Transarterial internal radiation therapy with I-131 lipiodol for multifoca hepatocellular carcinoma: Immediate and long-term results

Transarterial internal radiation with I-131 Lipiodol (TAIR) was performed in 21 patients with multifocal hepatic carcinoma. Eight patients were treated by TAIR alone and 13 by combination of TAIR and intraarterial infusion ofcis-diamminedichloroplatinum (CDDP) and/or adriamycin mitomycin C oil suspension (ADMOS). TAIR was found effective immediately and long-term. Serum α-fetoprotein (AFP) levels dropped to 50% or less in 7 of 14 patients. Eleven of 21 patients (52%) showed 50% or greater decrease in tumor size. The overall 1-year survival rate was 43% and 67% in patients who received 50 Gy or greater tumor dose. Lipiodol distribution pattern of the tumor indicated some difference in the prognosis between the scattered pattern and solid pattern. The solid pattern showed a statistically significant better survival rate. Patients treated with TAIR alone versus those treated with TAIR and chemotherapy showed no difference in their survival rate.     

Recurrent vitreous hemorrhage in boys with prepapillary arterial loops

We examined recurrent vitreous hemorrhage in two boys with prepapillary arterial loops. Both patients complained of visible floaters in the left eye during gymnastic exercise. Prepapillary arterial loops and vitreous hemorrhage were found in the left eye in both boys. The vitreous hemorrhage decreased gradually, but recurred. Prepapillary arterial loops may be a risk factor for recurrent vitreous hemorrhage in children. The authors have stated that they do not have a significant financial interest or other relationship with any product manufacturer or provider of services discussed in this article. The authors also do not discuss the use of off-label products, which includes unlabeled, unapproved, or investigative products or devices.     

Alpha9beta1: a novel osteoclast integrin that regulates osteoclast formation and function.

We identified a previously unknown integrin, alpha(9)beta(1), on OCLs and their precursors. Antibody to alpha(9) inhibited OCL formation in human marrow cultures, and OCLs from alpha(9) knockout mice had a defect in actin ring reorganization and an impaired bone resorption capacity. INTRODUCTION: Integrins play important roles in osteoclast (OCL) formation and function. Mature OCLs mainly express alpha(v)beta(3) integrin, a heterodimer adhesion receptor that has been implicated in osteoclastic bone resorption. We identified ADAM8, a disintegrin and metalloproteinase, as a novel stimulator of OCL differentiation and showed that the disintegrin domain of ADAM8 mediated its effects on OCL formation. Because the disintegrin domain of ADAM8 does not bind Arg-Gly-Asp (RGD) sequences, we determined which integrin bound ADAM8 and characterized its role in OCL formation and activity. MATERIALS AND METHODS: Chinese hamster ovary cells (CHO) expressing different integrin subunits were tested for their capacity to bind the disintegrin domain of ADAM8. Mouse or human bone marrow cells and purified OCL precursors were tested for alpha(9)beta(1) integrin expression by Western blot, immunocytochemistry, and real-time RT-PCR. A monoclonal antibody to human alpha(9) was used to block alpha(9)beta(1) on OCL precursors stimulated by 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] or RANKL. Vertebrae of 7-day-old alpha(9)(-/-) mice and wildtype (WT) littermates were compared using bone histomorphometry and 3D microCT analysis. RESULTS: Alpha(9) integrin was expressed by mouse and human bone marrow-derived OCLs and their precursors. Importantly, the anti-alpha(9) antibody inhibited human OCL formation stimulated by 1alpha,25(OH)(2)D(3) or RANKL dose-dependently. Furthermore, analysis of OCLs formed in marrow cultures from alpha(9)(-/-) mice showed that the OCLs formed were more contracted and formed significantly less bone resorption pits on dentin slices. Histologic analysis of alpha(9)(-/-) vertebrae showed thickened trabecular regions and retained cartilage within vertebral bodies of alpha(9)(-/-) mice. 3D microCT analysis of alpha(9)(-/-) vertebrae also showed a significant increase in trabecular bone volume/total tissue volume and a tendency for decreased trabecular separation compared with WT mice. CONCLUSIONS: These results support a previously unknown role for alpha(9)beta(1) integrin in OCL formation and function.     

Acetazolamide induced myocardial ischemia in patients with severe coronary artery disease

