulan (Pul) after intravenous injection to normal rats. The concentration of ³H-labeled CMPul in the spleen and lymph nodes was much higher than that of ³H-labeled Pul at 24 hours after the injection, whereas the concentration of ³H-labeled CMPul in the liver was significantly lower than that of ³H-labeled Pul. A similar targeting property of ³H-labeled CMPul for these immune tissues was observed in arthritic rats. A conjugate composed of a novel immunosuppressant PA-48153C and CMPul showed a suppressive effect on rat adjuvant arthritis judging from a reduction of the arthritic index and spleen weight and an increase of body weight. Conclusions. CMPul is expected to be a promising carrier for targeting immune tissues with an immunosuppressant to enable treatment of autoimmune diseases.     

Enhanced Accumulation of Sialyl Lewis X-Carboxymethylpullulan Conjugate in Acute Inflammatory Lesion

Purpose. E-selectin is a cell adhesion molecule that is specifically expressed in the inflammatory vascular endothelium in response to cytokines such as IL-1 and TNF-, and interacts with specific ligands containing sialyl Lewis X (Neu5Ac2-3Gall-4(Fucl-3)GlcNAc-, SLe^x). In order to investigate the ability of E-selectin ligands to target the inflammatory site, the tissue distribution of carboxymethylpullulan (CMPul) modified with SLe^x was studied. Methods. CMPul conjugates with various saccharides containing SLe^x and monovalent SLe^x were intravenously administered to mice with ear edema induced by arachidonic acid, and their distributions to the inflamed ear and other tissues were studied. To determine the microdistributions of these compounds, the inflamed ear was subjected to microautoradiography. Results. After intravenous administration AUC_0-24h of SLe^x-CMPul, which binds to E-selectin, in the inflamed ear was about 300-fold and 2.5-fold higher than that of monovalent SLe^x and CMPul conjugated with other saccharides, which can not serve as ligands for E-selectin. Microautoradiography also revealed SLe^x-CMPul accumulated at the microvessels in the inflammatory lesions. Conclusions. SLe^x-CMPul was found to have the potential to target drugs to the inflammatory lesion.