Acetazolamide (ACZ)-augmented brain SPECT is commonly used for evaluating cerebral vascular reserve in patients with cerebrovascular disease. ACZ may cause myocardial ischemia in patients with coronary artery disease. To evaluate the risk of induction of myocardial ischemia with ACZ-augmented myocardial SPECT, we performed combined ACZ-augmented Tl-201 myocardial SPECT (ACZ-myo SPECT) with Tc-99m HMPAO brain SPECT in patients with severe coronary artery disease.Methods: Nine patients underwent combined ACZ-myo SPECT with Tc-99m HMPAO brain SPECT. (1) For qualitative analysis, SPECT images were divided into 13 segments to calculate the total defect scores. (2) Six ROIs were placed on the slices in the myocardial SPECT short-axis images and the regional uptake ratio was obtained as the ratio of the mean counts in the myocardium to the maximal count in the slice. The total defect score and regional uptake ratio of ACZ-myo SPECT were compared with those of early and delayed dipyridamole T1-201 myocardial SPECT (DP-T1 SPECT) images.Results: (1) In the 21 coronary artery territories with coronary stenosis ≧ 75%, the total defect score in ACZ-myo SPECT, early and delayed DP-T1 SPECT images were 3.52 ± 4.14*, 4.19 ± 4.65* and 2.25 ± 3.34, respectively (*: p < 0.05 vs. delayed DP-Tl SPECT images). (2) In 44 of 54 ROIs with coronary stenosis ≧75%, the regional uptake ratio of ACZ-myo SPECT, early and delayed DP-Tl SPECT images were 0.670 ± 0.166**, 0.677 ± 0.194**, 0.721 ± 0.178, respectively (**: p < 0.01 vs. delayed DP-Tl SPECT images). Systolic blood pressure fell at 11 min after ACZ infusion without electrocardiographic ST-T changes or chest pain.Conclusion: As ACZ has the potential to cause myocardial ischemia, ACZ-augmented brain SPECT should be performed with caution in patients with severe coronary artery disease associated with cerebrovascular disease.     

Coronary flow velocity waveforms in aortic stenosis and the effects of valve replacement

In 6 patients with pure aortic stenosis, the flow velocity waveforms in the left anterior descending coronary artery were studied using an 80-channel 20-MHz pulsed Doppler velocimeter before and immediately after aortic valve replacement. All patients showed normal coronary arteriograms. The left anterior descending coronary artery flow velocity waveform in aortic stenosis was characterized by a reverse flow in the first half of systole and a slowly increasing diastolic inflow. After aortic valve replacement, the reverse flow in the first half of systole disappeared in all patients, but an end-systolic reverse flow was discerned in 5 of 6 patients. The increasing rate of the diastolic inflow was augmented in all patients. After aortic valve replacement, the time from onset of diastole to the diastolic peak velocity was shortened from 176.8 +/- 28.8 to 90.5 +/- 18.8 ms (p less than 0.01), and the diastolic peak velocity increased from 90.5 +/- 28.0 to 122.5 +/- 17.2 cm/s (p less than 0.05). Blood pressure and heart rate, however, did not change significantly before and after valve replacement. These changes in the left coronary artery velocity waveforms after valve replacement suggest the beneficial effects of removal of aortic stenosis on human coronary artery inflow.     

Anti-inflammatory effect of spironolactone on human peripheral blood mononuclear cells

We evaluated the effect of alacepril, CV-11974, and spironolactone on the production of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in cultured human peripheral blood mononuclear cells stimulated with angiotensin (Ang) II. Alacepril, CV-11974, and spironolactone significantly reduced the enhanced production of MCP-1 and TNF-alpha induced by exogenous Ang II. Specifically, 10 muM of spironolactone significantly reduced cytokine production, compared to the same dose of alacepril or CV-11974. These findings indicate that spironolactone may contribute to ameliorate the prognosis of patients with cardiovascular diseases by reducing Ang II-induced inflammation, although further exploration including determining the mechanisms would be required.     

Latanoprost rescues retinal neuro-glial cells from apoptosis by inhibiting caspase-3, which is mediated by p44/p42 mitogen-activated protein kinase

The purpose of this study was to investigate whether latanoprost, a prostaglandin F2alpha analogue, has a direct anti-apoptotic effect both in retinal neuro-glial cells in culture and in diabetic retina. R28 cells, immortalized retinal neuroglial progenitor cells, were induced apoptosis by 24h serum deprivation. Serum withdrawal made up to 15% of R28 cells pyknotic and activated caspase-3 immunoreactive, and latanoprost acid suppressed apoptosis with dose dependency at an optimum concentration of 1.0 microM (P<0.001). UO126, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK) 1 and 2 inhibitor reversed this effect. Streptozotocin induced one- or three-month diabetic rats received balanced-salt-solution (BSS) in the left eye and latanoprost eye drops in the right for 5 days. Retinal wholemount was subjected to terminal dUTP nick end labeling (TUNEL) staining, whereas eyeballs were enucleated for cleaved caspase-3 immunofluorescence. Retinal homogenates were probed for phospho- or total p44/p42 MAPK and Akt. One- and three-month diabetic retina had 30.2+/-15.3 and 23.6+/-9.0 TUNEL positive cells per 0.5 cm(2), respectively, whereas control retina had few TUNEL positive cells. Latanoprost instillation significantly reduced these cells (10.0+/-3.1 and 11.3+/-3.1 cells per 0.5 cm(2) for 1M and 3M, respectively, P<0.01), whereas BSS did not. Latanoprost also significantly reduced cleaved caspase-3 immunoreactive cells in ganglion cell and inner nuclear layers (P<0.05). Latanoprost increased phosphorylated to total protein ratio of p44/p42 MAPK (P<0.05), but not of Akt. Taken together, the present findings suggest that latanoprost rescues retinal neurons and/or glial cells from apoptosis, which is probably mediated by p44/p42 MAPK through caspase-3 inhibition.